Only a small fraction of adults with cancer (approximately 3 percent) are enrolled in clinical trials. The accrual figure may be slightly higher for patients with hematologic malignancies, but there is no question that accrual to clinical trials for hematologic cancers is suboptimal and a limiting factor in our ability to make progress. This problem is not limited to malignant hematology. Only a tiny fraction of patients with non-malignant hematologic disorders participate in clinical trials.
A recent report in The New York Times suggests patient reluctance to participate in trials represents a major factor in poor accrual.1 While there are some subjects who decline participation, too few patients are ever presented with an opportunity to participate in clinical trials. Clinical trials are expensive and time-consuming to run, and unless they are driven by a pharmaceutical company with a vested interest in the results, reimbursement rarely covers costs. Too many busy physicians, including hematologists, lack the time, resources, and incentives to open and enroll subjects in clinical trials.
Is there anything that can be done? The answer is “yes.” Many organizations, including the National Cancer Institute (NCI), are exploring the operational efficiency of clinical research by looking at multiple factors, including agreeing on contract clauses that commonly cause delays such as property rights and indemnification, tracking the status of protocols, and providing novel incentives based on performance and administrative efficiency. The goal of this important effort is to streamline the process at both the local and national levels. Additional efforts are geared toward strengthening clinical research training and mentorship, and identifying novel approaches to supporting physicians, particularly at major medical centers, who are committed to careers in clinical investigation. These are all worthwhile approaches.
One major issue that is the proverbial “elephant in the room” is the enormous regulatory burden associated with opening and running clinical trials and the resulting cost required to manage this burden. Internal Review Boards (IRBs) run by individual institutions have their own expectations and requirements; the preparation of paperwork for initial review, reporting of adverse events, and ongoing renewal of clinical trials takes an enormous administrative effort. The administrative burden is proportionally larger for multi-institutional trials. For rare disorders, the effort needed to open and maintain a trial may be rewarded, even at the largest medical centers, by accrual of only a handful of subjects each year. This burden is particularly concerning as multi-institutional studies are increasingly important. Even for more common disorders, larger studies are needed due to an increasing use of stratification and subset analysis of patients based on genetic analysis and other biomarkers.
Our current system involving local IRBs, as frustrating as it may be at times, was a thoughtful response to horrible human rights abuses of the past and has generally served well to protect the rights of subjects. There is absolutely no doubt that rigorous subject protection must be maintained. However, the current approach to protecting human subjects was developed in an era when multicenter studies were uncommon and communication and information technology were very different from what they are today.
An encouraging development is that we have made modest steps toward a national approach to reviewing and monitoring multicenter trials. Success in this regard will relieve local investigators, administrators, and IRBs of the immense and redundant administrative burden currently associated with multicenter studies. The national review and monitoring of multicenter clinical trials will, in turn, allow local investigators (and IRBs) to invest their time and effort in institutional studies.
Progress in this direction has been slow. A central IRB for NCI-supported cooperative group studies has been established, albeit with decidedly mixed results. Commercial IRBs, such as the Western IRB, now review many trials. The movement toward a national IRB for large multicenter studies is at the stage where more focused national dialogue is needed on issues such as legal and ethical accountability that are central to human subjects’ protection. As a community, we need to speak up about the need to decrease the redundant administrative burden associated with the current requirement that each institution’s IRB provide oversight of large multi-institutional studies, while emphasizing that any changes must be implemented in a way that allows the increased consistency of review to strengthen, not lessen, human subjects’ protection.
In summary, our future patients are depending on us to accelerate progress in hematology, and this requires redoubling our commitment to clinical research. Education of the public about the value of clinical trials needs to be enhanced, and physicians, including hematologists, must continue to invest time and effort in clinical research despite the challenges. We must continue to improve efficiency, support clinical research training, and identify additional sources of support for clinical investigators. We must do all of this, while also exploring rigorous but more efficient and less redundant ways of providing ethical oversight of human subjects research on which the future of hematology depends.
