Clinical Trials

❘❙❚■ Chapter 16 | Multicenter TrialsWhat is a multicenter trial?A multicenter trial is a trial that is performed simultaneously at many centersfollowing the same protocol. The activity at these centers is synchronized froma single command center – the coordinating center. A multicenter trial is notequivalent to a number of separate single-site trials, since the data collected fromthe different centers are analyzed as a whole.The earliest documented randomized trial was a multicenter study conducted in1948 by the UK Medical Research Council, evaluating streptomycin for thetreatment of pulmonary tuberculosis. This was discussed in a theme issue of theBMJ published to mark the 50th anniversary of this trial [1]. Since then, there havebeen hundreds more multicenter trials, mainly in the form of large randomizedcontrolled trials [2].The majority of these trials have commercial funding and are driven bypharmaceutical sponsors, but in Table 1 we have listed some multicenter trialsundertaken by independent clinical investigators. Most of these studies are uniqueas they are pragmatic trials with little commercial interest, designed with primaryoutcomes such as death. Such trials are usually published on behalf of all theinvestigators, acknowledging the team effort involved.Why are multicenter trials conducted?Multicenter rather than single center trials are carried out for several reasons:• When studying rare diseases, there will be a larger pool of patients to recruitfrom when using a multicenter trial. Therefore, the patient recruitmenttarget will be reached more quickly than in a single-center study [3,4].• For diseases with low event rates, treatments are likely to have a smallabsolute benefit and so large numbers (thousands) of patients mightbe needed in order to see a significant benefit.• Multicenter trials provide a better basis for the subsequent generalizationof the study findings [3,4] since the treatment benefits are not dependent onone specific center and, therefore, should be reproducible at other centers.• Any bias that might be related to the practice methods of a single unit –where methods may be tailored to address local issues – will be reduced.• Using many investigators to simultaneously evaluate a treatmentgives more sources of feedback, allows more doctors and healthcareprofessionals to gain experience and confidence with the experimentalintervention, and highlights any problems earlier. For example, the154