Clinical Trials

❘❙❚■ Chapter 12 | Equivalence TrialsConclusionEquivalence studies have important uses in clinical trials:• They are used for comparing similar treament compounds.• They are used for comparing the efficacy of the same treatmentcompound in differing formulations or in different cohorts of patients.The key things to remember are that:• They can have either an equivalence or a noninferiority endpoint.• The outcomes can be clinical or pharmacokinetic.While most published works concentrate on superiority endpoints, equivalencestudies are performed in large numbers, particularly for regulatory submissions,so understanding the basic issues related to these approaches is thereforeimportant. Other variables involved include scientific and ethical issues, andstatistical assessment of superiority, equivalence, and noninferiority.References1. Gradman AH, Lewin A, Bowling BT, et al. Comparative effects of candesartan cilexetiland losartan in patients with systemic hypertension. Heart Dis 1999;1:52–7.2. Tuomilehto J, Rastenyte D, Birkenhager WH, et al. Effects of calcium-channel blockade inolder patients with diabetes and systolic hypertension. Systolic Hypertension in Europe TrialInvestigators. N Engl J Med 1999;340:677–84.3. Guidance for industry: Bioavailability and bioequivalence studies for orally administrated drugproducts – general considerations. Rockville: US Department of Health and Human Services,Food and Drug Administration and Center for Drug Evaluation and Research, 2000.4. Guidance for industry: Statistical procedures for bioequivalence studies using a standardtwo-treatment crossover design. Rockville: US Department of Health and Human Services,Food and Drug Administration and Center for Drug Evaluation and Research, 1992.5. Guidance for industry: Statistical approaches to establishing bioequivalence. Rockville:US Department of Health and Human Services, Food and Drug Administration and Centerfor Drug Evaluation and Research, 2001.6. Ware JH, Antmann CG. Equivalence trials. N Engl J Med 1997;337:1159–62.7. Topol EJ, Moliterno DJ, Herrmann HC, et al. Comparison of two platelet glycoprotein IIb/IIIainhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneouscoronary revascularization. N Engl J Med 2001;344:1888–94.118