The author has seen even the simplest Phase 1 trials in normal male volunteers become a major recruitment problem for various reasons. These include scheduling issues, staffing issues, problems
with an excessive number of volunteers having participated in other trials in the recent past, unfounded optimism of the recruitment results to be obtained from advertisements, athletes who did not qualify for a trial because their daily exercising led to laboratory abnormalities, and so on; the list of actual problems that have occurred (just in Phase 1 trials) goes on and on. The point is that, if these types of issues can affect recruitment of normal male volunteers who are usually relatively easy to enroll in a trial, then the number of problems encountered seeking patients for a more complex Phase 2 or Phase 3 clinical trial is going to be several orders of magnitude greater.

A formal written recruitment plan based on the recruitment strategy is necessary to prepare, review, and approve for every clinical trial. The strategy must consider all aspects of the issues that will likely arise and then lead to creation of a plan that incorporates all relevant elements and techniques likely to attract and enroll a sufficient number of patients. While this is a clinical responsibility for almost every trial, the marketing group is likely to have valuable ideas of ways to find patients, and they should be contacted for input into the plan.

In creating a recruitment strategy, it is natural for most people to assume that it will be successful and that all the patients required will be enrolled. This happy event is too often unrealized for many reasons, and as a result, there is a need to incorporate some contingency plans if recruitment, enrollment, and/or patient retention are not achieving the results projected. While the issues of enrollment and retention usually differ from recruitment, they are often incorporated into the recruitment strategy. Those companies that specialize in patient recruitment usually are not involved in typical patient enrollment issues handled by the investigator’s site (e.g., discussion of requirements that patients must agree to for the trial, presenting and discussing the informed consent, ensuring the patient’s availability to attend all required sessions). Likewise, issues of retention in the trial are also not considered or addressed by companies focused on finding patients to recruit.

By assuming that there will be problems with recruitment, one is not only prepared to investigate the causes immediately, but one will also have contingency plans in place and know at what stages of less-than-acceptable recruitment levels one will initiate them. A worst-case scenario is important to create so that this contingency can be considered and a series of approaches considered of how this issue would be dealt with.

If a clinical trial sponsor delegates the preparation of a recruitment strategy to a contract research organization or a company specializing in patient recruitment, it still maintains the need to ensure that the strategy prepared meets its standards and is comprehensive. Indicating that the recruitment strategy is part of the sponsor’s responsibility is also stating that it is NOT the investigators’ responsibility. This is critically important because, for several decades, it was assumed by the industry that patient recruitment was the investigators’ responsibility. The author’s comments do not mean that the investigator is now able to sit back and wait for patients to arrive at his or her door for screening, but it means that the strategy is not theirs to create, monitor closely, and take corrective action without close cooperation with the contract research organization or company’s monitors. The investigator is part of the team that is responsible for finding and enrolling patients and often provides some, or even all, of the patients from his or her own practice. Also, the investigator may present the trial at grand rounds in his or her hospital or conduct any of many additional activities to enhance patient recruitment. This principle simply states that the overall recruitment strategy is not primarily the investigators’ responsibility to create and implement, even though they should be involved in as many steps of this strategy and plan as possible and definitely in its review.

Although one can track recruitment in a variety of ways apart from enrollment, it is the enrollment of a suitable patient in a trial that is the major result of the recruitment activity and is the main recruitment parameter that is measured and tracked in this matter. The most common method of monitoring recruitment is to measure numbers of patients enrolled at each site (and overall) versus time, usually on a weekly or monthly basis. Figures 70.1 and 70.2 illustrate two of the numerous graphs that may be used to track recruitment. Set time points are looked at to ensure that enrollment is on target, and if it is not, then trigger points are created in advance (e.g., a decrease of ten patients overall will trigger radio advertisements) at which point the recruitment strategy is consulted about which steps to follow to improve performance. Steps are also thought of as the tools or elements of the recruitment plan that are to be followed. The major step and the first one to undertake when enrollment is not meeting the planned numbers is to identify the reason or reasons for this problem so that they can be addressed.