Recruitment for patients in clinical trials has followed the same model for many years. This is also mostly true for clinical trials involving rare diseases. Given the added complexity of the rare disease, should we be looking at the enrollment model in a different way that may open the door to more participation and faster enrollment? It is clear that the current model creates a time-consuming process that is based on a large number of sites enrolling a small number of patients. Is there a model that will facilitate a smaller number of sites with a larger number of qualified patients and cut the time and cost of clinical trials significantly? In recent years there have been some attempts at a more centralized model, but we have yet to see this model become the standard.
Most clinical trials are conducted in the same manner. Sponsors, be they pharma or CROs, initiate a feasibility process where they search out sites that have the patient population and the appropriate clinical study experience. These sites are then contracted and initiated to the trial with the goal of enrolling patients from their own population. The issue with rare diseases is that experienced sites may have very few subjects to enroll. Qualified subjects are typically spread widely across a variety of practices, and many of these practices may not be set up to conduct a clinical trial or the necessary clinical trial recruitment. The current model is highly centralized and excludes most of the patients that may actually qualify for the trial.
Different Patient Recruitment Strategies
In recent years we have seen a couple of different models for enrolling rare diseases. One model recently employed through DaVita® sites involved a trial looking at an acute yet rare condition called Calciphylaxis. In this trial, a non-typical model was employed where established research centers were identified but not initiated to the trial. Sites were only initiated and trained once a qualified patient had been identified. The benefit of this model was that the sponsor was not bringing on sites that may never be able to identify a subject. A central Project Manager worked with potential sites to provide them with study information and maintained a connection with them to keep them interested in the trial until a potential patient was identified. Once a qualified subject was identified, the site would move into expedited start-up, and the subject was enrolled. This method keeps the sponsor from initiating a large number of sites that would not enroll yet would need to be maintained from an operational perspective.
Hub and Spoke Patient Recruitment
Another method that is much discussed but rarely employed is a hub and spoke model. A central Principal Investigator (PI) in a region would be contracted and the sponsor and site would work on a plan to obtain referrals from surrounding physicians and healthcare providers that may have the patients in their practice. While there are many trials that attempt to get information out to potential referring physicians, a good and viable connection with the physician is rarely achieved and the referral process breaks down. Roadblocks to this seem to be a reluctance of physicians to refer out to unknown physicians, PI physicians that are unwilling to accept external patients from other practices and patients themselves that are reluctant to see a new physician for a research study related to their condition. Many of these issues could be mitigated by a better communication strategy and follow-up between the sponsor and referring physicians as well as their potential patients. Improved inclusion and study materials provided to referring physicians, including face-to-face meetings to discuss their role in the trial, could go a long way in opening up the referral process. Could these referring physicians actually serve as sub-Investigators on the trial? Is there adequate compensation to the referring physician for the work related to transferring the patient over to the research site?
Centralized Coordinator and Study Team
Another potential solution that has recently seen some acceptance is a centralized study coordinator and a team that can assist novice PIs in the research process. Many of the sites that may have patients for rare disease studies do not have the research infrastructure to conduct a clinical trial. Recently DaVita Clinical Research has employed a model where there is a centralized coordinator and study team that will help the novice PI with start-up and study execution. The PI is given training in the research process and the well-trained and experienced centralized staff is on hand to assist with the completion of source documents other study documents that are required for a study. The support infrastructure for the site is external but available to assist with any of the study-related process that needs to be executed and documented.
It is clear that there are several viable solutions to enroll patients with rare diseases. It takes a lot of work and dedication to make these alternatives work. It takes a sponsor willing to explore new processes that may not be the standard practice for the conduct of a clinical trial. What these alternatives do provide is more access to the trial population and a potential to expedite enrollment and development timelines. We have only started to explore these alternative methods of enrollment for rare diseases, but it is clear that other methods will need to be employed if we are to improve overall enrollment rates.