Assigned Slot Allocation Offers A Fair Solution For Oncology Phase 1 Trials (Part 2)
By Nehal Lakhani, MD, Ph.D., director, clinical research, START Midwest
The first article in this series on slot allocation discusses the challenges of using competitive slot allocation and patient waitlists to select participants for Phase 1 trials. It also details the impact those approaches can have on patients, sites, and sponsors. Here, in part two, assigned slot allocation is presented as a new and potentially more equitable solution for all parties involved.
How Patients And Trial Sites Have Adapted
With the advent of social media, people are savvier than ever about seeking the best treatment options for themselves or their loved ones. A lot of patients share their experiences online, enabling others to learn about clinical trial participation. Knowledgeable patients will get waitlisted at multiple sites participating in the trial they are interested in for a chance of getting an earlier opening. This makes the process of waitlisting patients with the sponsor somewhat meaningless as the same patient could be listed multiple times.
Clinical trial sites are under constant pressure from patients and their families to obtain trial slots for patients as soon as possible. Busy clinical trial sites have figured out the changing dynamics of Phase 1 clinical trial slot assignment, and it is common for a site to include a patient on multiple waitlists to obtain a slot quickly. This approach also renders the sponsor waitlist somewhat meaningless. For example, if a patient is waitlisted for a slot on 10 trials and eventually opts for the first available trial, the other nine trial sponsors lose a patient from their waitlist. If this process is iterated across all early-phase clinical trial sites, it is easy to see how trial waitlists can be rendered meaningless.
Phase 1 clinical trials used to be performed at a handful of sites. Investigators on a dose-escalation study and medical experts on the sponsor side used to share a close working relationship. Now, it is common for 40 to 50 sites to run a dose-escalation study. Sites have recognized they will likely enroll and treat fewer patients and have compensated by opening a larger number of clinical trials at their sites to meet the demands of their patients.
Potential Solution: Assigned Slot Allocation
As a clinical investigator, I favor assigned slot allocation, whereby slots are awarded equitably to all sites and physicians are given the latitude and time to find the right patient for the trial and, conversely, the right trial for the patient, within a reasonable timeframe — say five to seven business days. This approach preserves sponsor efficiency and enables them to meet enrollment timelines while providing the predictability that both patients and investigators need. This allows physicians to be fair to their patients and sponsors to be fair to the participating clinical trial sites, patients, and investigators. This method also spreads regulatory compliance risk across all sites equally and makes sponsors less vulnerable to such mishaps.
Site Selection For Early-Phase Oncology Trials: Less Is More
Assigned slot allocation works very well with thoughtful site selection. Often, poor accrual on clinical trials is a result of inadequate site selection. Pharmaceutical companies and CROs now have a plethora of data on the performance of individual clinical trial sites, both in terms of patient enrollment and data quality. Sponsors have decades worth of retrospective data that could be analyzed to study site capabilities and pick the best available investigators. Despite all the data at their disposal, the recent trend among sponsors has been to open Phase 1 oncology clinical trials at many more sites than are needed. This may be partly driven by the FDA’s Project Optimus requirements.
Sponsors should start with a carefully selected network of five to eight sites for the dose-escalation part of a typical oncology Phase 1 trial and then expand to 20 or so sites depending on the trial design for the dose-optimization and expansion phase. If sponsors choose high-performing early-phase oncology trial sites and allow them to treat patients at predictable time intervals, clinical trials can be accrued very quickly while being fair to patients and investigators.
Putting Patients First In Early-Phase Oncology Trials
Society at large is indebted to the pharmaceutical industry for continuing to sponsor innovation. However, using competitive enrollment and patient waitlists as strategies for slot allocation takes away substantial decision-making power from the physician and patient and places it solely in the hands of pharmaceutical sponsors. The priorities of patients and their families, who take a massive leap of faith when starting treatment in a clinical trial, are rendered least important in the current clinical trial hierarchy. Cancer patients who participate in Phase 1 clinical trials make the most altruistic sacrifice, entrusting their bodies to unproven scientific innovations. Hence, the rights and well-being of a terminally ill patient should always take precedence over a pharmaceutical sponsor’s desire for shorter timelines at every stage of the clinical trial process.
Conclusion
Phase 1 oncology clinical trials work best if the needs of all parties involved — the sponsor, clinical trial sites, and patients — are met in a fair manner. The ICH-GCP guidelines for patient well-being and safety should not just apply after the patient signs the informed consent document but also to direct slot allocation practices, which have a tremendous impact on so many patients’ lives.
About The Author:
Nehal Lakhani, MD, Ph.D., is a medical oncologist and director of clinical research at START Midwest, part of The START Center for Cancer Research’s global network of clinical trial sites. Dr. Lakhani received his MD from the Maharaja Sayajirao University of Baroda in India and his Ph.D. in pharmaceutical sciences from the National Cancer Institute in Bethesda, MD. He was a Fogarty Fellow at the National Institutes of Health (NIH), trained in internal medicine at Michigan State University, and completed a medical oncology/hematology fellowship at the NIH in Bethesda. He has been involved in the development of several new anticancer therapies including immunotherapy agents, antibody drug conjugates, and targeted therapies.