Recruitment to randomised studies

Study designs that are conceptually simple, and that address questions of clinical relevance where genuine uncertainty exists, are likely to facilitate the recruitment of both investigators and participants. Also, studies with uncomplicated entry criteria are usually more attractive to investigators; those with complex eligibility criteria make recruitment more difficult, are more difficult to explain to participants, and, ultimately, their findings may have limited generalisability. Further, the enthusiasm of investigators may wane if trial protocols require substantial efforts on their part.

The choice of an appropriate control arm can enhance investigator interest and comfort, particularly if the control arm reflects best clinical practice. Studies should permit changes to best clinical care during the course of study follow-up. This will maintain both the ethical integrity of the study and investigator interest, and protect participants while retaining scientific efficiency. For example, in a study examining the effects of a fibrate to prevent vascular disease in diabetes, a new indication for statin treatment, based on existing trial evidence, may emerge for some participants during follow-up. In this instance, it would be preferable to allow those participants to use statins while continuing their study medication, rather than requiring them to withdraw from the study or stop taking study medication, potentially increasing the risk of participants being lost to follow-up because statin therapy is prohibited in the study protocol. This strategy also helps maintain the relevance of the study question.

Recruiting a large number of participants usually requires a considerable number of centres to be involved. However, all centres need to have a patient pool of adequate size, and the infrastructure and resources to recruit and manage the projected number of patients efficiently. Centres interested in participating in the study should identify through their screening logs (or equivalents) their potential participant numbers. However, only a proportion of these would eventually be recruited into the study. Research clinics should ideally be geographically accessible to the targeted patient group, and reimbursement of patient's expenses, as well as their transport and parking arrangements, should be considered. Payments to participating clinics for study costs are usually on a pro-rata basis, with funds matched to the number of participants recruited at each location.

A low accrual rate can undermine the viability of the study plan. Strategies to overcome this require a detailed understanding of the reasons for the slow accrual, so these can be addressed. This might involve adding more clinical centres, revising the study eligibility criteria or other trial requirements, or re-assessing resources.

As recruitment to trials may occur over several years, clinical changes may influence the continuing importance of the study question. Further recruitment may not be appropriate as another trial may have satisfactorily answered the same question, or a better treatment alternative may have become available. In this case, the study management committee should review the situation to determine whether the study should continue in its current form, whether a revised study (with a smaller sample size or modified end-points) could still be ethical and scientifically valuable, or whether the study should be abandoned.

Successful recruitment into clinical trials is best achieved by having a feasible recruitment plan, together with dedicated trial staff and adequate resources. The plan should be based on well-piloted recruitment strategies, involving clinical centres with demonstrated commitment to the proposed study and adequate numbers of patients for recruitment. Sites with previous clinical research experience can help newer sites to be successful. Central monitoring of recruitment and feedback to participating centres on the trial's progress, by means of email, newsletters, or meetings, will foster continued interest and participation, and will enable the effectiveness of different recruitment methods to be evaluated. Further, adequate resources and incentives for trial staff and potential participants are key requirements for success. A question worth answering and an uncomplicated design are more likely to attract investigators and participants.