Recruitment and retention issues in clinical trials.

Advances in exercise interventions and new medications are best documented by clinical trials. It seems intuitive that subjects with relevant conditions or diseases would be eager to participate in such trials, from which they may benefit and, in some cases, also receive monetary compensation. However, frequent and severe recruitment difficulties are encountered for randomized, controlled trials of new medications, often prompting large pharmaceutical companies to recruit subjects from developing countries where rules are less restrictive [1]. Of 3 clinical trials for which we have been investigators, 2 were randomized controlled rials, and in 1 trial we studied the biomechanical effects of and magnetic resonance imaging ndings for a medication that is the standard-of-care drug in the multiple sclerosis clinic of ur institution. All 3 trials had to be discontinued at one stage or another because of nsufficient subjects. Figure 1 shows a typical recruitment algorithm that applies to each of the 3 studies for hich we were investigators. The first study was conducted to compare the effects of wimming at warm (92°F) and cool (82°F) temperatures on weight changes without dieting n moderately obese postmenopausal women (the study included a treadmill control roup). Of 30 women initially recruited, 15 completed the study. In addition to potential ealth benefits, incentives included $25 for the first physical, $50 for the last physical, $4 for ach swim session (resulting in a total of $256 for sessions), $5 for each diet/activity log resulting in a total of $85 for completing logs), a $64 completion bonus, and all pool/gym ees. One of the authors (W.S.S.) actually swam with each subject at least once a month for he 4 months of the study. Reasons for dropping out were as follows: illness or injury unrelated to the study) that prevented further exercise (n 4); a death or serious illness in the subject’s family (n 2); “disappearance” of the subject (n 2); a new job that did not allow time for participation (n 1); inability to complete the initial fitness testing (n 1); decided to diet (n 1); resumed smoking (n 1); and lost interest (n 3). The second study was prompted by a published report [2] of the effects of an augmented xercise program versus usual care alone in survivors of a major burn. The intervention was n augmented exercise program, either work to quota or work to tolerance (WTT) plus sual care, on maximal aerobic capacity (or VO2max). The effect of exercise was significant nd striking versus baseline and versus usual care alone, but the WTT did not differ from ork to quota. This finding suggested that neither exercise pushed the subjects hard nough. In the subsequent study we randomly assigned subjects to usual care alone, usual are plus exercise at the intensity used in the published study (with a WTT, ie, symptomimited termination of each session), or usual care plus a higher rate of progression (also ymptom-limited). Slow recruitment prompted the researchers to use historical control ubjects (from the published study) and place all subjects in the higher intensity group. owever, even this modification did not allow enough subjects to be recruited quickly nough to satisfy the grantor, and the study was discontinued (interesting data were btained and will be submitted as a pilot study, but the scope of the original plan was not chieved). Reasons for recruitment failure included a lack of interest, distance from the enter, a new job, lost to follow-up, and a new injury. Patients were handed a scheduled mount of cash at the time of each visit, with a total of $1000 possible for full participation nd completion of the study. The third study involved use of a new medication (natalizumab), which has been pproved by the Food and Drug Administration to prevent relapses in relapsing-remitting j D