9 semester, Kursus iKlinisk Farmakologi og Forordningslære

Forelæsning:Farmakoepidemiologi Farmakogenetik

21 Februar 2005

Farmakoepidemiology

Definition: Undersøgelse af årsager til og resultater af at anvende lægemidler i befolkningen.

Udfald er både

•Positive (forebyggelse, lindring, øget livskvalitet, helbredelse, …)••Negative (bivirkninger, misbrug, sygdom, …. )

Et vigtigt formål med

farmakoepidemiologien

er

•Rationel og adækvat anvendelse af lægemidler –

•både ud fra en klinisk og økonomisk synsvinkel –

og for den enkelte og for samfundet

Statist. Med. 2004; 23:783–801

Den nye medicinforbruger:

Receptpligtig medicin vil udgøre 1/3 af væksten på det offentlige område frem til 2010 (Amternes nye magasin 27/1-03)

Nye anvendelsesområder for SSRI:Spiseforstyrrelser, rygestop, social fobi, panikangst

3 former for risikohåndtering:

• Traditionel (Gud, skæbne, karma, memesis)• Moderne (videnskabeligt baseret, stat. Faktorer• Postmoderne (at kræve, at vælge)

Farmakoepidemiologien anvender de klassiske epidemiologiske metoder:

Statistikker

Kohorte studie

Case –

control studier

Fortoklning

af : Relativ Risiko Odd’s Ratio

RR = 1,02 ( 0.85 –

1.25): 2% øget risiko, ikke signifikantRR = 2.21 ( 1.25 -

3.31)

2.21 x øget risiko, signifikant

RR = 0.45 ( 0.30 –

0.80) 55% reduceret risiko ???

Compliance

SSRI and pregnancy outcome

• SSRIs are widely used• Exposure in 1st trimester of unplanned

pregnancies• Animal studies• Cardiovascular congenital malformations

Objective

To examine the risk of adverse pregnancy and neonatal outcomes associated with maternal use of SSRIs during the pregnancy

Setting

• 4 Counties in Denmark

• ~1.6 million people

• 151,962 women who had a live birth or stillbirth identified through the Medical Birth Registry

Data on use of SSRIs

• County prescription databases- All redeemed prescriptions- The Anatomical Therapeutic Chemical

Classification System

Data on birth outcomes

• Danish Medical Birth Registry:- birth weight- gestational age- stillbirth- perinatal death

• County Hospital Discharge Registries:- congenital malformations

Analysis and data on confounders

• Logistic regression • Danish Medical Birth Registry

- maternal age - maternal smoking - parity

• County prescription databases- maternal use of antiepileptic drugs

Methods

Group

SSRI exposure during

Outcome30 days before

1. trimes.

2. trimes.

3. trimes.

1 Yes Yes Malform.

2 Yes Yes Yes Still birthPerinatal Low BWPreterm

Control No No No No

Results

SSRI Control Adj. ORMalformations(overall)

54 (5.1%) 5,240 (3.5%)

1.4*(1.1-1.9)

Malformations(cardiovascular)

17 (1.7%) 1,000 (1.0%)

1.6*(1.0-2.6)

*Adj for maternal smoking status, birthorder, maternal age, and maternal use of antiepileptics

ResultsSSRI Control Adj. OR

Stillbirth 3 (0.3%) 453 (0.3%)

Perinat. death

3 (0.3%) 382 (0.3%)

Low BW 52 (5.2%) 6,392 (4.2%) 1.1(0.7-1.7)

Preterm 74 (7.4%) 7,580 (5.0%) 1.4(1.1-1.7)

Wogelius et al. Epidemiology 2006; 17:701-04

Conclusion

increased risk of

• preterm birth,• congenital malformations,• congenital cardiovascular malformations

- associated with prenatal exposure toSSRIs

Strengths

• Complete prescription database: prevents selection bias

• Exposure measurements not based on recall• High number of exposed pregnancies • Confounder control

Limitations

? Surveillance bias- Newborn SSRI exposed children may be surveyed more intensely due to neonatal symptoms after exposure to SSRI in late pregnancy

• ? Confounding by indication- No information on the depression

Nature 405:857, 2000

Prediction of drug efficacy by SingleNucleotidePolymorphisms’s

MTHFR 677C>T MTHFR 1298A>C

Advanced colo-rectal cancer with metastasis and 5-FU treatmenMarie-Christine Etienne et al. Pharmacogenetics 2004, 14:785–792

The future is here already:

• Individualised risk assessment from genetic analysis

• Individualized drug treatment from genetic analysis

Fredag d. 23.2

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