Clinical Trials

❘❙❚■ Chapter 1 | Randomized Clinical TrialsPhase I and II studies, multicenter studies can be carried out at any stage ofclinical development (see Chapter 16). Multicenter studies are necessary for twomajor reasons:• to evaluate a new medication or procedure more efficiently in termsof accruing sufficient subjects over a shorter period of time• to provide a better basis for the subsequent generalization of thetrial’s findings, ie, the effects of the treatment are evaluated in manytypes of centersOther classificationsTrials can also be described as superiority studies, equivalence studies, ornoninferiority studies in terms of what the study was designed to prove. A superioritystudy aims to show that a new drug is more effective than the comparativetreatment (placebo or current best treatment) [4]. Most clinical trials belong tothis category. On the other hand, an equivalence study is designed to prove thattwo drugs have the same clinical benefit. Hence, the trial should demonstrate thatthe effect of the new drug differs from the effect of the current treatment by amargin that is clinically unimportant (see Chapters 12 and 13). A noninferioritystudy aims to show that the effect of a new treatment cannot be said to besignificantly weaker than that of the current treatment (see Chapter 14). In thelatter two trials the new treatment might still turn out to be more effective thanthe comparative treatment, but this is not the prior assumption of the trials.Clinical trials can also be classified by whether the trial is the first to comparea specific treatment (exploratory) or is a further trial trying to confirm a previousobservation (confirmatory) [10]. An exploratory study might also seek to identifykey issues rather than to confirm or challenge existing results regarding thetreatment effect. For example, it might look at the impact of a new drug in aspecific subset of patients who have additional diseases to the main disease ofinterest, such as diabetic patients with heart disease. On occasions, a study canhave both confirmatory and exploratory aspects. For instance, in a confirmatorytrial evaluating a specific treatment, the data can also be used to explore furtherhypotheses, ie, subgroup effects that have to be confirmed by later research.Why might clinical trial results not represent the true difference?In a clinical trial, the observed treatment effect regarding the safety and efficacyof a new drug may represent the ‘true’ difference between the new drug and thecomparative treatment or it may not. This is to say that if the trial were to berepeated with all the available patients in the world then the outcome would4