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International Journal of Clinical Pharmacy (2019) 41:630–666https://doi.org/10.1007/s11096-019-00816-4
1 3
REVIEW ARTICLE
Clinical pharmacy practice in the care of Chronic Kidney Disease patients: a systematic review
Fatma Al Raiisi1 · Derek Stewart1 · Fernando Fernandez‑Llimos2 · Teresa M. Salgado3 · Moustafa Fahmy Mohamed4 · Scott Cunningham1
Received: 11 October 2018 / Accepted: 27 March 2019 / Published online: 9 April 2019 © The Author(s) 2019
AbstractBackground Clinical pharmacy services have potential to contribute significantly to the multidisciplinary team providing safe, effective and economic care for patients. Given recent practice developments (e.g. polypharmacy reviews and pharmacist prescribing) there is a need to provide a current synthesis of the evidence base for characteristics and outcomes of clinical pharmacy practice in chronic kidney disease patients. Aim of the review To critically appraise, synthesise and present the available evidence of the characteristics (structures and processes) and outcomes of clinical pharmacy practice as part of the multidisciplinary care of patients with chronic kidney disease. Method PubMed, International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline and Scopus were searched for peer reviewed papers using improved search strategy. Included studies were quality assessed using Downs and Black tool for controlled studies and the mixed methods appraisal tool for all controlled and non-controlled studies. Data were extracted and synthesised using a narrative approach. Screening, quality assessment and data extraction were performed by two independent researchers. Ethics approval was not required. Results Forty-seven studies were identified from a variety of countries, with 31 based in a hospital setting. Controlled study designs were employed in 20, with only ten of these using randomisation. Resources available for service provision were poorly reported in all papers. Positive impact on clinical outcomes included significant improvement in parathyroid hormone, blood pressure, haemoglobin and creatinine clearance. Pharmacists identi-fied 5302 drug related problems in 2933 patients and made 3160 recommendations with acceptance rates up to 95%. Impact on humanistic outcomes was shown through improvement in health related quality of life and patient satisfaction. Economic benefits arose from significant cost savings through pharmaceutical care provision. Conclusion While there is some evidence of positive impact on clinical, humanistic and economic outcomes, this evidence is generally of low quality and insufficient volume. While the existing evidence is in favour of pharmacists’ involvement in the multidisciplinary team providing care to patients with chronic kidney disease, more high-quality research is warranted.
Keywords Chronic kidney disease · Clinical pharmacy · Pharmacist · Systematic review
Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s1109 6-019-00816 -4) contains supplementary material, which is available to authorized users.
* Scott Cunningham [email protected]
1 School of Pharmacy & Life Sciences, Robert Gordon University, Aberdeen, Scotland, UK
2 Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
3 Department of Pharmacotherapy & Outcomes Science, Center for Pharmacy Practice Innovation, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA
4 Oman Pharmacy Institute, Ministry of Health, Muscat, Oman
631International Journal of Clinical Pharmacy (2019) 41:630–666
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Impacts on practice
• Understanding fully the structures, processes and rel-evant outcomes associated with clinical roles of phar-macists is essential to make best use of resource for optimal patient care.
• There has been a significant volume of research of the clinical role of pharmacists in Chronic Kidney Disease, but it is of limited detail and quality.
• There is a need for agreed standard sets of outcomes for clinical pharmacy practice and research in chronic kidney disease.
Introduction
Chronic Kidney Disease (CKD) continues to be a global concern with a high risk of mortality, frequent hospitalisa-tion and reduced life expectancy [1]. Most patients have co-morbid conditions such as cardiovascular and mineral bone diseases [2]. Clinical pharmacy services have the potential to contribute significantly to the multidiscipli-nary team providing safe, effective and economic care [3]. Key clinical pharmacy roles in the multidisciplinary care of CKD patients were described by two renal pharmacy consultants Mason and Bakus in 2010 [4]. These roles included specific areas such as managing anaemia, renal mineral bone disease and hypertension, as well as more general medicines selection and review [4]. Another major role pharmacists can play is to contribute to renal drug cost management [5]. An emerging role is the potential for the pharmacist to prescribe and modify medicines, which has now been implemented into practice in the United Kingdom (UK), United States (USA) and New Zealand [6]. There is a need to establish the evidence base of the impact of clinical pharmacy in the care of CKD patients. In 2012, Salgado et al. published a systematic review which included synthesis of the peer reviewed literature up to March 2010 [7]. The original review identified 37 stud-ies (38 articles), involving 4743 participants. Majority of the papers were of uncontrolled design (80%) [7]. Twenty-one articles (55.3%) reported outcome measures and pro-cess indicators, 4 (10.5%) reported only outcome meas-ures, thirteen (34.2%) reported only process indicators and none reported structures [7]. Pharmacists identified 2683 drug-related problems in 1209 patients. The results from controlled studies (average quality score 0.57, SD = 0.10) reported that pharmacists’ interventions reduced all-cause hospitalisations, reduced the incidence of end-stage renal disease or death in patients with diabetic nephropathy,
improved management of anaemia, blood pressure, cal-cium and phosphate parameters and lipid management [7]. The uncontrolled studies included in the original review shown positive impact of pharmacists’ interventions on the reduction of transplant rejections and fewer adverse events [7]. The reviews main limitations were selection and language bias which might affect the quality of the systematic review. Salgado et al. concluded that the evi-dence of pharmacists’ interventions in patients with CKD is scarce, of variable quality and with heterogeneous out-comes [7]. Since the publication of the original review by Salgado et al., the prescribing practice has continually developed with new services and models of care being developed and embedded into clinical pharmacy practice. Hence, there is a need to update and extend the review. Given developments in clinical pharmacy globally, it is likely that further research has been reported thus an up-to-date synthesis is warranted.
Aim of the review
The aim of this review was to critically appraise, synthesise and present the available evidence for the structures, pro-cesses and related outcomes of clinical pharmacy practice as part of the multidisciplinary care of patients with CKD. The specific review questions were:
• What clinical pharmacy practice related resources (struc-tures, e.g. the multidisciplinary team, clinical pharmacy skill mix and time allocation) are in place and how are these matched to healthcare needs and demands to ena-ble provision of care to chronic kidney disease (CKD) patients?
• What activities are performed (processes, e.g. medication review, prescribing) to care for patients with CKD, how and when are they performed?
• What are the outcomes of the structure and the processes on the effectiveness (Economic, Clinical, and Humanistic Outcomes (ECHO) model) [8] of care provided?
Method
Data sources
The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (PROSPERO 2017 CRD42017065258). The protocol was constructed in accordance with PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) standards [9], and the review con-ducted and reported in accordance with PRISMA (Preferred
632 International Journal of Clinical Pharmacy (2019) 41:630–666
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Reporting Items for Systematic Review and Meta-Analysis) standards [10].
The Cochrane database was searched to identify any rel-evant systematic reviews. An electronic search of relevant databases (PubMed, International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Lit-erature (CINAHL), Medline and Scopus) was conducted from March 2010 to December 2018 thus providing an update on the review of Salgado et al. [7]. The search was carried out using Medical Subject Headings (MeSH) and other appropriate subject headings and text words. Scoping searches were conducted prior to finalising the search strat-egy. Boolean operators such as truncations (*), wild cards ($), adjacent search options (e.g. adj2) were used where rel-evant. The following grouped terms were initially searched separately then in combination by two independent review-ers (FA & SC). The primary search was conducted using the improved search strategy of the same terms as the original review as follows:
PubMed, IPA, CINAHL: (“pharmaceutical services” [MH+] OR “pharmacy” [MH+] OR “Pharmacies” [MH] OR “Pharmacists” [MH] OR “clinical pharmacist*” [TI/AB/SU] OR “clinical pharmacy” [TI/AB/SU] OR “clini-cal pharmacies” [TI/AB/SU] OR “pharmacist*” [TI/AB/SU] OR “pharmaceutical services” [TI/AB/SU] OR “phar-macies” [TI/AB/SU] OR “pharmacy” [TI/AB/SU]) AND (“kidney diseases” [MH+] OR “renal replacement therapy” [MH+] OR “proteinuria” [MH+] OR “CKD” [TI/AB/SU] OR “nephropathy” [TI/AB/SU]).
Scopus:(“Pharmaceutical care” [TI/ABS/KEY] OR “Pharmacist”
[TI/ABS/KEY] OR “Clinical pharmacy” [TI/ABS/KEY]) AND (“Chronic Kidney Disease” [TI/ABS/KEY] OR “Renal replacement Therapy” [TI/ABS/KEY] OR “Haemodialysis” [TI/ABS/KEY] OR “Kidney failure” [TI/ABS/KEY]). The bibliography list of included studies was reviewed to further identify additional references.
Study selection and data extraction
Only quantitative studies (randomised and non-randomised controlled and uncontrolled trials, cohort studies and before and after evaluations) published in peer-reviewed journals were included in the review. Papers published in English and focusing on researching clinical pharmacy practice and the role of the pharmacist in managing patients with CKD were included. Studies not addressing the topic, literature based only on conceptual models, i.e. lacking empirical evidence, grey literature including conference proceedings, abstracts and unpublished studies were excluded. Observational stud-ies were excluded since they did not address the aim of this review.
Title and abstract screening and quality assessment for inclusion were conducted independently by two reviewers (FA and SC), with any disagreements resolved by discus-sion with a third independent reviewer (DS).
Quality assessment
An independent, duplicate quality assessment of each study was undertaken (DS, TJ, FA & SC). All controlled, uncontrolled and descriptive studies were assessed using the mixed methods appraisal tool (MMAT), a validated and unique tool for appraising different types of study designs [11]. All controlled studies included in this review were additionally assessed for quality using the Downs and Black’s method in line with the original review [12], a validated tool with a scoring scale consisting of 27 ques-tions grouped into five domains (reporting, external valid-ity, bias, confounding and power). The total score is 32 and is expressed as rates, the higher the score the better the quality of the paper in terms of methodology (maximum is 1) [12]. To classify scores, the approach of Machado et al. was applied [13] (i.e. < 0.5 was considered ‘weak’, 0.5–0.69 were ‘fair’, 0.7–0.79 ‘good’ and 0.8–1.0 ‘very good’).
Data extraction
Data extracted included: primary author, year of publica-tion, aim/objectives, design, duration, setting, participants, pharmacist interventions, key findings or main outcomes and conclusion. Structures, processes and outcomes were adapted from Donabedian’s quality of care model [14]. Structure was defined as the ‘resources required for the pharmacist to be able to provide care to renal patients such as requiring special training, availability of policies and procedures for practice etc’. Process was defined as ‘the activities that are performed by the pharmacist on a daily basis or on specific intervals and how and when they are performed. These activities may include: daily clinical rounds, involvement in patients’ management plans, medi-cation reviews, therapeutic recommendations and phar-macist prescribing. Outcome measures included clinical outcomes such as: clinical parameters, medication-related adverse events, mortality and morbidities, humanistic out-comes such as: quality of life and economic outcomes such as: rate of hospitalisation and cost of inappropriate thera-pies. In addition, pharmacists’ intervention was defined in the previous review as “any action with the aim of modify-ing the process of use of drugs, either in patients’ activities or in medical or health care practitioners’ activities” [7].
633International Journal of Clinical Pharmacy (2019) 41:630–666
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Data synthesis
Due to heterogeneity in the data obtained from the included papers (type of patients, study design, outcomes measured), only descriptive and narrative synthesis was possible. All findings were considered by two independent reviewers to ensure robustness and consistency in execution of the review process.
Results
Study selection and data extraction
No systematic reviews were identified from the Cochrane database and no additional primary studies were identified from the bibliography lists of included studies.
Databases searches identified 4140 potential articles to screen further for eligibility (Fig. 1). Only 47 articles met
the inclusion criteria and after quality assessment were of a standard deemed acceptable for inclusion in the review.
Quality assessment
The Downs and Black’s mean score of the 20 controlled studies was 0.557 (SD = 0.075). All papers presented ‘fair’ quality with the exception of four that scored < 0.5 and was therefore considered ‘weak’ quality. The quality assessment of all the included studies using the MMAT tool for the ran-domised (n = 10), non-randomised (n = 20) and descriptive studies (n = 17) are shown in Figs. 2, 3 and 4.
Data extraction
Tables 1 and 2 detail the data extraction characteristics of controlled and uncontrolled studies included in the system-atic review [15–61].
Fig. 1 PRISMA Chart describ-ing study retrieval and selection
634 International Journal of Clinical Pharmacy (2019) 41:630–666
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Study characteristics
The 47 studies were carried out in a variety of geographic locations: USA (n = 10), Iran (n = 5), India (n = 7), France (n = 3), Spain (n = 3), Jordan (n = 2), China (n = 2), Japan (n = 3), Singapore (n = 2), Nigeria, Taiwan, Australia, Saudi Arabia, Germany, Netherlands, Indonesia, Norway, Canada and the UK (n = 1 in each country). Two studies from 2008 to 2009 were not included in the systematic review of Sal-gado et al. [7], hence were considered as part of this review.
Thirty-one studies were conducted in hospital settings (wards, intensive care units (ICU), clinics, departments and dialysis units) and 16 in primary care settings, including clinics and community pharmacies. The follow-up time in all included papers ranged from 4 weeks to 24 months with a mean of 9.4 (standard deviation, SD = 5.08) months, with four studies with unclear duration.
The majority of studies (n = 27) used an uncontrolled study design, 21 prospective and six retrospective. The remaining 20 were controlled, ten of which were randomised
Fig. 2 Stacked bar chart representing quality of quantitative Randomized Controlled Trials (n = 10). The % values above represents the propor-tion for each response as agreed between reviewers for the papers included for each study design
Fig. 3 Stacked bar chart representing quality of quantitative non-randomized studies (n = 20). The % values above represents the proportion for each response as agreed between reviewers for the papers included for each study design
Fig. 4 Stacked bar chart representing quality of quantitative descriptive studies (n = 17). The % values above represents the proportion for each response as agreed between reviewers for the papers included for each study design
635International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
Cha
ract
erist
ics o
f con
trolle
d stu
dies
incl
uded
in th
e sy
stem
atic
revi
ew
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Sant
schi
et a
l. (2
011)
Can
ada
[48]
Clu
ster,
ran-
dom
ised
stud
y (6
mon
ths)
Prim
ary
Car
e,
Com
mun
ity
Phar
mac
ies.
Mul
tidis
cipl
i-na
ry p
re-d
ialy
sis
clin
ic
To e
valu
ates
the
impa
ct o
f Pro
FiL
on B
P co
ntro
l an
d m
anag
emen
t of
hyp
erte
nsio
n tre
atm
ent
90 C
KD
pat
ient
sPr
oFiL
gro
up 7
1.9
(10.
4), a
nd u
sual
ca
re g
roup
73.
3 (7
.7)
(1) A
3-h
trai
ning
w
orks
hop
for
com
mun
ity p
har-
mac
ists
(2) A
com
mun
ica-
tion
netw
ork
to fa
cilit
ate
the
trans
fer o
f clin
i-ca
l inf
orm
atio
n be
twee
n th
e pr
e-di
alys
is c
linic
an
d co
mm
unity
ph
arm
acist
s(3
) A p
harm
aceu
ti-ca
l con
sulta
tion
serv
ice
by h
os-
pita
l pha
rmac
ists
with
exp
ertis
e in
nep
hrol
ogy
(n =
48)
Usu
al c
are
(n =
41)
Adj
uste
d m
ean
BP
chan
ges,
wer
e (−
6.9/
− 0.
4 m
mH
g in
Pro
FiL
patie
nts)
co
mpa
red
with
(+
4.7/
+ 2.
2 m
mH
g in
UC
) (be
twee
n gr
oups
diff
eren
ces,
p va
lue =
0.02
1/0.
348)
. A
t 6 m
onth
s, 44
% o
f Pr
oFiL
and
24%
of
UC
pat
ient
s ach
ieve
d th
eir B
P ta
rget
s. Pa
tient
s with
writ
ten
hype
rtens
ion
reco
m-
men
datio
ns h
ad a
gr
eate
r dec
reas
e in
m
ean
systo
lic B
P (−
11.6
mm
Hg;
p
valu
e = 0.
035)
, and
B
P w
as c
ontro
lled
in
a hi
gher
pro
porti
on
of th
em (r
elat
ive
risk,
2.
14; p
val
ue =
0.01
1)A
spin
all e
t al.
(201
2)U
SA [3
9]
Non
-ran
dom
ised
co
ntro
lled
study
(6
mon
ths)
Prim
ary
care
se
tting
, Med
ical
ce
nter
s
To c
ompa
re th
e qu
ality
of E
SA
pres
crib
ing
and
mon
itorin
g fo
r pa
tient
s with
N
DD
-CK
D in
Ve
tera
ns A
ffairs
M
edic
al C
ente
rs
with
and
with
out
phar
mac
ist-
man
aged
ESA
cl
inic
s
572
ND
D-C
KD
pa
tient
sPh
arm
acist
-Man
-ag
ed E
SA C
linic
73
.9 (1
0.9)
,U
sual
-Car
e 78
.4
(8.8
),U
sual
Car
e at
ES
A C
linic
76.
2 (1
2.0)
Dos
ing
and
mon
i-to
ring
ESA
ther
apy
by
phar
mac
ists
(n =
314)
Usu
al c
are
at
ESA
clin
ic si
te
(n =
91)
Usu
al c
are
(n =
167)
Mor
e ha
emog
lobi
n va
l-ue
s wer
e in
the
targ
et
rang
e in
pha
rmac
ist-
man
aged
ESA
clin
ics
(71.
1% v
s. 56
.9%
fo
r usu
al-c
are
site
s;
P <
0.00
1)Ve
tera
ns in
pha
rmac
ist-
man
aged
ESA
clin
ics
had
mor
e ha
emog
lo-
bin
mea
sure
men
ts o
n av
erag
e (5
.8 v
s. 3.
6 in
usu
al-c
are
site
s an
d 3.
8 in
usu
al c
are
at E
SA c
linic
site
s;
p = 0.
007)
.
636 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Das
hti-K
havi
daki
et
al.
(201
3)Ir
an [3
0]
Clu
ster,
ran-
dom
ised
stud
y (1
2 m
onth
s)
Hae
mod
ialy
sis
war
d of
a u
ni-
vers
ity a
ffilia
ted
terti
ary
hosp
ital
To a
sses
s the
im
pact
of p
har-
mac
eutic
al c
are
on H
RQ
oL o
f ha
emod
ialy
sis
patie
nts
92 H
D p
atie
nts
Inte
rven
tion
55.4
(1
5.7)
, con
trol
48.6
(14.
7)
Rece
ive
clin
ical
ph
arm
acist
-led
phar
mac
eutic
al
care
in a
dditi
on
to th
e st
anda
rd
care
of t
he w
ard
as th
e ca
se g
roup
(n
= 26
)
Con
trol g
roup
(n
= 34
)N
ot re
porte
d
Via
-Sos
a et
al.
(201
3)Sp
ain
[18]
Non
-ran
dom
ised
co
ntro
lled
study
(9
mon
ths)
Com
mun
ity p
har-
mac
ies
To e
valu
ate
the
effec
tiven
ess o
f th
e co
mm
unity
ph
arm
acist
in
terv
entio
n in
ad
dres
sing
the
prob
lem
of d
os-
ing
inad
equa
cy
as a
con
sequ
ence
of
rena
l im
pair-
men
t in
patie
nts
over
65
year
s tha
t w
ere
taki
ng 3
or
mor
e dr
ugs w
hen
com
pare
d w
ith
usua
l car
e
40 c
omm
unity
ph
arm
acie
s35
4 CK
D p
atie
nts
Inte
rven
tion
80.8
(7
.3),
cont
rol
82.9
(7.1
)
Phar
mac
ists u
sed
a qu
estio
nnai
re to
w
rite
a re
port
to
GPs
det
ailin
g th
e D
RPs
det
ecte
d an
d su
gges
t-in
g ch
ange
s in
ther
apy.
GPs
to
prov
ide
writ
ten
repl
y to
the
phar
-m
acist
s with
in
14 d
ays (
n = 17
8)
Con
trol g
roup
(n
= 17
6)Th
e di
ffere
nce
in th
e pr
eval
ence
of d
osin
g in
adeq
uacy
bet
wee
n th
e co
ntro
l and
in
terv
entio
n gr
oup
befo
re th
e ph
arm
a-ci
sts’ i
nter
vent
ion
was
0.7
3% [9
5%
CI (
− 6.
0)–7
.5] a
nd
afte
r the
pha
rma-
cists
’ int
erve
ntio
n it
was
13.
5% [9
5% C
I 8.
0–19
.5] (
p < 0.
001)
w
hile
the
diffe
renc
e in
the
mea
n of
dru
g-re
late
d pr
oble
ms
per p
atie
nt b
efor
e th
e ph
arm
acist
s’
inte
rven
tion
was
0.0
5 [9
5% C
I(−
0.2)
–0.3
] an
d fo
llow
ing
the
inte
rven
tion
it w
as
0.5
[95%
CI 0
.3–0
.7]
(p <
0.00
1).
637International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Cab
ello
-Mur
iel
et a
l. (2
014)
Spai
n [3
6]
Non
-ran
dom
ised
co
ntro
lled
study
(U
ncle
ar)
Inte
rnal
med
icin
e de
partm
ent o
f a
refe
rral
hos
pita
l
To d
emon
strat
e th
at th
e in
terv
en-
tion
of a
pha
rma-
cist
in a
mon
itor-
ing
prog
ram
for
patie
nts w
ith
CKD
impr
oves
th
e ou
tcom
e of
re
nal f
unct
ion
in
thes
e pa
tient
s
249
CKD
pat
ient
sIn
terv
entio
n 82
.4
(7.4
), C
ontro
l 81
.2 (8
.5)
Phar
mac
ist in
ter-
vent
ion
incl
udin
g pa
tient
inte
rvie
w,
med
icat
ion
histo
ry ta
king
, id
entifi
catio
n of
in
appr
opria
te
dose
s of n
ephr
o-to
xic
drug
s, da
ily
chec
k of
labo
ra-
tory
par
amet
ers
and
prop
osin
g do
se a
djus
tmen
ts
to p
hysi
cian
s (n
= 12
4)
Con
trol g
roup
(n
= 12
5)Si
gnifi
cant
diff
eren
ces
wer
e no
ted
whe
n co
mpa
ring
CrC
l be
twee
n di
scha
rge
and
adm
issi
on in
bo
th th
e co
ntro
l and
in
terv
entio
n gr
oups
(5
.1 ±
0.9
vs. 6
.4 ±
1.0
p < 0.
01).
The
rate
of
acc
epta
nce
of th
e ph
arm
acist
s’ re
com
-m
enda
tions
was
74%
Deb
enito
et a
l. (2
014)
USA
[44]
Non
-ran
dom
ised
co
ntro
lled
study
(6
mon
ths)
Prim
ary
care
set-
ting,
hea
lth c
are
syste
m
To a
sses
s adh
er-
ence
to m
onito
r-in
g gu
idel
ines
, al
ong
with
effi
-ca
cy a
nd sa
fety
ou
tcom
es, a
nd to
qu
antif
y m
edic
a-tio
n ut
iliza
tion
expe
nditu
res
amon
g pa
tient
s us
ing
ESA
th
erap
y m
anag
ed
by a
clin
ical
ph
arm
acy
serv
ice
com
pare
d w
ith
usua
l car
e
101
CKD
pat
ient
s (p
re-d
ialy
sis)
Inte
rven
tion
65.6
(1
4.1)
, UC
72
(13.
3)
Clin
ical
pha
r-m
acy
serv
ices
pr
ovid
ed to
pa
tient
s atte
nd-
ing
the
Clin
ical
Ph
arm
acy
Ant
i-co
agul
atio
n an
d A
naem
ia S
ervi
ce
(n =
31)
Usu
al c
are
(n =
70)
Tim
e to
ach
ieve
men
t of
haem
oglo
bin
targ
et
was
28
days
in th
e ph
arm
acist
-man
aged
gr
oup
com
pare
d w
ith 4
1 da
ys in
the
usua
l car
e gr
oup
(p =
0.13
5), w
hile
the
prop
ortio
n of
pat
ient
s ac
hiev
ing
targ
et
haem
oglo
bin
was
96
.8%
com
pare
d w
ith
95.7
%, r
espe
ctiv
ely
(p =
0.65
4). P
atie
nts
in th
e ph
arm
acist
-m
anag
ed g
roup
use
d le
ss E
SA d
urin
g th
e 6-
mon
th p
erio
d, le
ad-
ing
to a
n an
nual
ized
sa
ving
s of 1
288
USD
pe
r pat
ient
in d
rug
expe
nditu
res
638 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Jiang
et a
l. (2
014a
)C
hina
[35]
Non
-ran
dom
ised
co
ntro
lled
study
(1
2 m
onth
s)
Uni
vers
ity
affilia
ted
terti
ary
hosp
ital
To d
escr
ibe
the
deve
lopm
ent a
nd
impl
emen
tatio
n of
pha
rmac
ist
dosi
ng a
djus
t-m
ent f
or c
riti-
cally
ill p
atie
nts
rece
ivin
g C
RRT
an
d to
exa
min
e th
e eff
ectiv
enes
s of
pha
rmac
ist
inte
rven
tions
209
patie
nts o
n C
RRT
In
terv
entio
n58.
9 (1
7.3)
, No-
inte
rven
tion
61.3
(1
6.9)
The
phar
mac
ists
asse
ssed
the
patie
nts r
ecei
ving
C
RRT
dai
ly d
ur-
ing
ICU
roun
ds,
and
then
mad
e do
sage
adj
ust-
men
t int
erve
n-tio
ns w
hen
need
ed (n
= 10
6)
No-
inte
rven
tion
grou
p (n
= 10
3)Su
spec
ted
adve
rse
drug
eve
nts i
n th
e in
terv
entio
n gr
oup
wer
e si
gnifi
cant
ly
low
er th
an th
e pr
e-in
terv
entio
n gr
oup
(35
in 2
7 pa
tient
s ve
rsus
18
in 1
1 pa
tient
s, p <
0.00
1).
How
ever
, the
re
was
no
sign
ifica
nt
diffe
renc
e be
twee
n le
ngth
of I
CU
stay
an
d m
orta
lity
afte
r ph
arm
acist
dos
ing
adju
stmen
t, w
hich
w
as 8
.93
days
ver
sus
7.68
day
s (p =
0.26
) an
d 30
.10%
ver
sus
27.3
6% (p
= 0.
39),
resp
ectiv
ely.
The
m
ajor
ity o
f ide
ntifi
ed
AD
Es c
ause
d si
gnifi
-ca
nt in
jury
(48.
6% in
th
e pr
e-in
terv
entio
n pe
riod
and
44.4
% in
th
e po
st-in
terv
entio
n pe
riod)
to th
e pa
tient
s in
volv
ed; t
he n
umbe
r of
thes
e A
DEs
dif-
fere
d si
gnifi
cant
ly
betw
een
the
two
grou
ps (p
= 0.
02).
639International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Jiang
et a
l. (2
014b
)C
hina
[40]
Non
-ran
dom
ised
co
ntro
lled
study
(1
2 m
onth
s)
Uni
vers
ity
affilia
ted
terti
ary
hosp
ital
To e
valu
ate
the
effec
t of c
lini-
cal p
harm
acist
pa
rtici
patio
n in
an
ICU
team
on
antim
icro
bial
do
sing
adj
ust-
men
t int
erve
n-tio
n fo
r pat
ient
s re
ceiv
ing
CV
VH
180
patie
nts o
n C
VV
HIn
terv
entio
n 62
.0
(18.
4), C
ontro
l 59
.3 (2
0.6)
Phar
mac
ists
asse
ssed
crit
i-ca
lly il
l pat
ient
s re
ceiv
ing
CV
VH
da
ily d
urin
g IC
U
roun
ds, a
nd m
ade
antim
icro
bial
do
sage
adj
ust-
men
t int
erve
n-tio
ns w
hen
need
ed (n
= 93
)
Con
trol g
roup
(n
= 87
)Ph
arm
acist
s mad
e 25
6 an
timic
robi
al
dosi
ng a
djus
tmen
t re
com
men
datio
ns
for p
atie
nts r
ecei
ving
C
VV
H, o
f whi
ch 2
24
(87.
5%) r
ecom
men
-da
tions
wer
e ac
cept
ed
by p
hysi
cian
s. In
con
trol g
roup
, ph
arm
acist
dos
ing
adju
stmen
t res
ulte
d in
£16
37.7
(266
9.5
USD
) cos
t sav
ings
pe
r pat
ient
, and
2.3
6 tim
es re
duct
ion
of
antim
icro
bial
-rel
ated
ad
vers
e dr
ug e
vent
s (A
DEs
) (11
vs.
26,
p = 0.
002)
, whi
le
leng
th o
f IC
U st
ay
and
mor
talit
y in
ICU
sh
owed
no
sign
ifica
nt
diffe
renc
e (p
> 0.
05)
640 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Joos
t et a
l. 20
14)
Ger
man
y [4
7]N
on-r
ando
mis
ed
cont
rolle
d stu
dy
(12
mon
ths)
Rena
l tra
nspl
ant
unit
at a
uni
ver-
sity
hos
pita
l
To in
vesti
gate
the
effica
cy o
f a
phar
mac
eutic
al
care
pro
gram
me
for a
pply
ing
adhe
renc
e m
an-
agem
ent m
odul
e to
enh
ance
ki
dney
tran
spla
nt
patie
nts’
adh
er-
ence
to im
mu-
nosu
ppre
ssiv
e m
edic
atio
n
74 T
x pa
tient
sIC
G: 5
1 (1
3.3)
,SC
G: 5
4 (1
1.9)
Add
ition
al p
har-
mac
eutic
al c
are
and
coun
selli
ng
prov
ided
by
the
clin
ical
pha
r-m
acist
afte
r the
tra
nspl
anta
tion
Add
ition
al m
eet-
ings
with
clin
ical
ph
arm
acist
at
out
-pat
ient
tra
nspl
anta
tion
care
(min
imum
on
ce p
er q
uarte
r up
to m
axim
um
of o
nce
a m
onth
). (n
= 35
)
Stan
dard
car
e gr
oup
(n =
39)
Adh
eren
ce w
as si
g-ni
fican
tly im
prov
ed
in p
atie
nts o
f the
IC
G (9
1%) c
ompa
red
with
SC
G (7
5%)
durin
g th
e fir
st ye
ar
afte
r tra
nspl
anta
tion
(p =
0.01
4). D
aily
ad
here
nce
mea
s-ur
es w
ere
alre
ady
impr
oved
with
in
30–4
0 da
ys a
fter
star
t of i
nten
sifie
d pa
tient
care
. Int
ensi
-fie
d ca
re p
atie
nts a
lso
show
ed si
gnifi
cant
ly
bette
r res
ults
for
taki
ng a
dher
ence
(p
= 0.
006)
, pill
cou
nt
(p =
0.00
8) a
nd d
rug
holid
ays (
p = 0.
001)
.
641International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Coo
ney
et a
l. (2
015)
USA
[15]
Prag
mat
ic,
rand
omis
ed,
cont
rolle
d stu
dy
(12
mon
ths)
Prim
ary
care
To e
valu
ate
the
effec
t of a
ph
arm
acist
-bas
ed
qual
ity im
prov
e-m
ent p
rogr
am
on 1
) out
com
es
for p
atie
nts
with
CK
D a
nd
2) a
dher
ence
to
CKD
gui
delin
es
in th
e pr
imar
y ca
re se
tting
2199
CK
D p
atie
nts
Inte
rven
-tio
n75.
5(8.
2),
cont
rol 7
5.7(
8.2)
Phon
e-ba
sed
phar
-m
acist
inte
rven
-tio
n, p
harm
a-ci
st-ph
ysic
ian
colla
bora
tion,
pa
tient
edu
catio
n an
d a
CKD
regi
s-try
(n =
1070
)
Usu
al c
are
(n =
1129
)Im
prov
emen
t in
the
prim
ary
proc
ess o
ut-
com
e, m
easu
rem
ent
of P
TH (1
6.1%
in th
e co
ntro
l arm
vs.
46.9
%
in th
e in
terv
entio
n ar
m; p
< 0.
001)
. Sub
-je
cts i
n th
e in
terv
en-
tion
arm
wer
e pr
e-sc
ribed
mor
e cl
asse
s of
ant
ihyp
erte
nsiv
e m
edic
atio
ns th
an
thos
e in
the
cont
rol
arm
(p =
0.02
)In
crea
sed
% o
f sub
ject
s w
ith a
pho
spho
rus
and
urin
e al
bum
in to
cr
eatin
ine
ratio
mea
s-ur
ed fo
r int
erve
ntio
n ar
m. S
atis
fact
ion
with
th
e in
terv
entio
n w
as
very
pos
itive
; 92%
of
parti
cipa
nts
Stai
no e
t al.
(201
5)U
SA [2
0]N
on-r
ando
mis
ed
cont
rolle
d stu
dy
(3 m
onth
s)
Rena
l tra
nspl
ant
clin
ic a
t a m
edi-
cal u
nive
rsity
ho
spita
l
To d
eter
min
e if
a ph
arm
acist
-exe
-cu
ted
com
pre-
hens
ive
char
t re
view
cou
ld
serv
e as
suffi
cien
t su
bstit
utio
n fo
r di
rect
par
-tic
ipat
ion
durin
g ou
tpat
ient
clin
ic
visi
ts in
the
post-
disc
harg
e fo
llow
-up
trea
tmen
t of
kidn
ey tr
ansp
lant
re
cipi
ents
219
Tx p
atie
nts
Inte
rven
tion
50,
com
para
tor 5
2Ph
arm
acist
s pr
ovid
ed re
com
-m
enda
tions
via
ch
art r
evie
w fo
r pa
tient
s who
at
tend
ed th
e tra
nspl
ant n
eph-
rolo
gy c
linic
. (n
= 17
0)
Com
para
tor g
roup
(n
= 17
5)N
ot re
porte
d
642 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Cha
ng e
t al.
(201
6)U
SA [4
5]Pr
agm
atic
, clu
ster,
rand
omis
ed st
udy
(18
mon
ths)
Prim
ary
care
To e
xam
ine
the
feas
ibili
ty o
f us
ing
phar
mac
ist
MTM
to im
prov
e pr
otei
nuria
sc
reen
ing
and
CKD
man
age-
men
t in
a la
rge,
in
tegr
ated
hea
lth
syste
m
6 pr
imar
y ca
re
site
s, 47
CK
D
patie
nts
MTM
64.
0 (1
3.2)
, co
ntro
l 70.
6 (9
.7)
Phar
mac
ist M
TM
arm
rece
ived
ad
ditio
nal s
up-
port
from
the
phar
mac
ist a
t the
cl
inic
site
Thes
e ph
arm
acist
s re
ceiv
ed a
ddi-
tiona
l edu
catio
n ab
out K
DIG
O-
base
d sc
reen
ing
and
man
age-
men
t gui
delin
es
(n =
24)
Con
trol g
roup
(n
= 23
)Th
e ph
arm
acist
MTM
in
terv
entio
n di
d no
t si
gnifi
cant
ly im
prov
e to
tal p
rote
inur
ia
scre
enin
g at
the
pop-
ulat
ion
leve
l (O
R 2
.6,
95%
CI:
0.5–
14.0
; p =
0.3)
. How
ever
, it
tend
ed to
incr
ease
sc
reen
ing
of p
revi
-ou
sly u
nscr
eene
d pa
tient
s (78
.6%
in
the
phar
mac
ist M
TM
grou
p co
mpa
red
to
33.3
% in
the
cont
rol
grou
p; (O
R 7
.3,
95%
CI:
0.96
–56.
3;
p = 0.
05).
Qud
ah e
t al.
(201
6)Jo
rdan
[32]
Ran
dom
ised
co
ntro
lled
study
(6
mon
ths)
Out
patie
nt h
ae-
mod
ialy
sis u
nits
of
a u
nive
rsity
ho
spita
l
To e
valu
ate
clin
ical
ph
arm
acist
s rol
e in
the
man
age-
men
t of b
lood
pr
essu
re in
ha
emod
ialy
sis
patie
nts g
uide
d by
hom
e bl
ood
pres
sure
mon
itor-
ing
60 H
D p
atie
nts
Inte
rven
tion
55.3
(1
5.1)
, and
con
-tro
l 51.
7 (1
8.5)
Phys
icia
n-ph
arm
a-ci
st co
llabo
rativ
e ca
re to
opt
imiz
e an
tihyp
erte
nsiv
e ph
arm
acol
ogic
th
erap
y (n
= 29
)
Con
trol g
roup
(n
= 27
)46
% o
f pat
ient
s in
the
inte
rven
tion
arm
ach
ieve
d B
P ta
rget
(mea
n ho
me
BP
≤ 13
5/85
mm
Hg)
co
mpa
red
to o
nly
14.3
% o
f pat
ient
s in
the
cont
rol a
rm
(p =
0.02
). A
vera
ge
decl
ine
in w
eekl
y m
ean
hom
e SB
P w
as
10.9
± 17
.7 m
mH
g in
th
e in
terv
entio
n ar
m
(p =
0.00
4)W
eekl
y m
ean
hom
e sy
stolic
blo
od p
res-
sure
incr
ease
d by
3.
5 ± 18
.4 m
mH
g in
the
cont
rol a
rm
(p =
0.39
6)
643International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Chi
a et
al.
(201
7)Si
ngap
ore
[52]
Non
-ran
dom
ised
, co
ntro
lled
study
(2
4 m
onth
s)
Out
patie
nt n
eph-
rolo
gy c
linic
of a
te
rtiar
y ho
spita
l
To d
eter
min
e w
heth
er a
col
-la
bora
tive
care
(C
C) m
odel
w
ith p
harm
acist
in
volv
emen
t can
re
duce
adm
is-
sion
s and
hea
lth-
care
util
izat
ion
in
patie
nts r
ecei
ving
di
alys
is, c
om-
pare
d to
usu
al
care
(UC
)
134
patie
nts
CC
62
(11.
4), U
C
60.4
(10.
8)Ph
arm
acist
s pe
rform
ed
med
icat
ion
revi
ew, d
isea
se
and
med
icat
ion
coun
selli
ng.
They
com
plet
ed
train
ing
mod
ules
an
d re
ceiv
ed
4 se
ssio
ns o
f tra
inin
g w
ith
an e
xper
ienc
ed
phar
mac
ist
befo
re th
ey c
ould
pr
ovid
e th
e se
rvic
e in
depe
n-de
ntly
Usu
al c
are
(n =
190)
CC
redu
ced
adm
issi
ons
by 2
7% (I
RR
0.7
3,
95%
CI 0
.54–
0.99
, p =
0.04
7) a
nd
shor
tene
d m
ean
LOS
by 1
.3 d
ays [
6.7
(2.6
) ve
rsus
. 8.0
(3.2
), p <
0.00
1] c
ompa
red
to U
C. N
o si
gnifi
cant
di
ffere
nces
in m
orta
l-ity
(p =
0.18
9) o
r m
ean
heal
thca
re
utili
zatio
n co
st (p
= 0.
165)
bet
wee
n gr
oups
Phar
mac
ists i
dent
ified
51
5 D
RPs
with
429
(8
3.3%
) res
olve
d af
ter r
evie
w
644 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Mat
eti e
t al.
(201
7)In
dia
[53]
Ope
n-la
bel,
rand
omis
ed
cont
rol s
tudy
(1
5 m
onth
s)
Dia
lysi
s cen
tres o
f te
achi
ng (T
H),
gove
rnm
ent
(GH
), an
d co
r-po
rate
hos
pita
ls
(CH
)
To a
sses
s the
im
pact
of
Phar
mac
eutic
al
Car
e (P
C) o
n th
e H
RQ
oL a
mon
g H
D p
atie
nts
78 p
atie
nts
PC g
roup
52.
78
(10.
45) i
n TH
, 49
.15
(12.
57) i
n G
H a
nd 5
2.97
(1
5.12
) in
CH
. U
sual
car
e gr
oup
49.4
0 (1
2.47
) in
TH, 4
8 (1
7) in
G
H a
nd 5
3.77
(1
1.87
) in
CH
(1) T
he P
C g
roup
re
ceiv
ed th
e us
ual c
are
alon
g w
ith p
harm
a-ce
utic
al c
are
deliv
ered
by
a qu
alifi
ed re
gis-
tere
d ph
arm
acist
. Th
e cu
stom
ized
ca
re p
lan
was
de
sign
ed a
nd
deliv
ered
to
the
patie
nts o
n m
onth
ly b
asis
ba
sed
on th
e co
n-di
tion
and
need
of
the
patie
nt b
y th
e W
HO
-FIP
Ph
arm
aceu
ti-ca
l car
e m
odel
. (2
) The
QoL
w
as a
sses
sed
usin
g va
lidat
ed
KD
QoL
-36
instr
umen
t
Usu
al c
are
(n =
75)
The
HR
QoL
scor
es
wer
e si
gnifi
cant
ly
impr
oved
ove
r tim
e in
th
e do
mai
ns n
otic
ed
with
rega
rd to
the
“phy
sica
l fun
ctio
n-in
g, g
ener
al h
ealth
, em
otio
nal w
ell-b
eing
, so
cial
func
tioni
ng,
sym
ptom
/pro
blem
lis
t, an
d eff
ects
of
kidn
ey d
isea
se”
in a
ll th
e th
ree
cent
res o
f PC
gro
up c
ompa
red
to U
C g
roup
with
p <
0.05
The
base
line
HR
QoL
sc
ore
of K
DQ
oL-
36 d
omai
ns su
ch a
s ES
RD
-targ
eted
are
as
wer
e no
t sig
nific
antly
di
ffere
nt in
the
UC
gr
oup
vers
us P
C
grou
p in
all
the
thre
e H
D c
entre
sTh
e ph
arm
aceu
tical
ca
re p
rovi
ded
by a
tra
ined
pha
rmac
ist
had
posi
tive
impa
ct
in H
RQ
oL o
f HD
pa
tient
s
645International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
And
ereg
g et
al.
(201
8)U
SA [5
4]
Clu
ster r
ando
mis
ed
trial
32 m
edic
al o
ffice
s fro
m 1
5 st
ates
To d
eter
min
e if
hype
rtens
ive
patie
nts w
ith
com
orbi
d D
M
and
CKD
rece
iv-
ing
a ph
arm
acist
in
terv
entio
n ha
d im
prov
ed
BP
cont
rol a
nd
grea
ter r
educ
-tio
n in
mea
n B
P at
9 m
onth
s co
mpa
red
with
th
ose
rece
ivin
g us
ual c
are
227
patie
nts
Inte
rven
tion
grou
p 61
.7 (1
1.6)
, con
-tro
l 63.
1 (1
2.2)
Phar
mac
ist in
ter-
view
ed p
atie
nts
to re
view
med
i-ca
tions
, ass
esse
d kn
owle
dge
and
then
edu
cate
d th
e pa
tient
s on
HTN
. In
divi
dual
ised
ca
re p
lans
wer
e pr
epar
ed a
nd
pres
ente
d to
the
phys
icia
n
108
patie
nts
Inte
rven
tion
grou
p ha
d si
gnifi
cant
ly g
reat
er
mea
n sy
stolic
blo
od
pres
sure
redu
ctio
n co
mpa
red
with
usu
al
care
at 9
mon
ths
(8.6
4 m
m H
g; 9
5%,
CI −
12.8
to −
4.49
, p <
0.00
1). T
he
inte
rven
tion
grou
p ha
d si
gnifi
cant
ly
high
er B
P co
ntro
l at
9 m
onth
s tha
n us
ual
care
(adj
uste
d od
ds
ratio
[OR
] 1.9
7,
95%
, CI 1
.01–
3.86
, p =
0.04
7 an
d O
R
2.16
, 95%
CI 1
.21–
3.85
, p =
0.01
02,
resp
ectiv
ely)
Mat
eti e
t al.
(201
8 a)
Indi
a [5
5]
Ope
n-la
bel,
rand
omis
ed
cont
rol s
tudy
(1
5 m
onth
s)
Dia
lysi
s cen
tres o
f te
achi
ng (T
H),
gove
rnm
ent
(GH
), an
d co
r-po
rate
hos
pita
ls
(CH
)
To a
sses
s the
im
pact
of p
har-
mac
eutic
al c
are
on m
edic
atio
n ad
here
nce,
Hb
leve
ls, b
lood
pr
essu
re (B
P),
and
inte
rdia
lytic
w
eigh
t gai
n (I
DW
) am
ong
HD
pat
ient
s
78 p
atie
nts
As [
53]
Tailo
red
care
pl
an h
as b
een
desi
gned
and
pro
-vi
ded
to th
e PC
gr
oup
patie
nts
on m
onth
ly
basi
s bas
ed o
n th
e si
tuat
ion
of
the
patie
nt b
y th
e “W
HO
-FIP
Ph
arm
aceu
tical
ca
re m
odel
”
Usu
al c
are
(n =
75)
The
PC g
roup
had
sig-
nific
antly
redu
ced
its
IDW
and
BP
leve
ls
in c
ompa
rison
to U
C
grou
p at
diff
eren
t tim
e in
terv
als w
ith a
st
atist
ical
sign
ifica
nce
of p
< 0.
05. T
he H
b le
vels
and
med
ica-
tion
adhe
renc
e ra
te
scor
es o
f HD
pat
ient
s ha
d si
gnifi
cant
ly
incr
ease
d in
PC
gr
oup
com
pare
d to
U
C g
roup
at d
iffer
ent
time
inte
rval
s
646 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Mat
eti e
t al.
(201
8 b)
Indi
a [5
6]
Ope
n-la
bel,
rand
omis
ed
cont
rol s
tudy
(1
2 m
onth
s)
Dia
lysi
s cen
tres o
f te
achi
ng (T
H),
gove
rnm
ent
(GH
), an
d co
r-po
rate
hos
pita
ls
(CH
)
To a
sses
s the
cos
t-eff
ectiv
enes
s of
phar
mac
eutic
al
care
ver
sus u
sual
ca
re o
n tre
atm
ent
costs
in th
e pa
tient
s und
ergo
-in
g m
aint
enan
ce
HD
78 p
atie
nts
As [
53]
(1)T
he p
harm
acist
pr
ovid
ed P
C to
th
e PC
gro
up
patie
nts o
n m
onth
ly b
asis
re
gard
ing
the
know
ledg
e ab
out
the
med
icat
ions
, di
seas
e, li
festy
le
and
med
icat
ion
char
t rev
iew
(2) T
he a
nnua
l co
sts o
f m
edic
atio
ns, H
D,
labo
rato
ry te
sts,
and
trave
l wer
e co
llect
edTh
e ec
onom
ic
outc
omes
wer
e as
sess
ed b
y in
crem
enta
l co
st-eff
ectiv
enes
s ra
tio (I
CER
)
Usu
al c
are
(n =
75)
The
incr
emen
tal c
ost-
effec
tiven
ess r
atio
for
acad
emic
, gov
ern-
men
t, an
d co
rpor
ate
hosp
itals
HD
pat
ient
s of
PC
gro
up c
om-
pare
d w
ith U
C g
roup
w
ere
86,2
30 In
dian
Ru
pee
(IN
R)/Q
ual-
ity a
djus
ted
life
year
(Q
ALY
) ~ (1
223.
03
USD
), 23
1,01
6.66
IN
R/Q
ALY
~ (3
276.
6 U
SD),
and
87,4
30 IN
R/
QA
LY ~
(124
0.05
U
SD),
resp
ectiv
ely.
647International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Tuttl
e et
al.
(201
8)U
SA [5
7]Si
ngle
-blin
d,
rand
omiz
ed,
cont
rolle
d tri
al
(3 m
onth
s)
Hos
pita
l set
ting
and
hom
e vi
sits
.To
det
erm
ine
the
effec
t of a
med
i-ca
tion
ther
apy
man
agem
ent
inte
rven
tion
on a
cute
car
e ut
iliza
tion
afte
r ho
spita
lizat
ion
in p
atie
nts w
ith
CKD
not
on
dial
ysis
72 p
atie
nts
Inte
rven
tion
grou
p 70
(12)
, con
trol
grou
p 69
(10)
A 1
- to
2-ho
ur in
-ho
me
visi
t fro
m
a ph
arm
acist
for
a m
edic
atio
n th
erap
y m
anag
e-m
ent (
med
icat
ion
revi
ew, a
ctio
n pl
an a
nd li
st)
with
in 7
day
s of
hos
pita
l dis
-ch
arge
69 p
atie
nts
The
prim
ary
out-
com
e (c
ompo
site
of
hosp
italis
atio
n/em
er-
genc
y de
partm
ent/
urge
nt c
are
cent
re
visi
ts) o
ccur
red
in
44%
of t
he in
terv
en-
tion
grou
p an
d 41
%
in c
ontro
l gro
up
(p =
0.72
). H
ospi
tal
read
mis
sion
rate
was
n =
19 (2
6%) i
n th
e in
terv
entio
n gr
oup
and
n = 18
(26%
) in
the
cont
rol g
roup
(p
= 0.
95).
No
diffe
r-en
ce in
ach
ieve
men
t of
goa
ls fo
r BP,
hae
-m
oglo
bin,
pho
spho
-ru
s, or
par
athy
roid
ho
rmon
e
648 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 1
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn
(dur
atio
n)St
udy
setti
ngA
imPa
rtici
pant
sIn
terv
entio
nC
ontro
lM
ain
clin
ical
out
com
es
achi
eved
N (a
t bas
elin
e)A
ge (y
ears
), m
ean
(SD
)
Xu
et a
l. (2
018)
Taiw
an [5
8]N
on-r
ando
mis
ed,
cont
rolle
d stu
dy
(12
mon
ths)
Kid
ney
trans
plan
t cl
inic
s of a
med
i-ca
l cen
tre.
To e
valu
ate
the
beha
viou
ral a
nd
phys
iolo
gica
l ou
tcom
es o
f ph
arm
aceu
tical
ca
re in
kid
ney
trans
plan
t rec
ipi-
ents
43 T
x pa
tient
sR
E gr
oup
48.6
(8
.9).
RI g
roup
49
.0 (1
2.8)
The
phar
mac
ists
prov
ided
face
-to-
face
inte
rvie
ws,
chec
k-up
s for
la
bora
tory
ex
amin
atio
ns,
and
disc
over
y an
d do
cum
enta
-tio
n of
DR
Ps,
phar
mac
eutic
al
cons
ulta
tion,
and
ed
ucat
ion
12 T
x pa
tient
sPa
tient
s in
the
RE
grou
p po
sses
sed
bette
r kno
wle
dge
for
self-
care
(49.
6 ± 4.
8 vs
. 38.
8 ± 9.
1;
p < .0
01);
how
ever
, th
e di
ffere
nces
at
12 m
onth
s bec
ame
insi
gnifi
cant
(5
6.4 ±
5.9
vs.
56. ±
4.7;
p =
0.72
) af
ter p
atie
nts i
n th
e IR
gro
up h
ad a
lso
rece
ived
rout
ine
phar
mac
eutic
al
care
. Bes
ides
, ser
um
crea
tinin
e le
vel o
f th
e R
E pa
tient
s w
as st
able
with
out
sign
ifica
nt v
aria
-tio
n (p
= 0.
93),
but i
t de
mon
strat
ed a
risi
ng
trend
in IR
pat
ient
s (p
< .0
1). P
atie
nts
satis
fact
ory
with
th
e in
terv
entio
n w
as
95.2
%
ADEs
adv
erse
dru
g eff
ects
, BP
bloo
d pr
essu
re, C
I co
nfide
nce
inte
rval
, CK
D c
hron
ic k
idne
y di
seas
e, C
rCl c
reat
inin
e cl
eara
nce,
CRR
T co
ntin
uous
ren
al r
epla
cem
ent t
hera
py, C
VVH
Con
tinu-
ous
Veno
-Ven
ous
Hem
ofiltr
atio
n, D
RPs
drug
rela
ted
prob
lem
s, ES
A Er
ythr
opoi
esis
stim
ulat
ing
agen
t, G
Ps g
ener
al p
ract
ition
ers,
HD
hae
mod
ialy
sis,
HRQ
oL h
ealth
-rel
ated
qua
lity
of li
fe, I
CG
in
tens
ified
car
e gr
oup,
ICU
inte
nsiv
e ca
re u
nit,
KD
IGO
kid
ney
dise
ase:
Impr
ovin
g gl
obal
out
com
es, M
TM m
edic
atio
n th
erap
y m
anag
emen
t, N
DD
-CK
D n
on-d
ialy
sis
depe
ndan
t chr
onic
kid
ney
dise
ase,
OR
odds
ratio
, PTH
par
athy
roid
hor
mon
e, S
BP sy
stolic
blo
od p
ress
ure,
SC
G st
anda
rd c
are
grou
p, T
x tra
nspl
anta
tion,
UC
usu
al c
are
649International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
Cha
ract
erist
ics o
f unc
ontro
lled
studi
es in
clud
ed in
the
syste
mat
ic re
view
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Kel
ly e
t al.
(200
8)U
nite
d K
ingd
om [4
3]Pr
ospe
ctiv
e un
con-
trolle
d stu
dy
(18
mon
ths)
Dia
bete
s uni
t of a
se
cond
ary
hosp
ital
To o
ffer s
tepw
ise
inte
nsiv
e tre
atm
ent
to p
atie
nts w
ith
diab
etic
nep
hrop
a-th
y pi
cked
up
at th
e tra
ditio
nal s
econ
d-ar
y ca
re c
linic
116
diab
etic
nep
hrop
-at
hy p
atie
nts
63.4
(8.6
)Fr
eque
nt v
isits
to
phar
mac
ist le
d cl
inic
for t
reat
men
t op
timis
atio
n, c
heck
-in
g of
BP,
rena
l fu
nctio
n, H
bA1c
, A
CR
, FB
C, c
alci
um
and
phos
phat
e.
Med
ical
hist
ory
tak-
ing
by tw
o so
urce
s
Sign
ifica
nt im
prov
e-m
ents
in B
P (p
< 0.
001)
, tot
al c
ho-
leste
rol (
p < 0.
001)
an
d H
bA1c
(p <
0.05
)
Das
hti-K
havi
daki
et
al.
(200
9)Ir
an [5
1]
Pros
pect
ive
unco
n-tro
lled
study
(1
2 m
onth
s)
Nep
hrol
ogy
and
infe
c-tio
us d
isea
se w
ards
of
a la
rge
univ
ersi
ty
hosp
ital
To u
nder
stan
d th
e ty
pes o
f ser
vice
s pr
ovid
ed b
y cl
inic
al
phar
mac
ists i
n ne
ph-
rolo
gy a
nd in
fec-
tious
dis
ease
war
ds,
the
acce
ptan
ce b
y ph
ysic
ians
and
the
clin
ical
sign
ifica
nce
of th
ese
serv
ices
1105
CK
D p
atie
nts
52.5
(14.
1)U
nifo
rm d
ocum
enta
-tio
n of
all
clin
ical
ph
arm
acy
resi
dent
s ac
tiviti
es a
nd in
ter-
vent
ions
Not
repo
rted
Vess
al (2
010)
Iran
[17]
Pros
pect
ive
unco
n-tro
lled
study
(4
mon
ths)
Nep
hrol
ogy
war
d of
a
univ
ersi
ty h
ospi
tal
To d
eter
min
e th
e im
pact
of a
clin
ical
ph
arm
acist
on
dete
c-tio
n an
d pr
even
tion
of p
resc
riptio
n er
rors
at t
he n
eph-
rolo
gy w
ard
of a
re
ferr
al h
ospi
tal
76 C
KD
pat
ient
s47
.7 (1
7.2)
CP
revi
ewed
med
ica-
tion
orde
rs a
nd
inte
rven
tion
was
m
ade
afte
r agr
ee-
men
t of t
he a
ttend
-in
g ph
ysic
ian
Alth
ough
89.
5% o
f th
e de
tect
ed e
rror
s ca
used
no
harm
, 4(
4.7%
) of t
he e
rror
s in
crea
sed
the
need
for
mon
itorin
g, 2
(2.3
%)
incr
ease
d le
ngth
of
stay
, and
2 (2
.3%
) led
to
per
man
ent p
atie
nt
harm
Cas
telin
o et
al.
(201
1)In
dia
[29]
Pros
pect
ive
unco
n-tro
lled
study
(8
mon
ths)
Dep
artm
ent o
f nep
h-ro
logy
of a
teac
hing
ho
spita
l
To e
xplo
re th
e po
ten-
tial c
linic
al si
gnifi
-ca
nce
of th
e M
RPs
an
d th
e ac
cept
ance
of
reco
mm
enda
tions
m
ade
by c
linic
al
phar
mac
ists
308
CKD
pat
ient
sN
RM
edic
atio
n hi
story
in
terv
iew
, clin
ical
an
d m
edic
atio
n re
view
by
phar
ma-
cist.
Rec
omm
enda
-tio
n w
ere
repo
rted
to th
e he
alth
car
e te
am
Not
repo
rted
650 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Ohn
ishi
et a
l. (2
011)
Japa
n [3
4]Re
trosp
ectiv
e un
cont
rolle
d stu
dy
(12
mon
ths)
Out
patie
nt h
aem
odia
l-ys
is u
nit o
f a te
rtiar
y ho
spita
l
To e
xplo
re th
e ro
le
of th
e ph
arm
a-ci
sts’ p
artic
ipa-
tion,
we
exam
ined
th
e in
fluen
ce o
f ha
emog
lobi
n le
vels
an
tero
poste
rior t
he
parti
cipa
tion
84 H
D p
atie
nts
62Ph
arm
acist
s pro
vide
d dr
ug in
form
atio
n on
rena
l ana
emia
to
phy
sici
ans,
perfo
rmed
med
ica-
tion
use
eval
uatio
ns
base
d on
labo
rato
ry
data
, pro
pose
d pl
ans
to c
hang
e pr
escr
ip-
tions
bas
ed o
n m
edi-
catio
n us
e ev
alua
-tio
ns a
nd p
rovi
ded
drug
info
rmat
ion
and
lifes
tyle
car
e po
int t
o pa
tient
s
The
coun
selli
ng b
y ph
arm
acist
s sig
-ni
fican
tly d
ecre
ased
ha
emog
lobi
n le
vels
in
the
high
gro
up (1
2 g/
dl) a
nd si
gnifi
cant
ly
incr
ease
d th
em in
low
gr
oup
(10
g/dL
)
Bel
aich
e et
al.
(201
2a)
Fran
ce [2
1]
Pros
pect
ive
unco
n-tro
lled
study
(6
mon
ths)
Uni
vers
ity h
ospi
tal
base
d ne
phro
logy
cl
inic
To id
entif
y D
RPs
by
a tra
ined
CP,
thei
r fr
eque
ncy
and
asso
-ci
ated
com
orbi
ditie
s
67 C
KD
pat
ient
s70
The
CP
inte
r-vi
ewed
pat
ient
s an
d es
tabl
ishe
d a
phar
mac
olog
ical
pr
ofile
, che
cked
for
drug
–dru
g in
tera
c-tio
ns, v
erifi
ed d
ose
adap
tatio
n ac
cord
-in
g to
the
last
rena
l fu
nctio
n te
sts a
nd
sear
ched
for s
elf-
med
icat
ion
and
its
pote
ntia
l nep
hrot
ox-
icity
. The
pha
rma-
ceut
ical
pro
posa
ls
wer
e va
lidat
ed
with
the
cons
ultin
g ne
phro
logi
st so
as
to o
ptim
ise
ther
apy
durin
g th
e fo
llow
ing
rena
l con
sulta
tion
Not
repo
rted
Bel
aich
e et
al.
(201
2b)
Fran
ce [2
8]
Retro
spec
tive
unco
ntro
lled
study
(1
5 m
onth
s)
Nep
hrol
ogy
clin
ics o
f a
univ
ersi
ty h
ospi
tal
To a
sses
s the
impa
ct
of c
linic
al p
harm
acy
serv
ices
in o
utpa
-tie
nt n
ephr
olog
y cl
inic
s
42 C
KD
pat
ient
s64
.9 (2
.2)
Iden
tifica
tion
of
DR
Ps b
y C
P an
d do
cum
enta
tion
of
reco
mm
enda
tions
Not
repo
rted
651International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Das
hti-K
havi
daki
et
al.
(201
2)Ir
an [2
3]
Pros
pect
ive
unco
n-tro
lled
study
(6
mon
ths)
Hae
mod
ialy
sis t
reat
-m
ent c
entre
of a
te
achi
ng h
ospi
tal
To a
sses
s the
impa
ct
of c
linic
al p
harm
acy
serv
ices
on
the
man
-ag
emen
t of s
econ
d-ar
y co
mpl
icat
ions
in
patie
nts w
ho w
ere
on H
D, i
nclu
ding
bo
ne m
etab
olis
m
diso
rder
s, an
aem
ia
and
dysl
ipid
aem
ia
86 H
DN
RC
P re
view
ed p
atie
nts
med
icat
ions
and
pr
opos
ed m
odifi
ca-
tion
acco
rdin
g to
la
bora
tory
dat
a re
sults
to tr
eatin
g ph
ysic
ians
Seru
m C
alci
um w
as
incr
ease
d in
hyp
ocal
-ca
emia
pat
ient
s and
de
crea
sed
in h
yper
-ca
lcae
mia
pat
ient
s un
til it
reac
hed
the
optim
al ra
nge
in b
oth
grou
psA
dec
line
in se
rum
Ph
osph
ate
leve
l was
no
ted
in h
yper
phos
-ph
atae
mia
pat
ient
sTh
ere
was
an
incr
ease
an
d de
crea
se in
seru
m
iPTH
in su
bopt
imal
an
d su
prao
ptim
al
rang
e pa
tient
s, re
spec
tivel
yH
aem
oglo
bin
con-
cent
ratio
n in
crea
sed
in a
naem
ic p
atie
nts
and
seru
m fe
rriti
n re
ache
d ta
rget
val
ues
in a
ll pa
tient
s. To
tal
chol
este
rol,
low
-de
nsity
lipo
prot
ein
chol
este
rol a
nd tr
i-gl
ycer
ides
dec
reas
ed
to n
ear-o
ptim
al v
alue
s in
dys
lipid
aem
ia
patie
nts
652 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Gee
rts e
t al.
(201
2)N
ethe
rland
s [33
]Pr
ospe
ctiv
e un
con-
trolle
d stu
dy
(unc
lear
)
Prim
ary
heal
th c
are
To a
sses
s the
th
erap
eutic
adv
ice
form
ulat
ed b
y ph
ar-
mac
ists w
ith h
elp
of
a ph
arm
acy
med
ica-
tion
aler
t sys
tem
ba
sed
on th
e re
nal
func
tion
of p
atie
nts
aged
≥ 70
yea
rs w
ith
diab
etes
or c
ardi
o-va
scul
ar d
isea
se
650
CKD
pat
ient
s81
(6.7
)Th
e ph
arm
acist
s use
d a
phar
mac
y m
edic
a-tio
n al
ert s
yste
m to
as
sess
the
med
ica-
tion
in re
latio
n to
th
e re
porte
d eG
FR
and
prov
ided
an
aler
t for
targ
et d
rugs
ac
cord
ing
to th
e D
utch
gui
delin
es fo
r dr
ug a
dmin
istra
tion
in re
duce
d re
nal
func
tion
Not
repo
rted
Abu
Ruz
et a
l. (2
013)
Jord
an [3
7]Pr
ospe
ctiv
e un
con-
trolle
d stu
dy
(3 m
onth
s)
Nep
hrol
ogy
war
d of
a
gene
ral t
each
ing
hosp
ital
To im
plem
ent a
nd
eval
uate
the
impa
ct
of p
harm
aceu
tical
ca
re se
rvic
e fo
r ho
spita
lised
CK
D
patie
nts i
n Jo
rdan
130
CKD
pat
ient
s56
.3 (1
7.8)
The
phar
mac
ist
Iden
tified
TR
Ps
and
inte
rven
tions
w
ere
disc
usse
d du
ring
war
d ro
unds
. Pa
tient
s edu
catio
n an
d in
terv
iew
to
impr
ove
patie
nt
adhe
renc
e
17%
of a
ll TR
Ps w
ere
reso
lved
, 5.5
%w
ere
impr
oved
, and
37
.4%
wer
e pr
even
ted
thro
ugh
the
clin
ical
ph
arm
acist
inte
rven
-tio
ns
Che
n (2
013)
Sing
apor
e [2
5]Pr
ospe
ctiv
e un
con-
trolle
d stu
dy
(5 m
onth
s)
Hae
mod
ialy
sis c
entre
of
a g
ener
al h
ospi
tal
To e
valu
ate
the
prev
alen
ce o
f DR
Ps
iden
tified
and
the
type
s of i
nter
ven-
tions
mad
e by
MM
S ph
arm
acist
s
30 H
D62
.3 (1
0.0)
Patie
nts r
eque
sted
to
brin
g th
eir m
edic
a-tio
n an
d se
e th
e ph
arm
acist
bef
ore
the
appo
intm
ent
with
thei
r phy
sici
an.
Phar
mac
ist re
view
ed
patie
nts r
ecor
ds,
coun
sel t
he p
atie
nts,
iden
tified
and
re
porte
d D
RPs
Not
repo
rted
653International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Jiang
et a
l. (2
013)
Japa
n [3
8]Pr
ospe
ctiv
e un
con-
trolle
d stu
dy
(24
mon
ths)
Med
ical
and
surg
ical
IC
U o
f a u
nive
rsity
-affi
liate
d ho
spita
l
To e
valu
ate
the
ben-
efits
that
may
resu
lt fro
m in
volv
ing
phar
-m
acist
s in
the
care
of
sept
ic p
atie
nts
rece
ivin
g C
RRT
144
Pre-
inte
rven
tion
(71
patie
nts)
Post-
inte
rven
tion
(73
patie
nts)
CR
RT
Pre-
inte
rven
tion:
62.
3 (1
7.0)
Post-
inte
rven
tion:
57
.9 (1
5.4)
Phar
mac
ists c
om-
plet
ed 1
mon
th o
f tra
inin
g be
fore
the
study
was
star
ted
Dur
ing
the
inte
r-ve
ntio
n pe
riod,
th
e ph
arm
acist
s as
sess
ed se
ptic
pa
tient
s rec
eivi
ng
CR
RT d
aily
and
ad
juste
d th
e do
sage
of
ant
imic
robi
al
drug
s whe
n ne
eded
. Re
com
men
datio
ns
wer
e m
ade
to p
hysi
-ci
ans a
nd n
urse
s at
that
tim
e. A
ll ph
ar-
mac
ist re
com
men
-da
tions
wer
e ve
rbal
an
d re
cord
ed o
n a
spec
ially
des
igne
d ph
arm
acist
inte
rven
-tio
n fo
rm
Dos
ing
adju
stmen
ts
wer
e re
late
d to
a
redu
ced
leng
th
of IC
U st
ay fr
om
10.7
± 11
.1 d
ays
to 7
.7 ±
8.3
days
(p
= 0.
037)
in th
e in
terv
entio
n gr
oup,
an
d to
cos
t sav
-in
gs o
f 352
5 U
SD
(13,
463 ±
12,0
45
vs. 9
938 ±
8811
, p =
0.03
8) p
er se
ptic
pa
tient
rece
ivin
g C
RRT
in th
e IC
USu
spec
ted
antim
icro
bial
ad
vers
e dr
ug e
vent
s in
the
inte
rven
tion
grou
p w
ere
sign
ifi-
cant
ly fe
wer
than
in
the
pre-
inte
rven
tion
grou
p (1
9 ev
ents
vs.
8 ev
ents
, p =
0.04
8)D
osin
g er
ror e
vent
s w
ere
sign
ifica
ntly
fe
wer
in th
e po
st-in
terv
entio
n ph
ase
than
in th
e pr
e-in
ter-
vent
ion
phas
e (5
4 in
73
pat
ient
s vs.
194
in
71 p
atie
nts,
p < 0.
001)
654 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Mou
savi
et a
l. (2
013)
Iran
[22]
Retro
spec
tive/
Pros
pect
ive
unco
ntro
lled
study
(1
2 m
onth
s)
Uni
vers
ity h
ospi
tal
base
d ne
phro
logy
w
ards
To e
valu
ate
appr
o-pr
iate
ness
of a
cid
supp
ress
ion
ther
apy
in k
idne
y di
seas
e pa
tient
s and
to
asse
ss th
e ro
le o
f cl
inic
al p
harm
acist
s to
dec
reas
e in
appr
o-pr
iate
SU
P pr
escr
ib-
ing
and
rela
ted
costs
fo
r the
se p
atie
nts
Pre-
test
phas
e (3
75
patie
nts)
Post-
test
phas
e (2
36
patie
nts)
Pre-
test
phas
e 51
.2
(18.
3)Po
st-te
st ph
ase
50.2
(1
8.8)
Pre-
inte
rven
tion
phas
e: p
atie
nt c
hart
revi
ew b
y C
P,
deve
lop
SUP
pro-
toco
l, an
d pr
ovid
e ed
ucat
iona
l ses
sion
s to
doc
tors
on
SUP
Post-
inte
rven
tion
phas
e: C
linic
al
phar
mac
ists a
ccom
-pa
nied
phy
sici
ans
on th
e w
ard
roun
ds
and
advi
sed
on
star
ting
or st
oppi
ng
SUP
Not
repo
rted
Ran
i et a
l. (2
013)
Indi
a [5
0]Pr
ospe
ctiv
e un
con-
trolle
d stu
dy
(3 m
onth
s)
Dia
lysi
s uni
t of a
mul
-tis
peci
alty
uni
vers
ity
hosp
ital
To a
sses
s the
med
ica-
tion
know
ledg
e of
CK
D p
atie
nts u
nder
-go
ing
HD
, to
asse
ss
the
effec
t of a
CP
prov
ided
con
tinuo
us
patie
nt e
duca
tion
in
impr
ovin
g m
edic
a-tio
n ad
here
nce
and
to e
valu
ate
the
asso
ciat
ion
betw
een
med
icat
ion
know
l-ed
ge a
nd m
edic
atio
n ad
here
nce
beha
viou
r in
HD
pat
ient
s
85 H
D p
atie
nts
50.5
2 (1
3.28
)Pa
tient
cou
nsel
ling
and
educ
atio
n (v
er-
bally
and
writ
ten)
. Pa
tient
inte
rvie
w to
as
sess
med
icat
ion
know
ledg
e us
ing
MK
AQ
. To
asse
ss
med
icat
ion
adhe
r-en
ce p
atte
rn u
sing
B
MQ
Not
repo
rted
655International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Abe
rger
et a
l. (2
014)
USA
[41]
Pros
pect
ive
unco
n-tro
lled
study
(4
wee
ks)
Tran
spla
nt c
linic
of a
la
rge
urba
n ho
spita
lTo
des
crib
es a
te
lehe
alth
syste
m
appr
oach
and
pr
elim
inar
y re
sults
fo
r the
man
agem
ent
of B
P in
rena
l tra
ns-
plan
t rec
ipie
nts a
nd
to e
nhan
ce p
atie
nt
enga
gem
ent a
nd
impr
ove
adhe
renc
e to
med
icat
ions
via
a
colla
bora
tive
care
, ph
arm
acist
-bas
ed,
MTM
pro
gram
66 T
x pa
tietn
s54
Tele
heal
th sy
stem
en
com
pass
ing:
ho
me
elec
troni
c B
P m
onito
ring
desi
gned
to
ass
ess t
he e
ffica
cy
of a
ntih
yper
tens
ive
ther
apy.
The
pha
r-m
acist
com
mun
i-ca
tes B
P re
adin
g da
ta a
nd d
ose
mod
ifica
tions
to th
e ph
ysic
ian
Stat
istic
ally
sign
ifica
nt
redu
ctio
ns in
aver
age
systo
lic a
nd d
iasto
lic
BP
of 6
.0 m
m H
g an
d 3.
0 m
m H
g, re
spec
-tiv
ely,
at 3
0 da
ys a
fter
enro
lmen
t (p <
0.01
)
Arr
abal
-Dur
án e
t al.
(201
4)Sp
ain
[26]
Pros
pect
ive
unco
n-tro
lled
study
(1
0 m
onth
s)
Hos
pita
l war
ds a
nd
emer
genc
y de
part-
men
t of a
gen
eral
un
iver
sity
hos
pita
l
To a
sses
s the
cha
rac-
teris
tics o
f pha
rma-
ceut
ical
inte
rven
-tio
ns c
once
rnin
g th
e do
se a
djus
tmen
t of
thes
e dr
ugs i
n pa
tient
s with
CR
F w
ho a
re a
dmitt
ed
into
hos
pita
l
181
CKD
pat
ient
s77
.6 (1
2.5)
Med
ical
hist
ory
of
each
pat
ient
was
re
view
ed b
y C
P,
reco
mm
enda
tions
fo
r an
adju
stmen
t w
ere
put i
n w
ritin
g fo
r the
doc
tors
Not
repo
rted
Bar
nes e
t al.
(201
4)U
SA [2
7]Re
trosp
ectiv
e un
cont
rolle
d stu
dy
(12
mon
ths)
Prim
ary
care
setti
ng,
Patie
nt -C
entre
d M
edic
al H
ome
asso
-ci
ated
with
a m
ajor
, ac
adem
ic h
ealth
sy
stem
To in
crea
se th
e id
en-
tifica
tion
of C
KD
as
a m
edic
al p
robl
em,
incr
ease
the
use
of
aspi
rin a
nd A
CEI
s/A
RB
s in
patie
nts
with
CK
D, a
nd
ensu
re th
at a
ll m
edi-
catio
ns p
resc
ribed
to
pat
ient
s with
CK
D w
ere
dose
d ap
prop
riate
ly b
ased
on
CG
cal
cula
ted
CrC
l
146
CKD
pat
ient
s71
.6 (1
2.2)
Revi
ew E
MR
s to
iden
tify
CKD
pa
tient
s, re
view
m
edic
atio
n lis
t, es
timat
e C
rCl a
nd
reco
mm
enda
tions
re
porti
ng to
the
phys
icia
ns
Not
repo
rted
656 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Ghe
ewal
a et
al.
(201
4)A
ustra
lia [1
9]
Retro
spec
tive
unco
ntro
lled
study
(1
2 m
onth
s)
Age
d ca
re fa
cilit
ies
To in
vesti
gate
the
num
ber a
nd n
atur
e of
DR
Ps id
enti-
fied
and
reco
m-
men
datio
ns m
ade
by p
harm
acist
s in
resi
dent
s of a
ged
care
faci
litie
sTo
det
erm
ine
the
exte
nt o
f ina
ppro
-pr
iate
pre
scrib
ing
of re
nally
cle
ared
m
edic
atio
ns in
resi
-de
nts w
ith C
KD
847
CKD
pat
ient
s84
.9 (8
.8)
DR
Ps id
entifi
ed, a
nd
reco
mm
enda
tions
m
ade
to re
solv
e th
ose
DR
Ps b
y C
P
Not
repo
rted
Hol
m e
t al.
(201
5)N
orw
ay [2
4]Pr
ospe
ctiv
e un
con-
trolle
d stu
dy
(6 m
onth
s)
Inte
rnal
med
icin
e de
partm
ent o
f a
gene
ral h
ospi
tal
To d
escr
ibe
the
use
of re
nal r
isk
drug
s in
a p
opul
atio
n of
pa
tient
s with
RI i
n an
inte
rnal
med
icin
e de
partm
ent a
nd
inve
stiga
te p
ossi
ble
risk
fact
ors f
or su
ch
DR
Ps
79 C
KD
pat
ient
s78
.7 (1
0.2)
The
CP
revi
ewed
th
e pa
tient
s’ d
rug
regi
men
to c
lass
ify
DR
Ps re
late
d to
re
nal f
unct
ion.
D
RPs
iden
tified
w
ere
disc
usse
d w
ith
the
phys
icia
n
Ther
e w
as a
sign
ifica
nt
corr
elat
ion
betw
een
the
patie
nts’
GFR
and
th
e nu
mbe
r of D
RPs
, w
ith a
n in
crea
sing
nu
mbe
r of D
RPs
with
de
terio
ratin
g re
nal
func
tion
(p =
0.00
1,
r = 0.
371)
Pour
rat e
t al.
(201
5)Fr
ance
[16]
Pros
pect
ive
unco
n-tro
lled
study
(7
mon
ths)
Com
mun
ity p
harm
a-ci
es(1
) To
eval
uate
the
abili
ty o
f com
mu-
nity
pha
rmac
ists t
o id
entif
y dr
ug re
late
d pr
oble
ms (
DR
P) in
pa
tient
s at r
isk
for o
r su
fferin
g fro
m re
nal
impa
irmen
t. (2
) To
eval
uate
the
prop
or-
tions
of r
ecom
men
-da
tions
by
CPs
that
le
ad to
a m
odifi
ca-
tion
by G
P
177
CKD
pat
ient
s78
.1Th
e co
mm
unity
ph
arm
acist
fille
d an
el
ectro
nic
form
for
each
pre
scrip
tion
and
verif
y w
heth
er
the
drug
had
to b
e ad
apte
d to
rena
l fu
nctio
n or
was
co
ntra
indi
cate
dPo
tent
ial m
odifi
catio
n w
as p
ropo
sed
to
the
GP
Not
repo
rted
657International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Venk
ates
war
arao
et
al.
(201
5)In
dia
[49]
Pros
pect
ive
unco
n-tro
lled
study
(6
mon
ths)
Dia
lysi
s uni
t of a
te
achi
ng h
ospi
tal
To e
valu
ate
the
patie
nt p
erce
p-tio
n an
d de
gree
of
adhe
renc
e to
var
ious
tre
atm
ent m
odal
ities
(m
edic
atio
n us
e,
dial
ysis
, life
styl
e m
odifi
catio
ns) b
y re
nal f
ailu
re p
atie
nts
on H
DTo
ass
ess t
he e
ffect
of
phar
mac
ist’s
inte
r-ve
ntio
ns to
war
ds
impr
ovin
g th
e ad
here
nce
amon
g th
e stu
dy p
opul
atio
n
58 H
D p
atie
nts
46.7
(13.
3)Pa
tient
cou
nsel
ling
once
in 2
wee
ks
(tota
l 3 se
ssio
ns)
was
pro
vide
d.
Prin
ted
info
rma-
tion
leafl
ets a
nd
writ
ten
info
rmat
ion
on d
ialy
sis n
ote
in
regi
onal
lang
uage
w
ere
prov
ided
to th
e pa
tient
s. A
dher
ence
pa
ttern
bef
ore
and
afte
r pat
ient
edu
ca-
tiona
l int
erve
ntio
n w
as a
sses
sed
Not
repo
rted
Patri
cia
and
Foot
e (2
016)
USA
[46]
Pros
pect
ive
unco
n-tro
lled
study
(1
7 m
onth
s)
Regi
onal
dia
lysi
s uni
tsTo
iden
tify
the
exte
nt
and
type
of m
edic
a-tio
n di
scre
panc
ies
and
MR
Ps e
xper
i-en
ced
by d
ialy
sis
patie
nts d
urin
g ph
arm
acist
-initi
ated
m
edic
atio
n re
view
s an
d de
term
ine
if th
e re
sulti
ng re
com
-m
enda
tions
mad
e by
th
e ph
arm
acy
team
to
the
patie
nt’s
pro
-vi
der w
ere
acce
pted
90 H
DN
RPa
tient
s req
ueste
d to
br
ing
thei
r med
ica-
tion
to d
ialy
sis
unit
and
med
ica-
tion
reco
ncili
atio
n co
nduc
ted
by th
e ph
arm
acy
team
Not
repo
rted
Ram
adan
iati
et a
l. (2
016)
Indo
nesi
a [3
1]
Pros
pect
ive
unco
n-tro
lled
study
(3
mon
ths)
Med
ical
war
ds a
nd
an IC
CU
in a
maj
or
teac
hing
hos
pita
l
To id
entif
y an
d ev
alu-
ate
drug
-rel
ated
pr
oble
ms (
DR
Ps) i
n pa
tient
s with
CK
D
105
CKD
NR
Iden
tifica
tion
of D
RPs
th
roug
h th
e di
rect
pa
tient
inte
rvie
w,
disc
ussi
on w
ith
nurs
es a
nd a
sses
s-m
ent o
f pat
ient
s’
med
icat
ion
char
ts
and
med
ical
reco
rds
Not
repo
rted
658 International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
d)
Stud
y ye
arC
ount
rySt
udy
desi
gn (d
ura-
tion)
Stud
y se
tting
Aim
Parti
cipa
nts
Phar
mac
ist in
terv
en-
tions
Mai
n cl
inic
al o
utco
mes
ac
hiev
edN
(at b
asel
ine)
Age
(yea
rs),
mea
n (S
D)
Adi
be e
t al.
(201
7)N
iger
ia [4
2]Pr
ospe
ctiv
e un
con-
trolle
d stu
dy
(5 m
onth
s)
Nep
hrol
ogy
units
of
thre
e te
rtiar
y ho
spita
ls
To d
eter
min
e th
e pr
eval
ence
of D
TPs,
iden
tify
the
type
s of
DTP
s, an
d as
sess
th
e ou
tcom
es o
f D
TP in
terv
entio
ns
amon
g re
nal p
atie
nts
rece
ivin
g ca
re in
th
ree
Nig
eria
n te
rtiar
y ho
spita
ls
287
patie
nts w
ith
rena
l illn
esse
s72
.34
(7.5
6)Id
entif
y an
d re
port
DR
Ps. P
atie
nt
educ
atio
n an
d co
un-
selli
ng
Not
repo
rted
Als
ham
rani
et a
l. (2
018)
Saud
i Ara
bia
[59]
Retro
spec
tive
unco
ntro
lled
study
(3
mon
ths)
Out
patie
nt h
aem
odia
l-ys
is u
nit o
f a te
rtiar
y ho
spita
l
To d
eter
min
e th
e pr
eval
ence
of p
oly-
phar
mac
y an
d th
e M
edic
atio
n Re
late
d Pr
oble
ms i
n ha
emo-
dial
ysis
pat
ient
s
83 H
D p
atie
nts
Med
ian
age
63, I
QR
(4
9–1)
The
phar
mac
y re
side
nt re
view
ed
elec
troni
c m
edic
al
reco
rds a
nd a
naly
sed
each
med
icat
ion
regi
men
for e
ligib
le
patie
nts t
o id
entif
y M
RPs
Not
repo
rted
Cha
ndra
sekh
ar e
t al.
(201
8)In
dia
[60]
Pros
pect
ive
inte
r-ve
ntio
nal s
tudy
(1
2 m
onth
s)
Out
patie
nt n
ephr
olog
y de
partm
ent
To e
valu
ate
med
ica-
tion
adhe
renc
e be
havi
our o
f pa
tient
s usi
ng
ques
tionn
aire
and
en
hanc
e ad
here
nce
by v
ario
us c
ost
effec
tive
inte
rven
-tio
ns w
hich
hav
e gr
eate
r effe
ct o
n th
e he
alth
of p
atie
nts
with
CK
D
163
CKD
pat
ient
s–
Patie
nt c
ouns
ellin
g by
pha
rmac
ist a
nd
patie
nt in
form
atio
n le
aflet
was
car
ried
out u
sing
a p
rope
r m
anag
emen
t pla
n an
d w
ith th
e he
lp
of p
hysi
cian
and
fe
edba
ck in
form
a-tio
n w
as c
olle
cted
Not
repo
rted
659International Journal of Clinical Pharmacy (2019) 41:630–666
1 3
Tabl
e 2
(con
tinue
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660 International Journal of Clinical Pharmacy (2019) 41:630–666
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and ten non-randomised. According to Thomson Reuters Journal Citation Report at the time of publication the median impact factor of the journals of articles included was 1.348 (IQR 0.52–2.01), n = 45, two journals did not have an impact factor at the time of publication.
Patient mean age was 46.7–84.9 years, with five stud-ies failing to report age [23, 29, 31, 46, 60]. Of the total of 11,122 patients from all studies, 9151 were at various stages of chronic kidney disease not on dialysis, 1036 were haemo-dialysis (HD) dependent, 533 receiving other forms of renal replacement therapies such as continuous renal replacement therapy (CRRT) or continuous veno-venous hemofiltration (CVVH), and 402 were transplant patients.
Outcomes were reported in 37 papers, with 25 of these (67.6%) also reporting details of the processes of care, and four (10.8%) reporting structures, processes and out-comes. Outcomes reported were: clinical only (17, 45.9%), economic with linked clinical (5, 13.5%), humanistic with linked clinical (4, 10.8%), humanistic only (2, 5.4%) and economic only (2, 5.4%). The 10 remaining papers did not report outcomes measures with one (2.1%) that reported structure and process indicators only and 9 (19.1%) reported process indicators only.
Resources for care provision: structures
Structures were poorly reported in all studies, with only two giving some details of multidisciplinary team involvement [52, 61], while, none on the pharmacist skill mix or time allocation. The only aspect of structures reported relating to training which was given in five studies. In one, pharmacists and pharmacy residents were engaged in a two-week training of literature review and patient assessments [35]. A com-munity pharmacist based study described a workshop cov-ering clinical presentations of CKD, managing drug-related problems and discussing patient cases [48]. Similar training was described for community pharmacists, [18] and hospital clinical pharmacists [16], to enable them to identify patients with renal insufficiency and perform dose adjustments. A four session course to all members of the multidisciplinary team prior to the study was described in one article [61].
Characteristics of clinical pharmacy practice: processes
All studies provided some description of the processes undertaken by the pharmacists, although the detail pro-vided varied considerably and was generally lacking. The majority of processes (often labelled as interventions) included medication chart review to identify any drug-related problems (DRPs) [15–31]. Many studies reported pharmacists’ interventions in: modifying drug doses and recommending new pharmacotherapy; [16, 19, 21–23,
25–27, 29, 30, 32–40, 52, 59]; interacting with a member of the multidisciplinary team; [15–17, 19–21, 23–25, 27, 31, 32, 34–38, 40–43] requesting and monitoring labo-ratory parameters; [15, 23, 25, 27, 33, 34, 36, 37, 43] assessing appropriateness of medications prescribed for hospitalised patients at each point of care; [17, 22, 29, 30, 35–38, 40, 57]. Fewer studies described pharmacist processes at out-patient, pharmacist-led clinics relating to the management of specific CKD complications, such as anaemia; [34, 39, 44] hypertension and diabetes; [54] managing hypertension through telemedicine; [41] opti-mising dyslipidaemia management; [37, 45] improving haemoglobin A1c levels (HbA1c); [43] and emphasising smoking cessation. [37, 43] Development of protocols and compiling and updating guidelines were also described in two studies [22, 34]. Performing medication reconciliation [46]; providing patient medication counselling, education on disease status or medication, conducting motivational interviews to improve adherence were also reported [15, 25, 27, 29, 30, 34, 36, 37, 42, 43, 47–50, 55, 57, 58, 60]. A number of studies reported pharmacists’ participation in ward rounds [17, 22, 35, 37, 38, 40], providing educational sessions to healthcare professionals [22, 34] and perform-ing activities such as medication use evaluations [34]. There were no reports of pharmacist prescribing activi-ties; one study described the process of deprescribing to optimise medication use [59].
Fewer studies provided any data on time spent on specific activities. Interaction time between pharmacist and patients were reported in two studies, varying from 15 to 30 min [43, 50] and the timeframe in which the services were provided ranged from daily [35–38, 40] to every three months [47].
Across all studies, the pharmacists identified 5302 drug-related problems in 2933 patients. Pharmacists made 3160 recommendations to healthcare professionals with an accept-ance rate varying from 33.3% in a community setting; [16] 46.43% in a dialysis unit; [59] to around 95% in hospital settings [17, 24, 42, 51, 52, 57]. Only three studies reported the clinical significance of recommendations. Of these 26% were of moderate to [29], 48.8% of major clinical signifi-cance [51] and 47% serious severity [20].
A pharmacist-based quality improvement programme consisting of pharmacists’ interactions with the patients and electronic collaboration with the physicians was associated with a significant improvement in the measurement of PTH during the study period [15]. Pharmacists’ interventions led to medication therapy modifications [16–21, 24–29, 31, 33, 37, 42, 46] and resolving medication record discrepancies [46, 57]. Patients’ compliance with ongoing blood pressure (BP) monitoring post kidney transplantation was signifi-cantly improved with pharmacists’ input [41]. Counselling by pharmacists significantly improved medication adherence in patients with CKD [47, 50, 60].
661International Journal of Clinical Pharmacy (2019) 41:630–666
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Clinical outcomes
The final column of Tables 1 and 2 titled ‘Main outcomes achieved’ provides a detailed summary of main results and statistical significance values related to each of the studies summarised below. Clinical outcomes only were reported in (n = 17) studies. A pharmacist-based quality improve-ment programme in a pragmatic randomised controlled study reported that patients in the intervention arm were prescribed more classes of antihypertensive medications than those in the control arm [15]. In a 6-month cluster randomised trial, pharmacists attending a structured train-ing and communication-network programme (ProFil) and managing hypertension in CKD patients demonstrated larger reduction in systolic blood pressure (BP) of the intervention group compared to the usual care group [48].
Intervention in the management of BP in CKD and hae-modialysis resulted in achieving target BP in the inter-vention versus the control group [32, 54, 55], significant reductions in mean systolic and diastolic BP in a group of kidney transplant recipients [41], and significant reduc-tion in systolic and diastolic BP in diabetic nephropathy [43]. Only one article showed that pharmacists’ interven-tion in an intensive care unit (ICU) setting reduced the length of ICU stay [38]. Another study reported reduc-tion in the length of stay in the intervention group by 1.3 days (p < 0.001) and reduced unplanned admission by 27% (p = 0.047) [52]. One further study showed no dif-ference of pharmacists’ intervention compared to usual care on hospital readmission outcomes [57]. Pharmacists were also involved in the monitoring of kidney function in patients with CKD and demonstrated significant differ-ences in measuring CrCl between discharge and admission [36]. However, one study demonstrated no difference in the mean serum creatinine or estimated glomerular fil-tration rate (eGFR) between the intervention and control groups [58]. A retrospective controlled study reported improvement in eGFR, uric acid, cholesterol and HbA1c in the intervention group compared to the control group after multidisciplinary care, however, pharmacists’ contribution to the care was not clearly reported [61].
Four studies gave outcomes of pharmacists managing anaemia in CKD patients [34, 39, 44, 55], with significant haemoglobin values within target range in pharmacist-led clinic. Time to achieve target haemoglobin was 28 days in the pharmacist-managed group compared with 41 days in the usual care group [44]. While the proportion of patients achieving target haemoglobin was not significant, pharma-cist intervention significantly improved haemoglobin and iron monitoring by improving compliance to therapy [44]. Pharmacist counselling significantly improved haemoglobin levels in one study [34], with haemoglobin concentration and Transferrin saturation (TSAT%) increasing significantly
and serum ferritin reaching target values in a prospective uncontrolled study [23].
An uncontrolled study of the impact of on managing sec-ondary complications of haemodialysis patients resulted in significantly increased median serum calcium in those with hypocalcaemia and decreased values in hypercalcaemia, a decline in serum phosphate in patients with hyperphos-phataemia, and an increase and decrease in serum iPTH in patients with sub-optimal and supra-optimal levels respec-tively [23].
Pharmacists’ interventions in a pragmatic, cluster ran-domised study improved screening of proteinuria between an interventions compared to control group [45]. A non-randomised controlled study of pharmacist involvement in a monitoring program for CKD reported significant differ-ences in CrCl between discharge and admission in both the control and intervention groups [36].
Humanistic outcomes
In a cluster, randomised study health related quality of life (HRQoL) improved significantly compared to control in a group of haemodialysis patients receiving pharmacist inter-vention over a 6-month period [30]. In a non-randomised controlled study, HRQoL domains were not significantly impacted by the additional pharmacist care in kidney trans-plants [47]. A multicentre RCT reported significant improve-ment in HRQoL scores in the intervention group compared to control [53].
Patient satisfaction reported in two randomised controlled studies: 92% of patients had positive feelings about pharma-cists’ involvement in their care and felt that the pharmacist provided beneficial information [15] and 43% of patients were ‘very satisfied’ with the care received and were willing to receive future care from the pharmacist [45]. A cross-sectional prospective study demonstrated that patients were greatly satisfied with the intervention [58].
Economic outcomes
Only seven studies reported economic outcomes resulting from pharmacist input [22, 35, 38–40, 44, 56]. One study reported that pharmacists in the ICU could contribute to significant cost savings in septic patients, with antimicro-bial prescribing efficiencies accounted for 34.7% of total savings [38]. In a study investigating an ICU pharmacist dosing adjustment programme, the mean ICU hospitalisation costs per patient decreased significantly with total savings of 2669.5 USD per patient [40]. Jiang et al. demonstrated that pharmacist dosing adjustment resulted in drug cost savings per patient of 2345.98 USD with antibiotics accounting for 64.5% of all cost savings. The presence of an ICU phar-macist resulted in 2346 USD savings per patient receiving
662 International Journal of Clinical Pharmacy (2019) 41:630–666
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continuous renal replacement therapy [35]. Debenito et al. reported that the mean weekly dose of erythropoiesis-stimu-lating agents (ESAs) was significantly less in the pharmacist-managed group than the usual care group and the annualised ESA cost per patient reduced by 1288 USD [44], whereas, Aspinall et al. reported lower average dose of darbepoetin in the pharmacist-managed ESA clinic compared to the usual care [39]. Mousavi et al. showed that the cost per patient for inappropriate stress ulcer prophylaxis administration in patients with insufficient renal function was reduced by pharmacists’ intervention [22]. A multicentre RCT reported that pharmaceutical care costed more per quality adjusted life year (QALY) gained compared to usual care [56].
Discussion
There are a number of important key findings that have arisen from this review and these are outlined below. Forty-seven new studies have been published in the intervening 8 year period since a previous similar review [7]. Ten of these are of a ‘gold standard’ RCT design and the quality of the controlled studies included is generally poor. Struc-tures and processes were very poorly reported and none of the studies included consideration of pharmacist prescrib-ing—which is considered in several countries, where it has been implemented, to be a significant advance in pharmacy practice. The process indicators in the original review [7] and this review were very similar but this review identified papers with clear shift from only identifying drug-related problems to more involvement of the pharmacist in medica-tion therapy management. Most of the studies in this review continue to focus on and report details of DRPs as an indi-cator of the process of pharmacy practice. Some of these considered the clinical significance of these DRPs but this was not universal. Less focus on clinical, humanistic and economic outcomes was observed in majority of the papers in both reviews.
Many of the uncontrolled studies had a variety of quality deficiencies including; lack of comprehensive explanation of the pharmacists’ intervention, under-reporting of adverse events and insufficient information to allow reproduc-tion of the study for interested readers. Few studies lacked some important information leading to poor scoring of the study, such as lack of clarity in stating the study aim, [35] the number of participants, the population from where the sample was drawn, duration of the data collection or the study period, frequency of follow-up, and some studies were unable to clearly state the distribution of the confounders in both groups [15, 22, 30, 35, 39, 45].
The majority of the 20 controlled studies were of ‘fair’ quality with the exception of four that were considered ‘weak’ [22, 55, 56, 58]. High quality RCTs with low levels
of bias generate the highest level of evidence [62]. However, the availability of quality evidence in this area is limited with only 5 RCTs were included in this review and 4 in a previous review by Salgado et al. [7]. The RCTs in both reviews lacked sufficient information on the randomisation process, in addition to poor detail on any blinding process of the care-giver and the care-receiver (however, it might be a challenge to blind in some study designs) so jeopardising the quality of these studies [63]. It is therefore evident that there has been a limited amount of high quality research published for the benefits of clinical pharmacy practice in CKD. There is particularly a paucity of evidence from RCTs offering a robust evidence base for practice. Despite this criticism there is a growing body of information in relation to some aspects of clinical pharmacy practice that offers some insights to the developing quality of services provided making real and significant differences to the outcomes of patients. This, however, needs to be verified through even more robust RCTs that are better resourced, designed and executed.
The gathering of more gold standard evidence such as RCTs is essential to enable measuring the impact of clinical pharmacists’ intervention in patients with CKD compared to standard care. Furthermore, there is an identified need to carry out studies with explicit details and accurate defini-tions including the setting, the participants, the randomisa-tion process and the interventions of interest.
It is of paramount importance that detailed descriptions of the interventions, in terms of structures and processes and outcomes, are included in publications to allow them to be reproduced and for readers to consider the studies within the context of their own practice [64]. Most papers lacked sufficient details of the clinical pharmacy practices so making it difficult to fully understand the activity. Without full insight to practice it is difficult to fully understand the context and characteristics of practice and so reproduce the structures and processes in wider settings. This is not just a deficiency of studies in CKD since a study by Schroter et al. to assess the replicability of published clinical inter-ventions, in a variety of clinical settings, reported that 57% of the studies had insufficient description of the interven-tion of interest to make it replicable [65]. A tool produced by Correr et al. to address the lack of intervention descrip-tions in clinical pharmacy research (Descriptive Elements of Pharmacist Intervention Characterization Tool) DEPICT is a validated instrument for accurately describing the details of pharmacist interventions performed as part of clinical pharmacy practice [66]. This tool could be used as a guid-ance to structurally describe the intervention of interest in pharmacy practice research.
Additionally it should be noted that in CKD there are no studies that have specifically investigated prescrib-ing as part of clinical pharmacy practice and there are no
663International Journal of Clinical Pharmacy (2019) 41:630–666
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full description of structure, processes and outcomes as they relate to prescribing practice. A systematic review by Tesfaye et al. published in 2017 of the prevalence of inappropriate prescribing and the impact of pharmacists’ interventions reported significant reduction in inappro-priate prescribing when physicians received immediate concurrent feedback from a clinical pharmacist [67]. The review showed minimal involvement of the pharmacist in the role of prescribing for patients with CKD. Despite the increased recognition of prescribing models such as independent, supplementary or collaborative [6], there was limited published evidence to lead to the best practice model for prescribing.
There is also a need to stimulate more of a research cul-ture within clinical pharmacy practice. A paper by Peter-son et al. reported that lack of time, lack of opportunities, lack of training and never being asked to participate in a research were major barriers for pharmacists’ engagement in research [68]. A systematic review by Awaisu et al. con-cluded that pharmacists are aware of the value of research to enable them advance pharmacy practice and indicate their willingness to be involved in independent research and in practice-based research networks. However, lack of time, training and support were the main barriers [69].
A strength for this review is that the protocol was peer reviewed and registered with PROSPERO. The protocol was devised in accordance with PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) standards [9] and the systematic review was conducted and reported in accordance with PRISMA (Pre-ferred Reporting Items for Systematic Review and Meta-Analysis) standards [10]. In terms of limitations, publi-cation bias could potentially affect the selecting process of the articles, since no study was identified to show the negative impact of clinical pharmacy services in caring for patients with CKD. One further limitation is the exclusion of papers in languages other than English potentially lead-ing to the omission of relevant papers.
In conducting RCTs, it has been recognised that it is vital to be careful in the selection and recording of out-comes to build up a coherent dataset [70–73]. Moreover, consistency in the use of outcomes will aid future users of the services and those involved in resource alloca-tion, planning and implementation of clinical pharmacy services [72]. It is evident from this review that where RCTs were conducted, there was no consistency in the selection and reporting of outcomes. These issues could be addressed with the development and application of agreed standardised sets of outcomes [73]. Research on core outcome set definitions for clinical pharmacy prac-tice is ongoing in many areas such as polypharmacy [74] but this appears to be lacking in CKD, which could be a potential area of work in the future.
Conclusion
There is some evidence for the outcomes of pharmacists’ intervention in patients with CKD but this is generally of low quality and insufficient volume. The controlled studies in this systematic review showed that pharmacist inter-ventions improved patients’ clinical outcomes such as Hb levels, CrCl, PTH and calcium levels. However, these stud-ies lacked detail on reporting of the humanistic outcomes and there remains a paucity of evidence demonstrating economic impact of pharmacists’ interventions.
There is some evidence since the last review that shows positive contributions of pharmacists’ involvement in the multidisciplinary team to provide care to patients with CKD. This includes evidence on the structure, processes of care and the outcomes of pharmacists’ intervention in patients with CKD. More high-quality research in this area is warranted.
Acknowledgements Ms Tesnime Jebara for input to quality assessment of papers. Mr Hamed Al Naamani for production of graphs and figures and general technical support in production of the manuscript.
Authors’ contributions All authors were involved in all aspects of this work including; conception and design, analysis and interpretation of data, drafting and revising the article, providing intellectual content and final approval of the version to be published.
Funding None.
Conflicts of interest None of the authors has any financial interests or connections, direct or indirect, or other situations that might raise the question of bias in the work reported or the conclusions, implications or opinions stated. In addition, the authors confirm that results pre-sented in this paper have not been published previously in whole or part, except in abstract format.
Ethics approval The Ethics panel of the School of Pharmacy & Life Sciences, Robert Gordon University indicated that ethics approval was not required for this systematic review.
Open Access This article is distributed under the terms of the Crea-tive Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribu-tion, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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