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183Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)Protokół Badawczy Rejestru w wersji 3.0 – Europejska Sieć Choroby Huntingtona (EHDN)
Olivia J. Handley 1/, Marleen van Walsem 2/, Peter Juni 3/, Anne-Catherine Bachoud-Levi 4/,Anna Rita Bentivoglio 5/, Raphael M. Bonelli 6/, Jean-Marc Burgunder 7/, Joaquim Ferreira 8/, Arvid Heiberg 9/, Jørgen Nielsen 10/, Markku Päivärinta 11/, Sven Pålhagen 12/, María Ramos-Arroyo 13/, Raymund A. C. Roos 14/, Sarah Tabrizi 15/, Jiří Klempíř 16/, Wim Vandenberghe 17/, Christine Verellen-Dumoulin 18/, Jacek Zaremba 19/, Joseph Giuliano 20/, Ida Biunno 21/, Stephen Dunnett 22/, Torsten Illmann 23/, Susana Pro Kovisto 25/, Jamie Levey 25/, Bernhard G. Landwehrmeyer 26/ and the Registry investigators of the European Huntington’s Disease Network1/ University College of London, Institute of Neurology, Queen Square, London, U.K.2/ Rikshospitalet, Oslo universitetssykehus HF, Oslo, Norge3/ Division of Clinical Epidemiology & Biostatistics, Institute of Social and Preventive Medicine, University of Bern and Director CTU
Bern, Bern University Hospital, Bern, Switzerland4/ Service de Neurologie, Hôpital Henri Mondor, Créteil cedex, France5/ Institute of Neurology U.C.S.C Policlinico “A.Gemeli” Rome, Italy.6/ Sigmund-Freud Universität Wien, Austria7/ Neurologische Klinik des Inselspitals, Praxis, Bern Schweiz8/ Centro de Estudos Egas Moniz, Neurology, Lisbon, Portugal9/ Rikshospitalet, Dept. of Medical Genetics, Oslo, Norge10/ University Hospital of Copenhagen – Rigshospitalet, Dept of Neurology, Copenhagen, Danmark11/ Turky University Hospital, Dept. of Neurology, Turku, Finland12/ Karolinska University Hospital – Huddinge Division, Neurology, Stockholm, Sverige13/ Hospital Virgen del Camino, Medical Genetic, Pamplona, España14/ Leiden University Medical Centre (LUMC), Neurology K5-Q, Leiden, Nederlands. 15/ National Hospital for Neurology and Neurosurgery, Department for Neurology, London, U.K.16/ Centrum extrapyramidových onemocnění, Neurologická Klinika, 1. LF UK, Praha, Česká Republika17/ Universitair Ziekenhuis Gasthuisberg, Dienst Neurologie, Leuven, Belgique18/ Institut de Pathologie et de Génétique, Gosselies, Belgique19/ Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland20/ Director, Clinical Operations at CHDI Foundation21/ BioRep S.r.l., Milano, Italia22/ Cardiff University, School of Biosciences, Cardiff, U.K.23/ 2mt Software GmbH, Ulm, Deutschland24/ Rikshospitalet, Oslo Universitetssykehus HF, Oslo, Norge25/ Chief Operating Officer EHDN, Paris, France26/ Universitätsklinik Ulm, Abteilung Neurologie, Ulm, Germany
Adres do korespondencji / Address for correspondenceOberer Eselsberg 45/1, 89081 Ulm Deutschlandphone 1: +49 731 50063100, phone 2: +49 173 3281665 fax: +49 731 50063082e-mail: [email protected]
© Hygeia Public Health 2011, 46(2): 183-218
www.h-ph.pl
Hygeia Public Health 2011, 46(2): 183-218
184 Hygeia Public Health 2011, 46(2): 183-218
REGISTRY is a European-based observational, prospective, multi-centre study of individuals affected by Huntington’s disease (HD) in all stages, premanifest, people at risk of HD, and includes age and sex-matched controls. The major aim of REGISTRY is to obtain natural history data on a wide spectrum of HD mutation carriers and individuals who are part of an HD family in order to relate phenotypical characteristics with genetic factors and disease biomarkers. It also aims to expedite identification and recruitment for clinical trials and develop and validate sensitive and reliable clinical measures for detecting onset and change over the natural course of the disease which may also be potential outcome measures for use in future clinical trials and clinical care. The clinical assessment battery uses well-established standard rating scales for manifest HD, for example, the Unified Huntington’s Disease Rating Scale ’99, and collects biosamples for DNA, plasma, the generation of lymphoblastoid cell lines and lymphocytes. The study was initiated in 2004 and has undergone three protocol revisions. The most recent protocol amendment includes the REGISTRY sub-studies component. Substudies aim to assess the sensitivity and reliability of novel assessments designed to measure specific and/or rare clinical phenotypes currently not captured by standard clinical tools. The results of these substudies will make a valuable contribution to refining which clinical endpoints should be included into clinical trials.
Key words: Huntington disease, European Huntington’s Disease Network, Registry 3.0
REGISTRY 3.0 – jest europejskim obserwacyjnym, prospektywnym, wieloośrodkowym projektem badawczym nad osobami dotkniętymi chorobą Huntingtona (HD) w jej wszystkich stadiach, przedobjawowymi, osobami z grupy ryzyka zachorowania na HD oraz dobranych pod względem wieku i płci osobami z grupy kontrolnej. Głównym celem REGISTRY jest uzyskanie informacji na temat naturalnego przebiegu choroby od szerokiego spektrum osób z mutacją warunkującą HD i osób które pochodzą z rodzin dotkniętych HD, aby umożliwić odniesienie charakterystyki obrazu klinicznego do czynników genetycznych i biomarkerów HD. Projekt ma również na celu przyspieszenie identyfikacji i rekrutacji osób do badań klinicznych, rozwojowi i walidacji czułych i miarodajnych pomiarów klinicznych celem obserwacji zachorowania i zmian w przebiegu HD, które mogłyby być wykorzystanie do pomiaru skuteczności metod leczenia w przyszłych badaniach klinicznych. Bateria testów klinicznych jest złożona z powszechnie znanych skal oceny dla osób z objawami HD, np.: Unified Huntington’s Disease Rating Scale z roku 1999, pobiera się także próbki biologiczne na DNA, osocze, hodowlę limfoblastów i limfocyty. Projekt został zapoczątkowany w 2004 roku i podlegał trzykrotnej zmianie protokołu. Najnowszy przedstawiany protokół zawiera badania dodatkowe w ramach REGISTRY. Badania dodatkowe mają na celu ocenę czułości i wiarygodności nowo skonstruowanych testów do mierzenia specyficzności rzadkich postaci klinicznych choroby niemożliwych do oceny przy wykorzystaniu obecnych technik. Wyniki tych badań dodatkowych w znacznej mierze umożliwią odpowiedź na pytanie, do jakich celów powinno się zdążać prowadząc badania kliniczne.
Słowa kluczowe: choroba Huntingtona, Europejska Sieć Choroby Huntingtona, Registry 3.0
185Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
1
REG
ISTR
Y
Stud
y Pr
otoc
ol
Vers
ion
3.0
Rep
laci
ng V
ersi
on 2
.0
REG
ISTR
Y –
an o
bser
vatio
nal s
tudy
of t
he
Euro
pean
Hun
tingt
on-D
isea
se N
etw
ork
(EH
DN
)
Ver
sion
3.0
01 N
ovem
ber2
009
Spon
sore
d by
Euro
pean
Hun
tingt
on-D
isea
se N
etw
ork
(EH
DN
)
Fund
ed b
yC
HD
I Fou
ndat
ion,
Inc.
2
Tabl
e of
Con
tent
s1
Auth
ors.
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42
Abbr
evia
tions
and
term
s....
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53
Syn
opsi
s...
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63.
1St
udy
Sche
dule
of A
ctiv
ities
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.63.
2Pa
rtici
pant
s ov
ervi
ew...
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..7
3.3
REG
ISTR
Y O
verv
iew
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.....
73.
4Q
ualit
y C
ontro
l and
Qua
lity
Assu
ranc
e...
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...10
3.5
Dat
a st
orag
e an
d se
curit
y...
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113.
6D
ata
flow
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....1
13.
7O
rgan
isat
ion
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114
ETH
ICS
......
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...13
4.1
Inst
itutio
nal R
evie
w B
oard
or I
ndep
ende
nt E
thic
s C
omm
ittee
......
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.13
4.2
Ethi
cal C
ondu
ct o
f the
Stu
dy...
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.13
4.3
Parti
cipa
nt In
form
atio
n an
d In
form
ed C
onse
nt...
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...13
4.4
Inve
stig
ator
Obl
igat
ions
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135
ADM
INIS
TRAT
IVE
STR
UC
TUR
E...
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.15
5.1
Adm
inis
trativ
e re
spon
sibi
litie
s....
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....1
55.
2St
udy
Man
agem
ent.
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156
Det
aile
d St
udy
Des
crip
tion
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...17
6.1
Back
grou
nd a
nd ra
tiona
le...
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176.
2St
udy
obje
ctiv
es...
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..20
6.3
Stud
y de
sign
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.....
206.
4C
linic
al p
heno
typi
cal c
hara
cter
isat
ion
......
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..20
6.5
Col
lect
ion
of b
iolo
gica
l spe
cim
en...
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226.
6C
ompl
etio
n of
a fa
mily
his
tory
que
stio
nnai
re (F
HQ
)....
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236.
7Su
b-st
udie
s...
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...25
6.8
Ret
rosp
ectiv
e da
ta c
olle
ctio
n...
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256.
9R
EGIS
TRY
asse
ssm
ents
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...26
6.10
Obs
erva
tion
sche
dule
s....
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...27
6.11
Des
crip
tion
of th
e st
udy
popu
latio
n...
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...28
6.12
Met
hod
of Id
entif
icat
ion
and
Rec
ruitm
ent o
f stu
dy p
artic
ipan
ts...
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..29
6.13
Parti
cipa
nt in
form
ed c
onse
nt...
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.29
6.14
Doc
umen
tatio
n of
Con
sent
/Ass
ent.
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306.
15St
udy
Proc
edur
es -
Des
crip
tions
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....3
06.
16Sp
ecim
en R
epos
itory
: Bio
Rep
in M
ilano
(Ita
ly)..
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....3
27
Ethi
cal C
onsi
dera
tions
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....3
48
Stat
istic
al C
onsi
dera
tions
......
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368.
1D
ata
Anal
ysis
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...36
8.2
Form
s an
d da
ta h
andl
ing
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...37
186 Hygeia Public Health 2011, 46(2): 183-218
3
8.3
Mod
ifica
tion
of th
e pr
otoc
ol...
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...37
9Ap
pend
ix A
: Reg
istry
Ste
erin
g C
omm
ittee
......
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...38
10Ap
pend
ix B
Info
rmat
ion
and
Con
sent
For
ms.
......
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3910
.1Pa
rtici
pant
Info
rmat
ion
Shee
t (N
ew R
EGIS
TRY-
HD
Par
ticip
ants
)....
......
......
......
......
......
......
..39
10.2
Parti
cipa
nt C
onse
nt F
orm
(New
REG
ISTR
Y-H
D P
artic
ipan
ts).
......
......
......
......
......
......
......
.....
4410
.3Pa
rtici
pant
Info
rmat
ion
Shee
t (Ex
istin
g R
EGIS
TRY-
HD
Parti
cipa
nts)
......
......
......
......
......
......
.46
10.4
Parti
cipa
nt C
onse
nt F
orm
(Exi
stin
g R
EGIS
TRY-
HD
Parti
cipa
nts)
......
......
......
......
......
......
......
4910
.5Pa
rtici
pant
Info
rmat
ion
Shee
t (R
EGIS
TRY-
CO
MP
ANIO
NS)
......
......
......
......
......
......
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......
...51
10.6
Parti
cipa
nt C
onse
nt F
orm
(REG
ISTR
Y-C
OM
PAN
ION
S).
......
......
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......
......
......
......
......
......
.54
10.7
Parti
cipa
nt In
form
atio
n Sh
eet (
New
REG
ISTR
Y-C
ON
TRO
L)...
......
......
......
......
......
......
......
.....
5510
.8Pa
rtici
pant
Con
sent
For
m (N
ew R
EGIS
TRY-
CO
NTR
OL
Parti
cipa
nt).
......
......
......
......
......
......
5910
.9Pa
rtici
pant
Info
rmat
ion
Shee
t (Ex
istin
g R
EGIS
TRY-
CO
NTR
OL
Parti
cipa
nts)
......
......
......
......
6110
.10
Parti
cipa
nt C
onse
nt F
orm
(Exi
stin
g R
EGIS
TRY-
CO
NTR
OL
Parti
cipa
nts)
......
......
......
......
......
6410
.11
Fam
ily m
embe
r (In
vita
tion
lette
r)...
......
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.65
11R
efer
ence
s....
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.66
4
1A
UTH
OR
S
REG
ISTR
Yve
rsio
n 1.
0: G
.B. L
andw
ehrm
eyer
REG
ISTR
Yve
rsio
n 2.
0: G
.B. L
andw
ehrm
eyer
REG
ISTR
Yve
rsio
n 3.
0: G
.B. L
andw
ehrm
eyer
, O.J
.H
andl
ey, M
. van
Wal
sem
, P.J
uni
187Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
5
2A
BB
REV
IATI
ON
SA
ND
TER
MS
Abbr
evia
tion
ACD
Def
initi
onAc
id c
itrat
e de
xtro
seC
HD
IC
ure
Hun
tingt
on’s
dis
ease
Initi
ativ
eFo
unda
tion
Inc.
Co-
PIC
o-Pr
inci
ple
Inve
stig
ator
CSS
R-S
Col
umbi
a Su
icid
e S
ever
ity R
atin
gSc
ale
CSR
I-RC
lient
Ser
vice
Rec
eipt
Inve
ntor
y-R
evis
edeC
RF
Elec
troni
c C
RF
EHD
NEu
rope
an H
untin
gton
’s d
isea
se N
etw
ork
FHQ
Fam
ily H
isto
ry Q
uest
ionn
aire
HAD
SH
ospi
tal A
nxie
ty a
nd D
epre
ssio
n Sc
ale
HD
Hun
tingt
on's
dis
ease
HSG
Hun
tingt
on S
tudy
Gro
up
ICH
-GC
PG
ood
Clin
ical
Pra
ctic
e ac
cord
ing
to th
e pr
inci
ples
of t
he In
tern
atio
nal
Con
fere
nce
on H
arm
onis
atio
n (IC
H) g
uide
lines
IEC
Inde
pend
ent E
thic
al C
omm
ittee
IRB
Inst
itutio
nal R
evie
w B
oard
PIPr
inci
pal I
nves
tigat
orPB
A-s
Prob
lem
Beh
avio
urs
Asse
ssm
ent-s
hort
QA
Qua
lity
Assu
ranc
eQ
CQ
ualit
y C
ontro
lSB
ACSc
ient
ific
and
Bio
ethi
cal A
dvis
ory
Com
mitt
eeSF
-36
Shor
t For
m-3
6SI
Site
Inve
stig
ator
SIS
Snai
th Ir
ritab
ility
Scal
eSO
PSt
anda
rd O
pera
ting
Pro
cedu
reTF
CTo
tal F
unct
iona
l Cap
acity
UH
DR
SU
nifie
d H
untin
gton
's D
isea
se R
atin
g Sc
ale
6
3SY
NO
PSIS
REG
ISTR
Y is
a m
ulti-
cent
re, m
ulti-
natio
nal,
pros
pect
ive,
obs
erva
tiona
l stu
dy o
f Hun
tingt
on’s
dis
ease
(H
D) w
ith a
con
trol g
roup
of v
olun
teer
s. It
is a
n op
en-e
nded
stu
dy w
hich
will
incl
ude
as m
any
elig
ible
pa
rtici
pant
s as
willi
ng t
o pa
rtici
pate
.Th
e go
al o
f th
e pr
ojec
t is
to
colle
ct l
ongi
tudi
nal
data
on
the
phen
otyp
ical
cha
ract
eris
tics
of H
D g
ene
mut
atio
n ca
rrie
rs re
gard
less
of w
heth
er th
ey d
ispl
ay c
linic
al
sym
ptom
s an
d si
gns
of th
e di
seas
e an
d of
indi
vidu
als
who
are
par
t of a
n H
D fa
mily
(irr
espe
ctiv
e of
th
eir m
utat
ion
carr
ier s
tatu
s), i
n or
der t
o:ob
tain
nat
ural
his
tory
dat
a on
a w
ide
spec
trum
of H
D m
utat
ion
carr
iers
and
indi
vidu
als
who
ar
e p
art o
f an
HD
fam
ilyre
late
phe
noty
pica
l cha
ract
eris
tics
ow
ith g
enet
ic fa
ctor
s (‘g
enet
ic m
odifi
ers’
)o
with
dat
a de
rived
from
the
stud
y of
bod
y flu
ids
(blo
od, u
rine
–‘w
et b
iom
arke
r’) a
ndo
imag
ing
data
(‘d
ry b
iom
arke
r’)
expe
dite
iden
tific
atio
n an
d re
crui
tmen
t of p
artic
ipan
ts fo
r clin
ical
tria
ls
deve
lop
and
valid
ate
sens
itive
and
rel
iabl
e ou
tcom
e m
easu
res
for
dete
ctin
g on
set
and
chan
ge o
ver t
he n
atur
al c
ours
e of
pre
man
ifest
and
man
ifest
HD
whi
ch m
ay a
lso
be p
oten
tial
outc
ome
mea
sure
s fo
r use
in fu
ture
clin
ical
tria
ls a
nd c
linic
al c
are.
plan
for
fut
ure
rese
arch
stu
dies
(ob
serv
atio
nal
and
inte
rven
tiona
l tri
als
aim
ed a
t be
tter
sym
ptom
con
trol o
r aim
ed a
t slo
win
g or
pos
tpon
ing
the
onse
t and
pro
gres
sion
of H
D).
3.1
Stud
y Sc
hedu
le o
f Act
iviti
esTa
ble
1asu
mm
aris
es t
he o
vera
ll as
sess
men
t pl
anfo
r R
EGIS
TRY-
HD
par
ticip
ants
. Th
is in
clud
es
indi
vidu
als
who
are
HD
gen
e m
utat
ion
carr
iers
rega
rdle
ss o
f whe
ther
they
dis
play
clin
ical
sym
ptom
s an
d si
gns
of t
he d
isea
se a
nd f
amily
mem
bers
who
are
eith
er a
t ris
k of
the
dis
ease
or
who
hav
e be
en g
enet
ical
ly t
este
d an
d ar
e kn
own
not
to c
arry
the
gen
e (c
onfir
med
non
-mut
atio
n ca
rrie
rs).
Tabl
e 1b
sum
mar
ises
the
over
all a
sses
smen
t pla
n fo
r REG
ISTR
Y-C
ON
TRO
L pa
rtici
pant
s.
Tabl
e 1a
:Ove
rall
asse
ssm
ent p
lan
for R
EGIS
TRY-
HD
part
icip
ants
Bas
elin
e vi
sit
Ann
ual v
isit
Pseu
dony
mis
eD
emog
raph
ics
Bios
ampl
esFa
mily
His
tory
Clin
ical
/Mot
orBe
havi
oura
lC
ogni
tive
Qua
lity
of L
ifeH
ealth
Eco
nom
ics
Nov
el A
sses
smen
ts
188 Hygeia Public Health 2011, 46(2): 183-218
7
Tabl
e 1b
: Ove
rall
asse
ssm
ent p
lan
for R
EGIS
TRY-
CO
NTR
OL
part
icip
ants
Bas
elin
e vi
sit
Ann
ual v
isit
Pseu
dony
mis
eD
emog
raph
ics
Bios
ampl
esC
linic
al/N
euro
logi
cal
Beha
viou
ral
Cog
nitiv
eN
ovel
Ass
essm
ents
3.2
Part
icip
ants
ove
rvie
wEa
ch c
entre
is in
vite
d to
rec
ruit
as m
any
parti
cipa
nts
as p
ossi
ble.
Par
ticip
ants
may
incl
ude
indi
vidu
als
with
fam
ily h
isto
ry o
f HD
(co
nfirm
ed n
on-m
utat
ion
carr
iers
, mut
atio
n ca
rrie
rs, a
t ris
k an
d m
anife
st H
D),
and
indi
vidu
als
with
out f
amily
his
tory
of H
D w
ho m
ay p
artic
ipat
e as
REG
ISTR
Y-C
ON
TRO
L pa
rtici
pant
s.C
ompa
nion
s of
REG
ISTR
Y-H
D p
artic
ipan
ts m
ay p
artic
ipat
e as
REG
ISTR
Y-C
OM
PAN
ION
S.
3.3
REG
ISTR
Y O
verv
iew
3.3.
1St
udy
title
REG
ISTR
Y
3.3.
2Ty
pe o
f Stu
dyAn
obs
erva
tiona
l, pr
ospe
ctiv
e, m
ulti-
natio
nal,
mul
ti-ce
ntre
stu
dy o
f H
D a
ffect
ed a
tall
stag
es a
nd th
eir
fam
ilies
incl
udin
g pr
eman
ifest
gen
e ca
rrie
rs, c
onfir
med
non
-HD
mut
atio
n ca
rrie
rsan
d at
risk
indi
vidu
als,
and
a vo
lunt
eer c
ontro
l gro
up.
3.3.
3Fu
ndin
gR
EGIS
TRY
is f
unde
d by
CH
DI
Foun
datio
n,In
c.,
New
Yor
k, U
SA,
form
erly
kno
wn
as t
he H
igh
Q
Foun
datio
n.
3.3.
4Sp
onso
rTh
e sp
onso
r of R
EGIS
TRY
is th
e Eu
rope
an H
D N
etw
ork
(EH
DN
),le
gally
repr
esen
ted
by th
e U
nive
rsity
H
ospi
tal o
f Ulm
, Ger
man
y.
3.3.
5St
udy
Site
sSt
udy
site
s in
cou
ntrie
s w
ithin
and
out
side
ofEu
rope
cont
ribut
e to
REG
ISTR
Y.Th
e nu
mbe
r of
act
ivel
y pa
rtici
patin
g st
udy
site
s is
not
fix
ed a
nd c
ontin
ues
to e
xpan
d. F
or a
cur
rent
lis
t of
stu
dy s
ites,
site
in
vest
igat
ors
(SI’s
), ra
ters
an
d co
ordi
nato
rs
plea
se
see
the
EHD
N
web
site
(w
ww
.eur
o-hd
.net
/htm
l/net
wor
k/lo
catio
ns).
The
sele
ctio
n of
stu
dy s
ites
is b
ased
on
a se
t of c
riter
iain
clud
ing
inte
rest
in
res
earc
h in
HD
, prio
r ex
perie
nce
in p
rovi
ding
HD
-rel
ated
outp
atie
nt s
ervi
ces,
inte
rest
in p
artic
ipat
ing
in o
bser
vatio
nal a
nd in
terv
entio
nal c
linic
al s
tudi
es,
geog
raph
ic lo
catio
n/ca
tchm
ent
area
, av
aila
bilit
y of
ap
prop
riate
ly tr
aine
d si
te s
taff,
and
feas
ibilit
yof
the
tech
nica
l equ
ipm
ent o
f the
stu
dy s
ite (
e.g.
inte
rnet
ac
cess
etc.
).
In o
rder
to c
ontri
bute
to R
EGIS
TRY
in a
mea
ning
ful w
ay a
nd to
rec
eive
com
pens
atio
n fo
r R
EGIS
TRY
rela
ted
effo
rts,s
tudy
site
s ha
ve to
mee
t min
imum
qua
lific
atio
n cr
iteria
:
Rat
er
train
ing:
EHD
N
coor
dina
tes
annu
alra
ter
train
ing.
Vid
eo
asse
ssm
ents
are
dist
ribut
ed a
nnua
lly t
o st
udy
site
rat
ers
who
are
requ
ired
to s
ubm
it ra
tings
. R
atin
g sc
ores
are
rev
iew
ed b
y an
exp
ert
pane
l, w
ho a
war
dce
rtific
atio
n to
the
rat
er o
n th
e ba
sis
of s
core
s fa
lling
with
in a
n ac
cept
ed r
ange
.EH
DN
mak
es e
very
effo
rt to
ens
ure
that
rate
rs a
rece
rtifie
d.
8
Spec
ific
train
ing
mat
eria
l is
pro
vide
d fo
r m
otor
,co
gniti
ve a
nd b
ehav
iour
alra
ters
, Tr
aini
ng i
nclu
des
vide
o ra
tings
, in
tera
ctiv
e tra
inin
g se
ssio
ns,
and
stan
dard
ope
ratin
g pr
oced
ures
(SO
Ps)f
or te
st a
dmin
istra
tion
and
scor
ing.
All
mat
eria
ls
for
train
ing
and
certi
ficat
ion
are
avai
labl
e on
th
e EH
DN
w
ebpo
rtal
(http
s://w
ww
.eur
o-hd
.net
/htm
l/reg
istry
/cer
tific
atio
n).
Inve
stig
ator
/rate
r cr
eden
tials
:EH
DN
Lan
guag
e C
oord
inat
ion
team
s ob
tain
elec
troni
cC
Vs a
nd,
whe
re a
ppro
pria
te,
copi
es o
f m
edic
al l
icen
se,
reco
rds
of s
peci
fic t
rain
ing,
re
leva
ntpr
ofes
sion
altra
inin
g.
3.3.
6St
udy
Perio
dR
EGIS
TRY
is a
n op
en-e
nded
, pr
ospe
ctiv
est
udy.
Par
ticip
ants
are
ask
ed a
t th
e tim
e of
sig
ning
up
for
REG
ISTR
Y (=
at t
he b
asel
ine
visi
t) to
atte
nd a
s m
any
pros
pect
ive
annu
al fo
llow
up
visi
ts a
s po
ssib
le. I
n ad
ditio
n, p
artic
ipan
ts w
ill be
ask
ed t
o co
nsid
er g
ivin
gco
nsen
t to
the
stu
dy s
itefo
r th
e re
gist
ratio
n of
av
aila
ble
retro
spec
tive
clin
ical
da
ta
(e.g
. U
HD
RS)
obta
ined
prio
r to
en
rolm
ent
in
REG
ISTR
Y (‘r
etro
spec
tive
clin
ical
dat
a re
cord
ed fr
om p
revi
ous
cons
ulta
tions
’).
3.3.
7St
udy
Obj
ectiv
esTh
e pr
imar
y go
al o
f R
EGIS
TRY
is t
o co
llect
pro
spec
tivel
y da
ta o
n th
e ph
enot
ypic
al c
hara
cter
istic
s of
HD
mut
atio
n ca
rrie
rs a
tall
stag
es (
incl
udin
g th
e pr
e-m
otor
man
ifest
phas
e)an
dof
indi
vidu
als
who
are
pa
rt of
an
HD
fam
ily ir
resp
ectiv
e of
thei
r mut
atio
n ca
rrie
r sta
tus,
in o
rder
to:
obta
in n
atur
al h
isto
ry d
ata
on a
wid
e sp
ectru
m o
f HD
pat
ient
s, H
D m
utat
ion
carr
iers
,ind
ivid
uals
who
ar
e pa
rt of
an
HD
fam
ilyin
clud
ing
non-
HD
mut
atio
n ca
rryi
ng c
ontro
lsre
late
phe
noty
pica
l cha
ract
eris
tics
with
oge
netic
dat
a (‘g
enet
ic m
odifi
ers’
), in
clud
ing
a hi
gh d
ensi
ty S
NP
map
of a
ll do
nors
,o
data
der
ived
from
the
stud
y of
bod
y flu
ids
(blo
od, u
rine
–‘w
et b
iom
arke
r’) a
ndo
imag
ing
data
(‘d
ry b
iom
arke
r’)
expe
dite
iden
tific
atio
n an
d re
crui
tmen
t of a
ppro
pria
te p
artic
ipan
ts fo
r clin
ical
tria
ls
deve
lop
and
valid
ate
sens
itive
and
relia
ble
outc
ome
mea
sure
s fo
r det
ectin
g on
set a
nd c
hang
e ov
er
the
natu
ral c
ours
eof
pre
man
ifest
and
man
ifest
HD
whi
ch m
ay a
lso
be p
oten
tial o
utco
me
mea
sure
s fo
r use
in fu
ture
clin
ical
tria
ls a
nd c
linic
al c
are.
plan
for f
utur
e re
sear
ch s
tudi
es (o
bser
vatio
nal a
nd in
terv
entio
nal t
rials
aim
ed a
t bet
ter s
ympt
omco
ntro
l or a
imed
at s
low
ing
or p
ostp
onin
g th
e on
set a
nd p
rogr
essi
on o
f HD
).
To a
chie
ve t
hese
obj
ectiv
es, p
artic
ipan
ts a
re a
sked
to
unde
rgo
clin
ical
, no
n-in
vasi
ve a
sses
smen
ts,t
o do
nate
bio
sam
ples
(blo
od a
nd u
rine)
for s
tudi
es to
iden
tify
gene
tic m
odifi
ers
of H
D a
nd to
est
ablis
h an
d va
lidat
e bi
olog
ical
mar
kers
tra
ckin
g th
e pr
ogre
ssiv
e co
urse
of
HD
; in
thi
s co
ntex
t,a
fam
ily h
isto
ry is
re
ques
ted
as w
ell i
n or
der
to u
nder
stan
d th
e re
latio
nshi
ps o
f cl
inic
al d
ata
sets
and
bio
sam
ples
fro
m
rela
ted
dono
rs. I
n ad
ditio
n, n
on-m
utat
ion
carr
ying
fam
ily m
embe
rs o
f par
ticip
ants
are
ask
ed to
con
side
r do
natin
g bi
osam
ples
to s
erve
as
cont
rols
.
3.3.
8St
udy
Popu
latio
nR
EGIS
TRY-
HD
par
ticip
ants
inc
lude
ind
ivid
uals
who
are
HD
gen
e m
utat
ion
carr
iers
reg
ardl
ess
of
whe
ther
they
dis
play
clin
ical
sym
ptom
s an
d si
gns
of th
e di
seas
e an
d fa
mily
mem
bers
who
are
eith
er a
t ris
k of
the
dise
ase
or w
ho h
ave
been
gen
etic
ally
test
ed a
nd a
re k
now
n no
t to
carr
y th
e ge
ne (c
onfir
med
no
n-m
utat
ion
carr
iers
).Par
ticip
ants
may
be
mal
e or
fem
ale.
Whi
lst
ther
e ar
e no
age
res
trict
ions
, al
l pa
rtici
pant
s m
ust e
ither
be
able
to p
rovi
de c
onse
nt o
r hav
e a
pare
nt/g
uard
ian
who
can
pro
vide
par
enta
l pe
rmis
sion
, or h
ave
an a
utho
rised
repr
esen
tativ
e w
ho c
an p
rovi
de c
onse
nt.
3.3.
9St
udy
Des
ign
REG
ISTR
Y-H
D p
artic
ipan
tsar
eas
sess
ed a
t bas
elin
e an
d an
nual
vis
its th
erea
fter
(eve
ry tw
o ye
ars
for
indi
vidu
als
who
are
pre
man
ifest
HD
gen
em
utat
ion
carr
iers
). At
eac
h vi
sit,
parti
cipa
nts
unde
rgo
clin
ical
, m
otor
, co
gniti
vean
dbe
havi
oura
las
sess
men
ts
as
wel
l as
do
natin
g bl
ood
and
urin
e sa
mpl
es.
REG
ISTR
Y as
sess
men
ts la
st b
etw
een
30 m
inut
es to
2.5
hour
s de
pend
ing
on th
e le
vel o
f ass
essm
ent
189Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
9
adm
inis
tere
d to
the
parti
cipa
nt.F
or R
EGIS
TRY-
HD
par
ticip
ants
, the
re a
re th
ree
leve
ls o
f as
sess
men
t va
ryin
g in
dep
th o
f eva
luat
ion.
Tab
le 2
a de
fines
whi
ch a
sses
smen
ts fa
ll in
to e
ach
leve
l (m
inim
um, c
ore
and
exte
nded
).In
add
ition
, par
ticip
ants
are
invi
ted
to ta
ke p
art i
n op
tiona
l com
pone
nts
for
REG
ISTR
Y(d
escr
ibed
in m
ore
deta
il in
Sec
tion
6).
REG
ISTR
Y-C
ON
TRO
L pa
rtici
pant
s ar
eas
sess
ed a
t ba
selin
e an
d m
ay b
e fo
llow
ed p
rosp
ectiv
ely
with
ann
ual
visi
ts.
The
asse
ssm
ents
for
REG
ISTR
Y-C
ON
TRO
L pa
rtici
pant
s fa
ll in
to e
ither
a m
inim
um o
r ex
tend
ed le
vel o
f as
sess
men
t(s
ee T
able
2c)
. R
EGIS
TRY-
CO
NTR
OL
parti
cipa
nts
are
invi
ted
to ta
ke p
art i
n op
tiona
l com
pone
nts
for R
EGIS
TRY.
Tabl
e 2a
:REG
ISTR
Y-H
D A
sses
smen
t Bat
tery
Min
imum
Cor
eEx
tend
edO
ptio
nal*
Gen
eral
/Clin
ical
Info
rmed
con
sent
Pseu
dony
mis
atio
nH
isto
ry (m
edic
al, d
isea
se, p
sych
iatri
c)D
emog
raph
ics
(Fix
ed &
Var
iabl
e)C
omor
bid
cond
ition
sC
onco
mita
nt m
edic
atio
nC
AG re
port
(Loc
al L
abor
ator
y)En
d of
stu
dyFa
mily
His
tory
Mot
or/F
unct
ion
UH
DR
S '9
9 M
otor
UH
DR
S ’9
9 Fu
nctio
n (T
otal
Fun
ctio
nal
Cap
acity
, Fun
ctio
n As
sess
men
t Sca
le,
Inde
pend
ence
Sca
le)
UH
DR
S ’9
9 S
umm
ary
Glo
bal C
linic
al Im
pres
sion
Beh
avio
ur
UH
DR
S '9
9 Be
havi
our /
Pro
blem
Be
havi
ours
Ass
essm
ent-S
hort
(PBA
-s)
Hos
pita
l Anx
iety
/ Dep
ress
ion
Rat
ing
Scal
e (H
ADS)
Snai
th Ir
ritab
ility
Scal
e (S
IS)
Col
umbi
aSu
icid
e S
ever
ity R
atin
g Sc
ale
Cog
nitiv
eBr
ief C
ogni
tive
Exte
nded
Cog
nitiv
e H
ealth
Eco
nom
ics
Clie
nt S
ervi
ces
Rec
eipt
Inve
ntor
yQ
ualit
y of
Life
SF-3
6B
iosa
mpl
es30
ml b
lood
, 30
ml u
rine
*Opt
iona
l com
pone
nts
requ
ire e
xplic
it in
form
ed c
onse
nt.
10
Tabl
e 2b
: REG
ISTR
Y-C
OM
PAN
ION
Ass
essm
ent B
atte
ry
Info
rmed
con
sent
Qua
lity
of L
ifeC
areg
iver
que
stio
nnai
re
Tabl
e 2c
: REG
ISTR
Y-C
ON
TRO
LA
sses
smen
t Bat
tery
Min
imum
Exte
nded
Opt
iona
l*
Gen
eral
/Clin
ical
Info
rmed
con
sent
Pseu
dony
mis
atio
nPa
st M
edic
al H
isto
ryD
emog
raph
ics
(Fix
ed &
Var
iabl
e)C
omor
bid
cond
ition
sC
onco
mita
nt m
edic
atio
nEn
d of
stu
dyM
otor
/Fun
ctio
nG
ener
al n
euro
logi
cal a
sses
smen
t
Beh
avio
urU
HD
RS
'99
Beha
viou
r / P
robl
emBe
havi
ours
Ass
essm
ent-S
hort
(PBA
-s)
Cog
nitiv
eBr
ief C
ogni
tive
Exte
nded
Cog
nitiv
e B
iosa
mpl
es20
ml b
lood
, 30
ml u
rine
*Opt
iona
l com
pone
nts
requ
ire e
xplic
it in
form
ed c
onse
nt.
REG
ISTR
Y-H
D,
CO
MPA
NIO
N,
and
CO
NTR
OL
parti
cipa
nts
are
invi
ted
to
parti
cipa
te
in
nove
l as
sess
men
ts (
sub-
stud
ies)
in
addi
tion
to t
he a
sses
smen
t ba
tterie
s ou
tline
d in
Tab
les
2a-c
. Fu
rther
de
tails
are
list
ed in
the
Sum
mar
y of
REG
ISTR
Y Su
b-st
udie
san
d a
desc
riptio
n of
this
com
pone
nt c
an b
e fo
und
in S
ectio
n 6.
7.
3.4
Qua
lity
Con
trol
and
Qua
lity
Ass
uran
ce
To o
btai
n op
timal
dat
a qu
ality
and
reac
h th
e hi
ghes
t sta
ndar
ds o
f rel
iabi
lity,
REG
ISTR
Y is
mon
itore
d on
th
e ba
sis
of th
e pr
inci
ples
of G
ood
Clin
ical
Pra
ctic
e (G
CP)
acc
ordi
ng to
Inte
rnat
iona
l Con
fere
nce
on
Har
mon
isat
ion
(ICH
) gui
delin
es:
a)th
e rig
hts
and
wel
l-bei
ng o
f hum
an s
ubje
cts
are
prot
ecte
db)
the
repo
rted
data
are
acc
urat
e, c
ompl
ete
and
verif
iabl
e fro
m s
ourc
e da
tac)
the
cond
uct o
f the
tria
l is
in c
ompl
ianc
e w
ith th
e cu
rren
tly a
ppro
ved
prot
ocol
/am
endm
ents
and
th
e ap
plic
able
regu
lato
ry re
quire
men
ts (
EC20
01/2
0/E
C &
Dire
ctiv
es)
Qua
lity
assu
ranc
e(Q
A)re
fers
to
th
e pr
oced
ures
pu
t in
pl
ace
to
ensu
re
qual
ity,
whe
reas
qu
ality
cont
rol(
QC
) ref
ers
to th
e ev
alua
tion
of th
e ef
fect
iven
ess
of th
ose
proc
edur
es. T
he k
ey d
istin
ctio
n is
bet
wee
n pr
epar
ing
for
qual
ity i
n th
e st
udy
(QA)
and
che
ckin
g fo
r qu
ality
of
data
col
lect
ed (
QC
).In
vest
igat
ors’
mee
tings
, tra
inin
g an
d ex
tens
ive
writ
ten
guid
elin
es a
nd S
OPs
and
help
tex
ts a
nd
plau
sibi
lity
chec
ks b
uilt
into
the
ele
ctro
nic
Cas
e R
epor
t Fo
rm (
eCR
F) a
re p
ut i
n pl
ace
to e
nsur
e ap
prop
riate
con
duct
of t
he s
tudy
.
190 Hygeia Public Health 2011, 46(2): 183-218
11
QC
will
be
hand
led
by E
HD
N-a
ppoi
nted
dat
a m
onito
rs w
ith s
ite v
isits
to
ensu
re t
hat
proc
edur
es a
re
bein
g fo
llow
ed,
incl
udin
g ch
ecki
ng o
n-si
te a
sses
smen
ts,
givi
ng f
eedb
ack
to s
ites
and
ensu
ring
up-to
-da
te tr
aini
ng a
nd a
ccre
dita
tion.
Cen
tral c
heck
ing
of d
ata
for c
ompl
eten
ess
and
plau
sibi
lity
at th
e le
vel o
f th
e da
ta r
epos
itory
is in
pla
ce.
Site
s ar
e m
onito
red
at le
ast
annu
ally
to
chec
k so
urce
doc
umen
ts (
i.e.
info
rmed
con
sent
, dat
e of
birt
h, g
ende
r,m
edic
al h
isto
ry, g
enet
ic te
st re
sults
).
EHD
N h
as d
efin
ed a
REG
ISTR
Y m
onito
ring
plan
and
SOPs
whi
ch in
clud
egu
idel
ines
for t
he c
ondu
ct o
f hi
gh q
ualit
y ep
idem
iolo
gica
l re
sear
ch.
The
mon
itorin
g pl
an d
etai
ls t
heda
ta m
onito
ring
proc
ess
by
defin
ing
key
info
rmat
ion
rega
rdin
g eC
RF
com
plet
ion,
Sou
rce
Dat
a Ve
rific
atio
n, s
tudy
pro
cedu
res
and
the
data
flow
pro
cess
.
3.5
Dat
a st
orag
e an
d se
curit
yPa
rtici
pant
data
are
ent
ered
afte
r cr
eatin
g a
uniq
ue p
seud
onym
for
eac
h pa
rtici
pant
, ba
sed
on
unch
angi
ng i
nfor
mat
ion
(dat
e of
birt
h, b
irth
nam
e, p
lace
of
birth
and
mot
her’s
mai
den
nam
e).
The
pseu
dony
m
is
a ni
ne
figur
e nu
mbe
r cr
eate
d by
a
secu
re
one-
way
al
gorit
hm,
e.g.
: C
hris
tine
Mus
term
ann,
Dat
e of
Birt
h: 1
3 Ap
ril 1
964,
Pla
ce o
f B
irth:
Ber
lin,
Birt
h na
me:
Mai
er;
Mot
her´
s m
aide
n na
me:
Sch
mid
t. Th
ese
data
giv
e th
e ps
eudo
nym
: 3
44-2
59-1
92.
Mor
e de
tails
are
giv
en i
n th
e da
ta
secu
rity
info
rmat
ion
shee
t (pl
ease
see
App
endi
x B)
.The
iden
tifyi
ng d
ata
are
neve
r sto
red
elec
troni
cally
on th
e R
EGIS
TRY
web
porta
l. T
he in
vest
igat
or m
ust s
tore
the
orig
inal
dat
a an
d th
e ps
eudo
nym
in th
e so
urce
doc
umen
ts (p
atie
nt fi
le) a
nd in
the
inve
stig
ator
file
.
3.6
Dat
a flo
wD
ata
and
bios
ampl
es w
ill be
sto
red,
che
cked
and
mon
itore
d ce
ntra
lly b
y ap
poin
ted
data
rep
osito
ries
and
mon
itors
.
3.7
Org
anis
atio
nTh
e Pr
inci
pal I
nves
tigat
or(P
I)is
Pro
f G. B
ernh
ard
Land
weh
rmey
er, U
lm, G
erm
any
who
als
o is
hea
d of
a
Cen
tral C
oord
inat
ion
team
and
Chi
ef E
xecu
tive
Offi
cer
of t
he E
HD
N.
The
Co-
Prin
cipl
e In
vest
igat
or
(Co-
PI) i
s D
r Sar
ah T
abriz
i, Lo
ndon
, UK.
The
REG
ISTR
Y St
eerin
g C
omm
ittee
(mem
ber l
ist i
s av
aila
ble
in A
ppen
dix
A an
d w
ww
.eur
o-hd
.net
/htm
l/reg
istry
/ste
erin
g) i
s re
spon
sibl
e fo
r fin
alis
ing
the
stud
y pr
otoc
ol.
Cen
tral C
oord
inat
ion
is r
espo
nsib
le f
or im
plem
entin
g th
e pr
otoc
olan
d lia
isin
g w
ith s
ites
and
othe
r age
ncie
s (d
ata
repo
sito
ries,
dat
a m
onito
rs, e
xper
t adv
isor
s) to
ens
ure
that
the
stud
y ca
n be
run
at
all
site
s.W
here
app
ropr
iate
, th
e R
EGIS
TRY
Stee
ring
Com
mitt
eere
ceiv
esex
pert
advi
ce f
rom
the
re
spec
tive
Lead
Fac
ilita
tor o
f eac
h EH
DN
Wor
king
Gro
up.
form
ulat
ing
the
prot
ocol
for t
he s
tudy
,
The
PIof
REG
ISTR
Yis
resp
onsi
ble
for:
orga
nisi
ng th
e st
eerin
g co
mm
ittee
for t
hest
udy,
secu
ring
adeq
uate
spo
nsor
ship
and
sup
port
for
the
trial
and
ens
urin
g an
app
ropr
iate
fun
ding
m
echa
nism
, su
bcon
tract
ing,
thr
ough
his
or
her
inst
itutio
n, w
ith t
he p
artic
ipat
ing
inve
stig
ator
s an
d th
eir
inst
itutio
ns,
subc
ontra
ctin
g, th
roug
h hi
s or
her
inst
itutio
n, fo
r tria
l coo
rdin
atio
n se
rvic
es,
as a
ppro
pria
te, o
rgan
isin
g st
udy
subc
omm
ittee
s to
ass
ist i
n th
e pl
anni
ng a
nd im
plem
enta
tion
of
the
trial
. ov
erse
eing
the
impl
emen
tatio
n, a
nd s
uper
visi
ng th
e an
alys
is a
nd re
porti
ng fo
r the
stu
dy, a
nd
toge
ther
with
the
stee
ring
com
mitt
ee, t
he a
ccur
acy
of th
e da
ta c
olle
cted
in th
e st
udy.
The
Co-
PIof
REG
ISTR
Yas
sist
sth
e PI
in c
arry
ing
out
thes
e re
spon
sibi
litie
s an
d as
sum
esth
e re
spon
sibi
litie
s of
th
e PI
in
the
even
t th
at
the
PIis
ab
sent
or
in
capa
cita
ted.
REG
ISTR
Y St
eerin
g C
omm
ittee
is re
spon
sibl
e fo
r:
12
sele
ctin
g si
te
inve
stig
ator
s fo
r th
e st
udy,
an
d fo
r as
sist
ing
the
PI
and
Co-
PIin
th
e im
plem
enta
tion,
ana
lysi
s an
d re
porti
ng o
f the
stu
dy re
sults
. re
mov
ing
from
act
ive
stud
y pa
rtici
patio
n an
y st
eerin
g co
mm
ittee
mem
bers
, in
vest
igat
ors
or
othe
r stu
dy p
erso
nnel
who
doe
s no
t ful
filhi
s/he
r obl
igat
ions
to th
e tri
al o
r who
doe
s no
t mai
ntai
n th
e st
anda
rds
of E
HD
N w
ith r
espe
ct to
con
fiden
tialit
y, p
rofe
ssio
nal c
ondu
ct, r
ight
s of
res
earc
h su
bjec
ts, c
onfli
ct-o
f-int
eres
t, di
sclo
sure
or p
ublic
atio
n po
licie
s.Al
l EH
DN
ste
erin
g co
mm
ittee
s w
ill al
so e
nsur
e th
at t
rial
polic
ies
gove
rnin
g co
nfid
entia
lity,
hu
man
par
ticip
ants
, cl
inic
al p
ract
ice,
con
flict
-of
inte
rest
and
pub
licat
ion
are
cons
iste
nt w
ith
polic
ies
cont
aine
d in
this
EH
DN
con
stitu
tion.
191Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
13
4ET
HIC
S
4.1
Inst
itutio
nal R
evie
w B
oard
or I
ndep
ende
nt E
thic
s C
omm
ittee
Th
e Si
te In
vest
igat
or w
ill pr
ovid
e th
e IR
B/IE
C w
ith a
ll ap
prop
riate
mat
eria
l, in
clud
ing
the
prot
ocol
, the
in
form
ed c
onse
nt d
ocum
ent,
and
othe
r w
ritte
n in
form
atio
n pr
ovid
ed t
o th
e pa
rtici
pant
s.Th
e st
udy
will
not b
e in
itiat
ed u
ntil
appr
opria
te IR
B/IE
C a
ppro
val o
f the
pro
toco
l and
the
info
rmed
con
sent
doc
umen
t an
d al
l re
crui
ting
mat
eria
ls a
re o
btai
ned
in w
ritin
g by
Site
Inv
estig
ator
. IR
B/IE
C a
ppro
val
will
be
obta
ined
for
any
pro
toco
l am
endm
ents
and
inf
orm
ed c
onse
nt r
evis
ions
bef
ore
impl
emen
ting
the
chan
ges.
4.2
Ethi
cal C
ondu
ctof
the
Stud
yTh
is s
tudy
will
be c
ondu
cted
und
er th
e pr
inci
ples
of t
he W
orld
Med
ical
Ass
ocia
tion
(WM
A) D
ecla
ratio
n of
Hel
sink
i un
der
its m
ost
rece
nt a
men
dmen
t (b
y th
e 52
nd W
MA
Gen
eral
Ass
embl
y, E
dinb
urgh
,Sc
otla
nd,
Oct
ober
200
0, w
ith a
Not
e of
Cla
rific
atio
n on
Par
agra
ph 2
9 ad
ded
by t
he W
MA
Gen
eral
As
sem
bly,
Was
hing
ton
2002
and
on
Para
grap
h 30
add
ed b
y th
e W
MA
Gen
eral
Ass
embl
y, T
okyo
200
4,
and
incl
udin
g IC
H-G
CP
guid
elin
es).
Spe
cific
ally
, the
stu
dy w
ill be
con
duct
ed u
nder
a p
roto
col r
evie
wed
an
d ap
prov
ed b
y an
IR
B/IE
C;
the
stud
y w
ill be
con
duct
ed b
y sc
ient
ifica
lly a
nd m
edic
ally
qua
lifie
d pe
rson
s; th
e be
nefit
s of
the
stud
y ar
e in
pro
porti
on to
the
risks
; the
righ
ts a
nd w
elfa
re o
f the
par
ticip
ants
will
be re
spec
ted;
the
phys
icia
ns c
ondu
ctin
g th
e st
udy
do n
ot fi
nd th
e ha
zard
s to
out
wei
gh th
e po
tent
ial
bene
fits;
eac
h pa
rtici
pant
will
give
his
or
her
writ
ten,
info
rmed
con
sent
bef
ore
any
prot
ocol
-driv
en te
sts
or e
valu
atio
ns a
re p
erfo
rmed
.
4.3
Part
icip
antI
nfor
mat
ion
and
Info
rmed
Con
sent
A pr
oper
ly e
xecu
ted,
writ
ten,
info
rmed
con
sent
, in
com
plia
nce
with
the
Dec
lara
tion
of H
elsi
nki,
ICH
-G
CP,
and
loca
l reg
ulat
ions
, will
be o
btai
ned
from
eac
h pa
rtici
pant
prio
r to
ent
erin
g th
e pa
rtici
pant
into
th
e st
udy.
The
Site
Inve
stig
ator
will
keep
the
orig
inal
sig
ned
info
rmed
con
sent
and
plac
e a
copy
of i
t in
the
parti
cipa
nt’s
rec
ord
file.
The
Site
Inv
estig
ator
will
pro
vide
cop
ies
of t
he s
igne
d in
form
ed c
onse
nt
form
to e
ach
parti
cipa
ntan
d ca
regi
ver (
or th
e pa
rtici
pant
’s le
gal r
epre
sent
ativ
e).
The
parti
cipa
nts
will
be in
form
ed a
bout
the
natu
re a
nd im
porta
nce
of th
e st
udy;
they
will
rece
ive
a br
ief
desc
riptio
n of
the
for
esee
able
ris
ks a
nd d
isco
mfo
rts a
nd a
sho
rt de
scrip
tion
of t
he p
roce
dure
s to
be
follo
wed
. Th
e pa
rtici
pant
s w
ill be
info
rmed
tha
t th
ey a
re f
ree
to w
ithdr
aw f
rom
the
stu
dy a
t an
y tim
e w
ithou
t any
dis
adva
ntag
es. P
rior
to th
e st
art o
f the
stu
dy th
e pa
rtici
pant
s w
ill ag
ree
to th
e pa
rtici
patio
n in
the
stud
y by
sig
ning
the
info
rmed
con
sent
form
.
Volu
ntar
y w
ritte
n in
form
ed c
onse
nt w
ill be
obt
aine
d fro
m e
ach
parti
cipa
nt a
t scr
eeni
ng p
rior t
o an
y st
udy
rela
ted
proc
edur
es. E
ach
parti
cipa
ntsh
ould
be
give
n bo
th v
erba
l and
writ
ten
info
rmat
ion
(in a
lang
uage
th
at is
und
erst
anda
ble
to th
e pa
rtici
pant
) des
crib
ing
the
mea
ning
, aim
and
con
duct
of t
he s
tudy
. Thi
s w
ill
take
pla
ce u
nder
con
ditio
ns w
here
the
parti
cipa
nt h
as a
dequ
ate
time
to c
onsi
der
the
risks
and
ben
efits
as
soci
ated
with
his
par
ticip
atio
n in
the
stud
y. T
he p
artic
ipan
ts w
ill ha
ve th
e op
portu
nity
to a
sk a
ll th
eir
ques
tions
. The
con
sent
will
be
sign
ed a
nd d
ated
by
the
parti
cipa
ntan
d th
e pe
rson
who
con
duct
ed th
e in
form
ed c
onse
nt d
iscu
ssio
n.
It is
the
res
pons
ibilit
y of
the
inv
estig
ator
to
assu
re t
hat
info
rmed
con
sent
is
obta
ined
fro
m e
ach
parti
cipa
nt in
acc
orda
nce
with
Cha
pter
4.8
of t
he IC
H c
onso
lidat
ed g
uide
line
for
Goo
d C
linic
al P
ract
ice
from
Jul
y 19
96,
and
loca
l re
gula
tions
. Th
e si
gned
inf
orm
ed c
onse
nt w
ill be
ret
aine
d w
ith t
he s
tudy
re
cord
s. E
ach
parti
cipa
nt w
ill re
ceiv
e a
copy
of t
he s
igne
d in
form
ed c
onse
nt.
4.4
Inve
stig
ator
Obl
igat
ions
The
Site
Inve
stig
ator
(SI
) agr
ees
to c
ondu
ct th
ecl
inic
al s
tudy
in c
ompl
ianc
e w
ith th
e pr
otoc
ol. T
he S
ite
Inve
stig
ator
and
the
Spo
nsor
sho
uld
sign
a R
EGIS
TRY
stud
y su
bcon
tract
with
the
spon
sor
to c
onfir
m
this
agr
eem
ent.
The
SIco
nfirm
s th
at h
e/sh
e ha
s re
ad t
he e
ntire
stu
dy p
roto
col,
has
unde
rsto
od t
he
proc
edur
es, a
nd w
ill co
mpl
y st
rictly
to
the
form
ulat
ed g
uide
lines
.Th
e SI
at e
ach
site
mus
t pro
vide
on
requ
est
to C
entra
l C
oord
inat
ion
a cu
rren
t cu
rric
ulum
vita
e an
d co
pies
of
cred
entia
ls (
e.g.
med
ical
lic
ense
).
14
The
SI is
resp
onsi
ble
for t
he a
dequ
ate
med
ical
car
e of
the
parti
cipa
nt d
urin
g th
e st
udy.
The
Inve
stig
ator
m
ust
follo
w I
CH
-GC
P G
uide
lines
and
is
resp
onsi
ble
for
the
safe
ty a
nd t
he m
edic
al c
are
of t
he
parti
cipa
nt.
The
SIm
ust k
eep
a co
nfid
entia
l lis
t of
parti
cipa
nts,
whi
ch r
egis
ter
the
pseu
dony
m o
f th
epa
rtici
pant
s,
parti
cipa
nts’
nam
es a
nd a
ddre
sses
, and
thei
r dat
es o
f birt
h to
iden
tify
each
par
ticip
anta
t any
tim
e. T
he
inve
stig
ator
als
o m
akes
sur
e th
at t
he c
onfid
entia
lity
of p
artic
ipan
t’s d
ata
will
be r
espe
cted
and
gu
aran
teed
by
all e
mpl
oyee
s of
the
stud
y ce
ntre
.
The
SIag
rees
that
the
stud
y m
ight
be
supe
rvis
ed b
y a
mon
itor d
esig
nate
d by
the
Spon
sor.
In th
is c
ase,
th
e SI
unde
rtake
s to
sup
ply
all o
f the
nec
essa
ry b
ackg
roun
d in
form
atio
n re
late
d to
his
/her
rec
ords
on
requ
est t
o he
lp th
e m
onito
r mak
e a
reas
onab
le a
sses
smen
t of t
he c
ours
e of
the
stud
y. T
he S
Idec
lare
s hi
mor
her
self
read
y to
ass
ist
the
mon
itor
in s
olvi
ng a
ll pr
oble
ms,
whi
ch a
re r
evea
led
durin
g th
e m
onito
ring
visi
t. In
the
eve
nt o
f a
chec
k, a
udit,
or
insp
ectio
n, t
he S
Iw
ill m
ake
all
nece
ssar
y da
ta
avai
labl
e to
the
Spo
nsor
, mon
itor,
audi
tor,
or th
e co
mpe
tent
aut
horit
ies.
The
SIha
s th
e rig
ht t
o re
ques
t to
end
the
stu
dy p
rem
atur
ely
beca
use
of a
dmin
istra
tive
or o
ther
ci
rcum
stan
ces.
If th
is s
houl
d oc
cur,
proc
edur
es m
ust b
e es
tabl
ishe
d in
con
sulta
tion
with
thos
e in
volv
ed
whi
ch g
uara
ntee
that
the
inte
rest
s an
d he
alth
-rel
ated
wel
l-bei
ng o
f the
par
ticip
atio
n pa
rtici
pant
s re
mai
n sa
fegu
arde
d as
far a
s po
ssib
le.
The
SIor
his
/her
med
ical
ly e
duca
ted
repr
esen
tativ
e w
ill re
view
the
CR
F fo
r com
plet
enes
s an
d ac
cura
cy
and
will
sig
n th
e co
mpl
eted
CR
F an
d an
y ch
ange
s in
the
CR
F.
The
sign
atur
es s
erve
to a
ttest
that
the
info
rmat
ion
cont
aine
d on
the
CR
F is
tru
e an
d ha
s no
t be
en f
alsi
fied.
In
case
of
maj
or c
orre
ctio
n th
e re
ason
for
it s
hall
also
be
give
n. I
t is
the
SI’s
res
pons
ibili
ty t
o as
sure
com
plet
ion
and
to r
evie
w a
nd
appr
ove
all C
RFs
. A
t al
l tim
es t
he S
Iha
s fin
al r
espo
nsib
ility
for
the
accu
racy
and
aut
hent
icity
of
all
clin
ical
and
labo
rato
ry d
ata
ente
red
in th
e C
RF.
192 Hygeia Public Health 2011, 46(2): 183-218
15
5A
DM
INIS
TRA
TIVE
STR
UC
TUR
ETh
e st
udy
will
be
adm
inis
tere
d by
and
mon
itore
d by
em
ploy
ees
or r
epre
sent
ativ
es o
f EH
DN
. C
linic
al
Res
earc
h As
soci
ates
will
mon
itor
the
stud
y si
te o
n a
perio
dic
basi
s an
d pe
rform
ver
ifica
tion
of s
ourc
e do
cum
enta
tion
for e
ach
parti
cipa
nt.
5.1
Adm
inis
trat
ive
resp
onsi
bilit
ies
Aco
ntra
ct w
ill b
e is
sued
to re
gula
te th
e ob
ligat
ions
and
righ
ts o
f the
inve
stig
ator
and
the
resp
onsi
bilit
ies
of t
he R
EGIS
TRY
stud
yco
ordi
natio
n in
clud
ing
the
spon
sors
; th
e co
ntra
ct w
ill be
sig
ned
betw
een
auth
oris
ed r
epre
sent
ativ
es o
f th
e re
spec
tive
inst
itutio
ns w
ith w
hich
the
inve
stig
ator
s ar
e af
filia
ted
and
REG
ISTR
Y tri
al c
oord
inat
ion
repr
esen
ted
for
the
time
bein
g by
the
Uni
vers
ity H
ospi
tal
of U
lm
Uni
vers
ity.
The
spon
sor o
f the
REG
ISTR
Y st
udy
is th
e EH
DN
, fun
ded
byC
HD
I Fou
ndat
ion,
Inc.
The
REG
ISTR
Y St
eerin
g C
omm
ittee
is r
espo
nsib
le f
or o
vers
eein
g th
e m
onito
ring
and
data
QC
proc
edur
es. C
entra
l Coo
rdin
atio
n of
EH
DN
is r
espo
nsib
le fo
r th
e ex
ecut
ion
of m
onito
ring
acco
rdin
g to
th
e pr
inci
ples
of G
ood
Clin
ical
Pra
ctic
e (G
CP)
and
for s
uppl
ying
trai
ned
pers
onne
lfor
this
pur
pose
.The
R
egis
try S
teer
ing
Com
mitt
eeis
res
pons
ible
for
prom
otin
g in
clus
ion
into
REG
ISTR
Y an
d fo
r de
velo
ping
th
e pr
otoc
ol o
f th
e R
EGIS
TRY
stud
y fu
rther
(e.
g. b
y co
nsid
erin
g ad
ditio
nal
com
pone
nts
like
MR
I im
agin
g) a
nd b
y m
akin
g de
cisi
ons
on th
e bi
osam
ples
col
lect
ed in
futu
re fo
llow
up
visi
ts.
Acce
ss t
o th
e cl
inic
al d
atab
ase
and
to t
he b
iosa
mpl
es i
s re
gula
ted
by t
he p
olic
ies
of E
HD
N (
see
ww
w.e
uro-
hd.n
et/h
tml/n
etw
ork/
proj
ect/c
onst
itutio
n/do
c).
In b
rief,
rese
arch
ers
inte
rest
ed i
n ob
tain
ing
bios
ampl
es fo
r fu
rther
ana
lysi
s ha
ve to
sub
mit
brie
f out
lines
of t
heir
HD
rel
ated
res
earc
h pr
ojec
t to
the
Scie
ntifi
c an
d B
ioet
hica
l Adv
isor
y B
oard
(SB
AC)o
f EH
DN
. The
SBA
Cw
ill as
sess
whe
ther
the
prop
osed
pr
ojec
t fa
lls w
ithin
the
sub
ject
are
a to
whi
ch p
artic
ipan
ts g
ave
thei
r in
form
ed c
onse
nt (
i.e.
stud
ies
to
iden
tify
gene
tic m
odifi
ers
of H
D a
nd to
est
ablis
h an
d va
lidat
e bi
olog
ical
mar
kers
for
HD
) an
d w
heth
er
the
prop
osal
is e
thic
ally
and
sci
entif
ical
ly s
ound
. Onc
e a
proj
ect i
s ap
prov
ed b
y th
e SB
AC, t
he p
ropo
ser
has
to c
onfir
m in
writ
ing
to c
ompl
y w
ith th
e da
ta a
cces
s an
d pu
blic
atio
n po
licy
of E
HD
N a
nd w
ill pr
ovid
e a
shor
t abs
tract
on
the
appr
oved
pro
posa
l for
dis
play
at t
he E
HD
N w
eb p
orta
l. R
esea
rche
rs c
ondu
ctin
g an
app
rove
d pr
ojec
t will
then
be
gran
ted
acce
ss to
exp
lore
a re
code
d ex
cerp
t of t
he c
linic
al d
atab
ase
of
EHD
N fo
r se
lect
ion
of a
ppro
pria
te s
ampl
es b
ased
on
phen
otyp
ical
cha
ract
eris
tics
as w
ell a
s Bi
oRep
’s
data
base
to
expl
ore
avai
labi
lity
of s
ampl
es.
The
data
base
to
whi
ch t
he r
esea
rche
s co
nduc
ting
an
appr
oved
pro
ject
is g
rant
ed a
cces
s is
reco
ded
in o
rder
to (1
) con
trol f
or d
oubl
e pu
blic
atio
n of
the
sam
e da
ta s
ets
and
(2) t
o av
oid
that
rese
arch
ers
reco
gnis
e da
ta s
ets
as th
eir o
wn
cont
ribut
ion.
In p
aral
lel a
nd
prio
r to
the
rele
ase
of s
ampl
es c
onfir
mat
ion
is s
ough
t fro
m th
e re
spec
tive
lead
ing
natio
nal I
EC
that
no
obje
ctio
ns a
re ra
ised
aga
inst
the
asse
ssm
ent b
y th
e S
BAC
of E
HD
N th
at th
e pr
opos
ed re
sear
ch p
roje
ct
falls
with
in th
e su
bjec
t are
ato
whi
ch p
artic
ipan
ts g
ave
thei
r inf
orm
ed c
onse
nt.
5.2
Stud
y M
anag
emen
tTa
ble
3sh
ows
the
role
s an
d re
spon
sibi
litie
s de
sign
ated
to o
rgan
isat
ions
alre
ady
invo
lved
in th
e st
udy.
16
Rol
e
Tabl
e 3:
Stu
dy m
anag
emen
t rol
es a
nd re
spon
sibi
litie
s
Res
pons
ibili
tyPr
ojec
t man
agem
ent &
pla
nnin
gC
entra
l Coo
rdin
atio
nR
EGIS
TRY
Stee
ring
Com
mitt
eeR
egul
ator
y do
cum
ents
(IR
B)C
entra
l Coo
rdin
atio
nLa
ngua
ge C
oord
inat
ion
Con
duct
ing
inve
stig
ator
mee
tings
Cen
tral C
oord
inat
ion
Lang
uage
Coo
rdin
atio
nTr
aini
ng o
f per
sonn
elC
entra
l Coo
rdin
atio
nLa
ngua
ge C
oord
inat
ion
Site
iden
tific
atio
n an
d se
lect
ion
Cen
tral C
oord
inat
ion
Lang
uage
Coo
rdin
atio
nR
EGIS
TRY
Stee
ring
Com
mitt
eeIn
itiat
ion
visi
tsLa
ngua
ge C
oord
inat
ion
Mon
itorin
g vi
sits
EHD
N M
onito
rsM
anag
emen
t of l
abor
ator
y sa
mpl
esBi
oRep
Qua
lity
assu
ranc
eC
entra
l Coo
rdin
atio
nBi
oRep
193Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
17
6D
ETA
ILED
STU
DY
DES
CR
IPTI
ON
6.1
Bac
kgro
und
and
ratio
nale
HD
is
an
au
toso
mal
-dom
inan
tly
inhe
rited
, pr
ogre
ssiv
e ne
urod
egen
erat
ive
diso
rder
ch
arac
teris
ed
clin
ical
ly
by
a m
ovem
ent
diso
rder
(ty
pica
lly
chor
ea),
beha
viou
ral
dist
urba
nces
, an
d co
gniti
ve
impa
irmen
t. Th
e cl
inic
al f
eatu
res
of H
D u
sual
ly e
mer
ge i
n ad
ulth
ood
(mea
n ag
e of
37
year
s),
afte
r w
hich
illn
ess
prog
ress
es s
tead
ily o
ver a
per
iod
of 1
5-25
yea
rs. B
y im
plic
atio
n, g
enet
ic te
stin
g (p
rece
ded
by g
enet
ic c
ouns
ellin
g ac
cord
ing
to in
tern
atio
nally
acc
epte
d gu
idel
ines
) al
low
s to
det
erm
ine
whe
ther
a
clin
ical
ly n
orm
al p
erso
n ha
rbou
rs th
e H
D m
utat
ion
and
thus
pre
dict
that
a p
erso
n w
ill de
velo
p H
D b
efor
e cl
inic
al s
ympt
oms
and
sign
s de
velo
p. H
D h
as a
pre
vale
nce
of 5
-10
per
100,
000
in t
he g
ener
al
popu
latio
n of
the
Wes
tern
hem
isph
ere.
HD
affe
cts
at l
east
40,
000
peop
le l
ivin
g in
Eur
ope
(1).
In
addi
tion,
est
imat
ed 8
0,00
0 in
divi
dual
s ca
rry
the
HD
mut
atio
n bu
t rem
ain
yet u
naffe
cted
. HD
is c
ause
d by
an
expa
nsio
n of
a c
ytos
ine-
aden
ine-
guan
ine
(CAG
) tri
nucl
eotid
e re
peat
stre
tch
in e
xon
1 of
the
HD
ge
ne o
n ch
rom
osom
e 4
(2).
Indi
vidu
als
who
hav
e an
d si
gns
of H
D in
clud
ing
mot
or, c
ogni
tive
and
beha
viou
ral a
bnor
mal
ities
that
cau
se a
pro
gres
sive
loss
of
fun
ctio
nal c
apac
ity a
nd s
horte
n lif
e. T
he c
ours
e of
HD
is r
elen
tless
; to
dat
e, t
here
is n
o tre
atm
ent
whi
ch h
as b
een
show
n to
alte
r the
pro
gres
sion
of t
he d
isea
se.
Sinc
e th
e ge
ne m
utat
ion
resp
onsi
ble
for
HD
was
iden
tifie
d in
199
3, c
onsi
dera
ble
prog
ress
has
bee
n m
ade
in u
nder
stan
ding
the
path
ogen
esis
of t
his
diso
rder
and
in id
entif
ying
targ
ets
for p
oten
tial t
hera
pies
m
odify
ing
the
natu
ral c
ours
e of
the
dise
ase
(3).
Sys
tem
atic
scr
eeni
ng e
fforts
to id
entif
y co
mpo
unds
with
di
seas
e m
odify
ing
prop
ertie
s ar
e un
der w
ay (4
, 5)a
nd s
ome
com
poun
ds h
ave
been
repo
rted
to re
sult
in
bene
ficia
l effe
cts
whe
n ap
plie
d in
mod
el s
yste
ms
ofH
D(6
)th
us p
rovi
ding
a r
atio
nal f
or id
entif
ying
wel
l to
lera
ted
and
clin
ical
effe
ctiv
e no
vel t
reat
men
ts fo
r HD
. How
ever
, cur
rent
ly th
e pr
edic
tive
valu
e of
thes
e pr
omis
ing
resu
lts o
btai
ned
inm
odel
sys
tem
s fo
r H
D p
atie
nts
are
unkn
own.
In
addi
tion,
inc
rem
enta
l ad
vanc
es i
n cl
inic
al r
esea
rch
on H
D h
ave
been
mad
e. D
espi
te t
hese
adv
ance
s, a
mor
e se
amle
ss
inte
grat
ion
of b
asic
, tra
nsla
tiona
l and
clin
ical
HD
rese
arch
is re
quire
d to
pla
n an
d co
nduc
t fut
ure
clin
ical
st
udie
s, e
.g.
by id
entif
ying
and
val
idat
ing
biol
ogic
al s
urro
gate
mar
kers
whi
ch t
rack
the
cou
rse
of H
D
(‘sta
te b
iom
arke
rs’),
and
by
iden
tifyi
ng f
acto
rs th
at in
fluen
ce th
e on
set a
nd p
rogr
essi
on o
f illn
ess.
REG
ISTR
Y is
des
igne
d to
:
obta
in n
atur
al h
isto
ry d
ata
on a
wid
e sp
ectru
m o
f HD
pat
ient
s, H
D m
utat
ion
carr
iers
and
indi
vidu
als
who
are
par
t of a
n H
D fa
mily
rela
te p
heno
typi
cal c
hara
cter
istic
s w
itho
gene
tic fa
ctor
s (‘g
enet
ic m
odifi
ers’
),o
data
der
ived
from
the
stud
y of
bod
y flu
ids
(blo
od, u
rine
–‘w
et b
iom
arke
r’) a
ndo
imag
ing
data
(‘d
ry b
iom
arke
r’)
expe
dite
iden
tific
atio
n an
d re
crui
tmen
t of p
artic
ipan
ts fo
r clin
ical
tria
ls
deve
lop
and
valid
ate
sens
itive
and
relia
ble
outc
ome
mea
sure
s fo
r det
ectin
g on
set a
nd c
hang
e ov
er
the
natu
ral c
ours
e of
pre
man
ifest
and
man
ifest
HD
whi
ch m
ay a
lso
be p
oten
tial o
utco
me
mea
sure
s fo
r use
in fu
ture
clin
ical
tria
lsan
d cl
inic
al c
are.
to p
lan
for
futu
re r
esea
rch
stud
ies
(obs
erva
tiona
l and
inte
rven
tiona
l tria
ls a
imed
at b
ette
r sy
mpt
om
cont
rol o
r aim
ed a
t slo
win
g or
pos
tpon
ing
the
onse
t and
pro
gres
sion
of H
D).
REG
ISTR
Y in
tegr
ates
pr
ospe
ctiv
ely
and
syst
emat
ical
ly
colle
cted
cl
inic
al
rese
arch
da
ta
(e.g
. ph
enot
ypic
al c
linic
al f
eatu
res,
fam
ily h
isto
ry,
dem
ogra
phic
al c
hara
cter
istic
s) w
ith a
cces
s to
bio
logi
cal
spec
imen
s (e
.g.,
bloo
d, u
rine)
obt
aine
d fro
m in
divi
dual
s w
ith m
anife
st H
D, u
naffe
cted
indi
vidu
als
know
n to
car
ry th
e H
D m
utat
ion
or a
t ris
k of
car
ryin
g th
e H
D m
utat
ion,
and
con
trol r
esea
rch
parti
cipa
nts
(e.g
., sp
ouse
s, s
iblin
gs o
r of
fspr
ing
of H
D m
utat
ion
carr
iers
kno
wn
not t
o ca
rry
the
HD
mut
atio
n). B
iolo
gica
l sp
ecim
ens
and
phen
otyp
ical
dat
a w
ill be
pro
vide
d to
qua
lifie
d sc
ient
ists
who
se p
roje
cts
are
subm
itted
to
, re
view
ed b
y an
d ap
prov
ed b
y th
e Sc
ient
ific
and
Bioe
thic
al A
dvis
ory
Com
mitt
ee(S
BAC
)of
EH
DN
an
d w
ho d
ecla
red
in w
ritin
g th
at t
hey
acce
pt t
he p
olic
ies
of E
HD
N w
ith r
espe
ct t
o th
e us
e of
the
da
ta/m
ater
ials
pro
vide
d an
d w
ith r
espe
ct to
the
publ
icat
ion
of r
esul
ts (
see
data
sha
ring
and
publ
icat
ion
18
polic
ies
of E
HD
N,
atta
ched
). R
esea
rch
proj
ects
sho
uld
aim
to
adva
nce
scie
ntifi
c kn
owle
dge
tow
ards
es
tabl
ishi
ng c
linic
ally
effe
ctiv
e tre
atm
ents
that
del
ay o
nset
and
/or s
low
the
prog
ress
ion
of th
e di
seas
e.
REG
ISTR
Y w
as
conc
eive
d as
a
long
-term
pr
ojec
t to
in
tegr
ate
clin
ical
an
d pr
eclin
ical
re
sear
ch
appr
oach
es to
adv
ance
the
expe
rimen
tal t
hera
peut
ics
of H
D w
hile
ens
urin
g th
e pr
ivac
y an
d pr
otec
tions
of
con
sent
ing
rese
arch
par
ticip
ants
. R
EGIS
TRY
is c
ompl
emen
tary
to
the
CO
HO
RT
proj
ect
of t
he
Hun
tingt
on S
tudy
Gro
up (H
SG) a
nd b
uild
s on
stro
ng c
olla
bora
tive
rela
tions
hips
am
ong
basi
c sc
ient
ists
, cl
inic
al i
nves
tigat
ors
and
advo
cacy
org
anis
atio
ns f
or H
D i
n th
e co
ntex
t of
the
EH
DN
, a
Eur
opea
n co
nsor
tium
of
scie
ntis
ts,
rese
arch
ers
and
lay
orga
nisa
tions
to
impr
ove
treat
men
t op
tions
for
HD
; R
EGIS
TRY
was
pla
nned
and
is o
vers
een
by th
e EH
DN
. REG
ISTR
Y is
par
t a w
orld
wid
e co
llabo
rativ
e un
derta
king
to d
evel
op tr
eatm
ents
that
mak
e a
diffe
renc
e fo
r HD
. EH
DN
and
REG
ISTR
Y ar
e fu
nded
by
the
CH
DI
Foun
datio
n, I
nc.,
a no
t-for
-pro
fit o
rgan
isat
ion
that
sup
ports
a v
arie
ty o
f re
sear
ch p
roje
cts
seek
ing
to fi
nd tr
eatm
ents
for H
D.
In
addi
tion,
th
ere
is
som
e ov
erla
p w
ith
two
NIH
-spo
nsor
ed
pros
pect
ive
stud
ies:
'P
RED
ICT-
HD
' (p
rosp
ectiv
ely
exam
inin
g ph
enot
ypes
am
ong
unaf
fect
ed p
artic
ipan
ts w
ho fo
llow
ing
pred
ictiv
e te
stin
g ar
e kn
own
to c
arry
the
HD
mut
atio
n), a
nd 'P
HA
RO
S'(e
xam
inin
g ph
enot
ypes
am
ong
unaf
fect
ed p
artic
ipan
tsw
ith a
HD
par
ent w
ho h
ave
unkn
own
mut
atio
n ca
rrie
r st
atus
sin
ce h
avin
g ch
osen
not
to u
nder
go D
NA
test
ing)
. P
RED
ICT-
HD
has
a E
urop
ean
exte
nsio
n fo
r so
me
Euro
pean
cou
ntrie
s (a
t th
e tim
e of
thi
s w
ritin
g G
erm
any,
Spa
in a
nd t
he U
K) w
here
as P
HA
RO
S do
es n
ot a
llow
par
ticip
atio
n of
non
-Eng
lish
spea
king
par
ticip
ants
nor
of p
artic
ipan
ts fr
om o
utsi
de o
f the
US
A, C
anad
a or
Aus
tralia
. REG
ISTR
Y w
ill
ther
efor
e pr
ovid
e an
ong
oing
obs
erva
tiona
l stu
dy fo
r elig
ible
par
ticip
ants
who
are
not
abl
e to
par
ticip
ate
in P
RED
ICT-
HD
or
PHA
RO
S as
wel
l as
for
parti
cipa
nts
who
con
clud
e th
eir
rese
arch
par
ticip
atio
n in
PR
ED
ICT-
HD
and
PH
ARO
S.
The
stea
dy w
orse
ning
of
the
mot
or,
cogn
itive
, an
d be
havi
oura
l ca
paci
ties
of H
D p
atie
nts
resu
lts i
n pr
ogre
ssiv
e fu
nctio
nal
decl
ine.
Clin
ical
rat
ing
scal
es a
imed
at
capt
urin
g th
e cl
inic
al p
heno
type
and
m
irror
ing
the
prog
ress
ion
of th
e ill
ness
hav
e be
en w
idel
y us
ed to
est
ablis
h th
e ra
te o
f fun
ctio
nal d
eclin
e in
a v
arie
ty o
f H
D p
opul
atio
ns(7
-13)
. Th
e U
nifie
d H
untin
gton
's D
isea
se R
atin
g Sc
ale
(UH
DR
S) w
as
deve
lope
d by
the
HSG
in 1
993
and
revi
sed
in 1
999
as U
HD
RS
99 (
14, 1
5). T
he U
HD
RS’
99 a
sses
ses
four
maj
or c
linic
al d
omai
ns o
f im
pairm
ent:
1) m
otor
, 2)
cog
nitiv
e, 3
) be
havi
oura
l, an
d 4)
fun
ctio
nal
capa
city
. In
dev
isin
g th
is s
cale
, ite
ms
wer
e se
lect
ed t
hat
wer
e lik
ely
to b
e se
nsiti
ve t
o m
easu
re
prog
ress
ion
in e
arly
sta
ges
of th
e illn
ess.
The
UH
DR
S, w
hich
will
be e
mpl
oyed
in R
EGIS
TRY,
has
been
us
ed in
all
clin
ical
site
s co
llabo
ratin
g as
HSG
in N
orth
Am
eric
a, E
urop
e, a
nd A
ustra
lia. T
he U
HD
RS
has
unde
rgon
e ex
tens
ive
test
ing
of re
liabi
lity
and
inte
rnal
con
sist
ency
(14-
16)a
nd h
as b
een
show
n to
hav
ea
good
inte
r-ra
ter
relia
bilit
y fo
r th
e to
tal m
otor
sco
re. T
he m
otor
and
cog
nitiv
e se
ctio
ns o
f the
UH
DR
S co
rrel
ate
stro
ngly
and
sig
nific
antly
with
the
func
tiona
l com
pone
nt o
f the
UH
DR
S. I
nter
nal c
onsi
sten
cy,
as m
easu
red
by C
ronb
ach'
s al
pha
was
0.9
5 fo
r the
mot
or c
ompo
nent
, 0.9
0 fo
r the
cog
nitiv
e te
sts,
0.8
3 fo
r the
beh
avio
ural
com
pone
nt, a
nd 0
.95
for t
he fu
nctio
nal c
ompo
nent
of t
he U
HD
RS
(17)
. The
UH
DR
S
has
been
use
d w
idel
y in
HD
clin
ical
tria
ls (1
8, 1
9).
Sinc
e its
ini
tial
desc
riptio
n in
187
2, i
t ha
s be
en c
lear
tha
t H
D h
as a
stro
ng h
ered
itary
con
tribu
tion
resu
lting
in th
e ge
nera
tiona
l tra
nsm
issi
on o
f the
dis
ease
from
par
ent t
o of
fspr
ing,
reg
ardl
ess
of g
ende
r (2
0).
Begi
nnin
g in
198
1 an
d th
roug
h th
e co
llect
ion
of c
linic
al a
nd f
amily
his
tory
inf
orm
atio
n an
d bi
olog
ical
mat
eria
l (D
NA)
fro
m H
Dfa
milie
s th
e ge
ne a
nd t
he m
utat
ion
caus
ing
HD
was
iden
tifie
d in
19
93(2
, 21
-24)
. Th
e un
stab
le,
expa
nded
CAG
rep
eat
with
in t
he c
odin
g re
gion
of
the
HD
gen
e at
4p
16.3
exp
lain
s m
any
of th
e pu
zzlin
g ge
netic
feat
ures
of t
he d
isor
der,
incl
udin
g th
e va
riabl
e ag
e at
ons
et,
the
tend
ency
for
juv
enile
dis
ease
to
be i
nher
ited
from
fat
hers
, an
d th
e (r
are)
app
eara
nce
of n
ew
mut
atio
ns. T
here
is a
stro
ng a
nd c
onsi
sten
t inv
erse
rel
atio
nshi
p be
twee
n th
e le
ngth
of t
he C
AG r
epea
t an
dth
e cl
inic
al o
nset
of H
D (
2, 2
1-24
). H
owev
er, t
he s
ize
of th
e C
AG r
epea
t acc
ount
s fo
r on
ly a
bout
60
-70%
of t
he v
aria
nce
in a
ge a
t ons
et; o
ther
, as
yet u
nide
ntifi
ed fa
ctor
s in
fluen
ce a
ge a
t ons
et a
nd th
e ca
scad
e of
pat
hoge
nic
even
ts re
sulti
ng in
the
HD
phe
noty
pe. R
ecen
t stu
dies
sug
gest
that
the
rem
aini
ng
varia
tion
in a
ge a
t ons
et o
f HD
is s
trong
ly h
erita
ble
(25)
. The
se fi
ndin
gs in
dica
te th
at th
e on
set o
f HD
is
subs
tant
ially
influ
ence
d by
fact
ors
othe
r tha
n re
peat
siz
e, a
nd th
at o
ther
mod
ifier
gen
es m
ay d
eter
min
e th
e re
mai
ning
var
iatio
n in
age
at
onse
t. Fo
r ex
ampl
e, t
he U
CH
L1 g
ene,
whi
ch e
ncod
es u
biqu
itin
carb
oxyl
-term
inal
hyd
rola
se L
1, w
as r
epor
ted
to
influ
ence
age
at
onse
t of
HD
, w
ith t
he S
18Y
poly
mor
phis
ms
acco
untin
g fo
r 13
% o
f the
var
ianc
e in
age
at o
nset
in a
cas
e-an
d-co
ntro
l-stu
dy d
esig
n
194 Hygeia Public Health 2011, 46(2): 183-218
19
(26)
. Sev
eral
pre
viou
s st
udie
s ha
ve re
porte
d th
at a
gen
e co
ding
for a
sub
unit
of a
n io
notro
pic
glut
amat
e re
cept
ors
(Glu
R6;
GR
IK2)
act
s as
an
HD
mod
ifier
(27-
29).
Whe
n an
alys
ed in
con
junc
tion
with
UC
HL1
, 7%
of t
he v
aria
nce
in th
e ag
e at
ons
et o
f HD
cou
ld b
e at
tribu
ted
to th
e G
RIK
2 ge
noty
pe v
aria
tion,
13%
to
UC
HL1
, an
d 16
% t
o bo
th p
olym
orph
ism
s(2
9).
Find
ings
fro
m a
rec
ent
stud
y in
dica
te t
he r
ole
of
mod
ifier
gen
e PG
C-1
alph
a to
hav
e a
smal
l but
sta
tistic
ally
sig
nific
anta
mou
nt o
f the
var
iabi
lity
in a
ge o
f on
set f
or th
e di
seas
e, w
hich
sug
gest
s th
at th
is g
ene
has
mod
ifyin
g ef
fect
s on
the
path
ogen
ic p
roce
ss in
H
D(3
0).E
fforts
are
und
erw
ay to
sys
tem
atic
ally
iden
tify
and
char
acte
rise
mod
ifier
gen
es re
spon
sibl
e fo
r va
riatio
n in
the
age
at
onse
t of
Hun
tingt
on’s
dis
ease
usin
g ca
ndid
ate
gene
app
roac
hes
(e.g
. ht
t in
tera
ctio
n pa
rtner
s lik
e U
CH
LI g
ene
and
the
HIP
14ge
ne (
31))
or
unbi
ased
who
le g
enom
e st
rate
gies
(e.g
. hig
h de
nsity
SN
P-m
aps)
.
Chr
omos
omal
reg
ions
har
bour
ing
addi
tiona
l mod
ifier
gen
es h
ave
been
impl
icat
ed b
y a
rece
nt g
enom
e lin
kage
sca
n (th
e H
D-M
APS
stud
y; (3
2-34
).A
lthou
gh s
ome
prom
isin
g SN
Ps h
ave
been
det
ecte
d, n
one
has
so fa
r rea
ched
gen
ome-
wid
e si
gnifi
canc
e, s
ugge
stin
g th
at th
ere
is n
o si
ngle
or m
ajor
mod
ifier
whi
ch
alon
e de
term
ines
the
var
iatio
n in
age
of
onse
t.To
dat
e, t
he s
earc
h fo
r m
odify
ing
gene
s ha
s be
en
carr
ied
out u
sing
age
at o
nset
of m
otor
sig
ns a
s th
e ph
enot
ypic
al v
aria
ble
unde
r con
side
ratio
n, b
ut it
is
clea
r th
at
HD
di
spla
ys
othe
r ph
enot
ypic
va
riabi
lity
in
dise
ase
expr
essi
on,
incl
udin
g ps
ychi
atric
m
anife
stat
ions
(e.
g.,
depr
essi
on,
psyc
hosi
s) a
nd c
ogni
tive
impa
irmen
t (e
.g.,
impa
irmen
t of
exe
cutiv
e fu
nctio
n an
d/or
im
med
iate
m
emor
y).
Due
to
th
e lim
ited
avai
labi
lity
of
pros
pect
ivel
y co
llect
ed,
long
itudi
nal
data
of
suffi
cien
t qu
ality
, st
udie
s to
ide
ntify
gen
etic
mod
ifier
s of
the
rate
of
dise
ase
prog
ress
ion
or t
he p
ace
and
exte
nt o
f ne
uroi
mag
ing
abno
rmal
ities
hav
e no
t be
en p
erfo
rmed
to
date
. Id
entif
icat
ion
of g
enes
that
mod
ify th
e pa
thog
enic
pro
cess
in H
D o
ffers
a d
irect
rout
e to
val
idat
e ta
rget
s fo
r de
velo
pmen
t of
HD
exp
erim
enta
l th
erap
eutic
s. R
EGIS
TRY
will
prov
ide
a w
ide
rang
e of
HD
-as
soci
ated
phe
noty
pes
by w
hich
to
iden
tify
mod
ifier
gen
es.
Initi
ally
, th
e ph
enot
ypes
ava
ilabl
e w
ill be
de
rived
from
clin
ical
ass
essm
ents
(UH
DR
S), b
ut th
e co
llect
ion
of b
iolo
gica
l sam
ples
will
als
ope
rmit
the
stud
y of
add
ition
al p
heno
type
s at
the
leve
ls o
f RN
A, p
rote
in, m
etab
olite
s an
d cu
lture
d ce
lls. C
olle
ctio
n of
fam
ily h
isto
ry i
nfor
mat
ion
and
know
ledg
e of
fam
ilial
rela
tions
hips
of
REG
ISTR
Y pa
rtici
pant
s w
ill pe
rmit
asse
ssm
ent o
f the
var
iatio
n of
phe
noty
pes
with
in fa
milie
s an
d th
eir d
egre
e of
her
itabi
lity
and
will
be
cru
cial
for
sib
pair
anal
ysis
. DN
A sa
mpl
es fr
om R
EGIS
TRY
parti
cipa
nts
will
perm
it a
geno
me
wid
e se
arch
for
pol
ymor
phis
ms
outs
ide
the
HD
gen
e us
ing
stan
dard
app
roac
hes
(e.g
. SN
P m
aps)
. Th
eco
mbi
natio
n of
phe
noty
pic
and
geno
typi
c in
form
atio
n w
ill p
erm
it an
alys
is o
f re
latio
nshi
ps b
etw
een
indi
vidu
al
poly
mor
phis
ms
and
gene
s an
d th
e ef
fect
th
ey
have
on
m
odify
ing
the
phen
otyp
ical
pr
esen
tatio
n,
rate
of
pr
ogre
ssio
n an
d re
spon
se
to
treat
men
t of
H
Dus
ing
gene
tic
linka
ge
and
asso
ciat
ion
stra
tegi
es.
The
clin
ical
dat
abas
e on
HD
and
the
biom
ater
ials
to b
e co
llect
ed fo
r the
REG
ISTR
Y st
udy
will
be u
sed
for
a va
riety
of d
iffer
ent a
naly
ses
whi
ch m
ay b
e br
oadl
y ca
tego
rised
as
eith
er c
ross
-sec
tiona
l ana
lyse
s or
long
itudi
nal a
naly
ses.
The
des
ign
of R
EGIS
TRY
plac
es n
o lim
it on
the
sam
ple
size
to b
e co
llect
ed o
r a
timef
ram
e in
whi
ch th
e st
udy
will
be
com
plet
ed. I
t is
inte
nded
that
clin
ical
dat
a an
d bi
osam
ples
will
be
colle
cted
unt
il ef
fect
ive
treat
men
t opt
ions
for H
D a
re e
stab
lishe
d. T
he g
radu
al a
mas
sing
of p
heno
typi
cal
data
and
bio
logi
cal
sam
ples
w
ill re
sult
in c
umul
ativ
e in
crea
ses
in s
tatis
tical
pow
er i
n or
der
to
cont
inuo
usly
impr
ove
the
asse
ssm
ent t
ools
that
mon
itor t
he p
rogr
essi
on o
f HD
and
to d
etec
t mol
ecul
arde
term
inan
ts o
r mar
kers
for c
linic
ally
rele
vant
phe
noty
pic
char
acte
ristic
s or
out
com
es (e
.g. p
rogr
essi
on
of H
D a
nd a
bet
ter d
efin
ition
of t
he c
linic
al o
nset
of d
isea
se).
This
will,
in tu
rn, i
mpr
ove
the
effic
ienc
y of
th
erap
eutic
tria
ls b
y pr
ovid
ing
mor
e an
d m
ore
clea
rly d
efin
ed e
ndpo
ints
(e.
g. d
elay
ing
onse
t of c
linic
al
dise
ase)
.
Incl
usio
n of
a b
iolo
gica
l spe
cim
en re
posi
tory
in R
EGIS
TRY
evol
ved
from
dis
cuss
ions
abo
ut th
e cu
rren
t un
met
nee
ds o
f HD
rese
arch
. Adv
ance
s in
und
erst
andi
ng th
e pa
thog
enes
is o
f HD
and
the
disc
over
y of
pa
ralle
l bio
mar
kers
has
larg
ely
been
lim
ited
by th
e av
aila
bilit
y of
sui
tabl
e co
llect
ed b
iolo
gica
l spe
cim
ens
and
the
avai
labi
lity
of p
rosp
ectiv
ely
colle
cted
lon
gitu
dina
l da
ta.
The
REG
ISTR
Y bi
olog
ical
spe
cim
en
repo
sito
ry w
ill pr
ovid
e re
sear
ch s
ampl
es e
ssen
tial f
or c
urre
nt a
nd f
utur
e sc
ient
ific
rese
arch
aim
ed a
t de
velo
ping
use
ful b
iom
arke
rs o
f HD
.
20
6.2
Stud
y ob
ject
ives
To c
olle
ct p
rosp
ectiv
eda
ta o
n th
e ph
enot
ypic
al c
hara
cter
istic
s of
HD
mut
atio
n ca
rrie
rs r
egar
dles
s of
w
heth
er th
ey d
ispl
ay c
linic
al s
ympt
oms
and
sign
s of
HD
and
of i
ndiv
idua
ls w
ho a
re p
art o
f an
HD
fam
ily
(irre
spec
tive
of th
eir m
utat
ion
carr
ier s
tatu
s), i
n or
dert
o;
obta
in n
atur
al h
isto
ry d
ata
on a
wid
e sp
ectru
m o
f HD
pat
ient
s, H
D m
utat
ion
carr
iers
and
indi
vidu
als
who
are
par
t of a
n H
D fa
mily
rela
te p
heno
typi
cal c
hara
cter
istic
s w
itho
gene
tic fa
ctor
s (‘g
enet
ic m
odifi
ers’
),o
data
der
ived
from
the
stud
y of
bod
y flu
ids
(blo
od, u
rine
–‘w
et b
iom
arke
r’) a
ndo
imag
ing
data
(‘d
ry b
iom
arke
r’)
expe
dite
iden
tific
atio
n an
d re
crui
tmen
t of p
artic
ipan
ts fo
r clin
ical
tria
ls
deve
lop
and
valid
ate
sens
itive
and
relia
ble
outc
ome
mea
sure
s fo
r det
ectin
g on
set a
nd c
hang
e ov
er
the
natu
ral c
ours
e of
pre
man
ifest
and
man
ifest
HD
, and
whi
ch m
ay a
lso
be p
oten
tial o
utco
me
mea
sure
s fo
r use
in fu
ture
clin
ical
tria
lsan
d cl
inic
al c
are.
plan
for
fut
ure
rese
arch
stu
dies
(ob
serv
atio
nal a
nd i
nter
vent
iona
l tria
ls a
imed
at
bette
r sy
mpt
om
cont
rol o
r aim
ed a
t slo
win
g or
pos
tpon
ing
the
onse
t and
pro
gres
sion
of H
D).
To a
chie
ve th
ese
obje
ctiv
es, p
artic
ipan
ts a
re a
sked
to d
onat
e bi
osam
ples
(bl
ood
and
urin
e) fo
r st
udie
s to
ide
ntify
gen
etic
mod
ifier
s of
HD
and
to
esta
blis
h an
d va
lidat
e bi
olog
ical
mar
kers
tra
ckin
g th
e pr
ogre
ssiv
e co
urse
of H
D; i
n th
is c
onte
xt a
fam
ily h
isto
ry is
requ
este
d as
wel
l in
orde
r to
unde
rsta
nd th
e re
latio
nshi
ps o
f cl
inic
al d
ata
sets
and
bio
sam
ples
fro
m r
elat
ed d
onor
s. I
n ad
ditio
n, n
on-m
utat
ion
carr
ying
fam
ily m
embe
rs o
f par
ticip
ants
are
ask
ed to
con
side
r don
atin
g bi
osam
ples
to s
erve
as
cont
rols
.
6.3
Stud
y de
sign
All p
artic
ipan
ts w
ill be
ass
esse
d at
bas
elin
e an
d an
nual
vis
its th
erea
fter.
At e
ach
visi
t, pa
rtici
pant
s w
ill
unde
rgo
clin
ical
, m
otor
, co
gniti
vean
dne
urop
sych
iatri
c as
sess
men
ts a
s w
ell
as d
onat
ing
bloo
d an
d ur
ine
sam
ples
. R
EGIS
TRY
asse
ssm
ents
will
last
bet
wee
n 30
min
utes
to
2.5
hour
s de
pend
ing
on t
he
leve
l of a
sses
smen
t adm
inis
tere
d to
the
parti
cipa
nt.
In s
umm
ary,
REG
ISTR
Y co
nsis
ts o
f 6co
mpo
nent
si.
a cl
inic
al p
heno
typi
cal c
hara
cter
isat
ion
ii.th
e co
llect
ion
of b
iolo
gica
l spe
cim
eniii.
the
colle
ctio
n of
fam
ily h
isto
ry d
ata
iv.
the
colle
ctio
n of
dat
a on
nov
el c
linic
alas
sess
men
t too
lsv.
the
colle
ctio
n of
retro
spec
tive
data
vi.
perm
issi
on fo
r vid
eota
ping
6.4
Clin
ical
phe
noty
pica
l cha
ract
eris
atio
n
The
clin
ical
phe
noty
pe w
ill b
e as
sess
ed a
nd d
ocum
ente
d ba
sed
on i
nfor
mat
ion
obta
ined
fro
m t
hree
so
urce
s:tra
ined
rat
ers
(e.g
. ne
urol
ogis
ts,
psyc
hiat
rists
, ne
urop
sych
olog
ists
etc
.) w
ho r
ecor
d th
eir
clin
ical
im
pres
sion
usi
ng t
he U
nifie
d H
untin
gton
's D
isea
se R
atin
g Sc
ale
(UH
DR
S’99
),th
e P
BA-
san
d th
e C
olum
bia
Suic
ide
Sev
erity
Rat
ing
Scal
e (C
SSR
-S)1
affe
cted
/HD
mut
atio
n ca
rrie
r/per
son
at r
isk
for
HD
the
mse
lves
who
sel
f-rep
ort
on t
heir
perc
eive
d qu
ality
of
life
(SF-
36),
thei
r m
ood
(Hos
pita
l An
xiet
y/D
epre
ssio
n R
atin
g Sc
ale
&Sn
aith
Irr
itabi
lity
.
1Th
e R
EG
ISTR
Y S
OP
for
Ris
k As
sess
men
t fo
r ha
rm t
o se
lf_ot
hers
iden
tifie
s ris
k in
dica
tors
and
pro
toco
ls f
or p
erso
nnel
who
co
nsid
er a
par
ticip
ant t
o be
at r
isk
of s
elf h
arm
/sui
cide
, and
/or h
arm
to o
ther
s.
195Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
21
Scal
e; H
ADS-
SIS)
and
on t
he e
cono
mic
impa
ct H
D h
as o
n th
eir
lives
(C
lient
Ser
vice
s R
ecei
pt
Inve
ntor
y–R
evis
ed:C
SR
I-R)
com
pani
ons/
care
-giv
ers
who
rec
ord
the
impa
ct o
f H
D/m
utat
ion
carr
ier
stat
us/a
t ris
k st
atus
on
the
fam
ilies/
soci
al c
ore
units
(Car
e G
iver
Que
stio
nnai
re -
CG
Q)
The
impr
essi
ons
of t
rain
ed r
ater
s ar
e ca
ptur
ed u
sing
the
UD
HR
S ’9
9in
clud
ing
a m
easu
rem
ent
of
wei
ght a
nd h
eigh
tand
acl
inic
al ra
ting
scal
e fo
r sui
cida
lity
and
harm
to s
elf o
r oth
ers
(CSS
R-S
).
Spec
ifica
lly, t
he fo
llow
ing
info
rmat
ion
will
be c
olle
cted
onR
EGIS
TRY-
HD
parti
cipa
nts:
Dem
ogra
phic
s (d
ate
of b
irth,
gen
der,
educ
atio
n,oc
cupa
tion,
resi
denc
e, m
arita
l sta
tus)
Med
ical
His
tory
Co-
mor
bid
cond
ition
s(a
cute
and
chr
onic
, ser
ious
and
non
-ser
ious
)H
D-M
utat
ion
(CAG
repe
at a
naly
sis,
siz
e of
the
alle
les,
labo
rato
ry p
erfo
rmin
g th
e an
alys
is, d
ate
of th
e an
alys
is)
Cur
rent
med
icat
ion
Wei
ght &
heig
ht (+
BM
I)U
HD
RS
‘99
mot
or a
sses
smen
tC
ogni
tive
asse
ssm
ent:
a) B
rief:
UH
DR
S C
ogni
tive
(Stro
op;
Sym
bol D
igit
Mod
ality
Test
, Let
ter
Flue
ncy)
and
Cat
egor
y Fl
uenc
y; b
) Ext
ende
d: B
rief v
ersi
on a
nd T
rail
Mak
ing
Test
(Par
ts A
and
B)
, Hop
kins
Ver
bal L
earn
ing
Test
, and
Mat
tis D
emen
tia R
atin
g Sc
ale
(opt
iona
l).U
HD
RS
func
tion
asse
ssm
ent
(incl
udin
g Fu
nctio
nal
Asse
ssm
ent
Scal
e, I
ndep
ende
nce
Scal
e an
dTF
Csc
ale)
UH
DR
S be
havi
oura
l ass
essm
ent/P
BA-
s
Asid
e fro
m t
he i
mpr
essi
on o
f tra
ined
obs
erve
rs,
the
self-
asse
ssm
ent
of t
he a
ffect
ed/H
D m
utat
ion
carr
ier/p
erso
n at
ris
k fo
r H
D w
ith r
espe
ct t
o th
eir
Qua
lity
of L
ife a
nd m
ood
are
docu
men
ted
usin
g st
anda
rd to
ols
(SF-
36 fo
r the
mea
sure
men
t of q
ualit
y of
life
and
the
HAD
Sas
a m
easu
re o
f dep
ress
ion
and
anxi
ety,
and
the
SIS
as a
mea
sure
of
irrita
bilit
y).
The
econ
omic
impa
ct H
D h
as is
doc
umen
ted
(Clie
nt S
ervi
ce R
ecei
pt I
nven
tory
–Rev
ised
(C
SRI-R
);th
is q
uest
ionn
aire
is
com
plet
ed b
oth
by t
he
affe
cted
/HD
mut
atio
n ca
rrie
r/per
son
at ri
sk a
s w
ell a
s by
thei
r com
pani
ons/
care
-giv
ers)
.
Fina
lly, c
ompa
nion
s/ca
rer-
give
rs a
re a
sked
to r
ecor
d th
e im
pact
that
the
HD
/mut
atio
n ca
rrie
r st
atus
/at
risk
stat
us h
as o
n th
e fa
milie
s/so
cial
cor
e un
its b
y fil
ling
in a
que
stio
nnai
re (
Car
e G
iver
Que
stio
nnai
re;
CG
Q).
At t
he b
asel
ine
stud
y vi
sit,
train
ed r
ater
s w
ill a
dmin
iste
r th
e U
HD
RS
’99
and
the
CS
SR-S
. Th
e st
udy
parti
cipa
nts
will
com
plet
e th
e SF
-36
and
the
HA
DS-
SIS.
A c
ompa
nion
(if
avai
labl
e) w
ill co
mpl
ete
the
CG
Q a
nd w
ill as
sist
in fi
lling
in th
e C
SR
I-R. I
n ad
ditio
n, a
t the
bas
elin
e vi
sit,
parti
cipa
nts
will
be a
sked
to
cons
ider
the
follo
win
g op
tiona
l stu
dy p
roce
dure
s:
In
REG
ISTR
Y ve
rsio
ns1.
0 an
d 2.
0,
the
prot
ocol
was
co
nfin
ed
to
esta
blis
hed
inst
rum
ents
fo
r pa
rtici
pant
s w
ith m
anife
st d
isea
se (
show
ing
feat
ures
of
the
dise
ase
curr
ently
def
ined
as
diag
nost
ic).
The
UH
DR
S an
d th
e ot
her a
sses
smen
ts e
valu
ated
in R
EGIS
TRY
3.0
are
gear
ed to
war
ds c
aptu
ring
the
phen
otyp
e di
spla
yed
by t
his
popu
latio
n bu
t do
not
adeq
uate
ly c
aptu
re t
hem
ore
subt
le b
ut c
lear
ly
quan
tifia
ble
sym
ptom
s an
d si
gns
of in
divi
dual
s ap
proa
chin
gth
e on
set o
f mot
or s
igns
. Bo
th P
RED
ICT-
HD
(35)
and
TRAC
K-H
D (
36)
have
est
ablis
hed
uneq
uivo
cally
that
ther
e ar
e ab
norm
aliti
es th
at h
ave
a fu
nctio
nal
impa
ct i
n al
l th
ree
dom
ains
(cog
nitiv
e, b
ehav
iour
al,
and
mot
or)
if as
sess
ed w
ith s
ensi
tive
inst
rum
ents
. In
add
ition
,th
ese
clin
ical
phe
noty
pica
l alte
ratio
ns a
re c
orre
late
d w
ith c
lear
ly m
easu
rabl
e ch
ange
s in
regi
onal
brai
n vo
lum
es a
s as
sess
ed b
y M
R im
agin
g (3
5, 3
7, 3
8).
Like
wis
e, t
he U
HD
RS
does
not
allo
w a
mea
ning
ful a
sses
smen
t fo
r th
e ad
vanc
ed s
tage
s of
HD
for
a
num
ber
of r
easo
ns.
For
exam
ple,
the
sta
ndar
d U
HD
RS
cogn
itive
ass
essm
ent
cons
istin
g of
tim
ed
psyc
hom
otor
tas
ks,
cann
ot b
e ad
min
iste
red
to p
eopl
e in
mor
e ad
vanc
ed s
tage
s of
HD
due
to t
heir
mot
or im
pairm
ent a
nd d
ysar
thria
. The
refo
re, a
n im
porta
nt c
ompo
nent
of t
he c
ogni
tive
phen
otyp
e is
ver
y of
ten
not
asse
ssed
in
the
adva
nced
sta
ge H
D p
artic
ipan
ts.
Like
wis
e, c
omm
unic
atio
n im
pairm
ents
pr
eclu
de a
n in
terv
iew
-bas
ed b
ehav
iour
al a
sses
smen
t. La
stly
, the
mot
or p
heno
type
for
all
item
s of
the
22
mot
or s
cale
, req
uirin
g ac
tive
parti
cipa
tion
byth
e pa
rtici
pant
is n
ot in
form
ativ
e in
mor
e ad
vanc
ed s
tage
s.O
ther
asp
ects
lik
e im
paire
d m
obilit
y an
d co
ntro
l ov
er b
odily
fun
ctio
ns t
hat
cont
ribut
e gr
eatly
to
the
care
give
r bu
rden
and
the
med
ical
nee
ds o
f ad
vanc
ed s
tage
s of
HD
are
not
cap
ture
d in
the
sta
ndar
d U
HD
RS
ass
essm
ent.
Ther
efor
e R
EGIS
TRY
vers
ion
3.0
cont
ains
a s
ub-s
tudy
asse
ssm
ent o
f adv
ance
d st
age
HD
bas
ed o
n th
e pi
onee
ring
scal
e de
velo
pmen
t led
by
Prof
. Ann
e-C
athe
rine
Bac
houd
Lev
iand
Pr
of. R
aym
und
Roo
s(s
eesu
pple
men
tary
doc
umen
tSum
mar
y of
REG
ISTR
Y Su
b-st
udie
s).
Fina
lly,
expa
nsio
n m
utat
ion
carr
iers
with
ver
y la
rge
CAG
expa
nsio
ns (
>55
repe
ats)
pres
ent
clin
ical
ly
early
(Ju
veni
le H
D)
and
with
a d
istin
ct p
heno
type
tha
t is
not
cap
ture
d co
mpl
etel
y by
the
item
s of
the
cu
rren
t ve
rsio
n of
UH
DR
S,
whi
ch w
asor
igin
ally
dev
elop
ed t
o as
sess
the
mos
t pr
eval
ent
phen
otyp
e w
hich
is th
e ad
ult o
nset
of t
he d
isea
se.
Ther
efor
e, a
mod
ified
and
exp
ande
d U
HD
RS
scal
e is
prop
osed
by th
e E
HD
N J
uven
ile H
D W
G to
be
test
ed o
n a
broa
der
scal
e in
the
cont
exto
f REG
ISTR
Y3.
0(s
ee
supp
lem
enta
ry d
ocum
entS
umm
ary
of R
EGIS
TRY
Sub-
stud
ies)
.
Asse
ssm
ent
scal
es a
nd q
uest
ionn
aire
sto
cap
ture
spe
cific
clin
ical
phe
noty
pes
of H
D a
re u
nder
de
velo
pmen
t and
will
be v
alid
ated
as
part
of R
EGIS
TRY
sub-
stud
ies.
Onc
e va
lidat
ed a
s se
nsiti
ve a
nd
relia
ble
mea
sure
s th
at c
an b
e ad
min
iste
red
cros
s-cu
ltura
lly, t
he a
sses
smen
t too
ls w
ill be
com
e av
aila
ble
to t
he H
D c
omm
unity
and
will
be a
ccep
ted
as p
art
of t
he s
tand
ard
REG
ISTR
Y as
sess
men
t fo
r th
e re
leva
nt p
opul
atio
n gr
oups
.
6.5
Col
lect
ion
of b
iolo
gica
l spe
cim
enD
onat
ion
of b
iolo
gica
l spe
cim
ens
–30
mlo
f blo
od a
nd 3
0 m
l of u
rine
–at
the
base
line
visi
t and
at e
ach
annu
al v
isit.
Par
ticip
ants
will
be g
iven
the
opt
ion
of d
onat
ing
bloo
d an
d ur
ine
sam
ples
; th
e bi
olog
ical
sp
ecim
ens
are
dona
ted
with
the
unde
rsta
ndin
g th
at a
ll sp
ecim
ens
are
used
for H
D re
late
d re
sear
ch a
nd
that
they
are
sto
red
at a
cen
tral b
io-r
epos
itory
.
All
site
s:
Firs
t REG
ISTR
Y vi
sit:
Ever
y si
te is
enc
oura
ged
to ta
ke 2
0ml o
f blo
od to
obt
ain
the
follo
win
g:
DN
A an
d D
NA
deriv
ed fr
om ly
mph
obla
stoi
d ce
ll lin
es w
ill be
use
d (1
) to
con
firm
the
pres
ence
and
the
size
of t
he C
AG e
xpan
sion
mut
atio
n w
ithin
the
HD
gen
e fo
r re
sear
ch p
urpo
ses
only
and
(2)
to
iden
tify
gene
tic m
odifi
ers
of H
D, i
n pa
rticu
lar
gene
tic m
odifi
ers
of a
ge o
f ons
et, r
ate
of p
rogr
essi
on
and
phen
otyp
ical
cha
ract
eris
tics/
pres
enta
tions
(e.
g. th
e lif
e tim
e oc
curr
ence
of p
sych
osis
). Fo
r th
is
purp
ose,
two
tube
s of
AC
D b
lood
are
dra
wn
for
the
extra
ctio
n of
DN
A, f
or t
he g
ener
atio
n of
ly
mph
obla
stoi
d ce
ll lin
es a
nd f
or t
he c
ryop
rese
rvat
ion
of l
ymph
ocyt
es.
Sam
ples
for
DN
A a
nd
lym
phob
last
oid
cell
lines
will
be t
aken
onl
yon
ceat
the
firs
t vi
sit,
unle
ss d
irect
ed b
y B
ioR
ep t
hat
gene
ratio
n of
lym
phob
last
oid
cells
line
s fa
iled,
in w
hich
cas
e a
furth
er s
ampl
e w
ill b
e co
llect
ed.
Urin
e (3
0 m
l) fo
r st
udie
s to
est
ablis
h an
d va
lidat
e m
arke
rs tr
acki
ng th
e pr
ogre
ssiv
e co
urse
of
HD
(e
.g. m
etab
olom
ics)
Sele
cted
site
s
Parti
cipa
nts
will
be a
sked
to
dona
te b
lood
for
pla
sma
colle
ctio
n. T
he a
mou
nt r
equi
red
is 9
.5m
l.Pr
ecis
e tim
e of
day
of c
olle
ctio
n w
ill al
way
s be
doc
umen
ted,
and
whe
ther
the
parti
cipa
nt is
fast
ing
(no
food
/drin
k fo
r 8 h
ours
) or n
on-fa
stin
g. F
rom
9.5
ml w
hole
blo
od, ~
6m
l pla
sma
is c
olle
cted
.
All
site
s:
Subs
eque
nt R
EGIS
TRY
visi
ts;
196 Hygeia Public Health 2011, 46(2): 183-218
23
Ever
y si
te is
enc
oura
ged
to ta
ke 1
0m
l of b
lood
to o
btai
n th
e fo
llow
ing:
All p
artic
ipan
ts w
ill be
ask
ed to
don
ate
10 m
l of b
lood
for t
he p
repa
ratio
nof
lym
phoc
ytes
.
Urin
e (3
0 m
l) fo
r st
udie
s to
est
ablis
h an
d va
lidat
e m
arke
rs tr
acki
ng th
e pr
ogre
ssiv
e co
urse
of H
D
(e.g
. met
abol
omic
s)
Sele
cted
site
s:
Parti
cipa
nts
will
be in
vite
d to
don
ate
bloo
d in
for
plas
ma
colle
ctio
n.Th
e am
ount
requ
ired
is 9
.5m
l.Pr
ecis
e tim
e of
day
of c
olle
ctio
n w
ill al
way
s be
doc
umen
ted,
and
whe
ther
the
parti
cipa
nt is
fast
ing
(no
food
/drin
k fo
r 8 h
ours
) or n
on-fa
stin
g. F
rom
9.5
ml w
hole
blo
od, ~
6m
lpla
sma
is c
olle
cted
.
Toex
tract
goo
d qu
ality
pla
sma,
blo
od s
ampl
esw
ill be
pro
cess
ed o
n-si
te w
ithou
t del
ay a
ccor
ding
to a
va
lidat
ed S
OP
(REG
ISTR
Y SO
P fo
r Pl
asm
a C
olle
ctio
n). P
lasm
a sa
mpl
es w
ill be
div
ided
aliq
uots
for f
reez
ing
at -8
0C. A
ll pl
asm
a co
llect
ion
kits
will
be
prov
ided
by
BioR
ep o
n a
per-
patie
nt b
asis
. Pl
asm
a sa
mpl
es a
re s
tore
d lo
cally
at -
80C
unt
il sh
ipm
ento
n dr
y ic
e to
Bio
Rep
at re
gula
r tim
e po
ints
.
Not
e:
6.6
Com
plet
ion
of a
fam
ily h
isto
ry q
uest
ionn
aire
(FH
Q)
the
resu
lt of
the
gen
otyp
ing
by B
ioR
epw
ill be
mad
e av
aila
ble
to t
he s
tudy
site
whi
ch s
ent
the
spec
imen
to
the
BioR
ep.
The
size
of
both
the
sm
alle
r an
d th
e la
rger
alle
le w
ill be
dis
play
ed a
t th
e bi
osam
ple
page
with
in th
e R
EGIS
TRY
CR
F. It
is th
e re
spon
sibi
lity
of th
e st
udy
site
sen
ding
in s
ampl
es
to e
nsur
e th
at n
o pr
edic
tive
test
ing
is in
adve
rtent
ly p
erfo
rmed
thr
ough
thi
s pr
oced
ure.
To
redu
ce t
he
chan
ces
of a
n in
adve
rtent
pre
dict
ive
test
ing
of p
artic
ipan
ts a
t ris
k, t
he f
ollo
win
g pr
oced
ure
will
be
impl
emen
ted:
th
e re
sults
of
the
geno
typi
ng b
y th
e ce
ntra
l la
bora
tory
will
only
be
disp
laye
d at
the
bi
osam
ple
CR
F pa
ge p
rovi
ded
(i) t
he C
RF
page
on
CAG
is
com
plet
ed O
R (
ii) i
f th
e di
agno
stic
co
nfid
ence
lev
el f
or t
he c
linic
al d
iagn
osis
of
HD
(re
cord
ed i
n pa
rt III
-m
otor
ass
essm
ent
-of
the
UH
DR
S’9
9) e
qual
s 4
and
ifth
e m
otor
sco
re (
as w
ell r
ecor
ded
in p
art
III -
mot
or a
sses
smen
t -
of t
he
UH
DR
S’9
9) is
di
agno
stic
labo
rato
ry a
re u
nava
ilabl
e. F
urth
erm
ore,
the
stud
y si
te p
erso
nnel
per
iodi
cally
rece
ive
aC
AG
data
upd
ate
from
Cen
tral
Coo
rdin
atio
n. T
his
upda
te t
abul
ates
resu
lts f
rom
the
CAG
pag
e of
the
R
EGIS
TRY
CR
F ag
ains
t th
e re
sults
rep
orte
d by
Bio
Rep
. In
the
(ho
pefu
lly u
nlik
ely)
occ
asio
n of
di
scre
pant
res
ults
of c
linic
al r
elev
ance
(e.
g.a
repe
at s
ize
belo
w th
e 35
in a
n in
divi
dual
reg
arde
d as
a
sym
ptom
atic
mut
atio
n ca
rrie
r) a
rep
eat
test
in
a ce
rtifie
d di
agno
stic
lab
orat
ory
is a
dvis
ed.
Such
di
scre
panc
ies
and
the
reco
mm
enda
tion
for
a th
ird in
depe
nden
t ge
netic
tes
t ar
e co
mm
unic
ated
on
a ca
se-b
y-ca
se b
asis
to th
e Si
te P
I and
rel
evan
t site
sta
ff. C
entra
l Coo
rdin
atio
n hi
ghlig
hts
any
pote
ntia
l im
plic
atio
ns fo
r the
par
ticip
ant’s
HD
sta
tus.
The
proc
edur
es fo
r han
dlin
g di
scre
panc
ies
are
desc
ribed
in
an S
OP
(SO
P G
uide
lines
for B
ioR
ep C
AG re
sults
com
mun
icat
ion
to s
ites)
.
All p
artic
ipan
ts w
ill be
invi
ted
toco
mpl
ete
aFH
Q,
inpa
rticu
lar
indi
vidu
als
who
do
not
have
a k
now
n fa
mily
his
tory
of
the
dise
ase.
Thi
s is
an
optio
nal
com
pone
nt o
f R
EGIS
TRY.
Th
e FH
Q a
ttem
pts
to
colle
ct in
form
atio
n ab
out t
he h
isto
ry o
f HD
with
in a
fam
ily u
nit a
nd w
ill th
eref
ore
focu
s on
the
side
of t
he
fam
ily a
ffect
ed b
y H
D. W
ithin
the
FHQ
dat
a on
3 g
ener
atio
ns w
ill be
ass
embl
ed (
data
on
the
pare
nts
and
thei
r si
blin
gs (
i.e.
aunt
s an
dun
cles
), da
ta o
n th
e gr
andp
aren
ts,
and
data
on
the
child
ren
of t
he
affe
cted
and
the
offs
prin
g of
the
ir si
blin
gs (
i.e.
niec
es a
nd n
ephe
ws)
as
wel
l as
data
on
the
spou
se(s
pous
es).
The
purp
ose
of t
he F
HQ
is (
1) t
o re
nder
link
ed b
iosa
mpl
es o
r da
ta s
ets
iden
tifia
ble
whi
le
prot
ectin
g th
e pr
ivac
y of
all
dono
rs a
nd (
2) t
o ob
tain
a f
amily
tre
e as
an
impo
rtant
par
t of
sta
ndar
d m
edic
al c
are.
An
inte
rvie
w o
r a
ques
tionn
aire
will
be h
ande
d to
con
sent
ing
parti
cipa
nts
to s
hare
the
ir fa
mily
tree
by
indi
catin
g ho
w m
any
sibl
ings
, chi
ldre
n an
d re
lativ
es u
p to
the
seco
nd d
egre
e th
ey h
ave
and
to v
olun
teer
the
follo
win
g in
form
atio
n on
eac
h pe
rson
with
in th
e fa
mily
tree
:
gend
er
year
of b
irth
aliv
e/de
ado
for t
hose
dec
ease
d: y
ear o
f dea
th/a
ge a
t dea
th a
nd c
ause
of d
eath
(as
accu
rate
ly a
s po
ssib
le)
24
oop
inio
n of
the
cont
ribut
or a
s to
whe
ther
a m
embe
r of a
fam
ily is
affe
cted
with
HD
/car
ries
the
HD
m
utat
ion
ofo
r th
ose
affe
cted
with
HD
/car
ryin
g th
e H
D m
utat
ion:
age
at
time
of H
D d
iagn
osis
/pre
dict
ive
test
ing,
fir
st
sign
s an
d sy
mpt
oms
and
whe
ther
th
e di
agno
sis
of
HD
w
as
conf
irmed
by
ph
ysic
ian/
gene
tic te
stin
glo
cal a
vaila
bilit
y of
DN
A sa
mpl
es
From
thes
e da
ta a
fam
ily tr
ee w
ill be
gen
erat
ed u
sing
app
ropr
iate
sof
twar
e(S
OP
for c
reat
ion
of F
amily
H
isto
ry T
ree)
. W
ithin
thi
s fa
mily
tre
e th
e sy
mbo
ls r
epre
sent
ing
thos
e m
embe
rs o
f th
e fa
mily
who
co
nsen
ted
to p
artic
ipat
e in
REG
ISTR
Y w
ill be
ann
otat
ed w
ith th
eir
pseu
dony
ms;
fam
ily m
embe
rs w
ho
did
not
cons
ent
to p
artic
ipat
e in
REG
ISTR
Y w
ill be
rep
rese
nted
with
sym
bols
with
out
an a
nnot
ated
ps
eudo
nym
. B
y us
ing
this
pro
cedu
re,
bios
ampl
es a
nd c
linic
al d
ata
of r
elat
ed p
artic
ipan
ts (
whi
ch i
s es
sent
ial e
.g. t
o id
entif
y ge
netic
mod
ifier
s by
sib
pai
r ana
lysi
s) c
an b
e lin
ked
whi
le p
rote
ctin
g th
e pr
ivac
y of
eve
rybo
dy v
olun
teer
ing
info
rmat
ion
by u
sing
exc
lusi
vely
pse
udon
yms
in a
ll el
ectro
nic
data
bas
es.
In o
rder
to e
nsur
e an
app
ropr
iate
num
ber o
f lin
ked
bios
ampl
es a
nd li
nked
clin
ical
dat
a se
ts, p
artic
ipan
ts
are
aske
d (p
rovi
ded
that
the
fee
l co
mfo
rtabl
e to
do
so)
to f
orw
ard
an i
nvita
tion
to t
heir
rela
tives
to
cons
ider
taki
ng p
art i
n R
EGIS
TRY.
Rel
ativ
es o
f ind
ex p
artic
ipan
ts w
ould
then
be
info
rmed
abo
ut R
EGIS
TRY
by p
erso
nnel
of a
stu
dy s
ite o
f th
eir
choi
ce a
nd in
vite
d to
par
ticip
ate
in a
ll co
mpo
nent
s in
clud
ing
the
clin
ical
dat
a do
cum
enta
tion,
the
bi
osam
ples
com
pone
nt a
nd th
e fa
mily
his
tory
com
pone
nt. T
here
fore
fam
ily h
isto
ries
for
a gi
ven
fam
ily
unit
may
be
asce
rtain
ed s
ever
al t
imes
thu
s co
rrob
orat
ing
the
accu
rate
ness
of
the
data
pro
vide
d. I
n or
der
to a
llow
cro
ssch
ecks
of p
oten
tially
con
flict
ing
info
rmat
ion
give
n by
var
ious
mem
bers
of t
he s
ame
fam
ily u
nit a
nd to
acc
omm
odat
e th
e fa
ct th
at m
embe
rs o
f the
sam
e fa
mily
uni
t m
ay c
hose
mor
e th
an
one
stud
y si
te t
o in
tera
ct w
ith, p
artic
ipan
ts a
re in
form
ed th
at a
nnot
ated
fam
ily t
rees
are
sha
red
with
in
the
netw
ork
(i.e.
are
mad
e av
aila
ble
outs
ide
the
stud
y si
te th
e pa
rtici
pant
s ch
ose
to in
tera
ct w
ith)
and
that
ann
otat
ion
of fa
mily
tree
s w
ill be
com
plet
ed b
y ce
ntra
l coo
rdin
atio
n/m
onito
rs.
Exam
ple:
Auth
oris
edin
divi
dual
s (e
.g. r
esea
rche
rs w
ith a
n EH
DN
app
rove
d pr
ojec
t) w
ill ha
ve a
cces
s to
the
fam
ily
unit
data
base
thu
s al
low
ing
them
to
expl
ore
the
avai
labi
lity
of d
ata
and
bios
ampl
es t
o de
term
ine
the
feas
ibilit
y of
a g
iven
pro
ject
and
to a
cces
s th
e ap
prop
riate
dat
a/sa
mpl
es.
Parti
cipa
nt A
cho
oses
stu
dy s
ite X
to p
artic
ipat
e in
all
com
pone
nts
of R
EGIS
TRY.
As
a re
sult
of p
artic
ipan
t A’s
con
tribu
tion
to th
e fa
mily
his
tory
com
pone
nt, a
fam
ily tr
ee w
ill be
dra
wn
base
d on
the
info
rmat
ion
volu
ntee
red
by p
artic
ipan
t A
with
jus
t on
e sy
mbo
l an
nota
ted
by a
pse
udon
ym (
i.e.
the
sym
bol
repr
esen
ting
A).
Sinc
e pa
rtici
pant
A
felt
com
forta
ble
aler
ting
rela
tives
to
th
e op
tion
of
parti
cipa
ting
in R
EGIS
TRY,
thre
e re
lativ
es c
onta
cted
stu
dy s
ite X
and
con
sent
ed to
REG
ISTR
Y. A
s a
cons
eque
nce,
thr
ee m
ore
FHQ
wer
e fil
led
out
on t
he s
ame
fam
ily u
nit
corr
obor
atin
g th
e fa
mily
tre
e ob
tain
ed th
roug
h pa
rtici
pant
A a
nd a
llow
ing
the
anno
tatio
n of
sym
bols
repr
esen
ting
parti
cipa
nts
B-D
. In
addi
tion,
a m
embe
r of
thi
s fa
mily
uni
t re
sidi
ng f
ar a
way
, pa
rtici
pant
E,
choo
ses
stud
y si
te Y
to
parti
cipa
te i
n R
EGIS
TRY.
Bas
ed o
n th
e in
form
atio
n vo
lunt
eere
d by
par
ticip
ant
E, s
tudy
site
Y n
ow
gene
rate
s a
fam
ily t
ree
(whi
ch m
ay o
r m
ay n
ot b
e id
entic
al t
o th
e fa
mily
tre
e de
rived
fro
m t
he
info
rmat
ion
of p
artic
ipan
ts A
-D a
t st
udy
site
X)
and
anno
tate
s on
ly o
ne s
ymbo
l, th
e on
e re
pres
entin
g pa
rtici
pant
E. S
ince
stu
dy s
ite Y
was
told
by
parti
cipa
nt E
that
oth
er m
embe
rs o
f the
fam
ily c
ontri
bute
d to
REG
ISTR
Y at
ano
ther
site
, st
udy
site
Y
aler
ts c
entra
l co
ordi
natio
n ab
out
this
fac
t. C
entra
l co
ordi
natio
n w
ill th
en id
entif
y th
e re
spec
tive
fam
ily tr
ee a
nd w
ill an
nota
te th
e sy
mbo
ls r
epre
sent
ing
the
cons
entin
g m
embe
rs a
nd w
ill ge
nera
te a
n en
try in
the
fam
ily u
nit d
ata
base
. As
a re
sult,
the
fam
ily tr
ee
avai
labl
e fo
r st
udy
site
s X
and
Y w
ill no
w h
ave
5 sy
mbo
ls a
nnot
ated
(pr
evio
usly
4 s
ymbo
ls a
nnot
ated
fo
r stu
dy s
ite X
, 1 s
ymbo
l ann
otat
ed fo
r stu
dy s
ite Y
). Th
e cl
inic
al d
ata
on p
artic
ipan
ts A
-D w
ill co
ntin
ue
to b
e ex
clus
ivel
y ac
cess
ible
to s
tudy
site
X, a
nd th
e da
ta o
n pa
rtici
pant
E e
xclu
sive
ly fo
r st
udy
site
Y.
On
requ
est,
and
if st
udy
site
s co
ncer
ned
expr
ess
this
wis
h in
writ
ing,
acc
ess
to d
ata
of a
ll m
embe
rs o
f a
give
n fa
mily
uni
t can
be
mad
e av
aila
ble
to a
ll st
udy
site
s in
volv
ed in
the
care
of
the
mem
bers
of
this
fa
mily
uni
t.
Parti
cipa
nts
will
be g
iven
the
opt
ion
of c
ompl
etin
g th
e FH
Q d
urin
g th
e st
udy
visi
tor
can
tak
e th
e qu
estio
nnai
re (
alon
g w
ith a
sta
mpe
d, a
ddre
ssed
env
elop
e) h
ome
to c
ompl
ete
and
mai
l it
back
to
the
197Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
25
stud
y si
te. I
f the
com
plet
ed q
uest
ionn
aire
is n
ot re
ceiv
ed w
ithin
one
mon
th o
f the
stu
dy v
isit,
the
site
will
fo
llow
-up
with
the
parti
cipa
nt.
6.7
Sub-
stud
ies
Clin
ical
exp
erie
nce,
the
activ
ities
of E
HD
N w
orki
ng g
roup
s an
dR
EGIS
TRY
data
-min
ing
proj
ects
hav
e pr
ompt
ed th
e us
e of
est
ablis
hed
and
not y
et e
stab
lishe
d as
sess
men
ts to
bet
ter i
nfor
m u
s ab
out s
peci
fic
and/
or r
are
clin
ical
phe
noty
pes
not
pres
ently
cap
ture
d in
the
exi
stin
g st
anda
rdis
ed a
sses
smen
tsR
EGIS
TRY
vers
ion
3.0.
The
ben
efits
of v
alid
atin
g as
sess
men
t too
ls c
an b
e su
mm
aris
ed a
s fo
llow
s: T
oex
plor
e w
heth
er a
dditi
onal
ass
essm
ents
are
use
ful (
clin
ical
ly a
nd fo
r re
sear
ch p
urpo
ses)
;Val
idat
ion
ofth
e as
sess
men
t too
ls is
an
itera
tive
proc
ess
and
impl
ies
that
a f
irst b
est
gues
s in
stru
men
t is
appl
ied,
pr
ovid
ing
us w
ith a
sta
rting
poi
nt to
exp
lore
the
clin
ical
met
rics
of th
ese
asse
ssm
ents
as
wel
l as
inte
r-ra
ter
relia
bilit
y. S
yste
mat
ic r
evie
w o
f eac
h sc
ale
will
assi
st in
the
deve
lopm
ent o
f an
impr
oved
, rev
ised
as
sess
men
t too
l. Th
e fir
st p
hase
will
follo
w a
cro
ss-s
ectio
nal s
tudy
des
ign,
and
the
seco
nd p
hase
will
ex
tend
to a
long
itudi
nal s
tudy
to lo
ok a
t the
rate
of c
hang
es in
the
vario
us a
sses
smen
ts.
Parti
cipa
nts
have
the
optio
n to
par
ticip
ate
in th
e R
EGIS
TRY
sub-
stud
ies.
The
se s
ub-s
tudi
es p
erm
it th
e co
llect
ion
of d
ata
on a
sses
smen
t to
ols
to b
e ca
rrie
d ou
t in
an
expe
dien
t, tim
e-ef
ficie
nt m
anne
r. Ea
ch
REG
ISTR
Y su
b-st
udy
follo
ws
an i
tera
tive
proc
ess
in o
rder
to
fulfi
l tas
k va
lidat
ion.
Tha
t is
, st
atis
tical
an
alys
es w
ill be
car
ried
out a
t spe
cific
tim
e-po
ints
in o
rder
to re
view
task
sen
sitiv
ity a
nd re
liabi
lity
(intra
-an
d in
ter-
rate
r re
liabi
lity)
, w
ith th
e ai
m o
f re
finin
g (a
nd w
here
ver
poss
ible
sho
rteni
ng)
the
asse
ssm
ent
tool
ahe
ad o
f br
oade
r us
e in
the
HD
clin
ical
and
res
earc
h se
tting
.O
nce
suffi
cien
t da
ta h
ave
been
ob
tain
ed
to
achi
eve
pre-
spec
ified
po
wer
, st
atis
tical
an
alys
es
will
dete
rmin
e th
e va
lidity
of
th
e as
sess
men
ttoo
l. E
ach
asse
ssm
ent w
ill un
derg
o a
form
al re
view
by
the
REG
ISTR
Y St
eerin
g C
omm
ittee
(with
the
expe
rt ad
vice
from
resp
ectiv
e Le
ad F
acilit
ator
of e
ach
Wor
king
Gro
up).
The
REG
ISTR
Y su
b-st
udie
s co
mpo
nent
is
flexi
ble
(see
Sum
mar
y of
REG
ISTR
Y’s
Sub-
Stud
ies,
supp
lem
enta
ry d
ocum
ent).
A
list o
f the
ass
essm
ents
is p
rovi
ded
as a
sup
plem
ent t
o th
is d
ocum
ent.
It ou
tline
s th
e na
ture
of
each
tas
k an
d th
e es
timat
ed t
ime
to c
ompl
ete
the
asse
ssm
ents
. T
he o
ngoi
ng
revi
ew a
nd s
cale
dev
elop
men
t will
in m
any
case
s re
sult
in m
odifi
catio
ns to
ass
essm
ents
. Suc
h ch
ange
s w
ill be
reg
arde
d as
cha
nges
to
the
inte
rnal
pro
cedu
res
with
no
adde
d bu
rden
on
parti
cipa
nt t
ime.
Va
lidat
edas
sess
men
t too
ls w
ill be
impl
emen
ted
into
REG
ISTR
Y st
anda
rd a
sses
smen
t. Th
eref
ore
the
asse
ssm
ent p
roto
col i
slik
ely
to c
hang
e as
new
test
s be
com
e av
aila
ble.
The
aim
will
be t
oid
entif
y an
d va
lidat
e ad
ditio
nal c
linic
al o
utco
me
mea
sure
s ei
ther
ass
ocia
ted
with
a
spec
ific
stat
e of
the
dise
ase
or d
escr
ibin
g sp
ecifi
c do
mai
ns o
f the
dis
ease
, e.g
. cog
nitio
n, b
ehav
iour
and
fu
nctio
n. O
nce
fully
val
idat
ed,
thes
e ad
ditio
nal
asse
ssm
ents
may
ser
ve a
s se
nsiti
ve a
nd r
elia
ble
outc
ome
mea
sure
s fo
r clin
ical
tria
ls.
In a
n at
tem
pt to
take
full
adva
ntag
e of
the
exte
nt o
f the
Net
wor
k,pa
rtici
patio
n in
the
REG
ISTR
Y su
b-st
udie
s is
wid
ely
avai
labl
e. T
his
will
pro
mot
e th
e tim
ely
colle
ctio
n of
dat
a an
d in
crea
se th
e en
rolm
ent o
fad
equa
te n
umbe
rs fo
r st
udie
s of
rar
er p
heno
type
s, e
.g. s
peci
fic s
ympt
oms,
suc
h as
irrit
abilit
y, a
path
y,
or r
are
phen
otyp
es,
e.g.
juve
nile
-ons
et H
D.
Par
ticip
ants
are
invi
ted
to p
artic
ipat
e in
REG
ISTR
Y ‘s
ub-
stud
ies’
as
part
of a
col
labo
rativ
e ef
fort
to v
alid
ate
nov
el a
sses
smen
t to
ols
for
use
in c
linic
al a
nd
rese
arch
dom
ains
. The
pro
cedu
res
and
asse
ssm
ents
are
non
-inva
sive
and
hav
e m
inim
al b
urde
n on
the
parti
cipa
nt.
A pa
rtici
pant
may
cho
ose
to o
pt in
or
opt
out
of th
e op
tiona
l com
pone
nt.
The
REG
ISTR
Y st
udy
asse
ssm
ent
time
shou
ld n
ot e
xcee
d 2.
5 ho
urs.
The
cond
uct
of e
ach
sub-
stud
y w
ill fo
llow
ad
min
istra
tive
guid
elin
es s
et o
ut in
SO
Ps.E
ach
sub-
stud
y ha
s a
task
forc
e to
coo
rdin
ate
the
train
ing,
da
ta c
olle
ctio
n an
d st
atis
tical
ana
lysi
s, a
nd is
cha
rged
with
the
res
pons
ibili
ty t
o di
strib
ute
the
findi
ngs
from
the
sub-
stud
y in
a p
eer-
revi
ewed
pub
licat
ion.
6.8
Ret
rosp
ectiv
e da
ta c
olle
ctio
nPa
rtici
pant
s w
ill b
e sp
ecifi
cally
ask
ed f
or t
heir
perm
issi
on t
o en
ter
clin
ical
data
prio
r to
the
dat
e of
en
rolm
ent t
o R
EGIS
TRY,
and
they
will
be a
t lib
erty
to c
ontri
bute
to th
e pr
ospe
ctiv
e st
udy
only
. M
ultip
le
stud
y si
tes
have
sys
tem
atic
ally
col
lect
ed a
sses
smen
ts o
f H
D p
atie
nts
usin
g st
anda
rd t
ools
(e.
g.
UH
DR
S) th
at w
ere
gene
rate
d ei
ther
in th
e co
urse
of t
heir
norm
al c
linic
al p
ract
ice
or d
urin
g th
e co
urse
of
cond
uctin
g H
D–r
elat
ed r
esea
rch
proj
ects
. In
orde
r to
allo
w th
e re
sear
ch c
omm
unity
to h
ave
acce
ss to
26
thes
e sy
stem
atic
ally
col
lect
ed c
linic
al d
ata,
rec
orde
d pr
ior
to p
artic
ipat
ion
in R
EGIS
TRY,
stu
dy s
ites
have
the
opt
ion
to r
eque
st p
erm
issi
on f
rom
REG
ISTR
Y-H
Dpa
rtici
pant
s to
ent
er t
hese
dat
a. T
he
colle
ctio
n of
ret
rosp
ectiv
e da
ta w
ill si
gnifi
cant
ly e
nric
h th
e cl
inic
al d
ata
repo
sito
ry a
vaila
ble
on th
is H
D
coho
rt. T
he c
ombi
natio
n of
ret
rosp
ectiv
e an
d pr
ospe
ctiv
e cl
inic
al d
ata
will
prov
ide
a un
ique
and
in
valu
able
res
ourc
e th
at c
an b
e us
ed to
und
erst
and
mor
e ab
out c
linic
ally
sig
nific
ant c
hang
es o
ver
the
natu
ral c
ours
e of
HD
. C
onse
nt t
o pr
ovid
ing
thes
e da
ta is
no
addi
tiona
l bur
den
on t
hepa
rtici
pant
. A
pa
rtici
pant
may
cho
ose
to o
pt in
or o
pt o
ut o
f thi
s op
tiona
l com
pone
nt.
6.9
REG
ISTR
Y as
sess
men
ts
At th
e ba
selin
e st
udy
visi
t,th
e fo
llow
ing
will
take
pla
ce:
a)C
linic
al p
heno
typi
cal c
hara
cter
isat
ion
will
be a
sses
sed
and
docu
men
ted
base
d on
info
rmat
ion
obta
ined
from
:
Trai
ned
rate
rsw
ho r
ecor
d th
eir
clin
ical
impr
essi
on u
sing
rat
ing
scal
es (
i.e. U
HD
RS’
99,
the
PBA-
san
d co
gniti
ve te
sts;
CSS
R-S
).
Parti
cipa
nts
them
selv
es w
ho r
epor
t on
thei
r su
bjec
tive
expe
rienc
e (i.
e. H
ADS-
SIS
, SF-
36 a
nd a
hea
lth e
cono
mic
s sc
ale
(CSR
I-R)
Partn
ers/
Com
pani
ons
who
rep
ort o
n th
e le
vel o
f fun
ctio
n an
d ne
urop
sych
iatri
c as
pect
s of
the
parti
cipa
nt, a
nd q
ualit
y of
life
.
b)D
onat
ion
of b
iolo
gica
l sp
ecim
ens
–30
ml
of b
lood
and
30
ml
of u
rine
(REG
ISTR
Y-H
Dpa
rtici
pant
);20
ml o
f blo
od a
nd 3
0 m
l of u
rine
(REG
ISTR
Y-C
ON
TRO
Lpa
rtici
pant
).
c)C
ompl
etio
n of
a fa
mily
his
tory
que
stio
nnai
re (F
HQ
).
Allp
artic
ipan
ts w
ill be
invi
ted
toco
mpl
ete
aFH
Q,
in p
artic
ular
indi
vidu
als
who
do
not
have
a
know
n fa
mily
his
tory
of
the
dise
ase.
Thi
s is
an
optio
nal c
ompo
nent
of
REG
ISTR
Y.
The
FHQ
at
tem
pts
to c
olle
ctin
form
atio
n ab
out
the
hist
ory
of H
D w
ithin
a f
amily
uni
t an
d w
ill th
eref
ore
focu
s on
the
side
of t
he fa
mily
affe
cted
by
HD
. With
in th
e FH
Q d
ata
on th
ree
gene
ratio
ns w
ill be
as
sem
bled
as
wel
l as
data
on
the
spou
se(s
pous
es).
The
purp
ose
of th
e FH
Q is
(1) t
o ob
tain
a
fam
ily tr
ee a
s an
impo
rtant
par
t of s
tand
ard
med
ical
car
e an
d (2
) to
rend
er li
nked
bio
sam
ples
or
data
set
s id
entif
iabl
e w
hile
pro
tect
ing
the
priv
acy
of a
ll do
nors
. In
orde
r to
ensu
re a
n ap
prop
riate
nu
mbe
r of l
inke
d bi
osam
ples
and
link
ed c
linic
al d
ata
sets
, par
ticip
ants
are
ask
ed (p
rovi
ded
that
th
e fe
el c
omfo
rtabl
e to
do
so) t
o fo
rwar
d an
invi
tatio
n to
thei
r rel
ativ
es to
con
side
r tak
ing
part
in
REG
ISTR
Y.
d)Pa
rtici
pant
s ar
e as
ked
to i
ndic
ate
whe
ther
the
y ag
ree
to b
e co
ntac
ted
by t
he s
tudy
site
in-
betw
een
annu
al s
tudy
vis
its t
o co
llect
add
ition
al in
form
atio
n, t
o pr
ovid
e in
form
atio
n re
gard
ing
REG
ISTR
Y or
on
upco
min
g in
terv
entio
n st
udie
s fo
r w
hich
par
ticip
ants
in R
EGIS
TRY
may
be
elig
ible
in o
rder
to a
llow
them
to c
onsi
der t
heir
parti
cipa
tion.
e)Pa
rtici
pant
s w
ill be
ask
ed t
o gi
ve t
heir
cons
ent
for
regi
stra
tion
of t
heir
retro
spec
tive
data
ga
ther
ed d
urin
g co
nsul
tatio
ns p
rior
to t
heir
parti
cipa
tion
for
REG
ISTR
Y, p
rovi
ding
tha
t th
ese
data
wer
e as
sess
ed w
ith th
e sa
me
tool
s.
f)Pa
rtici
pant
s w
ill b
e as
ked
to g
ive
thei
r co
nsen
t to
take
par
t in
the
Nov
el A
sses
smen
t Pro
toco
l. Th
is w
ill pe
rmit
the
colle
ctio
n of
dat
a on
nov
el a
sses
smen
ts to
ols.
g)Pa
rtici
pant
s w
ill be
ask
ed to
con
side
r giv
ing
thei
r con
sent
to v
ideo
tapi
ng. T
he v
ideo
tape
s w
ill be
vi
sibl
e fo
r a re
stric
ted
num
ber o
f EH
DN
mem
bers
(e.g
. exp
erie
nced
phy
sici
ans,
for c
onsu
ltatio
n pu
rpos
es, p
hysi
cian
s in
trai
ning
) fo
r qu
ality
con
trol,
rese
arch
and
trai
ning
pur
pose
s on
ly.
The
reco
rdin
gs w
ill b
e tra
nsm
itted
via
sec
ure
inte
rnet
con
nect
ion
and
will
be s
tore
d on
the
R
EGIS
TRY
serv
er in
a p
seud
onym
ised
form
.
198 Hygeia Public Health 2011, 46(2): 183-218
27
At e
ach
annu
al fo
llow
up
stud
y vi
sit,
the
follo
win
g w
ill ta
ke p
lace
:
a)a
clin
ical
phe
noty
pica
l ch
arac
teris
atio
n id
entic
al t
o th
e on
e at
bas
elin
e vi
sit.
As
part
of t
he
UH
DR
S’9
9, in
form
atio
n ab
out e
vent
s w
hich
hav
e oc
curr
ed s
ince
the
last
vis
it (e
.g. c
hang
es in
oc
cupa
tion,
inte
rcur
rent
hea
lth p
robl
ems,
cha
nges
in m
edic
atio
n et
c.) w
ill be
reco
rded
.
REG
ISTR
Y-H
D p
artic
ipan
ts w
ho c
onse
nted
to d
onat
e bi
olog
ical
spe
cim
ens
and
to v
olun
teer
the
fam
ily
hist
ory
will
be
requ
este
dto
:
b)do
nate
a n
ext s
ampl
e of
bio
logi
cal s
peci
men
s (3
0m
l of b
lood
and
30
ml o
f urin
e)
c)up
date
the
FHQ
: par
ticip
ants
will
be a
sked
to p
rovi
de in
form
atio
n ab
out n
ew d
eath
s an
d on
sets
of
HD
.
All p
artic
ipan
ts w
ill b
e gi
ven
the
oppo
rtuni
ty to
re-
eval
uate
thei
r de
cisi
ons
rega
rdin
g pa
rtici
patio
n in
the
optio
nal c
ompo
nent
s of
RE
GIS
TRY.
6.10
Obs
erva
tion
sche
dule
sIn
vest
igat
ors
shou
ld e
valu
ate
REG
ISTR
Y-H
Dpa
rtici
pant
s at
leas
t onc
e a
year
. The
stu
dy c
alls
for
the
docu
men
tatio
nof
ann
ual a
sses
smen
ts. T
he p
rede
fined
rang
e of
tole
ranc
e fo
r the
ann
ual a
sses
smen
t is
±1
mon
th.
If th
e pa
rtici
pant
has
to
be s
een
mor
e fre
quen
tly t
han
once
a y
ear
for
med
ical
rea
sons
, as
sess
men
ts c
an b
e co
nduc
ted
and
can
be d
ocum
ente
d m
ore
frequ
ently
.
Atea
ch a
nnua
l vis
it, th
e fo
llow
ing
will
take
pla
ce:
A cl
inic
al p
heno
typi
cal c
hara
cter
isat
ion
as d
escr
ibed
abo
ve. A
s pa
rt of
the
UH
DR
S, in
form
atio
n ab
out
even
ts,
whi
ch h
ave
occu
rred
sin
ce t
he l
ast
visi
t (e
.g.
chan
ges
in o
ccup
atio
n, c
oncu
rren
t he
alth
pr
oble
ms,
cha
nges
in m
edic
atio
n et
c.) w
ill b
e co
llect
ed.
REG
ISTR
Y-H
D p
artic
ipan
ts w
ho c
onse
nted
to d
onat
e bi
olog
ical
spe
cim
ens
and
to v
olun
teer
the
fam
ily
hist
ory
will
be
requ
este
d to
:
upda
te th
e FH
Q: h
e or
she
will
be a
sked
to p
rovi
de in
form
atio
n ab
out n
ew d
eath
san
d on
sets
of
HD
dona
te a
sam
ple
of b
iolo
gica
l spe
cim
ens–
30 m
l of
bloo
d an
d 30
ml o
f ur
ine
–to
obt
ain
the
follo
win
g m
ater
ials
:o
One
10m
ltub
eof
blo
od fo
r the
cry
opre
serv
atio
n of
lym
phoc
ytes
(col
lect
ed a
nnua
lly)
oO
ne 1
0m
l tub
e of
bloo
d to
con
firm
the
size
of t
he C
AG
exp
ansi
on m
utat
ion
with
in th
e H
D g
ene
for r
esea
rch
purp
oses
onl
yan
d to
cre
ate
lym
phob
last
oid
cell
lines
.o
One
9.5
ml
tube
of w
hole
blo
od (
EDTA
)fo
r pl
asm
a co
llect
ion
(col
lect
ed a
nnua
lly a
t se
lect
ed s
ites)
oU
rine
(30
ml)
for
stud
ies
to e
stab
lish
and
valid
ate
mar
kers
tra
ckin
g th
e pr
ogre
ssiv
e co
urse
of H
D (e
.g. m
etab
olom
ics)
.
Not
e:
All p
artic
ipan
ts w
ill b
e gi
ven
the
oppo
rtuni
ty to
re-
eval
uate
thei
r de
cisi
ons
rega
rdin
g pa
rtici
patio
n in
the
optio
nal c
ompo
nent
s.
at th
e di
scre
tion
of th
e R
EGIS
TRY
Stee
ring
Com
mitt
ee, t
he a
dditi
ves
in th
e tu
bes
used
for b
lood
do
natio
n as
wel
l as
the
proc
edur
es f
or s
hipm
ent
(am
bien
t te
mpe
ratu
re,
on d
ry ic
e et
c.)
may
cha
nge;
th
ese
chan
ges
will
not
be r
egar
ded
as s
ubst
antia
l ch
ange
s in
the
stu
dy p
roce
dure
s, i
.e.
are
not
cons
ider
ed im
porta
nt e
noug
h to
just
ify a
n am
endm
ent.
AnSO
P f
or P
lasm
a C
olle
ctio
n is
in p
lace
to
ensu
re c
onsi
sten
cy in
pro
cedu
res
acro
ss s
ites
colle
ctio
n pl
asm
a sa
mpl
es.
28
Stud
y pe
rson
nel
will
wor
k in
con
junc
tion
with
the
stu
dy p
artic
ipan
ts t
o cr
eate
a m
echa
nism
to
best
co
ntac
t the
par
ticip
ants
to s
et u
p ye
arly
stu
dy v
isits
. Thi
s w
ill be
use
d to
max
imis
epa
rtici
pant
rete
ntio
n in
the
stud
y. R
EGIS
TRY
HD
par
ticip
ants
will
be g
iven
the
optio
n of
allo
win
g st
udy
pers
onne
l to
cont
act
them
in-
betw
een
visi
ts f
or a
dditi
onal
cla
rific
atio
ns o
r to
pro
vide
upd
ates
reg
ardi
ng R
EGIS
TRY
or t
o co
nsid
er u
pcom
ing
inte
rven
tion
stud
ies
for w
hich
par
ticip
ants
in R
EGIS
TRY
may
be
elig
ible
.
6.11
Des
crip
tion
of th
e st
udy
popu
latio
n6.
11.1
Parti
cipa
nt s
elec
tion
crite
riaR
EGIS
TRY-
HD
par
ticip
ants
incl
ude
thos
e w
ho a
re w
illin
g to
par
ticip
ate
in r
egul
ar (
annu
al)
eval
uatio
ns
cond
ucte
d by
the
inve
stig
ator
s an
d ha
ve a
dia
gnos
is o
f HD
, are
HD
mut
atio
n ca
rrie
rs o
r per
sons
at r
isk
for
HD
(fir
st a
nd s
econ
d de
gree
rel
ativ
es o
f pe
ople
affe
cted
by
HD
), ar
e no
n-H
D m
utat
ion
carr
ier
rela
tives
. Spo
uses
of p
artic
ipan
ts m
ayta
ke p
arta
s R
EG
ISTR
Y-C
ON
TRO
LS.
Incl
usio
n cr
iteria
The
follo
win
g in
divi
dual
s m
ay b
e el
igib
le to
par
ticip
ate
A. In
divi
dual
s, c
onfir
med
HD
mut
atio
n ca
rrie
rB.
Man
ifest
HD
, with
out C
AG
test
ing
C. H
D fa
mily
mem
ber a
t-ris
k,w
ithou
t CAG
test
ing
D. H
D fa
mily
mem
ber,
non-
HD
mut
atio
n ca
rrie
rE.
REG
ISTR
Y-C
ON
TRO
L pa
rtici
pant
s: c
ompa
nion
/indi
vidu
alw
ithou
t HD
his
tory
F. R
EGIS
TRY-
CO
MP
ANIO
N (a
ny o
f the
abo
ve).
Parti
cipa
nts
may
be
mal
e or
fem
ale
and
of a
ny a
ge. A
ll pa
rtici
pant
s m
ust b
e ab
le to
pro
vide
con
sent
for
them
selv
es, h
ave
a pa
rent
/gua
rdia
n w
ho c
an p
rovi
de p
aren
tal p
erm
issi
on, o
r ha
ve a
n au
thor
ised
lega
l re
pres
enta
tive
who
can
pro
vide
con
sent
.
Chi
ldre
n an
d m
enta
lly c
ompr
omis
ed i
ndiv
idua
ls m
ay b
e in
clud
ed i
n R
EGIS
TRY.
Chi
ldre
n w
ith H
D
shou
ld b
e in
clud
ed in
this
stu
dy b
ecau
se R
EGIS
TRY
shou
ld re
flect
the
entir
e sp
ectru
m o
f HD
incl
udin
g ju
veni
le H
D. J
uven
ile H
D p
atie
nts
pres
ent w
ith a
clin
ical
phe
noty
pe q
uite
dis
tinct
from
the
phen
otyp
e of
ad
ult
onse
t pa
tient
s. T
heir
inci
denc
e is
app
roxi
mat
ely
10%
of
all a
ffect
ed b
y H
D.
A be
tter
desc
riptio
n an
d un
ders
tand
ing
of j
uven
ile H
D p
atie
nts
is a
pre
requ
isite
to
deve
lop
treat
men
t op
tions
for
thi
s im
porta
nt s
ubpo
pula
tion.
In
addi
tion,
it
is p
ossi
ble
that
chi
ldre
n w
ill be
elig
ible
bec
ause
the
y ha
ve
pare
nts
or
sibl
ings
w
ho
are
affe
cted
by
H
D.
Par
enta
l pe
rmis
sion
w
ill be
ob
tain
ed
from
on
e pa
rent
/gua
rdia
n fo
r ea
ch p
artic
ipan
tun
der
the
age
of 1
8 w
ho p
artic
ipat
es i
n th
is s
tudy
. In
add
ition
, ve
rbal
or
writ
ten
asse
nt b
y th
e pa
rtici
patin
g ch
ild w
ill be
obt
aine
d w
hen
appr
opria
te.
Gui
delin
es f
or
obta
inin
g as
sent
are
det
aile
d be
low
(ple
ase
see
the
para
grap
h: ‘P
artic
ipan
t inf
orm
ed c
onse
nt’).
Not
e on
vul
nera
ble
parti
cipa
nts
and
parti
cipa
nts
with
redu
ced
capa
city
for c
onse
nt:
Indi
vidu
als
with
HD
who
se d
isea
se h
as p
rogr
esse
d to
the
poin
t of m
enta
l inc
apac
ity m
ay b
e en
rolle
d in
R
EGIS
TRY.
Pat
ient
s in
ver
y ad
vanc
ed s
tage
s of
HD
sho
uld
be i
nclu
ded
in t
his
stud
y, b
ecau
se
REG
ISTR
Y sh
ould
asc
erta
in th
e en
tire
spec
trum
of H
D. A
stu
dy s
ite in
vest
igat
or w
ill de
term
ine
men
tal
inca
paci
ty a
t the
bas
elin
e vi
sit.
Men
tally
com
prom
ised
indi
vidu
als
will
be a
sked
to p
artic
ipat
e w
ith t
he
cons
ent o
f an
auth
oris
ed le
gal r
epre
sent
ativ
e.
Exc
lusi
on c
riter
ia
Parti
cipa
nts
who
are
una
ble
to u
nder
stan
d th
e st
udy
prot
ocol
or u
nabl
e to
giv
e in
form
ed c
onse
nt,
and
have
no
lega
l rep
rese
ntat
ive.
Parti
cipa
nts
with
cho
reic
mov
emen
t dis
orde
r ot
her
than
HD
.(EH
DN
pro
vide
s a
Reg
istry
-like
tool
to
reco
rd f
indi
ngs
in p
atie
nts
affe
cted
with
cho
reat
icm
ovem
ent
diso
rder
s ot
her
than
HD
und
er t
he
labe
l “N
euro
acan
thoc
ytos
is”;
ww
w.e
uro-
hd.n
et/h
tml/n
a/re
gist
ry).
199Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
29
6.12
Met
hod
of Id
entif
icat
ion
and
Rec
ruitm
ent o
f stu
dy p
artic
ipan
tsTh
e re
sear
ch s
taff
at t
he s
ite w
ill re
crui
t po
tent
ially
elig
ible
parti
cipa
nts
and
inqu
ire a
s to
the
ir w
illing
ness
to p
artic
ipat
e in
this
stu
dy.
6.13
Part
icip
ant i
nfor
med
con
sent
Th
e re
sear
ch s
taff
at th
e st
udy
site
s w
ill s
eek
cons
ent f
rom
any
elig
ible
par
ticip
antw
illing
to p
artic
ipat
e.
At t
he t
ime
of t
he p
oten
tial
parti
cipa
nt's
vis
it an
exp
lana
tion
of t
he s
tudy
and
a c
opy
of t
he P
atie
nt
Info
rmat
ion
Shee
t (se
e A
ppen
dix
B) p
repa
red
in th
e re
spec
tive
nativ
e la
ngua
ge a
nd a
ppro
ved
by th
e re
spec
tive
IRB
will
be p
rovi
ded.
The
opp
ortu
nity
to
read
the
con
sent
will
be g
iven
and
que
stio
ns
answ
ered
by
the
rese
arch
sta
ff. T
he p
artic
ipan
twill
be g
iven
the
oppo
rtuni
ty to
take
the
cons
ent f
orm
ho
me
to d
iscu
ss w
ith fa
mily
mem
bers
, and
con
sent
will
be o
btai
ned
at a
futu
re v
isit.
Par
ticip
atio
n in
the
stud
y w
ill no
t be
purs
ued
if th
e po
tent
ial p
artic
ipan
t dec
lare
s no
t to
be c
onta
cted
, unl
ess
the
pote
ntia
l pa
rtici
pant
agr
ees
to fu
ture
dis
cuss
ion.
The
site
inv
estig
ator
will
det
erm
ine
whe
ther
or
not
a po
tent
ial
parti
cipa
nt h
as d
imin
ishe
d m
enta
l ca
paci
ty w
hich
may
int
erfe
re w
ith g
ivin
g in
form
ed c
onse
nt.
If a
pote
ntia
l pa
rtici
pant
with
men
tal
inca
paci
ty is
app
roac
hed
for e
nrol
men
t, th
e re
sear
ch s
taff
will
seek
con
sent
from
that
par
ticip
ant's
lega
l re
pres
enta
tive.
A le
gal r
epre
sent
ativ
e m
ay b
e de
fined
as
an in
divi
dual
with
gua
rdia
nshi
p or
a h
ealth
ca
re p
roxy
, pr
ovid
ed c
onse
ntin
g fo
r re
sear
ch s
tudi
es i
s w
ithin
the
sco
pe o
f th
e pr
oxy'
s de
lega
ted
resp
onsi
bilit
ies.
Hea
lth c
are
prox
ies
may
be
the
pote
ntia
l par
ticip
ant's
nex
t-of-k
in, a
rel
ativ
e, o
r a lo
ng-
term
car
egiv
er/s
igni
fican
t ot
her
or a
n ap
poin
tee
by a
cou
rt of
law
; th
is p
erso
n m
ust
be m
enta
lly
cogn
isan
t and
be
able
to u
nder
stan
d th
e pr
oced
ures
, ris
ks, a
nd b
enef
its in
volv
ed w
ith th
e st
udy.
At t
he
time
of th
e pa
rtici
pant
's v
isit,
an
expl
anat
ion
of th
e st
udy
and
a co
py o
f the
con
sent
will
be p
rovi
ded
tobo
th th
e pa
rtici
pant
and
the
auth
oris
ed re
pres
enta
tive.
Opp
ortu
nity
to re
ad th
e co
nsen
t will
be g
iven
and
qu
estio
ns a
nsw
ered
by
the
rese
arch
sta
ff. T
he p
artic
ipan
t/aut
horis
ed r
epre
sent
ativ
e w
ill be
giv
en t
he
oppo
rtuni
ty t
o ta
ke t
he c
onse
nt f
orm
hom
e w
ithth
em f
or f
urth
er d
iscu
ssio
ns a
nd c
onse
nt w
ill b
e ob
tain
ed a
t a fu
ture
vis
it. A
lthou
gh th
e au
thor
ised
rep
rese
ntat
ive
will
be o
ffici
ally
pro
vidi
ng c
onse
nt fo
r th
e pa
rtici
pant
to p
artic
ipat
e, th
e pa
rtici
pant
mus
t als
o ag
ree
to p
artic
ipat
e.
Parti
cipa
nts
with
HD
may
lose
men
tal c
apac
ity to
pro
vide
con
tinue
d co
nsen
t dur
ing
the
cour
se o
f thi
s st
udy
beca
use
of th
e st
udy'
s lo
ng-te
rm n
atur
e. T
here
fore
, par
ticip
ants
who
hav
e be
en d
iagn
osed
with
H
D w
ill be
ask
ed t
o co
nsid
er a
ppoi
ntin
g a
rese
arch
pro
xy t
o ai
d in
the
dec
isio
n m
akin
g pr
oces
s fo
r co
ntin
ued
parti
cipa
tion.
Par
ticip
ants
will
be e
ncou
rage
d to
dis
cuss
thei
r fut
ure
stud
y pa
rtici
patio
n w
ishe
s w
ith th
e re
sear
ch p
roxy
.
For p
oten
tial p
artic
ipan
ts w
ho a
re c
hild
ren
at th
e tim
e of
enr
olm
ent,
pare
ntal
per
mis
sion
will
be o
btai
ned
from
one
par
ent/g
uard
ian
for
each
par
ticip
ant
unde
r th
e ag
e of
18
who
par
ticip
ates
in t
his
stud
y. I
n ad
ditio
n, v
erba
l or w
ritte
n as
sent
by
the
parti
cipa
ting
child
will
be o
btai
ned
whe
n ap
prop
riate
. Gui
delin
es
for o
btai
ning
ass
ent i
nclu
de:
for c
hild
ren
unde
r the
age
of 7
, onl
y w
ritte
n pa
rent
al p
erm
issi
on w
ill be
obt
aine
d an
d do
cum
ente
dfo
r chi
ldre
n 7
to 1
2 ye
ars
of a
ge, w
ritte
n pa
rent
al p
erm
issi
on a
nd v
erba
l ass
ent b
y th
e pa
rtici
patin
g ch
ild w
ill be
obt
aine
d an
d do
cum
ente
d.fo
r chi
ldre
n 13
to 1
7 ye
ars
of a
ge, p
aren
tal p
erm
issi
on w
ith w
ritte
n as
sent
by
the
parti
cipa
ting
child
w
ill be
obt
aine
d an
d do
cum
ente
d th
roug
h si
gnat
ure.
Any
parti
cipa
ntw
ho b
egin
s pa
rtici
patio
n in
this
stu
dy a
s a
min
or (
unde
r th
e ag
e of
18)
will
be a
sked
to
reco
nsen
t for
this
stu
dy a
fter t
urni
ng 1
8 ye
ars
of a
ge.
For t
he U
K, th
e M
enta
l Cap
acity
Act
requ
ires
spec
ific
proc
edur
es w
hich
are
des
crib
ed b
elow
.
If a
pote
ntia
l pa
rtici
pant
with
men
tal
inca
paci
ty i
s ap
proa
ched
for
enr
olm
ent,
the
rese
arch
sta
ff w
ill id
entif
y an
app
ropr
iate
con
sulte
e w
ho c
an a
dvis
e on
the
pre
sum
ed w
ishe
s an
d fe
elin
gs o
f th
e pa
rtici
pant
.
30
The
follo
win
g st
eps
will
be ta
ken
in o
rder
to id
entif
y a
suita
ble
cons
ulte
e:
Iden
tifyi
ng a
con
sulte
e
If an
unp
aid
care
r (e
.g. s
pous
e or
fam
ily m
embe
r) c
an b
e id
entif
ied
and
they
are
willi
ng to
be
invo
lved
, th
ey w
ill ha
ve t
he r
esea
rch
expl
aine
d to
the
m a
nd w
ill be
ask
ed f
or t
heir
advi
ce o
n in
volv
ing
the
pers
on in
the
rese
arch
. The
con
sulte
e m
ust b
e so
meo
ne w
ho k
now
s th
e po
tent
ial
parti
cipa
nt w
ell a
nd w
ho w
ill be
abl
e to
giv
e an
opi
nion
abo
ut t
he p
erso
n’s
pres
umed
wis
hes
and
feel
ings
.If
the
care
r atte
ndin
g th
e re
sear
ch a
ppoi
ntm
ent i
s a
heal
th c
are
prof
essi
onal
, the
n at
tem
pts
will
be
mad
e to
find
a fr
iend
or
fam
ily m
embe
r (o
r so
meo
ne w
ith L
astin
g Po
wer
of A
ttorn
ey (
LPA)
fo
r the
pers
on) w
ho k
now
s th
e pe
rson
wel
l and
they
will
be a
sked
for t
heir
advi
ce.
If th
ere
is n
o un
paid
car
er, f
riend
or f
amily
mem
ber a
nd n
o-on
e w
ith L
PA
then
a c
onsu
ltee
who
is
not
invo
lved
with
the
pro
ject
will
be
nom
inat
ed.
An
inde
pend
ent
cons
ulte
e co
uld
eith
er b
e id
entif
ied
by th
e cl
inic
al r
esea
rch
team
or
the
Hun
tingt
on’s
dis
ease
Ass
ocia
tion
Reg
iona
l Car
e Ad
viso
r(R
CA)
. In
som
e in
stan
ces,
the
RC
A m
ay a
lso
be w
illing
to p
rovi
de a
dvic
e on
beh
alf o
f th
e pa
rtici
pant
and
is a
n in
depe
nden
t pe
rson
who
cou
ld e
ither
act
as
cons
ulte
e or
ass
ist
in
iden
tifyi
ng s
omeo
ne fa
milia
r with
HD
to a
ct in
this
role
.
The
follo
win
g st
eps
will
be t
aken
to
disc
uss
the
rese
arch
with
the
con
sulte
e an
d th
e po
tent
ial
parti
cipa
nt:
Invi
tatio
n to
par
ticip
ate
in re
sear
ch
An e
xpla
natio
n of
the
stud
y an
d a
copy
of t
he p
atie
nt in
form
atio
n sh
eet,
cons
ulte
e in
form
atio
n sh
eet a
nd p
atie
nt c
onse
nt fo
rm w
ill be
pro
vide
d to
bot
h th
e pa
rtici
pant
and
the
cons
ulte
e.C
arer
s or
nom
inat
ed th
ird p
artie
s m
ust b
e co
nsul
ted
and
agre
e th
at th
e pe
rson
wou
ld w
ant t
o jo
in th
e re
sear
ch p
roje
ct. I
n pa
rticu
lar,
the
cons
ulte
e sh
ould
adv
ise
abou
t:o
whe
ther
the
pers
on w
ho la
cks
capa
city
sho
uld
take
par
t in
the
proj
ect,
and
wha
t the
y th
ink
the
pers
on’s
feel
ings
and
wis
hes
wou
ld b
e, if
they
had
cap
acity
to d
ecid
e w
heth
er
to ta
ke p
art.
If th
e pe
rson
sho
ws
any
sign
s of
resi
stan
ce o
r ind
icat
es in
any
way
that
he
or s
he d
oes
not w
ish
to ta
ke p
art,
the
pers
on m
ust b
e w
ithdr
awn
from
the
proj
ect i
mm
edia
tely
. So
met
imes
the
cons
ulte
e w
ill sa
y th
at th
e pe
rson
wou
ld p
roba
bly
not t
ake
part
in th
e pr
ojec
t or
that
the
y w
ould
ask
to
be w
ithdr
awn.
In
this
situ
atio
n, t
he r
esea
rche
r m
ust
not
incl
ude
the
pers
on in
the
proj
ect,
or th
ey s
houl
d w
ithdr
aw th
em fr
om it
Ev
en w
hen
a co
nsul
tee
agre
es t
hat
a pe
rson
can
tak
e pa
rt in
res
earc
h, t
he r
esea
rche
r m
ust
pay
extra
atte
ntio
n to
mon
itorin
g th
e pe
rson
’s w
ishe
s an
d fe
elin
gs.
If pa
rtici
pant
s lo
se m
enta
l cap
acity
dur
ing
the
cour
se o
f thi
s st
udy
the
abov
e st
eps
will
also
be
take
n to
id
entif
y a
suita
ble
cons
ulte
e w
ho c
an a
dvis
e on
the
pres
umed
wis
hes
ofth
e pa
rtici
pant
.
6.14
Doc
umen
tatio
n of
Con
sent
/Ass
ent
Sign
ed c
onse
nt/a
ssen
t fo
rms
will
be s
tore
d in
a d
esig
nate
d lo
catio
n at
the
site
. A
sign
ed c
opy
of t
he
cons
ent/a
ssen
t w
ill be
pro
vide
d to
the
par
ticip
ant/p
aren
t/gua
rdia
n an
d, i
f ap
plic
able
, th
eir
auth
oris
ed
repr
esen
tativ
e.
6.15
Stud
y Pr
oced
ures
-D
escr
iptio
ns6.
15.1
Clin
ical
Cha
ract
eris
tics
The
clin
ical
cha
ract
eris
tics
ques
tionn
aire
will
capt
ure
esse
ntia
l and
mor
e de
taile
d in
form
atio
n of
whe
n si
gns
and
sym
ptom
s fir
st a
ppea
r. Th
e ex
amin
er is
inst
ruct
ed to
pro
vide
a b
est e
stim
ate
onse
t age
for a
ra
nge
of c
linic
al fe
atur
es. D
ata
obta
ined
from
this
que
stio
nnai
re w
ill pe
rmit
futu
re s
tudi
es to
eva
luat
e th
e ex
tent
to w
hich
oth
er g
enet
ic o
r en
viro
nmen
tal m
odifi
ers
influ
ence
the
age
of o
nset
of s
ympt
oms
othe
r th
an th
e m
ovem
ent d
isor
der i
n H
D.
200 Hygeia Public Health 2011, 46(2): 183-218
31
6.15
.2U
nifie
d H
untin
gton
's D
isea
se R
atin
g Sc
ale
99 (U
HD
RS
99)
The
Uni
fied
Hun
tingt
on's
Dis
ease
Rat
ing
Scal
e 99
(UH
DR
S’99
) will
be u
sed
by tr
aine
d ra
ters
to a
sses
s an
d do
cum
ent t
he c
linic
al a
spec
ts o
f HD
. The
UH
DR
Sco
nsis
ts o
f fou
r par
ts: c
ogni
tion,
mot
or fu
nctio
n,
beha
viou
r, an
d fu
nctio
nal c
apac
ity.
Mod
ified
ver
sion
s of
the
se s
cale
s an
d ot
her
scal
es m
ay b
e us
ed
whe
re th
ese
may
be
appr
opria
te fo
r m
easu
ring
the
prog
ress
ion
of H
D in
pat
ient
s of
oth
er a
ge g
roup
s (e
.g.,
juve
nile
-ons
et a
nd la
te-o
nset
HD
)or d
iffer
ent d
egre
es o
f cap
acity
.
The
mot
or s
ectio
nof
the
UH
DR
S as
sess
es m
otor
fea
ture
s of
HD
usi
ng s
tand
ardi
zed
ratin
gs o
f oc
ulom
otor
func
tion,
dys
arth
ria, m
otor
impe
rsis
tenc
e, c
hore
a, d
ysto
nia,
bra
dyki
nesi
a, g
ait,
and
post
ural
st
abilit
y. T
he to
tal m
otor
impa
irmen
t sco
re is
the
sum
of
the
indi
vidu
al m
otor
rat
ings
(ra
nge
0 –
124)
; hi
gher
sco
res
indi
cate
mor
e se
vere
mot
or im
pairm
ent.
Cog
nitio
nis
ass
esse
d by
a v
erba
l flu
ency
test
(let
ter a
nd c
ateg
ory
fluen
cy),
Sym
bol D
igit
Mod
ality
Tes
t an
d St
roop
Int
erfe
renc
e Te
st.
Hig
her
scor
es i
ndic
ate
bette
r co
gniti
ve p
erfo
rman
ce.
An e
xten
ded
cogn
itive
ass
essm
ent i
nclu
des
the
follo
win
g st
anda
rdis
ed n
euro
psyc
holo
gica
l tes
ts: t
he H
opki
ns V
erba
l Le
arni
ng T
est;
Trai
l Mak
ing
(Par
ts A
& B
); M
attis
Dem
entia
Rat
ing
Scal
e (o
ptio
nal).
The
beha
viou
ral a
sses
smen
tmea
sure
s fre
quen
cy a
nd s
ever
ity o
f sym
ptom
s re
late
d to
alte
red
affe
ct,
thou
ght c
onte
nt a
nd c
opin
g st
yles
. The
tota
l beh
avio
ur s
core
is th
e su
m o
f all
resp
onse
s; h
ighe
r sco
res
indi
cate
mor
e se
vere
impa
irmen
t. N
ote:
PB
A-s
train
ed s
ite in
vest
igat
ors
are
perm
itted
to a
dmin
iste
r the
PB
A-s
in p
lace
of t
he U
HD
RS-
Beha
viou
ral s
cale
.To
gaug
e an
indi
vidu
al’s
sui
cida
lity
and
risk
of h
arm
to
self
and
othe
rs, t
he C
SSR
Sca
n be
adm
inis
tere
d by
a r
ater
follo
win
g a
stru
ctur
ed in
terv
iew
. Thi
s sc
ale
was
dev
elop
ed in
the
Nat
iona
l Ins
titut
e of
Men
tal H
ealth
Tre
atm
ent o
f Ad
oles
cent
Sui
cide
Atte
mpt
ers
Stud
y to
ass
ess
seve
rity
and
mon
itor
suic
idal
eve
nts
durin
g a
treat
men
t per
iod
(39)
. The
inte
rvie
w c
an
prov
ide
an o
vera
ll as
sess
men
t of s
uici
dal i
deat
ion
as w
ell a
s be
havi
our i
n or
der t
o ge
nera
te a
sum
mar
y m
easu
re o
f su
icid
ality
. Th
is r
atin
g sc
ale
has
been
use
d in
prio
r in
terv
entio
nal
stud
ies
for
both
ps
ycho
tropi
c an
d no
n-ps
ycho
tropi
c co
mpo
unds
ove
r re
cent
year
s.Al
l pe
rson
nel
invo
lved
in
this
as
sess
men
t w
ill be
info
rmed
of
the
risk
indi
cato
rs a
nd p
roto
cols
out
lined
in t
he R
EGIS
TRY
SOP
for
R
isk
Asse
ssm
ent f
or h
arm
to s
elf_
othe
rs.
The
HA
DS-
SIS
com
bine
d is
a s
elf-r
epor
t rat
ing
scal
e. T
he H
AD
Sof
fers
a b
rief r
atin
g of
dep
ress
ion
and
anxi
ety
sym
ptom
s th
at r
efle
cts
prim
arily
moo
d ra
ther
tha
n co
gniti
ve a
nd s
omat
ic s
ympt
oms.
Thi
s co
mm
erci
ally
ava
ilabl
e sc
ale
has
14 it
ems,
7 m
easu
ring
anxi
ety
and
7 m
easu
ring
depr
essi
on p
rodu
cing
se
para
te a
nxie
ty a
nd d
epre
ssio
n su
b-sc
ores
. Eac
h ite
m is
rat
ed o
n a
four
-poi
nt s
cale
. Ind
ivid
ual i
tem
an
d gl
obal
(su
mm
ed)
depr
essi
on a
nd a
nxie
ty s
ub-s
core
s w
ill b
e an
alys
ed.
The
HAD
S h
as a
n ad
vant
age
over
the
BDI i
n th
at th
e H
ADS
is le
ss s
usce
ptib
le to
con
foun
ds fr
om th
e so
mat
ic s
ympt
oms
in H
D. M
oreo
ver,
is a
rece
nt v
alid
atio
n st
udy
(aga
inst
the
SCAN
–Sc
hedu
le fo
r C
linic
al A
sses
smen
t in
Neu
rops
ychi
atry
) by
Jen
ny K
eylo
ck fr
om H
ugh
Ric
kard
’s g
roup
at t
he B
arbe
rry
Cen
tre in
Birm
ingh
am,
UK,
the
dep
ress
ion
sub-
scal
e of
the
HAD
S (H
ADS-
D)
was
fou
nd t
o di
scrim
inat
e m
axim
ally
bet
wee
n de
pres
sed
and
non-
depr
esse
d H
D p
atie
nts
whe
reas
the
BDI-I
I per
form
ed th
e le
ast s
atis
fact
orily
of a
ll sc
ales
(40)
.
The
SIS
is a
brie
f ra
ting
scal
e of
irrit
abilit
y by
sel
f an
d co
mpa
nion
(tw
o se
para
te f
orm
s). T
he s
cale
is
com
pose
d of
8 it
ems
each
rat
ed o
n a
four
-poi
nt s
cale
. Fo
ur it
ems
are
focu
sed
on in
war
dly
focu
sed
irrita
bilit
y an
d fo
ur it
ems
are
focu
sed
on o
utw
ard
irrita
bilit
y. In
divi
dual
item
and
glo
bal (
sum
med
) inw
ard
and
outw
ard
irrita
bilit
y su
b-sc
ores
will
be
anal
ysed
as
wel
l as
a to
tal s
cale
sco
re.
Func
tiona
l ass
essm
ents
incl
ude
the
tota
l fun
ctio
nal c
apac
ity (
TFC
), th
e in
depe
nden
ce s
cale
, an
d a
chec
klis
t of
com
mon
dai
ly t
asks
; hi
gher
sco
res
indi
cate
bet
ter
func
tioni
ng.
The
exte
nt o
f fu
nctio
nal
disa
bilit
y co
rrel
ates
wel
l with
the
exte
nt o
f bas
al g
angl
ia d
egen
erat
ion
dete
cted
by n
euro
imag
ing.
The
tota
l UH
DR
Sta
kes
appr
oxim
atel
y 45
min
utes
to
com
plet
e. T
o m
aint
ain
cons
iste
ncy
of t
he d
ata
colle
cted
for
REG
ISTR
Y, a
t ea
ch s
tudy
site
the
ass
essm
ent
shou
ld b
e pe
rform
ed b
y th
e sa
me
indi
vidu
al(s
) at e
ach
visi
t.
32
6.15
.3Fa
mily
His
tory
Que
stio
nnai
re (F
HQ
)A
ques
tionn
aire
will
be h
ande
d to
con
sent
ing
parti
cipa
nts
to s
hare
the
ir fa
mily
tre
e by
indi
catin
g ho
w
man
y si
blin
gs, c
hild
ren
and
rela
tives
up
to t
he s
econ
d de
gree
they
got
and
to v
olun
teer
the
fol
low
ing
info
rmat
ion
on e
ach
pers
on w
ithin
the
fam
ily tr
ee:
gend
er
year
of b
irth
aliv
e/de
ado
for
thos
e de
ceas
ed:
year
of
deat
h/ag
e at
dea
th a
nd –
as b
est
as p
artic
ipan
ts c
an t
ell –
caus
e of
dea
thlo
cala
vaila
bilit
yof
DN
A sa
mpl
esop
inio
n w
heth
er in
the
view
of t
he c
ontri
buto
r a
mem
ber
of a
fam
ily is
affe
cted
with
HD
/car
ries
the
HD
mut
atio
no
for t
hose
affe
cted
with
HD
/car
ryin
g th
e H
D m
utat
ion:
age
at t
ime
of H
D d
iagn
osis
/pre
dict
ive
test
ing,
firs
t si
gns
and
sym
ptom
s an
d w
heth
er t
he d
iagn
osis
of
HD
was
con
firm
ed b
y ph
ysic
ian/
gene
tic te
stin
g
From
thes
e da
taa
fam
ily tr
ee w
ill be
gen
erat
ed u
sing
app
ropr
iate
sof
twar
e. W
ithin
this
fam
ily tr
ee th
e sy
mbo
ls r
epre
sent
ing
thos
e m
embe
rs o
f the
fam
ily w
ho c
onse
nted
to p
artic
ipat
e in
REG
ISTR
Y w
ill be
an
nota
ted
with
thei
r pse
udon
yms;
fam
ily m
embe
rs w
ho d
id n
ot c
onse
nt to
par
ticip
ate
in R
EGIS
TRY
will
be
rep
rese
nted
with
sym
bols
with
out
an a
nnot
ated
pse
udon
ym.
By
usin
g th
is p
roce
dure
, bi
osam
ples
an
d cl
inic
al d
ata
of r
elat
ed p
artic
ipan
ts (
whi
ch is
ess
entia
l e.g
. to
iden
tify
gene
tic m
odifi
ers
by s
ib p
air
anal
ysis
) can
be
linke
d w
hils
t als
o pr
otec
ting
the
priv
acy
of in
divi
dual
s vo
lunt
eerin
g in
form
atio
n th
roug
h th
e us
e of
thei
r pse
udon
yms.
In o
rder
to e
nsur
e an
app
ropr
iate
num
ber o
f lin
ked
bios
ampl
es a
nd li
nked
clin
ical
dat
a se
ts, p
artic
ipan
ts
are
aske
d (p
rovi
ded
that
the
fee
lco
mfo
rtabl
e to
do
so)
to f
orw
ard
an i
nvita
tion
to t
heir
rela
tives
to
cons
ider
taki
ng p
art i
n R
EGIS
TRY.
Rel
ativ
es o
f ind
ex p
artic
ipan
ts w
ould
then
be
info
rmed
abo
ut R
EGIS
TRY
by p
erso
nnel
of a
stu
dy s
ite o
f th
eir
choi
ce a
nd in
vite
d to
par
ticip
ate
in a
ll co
mpo
nent
s in
clud
ing
the
clin
ical
dat
a do
cum
enta
tion,
the
bi
osam
ple
com
pone
nt a
nd th
e fa
mily
his
tory
com
pone
nt.
6.15
.4C
AG G
enot
ypin
gIf
the
parti
cipa
nt a
gree
s to
par
ticip
ate
in t
he C
AG g
enot
ypin
g, b
lood
(10
ml)
will
be d
raw
n on
e tim
e du
ring
the
stud
y. T
his
porti
on o
f the
stu
dy is
opt
iona
l. Th
e pa
rtici
pant
may
cho
ose
to p
artic
ipat
e at
the
base
line
visi
t or a
t any
of t
he s
ubse
quen
t yea
rly v
isits
. CAG
gen
otyp
ing
will
be p
erfo
rmed
to d
etec
t the
le
ngth
of t
he C
AG re
peat
exp
ansi
on in
the
HD
gen
e. B
ioR
ep w
ill pr
oces
s bl
ood
for D
NA
extra
ctio
n an
d ge
noty
ping
.
CAG
gen
otyp
ing
is p
erfo
rmed
by
BioR
ep a
ccor
ding
to th
e fo
llow
ing
proc
edur
es:
One
tube
of p
erip
hera
l blo
od w
ill be
col
lect
ed in
a 1
0 m
l yel
low
topp
ed A
CD
(ac
id c
itrat
e de
xtro
se
solu
tion
A) tu
be a
nd s
hipp
ed b
y a
fast
cou
rier s
ervi
ce.
BioR
ep w
ill as
sign
a u
niqu
e id
entif
ier t
o th
e sa
mpl
e.D
NA
will
be o
btai
ned
from
the
bloo
d us
ing
stan
dard
pro
cedu
res.
Rou
tine
QC
stud
ies
will
be
cond
ucte
d to
est
imat
e th
e qu
ality
and
inte
grity
of t
he D
NA.
Gen
otyp
ing
will
be p
erfo
rmed
acc
ordi
ng to
sta
ndar
d pr
oced
ures
usi
ng tw
o se
ts o
f prim
er p
airs
(41
-43
).Al
l act
iviti
es a
nd te
stin
g w
ill b
e do
cum
ente
d.
6.16
Spec
imen
Rep
osito
ry: B
ioR
ep in
Mila
no (I
taly
)If
the
parti
cipa
nt a
gree
s to
don
ate
bios
ampl
es fo
r re
sear
ch in
to g
enet
ic m
odifi
ers
and
into
est
ablis
hing
bi
omar
kers
to
track
the
pro
gres
sive
cou
rse
of H
D a
nd f
or s
tora
ge i
n a
cent
ral
spec
imen
rep
osito
ry,
bloo
d (3
0 m
l) an
d ur
ine
(30
ml)
will
be c
olle
cted
at e
ach
visi
t. Th
is c
ompo
nent
of t
he s
tudy
is o
ptio
nal.
201Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
33
The
parti
cipa
nt m
ay c
hoos
e to
par
ticip
ate
at th
e ba
selin
e vi
sit o
r at a
ny o
f the
sub
sequ
ent a
nnua
l fol
low
up
vis
its. A
por
tion
of th
e bl
ood
will
be u
sed
to g
ener
ate
lym
phob
last
oid
cell
lines
, whi
ch w
ill se
rve
as a
n in
exha
ustib
le re
sour
ce fo
r fut
ure
rese
arch
into
gen
etic
mod
ifier
s of
HD
. Ano
ther
por
tion
of th
e bl
ood
will
be
pro
cess
ed to
rem
ove
the
lym
phoc
ytes
and
pla
sma.
Lym
phoc
ytes
will
be c
ryop
rese
rved
and
sto
red
as b
acku
p in
cas
e ce
ll lin
es f
ail,
and
in o
rder
to
use
them
for
fun
ctio
nal a
s w
ell a
s R
NA
and
prot
ein
stud
ies.
The
follo
win
g pr
oces
s w
ill be
per
form
ed fo
r the
cre
atio
n of
lym
phob
last
oid
cell
lines
:O
ne tu
be o
f per
iphe
ral b
lood
will
be c
olle
cted
in a
10
ml y
ello
w to
pped
AC
D tu
be a
nd s
hipp
ed b
y a
cour
ier s
ervi
ce.
BioR
ep w
ill as
sign
a u
niqu
e id
entif
ier t
oth
e sa
mpl
e.0.
5 m
l of b
lood
will
be re
tain
ed a
s a
qual
ity c
ontro
l spe
cim
en fo
r ide
ntity
test
ing
Lym
phob
last
oid
cell
lines
w
ill be
cr
eate
d in
clud
ing
appr
opria
te
test
ing
for
viab
ility
and
cont
amin
atio
n.Al
l ac
tiviti
es a
nd t
estin
g w
ill be
doc
umen
ted
acco
rdin
g to
Bio
Rep
SO
Ps (
Cer
tific
ates
for
eac
h sa
mpl
e do
cum
ent a
ll th
e pr
oces
ses
perfo
rmed
and
inst
rum
ents
use
dac
cord
ingl
y).
The
follo
win
g pr
oces
s w
ill be
per
form
ed fo
r the
isol
atio
n of
lym
phoc
ytes
from
the
bloo
d sa
mpl
e:O
ne tu
be o
f per
iphe
ral b
lood
will
be c
olle
cted
in a
10
ml y
ello
w to
pped
AC
D tu
be a
nd s
hipp
ed b
y a
cour
ier s
ervi
ce.
BioR
ep w
ill as
sign
a u
niqu
e id
entif
ier t
o th
e sa
mpl
e.0.
5 m
l of b
lood
will
be re
tain
ed a
s a
qual
ity c
ontro
l spe
cim
en fo
r ide
ntity
test
ing
Lym
phoc
ytes
will
be is
olat
ed fr
om th
e bl
ood
sam
ple
and
cryo
pres
erve
d.Al
l ac
tiviti
es a
nd t
estin
g w
ill be
doc
umen
ted
acco
rdin
g to
Bio
Rep
SO
Ps (
Cer
tific
ates
for
eac
h sa
mpl
e do
cum
ent a
ll th
e pr
oces
ses
perfo
rmed
and
inst
rum
ents
use
d ac
cord
ingl
y).
The
follo
win
g pr
oces
s w
ill be
per
form
ed fo
r the
isol
atio
n pl
asm
a fro
m th
e bl
ood
sam
ple
Dra
w b
lood
and
inse
rt in
to 1
x9.
5m
l ED
TA tu
bes.
R
apid
pro
cess
ing
of t
he s
ampl
e is
opt
imal
. C
entri
fuga
tion
(ref
riger
ated
cen
trifu
ge)
isca
rrie
d ou
t w
ithin
30
min
utes
of b
lood
dra
w.
Plas
ma
is a
liquo
tted
into
ste
rile
cryo
tube
s an
d pu
t dire
ctly
into
a -8
0°C
free
zer.
Ship
ping
labe
ls a
nd d
etai
led
pack
agin
g in
stru
ctio
n w
ill b
e pr
ovid
ed b
y Bi
oRep
and
ship
ped
on d
ry
ice
by a
cou
rier s
ervi
ce.
Gen
otyp
ic E
valu
atio
n –
To e
nsur
e un
iform
ity o
f C
AG
rep
eat
sizi
ng,
REG
ISTR
Y-H
D p
artic
ipan
tsar
e as
ked
for t
heir
perm
issi
on fo
r rep
eat g
enot
ypin
g of
the
mut
ant a
nd n
orm
al H
D a
llele
s. T
he re
sults
of t
his
geno
typi
ng w
ill be
use
d fo
r res
earc
h pu
rpos
es o
nly.
Urin
e -
If th
e pa
rtici
pant
con
sent
s, u
rine
(30
ml)
will
be c
olle
cted
at a
ll vi
sits
and
sto
red
at B
ioR
ep. F
or
addi
tiona
l inf
orm
atio
n, s
ee th
e R
epos
itory
Des
crip
tion
by B
ioR
ep.
34
7ET
HIC
AL
CO
NSI
DER
ATI
ON
S
7.1.
1C
osts
to th
e Pa
rtici
pant
Parti
cipa
nts
will
incu
r no
cost
for p
artic
ipat
ion
in th
is s
tudy
. The
par
ticip
ant o
r the
par
ticip
ant's
insu
ranc
e w
ill be
res
pons
ible
for
the
cos
t of
all
proc
edur
es a
ssoc
iate
d w
ith s
tand
ard
of c
are.
Par
ticip
ants
will
re
ceiv
e no
pay
men
t fo
r pa
rtici
patio
n in
thi
s st
udy
but
may
on
requ
est
rece
ive
com
pens
atio
n fo
r th
eir
trave
l exp
ense
s.
7.1.
2Pa
rtici
pant
risk
Sinc
e R
EGIS
TRY
is a
n ob
serv
atio
nal s
tudy
, par
ticip
ants
do
not u
nder
go s
peci
fic r
isks
by
parti
cipa
ting.
Th
eref
ore
no m
edic
al i
nsur
ance
is
prov
ided
. Pa
rtici
pant
s m
ay e
xper
ienc
e an
xiet
y or
psy
chol
ogic
al
disc
omfo
rt w
hile
com
plet
ing
the
UH
DR
S’99
and
/or
the
FHQ
. In
add
ition
, de
spite
bes
t ef
forts
, it
is n
ot
hum
anly
pos
sibl
e to
exc
lude
with
100
% c
erta
inty
a b
reac
h of
con
fiden
tialit
y by
una
utho
rised
peo
ple
getti
ng a
cces
s to
inf
orm
atio
n in
med
ical
file
s an
d re
cord
s th
us r
esul
ting
in a
los
s of
con
fiden
tialit
y.
How
ever
, all
reas
onab
le s
afeg
uard
sto
pre
vent
an
inci
denc
e lik
e th
at w
ere
unde
rtake
n. F
or in
stan
ce, a
ll da
ta e
nter
ed in
to th
e el
ectro
nic
data
bas
e of
REG
ISTR
Y ar
e st
ored
und
er a
cod
e (o
r ‘ps
eudo
nym
’ -a
3 x
3 nu
mbe
r lik
e 34
6-59
9-32
1 -s
ee a
lso
data
pro
tect
ion
leaf
let)
inst
ead
of th
e na
me
or o
ther
iden
tifyi
ng
data
. The
refo
re a
t all
times
onl
y th
e st
udy
site
cho
sen
by th
e pa
rtici
pant
s fo
r in
clus
ion
into
REG
ISTR
Y is
aw
are
of th
e id
entif
ying
dat
a (e
.g. n
ame,
dat
e of
birt
h, a
ddre
ss)
asso
ciat
ed w
ith th
e ps
eudo
nym
. All
user
s of
the
EH
DN
dat
abas
e ou
tsid
e th
e st
udy
site
cho
sen
by t
he p
artic
ipan
t EX
CLU
SIV
ELY
wor
k ex
clus
ivel
y w
ith c
oded
(‘p
seud
onym
ised
’) da
ta.
For
the
prot
ectio
n of
the
EH
DN
dat
a ba
se c
onta
inin
g th
ese
pseu
dony
mis
ed d
ata
agai
nst
unau
thor
ised
acc
ess,
EH
DN
has
sev
eral
pre
caut
ions
in
plac
e to
m
aint
ain
inte
grity
, con
fiden
tialit
y an
d se
curit
y of
the
data
base
. The
EH
DN
ser
vers
are
man
aged
by
full-
time
syst
em
adm
inis
trato
rs.
All
netw
ork
traffi
c is
en
cryp
ted
via
netw
ork
hubs
to
m
inim
ize
‘eav
esdr
oppi
ng’ a
ttack
s us
ing
SSL
/TLS
with
a k
ey le
ngth
of 1
28 o
r m
ore.
All
PC's
run
viru
s pr
otec
tion
softw
are
full-
time
and
are
upda
ted
with
the
late
st v
irus
dete
ctio
n st
rings
reg
ular
ly. S
erve
rs h
ave
been
cu
stom
ised
to r
un t
he b
are
min
imum
of
netw
ork
serv
ices
in
orde
r to
min
imis
epo
tent
ial
‘bac
k do
or’
atta
cks,
and
are
upda
ted
on a
reg
ular
bas
is w
ith t
he l
ates
t ve
ndor
rec
omm
ende
d so
ftwar
e fix
es.
In
addi
tion,
oth
er s
ecur
ity s
oftw
are
runs
con
tinuo
usly
min
imis
ing
othe
r po
tent
ial a
ttack
s. A
ll ac
coun
ts a
re
pass
wor
d pr
otec
ted.
All
stud
y da
ta is
sto
red
in P
ostg
reSQ
L, a
rela
tiona
l dat
abas
e m
anag
emen
t sys
tem
, w
hich
resi
des
on a
Lin
ux S
erve
r run
ning
the
Linu
x O
pera
ting
Envi
ronm
ent.
The
serv
er re
side
s in
side
a
lock
ed c
ompu
ter
room
tha
t is
phy
sica
lly a
cces
sibl
e on
ly b
y th
e au
thor
ised
per
sona
l. Th
is r
oom
is
loca
ted
in t
he c
entra
lcoo
rdin
atio
n su
ite o
f EH
DN
tha
t is
als
o lo
cked
-di
ffere
nt k
eys
are
requ
ired
for
both
the
com
pute
r ro
om a
nd t
he s
uite
. Th
e C
ompu
ter
room
is
tem
pera
ture
con
trolle
d. I
t is
als
o eq
uipp
ed w
ith s
mok
e/fir
e de
tect
ion
sens
ors.
To
ensu
re h
igh
syst
em a
vaila
bilit
y th
e se
rver
is e
quip
ped
with
dua
l pow
er s
uppl
ies,
hot
-sw
appa
ble
RAI
D 5
dis
k dr
ives
, and
an
APC
uni
nter
rupt
ible
pow
er s
uppl
y.
Ever
y 24
hou
rs th
e sy
stem
is b
acku
p to
DLT
tape
. In
addi
tion,
the
data
bas
e is
mirr
ored
by
a se
cond
se
ver
in a
sim
ilarly
pro
tect
ed e
nviro
nmen
t loc
ated
at a
phy
sica
lly d
ista
nt (
> 50
km
) si
te. A
ll C
RF
data
an
d ot
her c
ritic
al s
tudy
dat
a ar
e fu
lly a
udit
trail
enab
led
so th
at a
ll ch
ange
s to
the
data
can
be
mon
itore
d an
d/or
reco
vere
d. W
EBSP
IRIT
impl
emen
ts a
per
mis
sion
-bas
ed s
ecur
ity m
etho
dolo
gy th
at li
mits
acc
ess
to s
tudy
dat
a ba
sed
on th
e pa
rticu
lar s
tudy
, use
r ID
, and
gro
up ID
. Per
mis
sion
s ar
e ca
refu
lly m
aint
aine
d to
al
low
on
ly
the
requ
ired
leve
l of
ac
cess
to
st
udy
data
. Th
e op
erat
ing
envi
ronm
ent
requ
ires
user
nam
e/pa
ssw
ord
auth
entic
atio
n, a
nd i
mpl
emen
ts it
s ow
n pe
rmis
sion
s st
ruct
ure
at t
he f
ile s
yste
m
leve
l bas
ed o
n us
er ID
and
gro
up ID
. File
s an
d di
rect
orie
s ar
e ca
refu
lly s
et w
ith o
nly
the
requ
ired
leve
l of
acc
ess.
Use
r ID
's a
re r
equi
red
to c
hang
e pa
ssw
ord
on a
reg
ular
bas
is. E
very
pre
caut
ion
has
been
ta
ken
to a
ssur
e th
at c
ompu
ter c
onfid
entia
lity
is m
aint
aine
d.
For
parti
cipa
nts
cons
entin
g to
don
ate
bios
ampl
es th
ere
are
som
e ad
ditio
nal p
oten
tial r
isks
ass
ocia
ted
with
blo
od d
raw
. The
col
lect
ion
of b
lood
spe
cim
ens
may
cau
se p
ain
and/
or b
ruis
ing
at th
e si
te w
here
bl
ood
is d
raw
n. F
aint
ing
or fe
elin
g lig
ht-h
eade
d m
ay o
ccur
dur
ing
or s
hortl
y af
ter h
avin
g bl
ood
draw
n. If
a
parti
cipa
nt e
xper
ienc
es th
is, t
he p
artic
ipan
t will
be in
stru
cted
to li
e do
wn
imm
edia
tely
to a
void
pos
sibl
e in
jurie
s. L
ocal
ised
clot
form
atio
n an
d in
fect
ions
may
occ
ur, b
ut th
is is
ver
y ra
re. O
nly
expe
rienc
ed s
taff
will
draw
the
blo
od f
or t
his
stud
y. I
n or
der
to e
nsur
e th
e co
nfid
entia
lity
of d
onor
s co
ntrib
utin
g to
the
ce
ntra
l bio
repo
sito
ry, B
ioR
ep, w
ill B
ioR
ep n
ever
rece
ive
iden
tifyi
ng d
ata
alon
g w
ith th
e bi
osam
ples
sen
t fo
r st
orag
e. In
stea
d, B
ioR
ep w
ill re
ceiv
e th
e bi
osam
ples
from
stu
dy s
ites
with
onl
y th
e ps
eudo
nym
as
iden
tifie
r.
202 Hygeia Public Health 2011, 46(2): 183-218
35
7.1.
3Po
tent
ial B
enef
itPa
rtici
pant
s w
ill re
ceiv
e no
imm
edia
te b
enef
it fro
m p
artic
ipat
ion
in th
is s
tudy
. The
onl
y po
tent
ial b
enef
it is
a b
ette
r un
ders
tand
ing
of H
D a
nd t
he p
ossi
bilit
y th
at t
he in
form
atio
n ob
tain
ed in
thi
s st
udy
lead
to
pote
ntia
l tre
atm
ents
and
to p
lan
futu
re re
sear
ch s
tudi
es o
f exp
erim
enta
l dru
gs a
imed
at s
low
ing
dise
ase
prog
ress
ion
or p
ostp
onin
g th
e on
set o
f HD
.
7.1.
4Al
tern
ativ
es to
Par
ticip
atio
nTh
e on
ly a
ltern
ativ
e to
par
ticip
atio
n in
this
stu
dy is
not
to p
artic
ipat
e. T
he p
artic
ipan
t can
cho
ose
not t
o ta
ke p
art i
n th
e op
tiona
l com
pone
nts
of th
e st
udy.
7.1.
5W
ithdr
awal
from
Par
ticip
atio
nIf
a pa
rtici
pant
doe
s no
t wan
t to
cont
inue
, the
par
ticip
ant c
an a
t eve
ry ti
me
leav
e th
e st
udy.
Par
ticip
ants
do
not
hav
e to
dis
clos
e th
eir
reas
ons
for
with
draw
al o
f co
nsen
t. O
n th
e pa
rtici
pant
’s r
eque
st a
ll in
form
atio
n ob
tain
ed s
o fa
r w
ill be
ano
nym
ised
. S
imila
rly,
on t
he p
artic
ipan
t’s r
eque
st a
ll bi
osam
ples
co
llect
ed a
nd s
tore
d at
the
cen
tral b
iore
posi
tory
will
be d
estro
yed.
Par
ticip
ants
hav
e to
be
awar
e th
at
The
‘End
of S
tudy
form
’ mus
t be
com
plet
ed b
y th
e in
vest
igat
or, d
etai
ling
the
reas
ons
for w
ithdr
awal
(eg.
m
arki
ng “p
atie
nt re
ques
t”).
Parti
cipa
nts
may
be
with
draw
n fro
m th
e st
udy
for t
he fo
llow
ing
reas
ons:
Failu
re to
com
plet
e th
e re
quire
d st
udy
proc
edur
es, r
egar
dles
s of
reas
on.
The
site
inve
stig
ator
feel
s th
at it
is in
the
best
inte
rest
of t
he p
artic
ipan
t.If
the
parti
cipa
nt is
with
draw
n by
the
inve
stig
ator
the
‘End
of S
tudy
form
’ mus
t als
o be
com
plet
ed.
7.1.
6En
d of
stu
dy/w
ithdr
awal
s Th
ere
is n
o fix
ed e
nd o
f st
udy.
Afte
r pa
tient
dea
th t
he ‘
Dea
th R
epor
t fo
rm’
(stu
dy f
orm
) m
ust
be
com
plet
ed b
y th
e in
vest
igat
or.
If a
parti
cipa
nt d
oes
not
wan
t to
con
tinue
, th
e pa
rtici
pant
can
at
ever
y tim
e le
ave
the
stud
y. I
n ad
ditio
n, p
artic
ipan
ts m
ay b
e w
ithdr
awn
from
the
stud
y fo
r th
e re
ason
s lis
ted
abov
e. In
thes
e in
stan
ces,
an
‘End
of S
tudy
form
’ mus
t be
com
plet
ed b
y th
e in
vest
igat
or, d
etai
ling
the
reas
ons
for w
ithdr
awal
(e.g
. ‘pa
tient
requ
est’)
.
36
8ST
ATI
STIC
AL
CO
NSI
DER
ATI
ON
S As
HD
is
a re
lativ
ely
rare
dis
ease
, no
sin
gle
stud
y si
te i
s in
the
pos
ition
to
obta
in s
ingl
e-ha
nded
ph
enot
ypic
al
(clin
ical
) da
ta
or
bios
ampl
es
in
suffi
cien
t nu
mbe
rs
to
cond
uct
conc
lusi
ve
stud
ies
conc
erni
ng th
e m
ajor
ity o
f que
stio
ns o
f clin
ical
rele
vanc
e in
HD
. The
refo
re a
coo
pera
tive
effo
rt ap
pear
s an
app
ealin
g av
enue
to p
rovi
de la
rge
enou
gh c
linic
al d
ata
sets
and
suf
ficie
nt n
umbe
rs o
f bio
sam
ples
to
answ
er q
uest
ions
con
clus
ivel
y by
con
duct
ing
wel
l pow
ered
stu
dies
. O
bvio
usly
, th
e nu
mbe
rs n
eed
to
answ
er
scie
ntifi
c qu
estio
ns
conc
lusi
vely
w
ill de
pend
on
th
e ou
tcom
es
and
read
-out
s un
der
cons
ider
atio
n. F
or e
xam
ple,
per
form
ing
a m
eani
ngfu
l fac
toria
l ana
lysi
s to
impr
ove
and
cond
ense
clin
ical
ra
ting
scal
es m
ay r
equi
re s
ever
al h
undr
ed c
linic
al d
ata
sets
with
a w
ide
spre
ad o
f ph
enot
ypic
al
pres
enta
tions
. A
gen
ome-
wid
e se
arch
for
gen
etic
mod
ifier
s m
ay w
ell
requ
ire –
give
n pr
esen
t da
ys
tech
nolo
gies
–m
ore
than
300
0 sa
mpl
es fo
r an
info
rmat
ive
stud
y, d
epen
ding
–am
ong
othe
r fac
tors
-on
th
e de
gree
of
herit
abilit
y of
the
tra
it un
der
cons
ider
atio
n, t
he e
xten
t of
gen
etic
het
erog
enei
ty i
n th
e sa
mpl
es, a
nd th
e de
nsity
of t
he m
olec
ular
mar
kers
bei
ng te
sted
. At t
he o
ther
ext
rem
e of
the
spec
trum
, a
care
fully
sel
ecte
d, s
mal
l (e
.g.
n =
60)
sam
ple
repr
esen
ting
all
clin
ical
sta
ges
of H
D m
ay w
ell
be
suffi
cien
t to
stro
ngly
sug
gest
the
use
fuln
ess
of a
rea
d-ou
t fro
m p
lasm
a as
a b
iom
arke
r tra
ckin
g th
e pr
ogre
ssiv
e co
urse
of H
D. I
n th
e fu
ture
, the
ava
ilabi
lity
of p
rosp
ectiv
ely
asce
rtain
ed b
iosa
mpl
es li
nked
to
phe
noty
pica
l sta
tes
at th
e tim
e of
sam
ple
colle
ctio
n w
ill pe
rmit
robu
st c
oncl
usio
ns a
bout
the
valid
ity o
f su
gges
ted
biom
arke
rs w
ithin
a s
hort
time
fram
e. O
vera
ll, d
ata
from
REG
ISTR
Y sh
ould
ass
ist
in
dete
rmin
ing
the
robu
stne
ss o
f co
nclu
sion
s de
rived
fro
m p
revi
ous
stud
ies
cond
ucte
d on
sm
all s
ampl
e si
zes
usin
g in
depe
nden
t dat
a se
ts. A
s a
resu
lt of
thes
e co
nsid
erat
ions
, eac
h pr
ojec
t pro
posa
l def
inin
g a
spec
ific-
read
out
or
endp
oint
will
incl
uded
a s
ampl
e si
ze c
alcu
latio
n an
d –
if ap
prop
riate
–a
pow
er
anal
ysis
spe
cific
to th
e ob
ject
ives
of t
his
stud
y.
As a
n ex
ampl
e on
e m
ay c
onsi
der
a sa
mpl
e si
ze c
alcu
latio
n fo
r st
udie
s ai
min
g to
ide
ntify
gen
etic
de
term
inan
ts o
f cer
tain
cha
ract
eris
tics
of th
e di
seas
e ph
enot
ype
(e.g
. the
life
tim
e oc
curr
ence
of a
maj
or
psyc
hosi
s in
HD
pat
ient
s).
Firs
t, it
is e
ssen
tial t
o es
timat
e w
hat
fract
ion
of t
he p
heno
typi
c va
riatio
n is
du
e to
gen
etic
fac
tors
. A
com
mon
ly e
mpl
oyed
des
ign
to p
erfo
rm s
uch
an a
naly
sis
is th
e co
llect
ion
of
sibl
ing
pairs
with
the
goa
l of
estim
atin
g th
e he
ritab
ility
of t
he p
heno
type
of
inte
rest
. Th
e R
EGIS
TRY
sam
ple
will
striv
e to
rec
ruit
mul
tiple
mem
bers
from
a g
iven
fam
ily a
nd th
roug
h th
e co
llect
ion
of f
amily
hi
stor
y in
form
atio
n, w
ill be
abl
e to
est
ablis
h th
e bi
olog
ical
rel
atio
nshi
p am
ong
indi
vidu
als
and
use
this
in
form
atio
n fo
r ge
netic
ana
lyse
s. S
iblin
gs a
re t
ypic
ally
em
ploy
ed f
or h
erita
bilit
y st
udie
s si
nce
they
are
cl
osel
y re
late
d an
d ar
e ex
pect
ed to
sha
re, o
n av
erag
e, h
alf t
heir
gene
tic m
ater
ial.
Stud
ies
in R
EGIS
TRY
will
focu
s on
est
imat
ing
the
herit
abilit
y of
a n
umbe
r of
diff
eren
t qu
antit
ativ
e ph
enot
ypes
incl
udin
g th
e ag
e of
ons
et o
f di
seas
e an
d th
e ra
te o
f di
seas
e pr
ogre
ssio
n (a
s m
easu
red
by a
num
ber
of d
iffer
ent
para
met
ers)
. For
thos
e ph
enot
ypes
and
trai
ts w
hich
are
her
itabl
e, th
e co
llect
ion
of D
NA
and
of fa
mily
da
ta w
ill al
low
stu
dies
to
iden
tify
the
gene
s an
d po
lym
orph
ism
s co
ntrib
utin
g to
tra
it va
riabi
lity.
Bro
ad-
sens
e he
ritab
ility
(H2)
is e
stim
ated
as
twic
e th
e si
blin
g in
tracl
ass
corr
elat
ion,
acc
ordi
ng to
the
met
hod
of
Falc
oner
(19
89).
This
im
plie
s fo
r a
phen
otyp
ic t
rait
with
50%
her
itabi
lity
(i.e.
hal
f th
e ph
enot
ypic
va
riatio
n is
due
to g
enet
ic e
ffect
s), a
sam
ple
of a
ppro
xim
atel
y 10
0 si
blin
g pa
irs w
ill ha
ve 8
0%>
pow
er
(with
alp
ha=0
.05)
. As
the
gene
tic c
ontri
butio
n to
the
trait
decr
ease
s, th
e re
quire
d sa
mpl
e si
ze in
crea
ses.
Fo
r a
trait
with
onl
y 20
% h
erita
bilit
y, a
sam
ple
of a
ppro
xim
atel
y 60
0 si
blin
g pa
irs is
req
uire
d fo
r 80
%
pow
er.
In a
dditi
on,
it is
ess
entia
l to
per
form
alte
rnat
e an
alys
es s
uch
as f
amily
bas
ed a
ssoc
iatio
n an
alys
es.
This
typ
e of
ana
lysi
s ca
n be
rel
ativ
ely
inef
ficie
nt i
n its
use
of
fam
ily r
esou
rces
, bu
t is
pa
rticu
larly
resi
stan
t to
poss
ible
sou
rces
of d
ata
bias
suc
h as
sam
ple
stra
tific
atio
n.
8.1
Dat
a A
naly
sis
Dat
a an
alys
is is
per
form
ed b
y in
vest
igat
ors
with
app
rove
d E
HD
N p
ropo
sals
. S
tatis
tical
and
ana
lytic
al
met
hods
hav
e to
be
defin
ed a
s pa
rt of
the
pro
posa
ls a
nd a
re u
ltim
atel
y th
e re
spon
sibi
lity
of t
he
prop
oser
s. H
owev
er, g
uida
nce
from
bio
stat
istic
ians
ass
ocia
ted
with
EH
DN
can
be
prov
ided
on
requ
est
and
is fa
cilit
ated
thro
ugh
cent
ral c
oord
inat
ion
of E
HD
N.
Pote
ntia
l pr
oteo
mic
, ne
uroi
nfla
mm
ator
y, e
ndoc
rine
and
met
abol
ic m
arke
rs i
dent
ified
fro
m c
urre
nt
ongo
ing
biom
arke
r re
sear
ch i
nitia
tives
will
be f
urth
er v
alid
ated
usi
ng t
he E
HD
N p
lasm
a sa
mpl
es.
Spec
ific
a pr
iori
cand
idat
es w
ill th
en b
e an
alys
ed u
sing
long
itudi
nal a
naly
ses
of s
ampl
es o
ver s
peci
fied
time
inte
rval
s (i.
e.12
–24
mon
ths)
. Any
add
ition
al s
cree
ning
for n
ew c
andi
date
mar
kers
will
be s
ubje
ct
to m
ultip
le c
ompa
rison
cor
rect
ions
(e.
g. f
alse
dis
cove
ry r
ate)
in a
sses
sing
the
prob
able
sta
tistic
al a
nd
203Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
37
scie
ntifi
c si
gnifi
canc
e of
the
res
ults
. C
hang
es in
eac
h of
the
labo
rato
ry b
iom
arke
rs id
entif
ied
will
be
corr
elat
ed w
ith th
e cl
inic
al p
heno
typi
c da
ta u
sing
mul
ti-va
riate
ass
essm
ents
.
8.2
Form
s an
d da
ta h
andl
ing
The
data
are
ent
ered
ele
ctro
nica
lly v
ia in
tern
et-b
ased
tech
nolo
gy. T
he E
HD
N w
eb-p
orta
l is
sepa
rate
d in
to s
ever
al p
arts
with
diff
eren
t acc
ess
rule
s. A
ny g
iven
site
inve
stig
ator
in R
EGIS
TRY
is a
llow
ed to
see
on
ly d
ata
on p
artic
ipan
ts u
nder
the
car
e of
the
stu
dy s
ite t
o w
hich
the
site
inv
estig
ator
is
affil
iate
d.
Cen
tral C
oord
inat
ion
is a
llow
ed to
vie
w a
ll da
ta o
f all
cent
res
for p
laus
ibilit
y ch
ecks
, QC
and
mon
itorin
g.
As d
etai
led
in t
he d
ata
acce
ss p
olic
y of
EH
DN
, in
vest
igat
ors
who
se p
roje
cts
wer
e ap
prov
ed b
y th
e sc
ient
ific
revi
ew c
omm
ittee
of E
HD
N re
ceiv
e a
reco
ded,
per
tinen
t ext
ract
out
of t
he d
ata
base
. By
orde
r of
the
stee
ring
com
mitt
ee o
f REG
ISTR
Y, C
entra
l Coo
rdin
atio
n is
per
mitt
ed to
sta
tistic
ally
eva
luat
e th
e w
hole
dat
a se
t. T
he w
hole
dat
abas
e is
sav
ed o
n a
serv
er.
8.3
Mod
ifica
tion
of th
e pr
otoc
olAn
y m
odifi
catio
n of
the
prot
ocol
whi
ch m
ay h
ave
an im
pact
on
the
cond
uct o
f the
stu
dy, i
nclu
ding
stu
dy
obje
ctiv
es, s
tudy
des
ign,
par
ticip
ant p
opul
atio
n, s
tudy
pro
cedu
res
or s
igni
fican
t adm
inis
trativ
e as
pect
s,
will
requ
ire a
for
mal
am
endm
ent
to t
he p
roto
col.
The
EHD
N,
the
inve
stig
ator
s an
d th
e IR
B w
ill ag
ree
upon
suc
h am
endm
ents
prio
r to
impl
emen
tatio
n.
38
9A
PPEN
DIX
A:R
EGIS
TRY
STEE
RIN
G C
OM
MIT
TEE
As o
f 01
Nov
embe
r, 20
09 th
e R
EGIS
TRY
Stee
ring
Com
mitt
ee in
clud
esth
efo
llow
ing
EH
DN
mem
bers
:
A.-C
. Bac
houd
-Lev
i,M
D P
hD (H
ôpita
l Hen
ri M
ondo
r, C
réte
il)
A. R
. Ben
tivog
lio, M
D (U
nive
rsità
Cat
tolic
a de
l Sac
ro C
uore
, Rom
e)
I. B
iunn
o, P
hD(B
ioR
ep, M
ilan)
R. B
onel
li, M
D (V
ienn
a, A
ustri
a)
J. M
. Bur
gund
er, M
D (N
euro
logi
sche
Klin
ikde
s In
sels
pita
ls, B
ern,
Sw
itzer
land
)
S. D
unne
tt, D
Sc (C
ardi
ff U
nive
rsity
, Uni
ted
King
dom
)
J. F
erre
ira, M
D (C
entro
de
Estu
dos
Egas
Mon
iz, L
isbo
n, P
ortu
gal)
O. H
andl
ey, P
hD (U
nive
rsity
Col
lege
Lon
don,
Uni
ted
Kin
gdom
)
A. H
eibe
rg, M
D, P
hD (R
iksh
ospi
tale
t, O
slo,
Nor
way
)
T. Il
lman
n (2
mt,
Ger
man
y)
S. Il
lario
shki
n, M
D(R
ussi
an A
cade
my
of M
edic
al S
cien
ces,
Mos
cow
, Rus
sia)
G. B
. Lan
dweh
rmey
er, M
D (P
rinci
ple
Inve
stig
ator
, Uni
vers
ity o
fUlm
, Ger
man
y)
J. L
evey
(EH
DN
, Par
is, F
ranc
e)
J. N
iels
en, M
D (U
nive
rsity
Hos
pita
l of C
open
hage
n, C
open
hage
n, D
enm
ark)
H. P
adie
u (E
HD
N, P
aris
, Fra
nce)
S. P
ålha
gen,
MD
(Kar
olin
ska
Inst
itute
, Lun
d, S
wed
en)
M. P
äivä
rinta
, MD
(Tur
ku U
nive
rsity
, Fin
land
)
R.A
.C. R
oos,
MD
(Lei
den
Uni
vers
ity M
edic
al C
entre
(LU
MC
), Le
iden
, Net
herla
nds)
M. R
amos
-Arr
oyo
MD
, PhD
(Dep
t.of
Med
ical
Gen
etic
s, P
ampl
ona,
Spa
in)
S. T
abriz
i, M
D P
hD (C
o-In
vest
igat
or;U
nive
rsity
Col
lege
Lon
don,
Uni
ted
King
dom
)
T. U
hrov
a, M
D (C
entru
m E
xtra
pyra
mid
ovýc
h O
,Pra
gue,
Cze
ch R
epub
lic)
D. v
an K
amm
en, M
D(C
hief
Med
ical
Offi
cer,
CH
DI F
ound
atio
n, In
c.)
M. v
an W
alse
m, M
Sc(E
HD
N,R
iksh
ospi
tale
t, O
slo,
Nor
way
)
W. V
ande
nber
ghe,
MD
(Uni
vers
itair
Ziek
enhu
is G
asth
uisb
erg,
Leu
ven,
Bel
gium
)
C. V
erel
len-
Dum
oulin
, MD
(UC
L-St
Luc
, Bru
ssel
ls, B
elgi
um)
J. Z
arem
ba, M
D (W
arsa
w, P
olan
d)
204 Hygeia Public Health 2011, 46(2): 183-218
39
10A
PPEN
DIX
BIN
FOR
MA
TIO
N A
ND
CO
NSE
NT
FOR
MS
10.1
Part
icip
ant I
nfor
mat
ion
Shee
t (N
ew R
EGIS
TRY-
HD
Part
icip
ants
)
Nam
e of
stu
dy:
REG
ISTR
Y –
an o
bser
vatio
nal
stud
y of
the
Eur
opea
n H
untin
gton
’sdi
seas
eN
etw
ork
(EH
DN
)
Dea
r Par
ticip
ant,
You
are
eith
er s
uffe
ring
from
Hun
tingt
on’s
dis
ease
(H
D)
or y
ou b
elon
g to
an
HD
fam
ily.
The
clin
ical
te
amtre
atin
g yo
u or
you
r re
lativ
e ha
s as
ked
you
whe
ther
you
are
will
ing
to p
artic
ipat
e in
a s
tudy
(‘R
EGIS
TRY’
) co
nduc
ted
at m
any
cent
res
thro
ugho
ut E
urop
e st
rivin
g to
und
erst
and
HD
bet
ter
and
to
impr
ove
the
curr
ently
ava
ilabl
e to
ols
to fo
llow
the
cour
se o
f the
dis
ease
. In
addi
tion,
REG
ISTR
Y ai
ms
to
help
in
unde
rsta
ndin
g w
hich
gen
e(s)
oth
er t
han
the
HD
mut
atio
n w
ithin
the
HD
gen
e in
fluen
ce t
he
pres
enta
tion
and
the
rate
of p
rogr
essi
on o
f HD
(e.
g. a
t wha
t age
mut
atio
n ca
rrie
rs d
evel
op s
igns
and
sy
mpt
oms)
. Fin
ally
, REG
ISTR
Y w
ants
to fa
cilit
ate
and
expe
dite
futu
re s
tudi
es in
HD
by
assi
stin
g e.
g. in
th
e re
crui
tmen
t of
par
ticip
ants
acr
oss
Euro
pe;
this
will
enab
le y
ou t
o en
rol
in s
tudi
es r
elat
ing
to t
he
natu
ral
prog
ress
ion
of H
D a
nd i
n so
-cal
led
inte
rven
tiona
l st
udie
s (‘d
rug
trial
s’)
aim
ed a
t de
layi
ng
dise
ase
prog
ress
ion
or fo
cuse
d on
am
elio
ratin
g de
fined
com
plai
nts
(e.g
. apa
thy,
irrit
abilit
y). T
here
fore
, it
is im
porta
nt th
at y
ou a
re in
terv
iew
ed a
nd e
xam
ined
by
expe
rienc
ed c
linic
ians
in o
rder
to r
ecor
d ho
w
muc
h, o
r how
littl
e, y
ou a
re a
ffect
ed o
r im
paire
d by
HD
. In
othe
r wor
ds, a
t eac
h st
udy
visi
t, yo
ur p
hysi
cal
and
men
tal a
bilit
y w
ill be
ass
esse
d; t
hese
exa
min
atio
ns a
re n
o di
ffere
nt f
rom
tho
se y
ou a
re a
lread
y fa
milia
r w
ith f
rom
pre
viou
s co
nsul
tatio
ns.
In a
dditi
on,
you
will
be
aske
d to
com
plet
e qu
estio
nnai
res
asse
ssin
g yo
ur w
ellb
eing
. La
stly
, yo
ur c
ompa
nion
or
othe
r in
divi
dual
s in
volv
ed in
you
r ca
re (
prov
ided
yo
u re
quire
any
due
to
HD
) w
ill be
ask
ed t
o co
mpl
ete
ques
tionn
aire
s to
und
erst
and
the
care
give
r bu
rden
and
the
pos
sibl
e ec
onom
ic c
onse
quen
ces
of H
D f
or y
ou,
your
fam
ily a
nd y
our
heal
thca
re
prov
ider
.
The
resu
lts o
f the
se e
xam
inat
ions
will
be e
nter
ed o
nto
an e
lect
roni
c da
taba
se. Y
our
nam
e, a
ddre
ss o
r an
y ot
her
info
rmat
ion
whi
ch c
ould
allo
w p
erso
nal i
dent
ifica
tion
will
nev
er b
e re
cord
ed in
the
data
base
. Yo
ur d
ata
will
be
‘pse
udon
ymis
ed’,
i.e.
reco
rded
und
er a
‘co
de n
ame’
(or
‘ps
eudo
nym
’), w
hich
is
a se
ries
of 9
dig
its. T
here
fore
, nob
ody
but t
he te
am o
f phy
sici
ans
and
heal
thca
re w
orke
rs y
ou c
hoos
e to
in
tera
ct w
ith a
nd w
ho p
rovi
des
you
with
this
info
rmat
ion
abou
t REG
ISTR
Y kn
ows
your
iden
tity
and
can
trace
you
r ‘ps
eudo
nym
’ or c
ode
nam
e ba
ckto
you
r rea
l nam
e an
d ot
her i
nfor
mat
ion
whi
ch m
ight
iden
tify
you
like
date
of
birth
or
addr
ess
(for
deta
ils p
leas
e se
e ‘In
form
atio
n re
gard
ing
data
pro
cess
ing,
dat
a pr
otec
tion
and
data
saf
ety’
bel
ow fo
r iss
ues
rela
ting
to d
ata
secu
rity,
incl
udin
g re
stric
tion
of d
ata
acce
ss
to a
utho
rised
per
sons
and
sec
ure
trans
mis
sion
of
data
). D
ata
entry
and
the
use
of
the
REG
ISTR
Y da
taba
se w
ill be
car
ried
out
usin
g th
e in
tern
et.
The
data
base
is
held
at
Cen
tral
Coo
rdin
atio
n, U
lm
Uni
vers
ity H
ospi
tal,
Ulm
, G
erm
any.
Eva
luat
ion
and
publ
icat
ion
of s
tudy
res
ults
will
be c
arrie
d ou
t an
onym
ousl
y an
d in
the
for
m o
f st
atis
tics.
As
a re
sult,
non
e of
you
r pe
rson
al d
ata
will
ever
be
mad
e pu
blic
.
REG
ISTR
Y is
a s
tudy
con
duct
ed b
y th
e Eu
rope
an H
untin
gton
’s D
isea
se N
etw
ork
(EH
DN
). EH
DN
is a
sc
ient
ific
netw
ork
of p
hysi
cian
s, s
cien
tists
and
orga
nisa
tions
for
fam
ilies
affe
cted
by
HD
to c
olla
bora
te in
su
ppor
t of r
esea
rch
com
mitt
ed to
HD
. The
aim
of t
he n
etw
ork
is to
car
ry o
ut c
linic
al re
sear
ch in
to H
D, t
o im
prov
e kn
owle
dge
of th
e na
tura
l cou
rse
of th
e di
seas
e, a
nd (u
ltim
atel
y) to
find
a c
ure
for H
D. E
HD
N is
su
ppor
ted
by t
he C
HD
I Fo
unda
tion,
Inc
., a
priv
ate,
not
-for-
prof
itAm
eric
an r
esea
rch
orga
nisa
tion.
For
m
ore
info
rmat
ion
abou
t CH
DI,
plea
se v
isit
the
web
site
at w
ww
.chd
ifoun
datio
n.or
g.
Ther
e ar
e no
spe
cific
ris
ks a
risin
g fro
m y
our
parti
cipa
tion
in th
e st
udy
give
n th
at it
is a
n ob
serv
atio
nal
stud
y. If
you
are
willi
ng to
par
ticip
ate
it is
impo
rtant
that
you
(and
a p
erso
n ac
com
pany
ing
you)
atte
nd a
fo
llow
-up
exam
inat
ion
at re
gula
r int
erva
ls (e
.g. y
early
).
We
wou
ld li
ke to
ask
you
to c
onsi
der
your
con
sent
to
a th
orou
gh s
tand
ard
exam
inat
ion
and
the
docu
men
tatio
n of
the
dat
a ob
tain
ed
durin
g yo
ur c
linic
al e
xam
inat
ion
stor
ed u
nder
a p
seud
onym
in a
n el
ectro
nic
data
base
and
your
con
sent
to re
gula
r (e.
g. y
early
)fol
low
-up
visi
ts
40
Any
addi
tiona
l res
earc
h co
mpo
nent
s de
scrib
ed b
elow
are
opt
iona
l and
req
uire
you
r ex
plic
it co
nsen
t by
chec
king
the
box
‘YE
S’ o
r ‘N
O’i
n th
e co
nsen
t for
m. T
he o
ptio
nal c
ompo
nent
s ar
epe
rmis
sion
to b
e co
ntac
ted
in-b
etw
een
visi
ts, (
Opt
iona
l com
pone
nt 1
)do
natio
n of
blo
od a
nd u
rine
for
stud
ies
to i
dent
ify g
enet
ic m
odifi
ers
of H
D a
nd t
o es
tabl
ish
and
valid
ate
biol
ogic
al m
arke
rs fo
r HD
(
,
Opt
iona
l com
pone
nt 2
)an
alys
is o
f a b
lood
sam
ple
for t
he H
D m
utat
ion
(,
Opt
iona
l com
pone
nt 3
)co
mpl
etio
n of
a fa
mily
his
tory
que
stio
nnai
re (
,O
ptio
nal c
ompo
nent
4)
colle
ctio
n of
retro
spec
tive
clin
ical
dat
a,(
,
parti
cipa
tion
in n
ovel
ass
essm
ents
(O
ptio
nal c
ompo
nent
5)
Opt
iona
l com
pone
nt 6
)vi
deot
apin
g of
ass
essm
ents
for r
esea
rch/
teac
hing
pur
pose
s(
, and O
ptio
nal c
ompo
nent
7).
You
may
cho
ose
to p
artic
ipat
e in
all,
in n
one
or in
sel
ecte
d op
tiona
l com
pone
nts.
We
ask
you
for
your
per
mis
sion
to b
e co
ntac
ted
in-b
etw
een
visi
ts, b
ecau
se w
e w
ould
like
to h
ave
the
optio
n to
:
Opt
iona
l com
pone
nt 1
: per
mis
sion
to b
e co
ntac
ted
in-b
etw
een
visi
ts
clar
ify q
uest
ions
with
you
(e.g
. con
cern
ing
your
ans
wer
s in
REG
ISTR
Y qu
estio
nnai
res)
,pr
ovid
e yo
u w
ith u
pdat
es o
n R
EGIS
TRY
orin
form
you
abo
ut u
pcom
ing
treat
men
t tria
ls fo
r w
hich
you
wou
ld b
e el
igib
le a
nd in
whi
ch y
ou m
ay
wan
t to
cons
ider
you
r par
ticip
atio
n.
We
ask
you
to c
onsi
der
dona
ting
bloo
d to
allo
w s
cien
tific
stu
dies
to
find
gene
s w
hich
inf
luen
ce t
he
feat
ures
and
the
cour
se o
f HD
. The
way
HD
pre
sent
s di
ffer
quite
a lo
t fro
m in
divi
dual
to in
divi
dual
; an
impo
rtant
par
t of
thi
s va
riatio
n is
cau
sed
by g
enes
oth
er t
han
the
HD
gen
e. S
imila
rly,
the
rate
of
prog
ress
ion
of th
e di
seas
e di
ffers
from
fam
ily to
fam
ily. K
now
ing
abou
t the
se s
o ca
lled
gene
tic m
odifi
ers
is im
porta
nt s
ince
gen
es w
hich
influ
ence
HD
may
be
usef
ul th
erap
eutic
targ
ets
and
may
be
very
hel
pful
un
ders
tand
ing
diffe
renc
es b
etw
een
HD
pat
ient
s th
us im
prov
ing
the
unde
rsta
ndin
g of
the
out
com
e of
cl
inic
al s
tudi
es a
nd t
reat
men
t tri
als.
For
thi
s pu
rpos
e w
e as
k yo
u to
don
ate
bloo
d on
ce f
or t
he
gene
ratio
n of
cel
l lin
es f
rom
blo
od c
ells
whi
ch w
ill en
sure
tha
t suf
ficie
nt D
NA
is a
vaila
ble
to c
arry
out
th
ese
stud
ies.
In a
dditi
on, w
e as
k yo
u to
con
side
r don
atin
g bl
ood
and
urin
e to
allo
w s
cien
tific
stu
dies
to
find
mar
kers
whi
ch r
efle
ct t
he s
ever
ity o
f th
e di
seas
e. T
hese
so
calle
d bi
omar
kers
are
alre
ady
wel
l es
tabl
ishe
d fo
r e.g
. liv
er d
isor
ders
: you
r doc
tor c
an te
ll by
a s
impl
e bl
ood
test
, how
you
r liv
er is
doi
ng. I
t is
impo
rtant
to
find
out
whe
ther
sim
ilar
test
can
be
foun
d fo
r H
D p
atie
nts
and
how
wel
l cha
nges
in
mar
kers
in b
lood
or u
rine
will
track
the
prog
ress
ive
cour
se o
f HD
. Val
idat
ed b
iom
arke
rs a
re e
xpec
ted
to
allo
w to
sho
w th
e ef
ficac
y of
trea
tmen
ts fa
ster
and
with
few
er p
artic
ipan
ts in
clin
ical
tria
ls c
ompa
red
to
stan
dard
clin
ical
ratin
g sc
ales
to m
easu
re th
e pr
ogre
ssio
n of
HD
. For
this
pur
pose
we
ask
you
to d
onat
e bl
ood
and
urin
e re
gula
rly (e
.g. y
early
)for
at l
east
5 y
ears
. Sam
plin
g of
blo
od a
nd u
rine
is re
quire
d ev
ery
year
sin
ce fi
ndin
g ou
t how
muc
h m
arke
rs c
hang
e ov
er th
e ye
ars
is c
ritic
al.
Opt
iona
l com
pone
nt 2
: Don
atio
n of
blo
od a
nd u
rine
for
stud
ies
to id
entif
y ge
netic
mod
ifier
s of
HD
and
tre
atm
ent r
espo
nses
in H
D a
nd to
est
ablis
h an
d va
lidat
e bi
olog
ical
mar
kers
for H
D.
In o
rder
to
obta
in v
alid
res
ults
as
fast
as
hum
anly
pos
sibl
e, b
iosa
mpl
es s
houl
d be
sto
red
very
saf
ely
and
dist
ribut
ed t
o ca
pabl
e re
sear
cher
s in
a s
afe
and
cont
rolle
d w
ay.
Ther
efor
e, a
ll bi
osam
ples
are
ps
eudo
nym
ised
and
sto
red
cent
rally
in
a bi
orep
osito
ry d
evot
ed t
o th
e sa
fe s
tora
ge a
nd h
andl
ing
of
biom
ater
ials
. Bio
Rep
S.r.l
.is
an in
depe
nden
t org
anis
atio
n ba
sed
in M
ilan,
Ital
y, th
at o
ffers
bio
repo
sito
ry
serv
ices
to
publ
ic a
nd p
rivat
e re
sear
ch in
stitu
tes,
to
the
high
est
stan
dard
s of
qua
lity
and
safe
ty.
For
mor
e in
form
atio
n on
Bio
Rep
, ple
ase
visi
t the
web
site
at w
ww
.bio
rep.
it.
Acce
ss t
o bi
osam
ples
will
be g
rant
ed t
o re
sear
cher
s w
hose
pro
posa
ls w
ere
appr
oved
by
a pa
nel o
f ex
perie
nced
sci
entis
ts a
nd c
linic
ians
who
form
the
Scie
ntifi
c an
d B
ioet
hica
lAdv
isor
y C
omm
ittee
(SBA
C)
of E
HD
N a
ndw
hose
pro
posa
ls w
ere
judg
ed t
o be
wel
l w
ithin
the
sub
ject
are
a fo
r w
hich
you
gav
e in
form
ed c
onse
nt, i
.e. r
epre
sent
stu
dies
into
gen
etic
mod
ifier
s an
d bi
olog
ical
mar
kers
for H
D.
We
ask
you
for
your
per
mis
sion
to c
onsi
der
allo
win
gus
to m
easu
re th
e nu
mbe
r of
CAG
rep
eats
in th
e H
D g
ene.
Thi
s ex
amin
atio
n w
ill al
low
eve
rybo
dy t
o be
ver
y ce
rtain
abo
ut t
he H
D m
utat
ion
and
the
Opt
iona
l com
pone
nt 3
: Ana
lysi
s of
a b
lood
sam
ple
for t
he H
D m
utat
ion
205Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
41
prec
ise
leng
th o
f the
CAG
repe
at. G
iven
the
impo
rtanc
e of
the
HD
mut
atio
n it
is fe
lt to
be
of a
dvan
tage
to
hav
e th
e re
sults
of
mor
e th
an o
ne a
naly
sis
base
d on
an
inde
pend
ently
obt
aine
d sa
mpl
e. T
he
colle
ctio
n of
blo
od m
ay c
ause
pai
n an
d/or
bru
isin
g at
the
site
whe
re b
lood
is d
raw
n. F
aint
ing
or fe
elin
g lig
ht-h
eade
d m
ay o
ccur
dur
ing
or s
hortl
y af
ter
havi
ng b
lood
dra
wn.
If y
ou e
xper
ienc
e th
is,
you
will
be
inst
ruct
ed to
lie
dow
n im
med
iate
ly to
avo
id p
ossi
ble
inju
ries.
Loc
aliz
ed c
lot f
orm
atio
n an
d in
fect
ions
may
oc
cur,
but
this
is v
ery
rare
. Th
e am
ount
of
bloo
d co
llect
ed is
sm
all (
30m
l) an
d th
e in
terv
al b
etw
een
colle
ctio
ns is
long
(e.g
.yea
rly),
so th
ere
is n
o ris
k of
dev
elop
ing
an a
naem
ia.
We
ask
you
to c
onsi
der
answ
erin
g so
me
ques
tions
reg
ardi
ng y
our
fam
ily h
isto
ry.
HD
is a
n in
herit
ed
dise
ase
and
it is
par
t of s
tand
ard
med
ical
car
e to
obt
ain
a fa
mily
tree
. Mos
t im
porta
ntly
, with
the
help
of
the
fam
ily h
isto
ry q
uest
ionn
aire
as
desi
gned
for
REG
ISTR
Y on
e ca
n re
cogn
ize
whe
ther
bio
sam
ples
or
clin
ical
dat
a se
ts a
re li
nked
and
ther
efor
e ap
ply
the
very
pow
erfu
l tec
hniq
ue o
f sib
-pai
r an
alys
is w
hile
pr
otec
ting
the
priv
acy
of a
ll do
nors
. Pa
rtici
pant
s ar
e as
ked
to l
ist,
how
man
y si
blin
gs,
child
ren
and
rela
tives
up
to t
he s
econ
d de
gree
the
y ha
ve a
nd t
o vo
lunt
eer
non-
iden
tifyi
ng i
nfor
mat
ion
such
as
gend
er a
nd y
ear
of b
irth
and
whe
ther
the
ir re
lativ
es a
re s
till
aliv
e or
alre
ady
dead
and
an
opin
ion
whe
ther
a m
embe
r of
a f
amily
is
affe
cted
with
HD
or
carr
ies
the
HD
mut
atio
n. T
he i
dent
ity o
f th
e pa
rtici
pant
s an
d of
all
furth
er d
onor
s of
bio
sam
ples
is p
rote
cted
by
the
excl
usiv
e us
e of
cod
e na
mes
(‘p
seud
onym
s’)
for
all
dono
rs.
In a
dditi
on,
parti
cipa
nts
are
aske
d w
heth
er t
hey
feel
com
forta
ble
to
forw
ard
an in
vita
tion
to th
eir r
elat
ives
to c
onsi
der t
akin
g pa
rt in
REG
ISTR
Y.
Opt
iona
l com
pone
nt 4
: Fam
ily H
isto
ry Q
uest
ionn
aire
We
wou
ld l
ike
to a
sk y
ou t
o co
nsid
er g
ivin
g pe
rmis
sion
to
use
info
rmat
ion
from
you
r pa
st c
linic
al
asse
ssm
ents
that
wer
e pe
rform
edbe
fore
you
r pa
rtici
patio
n in
REG
ISTR
Y. M
any
peop
le ta
king
par
t in
REG
ISTR
Y ha
ve u
nder
gone
reg
ular
ass
essm
ents
for
a n
umbe
r of
yea
rs.
The
info
rmat
ion
held
with
in
thes
e pa
st c
linic
al e
valu
atio
ns m
ay h
elp
us to
und
erst
and
the
cour
se o
f HD
bet
ter.
Opt
iona
l com
pone
nt 5
: Ret
rosp
ectiv
e cl
inic
al d
ata
A nu
mbe
r of
nov
el a
sses
smen
ts (
e.g.
que
stio
nnai
res,
int
ervi
ews,
rat
ing
scal
es)
may
hel
p us
to
unde
rsta
nd m
ore
abou
t th
e on
set,
cour
se a
nd t
reat
men
t of
Hun
tingt
on’s
dis
ease
. W
ene
ed t
o co
llect
m
ore
data
on
each
ass
essm
ent i
n or
der
to k
now
whe
ther
they
sho
uld
be u
sed
in th
e de
sign
of f
utur
e re
sear
ch a
nd c
linic
al c
are
prac
tices
.
Opt
iona
l com
pone
nt 6
: Nov
el a
sses
smen
ts
We
wou
ld li
ke to
ask
you
to c
onsi
der
taki
ng p
art i
n th
ese
nove
l ass
essm
ents
. The
nov
el a
sses
smen
ts
cove
r a w
ide
rang
e of
are
as (e
.g. i
nfor
mat
ion
on y
our w
ell-b
eing
, you
r qua
lity
of li
fe, a
nd p
artic
ular
sig
ns
and
sym
ptom
s yo
u m
ay b
e fe
elin
g) a
nd y
ou m
ay b
e ap
proa
ched
to ta
ke p
art.
The
over
all d
urat
ion
of th
e no
vel a
sses
smen
ts to
geth
er w
ith th
e st
anda
rd R
EGIS
TRY
asse
ssm
ents
sho
uld
not e
xcee
d 2.
5 ho
urs.
You
can
deci
de w
heth
er y
ou w
ant t
o do
the
addi
tiona
l ass
essm
ents
or n
ot d
urin
g yo
ur v
isit.
For
certa
in a
sses
smen
ts i
nclu
ded
in R
EGIS
TRY,
you
may
als
o be
ask
ed t
o be
vid
eota
ped.
The
vi
deot
apes
will
be v
isib
le f
or a
res
trict
ed n
umbe
r of
EH
DN
mem
bers
(e.
g. e
xper
ienc
ed p
hysi
cian
s, fo
r co
nsul
tatio
n pu
rpos
es,
phys
icia
ns in
tra
inin
g) f
or q
ualit
y co
ntro
l, re
sear
ch a
nd t
rain
ing
purp
oses
onl
y.
The
reco
rdin
gs w
ill b
e tra
nsm
itted
via
sec
ure
inte
rnet
con
nect
ion
and
will
be s
tore
d on
the
REG
ISTR
Y se
rver
in a
pse
udon
ymis
ed fo
rm.
Opt
iona
l com
pone
nt 7
: Vid
eota
ping
VOLU
NTE
ERIN
GYo
ur p
artic
ipat
ion
in th
is r
esea
rch
proj
ect i
s vo
lunt
ary.
You
are
free
to w
ithdr
aw fr
om th
e st
udy
at a
ny
time
and
with
out
givi
ng r
easo
n. T
his
pote
ntia
l w
ithdr
awal
doe
s no
t af
fect
you
r co
ntin
uing
med
ical
tre
atm
ent.
On
your
req
uest
eve
ry li
nk b
etw
een
your
sto
red
data
and
you
r pe
rson
can
be
perm
anen
tly
dele
ted
(for
deta
ils s
ee In
form
atio
n re
gard
ing
data
pro
cess
ing,
dat
a pr
otec
tion
and
data
sec
urity
, po
int ‘
E’)
INSU
RAN
CE
Beca
use
the
REG
ISTR
Yis
nei
ther
a p
harm
acol
ogic
al s
tudy
nor
a s
tudy
to
test
new
dia
gnos
tic
proc
edur
es, t
here
are
no
addi
tiona
l hea
lth ri
sks
and
the
parti
cipa
nts
ther
efor
e do
not
nee
d in
sura
nce.
42
CLI
NIC
IAN
CO
NTA
CT
Shou
ld y
ou h
ave
any
ques
tions
at
anyt
ime
durin
g th
e co
urse
of
the
rese
arch
pro
ject
you
can
rea
ch
(loca
l inv
estig
ator
s) o
n te
leph
one
num
ber
(tele
phon
e nu
mbe
r of
loca
l inv
estig
ator
) at
any
tim
e du
ring
wor
king
hou
rs. F
or e
mer
genc
ies
out o
f hou
rs, r
ing
(loca
l em
erge
ncy
num
ber)
.
CO
NFI
DEN
TIAL
ITY/
DAT
A PR
OTE
CTI
ON
:Al
l clin
icia
ns a
nd r
elat
ed m
edic
al s
taff
invo
lved
in lo
okin
g af
ter
you
durin
g th
is c
linic
al s
tudy
are
bou
nd
by m
edic
al c
onfid
entia
lity
and
are
oblig
ed t
o co
mpl
y w
ith d
ata
prot
ectio
n. R
esea
rch
resu
lts r
elat
ing
to
this
stu
dy a
re in
tend
ed fo
r us
e in
an
anon
ymou
s fo
rm in
sci
entif
ic p
ublic
atio
ns. A
s fa
r as
is n
eces
sary
fo
r ens
urin
g co
rrec
t dat
a en
try, a
utho
rised
indi
vidu
als
(e.g
. the
spo
nsor
, the
uni
vers
ity) a
re p
erm
itted
to
revi
ew y
our l
ocal
med
ical
reco
rds.
If in
divi
dual
s au
thor
ised
to v
iew
rec
ords
are
not
bou
nd b
y m
edic
al c
onfid
entia
lity
as m
entio
ned
abov
e,
pers
onal
dat
a th
at c
ome
to th
eir a
ttent
ion
durin
g ch
ecks
are
con
fiden
tial u
nder
the
Dat
a Pr
otec
tion
Act.
Euro
pean
H
D
Net
wor
k:
Info
rmat
ion
rega
rdin
g da
ta
proc
essi
ng,
data
pr
otec
tion
and
data
se
curit
y.
An
esse
ntia
l sa
fety
asp
ect
of t
he p
roje
ct i
s th
e pr
oces
sing
of
my
data
in
an e
xclu
sive
ly
pseu
dony
mis
ed m
anne
r.
A.W
hat d
oes
that
mea
n an
d ho
w is
it c
arrie
d ou
t?
Dur
ing
your
firs
t vi
sit,
your
clin
icia
n w
ill e
nter
cer
tain
dat
a ab
out
you
into
the
com
pute
r. Fr
om t
hese
pe
rson
al d
ata
a un
ique
cod
e na
me
(‘pse
udon
ym’)
is c
alcu
late
d, c
onsi
stin
g of
a s
erie
s of
9 d
igits
. The
fo
llow
ing
pers
onal
data
are
use
d: f
irst
nam
e, b
irth
nam
e (s
urna
me)
, da
te o
f bi
rth,
plac
e of
birt
h an
d m
othe
r’s m
aide
n na
me.
Exam
ple:
Mar
ia,
Mill
er
nee
Mus
term
ann,
bo
rn
10.1
1.19
64
in
Ulm
, m
othe
r’s m
aide
n na
me
Schm
idt.
This
in
form
atio
n re
sults
in
the
code
nam
e (‘p
seud
onym
’) 42
5-49
1-32
6. I
mpo
rtant
ly,
the
pseu
dony
m i
s cr
eate
d on
the
bas
is o
f a
so-c
alle
d ‘s
ecur
e ha
sh-a
lgor
ithm
’. B
y th
is m
athe
mat
ical
ope
ratio
n a
uniq
ue
valu
e is
ass
igne
d du
ring
a co
mpl
icat
ed, o
ne-w
ay p
roce
dure
. The
mat
hem
atic
al a
lgor
ithm
use
d en
sure
s th
at n
obod
y (n
ot e
ven
the
syst
em p
rogr
amm
er)
can
reco
nstru
ct f
rom
the
resu
lt (th
e ‘p
seud
onym
’) th
e in
form
atio
n w
hich
was
use
d to
gen
erat
e th
e ps
eudo
nym
(i.e
. yo
ur u
niqu
e pe
rson
al d
ata)
in t
he f
irst
plac
e. T
he p
erso
nal d
ata
trans
mitt
ed t
o ge
nera
te t
he p
seud
onym
are
hel
don
ly f
or t
he c
alcu
latio
n of
yo
ur c
ode
nam
e (‘p
seud
onym
’) in
the
wor
king
mem
ory
of a
larg
e co
mpu
ter (
‘ser
ver’)
. The
cal
cula
tion
of
the
pseu
dony
m r
equi
res
a ve
ry s
hort
time
(milli
seco
nds)
. V
iew
ing
pers
onal
dat
a du
ring
this
tim
e is
im
poss
ible
. The
reaf
ter a
llda
ta u
sed
to c
reat
e th
e ps
eudo
nym
are
per
man
ently
era
sed
from
the
wor
king
m
emor
y of
the
serv
er s
o th
at n
o id
entif
ying
det
ails
rem
ain;
dat
a us
ed to
gen
erat
e th
e ps
eudo
nym
are
ne
ver
stor
ed in
any
for
m o
f pe
rman
ent m
emor
y (e
.g.
on t
he h
ard
driv
e). F
ollo
win
g th
is,
all d
ata
base
en
tries
and
eve
ry u
se o
f dat
a is
exc
lusi
vely
car
ried
out u
nder
the
assi
gned
pse
udon
ym.
B.W
hich
dat
a do
I ha
ve to
dis
clos
e ap
art f
rom
the
data
req
uire
d to
cre
ate
my
pseu
dony
min
the
cour
se o
f the
REG
ISTR
Y st
udy
and
subs
eque
nt s
tudi
es?
Dur
ing
the
cour
se o
f th
e R
EGIS
TRY
stud
y, s
ome
heal
th a
nd/o
r m
edic
al d
ata
will
be r
ecor
ded
(see
Pa
rtici
pant
Info
rmat
ion
Shee
t for
furth
er d
etai
ls).
If yo
u ar
e pa
rtici
patin
g in
any
sub
sequ
ent s
tudi
es, y
our
clin
icia
n w
ill gi
ve y
ou d
etai
led
info
rmat
ion
abou
t the
stu
dy a
nd th
e da
ta re
quire
d fo
r it a
ccor
ding
ly. E
ach
subs
eque
nt s
tudy
requ
ires
sepa
rate
par
ticip
ant c
onse
nt.
C.W
ho c
an s
ee a
nd u
se m
y da
ta?
1. Y
ou: i
f you
wis
h so
, the
clin
icia
n tre
atin
g yo
u ca
n le
t you
to s
ee a
ll da
ta s
tore
d ab
out y
ou. I
t is
advi
sed
that
you
rev
iew
the
se d
ata
toge
ther
with
the
phy
sici
an t
reat
ing
you
to e
xpla
in m
edic
al t
erm
inol
ogy
to
you
and
to a
nsw
er q
uest
ions
you
may
hav
e.
206 Hygeia Public Health 2011, 46(2): 183-218
43
2. T
he c
linic
ian
treat
ing
you:
The
stu
dy s
ite te
am e
nrol
ling
you
for R
EGIS
TRY
is th
e on
ly o
ne a
part
from
yo
urse
lf w
ho c
an l
ink
your
pse
udon
ym t
o yo
ur i
dent
ifyin
g da
ta (
i.e.
nam
e, a
ddre
ss e
tc.).
Afte
r ge
nera
tion
of th
e ps
eudo
nym
all
entry
of c
linic
al in
form
atio
n in
the
data
bas
e is
car
ried
out u
nder
you
r co
de n
ame
(‘pse
udon
ym’).
You
r st
udy
site
tea
m in
clud
ing
your
tre
atin
g cl
inic
ian
can
view
all
clin
ical
da
ta re
cord
ed u
nder
pse
udon
ym.
3.
EHD
Nst
aff
(Lan
guag
e ar
ea
coor
dina
tors
ac
ting
as
mon
itors
, m
onito
rs
base
d in
C
entra
l C
oord
inat
ion)
:EH
DN
sta
ff ca
n vi
ew th
e da
ta s
tore
d un
der
your
pse
udon
ym in
ord
er to
ens
ure
corr
ect
docu
men
tatio
n an
d hi
gh d
ata
qual
ity to
con
tact
the
stud
y si
te te
am fo
r cl
arify
ing
ques
tions
. EH
DN
sta
ff ca
n on
ly v
iew
and
use
pse
udon
ymis
ed d
ata
ente
red
on t
he E
HD
N n
etw
ork.
For
the
pur
pose
of
data
co
ntro
l, EH
DN
sta
ff (‘m
onito
rs’ a
nd ‘a
udito
rs’)
are
allo
wed
to c
heck
with
you
r st
udy
site
team
that
the
data
en
tere
d on
to
the
netw
ork
mat
ches
w
ith
the
data
fo
und
in
your
lo
cal
med
ical
re
cord
s.
Mon
itors
/aud
itors
are
bou
nd b
y m
edic
al c
onfid
entia
lity.
4. A
utho
rised
res
earc
hers
(sc
ient
ist/c
linic
ians
): Sc
ient
ists
/clin
icia
ns w
ho a
re i
nvol
ved
in H
D r
esea
rch
can
appl
y to
the
Scie
ntifi
c an
d B
ioet
hica
lAdv
isor
y C
omm
ittee
(SBA
C)o
f EH
DN
(a g
roup
of e
xper
ienc
ed
clin
icia
ns a
nd s
cien
tists
) for
aut
horis
atio
n to
obt
ain
acce
ss to
the
data
bas
e. A
utho
rised
rese
arch
ers
can
only
vie
w c
oded
dat
a. T
o en
sure
the
high
est d
egre
e of
con
fiden
tialit
y ps
eudo
nym
s ar
e re
code
d be
fore
th
e da
ta b
ank
is m
ade
avai
labl
e to
aut
horis
ed re
sear
cher
s. T
here
by it
is g
uara
ntee
d th
at a
ll pu
blic
atio
ns
repo
rting
on
the
findi
ngs
of a
utho
rised
rese
arch
exc
lusi
vely
use
ano
nym
ised
dat
a re
port
form
at (i
.e. n
ot
even
usi
ng th
e ps
eudo
nym
).
5. S
yste
m a
dmin
istra
tors
: In
ord
er t
o sa
fegu
ard
the
EHD
N c
entra
l da
taba
se,
a sm
all
num
ber
of
auth
oris
ed s
yste
m a
dmin
istra
tors
can
vie
w p
seud
onym
ised
dat
a.
6. O
ther
gro
ups
and
indi
vidu
als:
No-
one
othe
r th
an t
he g
roup
s an
d in
divi
dual
s de
scrib
ed a
bove
can
ga
in a
cces
s to
or r
ecei
ve th
e da
ta s
tore
d ab
out y
ou.
D.H
ow c
an I
be s
ure
that
una
utho
rised
peo
ple
cann
ot g
ain
acce
ss t
o m
y da
ta w
hile
the
y ar
e se
nt v
ia th
e In
tern
et?
All
data
tra
velli
ng v
ia t
he i
nter
net
are
encr
ypte
d. T
his
impl
ies
for
all
prac
tical
pur
pose
s th
at n
obod
y as
ide
from
the
inte
nded
rec
eive
r ca
n re
ad o
r ac
cess
the
se d
ata.
The
ser
ver
whe
re t
he d
atab
ase
is
stor
ed is
loc
ated
beh
ind
a ‘fi
rew
all’.
Thi
s so
phis
ticat
ed s
ecur
ity s
yste
m e
nsur
es t
hat
only
aut
horis
ed
com
pute
rs a
nd in
divi
dual
s ca
n ga
in a
cces
s to
the
dat
abas
e. F
urth
erm
ore,
the
cen
tral d
atab
ase
does
no
t con
tain
iden
tifyi
ng d
ata
as a
ll da
ta a
re s
tore
d un
der a
cod
e na
me
(‘pse
udon
ym’).
E.H
ow lo
ng a
re m
y da
ta s
tore
d fo
r?Al
l dat
a w
ill be
sto
red
as e
nter
ed:
until
you
with
draw
you
r par
ticip
atio
n an
d re
ques
t the
ano
nym
isat
ion
of y
our d
ata
until
10
year
s af
ter a
n ef
ficie
nt th
erap
y fo
r HD
has
bee
n es
tabl
ishe
da
max
imum
per
iod
of 6
0 ye
ars
(2 g
ener
atio
ns +
10
year
s),o
rup
to a
max
imum
of 1
0 ye
ars
afte
r the
pro
ject
act
iviti
es h
ave
stop
ped.
A co
mpl
ete
dele
tion
of d
ata
is d
iffic
ult,
sinc
e da
ta a
re li
kely
to h
ave
beco
me
part
of s
cien
tific
stu
dies
and
th
eref
ore
need
to b
e ke
pt o
n re
cord
in c
ompl
ianc
e to
law
s an
d re
gula
tions
to a
llow
futu
re c
ross
che
cks
and
data
ver
ifica
tions
, eve
n ye
ars
afte
r th
e re
sear
ch w
as c
ompl
eted
. How
ever
, all
links
to y
ou c
an b
e de
lete
d an
d irr
ever
sibl
y de
stro
yed.
As
a re
sult,
thu
s no
t ev
en t
he p
hysi
cian
s ch
osen
by
you
for
enro
lmen
t int
o R
EGIS
TRY
will
any
long
er b
e ab
le to
rec
ogni
ze d
ata
as d
ata
belo
ngin
g to
you
. Suc
h a
com
plet
e an
onym
isat
ion
will
be c
arrie
d ou
t in
the
follo
win
gca
ses:
If yo
u w
ithdr
aw y
our c
onse
nt fo
r fur
ther
par
ticip
atio
n in
REG
ISTR
Y an
d if
you
requ
est t
hat y
our p
ast
data
are
ano
nym
ised
.If
you
requ
est c
ompl
ete
anon
ymis
atio
n of
you
r dat
a.
Loca
tion,
dat
e,N
ame
of th
e co
nsen
ting
clin
icia
n
44
10.2
Part
icip
ant C
onse
nt F
orm
(New
REG
ISTR
Y-H
DPa
rtic
ipan
ts)
Nam
e of
stu
dy:
REG
ISTR
Y –
an o
bser
vatio
nal
stud
y of
the
Eur
opea
n H
untin
gton
’sdi
seas
e N
etw
ork
(EH
DN
)
Con
tent
, pro
cedu
res,
ris
ks a
nd a
ims
of th
e re
sear
ch p
roje
ct n
amed
abo
ve a
s w
ell a
s th
e rig
ht to
vie
w
the
data
reco
rded
was
exp
lain
ed to
me
in d
etai
l by
……
..……
..……
..……
.. I h
ad th
e op
portu
nity
to a
sk
ques
tions
and
obt
ain
answ
ers
whi
ch I
felt
wer
e sa
tisfa
ctor
y. I
had
suffi
cien
t tim
e to
dec
ide
whe
ther
or
not I
wan
t to
parti
cipa
te in
the
proj
ect.
I rec
eive
d a
copy
of t
he p
atie
nt in
form
atio
n an
d of
the
cons
ent
form
. Pl
ease
che
ck Y
es o
r N
o fo
r ea
ch q
uest
ion
belo
w,
refe
rrin
g to
the
fol
low
ing
optio
nal
stud
y pr
oced
ures
:
I agr
ee to
par
ticip
ate
in th
e st
anda
rd R
EGIS
TRY
asse
ssm
ent a
nd re
ceiv
e re
gula
r (e.
g. y
early
) fol
low
-up
visi
ts.M
y de
cisi
ons
to p
artic
ipat
e in
eac
h of
the
optio
nal c
ompo
nent
s ar
e pr
ovid
ed b
elow
:
I gi
ve m
y pe
rmis
sion
for
my
stud
y si
te t
eam
to
cont
act m
e in
-bet
wee
n vi
sits
to
clar
ify q
uest
ions
(e.
g.
conc
erni
ng m
y an
swer
s in
REG
ISTR
Y qu
estio
nnai
res)
, to
prov
ide
me
with
upd
ates
on
REG
ISTR
Y or
to
info
rm m
e ab
out
upco
min
g tre
atm
ent
trial
s fo
r w
hich
I w
ould
be
elig
ible
and
in w
hich
I m
ay w
ant
to
cons
ider
par
ticip
atio
n.
Opt
iona
l com
pone
nt 1
:Con
tact
in-b
etw
een
stud
y vi
sits
I giv
e m
y pe
rmis
sion
for
the
colle
ctio
n of
blo
od (
30 m
l or
3 tu
bes
each
con
tain
ing
two
teas
poon
s) a
nd
urin
e (3
0 m
l) fro
m m
e at
eac
h vi
sit
(e.g
. ye
arly
)an
d de
clar
e to
don
ate
them
for
stu
dies
to
iden
tify
gene
tic m
odifi
ers
of H
D a
nd to
est
ablis
h an
d va
lidat
e bi
olog
ical
mar
kers
for
HD
. I u
nder
stan
d th
at m
y sa
mpl
es a
re s
ubm
itted
to a
nd s
tore
d at
Bio
Rep
S.r.
l., a
cen
tral b
iore
posi
tory
loca
ted
in M
ilan
(Ital
y) fo
r th
e ne
xt tw
o ge
nera
tions
(60
year
s) o
r un
til a
n ef
ficie
nt th
erap
y fo
r H
D is
est
ablis
hed.
I ca
n co
ntac
t my
stud
y si
te a
t any
tim
e an
d ca
n re
ques
t des
truct
ion
of th
e sa
mpl
es s
tore
d fro
m m
e.
Opt
iona
l com
pone
nt 2
:Don
atio
n of
blo
od a
nd u
rine
for s
tudi
es to
iden
tify
gene
tic m
odifi
ers
of H
D a
nd to
es
tabl
ish
and
valid
ate
biol
ogic
al m
arke
rs fo
r HD
I giv
e m
y pe
rmis
sion
for a
CAG
ana
lysi
s on
my
DN
A; th
ese
resu
lts a
re fo
r res
earc
h on
ly.
Opt
iona
l com
pone
nt 3
:Ana
lysi
s of
a b
lood
sam
ple
for t
he H
D m
utat
ion
I ag
ree
to p
artic
ipat
e in
the
col
lect
ion
of f
amily
his
tory
info
rmat
ion.
I u
nder
stan
d th
at in
add
ition
I a
m
offe
red
info
rmat
ion
shee
ts o
n R
EGIS
TRY
to a
llow
me
to in
form
my
rela
tives
abo
ut t
his
optio
n; I
am
un
der n
o ob
ligat
ion
to d
istri
bute
them
.
Opt
iona
l com
pone
nt 4
:Fam
ily H
isto
ry Q
uest
ionn
aire
I agr
ee th
at m
y pa
st c
linic
al d
ata
gene
rate
d at
my
stud
y si
te c
an b
e st
ored
as
part
of th
e R
EGIS
TRY
data
base
.
Opt
iona
l com
pone
nt 5
: Ret
rosp
ectiv
e cl
inic
al d
ata
I agr
ee to
rece
ive
info
rmat
ion
abou
t the
nov
el a
sses
smen
t bat
tery
and
to p
artic
ipat
e in
the
deve
lopm
ent
of n
ovel
ass
essm
ents
.
Opt
iona
l com
pone
nt 6
: Nov
el a
sses
smen
ts
207Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
45
I con
sent
to c
onsi
der
vide
o re
cord
ing
of c
linic
al a
sses
smen
ts, t
he tr
ansm
issi
on o
f the
se r
ecor
ding
s vi
a se
cure
inte
rnet
con
nect
ion
and
thei
r vi
ewin
g by
aut
horis
ed p
erso
nnel
for
qual
ity c
ontro
l, re
sear
ch a
nd
train
ing
purp
oses
.
Opt
iona
l com
pone
nt 7
: Vid
eota
ping
Dur
ing
scie
ntifi
c st
udie
s, p
erso
nal
data
and
med
ical
fin
ding
s ab
out
you
are
reco
rded
. Th
e st
orag
e,
anal
ysis
and
com
mun
icat
ion
of d
ata
rela
ting
to th
e st
udy
are
carr
ied
out a
ccor
ding
to le
gal r
equi
rem
ents
an
d en
tail
the
follo
win
g co
nsen
t bef
ore
parti
cipa
ting
in th
e st
udy.
Info
rmat
ion
and
cons
ent f
orm
rega
rdin
g da
ta p
rote
ctio
n
1. I
agr
ee t
hat
data
/med
ical
dat
a ob
tain
ed d
urin
g th
e co
urse
of
this
stu
dy c
anbe
rec
orde
d in
qu
estio
nnai
res
and
on e
lect
roni
c da
ta c
arrie
rs a
nd p
roce
ssed
with
out
prov
idin
g pe
rson
al id
entit
y. A
ll ps
eudo
nym
ised
dat
a ar
e st
ored
at
a se
rver
loc
ated
at
the
Uni
vers
ity o
f U
lm,
Ger
man
y. I
n ad
ditio
n,
som
e se
lect
ed d
ata
(pse
udon
ym, a
ge, s
ex a
nd d
isea
se s
tate
-whe
ther
one
rep
rese
nts
a co
ntro
l or
HD
m
utat
ion
carr
ier)
will
be s
tore
d at
the
serv
er o
fthe
cen
tral b
iore
posi
tory
in M
ilano
, whe
re th
e bi
olog
ical
sa
mpl
es a
re s
tore
d.
2. I
also
agr
ee th
at a
utho
rised
per
sons
(e.g
. EH
DN
mon
itors
, reg
ulat
ory
auth
oriti
es)
who
are
bou
nd b
y co
nfid
entia
lity
(e.g
. fro
m th
e sp
onso
r EH
DN
, or
the
Uni
vers
ity)
can
view
the
pers
onal
dat
a re
cord
ed a
s fa
r as
it is
nec
essa
ry o
r leg
ally
requ
ired
for d
ata
cont
rol.
For t
his
purp
ose
only
, I e
xem
pt th
e cl
inic
ian
as
wel
l as
the
med
ical
tea
m a
t m
y st
udy
site
from
the
obl
igat
ion
to e
nsur
e m
edic
al c
onfid
entia
lity
at a
ll tim
es.
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
Nam
e of
the
Parti
cipa
nt
Sign
atur
e of
the
parti
cipa
nt
Plac
e, d
ate
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
Nam
e of
Leg
al R
epre
sent
ativ
e (if
app
licab
le)
Sign
atur
e of
the
Lega
l Rep
rese
ntat
ive
Plac
e, d
ate
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
…
……
……
…N
ame
of C
onsu
ltee/
Witn
ess
(opt
iona
l)Si
gnat
ure
of th
e C
onsu
ltee/
Witn
ess
Plac
e, d
ate
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
…
……
……
…N
ame
of P
erso
n O
btai
ning
Con
sent
Sign
atur
e of
Per
son
Obt
aini
ng C
onse
ntPl
ace,
dat
e(P
rinte
d N
ame
and
Title
)
REG
ISTR
Y PS
EUD
ON
YM:
46
10.3
Part
icip
ant I
nfor
mat
ion
Shee
t (Ex
istin
g R
EGIS
TRY-
HD
Part
icip
ants
)
Nam
e of
stu
dy:
REG
ISTR
Y –
anob
serv
atio
nal
stud
y of
the
Eur
opea
n H
untin
gton
’sdi
seas
eN
etw
ork
(EH
DN
)
Dea
r Par
ticip
ant,
You
are
alre
ady
a pa
rtici
pant
of
REG
ISTR
Y an
d yo
u ar
e ei
ther
suf
ferin
g fro
m H
untin
gton
’s d
isea
se
(HD
), be
long
to
a fa
mily
at
risk
for
HD
, or
are
a r
elat
ive
of a
pat
ient
with
HD
. To
dat
e, y
ou h
ave
cons
ente
d to
par
ticip
atin
g in
REG
ISTR
Y, w
hich
mea
ns t
hat
with
you
r pe
rmis
sion
, w
e ca
rry
out
a th
orou
gh s
tand
ard
exam
inat
ion
and
the
docu
men
tatio
n of
the
dat
a ob
tain
ed d
urin
g yo
ur c
linic
al
exam
inat
ion
stor
ed u
nder
a p
seud
onym
on a
n el
ectro
nic
data
base
and
you
r co
nsen
t to
reg
ular
(e.
g.
year
ly)
follo
w-u
p vi
sits
. Yo
u m
ay o
r m
ay n
ot h
ave
cons
ente
d to
a n
umbe
r of
opt
iona
l co
mpo
nent
s,
incl
udin
g th
e co
llect
ion
of fa
mily
his
tory
info
rmat
ion,
the
colle
ctio
n of
blo
od a
nd u
rine
for b
iom
arke
r and
ge
netic
mod
ifier
stu
dies
, H
D g
ene
test
ing
for
rese
arch
pur
pose
s an
d pe
rmis
sion
to
be c
onta
cted
be
twee
n vi
sits
.
Sinc
e yo
u en
rolle
d to
take
par
t in
this
stu
dy, R
EGIS
TRY
has
adop
ted
addi
tiona
l opt
iona
l com
pone
nts.
W
e w
ould
like
to in
vite
you
to ta
ke p
art i
n an
y or
all
of th
e fo
llow
ing
optio
nal c
ompo
nent
s:co
llect
ion
of re
trosp
ectiv
e cl
inic
al d
ata,
(pa
rtici
patio
n in
nov
el a
sses
smen
ts(
Opt
iona
l com
pone
nt 1
)O
ptio
nal c
ompo
nent
2)
vide
otap
ing
of a
sses
smen
ts fo
r res
earc
h/te
achi
ngpu
rpos
es(
, and O
ptio
nal c
ompo
nent
3).
We
wou
ld l
ike
to a
sk y
ou t
o co
nsid
er g
ivin
g pe
rmis
sion
to
use
info
rmat
ion
from
your
pas
t cl
inic
al
asse
ssm
ents
that
wer
epe
rform
ed b
efor
e yo
ur p
artic
ipat
ion
in R
EGIS
TRY.
Man
y pe
ople
taki
ng p
art i
n R
EGIS
TRY
have
und
ergo
ne r
egul
ar a
sses
smen
ts f
or a
num
ber
of y
ears
. Th
e in
form
atio
n he
ld w
ithin
th
ese
past
clin
ical
eva
luat
ions
may
hel
p us
to u
nder
stan
d th
e co
urse
of H
D b
ette
r.
Opt
iona
l com
pone
nt 1
: Ret
rosp
ectiv
e cl
inic
al d
ata
A nu
mbe
r of
nov
el a
sses
smen
ts (
e.g.
que
stio
nnai
res,
int
ervi
ews,
rat
ing
scal
es)
may
hel
p us
to
unde
rsta
nd m
ore
abou
t th
e on
set,
cour
se a
nd t
reat
men
t of
Hun
tingt
on’s
dis
ease
. W
ene
ed t
o co
llect
m
ore
data
on
each
ass
essm
ent i
n or
der
to k
now
whe
ther
they
sho
uld
be u
sed
in th
e de
sign
of f
utur
e re
sear
ch a
nd c
linic
al c
are
prac
tices
.
Opt
iona
l com
pone
nt 2
: Nov
el a
sses
smen
ts
We
wou
ld li
ke to
ask
you
to c
onsi
der
taki
ng p
art i
n th
ese
nove
l ass
essm
ents
. The
nov
el a
sses
smen
ts
cove
r a w
ide
rang
e of
are
as (e
.g. i
nfor
mat
ion
on y
our w
ell-b
eing
, you
r qua
lity
of li
fe, a
nd p
artic
ular
sig
ns
and
sym
ptom
s yo
u m
ay b
e fe
elin
g) a
nd y
ou m
ay b
e ap
proa
ched
to ta
ke p
art.
The
over
all d
urat
ion
of th
e no
vel a
sses
smen
ts to
geth
er w
ith th
e st
anda
rd R
EGIS
TRY
asse
ssm
ents
sho
uld
not e
xcee
d 2.
5 ho
urs.
You
can
deci
de w
heth
er y
ou w
ant t
o do
the
addi
tiona
l ass
essm
ents
or n
ot d
urin
g yo
ur v
isit.
For
certa
in a
sses
smen
ts i
nclu
ded
in R
EGIS
TRY,
you
may
als
o be
ask
ed t
o be
vid
eota
ped.
The
vi
deot
apes
will
be v
isib
le f
or a
res
trict
ed n
umbe
r of
EH
DN
mem
bers
(e.
g. e
xper
ienc
ed p
hysi
cian
s, fo
r co
nsul
tatio
n pu
rpos
es,
phys
icia
ns in
tra
inin
g) f
or q
ualit
y co
ntro
l, re
sear
ch a
nd t
rain
ing
purp
oses
onl
y.
The
reco
rdin
gs w
ill b
e tra
nsm
itted
via
sec
ure
inte
rnet
con
nect
ion
and
will
be s
tore
d on
the
REG
ISTR
Y se
rver
in a
pse
udon
ymis
ed fo
rm.
Opt
iona
l com
pone
nt 3
: Vid
eota
ping
.
VOLU
NTE
ERIN
GYo
ur p
artic
ipat
ion
in th
is r
esea
rch
proj
ect i
s vo
lunt
ary.
You
are
free
to w
ithdr
aw fr
om th
e st
udy
at a
ny
time
and
with
out
givi
ng r
easo
n. T
his
pote
ntia
l w
ithdr
awal
doe
s no
t af
fect
you
r co
ntin
uing
med
ical
tre
atm
ent.
On
your
req
uest
eve
ry li
nk b
etw
een
your
sto
red
data
and
you
r pe
rson
can
be
perm
anen
tly
dele
ted
(for
deta
ils s
ee In
form
atio
n re
gard
ing
data
pro
cess
ing,
dat
a pr
otec
tion
and
data
sec
urity
, po
int ‘
E’).
INSU
RAN
CE
208 Hygeia Public Health 2011, 46(2): 183-218
47
Beca
use
the
Reg
istry
is n
eith
er a
pha
rmac
olog
ical
stu
dy n
or a
stu
dy to
test
new
dia
gnos
tic p
roce
dure
s,
ther
e ar
e no
add
ition
al h
ealth
risk
s an
d th
e pa
rtici
pant
s th
eref
ore
do n
ot n
eed
insu
ranc
e.
CLI
NIC
IAN
CO
NTA
CT
Shou
ld y
ou h
ave
any
ques
tions
at
anyt
ime
durin
g th
e co
urse
of
the
rese
arch
pro
ject
you
can
rea
ch
(loca
l inv
estig
ator
s) o
n te
leph
one
num
ber
(tele
phon
e nu
mbe
r of
loca
l inv
estig
ator
) at
any
tim
e du
ring
wor
king
hou
rs. F
or e
mer
genc
ies
out o
f hou
rs, r
ing
(loca
l em
erge
ncy
num
ber)
.
CO
NFI
DEN
TIAL
ITY/
DAT
A PR
OTE
CTI
ON
:Al
l clin
icia
ns a
nd r
elat
ed m
edic
al s
taff
invo
lved
in lo
okin
g af
ter
you
durin
g th
is c
linic
al s
tudy
are
bou
nd
by m
edic
al c
onfid
entia
lity
and
are
oblig
ed t
o co
mpl
y w
ith d
ata
prot
ectio
n. R
esea
rch
resu
lts r
elat
ing
to
this
stu
dy a
re in
tend
ed fo
r us
e in
an
anon
ymou
s fo
rm in
sci
entif
ic p
ublic
atio
ns. A
s fa
r as
is n
eces
sary
fo
r ens
urin
g co
rrec
t dat
a en
try, a
utho
rised
indi
vidu
als
(e.g
. the
spo
nsor
, the
uni
vers
ity) a
re p
erm
itted
to
revi
ew y
our l
ocal
med
ical
reco
rds.
If in
divi
dual
s au
thor
ised
to v
iew
rec
ords
are
not
bou
nd b
y m
edic
al c
onfid
entia
lity
as m
entio
ned
abov
e,
pers
onal
dat
a th
at c
ome
to th
eir a
ttent
ion
durin
g ch
ecks
are
con
fiden
tial u
nder
the
Dat
a Pr
otec
tion
Act.
Euro
pean
H
D
Net
wor
k:
Info
rmat
ion
rega
rdin
g da
ta
proc
essi
ng,
data
pr
otec
tion
and
data
se
curit
y.
A.
An
esse
ntia
l sa
fety
asp
ect
of t
he p
roje
ct i
s th
e pr
oces
sing
of
my
data
in
an e
xclu
sive
ly
pseu
dony
mis
ed m
anne
r. W
hat d
oes
that
mea
n an
d ho
w is
it c
arrie
d ou
t?
Dur
ing
your
firs
t vi
sit,
your
clin
icia
n w
ill e
nter
cer
tain
dat
a ab
out
you
into
the
com
pute
r. Fr
om t
hese
pe
rson
al d
ata
a un
ique
cod
e na
me
(‘pse
udon
ym’)
is c
alcu
late
d, c
onsi
stin
g of
a s
erie
s of
9 d
igits
. The
fo
llow
ing
pers
onal
dat
a ar
e us
ed:
first
nam
e, b
irth
nam
e (s
urna
me)
, da
te o
f bi
rth,
plac
e of
birt
h an
d m
othe
r’s m
aide
n na
me.
Exam
ple:
Mar
ia,
Mill
er
nee
Mus
term
ann,
bo
rn
10.1
1.19
64
in
Ulm
, m
othe
r’s m
aide
n na
me
Schm
idt.
This
in
form
atio
n re
sults
in
the
code
nam
e (‘p
seud
onym
’) 42
5-49
1-32
6. I
mpo
rtant
ly,
the
pseu
dony
m i
s cr
eate
d on
the
bas
is o
f a
so-c
alle
d ‘s
ecur
e ha
sh-a
lgor
ithm
’. B
y th
is m
athe
mat
ical
ope
ratio
n a
uniq
ue
valu
e is
ass
igne
d du
ring
a co
mpl
icat
ed, o
ne-w
ay p
roce
dure
. The
mat
hem
atic
al a
lgor
ithm
use
d en
sure
s th
at n
obod
y (n
ot e
ven
the
syst
em p
rogr
amm
er)
can
reco
nstru
ct f
rom
the
resu
lt (th
e ‘p
seud
onym
’) th
e in
form
atio
n w
hich
was
use
d to
gen
erat
e th
e ps
eudo
nym
(i.e
. yo
ur u
niqu
e pe
rson
al d
ata)
in t
he f
irst
plac
e. T
he p
erso
nal d
ata
trans
mitt
ed t
o ge
nera
te t
he p
seud
onym
are
hel
d on
ly f
or t
he c
alcu
latio
n of
yo
ur c
ode
nam
e (‘p
seud
onym
’) in
the
wor
king
mem
ory
of a
larg
e co
mpu
ter (
‘ser
ver’)
. The
cal
cula
tion
of
the
pseu
dony
m r
equi
res
a ve
ry s
hort
time
(milli
seco
nds)
. V
iew
ing
pers
onal
dat
a du
ring
this
tim
e is
im
poss
ible
. The
reaf
ter a
ll da
ta u
sed
to c
reat
e th
e ps
eudo
nym
are
per
man
ently
era
sed
from
the
wor
king
m
emor
y of
the
serv
er s
o th
at n
o id
entif
ying
det
ails
rem
ain;
dat
a us
ed to
gen
erat
e th
e ps
eudo
nym
are
ne
ver
stor
ed in
any
for
m o
f pe
rman
ent
mem
ory
(e.g
. on
the
har
d dr
ive)
. Fol
low
ing
this
, al
l dat
a ba
se
entri
es a
nd e
very
use
of d
ata
is e
xclu
sive
ly c
arrie
d ou
t und
er th
e as
sign
ed p
seud
onym
.
B.W
hich
dat
a do
I ha
ve to
dis
clos
e ap
art f
rom
the
data
requ
ired
to c
reat
e m
y ps
eudo
nym
in th
e co
urse
oft
he R
EGIS
TRY
stud
y an
d su
bseq
uent
stu
dies
?D
urin
g th
e co
urse
of
the
REG
ISTR
Y st
udy,
som
e he
alth
and
/or
med
ical
dat
a w
ill be
rec
orde
d (s
ee
Parti
cipa
nt In
form
atio
n Sh
eet f
or fu
rther
det
ails
). If
you
are
parti
cipa
ting
in a
ny s
ubse
quen
t stu
dies
, you
r cl
inic
ian
will
give
you
det
aile
d in
form
atio
n ab
out t
he s
tudy
and
the
data
requ
ired
for i
t acc
ordi
ngly
. Eac
h su
bseq
uent
stu
dy re
quire
s se
para
te p
artic
ipan
t con
sent
.
C.W
ho c
an s
ee a
nd u
se m
y da
ta?
1. Y
ou: i
f you
wis
h so
, the
clin
icia
n tre
atin
g yo
u ca
n le
t you
to s
ee a
ll da
ta s
tore
d ab
out y
ou. I
t is
advi
sed
that
you
rev
iew
the
se d
ata
toge
ther
with
the
phy
sici
an t
reat
ing
you
to e
xpla
in m
edic
al t
erm
inol
ogy
to
you
and
to a
nsw
er q
uest
ions
you
may
hav
e.
48
2. T
he c
linic
ian
treat
ing
you:
The
stu
dy s
ite te
am e
nrol
ling
you
for R
EGIS
TRY
is th
e on
ly o
ne a
part
from
yo
urse
lf w
ho c
an l
ink
your
pse
udon
ym t
o yo
ur i
dent
ifyin
g da
ta (
i.e.
nam
e, a
ddre
ss e
tc.).
Afte
r ge
nera
tion
of th
e ps
eudo
nym
all
entry
of c
linic
al in
form
atio
n in
the
data
bas
e is
car
ried
out u
nder
you
r co
de n
ame
(‘pse
udon
ym’).
You
r st
udy
site
tea
m in
clud
ing
your
tre
atin
g cl
inic
ian
can
view
all
clin
ical
da
ta re
cord
ed u
nder
pse
udon
ym.
3. E
HD
N s
taff:
EH
DN
sta
ff ca
n vi
ew th
e da
ta s
tore
d un
der
your
pse
udon
ym in
ord
er to
ens
ure
corr
ect
docu
men
tatio
n an
d hi
gh d
ata
qual
ity to
con
tact
the
stud
y si
te te
am fo
r cl
arify
ing
ques
tions
. EH
DN
sta
ff ca
n on
ly v
iew
and
use
pse
udon
ymis
ed d
ata
ente
red
on t
he E
HD
N n
etw
ork.
For
the
pur
pose
of
data
co
ntro
l, EH
DN
sta
ff (‘m
onito
rs’ a
nd ‘a
udito
rs’)
are
allo
wed
to c
heck
with
you
r st
udy
site
team
that
the
data
en
tere
d on
to
the
netw
ork
mat
ches
w
ith
the
data
fo
und
in
your
lo
cal
med
ical
re
cord
s.
Mon
itors
/aud
itors
are
bou
nd b
y m
edic
al c
onfid
entia
lity.
4. A
utho
rised
res
earc
hers
(sc
ient
ist/c
linic
ians
): Sc
ient
ists
/clin
icia
ns w
ho a
re i
nvol
ved
in H
D r
esea
rch
can
appl
y to
the
Scie
ntifi
c an
d B
ioet
hica
lAdv
isor
y C
omm
ittee
(SBA
C)o
f EH
DN
(a g
roup
of e
xper
ienc
ed
clin
icia
ns a
nd s
cien
tists
) for
aut
horis
atio
n to
obt
ain
acce
ss to
the
data
bas
e. A
utho
rised
rese
arch
ers
can
only
vie
w c
oded
dat
a. T
o en
sure
the
high
est d
egre
e of
con
fiden
tialit
y ps
eudo
nym
s ar
e re
code
d be
fore
th
e da
ta b
ank
is m
ade
avai
labl
e to
aut
horis
ed re
sear
cher
s. T
here
by it
is g
uara
ntee
d th
at a
ll pu
blic
atio
ns
repo
rting
on
the
findi
ngs
of a
utho
rised
rese
arch
exc
lusi
vely
use
ano
nym
ised
dat
a re
port
form
at (i
.e. n
ot
even
usi
ng th
e ps
eudo
nym
).
5. S
yste
m a
dmin
istra
tors
: In
ord
er t
o sa
fegu
ard
the
EHD
N c
entra
l da
taba
se,
a sm
all
num
ber
of
auth
oris
ed s
yste
m a
dmin
istra
tors
can
vie
w p
seud
onym
ised
dat
a.
6. O
ther
gro
ups
and
indi
vidu
als:
No-
one
othe
r th
an t
he g
roup
s an
d in
divi
dual
s de
scrib
ed a
bove
can
ga
in a
cces
s to
or r
ecei
ve th
e da
ta s
tore
d ab
out y
ou.
D.H
ow c
an I
be s
ure
that
una
utho
rised
peo
ple
cann
ot g
ain
acce
ss t
o m
y da
ta w
hile
the
y ar
e se
nt v
ia th
e In
tern
et?
All
data
tra
velli
ng v
ia t
he i
nter
net
are
encr
ypte
d. T
his
impl
ies
for
all
prac
tical
pur
pose
s th
at n
obod
y as
ide
from
the
inte
nded
rec
eive
r ca
n re
ad o
r ac
cess
the
se d
ata.
The
ser
ver
whe
re t
he d
atab
ase
is
stor
ed is
loc
ated
beh
ind
a ‘fi
rew
all’.
Thi
s so
phis
ticat
ed s
ecur
ity s
yste
m e
nsur
es t
hat
only
aut
horis
ed
com
pute
rs a
nd in
divi
dual
s ca
n ga
in a
cces
s to
the
dat
abas
e. F
urth
erm
ore,
the
cen
tral d
atab
ase
does
no
t con
tain
iden
tifyi
ng d
ata
as a
ll da
ta a
re s
tore
d un
der a
cod
e na
me
(‘pse
udon
ym’).
E.H
ow lo
ng a
re m
y da
ta s
tore
d fo
r?Al
l dat
a w
ill be
sto
red
as e
nter
ed:
until
you
with
draw
you
r par
ticip
atio
n an
d re
ques
t the
ano
nym
isat
ion
of y
our d
ata
until
10
year
s af
ter a
n ef
ficie
nt th
erap
y fo
r HD
has
bee
n es
tabl
ishe
da
max
imum
per
iod
of 6
0 ye
ars
(2 g
ener
atio
ns +
10
year
s),o
rup
to a
max
imum
of 1
0 ye
ars
afte
r the
pro
ject
act
iviti
es h
ave
stop
ped.
A co
mpl
ete
dele
tion
of d
ata
is d
iffic
ult,
sinc
e da
ta a
re li
kely
to h
ave
beco
me
part
of s
cien
tific
stu
dies
and
th
eref
ore
need
to b
e ke
pt o
n re
cord
in c
ompl
ianc
e to
law
s an
d re
gula
tions
to a
llow
futu
re c
ross
che
cks
and
data
ver
ifica
tions
, eve
n ye
ars
afte
r th
e re
sear
ch w
as c
ompl
eted
. How
ever
, all
links
to y
ou c
an b
e de
lete
d an
d irr
ever
sibl
y de
stro
yed.
As
a re
sult,
thu
s no
t ev
en t
he p
hysi
cian
s ch
osen
by
you
for
enro
lmen
t int
o R
EGIS
TRY
will
any
long
er b
e ab
le to
rec
ogni
zeda
ta a
s da
ta b
elon
ging
to y
ou. S
uch
a co
mpl
ete
anon
ymis
atio
n w
ill be
car
ried
out i
n th
e fo
llow
ing
case
s:
If yo
u w
ithdr
aw y
our c
onse
nt fo
r fur
ther
par
ticip
atio
n in
REG
ISTR
Y an
d if
you
requ
est t
hat y
our p
ast
data
are
ano
nym
ised
.If
you
requ
est c
ompl
ete
anon
ymis
atio
n of
you
r dat
a.
Loca
tion,
dat
e,N
ame
of th
e co
nsen
ting
clin
icia
n
209Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
49
10.4
Part
icip
ant C
onse
nt F
orm
(Exi
stin
g R
EGIS
TRY-
HD
Part
icip
ants
)
Nam
e of
stu
dy:
REG
ISTR
Y –
an o
bser
vatio
nal
stud
y of
the
Eur
opea
n H
untin
gton
’sdi
seas
eN
etw
ork
(EH
DN
)
Con
tent
, pro
cedu
res,
ris
ks a
nd a
ims
of th
e re
sear
ch p
roje
ct n
amed
abo
ve a
s w
ell a
s th
e rig
ht to
vie
w
the
data
reco
rded
was
exp
lain
ed to
me
in d
etai
l by
……
..……
..……
..……
.. I h
ad th
e op
portu
nity
to a
sk
ques
tions
and
obt
aine
d an
swer
s w
hich
I fe
lt w
ere
satis
fact
ory.
I ha
d su
ffici
ent t
ime
to d
ecid
e w
heth
er o
r no
t I w
ant t
o pa
rtici
pate
in th
e pr
ojec
t. I r
ecei
ved
a co
py o
f the
pat
ient
info
rmat
ion
and
of th
e co
nsen
t fo
rm.
Plea
se c
heck
YE
S or
NO
for
eac
h qu
estio
n be
low
, re
ferr
ing
to t
he f
ollo
win
g op
tiona
l st
udy
proc
edur
es:
I agr
ee th
at m
y pa
st c
linic
al d
ata
gene
rate
d at
my
stud
y si
te c
an b
e st
ored
as
part
of th
e R
EGIS
TRY
data
base
.
Opt
iona
l com
pone
nt 1
: Ret
rosp
ectiv
e cl
inic
al d
ata
I ag
ree
to r
ecei
ve i
nfor
mat
ion
abou
t th
e in
the
nov
el a
sses
smen
t ba
ttery
and
to
parti
cipa
te i
n th
e de
velo
pmen
t of n
ovel
ass
essm
ents
.
Opt
iona
l com
pone
nt 2
: Nov
el a
sses
smen
ts
I con
sent
to c
onsi
der
vide
o re
cord
ing
of c
linic
al a
sses
smen
ts, t
he tr
ansm
issi
on o
f the
se r
ecor
ding
s vi
a se
cure
inte
rnet
con
nect
ion
and
thei
r vi
ewin
g by
aut
horis
ed p
erso
nnel
for
qual
ity c
ontro
l, re
sear
ch a
nd
train
ing
purp
oses
.
Opt
iona
l com
pone
nt 3
: Vid
eota
ping
Dur
ing
scie
ntifi
c st
udie
s, p
erso
nal
data
and
med
ical
fin
ding
s ab
out
you
are
reco
rded
. Th
e st
orag
e,
anal
ysis
and
com
mun
icat
ion
of d
ata
rela
ting
to th
e st
udy
are
carr
ied
out a
ccor
ding
to le
gal r
equi
rem
ents
an
d en
tail
the
follo
win
g co
nsen
t bef
ore
parti
cipa
ting
in th
e st
udy.
Info
rmat
ion
and
cons
ent f
orm
rega
rdin
g da
ta p
rote
ctio
n
1. I
agr
ee t
hat
data
/med
ical
dat
a ob
tain
ed d
urin
g th
e co
urse
of
this
stu
dy c
an b
e re
cord
ed i
n qu
estio
nnai
res
and
on e
lect
roni
c da
ta c
arrie
rs a
nd p
roce
ssed
with
out
prov
idin
g pe
rson
al id
entit
y. A
ll ps
eudo
nym
ised
dat
a ar
e st
ored
at
a se
rver
loc
ated
at
the
Uni
vers
ity o
f U
lm,
Ger
man
y. I
n ad
ditio
n,
som
e se
lect
ed d
ata
(pse
udon
ym, a
ge, s
ex a
nd d
isea
se s
tate
-whe
ther
one
rep
rese
nts
a co
ntro
l or
HD
m
utat
ion
carr
ier)
will
be s
tore
d at
the
serv
er o
f the
cen
tral b
iore
posi
tory
in M
ilano
, whe
re th
e bi
olog
ical
sa
mpl
es a
re s
tore
d.
2. I
also
agr
ee th
at a
utho
rised
per
sons
(e.g
. EH
DN
mon
itors
, reg
ulat
ory
auth
oriti
es)
who
are
bou
nd b
y co
nfid
entia
lity
(e.g
. fro
m th
e sp
onso
r, or
the
Uni
vers
ity) c
an v
iew
the
pers
onal
dat
a re
cord
ed a
s fa
r as
itis
nec
essa
ry o
r le
gally
req
uire
d fo
r da
ta c
ontro
l. Fo
r th
is p
urpo
se o
nly,
I ex
empt
the
clin
icia
n fro
m th
e ob
ligat
ion
to e
nsur
e m
edic
al c
onfid
entia
lity
at a
ll tim
es.
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
Nam
e of
the
Parti
cipa
nt
Sign
atur
e of
the
parti
cipa
nt
Plac
e, d
ate
50
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
…
……
……
…N
ame
of L
egal
Rep
rese
ntat
ive
(if a
pplic
able
)Si
gnat
ure
of th
e Le
gal R
epre
sent
ativ
ePl
ace,
dat
e
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
…
……
……
…N
ame
of C
onsu
ltee/
Witn
ess
(opt
iona
l)Si
gnat
ure
of th
e C
onsu
ltee/
Witn
ess
Plac
e, d
ate
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
…
……
……
…N
ame
of P
erso
n O
btai
ning
Con
sent
Sign
atur
e of
Per
son
Obt
aini
ng C
onse
ntPl
ace,
dat
e(P
rinte
d N
ame
and
Title
)
REG
ISTR
Y PS
EUD
ON
YM:
210 Hygeia Public Health 2011, 46(2): 183-218
51
10.5
Part
icip
ant I
nfor
mat
ion
Shee
t (R
EGIS
TRY-
CO
MPA
NIO
NS)
Nam
e of
stu
dy:
REG
ISTR
Y –
an o
bser
vatio
nal
stud
y of
the
Eur
opea
n H
untin
gton
’s d
isea
seN
etw
ork
(EH
DN
)
Dea
r Com
pani
on,
You
are
acco
mpa
nyin
g/as
sist
ing
som
ebod
y fro
m a
fam
ily a
ffect
edby
Hun
tingt
on’s
dis
ease
(HD
). Yo
ur
partn
er/re
lativ
e/fri
end
take
s pa
rt in
a r
esea
rch
proj
ect
cond
ucte
d at
man
y ce
ntre
s th
roug
hout
Eur
ope
(REG
ISTR
Y) s
trivi
ng to
und
erst
and
HD
bet
ter
and
to im
prov
e th
e cu
rren
tly a
vaila
ble
tool
s to
follo
w th
e co
urse
of t
he d
isea
se.
Sinc
e aw
aren
ess
of t
he s
ympt
oms
and
sign
s of
HD
may
diff
er b
etw
een
the
parti
cipa
ntan
d th
eir
com
pani
ons,
and
giv
en th
e fa
ct th
at a
n illn
ess
of a
clo
se o
ne h
as a
n im
pact
on
your
ow
n lif
e, w
e w
ould
lik
e to
ask
you
to c
ompl
ete
a qu
estio
nnai
re a
t eac
h an
nual
vis
it. T
his
ques
tionn
aire
inqu
ires
abou
t the
im
pact
of
the
illnes
s of
you
r co
mpa
nion
on
you.
If
you
deci
de t
o ta
ke p
art
in t
his
proj
ect
it w
ould
be
impo
rtant
to jo
in y
our c
ompa
nion
at r
egul
arly
(e.g
. yea
rly)f
or th
e fo
llow
-up
visi
t.
The
resu
lts o
f yo
ur c
ompa
nion
’s e
xam
inat
ions
will
be
stor
edun
der
a ps
eudo
nym
on
an e
lect
roni
c da
taba
se b
y th
e m
edic
al s
taff
inte
rvie
win
g an
d ex
amin
ing
you,
obv
ious
ly w
ithou
t sav
ing
nam
e, a
ddre
ss
or o
ther
dat
a th
at w
ould
allo
w th
e id
entif
icat
ion
of y
our c
ompa
nion
. The
que
stio
nnai
re th
at y
ou fi
ll in
will
be h
andl
ed li
kew
ise.
Ther
e is
a fu
rther
, opt
iona
l res
earc
h co
mpo
nent
des
crib
ed b
elow
. Thi
s re
quire
s yo
ur e
xplic
it co
nsen
t by
chec
king
the
box
‘YE
S’ o
r ‘N
O’ i
n th
e co
nsen
t for
m.
A nu
mbe
r of
nov
el a
sses
smen
ts (
e.g.
que
stio
nnai
res,
int
ervi
ews,
rat
ing
scal
es)
may
hel
p us
to
unde
rsta
nd m
ore
abou
t th
e on
set,
cour
se a
nd t
reat
men
t of
Hun
tingt
on’s
dis
ease
. W
ene
ed t
o co
llect
m
ore
data
on
each
of a
sses
smen
t in
orde
r to
know
whe
ther
they
sho
uld
be u
sed
in th
e de
sign
of f
utur
e re
sear
ch a
nd c
linic
al c
are
prac
tices
.
Opt
iona
l com
pone
nt 1
: Nov
el a
sses
smen
ts
We
wou
ld li
ke to
ask
you
to c
onsi
der
taki
ng p
art i
n th
ese
nove
l ass
essm
ents
. The
nov
el a
sses
smen
ts
cove
r a w
ide
rang
e of
are
as (e
.g. i
nfor
mat
ion
on y
our w
ell-b
eing
, you
r qua
lity
of li
fe, a
nd p
artic
ular
sig
ns
and
sym
ptom
syo
ur c
ompa
nion
may
be
feel
ing)
and
you
may
be
appr
oach
ed t
o ta
ke p
art.
You
can
deci
de w
heth
er y
ou w
ant t
o do
the
addi
tiona
l ass
essm
ents
or n
ot d
urin
g yo
ur v
isit.
REG
ISTR
Y is
a s
tudy
con
duct
ed b
y th
e Eu
rope
an H
untin
gton
’s D
isea
se N
etw
ork
(EH
DN
). EH
DN
isa
scie
ntifi
c ne
twor
k of
phy
sici
ans,
sci
entis
ts a
nd o
rgan
isat
ions
for
fam
ilies
affe
cted
by
HD
to c
olla
bora
te in
su
ppor
t of r
esea
rch
com
mitt
ed to
HD
. The
EH
DN
is s
uppo
rted
by th
e C
HD
I Fou
ndat
ion,
Inc.
, a p
rivat
e,
not-f
or-p
rofit
Am
eric
an r
esea
rch
orga
nisa
tion.
For
mor
e in
form
atio
n ab
out
CH
DI,
plea
se v
isit
the
web
site
at w
ww
.chd
ifoun
datio
n.or
g. T
he a
im o
f the
net
wor
k is
to c
arry
out
clin
ical
res
earc
h in
to H
D, t
o im
prov
e kn
owle
dge
of t
he n
atur
al c
ours
e of
the
dis
ease
, an
d (u
ltim
atel
y) t
o fin
d a
cure
for
HD
.Yo
ur
cons
ent s
olel
y re
late
s to
the
elec
troni
c re
gist
ratio
n of
you
r st
atem
ents
in th
e qu
estio
nnai
re. D
ata
entry
an
d th
e us
e of
the
dat
abas
e, w
hich
is h
eld
at t
he p
roje
ct’s
Cen
tral C
oord
inat
ion
in U
lm,
Ger
man
y, is
ca
rrie
d ou
t usi
ng th
e in
tern
et.
How
it i
s en
sure
d th
at o
nly
auth
oris
ed p
eopl
e ha
ve a
cces
s to
the
dat
a, a
nd h
ow it
is
prov
ided
tha
t th
roug
h th
e co
mm
unic
atio
n vi
a th
e in
tern
et t
he d
ata
prot
ectio
n do
es n
ot g
et h
urt,
plea
se r
ead
“Info
rmat
ion
rega
rdin
g da
ta p
roce
ssin
g, d
ata
prot
ectio
n an
d da
ta s
ecur
ity”.
Eval
uatio
n an
d pu
blic
atio
n of
stu
dy re
sults
will
be c
arrie
d ou
t ano
nym
ousl
y an
d in
the
form
of s
tatis
tics.
As
a re
sult,
non
e of
you
r or y
our c
ompa
nion
’s p
erso
nal d
ata
will
be m
ade
publ
ic.
VOLU
NTE
ERIN
GYo
ur p
artic
ipat
ion
in th
is r
esea
rch
proj
ect i
s vo
lunt
ary.
You
are
free
to w
ithdr
aw fr
om th
e st
udy
at a
ny
time
and
with
out g
ivin
g re
ason
.With
draw
al fr
om th
e st
udy
will
not a
ffect
the
care
giv
en to
you
or
your
52
com
pani
on.O
n yo
ur re
ques
t eve
ry li
nk b
etw
een
your
sto
red
data
and
you
r per
son
can
be p
erm
anen
tly
dele
ted
(for
deta
ils s
ee In
form
atio
n re
gard
ing
data
pro
cess
ing,
dat
a pr
otec
tion
and
data
sec
urity
, po
int ‘
E’).
CO
NTA
CT
Shou
ld y
ou h
ave
any
ques
tions
at
anyt
ime
durin
g th
e co
urse
of
the
rese
arch
pro
ject
you
can
rea
ch
(loca
l inv
estig
ator
s) o
n te
leph
one
num
ber
(tele
phon
e nu
mbe
r of
loca
l inv
estig
ator
) at
any
tim
e du
ring
wor
king
hou
rs. F
or e
mer
genc
ies
out o
f hou
rs, r
ing
(loca
l em
erge
ncy
num
ber)
.
CO
NFI
DEN
TIAL
ITY/
DAT
APR
OTE
CTI
ON
All c
linic
ians
and
rel
ated
med
ical
sta
ff in
volv
ed in
look
ing
afte
r yo
u du
ring
this
clin
ical
stu
dy a
re b
ound
by
med
ical
con
fiden
tialit
y an
d ar
e ob
liged
to c
ompl
y w
ith d
ata
prot
ectio
n.R
esea
rch
resu
lts r
elat
ing
to t
his
stud
y ar
e in
tend
ed f
or u
se i
n an
ano
nym
ous
form
in
scie
ntifi
c pu
blic
atio
ns.
As f
ar a
s is
nec
essa
ry f
or e
nsur
ing
corr
ect
data
ent
ry,
auth
oris
ed i
ndiv
idua
ls (
e.g.
the
sp
onso
r, th
e un
iver
sity
) are
per
mitt
ed to
revi
ew y
our l
ocal
med
ical
reco
rds.
If in
divi
dual
s au
thor
ised
to v
iew
rec
ords
are
not
bou
nd b
y m
edic
al c
onfid
entia
lity
as m
entio
ned
abov
e,
pers
onal
dat
a th
at c
ome
to th
eir a
ttent
ion
durin
g ch
ecks
are
con
fiden
tial u
nder
the
Dat
a Pr
otec
tion
Act.
Euro
pean
HD
N
etw
ork:
In
form
atio
n re
gard
ing
data
pr
oces
sing
, da
ta
prot
ectio
n an
d da
ta
secu
rity.
A.
An
esse
ntia
l sa
fety
asp
ect
of t
he p
roje
ct i
s th
e pr
oces
sing
of
the
data
in
an e
xclu
sive
ly
pseu
dony
mis
ed m
anne
r. W
hat d
oes
that
mea
n an
d ho
w is
it c
arrie
d ou
t?Yo
ur c
ompa
nion
’s c
linic
ian
will
ente
r cer
tain
dat
a ab
out h
im/h
er in
to th
e co
mpu
ter.
From
thes
e pe
rson
al
data
a u
niqu
e co
de n
ame
(‘pse
udon
ym’)
is c
alcu
late
d, c
onsi
stin
g of
a s
erie
s of
9 d
igits
. The
follo
win
g pe
rson
al d
ata
are
used
: fir
st n
ame,
birt
h na
me
(sur
nam
e),
date
of
birth
, pl
ace
of b
irth
and
mot
her’s
m
aide
n na
me.
Exam
ple:
Mar
ia,
Mill
er
nee
Mus
term
ann,
bo
rn
10.1
1.19
64
in
Ulm
, m
othe
r’s m
aide
n na
me
Schm
idt.
This
in
form
atio
n re
sults
in
the
code
nam
e (‘p
seud
onym
’) 42
5-49
1-32
6. I
mpo
rtant
ly,
the
pseu
dony
m i
s cr
eate
d on
the
bas
is o
f a
so-c
alle
d ‘s
ecur
e ha
sh-a
lgor
ithm
’. B
y th
is m
athe
mat
ical
ope
ratio
n a
uniq
ue
valu
e is
ass
igne
d du
ring
a co
mpl
icat
ed, o
ne-w
ay p
roce
dure
. The
mat
hem
atic
al a
lgor
ithm
use
d en
sure
s th
at n
obod
y (n
ot e
ven
the
syst
em p
rogr
amm
er)
can
reco
nstru
ct f
rom
the
resu
lt (th
e ‘p
seud
onym
’) th
e in
form
atio
n w
hich
was
use
d to
gen
erat
e th
e ps
eudo
nym
(i.e
. th
e un
ique
per
sona
l da
ta o
f yo
ur
com
pani
on) i
n th
e fir
st p
lace
.Th
e pe
rson
al d
ata
trans
mitt
ed to
gen
erat
e th
e ps
eudo
nym
are
hel
d on
ly fo
r the
cal
cula
tion
of y
our c
ode
nam
e (‘p
seud
onym
’) in
the
wor
king
mem
ory
of a
lar
ge c
ompu
ter
(‘ser
ver’)
. Th
e ca
lcul
atio
n of
the
ps
eudo
nym
req
uire
s a
very
sho
rt tim
e (m
illise
cond
s).
View
ing
pers
onal
dat
a du
ring
this
tim
e is
im
poss
ible
. The
reaf
ter a
ll da
ta u
sed
to c
reat
e th
e ps
eudo
nym
are
per
man
ently
era
sed
from
the
wor
king
m
emor
y of
the
serv
er s
o th
at n
o id
entif
ying
det
ails
rem
ain;
dat
a us
ed to
gen
erat
e th
e ps
eudo
nym
are
ne
ver
stor
ed in
any
for
m o
f pe
rman
ent m
emor
y (e
.g.
on t
he h
ard
driv
e). F
ollo
win
g th
is,
all d
ata
base
en
tries
and
eve
ry u
se o
f dat
a is
exc
lusi
vely
car
ried
out u
nder
the
assi
gned
pse
udon
ym.
B.W
hich
dat
a do
I ha
ve to
dis
clos
e in
the
cour
se o
f the
REG
ISTR
Y st
udy?
Dur
ing
the
cour
se o
f th
e R
EGIS
TRY
stud
y, y
ou w
ill b
e as
ked
abou
t th
e im
pact
of
your
com
pani
on’s
di
seas
e on
you
. You
r sta
tem
ents
will
be re
late
d to
all
othe
r med
ical
dat
a of
you
r com
pani
on.
C.W
ho c
an s
ee a
nd u
se m
y da
ta?
1. T
he c
linic
ian
treat
ing
your
com
pani
onTh
e st
udy
site
team
enr
ollin
g yo
ur c
ompa
nion
for R
EGIS
TRY
is th
e on
ly o
ne w
ho c
an li
nk y
our d
ata.
All
entry
of
clin
ical
inf
orm
atio
n in
the
dat
a ba
se i
s ca
rrie
d ou
t un
der
your
com
pani
on’s
cod
e na
me
(‘pse
udon
ym’).
The
stu
dy s
ite t
eam
incl
udin
g th
e tre
atin
g cl
inic
ian
can
view
all
clin
ical
dat
a re
cord
ed
unde
r the
pse
udon
ym.
2. E
HD
Nst
aff:
EHD
Nst
aff c
an v
iew
the
data
sto
red
unde
r yo
ur c
ompa
nion
’s p
seud
onym
in o
rder
to
ensu
re c
orre
ct d
ocum
enta
tion
and
to r
ectif
y tra
nscr
iptio
n er
rors
by
cont
actin
g th
e st
udy
site
tea
m f
or
211Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
53
clar
ifyin
g qu
estio
ns.
EHD
Nst
aff c
an o
nly
view
and
use
pse
udon
ymis
ed d
ata
ente
red
on th
e Eu
rope
an-
HD
net
wor
k. F
or th
e pu
rpos
e of
dat
a co
ntro
l, E
HD
Nst
aff (
‘mon
itors
’ and
‘aud
itors
’) ar
e al
low
ed to
che
ck
with
the
stud
y si
te te
am th
at th
e da
ta e
nter
ed o
nto
the
netw
ork
mat
ches
with
the
data
foun
d in
the
loca
lm
edic
al re
cord
s. M
onito
rs/ a
udito
rs a
re b
ound
by
med
ical
con
fiden
tialit
y.
3. A
utho
rised
res
earc
hers
(sc
ient
ist/c
linic
ians
): Sc
ient
ists
/clin
icia
ns w
ho a
re i
nvol
ved
in H
D r
esea
rch
can
appl
y to
the
Scie
ntifi
c an
d B
ioet
hica
lAdv
isor
y C
omm
ittee
(SBA
C)o
f EH
DN
(a g
roup
of e
xper
ienc
ed
clin
icia
ns a
nd s
cien
tists
) for
aut
horis
atio
n to
obt
ain
acce
ss to
the
data
bas
e. A
utho
rised
rese
arch
ers
can
only
vie
w c
oded
dat
a. T
o en
sure
the
high
est d
egre
e of
con
fiden
tialit
y ps
eudo
nym
s ar
e re
code
d be
fore
th
e da
ta b
ank
is m
ade
avai
labl
e to
aut
horis
ed re
sear
cher
s. T
here
by it
is g
uara
ntee
d th
at a
ll pu
blic
atio
ns
repo
rting
on
the
findi
ngs
of a
utho
rised
rese
arch
exc
lusi
vely
use
ano
nym
ised
dat
a re
port
form
at (i
.e. n
ot
even
usi
ng th
e ps
eudo
nym
).
4. S
yste
m a
dmin
istra
tors
: In
ord
er t
o sa
fegu
ard
the
EHD
Nce
ntra
l da
taba
se,
a sm
all
num
ber
of
auth
oris
ed s
yste
m a
dmin
istra
tors
can
vie
w p
seud
onym
ised
dat
a.
5. O
ther
gro
ups
and
indi
vidu
als:
No-
one
othe
r th
an t
he g
roup
s an
d in
divi
dual
s de
scrib
ed a
bove
can
ga
in a
cces
s to
or r
ecei
ve th
e da
ta s
tore
d ab
out y
ou.
D.H
ow c
an I
be s
ure
that
una
utho
rised
peo
ple
cann
ot g
ain
acce
ss t
o m
y an
d m
y co
mpa
nion
’s
data
whi
le th
ey a
re s
ent v
ia th
e In
tern
et?
All
data
tra
velli
ng v
ia t
he i
nter
net
are
encr
ypte
d. T
his
impl
ies
for
all
prac
tical
pur
pose
s th
at n
obod
y as
ide
from
the
inte
nded
rec
eive
r ca
n re
ad o
r ac
cess
the
se d
ata.
The
ser
ver
whe
re t
he d
atab
ase
is
stor
ed is
loc
ated
beh
ind
a ‘fi
rew
all’.
Thi
s so
phis
ticat
ed s
ecur
ity s
yste
m e
nsur
es t
hat
only
aut
horis
ed
com
pute
rs a
nd in
divi
dual
s ca
n ga
in a
cces
s to
the
dat
abas
e. F
urth
erm
ore,
the
cen
tral d
atab
ase
does
no
t con
tain
iden
tifyi
ng d
ata
as a
ll da
ta a
re s
tore
d un
der a
cod
e na
me
(‘pse
udon
ym’).
E.H
ow lo
ng is
my
and
my
com
pani
on’s
dat
a st
ored
for?
All d
ata
will
be s
tore
d as
ent
ered
:un
til y
ou w
ithdr
aw y
our p
artic
ipat
ion
and
requ
est t
he a
nony
mis
atio
n of
you
r dat
aun
til 1
0 ye
ars
afte
r an
effic
ient
ther
apy
for H
D h
as b
een
esta
blis
hed
a m
axim
um p
erio
d of
60
year
s (2
gen
erat
ions
+ 1
0 ye
ars)
,or
upto
a m
axim
um o
f 10
year
s af
ter t
he p
roje
ct a
ctiv
ities
hav
e st
oppe
d.
A co
mpl
ete
dele
tion
of d
ata
is d
iffic
ult,
sinc
e da
ta a
re li
kely
to h
ave
beco
me
part
of s
cien
tific
stu
dies
and
th
eref
ore
need
to b
e ke
pt o
n re
cord
in c
ompl
ianc
e to
law
s an
d re
gula
tions
to a
llow
futu
re c
ross
che
cks
and
data
ver
ifica
tions
, eve
n ye
ars
afte
r th
e re
sear
ch w
as c
ompl
eted
. How
ever
, all
links
to y
ou c
an b
e de
lete
d an
d irr
ever
sibl
y de
stro
yed.
As
a re
sult,
thu
s no
t ev
en t
he p
hysi
cian
s ch
osen
by
you
for
enro
lmen
t int
o R
EGIS
TRY
will
any
long
er b
e ab
le to
rec
ogni
ze d
ata
as d
ata
belo
ngin
g to
you
. Suc
h a
com
plet
e an
onym
isat
ion
will
be c
arrie
d ou
t in
the
follo
win
g ca
ses:
If yo
u w
ithdr
aw y
our c
onse
nt fo
r fur
ther
par
ticip
atio
n in
REG
ISTR
Y an
d if
you
requ
est t
hat y
our p
ast
data
are
ano
nym
ised
.If
you
requ
est c
ompl
ete
anon
ymis
atio
n of
you
r dat
a.
Loca
tion,
dat
e N
ame
of th
e co
nsen
ting
clin
icia
n
54
10.6
Part
icip
ant C
onse
nt F
orm
(REG
ISTR
Y-C
OM
PAN
ION
S)N
ame
of s
tudy
: R
EGIS
TRY
–an
obs
erva
tiona
l st
udy
of t
he E
urop
ean
Hun
tingt
on’s
dis
ease
Net
wor
k (E
HD
N)
Con
tent
, pro
cedu
res,
ris
ks a
nd a
ims
of th
e re
sear
ch p
roje
ct n
amed
abo
ve a
s w
ell a
s th
e rig
ht to
vie
w
the
data
reco
rded
has
bee
n ex
plai
ned
to m
e in
suf
ficie
nt d
etai
l by
……
……
……
……
……
…..
I hav
e ha
d th
e op
portu
nity
to a
sk q
uest
ions
and
hav
e re
ceiv
ed a
nsw
ers
to th
em.
I hav
e ha
d su
ffici
ent t
ime
to d
ecid
e w
heth
er to
par
ticip
ate
in th
e pr
ojec
t.I h
ave
rece
ived
a c
opy
of th
e pa
rtici
pant
info
rmat
ion
(com
pani
ons)
and
con
sent
form
(com
pani
ons)
.
Plea
se c
heck
‘YES
’or ‘
NO
’for
the
ques
tion
belo
w, r
efer
ring
to th
e op
tiona
l stu
dy p
roce
dure
s:
I agr
ee to
rece
ive
info
rmat
ion
abou
t the
nov
el a
sses
smen
t bat
tery
and
to p
artic
ipat
e in
the
deve
lopm
ent
of n
ovel
ass
essm
ents
.
Opt
iona
l com
pone
nt 1
: Nov
el a
sses
smen
ts
Dur
ing
scie
ntifi
c st
udie
s, p
erso
nal
data
and
med
ical
fin
ding
s ab
out
you
are
reco
rded
. Th
e st
orag
e,
anal
ysis
and
com
mun
icat
ion
of d
ata
rela
ting
to th
e st
udy
are
carr
ied
out a
ccor
ding
to le
gal r
equi
rem
ents
an
d en
tail
the
follo
win
g co
nsen
t bef
ore
parti
cipa
ting
in th
e st
udy:
Info
rmat
ion
and
cons
ent f
orm
rega
rdin
g D
ata
Prot
ectio
n
1. I
agr
ee t
hat
data
/m
edic
al d
ata
take
n du
ring
the
cour
se o
f th
is s
tudy
ca
n be
rec
orde
d in
qu
estio
nnai
res
and
on e
lect
roni
c da
ta c
arrie
rs a
nd p
roce
ssed
with
out p
rovi
ding
per
sona
l ide
ntity
.
2. I
also
agr
ee th
at a
n au
thor
ised
per
sons
(e.g
. EH
DN
mon
itors
, reg
ulat
ory
auth
oriti
es)w
ho is
bou
nd b
y co
nfid
entia
lity
(e.g
. fro
m th
e sp
onso
r, or
the
Uni
vers
ity) c
an v
iew
the
pers
onal
dat
a re
cord
ed a
s fa
r as
it is
nec
essa
ry fo
r dat
a co
ntro
l of t
he p
roje
ct. F
or th
is a
im, I
rele
ase
the
clin
icia
n fro
m th
e re
quire
men
t for
m
edic
al c
onfid
entia
lity.
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
…
……
……
……
Nam
e of
the
Parti
cipa
nt (c
ompa
nion
) Si
gnat
ure
of th
e P
artic
ipan
t (co
mpa
nion
) Pl
ace,
dat
e
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
Nam
e of
Per
son
Obt
aini
ngC
onse
ntSi
gnat
ure
of P
erso
n O
btai
ning
Con
sent
Plac
e, d
ate
Prin
ted
Nam
e an
d Ti
tle
……
……
……
……
……
……
……
…N
ame
of th
e R
egis
try p
artic
ipan
t kno
wn
to c
ompa
nion
REG
ISTR
Y (H
D) P
AR
TIC
IPA
NT*
PSE
UD
ON
YM:
*Par
ticip
ant f
rom
HD
fam
ily k
now
n to
com
pani
on
212 Hygeia Public Health 2011, 46(2): 183-218
55
10.7
Part
icip
ant I
nfor
mat
ion
Shee
t (N
ew R
EGIS
TRY-
CO
NTR
OL)
Nam
e of
stu
dy:
REG
ISTR
Y –
an o
bser
vatio
nal
stud
y of
the
Eur
opea
n H
untin
gton
’s d
isea
seN
etw
ork
(EH
DN
)
Dea
r Par
ticip
ant,
You
are
a pe
rson
with
out
aH
Dfa
mily
his
tory
.W
e w
ould
lik
e to
inv
ite y
ou t
o be
int
ervi
ewed
and
ex
amin
ed b
y an
exp
erie
nced
clin
icia
n. I
n ot
her
wor
ds,
at e
ach
stud
y vi
sit,
your
phy
sica
l and
men
tal
abilit
y w
ill be
ass
esse
d; t
hese
exa
min
atio
ns w
ill be
ver
y si
mila
r to
the
sta
ndar
dise
d as
sess
men
ts
unde
rtake
n by
you
r co
mpa
nion
and
it m
ay b
e th
at y
ou a
re a
lread
y fa
milia
r w
ith t
hem
fro
m p
revi
ous
cons
ulta
tions
with
you
r com
pani
on. I
n ad
ditio
n, y
ou w
ill be
ask
ed to
com
plet
e qu
estio
nnai
res
asse
ssin
g yo
ur w
ellb
eing
.
You
can
also
help
in fi
ndin
g ne
w a
nd im
prov
ed to
ols
to fo
llow
the
cour
se o
f HD
by
cons
entin
g to
don
ate
a sm
all a
mou
nt o
f you
r bl
ood
(20
ml =
4 te
aspo
ons)
and
a s
mal
l am
ount
of u
rine
(30
ml)
at e
ach
visi
t (e
.g. y
early
). To
mak
e su
re th
at y
our
own
stat
e of
hea
lth (
espe
cial
ly if
you
are
suf
ferin
g fro
m a
chr
onic
di
seas
e) c
an b
e co
nsid
ered
whe
n ex
amin
ing
bloo
d an
d ur
ine
sam
ples
don
ated
by
you
as c
ontro
l, w
e as
k yo
u to
agr
ee to
an
inte
rvie
w a
bout
you
r sta
te o
f hea
lth.
The
resu
lts o
f you
r int
ervi
ew a
nd o
f you
r cl
inic
al a
sses
smen
ts w
ill be
sto
red
unde
r a p
seud
onym
onan
el
ectro
nic
data
base
by
the
med
ical
sta
ff in
terv
iew
ing
and
exam
inin
g yo
u, o
bvio
usly
with
out
savi
ng
nam
e, a
ddre
ss o
r oth
er d
ata
that
wou
ld a
llow
you
r (or
you
r com
pani
ons)
iden
tific
atio
n.
We
ask
you
for y
our p
erm
issi
on fo
r:a
stan
dard
int
ervi
ew a
nd e
xam
inat
ion
and
the
docu
men
tatio
n of
the
dat
a ob
tain
ed d
urin
g yo
ur
clin
ical
exa
min
atio
n in
an
elec
troni
c da
taba
se a
nd tw
o op
tiona
l com
pone
nts
whi
ch y
ou m
ay w
ish
to
cons
ider
.
Any
addi
tiona
l res
earc
h co
mpo
nent
s de
scrib
ed b
elow
are
opt
iona
l and
req
uire
you
r ex
plic
it co
nsen
t by
chec
king
the
box
‘YE
S’ o
r ‘N
O’ i
n th
e co
nsen
t for
m. T
he o
ptio
nal c
ompo
nent
s ar
eth
e do
natio
n of
blo
od a
nd u
rine
for
stud
ies
to id
entif
y ge
netic
mod
ifier
s of
HD
and
to e
stab
lish
and
valid
ate
biol
ogic
al m
arke
rs fo
r HD
,pa
rtici
patio
n in
nov
el a
sses
smen
ts
You
may
cho
ose
to p
artic
ipat
e in
all,
in n
one
or in
sel
ecte
d op
tiona
l com
pone
nts.
Opt
iona
l Com
pone
nt 1
:
Don
atin
gbl
ood
to a
llow
sci
entif
ic s
tudi
es t
o fin
d ge
nes
help
s us
und
erst
and
thei
rin
fluen
ce o
nth
e fe
atur
es a
nd t
he c
ours
e of
HD
. Kn
owin
g ab
out
thes
e so
cal
led
gene
tic m
odifi
ers
is im
porta
nt s
ince
ge
nes
whi
ch in
fluen
ce H
D m
ay b
e us
eful
for t
hera
peut
ic ta
rget
s an
d m
ay b
e ve
ry h
elpf
ul u
nder
stan
ding
di
ffere
nces
bet
wee
n H
D p
atie
nts
thus
impr
ovin
g th
e un
ders
tand
ing
of t
he o
utco
me
of c
linic
al s
tudi
es
and
treat
men
t tria
ls. B
lood
sam
ples
of p
eopl
e w
ho d
o no
t car
ry th
e H
D m
utat
ion
and
who
do
not s
uffe
r fro
m n
euro
logi
cal o
r ps
ychi
atric
dis
orde
rs a
re e
ssen
tial f
or c
ompa
rison
. For
this
rea
son
we
ask
you
to
dona
te b
lood
onc
e fo
r the
gen
erat
ion
of c
ell l
ines
from
blo
od c
ells
whi
ch w
ill en
sure
that
suf
ficie
nt D
NA
is a
vaila
ble
to c
arry
out
thes
e st
udie
s. In
add
ition
, we
ask
you
to c
onsi
der
dona
ting
bloo
d an
d ur
ine
to
allo
w s
cien
tific
stu
dies
to
find
mar
kers
whi
ch r
efle
ct t
he s
ever
ity o
f th
e di
seas
e. T
hese
so
calle
d bi
omar
kers
are
alre
ady
wel
l est
ablis
hed
for
e.g.
live
r di
sord
ers:
you
r do
ctor
can
tell
by a
sim
ple
bloo
d te
st, h
ow y
our l
iver
is d
oing
. It i
s im
porta
nt to
find
out
whe
ther
sim
ilar t
est c
an b
e fo
und
for H
D p
atie
nts
and
how
wel
l cha
nges
in m
arke
rs in
blo
od o
r ur
ine
will
track
the
prog
ress
ive
cour
se o
f HD
. Val
idat
ed
biom
arke
rs a
re e
xpec
ted
to a
llow
to s
how
the
effic
acy
of tr
eatm
ents
fast
er a
nd w
ith fe
wer
par
ticip
ants
in
clin
ical
tria
ls c
ompa
red
to s
tand
ard
clin
ical
rat
ing
scal
es t
o m
easu
re t
he p
rogr
essi
on o
f H
D.
As f
or
stud
ies
into
gen
etic
mod
ifier
s, a
com
paris
on w
ith b
lood
sam
ples
of
peop
le w
ho d
o no
t ca
rry
the
HD
m
utat
ion
and
who
do
not s
uffe
r fro
m n
euro
logi
cal o
r psy
chia
tric
diso
rder
s is
indi
spen
sabl
e.
Don
atio
n of
blo
od a
nd u
rine
for
stud
ies
to id
entif
y ge
netic
mod
ifier
s of
HD
and
to
est
ablis
h an
d va
lidat
e bi
olog
ical
mar
kers
for H
D
56
In o
rder
to
obta
in v
alid
res
ults
as
fast
as
hum
anly
pos
sibl
e, b
iosa
mpl
es s
houl
d be
sto
red
very
saf
ely
and
dist
ribut
ed t
o ca
pabl
e re
sear
cher
s in
a s
afe
and
cont
rolle
d w
ay.
Ther
efor
e, a
ll bi
osam
ples
are
ps
eudo
nym
ised
and
sto
red
cent
rally
in
a bi
orep
osito
ry d
evot
ed t
o th
e sa
fe s
tora
ge a
nd h
andl
ing
of
biom
ater
ials
. Bio
Rep
S.r.
l. is
an
inde
pend
ent o
rgan
isat
ion
base
d in
Mila
n, It
aly,
that
offe
rs b
iore
posi
tory
se
rvic
es t
o pu
blic
and
priv
ate
rese
arch
inst
itute
s, t
oth
e hi
ghes
t st
anda
rds
of q
ualit
y an
d sa
fety
. Fo
r m
ore
info
rmat
ion
on B
ioR
ep, p
leas
e vi
sit t
he w
ebsi
te a
t ww
w.b
iore
p.it.
The
colle
ctio
n of
blo
od m
ay c
ause
pai
n an
d/or
bru
isin
g at
the
site
whe
re b
lood
is d
raw
n. F
aint
ing
or
feel
ing
light
-hea
ded
may
occ
ur d
urin
g or
sho
rtly
afte
r ha
ving
blo
od d
raw
n. If
you
exp
erie
nce
this
, yo
u w
ill be
ins
truct
ed t
o lie
dow
n im
med
iate
ly t
o av
oid
poss
ible
inj
urie
s. L
ocal
ized
clo
t fo
rmat
ion
and
infe
ctio
ns m
ay o
ccur
, but
this
is v
ery
rare
. The
am
ount
of b
lood
col
lect
ed is
sm
all (
20m
l) an
d th
e in
terv
al
betw
een
colle
ctio
ns is
long
(e.g
. yea
rly),
so th
ere
is n
o ris
k of
dev
elop
ing
an a
naem
ia.
A nu
mbe
r of
nov
el a
sses
smen
ts (
e.g.
que
stio
nnai
res,
int
ervi
ews,
rat
ing
scal
es)
may
hel
p us
to
unde
rsta
nd m
ore
abou
t th
e on
set,
cour
se a
nd t
reat
men
t of
Hun
tingt
on’s
dis
ease
. W
ene
ed t
o co
llect
m
ore
data
on
each
ass
essm
ent i
n or
der
to k
now
whe
ther
they
sho
uld
be u
sed
in th
e de
sign
of f
utur
e re
sear
ch a
nd c
linic
al c
are
prac
tices
.
Opt
iona
l com
pone
nt 2
: Nov
el a
sses
smen
ts
We
wou
ld li
ke to
ask
you
to c
onsi
der
taki
ng p
art i
n th
ese
nove
l ass
essm
ents
. The
nov
el a
sses
smen
ts
cove
r a
wid
e ra
nge
of a
reas
(e.
g. in
form
atio
n on
you
r w
ell-b
eing
, you
r qu
ality
of l
ife)
and
you
may
be
appr
oach
ed t
o ta
ke p
art.
The
over
all
dura
tion
of t
he n
ovel
ass
essm
ents
tog
ethe
r w
ith t
he s
tand
ard
REG
ISTR
Y as
sess
men
ts s
houl
d no
t ex
ceed
2.5
hou
rs.
You
can
deci
de w
heth
er y
ou w
ant
to d
o th
e ad
ditio
nal a
sses
smen
ts o
r not
dur
ing
your
vis
it.
REG
ISTR
Y is
a s
tudy
con
duct
ed b
y th
e Eu
rope
an H
untin
gton
’s D
isea
se N
etw
ork
(EH
DN
). EH
DN
is a
sc
ient
ific
netw
ork
of p
hysi
cian
s, s
cien
tists
and
org
anis
atio
ns fo
r fa
mili
es a
ffect
ed b
y H
D to
col
labo
rate
in
supp
ort o
f res
earc
h co
mm
itted
to H
D.T
he a
im o
f the
net
wor
k is
to c
arry
out
clin
ical
rese
arch
into
HD
, to
impr
ove
know
ledg
e of
the
nat
ural
cou
rse
of t
he d
isea
se,
and
(ulti
mat
ely)
to
find
a cu
re f
or H
D.
Dat
a en
try a
nd th
e us
e of
the
data
base
, whi
ch is
hel
d at
the
proj
ect’s
Cen
tral C
oord
inat
ion
in U
lm, G
erm
any,
is
car
ried
out
usin
g th
e in
tern
et.
EH
DN
is s
uppo
rted
by t
he C
HD
I Fo
unda
tion,
Inc
., a
priv
ate,
not
-for-
prof
it Am
eric
an r
esea
rch
orga
nisa
tion.
For
mor
e in
form
atio
n ab
out
CH
DI,
plea
se v
isit
the
web
site
at
ww
w.c
hdifo
unda
tion.
org.
To u
nder
stan
d ho
w it
is e
nsur
ed t
hat
only
aut
horis
ed p
eopl
e ha
ve a
cces
s to
the
dat
a, a
nd h
ow s
afe
com
mun
icat
ion
via
the
inte
rnet
is
achi
eved
, pl
ease
rea
d th
e pa
ragr
aph
belo
w e
ntitl
ed “
Info
rmat
ion
rega
rdin
g da
ta p
roce
ssin
g, d
ata
prot
ectio
n an
d da
ta s
ecur
ity”.
Eval
uatio
n an
d pu
blic
atio
n of
stu
dy re
sults
will
be c
arrie
d ou
t ano
nym
ousl
y an
d in
the
form
of s
tatis
tics.
As
a re
sult,
non
e of
you
r or y
our c
ompa
nion
’s p
erso
nal d
ata
will
be m
ade
publ
ic.
VOLU
NTE
ERIN
GYo
ur p
artic
ipat
ion
in th
is r
esea
rch
proj
ect i
s vo
lunt
ary.
You
are
free
to w
ithdr
aw fr
om th
e st
udy
at a
ny
time
and
with
out g
ivin
g re
ason
.On
your
req
uest
eve
ry li
nk b
etw
een
your
sto
red
data
and
you
r pe
rson
ca
n be
per
man
ently
del
eted
(for
det
ails
see
Info
rmat
ion
rega
rdin
g da
ta p
roce
ssin
g, d
ata
prot
ectio
n an
d da
ta s
ecur
ity, p
oint
‘E’).
CO
NTA
CT
Shou
ldyo
u ha
ve a
ny q
uest
ions
at
anyt
ime
durin
g th
e co
urse
of
the
rese
arch
pro
ject
you
can
rea
ch
(loca
l inv
estig
ator
s) o
n te
leph
one
num
ber
(tele
phon
e nu
mbe
r of
loca
l inv
estig
ator
) at
any
tim
e du
ring
wor
king
hou
rs. F
or e
mer
genc
ies
out o
f hou
rs, r
ing
(loca
l em
erge
ncy
num
ber)
.
CO
NFI
DEN
TIAL
ITY/
DAT
APR
OTE
CTI
ON
All c
linic
ians
and
rel
ated
med
ical
sta
ff in
volv
ed in
look
ing
afte
r yo
u du
ring
this
clin
ical
stu
dy a
re b
ound
by
med
ical
con
fiden
tialit
y an
d ar
e ob
liged
to c
ompl
y w
ith d
ata
prot
ectio
n.R
esea
rch
resu
lts r
elat
ing
to t
his
stud
y ar
e in
tend
ed f
or u
se i
n an
ano
nym
ous
form
in
scie
ntifi
c pu
blic
atio
ns.
213Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
57
As f
ar a
s is
nec
essa
ry f
or e
nsur
ing
corr
ect
data
ent
ry,
auth
oris
ed i
ndiv
idua
ls (
e.g.
the
spo
nsor
, th
e un
iver
sity
) ar
e pe
rmitt
ed to
rev
iew
you
r lo
calm
edic
al r
ecor
ds. I
f ind
ivid
uals
aut
horis
ed to
vie
w r
ecor
ds
are
not b
ound
by
med
ical
con
fiden
tialit
y as
men
tione
d ab
ove,
per
sona
l dat
a th
at c
ome
to th
eir a
ttent
ion
durin
g ch
ecks
are
con
fiden
tial u
nder
the
Dat
a Pr
otec
tion
Act.
Euro
pean
HD
N
etw
ork:
In
form
atio
n re
gard
ing
data
pr
oces
sing
, da
ta
prot
ectio
n an
d da
ta
secu
rity.
A.
An
esse
ntia
l sa
fety
asp
ect
of t
he p
roje
ct i
s th
e pr
oces
sing
of
my
data
in
an e
xclu
sive
ly
pseu
dony
mis
ed m
anne
r. W
hat d
oes
that
mea
n an
d ho
w is
it c
arrie
d ou
t?D
urin
g yo
ur fi
rst v
isit,
you
r clin
icia
n w
ill en
ter c
erta
in d
ata
abou
t you
into
the
com
pute
r.Fr
om th
ese
pers
onal
dat
a a
uniq
ue c
ode
nam
e (‘p
seud
onym
’) is
cal
cula
ted,
con
sist
ing
of a
ser
ies
of 9
di
gits
. The
fol
low
ing
pers
onal
dat
a ar
e us
ed: f
irst n
ame,
birt
h na
me
(sur
nam
e), d
ate
of b
irth,
pla
ce o
f bi
rth a
nd m
othe
r’s m
aide
n na
me.
Exam
ple:
Mar
ia, M
iller n
ee M
uste
rman
n, b
orn
10.1
1.19
64 in
Ulm
, mot
her’s
mai
den
nam
e Sc
hmid
t.Th
is in
form
atio
n re
sults
in t
he c
ode
nam
e (‘p
seud
onym
’) 42
5-49
1-32
6. I
mpo
rtant
ly,
the
pseu
dony
m is
cr
eate
d on
the
bas
is o
f a
so-c
alle
d ‘s
ecur
e ha
sh-a
lgor
ithm
’. B
y th
is m
athe
mat
ical
ope
ratio
n a
uniq
ue
valu
e is
ass
igne
d du
ring
a co
mpl
icat
ed, o
ne-w
ay p
roce
dure
. The
mat
hem
atic
al a
lgor
ithm
use
d en
sure
s th
at n
obod
y (n
ot e
ven
the
syst
em p
rogr
amm
er)
can
reco
nstru
ct f
rom
the
resu
lt (th
e ‘p
seud
onym
’)th
e in
form
atio
n w
hich
was
use
d to
gen
erat
e th
e ps
eudo
nym
(i.e
. yo
ur u
niqu
e pe
rson
al d
ata)
in t
he f
irst
plac
e. T
he p
erso
nal d
ata
trans
mitt
ed t
o ge
nera
te t
he p
seud
onym
are
hel
d on
ly f
or t
he c
alcu
latio
n of
yo
ur c
ode
nam
e (‘p
seud
onym
’) in
the
wor
king
mem
ory
of a
larg
e co
mpu
ter (
‘ser
ver’)
. The
cal
cula
tion
of
the
pseu
dony
m r
equi
res
a ve
ry s
hort
time
(milli
seco
nds)
. V
iew
ing
pers
onal
dat
a du
ring
this
tim
e is
im
poss
ible
. The
reaf
ter a
ll da
ta u
sed
to c
reat
e th
e ps
eudo
nym
are
per
man
ently
era
sed
from
the
wor
king
m
emor
yof
the
serv
er s
o th
at n
o id
entif
ying
det
ails
rem
ain;
dat
a us
ed to
gen
erat
e th
e ps
eudo
nym
are
ne
ver
stor
ed in
any
for
m o
f pe
rman
ent m
emor
y (e
.g.
on t
he h
ard
driv
e). F
ollo
win
g th
is,
all d
ata
base
en
tries
and
eve
ry u
se o
f dat
a is
exc
lusi
vely
car
ried
out u
nder
the
assi
gned
pse
udon
ym.
B.W
hich
dat
a do
I ha
ve to
dis
clos
e ap
art f
rom
the
data
req
uire
d to
cre
ate
my
pseu
dony
m in
the
cour
se o
f the
REG
ISTR
Y st
udy
and
subs
eque
nt s
tudi
es?
Dur
ing
the
cour
se o
f th
e R
EGIS
TRY
stud
y, s
ome
heal
th a
nd/o
r m
edic
al d
ata
will
be r
ecor
ded
(see
Pa
rtici
pant
Info
rmat
ion
Shee
t for
furth
er d
etai
ls).
If yo
u ar
e pa
rtici
patin
g in
any
sub
sequ
ent s
tudi
es, y
our
clin
icia
n w
ill gi
ve y
ou d
etai
led
info
rmat
ion
abou
t the
stu
dy a
nd th
e da
ta re
quire
d fo
r it a
ccor
ding
ly. E
ach
subs
eque
nt s
tudy
requ
ires
sepa
rate
par
ticip
ant c
onse
nt.
C.W
ho c
an s
ee a
nd u
se m
y da
ta?
1. Y
ou: i
f you
wis
h so
, the
clin
icia
n tre
atin
g yo
u ca
n le
t you
to s
ee a
ll da
ta s
tore
d ab
out y
ou. I
t is
advi
sed
that
you
rev
iew
the
se d
ata
toge
ther
with
the
phy
sici
an t
reat
ing
you
to e
xpla
in m
edic
al t
erm
inol
ogy
to
you
and
to a
nsw
er q
uest
ions
you
may
hav
e.
2. T
he c
linic
ian
treat
ing
you:
The
stu
dy s
ite te
am e
nrol
ling
you
for R
EGIS
TRY
is th
e on
ly o
ne a
part
from
yo
urse
lf w
ho c
an l
ink
your
pse
udon
ym t
o yo
ur i
dent
ifyin
g da
ta (
i.e.
nam
e, a
ddre
ss e
tc.).
Afte
r ge
nera
tion
of th
e ps
eudo
nym
all
entry
of c
linic
al in
form
atio
n in
the
data
bas
e is
car
ried
out u
nder
you
r co
de n
ame
(‘pse
udon
ym’).
You
r st
udy
site
tea
m in
clud
ing
your
tre
atin
g cl
inic
ian
can
view
all
clin
ical
da
ta re
cord
ed u
nder
pse
udon
ym.
3. E
HD
Nst
aff:
EHD
Nst
aff c
an v
iew
the
data
sto
red
unde
r yo
ur p
seud
onym
in o
rder
to e
nsur
e co
rrec
t do
cum
enta
tion
and
high
dat
a qu
ality
to c
onta
ct th
e st
udy
site
team
for
clar
ifyin
g qu
estio
ns. E
HD
N s
taff
can
only
vie
w a
nd u
se p
seud
onym
ised
dat
a en
tere
d on
the
Eur
opea
nH
D n
etw
ork.
For
the
purp
ose
of
data
con
trol,
EHD
Nst
aff (
‘mon
itors
’ and
‘aud
itors
’) ar
e al
low
ed to
che
ck w
ith y
our
stud
y si
te te
am th
at
the
data
ent
ered
ont
o th
e ne
twor
k m
atch
es w
ith t
he d
ata
foun
d in
you
rlo
cal
med
ical
rec
ords
. M
onito
rs/a
udito
rs a
re b
ound
by
med
ical
con
fiden
tialit
y.
4. A
utho
rised
res
earc
hers
(sc
ient
ist/c
linic
ians
): Sc
ient
ists
/clin
icia
ns w
ho a
re i
nvol
ved
in H
D r
esea
rch
can
appl
y to
the
Scie
ntifi
c an
d B
ioet
hica
lAdv
isor
y C
omm
ittee
(SBA
C)o
f EH
DN
(a g
roup
of e
xper
ienc
ed
58
clin
icia
ns a
nd s
cien
tists
) for
aut
horis
atio
n to
obt
ain
acce
ss to
the
data
bas
e. A
utho
rised
rese
arch
ers
can
only
vie
w c
oded
dat
a. T
o en
sure
the
high
est d
egre
e of
con
fiden
tialit
y ps
eudo
nym
s ar
e re
code
d be
fore
th
e da
ta b
ank
is m
ade
avai
labl
e to
aut
horis
ed re
sear
cher
s. T
here
by it
is g
uara
ntee
d th
at a
ll pu
blic
atio
ns
repo
rting
on
the
findi
ngs
of a
utho
rised
rese
arch
exc
lusi
vely
use
ano
nym
ised
dat
a re
port
form
at (i
.e. n
ot
even
usi
ng th
e ps
eudo
nym
).
5. S
yste
m a
dmin
istra
tors
: In
ord
er t
o sa
fegu
ard
the
Eur
opea
nH
D N
etw
ork
cent
ral d
atab
ase,
a s
mal
l nu
mbe
r of a
utho
rised
sys
tem
adm
inis
trato
rs c
an v
iew
pse
udon
ymis
ed d
ata.
6. O
ther
gro
ups
and
indi
vidu
als:
No-
one
othe
r th
an t
he g
roup
s an
d in
divi
dual
s de
scrib
ed a
bove
can
ga
in a
cces
s to
or r
ecei
ve th
e da
ta s
tore
d ab
out y
ou.
D.H
ow c
an I
be s
ure
that
una
utho
rised
peo
ple
cann
ot g
ain
acce
ss t
o m
y da
ta w
hile
the
y ar
e se
nt v
ia th
e In
tern
et?
All
data
tra
velli
ng v
ia t
he i
nter
net
are
encr
ypte
d. T
his
impl
ies
for
all
prac
tical
pur
pose
s th
at n
obod
y as
ide
from
the
inte
nded
rec
eive
r ca
n re
ad o
r ac
cess
the
se d
ata.
The
ser
ver
whe
re t
he d
atab
ase
is
stor
ed is
loc
ated
beh
ind
a ‘fi
rew
all’.
Thi
s so
phis
ticat
ed s
ecur
ity s
yste
m e
nsur
es t
hat
only
aut
horis
ed
com
pute
rs a
nd in
divi
dual
s ca
n ga
in a
cces
s to
the
dat
abas
e. F
urth
erm
ore,
the
cen
tral d
atab
ase
does
no
t con
tain
iden
tifyi
ng d
ata
as a
ll da
ta a
re s
tore
d un
der a
cod
e na
me
(‘pse
udon
ym’).
E.H
ow lo
ng a
re m
y da
ta s
tore
d fo
r?Al
l dat
a w
ill be
sto
red
as e
nter
ed:
until
you
with
draw
you
r par
ticip
atio
n an
d re
ques
t the
ano
nym
isat
ion
of y
our d
ata
until
10
year
s af
ter a
n ef
ficie
nt th
erap
y fo
r HD
has
bee
n es
tabl
ishe
da
max
imum
per
iod
of 6
0 ye
ars
(2 g
ener
atio
ns +
10
year
s),o
rup
to a
max
imum
of 1
0 ye
ars
afte
r the
pro
ject
act
iviti
es h
ave
stop
ped.
A co
mpl
ete
dele
tion
of d
ata
is d
iffic
ult,
sinc
e da
ta a
re li
kely
to h
ave
beco
me
part
of s
cien
tific
stu
dies
and
th
eref
ore
need
to b
e ke
pt o
n re
cord
in c
ompl
ianc
e to
law
s an
d re
gula
tions
to a
llow
futu
re c
ross
che
cks
and
data
ver
ifica
tions
, eve
n ye
ars
afte
r th
e re
sear
ch w
as c
ompl
eted
. How
ever
, all
links
to y
ou c
an b
e de
lete
d an
d irr
ever
sibl
y de
stro
yed.
As
a re
sult,
thu
s no
t ev
en t
he p
hysi
cian
s ch
osen
by
you
for
enro
lmen
t int
o R
EGIS
TRY
will
any
long
er b
e ab
le to
reco
gniz
e da
ta a
s da
ta b
elon
ging
to y
ou. S
uch
a co
mpl
ete
anon
ymis
atio
n w
ill be
car
ried
out i
n th
e fo
llow
ing
case
s:If
you
with
draw
you
r con
sent
for f
urth
er p
artic
ipat
ion
in R
EGIS
TRY
and
if yo
u re
ques
t tha
t you
r pas
t da
ta a
re a
nony
mis
ed.
If yo
u re
ques
t com
plet
e an
onym
isat
ion
of y
our d
ata.
Loca
tion,
dat
eN
ame
of th
e co
nsen
ting
clin
icia
n
214 Hygeia Public Health 2011, 46(2): 183-218
59
10.8
Part
icip
ant C
onse
nt F
orm
(New
REG
ISTR
Y-C
ON
TRO
L Pa
rtic
ipan
t)
Nam
e of
stu
dy:
REG
ISTR
Y –
an o
bser
vatio
nal
stud
y of
the
Eur
opea
n H
untin
gton
’sdi
seas
eN
etw
ork
(EH
DN
)
Con
tent
, pro
cedu
res,
ris
ks a
nd a
ims
of th
e re
sear
ch p
roje
ct n
amed
abo
ve a
s w
ell a
s th
e rig
ht to
vie
w
the
data
reco
rded
was
exp
lain
ed to
me
in d
etai
l by
……
..……
..……
..……
..I h
ad th
e op
portu
nity
to a
sk q
uest
ions
and
obt
ain
answ
ers
whi
ch I
felt
wer
e sa
tisfa
ctor
y. I
had
suffi
cien
t tim
e to
dec
ide
whe
ther
or
not
I w
ant
to p
artic
ipat
e in
the
pro
ject
. I
rece
ived
a c
opy
of t
he p
artic
ipan
tin
form
atio
n an
d of
the
cons
ent f
orm
.
I ag
ree
to p
artic
ipat
e in
the
sta
ndar
d R
EGIS
TRY
(CO
NTR
OL)
ass
essm
ent
and
rece
ive
regu
lar
(e.g
. ye
arly
) fo
llow
-up
visi
ts.
My
deci
sion
s to
par
ticip
ate
in e
ach
of t
he o
ptio
nal c
ompo
nent
s ar
e pr
ovid
ed
belo
w:
Plea
se c
heck
YE
S or
NO
for e
ach
ques
tion
belo
w, r
efer
ring
to th
e fo
llow
ing
optio
nal s
tudy
pro
cedu
res:
Your
blo
od s
ampl
e is
use
d as
hea
lthy
cont
rol.
I giv
e m
y pe
rmis
sion
for t
he c
olle
ctio
n of
blo
od (2
0 m
l or
2 tu
bes
each
con
tain
ing
two
teas
poon
s) a
nd u
rine
(30
ml)
from
me
and
decl
are
to d
onat
e th
em f
or
scie
ntifi
c st
udie
s to
iden
tify
gene
tic m
odifi
ers
of H
D a
nd to
est
ablis
h an
d va
lidat
ebi
olog
ical
mar
kers
for
HD
. I
unde
rsta
nd t
hat
my
sam
ples
are
sub
mitt
ed t
o an
d st
ored
at
a ce
ntra
l bio
repo
sito
ry l
ocat
ed i
n M
ilano
(Ita
ly) f
or th
e ne
xt tw
o ge
nera
tions
(60
year
s) o
r unt
il an
effi
cien
t the
rapy
for H
D is
est
ablis
hed.
I ca
n co
ntac
t my
stud
y si
te a
t any
tim
e an
d ca
n re
ques
t des
truct
ion
of th
e sa
mpl
es s
tore
d fro
m m
e.
Opt
iona
l com
pone
nt 1
:Don
atio
n of
blo
od a
nd u
rine
for s
tudi
es to
iden
tify
gene
tic m
odifi
ers
of H
D a
nd to
es
tabl
ish
and
valid
ate
biol
ogic
al m
arke
rs fo
r HD
.
I agr
ee to
rece
ive
info
rmat
ion
abou
t the
nov
el a
sses
smen
t bat
tery
and
to p
artic
ipat
e in
the
deve
lopm
ent
of n
ovel
ass
essm
ents
.
Opt
iona
l com
pone
nt 2
: Nov
el a
sses
smen
ts
Dur
ing
scie
ntifi
c st
udie
s, p
erso
nal
data
and
med
ical
fin
ding
s ab
out
you
are
reco
rded
. Th
e st
orag
e,
anal
ysis
and
com
mun
icat
ion
of d
ata
rela
ting
to th
e st
udy
are
carr
ied
out a
ccor
ding
to le
gal r
equi
rem
ents
an
d en
tail
the
follo
win
g co
nsen
t bef
ore
parti
cipa
ting
inth
e st
udy.
Info
rmat
ion
and
cons
ent f
orm
rega
rdin
g da
ta p
rote
ctio
n
1. I
agr
ee t
hat
data
/med
ical
dat
a ob
tain
ed d
urin
g th
e co
urse
of
this
stu
dy c
an b
e re
cord
ed i
n qu
estio
nnai
res
and
on e
lect
roni
c da
ta c
arrie
rs a
nd p
roce
ssed
with
out
prov
idin
g pe
rson
al id
entit
y. A
ll ps
eudo
nym
ised
dat
a ar
e st
ored
at
a se
rver
loc
ated
at
the
Uni
vers
ity o
f U
lm,
Ger
man
y. I
n ad
ditio
n,
som
e se
lect
ed d
ata
(pse
udon
ym, a
ge, s
ex a
nd d
isea
se s
tate
–w
heth
er o
ne re
pres
ents
a c
ontro
l or H
D
mut
atio
n ca
rrie
r) w
ill be
sto
red
at th
e se
rver
of t
he c
entra
l bio
repo
sito
ry in
Mila
no, w
here
the
biol
ogic
alsa
mpl
es a
re s
tore
d.
2. I
also
agr
ee th
at a
utho
rised
per
sons
(e.
g. E
HD
N m
onito
rs, r
egul
ator
y au
thor
ities
)w
ho a
re b
ound
by
conf
iden
tialit
y (e
.g. f
rom
the
spon
sor,
or th
e U
nive
rsity
) can
vie
w th
e pe
rson
al d
ata
reco
rded
as
far a
s it
is n
eces
sary
or
lega
llyre
quire
d fo
r da
ta c
ontro
l. Fo
r th
is p
urpo
se o
nly,
I ex
empt
the
clin
icia
n fro
m th
e ob
ligat
ion
to e
nsur
e m
edic
al c
onfid
entia
lity
at a
ll tim
es.
……
……
……
……
……
……
…
……
……
……
……
……
……
……
……
……
……
Nam
e of
the
Parti
cipa
nt
Sign
atur
e of
the
parti
cipa
nt
Plac
e, d
ate
60
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
Nam
e of
Per
son
Obt
aini
ng C
onse
ntSi
gnat
ure
of P
erso
n O
btai
ning
Con
sent
Plac
e, d
ate
Prin
ted
Nam
e an
d Ti
tle
REG
ISTR
Y (C
ON
TRO
L) P
SEU
DO
NYM
:
215Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
61
10.9
Part
icip
ant I
nfor
mat
ion
Shee
t (Ex
istin
g R
EGIS
TRY-
CO
NTR
OL
Part
icip
ants
)
Nam
e of
stu
dy:
REG
ISTR
Y –
an o
bser
vatio
nal
stud
y of
the
Eur
opea
n H
untin
gton
’sdi
seas
eN
etw
ork
(EH
DN
)
Dea
r Par
ticip
ant,
You
are
alre
ady
a pa
rtici
pant
of
REG
ISTR
Y. T
o da
te,
you
have
con
sent
ed t
o pa
rtici
patin
g in
R
EGIS
TRY,
whi
ch m
eans
that
with
you
r per
mis
sion
, we
carr
y ou
t a th
orou
gh s
tand
ard
exam
inat
ion
and
the
docu
men
tatio
n of
the
data
obt
aine
d du
ring
your
clin
ical
exa
min
atio
n st
ored
und
er a
pse
udon
ymon
an
ele
ctro
nic
data
base
and
you
r co
nsen
t to
regu
lar
(e.g
. ye
arly
)fo
llow
-up
visi
ts. Y
ou m
ay o
rm
ay n
ot
have
con
sent
ed t
o an
opt
iona
l co
mpo
nent
s do
nate
of b
lood
and
urin
e fo
r bi
omar
ker
and
gene
tic
mod
ifier
stu
dies
.
Sinc
e yo
u en
rolle
d to
take
par
t in
this
stu
dy, R
EGIS
TRY
has
adop
ted
anad
ditio
nal o
ptio
nal c
ompo
nent
. W
e w
ould
like
to in
vite
you
to ta
ke p
art i
n th
efo
llow
ing:
parti
cipa
tion
in n
ovel
ass
essm
ents
(Opt
iona
l com
pone
nt 1
)
A nu
mbe
r of
nov
el a
sses
smen
ts (
e.g.
que
stio
nnai
res,
int
ervi
ews,
rat
ing
scal
es)
may
hel
p us
to
unde
rsta
nd m
ore
abou
t th
e on
set,
cour
se a
nd t
reat
men
t of
Hun
tingt
on’s
dis
ease
. W
ene
ed t
o co
llect
m
ore
data
on
each
ass
essm
ent i
n or
der
to k
now
whe
ther
they
sho
uld
be u
sed
in th
e de
sign
of f
utur
e re
sear
ch a
nd c
linic
al c
are
prac
tices
.
Opt
iona
l com
pone
nt 1
: Nov
el a
sses
smen
ts
We
wou
ld li
ke to
ask
you
to c
onsi
der
taki
ng p
art i
n th
ese
nove
l ass
essm
ents
. The
nov
el a
sses
smen
ts
cove
r a
wid
e ra
nge
of a
reas
(e.
g. in
form
atio
n on
you
r w
ell-b
eing
, you
r qu
ality
of l
ife)
and
you
may
be
appr
oach
ed t
o ta
ke p
art.
The
over
all
dura
tion
of t
he n
ovel
ass
essm
ents
tog
ethe
r w
ith t
he s
tand
ard
REG
ISTR
Y as
sess
men
ts s
houl
d no
t ex
ceed
2.5
hou
rs.
You
can
deci
de w
heth
er y
ou w
ant
to d
o th
e ad
ditio
nal a
sses
smen
ts o
r not
dur
ing
your
vis
it.
VOLU
NTE
ERIN
GYo
ur p
artic
ipat
ion
in th
is r
esea
rch
proj
ect i
s vo
lunt
ary.
You
are
free
to w
ithdr
aw fr
om th
e st
udy
at a
ny
time
and
with
out
givi
ng r
easo
n. T
his
pote
ntia
l w
ithdr
awal
doe
s no
t af
fect
you
r co
ntin
uing
med
ical
tre
atm
ent.
On
your
req
uest
eve
ry li
nk b
etw
een
your
sto
red
data
and
you
r pe
rson
can
be
perm
anen
tly
dele
ted
(for
deta
ils s
ee In
form
atio
n re
gard
ing
data
pro
cess
ing,
dat
a pr
otec
tion
and
data
sec
urity
, po
int ‘
E’).
INSU
RAN
CE
Beca
use
the
Reg
istry
is n
eith
er a
pha
rmac
olog
ical
stu
dy n
or a
stu
dy to
test
new
dia
gnos
tic p
roce
dure
s,
ther
e ar
e no
add
ition
al h
ealth
risk
s an
d th
e pa
rtici
pant
s th
eref
ore
do n
ot n
eed
insu
ranc
e.
CLI
NIC
IAN
CO
NTA
CT
Shou
ld y
ou h
ave
any
ques
tions
at
anyt
ime
durin
g th
e co
urse
of
the
rese
arch
pro
ject
you
can
rea
ch
(loca
l inv
estig
ator
s) o
n te
leph
one
num
ber
(tele
phon
e nu
mbe
r of
loca
l inv
estig
ator
) at
any
tim
e du
ring
wor
king
hou
rs. F
or e
mer
genc
ies
out o
f hou
rs, r
ing
(loca
l em
erge
ncy
num
ber)
.
CO
NFI
DEN
TIAL
ITY/
DAT
A PR
OTE
CTI
ON
:Al
l clin
icia
ns a
nd r
elat
ed m
edic
al s
taff
invo
lved
in lo
okin
g af
ter
you
durin
g th
is c
linic
al s
tudy
are
bou
nd
by m
edic
al c
onfid
entia
lity
and
are
oblig
ed t
o co
mpl
y w
ith d
ata
prot
ectio
n. R
esea
rch
resu
lts r
elat
ing
to
this
stu
dy a
re in
tend
ed fo
r us
e in
an
anon
ymou
s fo
rm in
sci
entif
ic p
ublic
atio
ns. A
s fa
r as
is n
eces
sary
fo
r ens
urin
g co
rrec
t dat
a en
try, a
utho
rised
indi
vidu
als
(e.g
. the
spo
nsor
, the
uni
vers
ity) a
re p
erm
itted
to
revi
ew y
our l
ocal
med
ical
reco
rds.
If in
divi
dual
s au
thor
ised
to v
iew
rec
ords
are
not
bou
nd b
y m
edic
al c
onfid
entia
lity
as m
entio
ned
abov
e,
pers
onal
dat
a th
at c
ome
to th
eir a
ttent
ion
durin
g ch
ecks
are
con
fiden
tial u
nder
the
Dat
a Pr
otec
tion
Act.
62
Euro
pean
H
D
Net
wor
k:
Info
rmat
ion
rega
rdin
g da
ta
proc
essi
ng,
data
pr
otec
tion
and
data
se
curit
y.
A.
An
esse
ntia
l sa
fety
asp
ect
of t
he p
roje
ct i
s th
e pr
oces
sing
of
my
data
in
an e
xclu
sive
ly
pseu
dony
mis
ed m
anne
r. W
hat d
oes
that
mea
n an
d ho
w is
it c
arrie
d ou
t?
Dur
ing
your
firs
t vi
sit,
your
clin
icia
n w
ill e
nter
cer
tain
dat
a ab
out
you
into
the
com
pute
r. Fr
om t
hese
pe
rson
al d
ata
a un
ique
cod
e na
me
(‘pse
udon
ym’)
is c
alcu
late
d, c
onsi
stin
g of
a s
erie
s of
9 d
igits
. The
fo
llow
ing
pers
onal
dat
a ar
e us
ed:
first
nam
e, b
irth
nam
e (s
urna
me)
, da
te o
f bi
rth,
plac
e of
birt
h an
d m
othe
r’s m
aide
n na
me.
Exam
ple:
Mar
ia,
Mill
er
nee
Mus
term
ann,
bo
rn
10.1
1.19
64
in
Ulm
, m
othe
r’s m
aide
n na
me
Schm
idt.
This
in
form
atio
n re
sults
in
the
code
nam
e (‘p
seud
onym
’) 42
5-49
1-32
6. I
mpo
rtant
ly,
the
pseu
dony
m i
s cr
eate
d on
the
bas
is o
f a
so-c
alle
d ‘s
ecur
e ha
sh-a
lgor
ithm
’. B
y th
is m
athe
mat
ical
ope
ratio
n a
uniq
ue
valu
e is
ass
igne
d du
ring
a co
mpl
icat
ed, o
ne-w
ay p
roce
dure
. The
mat
hem
atic
al a
lgor
ithm
use
d en
sure
s th
at n
obod
y (n
ot e
ven
the
syst
em p
rogr
amm
er)
can
reco
nstru
ct f
rom
the
resu
lt (th
e ‘p
seud
onym
’) th
e in
form
atio
n w
hich
was
use
d to
gen
erat
e th
e ps
eudo
nym
(i.e
. yo
ur u
niqu
e pe
rson
al d
ata)
in t
he f
irst
plac
e. T
he p
erso
nal d
ata
trans
mitt
ed t
o ge
nera
te t
he p
seud
onym
are
hel
d on
ly f
or t
he c
alcu
latio
n of
yo
ur c
ode
nam
e (‘p
seud
onym
’) in
the
wor
king
mem
ory
of a
larg
e co
mpu
ter (
‘ser
ver’)
. The
cal
cula
tion
of
the
pseu
dony
m r
equi
res
a ve
ry s
hort
time
(milli
seco
nds)
. V
iew
ing
pers
onal
dat
a du
ring
this
tim
e is
im
poss
ible
. The
reaf
ter a
ll da
ta u
sed
to c
reat
e th
e ps
eudo
nym
are
per
man
ently
era
sed
from
the
wor
king
m
emor
y of
the
serv
er s
o th
at n
o id
entif
ying
det
ails
rem
ain;
dat
a us
ed to
gen
erat
e th
e ps
eudo
nym
are
ne
ver
stor
ed in
any
for
m o
f pe
rman
ent m
emor
y (e
.g.
on t
he h
ard
driv
e). F
ollo
win
g th
is,
all d
ata
base
en
tries
and
eve
ry u
se o
f dat
a is
exc
lusi
vely
car
ried
out u
nder
the
assi
gned
pse
udon
ym.
B.W
hich
dat
a do
I ha
ve to
dis
clos
e ap
art f
rom
the
data
requ
ired
to c
reat
e m
y ps
eudo
nym
in th
e co
urse
of t
he R
EGIS
TRY
stud
y an
d su
bseq
uent
stu
dies
?D
urin
g th
e co
urse
of
the
REG
ISTR
Y st
udy,
som
e he
alth
and
/or
med
ical
dat
a w
ill be
rec
orde
d (s
ee
Parti
cipa
nt In
form
atio
n Sh
eet f
or fu
rther
det
ails
). If
you
are
parti
cipa
ting
in a
ny s
ubse
quen
t stu
dies
, you
r cl
inic
ian
will
give
you
det
aile
d in
form
atio
n ab
out t
he s
tudy
and
the
data
requ
ired
for i
t acc
ordi
ngly
. Eac
h su
bseq
uent
stu
dy re
quire
s se
para
te p
artic
ipan
t con
sent
.
C.W
ho c
an s
ee a
nd u
se m
y da
ta?
1. Y
ou: i
f you
wis
h so
, the
clin
icia
n tre
atin
g yo
u ca
n le
t you
to s
ee a
ll da
ta s
tore
d ab
out y
ou. I
t is
advi
sed
that
you
rev
iew
the
se d
ata
toge
ther
with
the
phy
sici
an t
reat
ing
you
to e
xpla
in m
edic
al t
erm
inol
ogy
to
you
and
to a
nsw
er q
uest
ions
you
may
hav
e.
2. T
he c
linic
ian
treat
ing
you:
The
stu
dy s
ite te
am e
nrol
ling
you
for R
EGIS
TRY
is th
e on
ly o
ne a
part
from
yo
urse
lf w
ho c
an l
ink
your
pse
udon
ym t
o yo
ur i
dent
ifyin
g da
ta (
i.e.
nam
e, a
ddre
ss e
tc.).
Afte
r ge
nera
tion
of th
e ps
eudo
nym
all
entry
of c
linic
al in
form
atio
n in
the
data
bas
e is
car
ried
out u
nder
you
r co
de n
ame
(‘pse
udon
ym’).
You
r st
udy
site
tea
m in
clud
ing
your
tre
atin
g cl
inic
ian
can
view
all
clin
ical
da
ta re
cord
ed u
nder
pse
udon
ym.
3. E
HD
N s
taff:
EH
DN
sta
ff ca
n vi
ew th
e da
ta s
tore
d un
der
your
pse
udon
ym in
ord
er to
ens
ure
corr
ect
docu
men
tatio
n an
d hi
gh d
ata
qual
ity to
con
tact
the
stud
y si
te te
am fo
r cl
arify
ing
ques
tions
. EH
DN
sta
ff ca
n on
ly v
iew
and
use
pse
udon
ymis
ed d
ata
ente
red
on t
he E
HD
N n
etw
ork.
For
the
pur
pose
of
data
co
ntro
l, EH
DN
sta
ff (‘m
onito
rs’ a
nd ‘a
udito
rs’)
are
allo
wed
to c
heck
with
you
r st
udy
site
team
that
the
data
en
tere
d on
to
the
netw
ork
mat
ches
w
ith
the
data
fo
und
in
your
lo
cal
med
ical
re
cord
s.
Mon
itors
/aud
itors
are
bou
nd b
y m
edic
al c
onfid
entia
lity.
4. A
utho
rised
res
earc
hers
(sc
ient
ist/c
linic
ians
): Sc
ient
ists
/clin
icia
ns w
ho a
re i
nvol
ved
in H
D r
esea
rch
can
appl
y to
the
Scie
ntifi
c an
d B
ioet
hica
lAdv
isor
y C
omm
ittee
(SBA
C)o
f EH
DN
(a g
roup
of e
xper
ienc
ed
clin
icia
ns a
nd s
cien
tists
) for
aut
horis
atio
n to
obt
ain
acce
ss to
the
data
bas
e. A
utho
rised
rese
arch
ers
can
only
vie
w c
oded
dat
a. T
o en
sure
the
high
est d
egre
e of
con
fiden
tialit
y ps
eudo
nym
s ar
e re
code
d be
fore
th
e da
ta b
ank
is m
ade
avai
labl
e to
aut
horis
ed re
sear
cher
s. T
here
by it
is g
uara
ntee
d th
at a
ll pu
blic
atio
ns
repo
rting
on
the
findi
ngs
of a
utho
rised
rese
arch
exc
lusi
vely
use
ano
nym
ised
dat
a re
port
form
at (i
.e. n
ot
even
usi
ng th
e ps
eudo
nym
).
216 Hygeia Public Health 2011, 46(2): 183-218
63
5. S
yste
m a
dmin
istra
tors
: In
ord
er t
o sa
fegu
ard
the
EHD
N c
entra
l da
taba
se,
a sm
all
num
ber
of
auth
oris
ed s
yste
m a
dmin
istra
tors
can
vie
w p
seud
onym
ised
dat
a.
6. O
ther
gro
ups
and
indi
vidu
als:
No-
one
othe
r th
an t
he g
roup
s an
d in
divi
dual
s de
scrib
ed a
bove
can
ga
in a
cces
s to
or r
ecei
ve th
e da
ta s
tore
d ab
out y
ou.
D.H
ow c
an I
be s
ure
that
una
utho
rised
peo
ple
cann
ot g
ain
acce
ss t
o m
y da
ta w
hile
the
y ar
e se
nt v
ia th
e In
tern
et?
All
data
tra
velli
ng v
ia t
he i
nter
net
are
encr
ypte
d. T
his
impl
ies
for
all
prac
tical
pur
pose
s th
at n
obod
y as
ide
from
the
inte
nded
rec
eive
r ca
n re
ad o
r ac
cess
the
seda
ta.
The
serv
er w
here
the
dat
abas
e is
st
ored
is l
ocat
ed b
ehin
d a
‘fire
wal
l’. T
his
soph
istic
ated
sec
urity
sys
tem
ens
ures
tha
t on
ly a
utho
rised
co
mpu
ters
and
indi
vidu
als
can
gain
acc
ess
to t
he d
atab
ase.
Fur
ther
mor
e, t
he c
entra
l dat
abas
e do
es
not c
onta
in id
entif
ying
dat
a as
all
data
are
sto
red
unde
r a c
ode
nam
e (‘p
seud
onym
’).
E.H
ow lo
ng a
re m
y da
ta s
tore
d fo
r?Al
l dat
a w
ill be
sto
red
as e
nter
ed:
until
you
with
draw
you
r par
ticip
atio
n an
d re
ques
t the
ano
nym
isat
ion
of y
our d
ata
until
10
year
s af
ter a
n ef
ficie
nt th
erap
y fo
r HD
has
bee
n es
tabl
ishe
da
max
imum
per
iod
of 6
0 ye
ars
(2 g
ener
atio
ns +
10
year
s),o
rup
to a
max
imum
of 1
0 ye
ars
afte
r the
pro
ject
act
iviti
es h
ave
stop
ped.
A co
mpl
ete
dele
tion
of d
ata
is d
iffic
ult,
sinc
e da
ta a
re li
kely
to h
ave
beco
me
part
ofsc
ient
ific
stud
ies
and
ther
efor
e ne
ed to
be
kept
on
reco
rd in
com
plia
nce
to la
ws
and
regu
latio
ns to
allo
w fu
ture
cro
ss c
heck
s an
d da
ta v
erifi
catio
ns, e
ven
year
s af
ter
the
rese
arch
was
com
plet
ed. H
owev
er, a
ll lin
ks to
you
can
be
dele
ted
and
irrev
ersi
bly
dest
roye
d. A
s a
resu
lt, t
hus
not
even
the
phy
sici
ans
chos
en b
y yo
u fo
r en
rolm
ent i
nto
REG
ISTR
Y w
ill an
y lo
nger
be
able
to r
ecog
nize
data
as
data
bel
ongi
ng to
you
. Suc
h a
com
plet
e an
onym
isat
ion
will
be c
arrie
d ou
t in
the
follo
win
g ca
ses:
If yo
u w
ithdr
aw y
our c
onse
nt fo
r fur
ther
par
ticip
atio
n in
REG
ISTR
Y an
d if
you
requ
est t
hat y
our p
ast
data
are
ano
nym
ised
.If
you
requ
est c
ompl
ete
anon
ymis
atio
n of
you
r dat
a.
Loca
tion,
dat
eN
ame
of th
e co
nsen
ting
clin
icia
n
64
10.1
0Pa
rtic
ipan
t Con
sent
For
m (E
xist
ing
REG
ISTR
Y-C
ON
TRO
LPa
rtic
ipan
ts)
Nam
e of
stu
dy:
REG
ISTR
Y –
an o
bser
vatio
nal
stud
y of
the
Eur
opea
n H
untin
gton
’sdi
seas
eN
etw
ork
(EH
DN
)
Con
tent
, pro
cedu
res,
ris
ks a
nd a
ims
of th
e re
sear
ch p
roje
ct n
amed
abo
ve a
s w
ell a
s th
e rig
ht to
vie
w
the
data
reco
rded
was
exp
lain
ed to
me
in d
etai
l by
……
..……
..……
..……
.. I h
ad th
e op
portu
nity
to a
sk
ques
tions
and
obt
aine
d an
swer
s w
hich
I fe
lt w
ere
satis
fact
ory.
I ha
d su
ffici
ent t
ime
to d
ecid
e w
heth
er o
r no
t I w
ant t
o pa
rtici
pate
in th
e pr
ojec
t. I r
ecei
ved
a co
py o
f the
pat
ient
info
rmat
ion
and
of th
e co
nsen
t fo
rm.
Plea
se c
heck
YE
S or
NO
for e
ach
ques
tion
belo
w, r
efer
ring
to th
e fo
llow
ing
optio
nal s
tudy
pro
cedu
res:
I ag
ree
to r
ecei
ve i
nfor
mat
ion
abou
t th
e in
the
nov
el a
sses
smen
t ba
ttery
and
to
parti
cipa
te i
n th
e de
velo
pmen
t of n
ovel
ass
essm
ents
.
Opt
iona
l com
pone
nt 1
: Nov
el a
sses
smen
ts
Dur
ing
scie
ntifi
c st
udie
s, p
erso
nal
data
and
med
ical
fin
ding
s ab
out
you
are
reco
rded
. Th
e st
orag
e,
anal
ysis
and
com
mun
icat
ion
of d
ata
rela
ting
to th
e st
udy
are
carr
ied
out a
ccor
ding
to le
gal r
equi
rem
ents
an
d en
tail
the
follo
win
g co
nsen
t bef
ore
parti
cipa
ting
in th
e st
udy.
Info
rmat
ion
and
cons
ent f
orm
rega
rdin
g da
ta p
rote
ctio
n
1. I
agr
ee t
hat
data
/med
ical
dat
a ob
tain
ed d
urin
g th
e co
urse
of
this
stu
dy c
an b
e re
cord
ed i
n qu
estio
nnai
res
and
on e
lect
roni
c da
ta c
arrie
rs a
nd p
roce
ssed
with
out
prov
idin
g pe
rson
al id
entit
y. A
ll ps
eudo
nym
ised
dat
a ar
e st
ored
at
a se
rver
loc
ated
at
the
Uni
vers
ity o
f U
lm,
Ger
man
y. I
n ad
ditio
n,
som
e se
lect
ed d
ata
(pse
udon
ym, a
ge, s
ex a
nd d
isea
se s
tate
-whe
ther
one
rep
rese
nts
a co
ntro
l or
HD
m
utat
ion
carr
ier)
will
be s
tore
d at
the
serv
er o
f the
cen
tral b
iore
posi
tory
in M
ilano
, whe
re th
e bi
olog
ical
sa
mpl
es a
re s
tore
d.
2. I
also
agr
ee th
at a
utho
rised
per
sons
(e.g
. EH
DN
mon
itors
, reg
ulat
ory
auth
oriti
es)
who
are
bou
nd b
y co
nfid
entia
lity
(e.g
. fro
m th
e sp
onso
r, or
the
Uni
vers
ity)c
an v
iew
the
pers
onal
dat
a re
cord
ed a
s fa
r as
it is
nec
essa
ry o
r le
gally
req
uire
d fo
r da
ta c
ontro
l. Fo
r th
is p
urpo
se o
nly,
I ex
empt
the
clin
icia
n fro
m th
e ob
ligat
ion
to e
nsur
e m
edic
al c
onfid
entia
lity
at a
ll tim
es.
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
Nam
e of
the
Parti
cipa
nt
Sign
atur
e of
the
parti
cipa
nt
Plac
e, d
ate
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
……
…
……
……
…N
ame
of P
erso
n O
btai
ning
Con
sent
Sign
atur
e of
Per
son
Obt
aini
ng C
onse
ntPl
ace,
dat
e(P
rinte
d N
ame
and
Title
)
REG
ISTR
Y(C
ON
TRO
L) P
SEU
DO
NYM
217Study Protocol of Registry – version 3.0 – European Huntington’s Disease Network (EHDN)
65
10.1
1Fa
mily
mem
ber (
Invi
tatio
n le
tter)
Invi
tatio
n to
take
par
t in
REG
ISTR
Y, a
larg
e Eu
rope
an s
tudy
into
Hun
tingt
on’s
dis
ease
We
are
appr
oach
ing
you
beca
use
we
unde
rsta
nd y
ou h
ave
a re
lativ
e w
ho h
as a
fam
ily h
isto
ry o
f H
untin
gton
’s d
isea
se (
HD
). T
his
info
rmat
ion
shee
t ha
s be
en g
iven
to
you
by a
rel
ativ
e w
ho a
lread
y pa
rtici
pate
s in
REG
ISTR
Y an
d w
as k
ind
enou
gh to
giv
e it
to y
ou o
n ou
r req
uest
.
REG
ISTR
Y is
a s
tudy
con
duct
ed b
y a
netw
ork
of c
linic
ians
and
sci
entis
ts fr
om a
cros
s Eu
rope
. The
aim
sof
the
stud
y ar
e to
(i) i
mpr
ove
the
unde
rsta
ndin
g of
HD
, (ii)
impr
ove
man
agem
ent a
nd tr
eatm
ent o
ptio
ns
for H
D.
In a
dditi
on,
a m
ajor
goa
l of
REG
ISTR
Y is
to
dete
rmin
e ho
w e
nviro
nmen
tal a
nd g
enet
ic f
acto
rs m
ay
influ
ence
the
onse
t and
cou
rse
of th
e di
seas
e an
d al
so h
ow it
diff
ers
in fa
milie
s. W
e ho
pe th
at o
btai
ning
th
is i
nfor
mat
ion
will
assi
st u
s in
det
erm
inin
g m
ore
effe
ctiv
e tre
atm
ent
stra
tegi
es.
Ther
efor
e, a
s th
e or
gani
sers
of R
EGIS
TRY,
we
are
info
rmin
g yo
u ab
out t
his
stud
y to
see
if y
ou w
ould
like
to ta
kepa
rt.
Wha
t is
REG
ISTR
Y?R
EGIS
TRY
is a
long
-term
, obs
erva
tiona
l stu
dy th
at h
as th
e ai
m o
f gat
herin
g a
larg
e am
ount
of r
elia
ble
data
on
the
sym
ptom
s an
d co
urse
of H
D. A
s th
e di
seas
e ha
s no
t ye
t bee
n fu
lly c
hara
cter
ised
, thi
s is
es
sent
ial f
or in
form
ing
treat
men
t stra
tegi
es.
Who
spo
nsor
s R
EGIS
TRY?
The
stud
y is
spo
nsor
ed b
ya
priv
ate
Amer
ican
Fou
ndat
ion
(CH
DIF
ound
atio
n, In
c.).
Who
can
take
par
t?If
you
are
a fa
mily
mem
ber
of s
omeo
ne w
ho h
as H
D (
even
if y
ou d
o no
t ca
rry
the
gene
you
rsel
f) or
ha
ve H
D y
ou a
re e
ligib
le t
o ta
ke p
art
in R
EGIS
TRY.
S
pous
es a
nd c
arer
s ca
n al
so c
ontri
bute
in
form
atio
n an
d bi
osam
ples
to th
e st
udy.
I wou
ld li
ke to
hav
e m
ore
info
rmat
ion
on R
EGIS
TRY
and
the
Euro
pean
-HD
Net
wor
k –
whe
re d
o I
find
mor
e de
tails
? Pl
ease
vis
it th
e Eu
ro-H
D w
ebsi
te (
http
://w
ww
.eur
o-hd
.net
) or
if y
ou w
ould
pre
fer
dire
ct c
onta
ct, g
et in
to
uch
with
PI N
AME
at th
e st
udy
whi
ch e
nrol
led
your
rela
tive.
PI N
AM
Eca
n be
reac
hed
at x
xxx
(pho
ne)
or x
xx(fa
x); t
he p
osta
l add
ress
is (x
xx,x
xx).
If yo
u w
ould
like
to h
ave
info
rmat
ion
on o
ther
par
ticip
atin
g st
udy
site
s po
tent
ially
mor
e co
nven
ient
ly l
ocat
ed f
or y
ou p
leas
e ge
t in
tou
ch w
ith t
he E
urop
ean-
HD
N
etw
ork
lang
uage
are
a co
ordi
nato
r (xx
x, T
el: x
xx, E
mai
l: xx
x, F
ax: x
xx,A
ddre
ss).
Det
ails
of t
he n
eare
st
parti
cipa
ting
cent
re c
an a
lso
be fo
und
on th
e w
ebsi
te u
nder
Net
wor
k> L
ocat
ions
.
We
wou
ld b
e ex
trem
ely
grat
eful
if y
ou w
ould
con
side
r par
ticip
atin
g in
this
rese
arch
. We
wis
h to
mak
e it
clea
r th
at y
our
part
icip
atio
n in
our
stu
dy is
vol
unta
ry a
nd a
ref
usal
to ta
ke p
art o
r a
deci
sion
to
with
draw
at a
ny ti
me
wou
ld n
ot a
ffect
cur
rent
or f
utur
e m
edic
al tr
eatm
ent.
66
11R
EFER
ENC
ES1.
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per P
. Hun
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.B. S
aund
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Com
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; 199
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on's
D
isea
se
Col
labo
rativ
e R
esea
rch
Gro
up.
A
nove
l ge
ne
cont
aini
ng
a tri
nucl
eotid
e re
peat
that
is e
xpan
ded
and
unst
able
on
Hun
tingt
on's
dis
ease
chr
omos
omes
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ell.
1993
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ar 2
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ecul
ar p
atho
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untin
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th in
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huga
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et a
l. In
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tion
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ingt
in f
ibril
loge
nesi
s by
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cific
ant
ibod
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l m
olec
ules
: im
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atio
ns f
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untin
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's
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ase
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apy.
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5.Zh
ang
X,
Smith
DL,
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iin A
B, E
ngem
ann
S, R
usse
l D
E, R
oark
M,
et a
l. A
pote
nt s
mal
l m
olec
ule
inhi
bits
po
lygl
utam
ine
aggr
egat
ion
in
Hun
tingt
on's
di
seas
e ne
uron
s an
d su
ppre
sses
ne
urod
egen
erat
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in v
ivo.
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c N
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cad
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Beal
MF,
Fer
rant
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xper
imen
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ck D
J. A
new
pol
ymer
ase
chai
n re
actio
n (P
CR
) as
say
for
the
trinu
cleo
tide
repe
at t
hat
is u
nsta
ble
and
expa
nded
on
Hun
tingt
on's
dis
ease
chr
omos
omes
. M
ol C
ell
Prob
es. 1
993
Jun;
7(3)
:235
-9.
42.
Potte
r N
T, S
pect
or E
B, P
rior
TW. T
echn
ical
sta
ndar
ds a
nd g
uide
lines
for
Hun
tingt
on d
isea
se
test
ing.
Gen
et M
ed. 2
004
Jan-
Feb;
6(1)
:61-
5.43
.R
iess
O, N
oerr
emoe
lle A
, Soe
rens
en S
A, E
pple
n JT
. Im
prov
ed P
CR
con
ditio
ns fo
r th
e st
retc
h of
(CAG
)n re
peat
s ca
usin
g H
untin
gton
's d
isea
se. H
um M
ol G
enet
. 199
3 Se
p;2(
9):1
523.
