Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘The RITA 3 trial was set up to investigate the policy of early intervention versusconservative medical management in unstable angina. During the follow-up of thetrial, the definition of myocardial infarction changed. Therefore, the investigatorscarried out two analyses: one using the original trial definition of the endpointmyocardial infarction, and another using the new definition. This approachexplained some discrepancies in estimated effects of previous and contemporarytrials in the field [7].Incorrect reportingWe discuss examples related to testing more than one outcome or testing formultiple subgroup effects in more detail in other chapters of this book (seeChapters 23 and 29). Particular examples related to incorrect reporting can befound in Pocock et al [8]. The description and discussion of inclusion criteria andtrial procedures are particularly important to judge external validity. This field inparticular has sparked many discussions and is probably a factor for the relativelylow adherence to guidelines found in clinical practice [9]. The tension betweentreating a single patient who might or might not correspond to the inclusioncriteria of a particular published trial is difficult to solve.Prerandomization run-inAdditionally, prerandomization run-in periods can lead to a distorted picture.Active run-in periods in which patients are excluded if they have adverseoutcomes are likely to invalidate the applicability of the trial to the clinicalsituation. For example, trials examining carvedilol in the setting of heart failureexcluded up to 9% of patients in the run-in period because of adverse events(some of which were fatal), with subsequent much lower complication ratespostrandomization than in the run-in phase [10,11].Press releasesThe requirements of a press release are different from those of a publication in amedical journal. The key findings and overall structure of the report must be thesame – however, the style in which they are conveyed is different. The audienceconsists of the general public, so press releases should avoid technical jargon orextensive explanation of the processes of the study. The report must also be verycareful not to over-emphasize the clinical significance of the findings and to makesure that the study population is explicitly stated. Short sentences should be used,and graphs should be avoided altogether. Percentages may be quoted, but theirdenominators should also be explicitly given; other measures of effect, such asodds ratios, should be explained in words. Some statement should be made aboutthe power of the study, again avoiding technical jargon. It is useful to give some373