Purpose: To identify methodological features that affect the validity of conclusions drawn from active-control equivalence trials and to apply these criteria to recently published trials comparing antihypertensive agents from different classes.
Methods: Standard methodological criteria for randomized clinical trials and six additional methodological features that affect the validity of active-control equivalence trials were applied to four recently published large trials that compared different antihypertensive classes and that concluded that their results showed equivalence.
Results: All four of these trials fulfilled standard criteria for randomized trials. However, none fulfilled all of the six additional methodological criteria that affect the validity of active-control equivalence trials, one fulfilled five criteria, two fulfilled two criteria, and one failed to fulfill any of the criteria.
Conclusion: Standard methodological criteria for evaluating superiority trials are inadequate for the interpretation of active-control equivalence trials. The methodological criteria outlined in this article for judging the validity of active-control equivalence trials are not specific to antihypertensive trials and may be applied to trials that test a wide variety of interventions.