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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
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 ???
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)
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
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