How real is intention-to-treat (ITT) analysis in non-interventional post authorization safety studies? We can do better.
Although cohort studies which are based on intention-to-treat (ITT) approach offer a simple design with data which are simpler to analyse and results easier to interpret, such studies also intrinsically assume that any time-varying treatment effect that exits can be adequately estimated by a fixed-effect component. However, such an assumption may not reflect real-life drug use. Reflection of real-life clinical practice is a major strength of epidemiologic safety studies. The failure to properly reflect reality may result in effect under-estimation leading to false and irreproducible conclusions due to exposure misclassification. In effect, the use of nested case-control design is a concesion that ITT in cohort design may not be adequate. But the nested design also has its own sources of bias, including confounding by indication. We present an overview of the counter-matched version of the nested case-control, case-crossover, case-in-time, case series and case-cohort designs as alternatives in prospective post-authorization safety studies.
Kiri
Victor A
VA
Peri-Approval, Clinical Research Services, PAREXEL International, Uxbridge, UK. Victor.Kiri@PAREXEL.com
MacKenzie
Gilbert
G
D015982:Bias; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D064420:Drug-Related Side Effects and Adverse Reactions; D004812:Epidemiologic Methods; D006801:Humans; D015233:Models, Statistical; D016017:Odds Ratio; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D012107:Research Design; D013997:Time Factors