This paper provides recommendations when the requirement to demonstrate the superiority of a new therapeutic regimen compared to placebo or to an accepted standard therapy before bringing it into practice is abandoned. In this situation a study can only aim at demonstrating therapeutic equivalence of different treatments. This procedure is justified if in addition to therapeutic equivalence in a main outcome variable, other advantages of the new therapy can be expressed. In general, more detailed information must be available for the justification of an equivalence trial compared to the common investigations planned to show the superiority of a new therapy. This also concerns the adequate interpretation of the results.
DunnettCWGentM.Significance testing to establish equivalence between treatments with special reference to data in the form of 2 × 2 tables. Biometrics.1977;33:593–602.
5.
FarringtonCPManningG.Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med.1990;9:1447–1454.
6.
HuqueMFDubeyS.Design and analysis for therapeutic equivalence clinical trials with a binary clinical endpoint. American Statistical Association 1990. Proceedings of the Biopharmaceutical Section.91–97.
7.
HuqueMFDubeySFreddS.Establishing therapeutic equivalence with clinical endpoints. American Statistical Association 1990. Proceedings of the Biopharmaceutical Section.46–52.
8.
LeeMLLusherJM.The problem of therapeutic equivalence with paired qualitative data: An example from a clinical trial using haemophiliacs with an inhibitor to factor VIII. Stat Med.1991;10:433–441.
9.
MauJ.A statistical assessment of clinical equivalence. Stat Med.1988;7:1267–1277.
10.
MehtaCRPatelNRTsiatisAA.Exact significance testing to establish treatment equivalence with ordered categorical data. Biometrics.1984;40:819–825.
11.
RodaryCCom-NougueCTournadeMF.How to establish equivalence between treatments: A one-sided clinical trials in pediatric oncology. Stat Med.1989;8:593–598.
12.
RöhmelJ.Der Gebrauch des Begriffes “Äquivalenz” beim Nachweis der Wirksamkeit von Arzneimitteln. In: MichaelisJHommelGWellekS (Hrsg.): Europäische Perspektiven der Medizinischen Informatik, Biometrie und Epidemiologie. München: MMV Medizin Verlag; 1983:139–142.
13.
SteinijansVHauschkeDDilettE.Biometrische Bewertung der therapeutischen Äquivalenz. In: BlumeH (Hrsg.): Qualitätsbewertung von nicht-systemisch wirkenden Arzneimitteln. Proc. 9. ZL-Expertentreffen Frankfurt/Main: Govi-Verlag; 1992.
WellekS.Methoden zum Nachweis von Äquivalenz. Stuttgart: Gustav Fischer; 1994.
16.
DurrlemanSSimonR.Planning and monitoring of equivalence studies. Biometrics.1990;46: 329–336.
17.
GarbeERöhmelJGundert-RemyU.Clinical and statistical issues in therapeutic equivalence trials. Eur J Clin Pharm.1993;45:1–7.
18.
GouldAL.Another view of active controlled trials. Control Clin Trials.1991;12:474–485.
19.
MakuchRPledgerGHallDBJohnsonMFH-ersonJHsuJP.Active control equivalence studies. In: PeaceKE (Ed.): Statistical issues in drug research and development.New York: Marcel Dekker; 1990.
20.
MakuchRJohnsonM.Issues in planning and interpreting active control equivalence studies. J Clin Epidemiol.1989;42:503–511.
21.
PledgerGWHallD.Active control trials: Do they address the efficacy issue? American Statistical Association 1990. Proceedings of the Biopharmaceutical Section.1–10.
22.
SennS.Inherent difficulties with active control equivalence studies. Stat Med.1993;12:2367–2375.
23.
SennS.Falsificationism and clinical trials. Stat Med.1992;10:1679–1692.
24.
TempleR.Difficulties in evaluating positive control trials. American Statistical Association 1983. Proceedings of the Biopharmaceutical Section.48–54.
