6 Considerations for Successful Patient Recruitment in Phase 1 Clinical Trials
Most Phase 1 clinical trials are conducted with “normal healthy volunteers” (NHVs), meaning that trial participants:
- Are in generally good health
- Have no chronic medical conditions
- Are not taking prescription medicines
- Have “normal” lab values as defined by ranges at local or central labs
However, there may be times when a Sponsor wants to incorporate a cohort(s) of patients or a “specialty” population into the trial to gain early insights into how their drug might perform in that population. Examples of a specialty population could be the following:
- Atopic patients
- Glaucoma patients
- Elevated triglycerides
- High Body Mass Index (BMI)
- Women of child-bearing potential (WOCBP)
- Post-menopausal females
- Elderly participants
- Ethnic participants
When one of these populations is to be included, we’ve found that there are many additional volunteer-centric factors which should be considered when planning for patient recruitment, retention initiatives, and overall project execution.
Considerations for Patient Recruitment in Phase 1 Trials
1. Cohort Scheduling
The timeframe in which the specialty population cohort(s) will be initiated will have an impact on patient identification. For example, if the specialty population cohort won’t be enrolled until all NHV cohorts have been completed, then Sponsors should be certain that the Phase 1 site is actively working to identify patients during that time such that there are no delays when its time to randomize.
On the other hand, if the study is enrolling the specialty population simultaneously as the NHVs, it can be challenging to randomize a full cohort of 8-10 participants concurrently in the same way a NHV cohort would be structured. In our experience, allowing for flexibility in scheduling confinement and follow-up visits can be beneficial and attractive to patients and in turn make the study easier to enroll.
2. Standard of Care
Oftentimes, what’s specified within the protocol doesn’t always translate well to what is done in a healthcare setting and may even present an unrealistic expectation for the specialty population (such as certain medication requirements). Before beginning patient recruitment initiatives, it is important to consult with recruiting physicians to understand if there are any discrepancies between what is required in the protocol and the standard of care for that population. So long as trial objectives can still be achieved, it may be worthwhile to remove or adjust certain criteria that would exclude otherwise-eligible trial participants.
3. Planning a Patient Recruitment Strategy
Building timelines to recruit specialty and patient populations will involve multiple stakeholders, as it is not as straightforward as recruiting NHVs. For example, if the Phase 1 trial involves patients of varying disease states or severities, the approach for recruiting and engaging those patients will change. These strategies need to be developed up front to determine what resources or expertise will be necessary. In many cases, a specialist will be needed to confirm eligibility, which adds complexity (and time) when deciding on enrollable patients. Ensure that time for the specialist’s review is built into the screening windows and accrual rate projections.
4. Phase 1 Trial Commitment
In Phase 1 trials, NHVs regularly participate in multiple studies and become familiarized with the processes of screening, admission, confinement, and expectations when it comes to procedures. If you plan your project under the assumption that specialty populations or patients will have that same level of familiarity you will likely find yourself encountering many obstacles that could have been avoided.
Consider designing the trial to accommodate patients’ unique lifestyles and other obligations, which may include managing their own health. Simple measures such as scheduling overnight visits to take place on weekends and having rolling enrollment can encourage patients to participate since their normal schedules will be minimally impacted. Similarly, be prepared to provide other accommodations (such as transportation) to minimize the burden of participation.
5. Procedures and Assessments
Be sure to take into consideration the frequency and invasiveness of the protocol procedures. If scheduled too often or too invasive, this may deter potential participants and make patient recruitment more difficult for your Phase 1 trial. Also, even if you enroll the patient, they may deem participation too strenuous to continue after too many procedures. Furthermore, this is an opportunity for Sponsors to assess the value in requiring certain procedures. They should ask themselves whether it is beneficial to conduct an invasive procedure on a patient for the sake of an exploratory endpoint, or if they can still obtain necessary data in a manner that removes burden from the participant.
6. Budget Impact
Phase 1 trials in patient populations are complex because they involve the intensity that is common in standard Phase 1 trials in NHVs, but also the nuances of patient recruitment and management that is seen in late stage trials. As a result, expect your study budget to be distinct and higher in value. One element which drives patient recruitment success is the stipend for participation—since Phase 1 studies have increased commitments from participants and the procedures are not typically a part of their standard care, its reasonable to expect that subjects will need to be compensated at a higher amount for their time.
Furthermore, in order to successfully manage subjects during their participation, you will need to adequately staff your site to not only perform procedures but to manage care and address questions or concerns that will come up over the course of clinical conduct. For this, you may also need to involve therapeutic area specialists which will have an upward impact on the overall study budget—but it is a worthwhile expense to ensure that the patients feel comfortable regarding their participation and do not drop out mid-study.