Over the last three years, many of us who work in clinical research have felt an increased strain on our fragile infrastructures. I am tempted to blame the pandemic, and all the restrictions that occurred in response to it. The pandemic abruptly shut down a majority of ongoing clinical research, with most clinical sites initially pausing all but the most essential research studies while we minimized patient visits. This led to an increase in staff turnover, particularly among the nurses who perform essential roles in our clinical research studies. When we finally rebooted our research portfolios, many of us found that patients were reluctant to agree to the extra tests, visits, and costs required in our trials. Clinical practices also had become more siloed, reducing interactions and communications among health care providers that are so critical to keeping research top-of-mind. Culturally, we have struggled to return to pre-pandemic workflows, or to find a new way of working that meets the needs of our trial portfolio. But did all of these changes really begin in March 2020, or was something already changing in clinical research that left us ill-prepared for the stresses the pandemic caused?
There is little doubt that for the past decade or more, the complexities and costs of conducting clinical research have skyrocketed, along with expanded regulations. The real question is, to what end? Have we made clinical research more efficient, accessible, or effective? I suspect not. Quite the opposite—we have made clinical research less efficient and accessible, and potentially less effective. To understand how we got here, let us examine these issues individually.
When I finished my fellowship in medical oncology in 1998, I wrote interventional protocols that were typically 20 to 40 pages long, along with informed consent forms that were, on average, 8 to 12 pages long. Fast forward 25 years, and protocols for our typical investigator-initiated studies now span 80 to 100 pages long, with consent forms of 20 to 25 pages or more. For industry-sponsored studies, I have seen these numbers reach double these amounts! These latest versions of clinical trials are more comprehensive, but they are also more complicated, increasing staff workload and the likelihood of medical errors. The stress associated with these burdens has added to the burnout many researchers and staff are experiencing. It is time to swing back the pendulum on clinical study complexity.
Institutional Review Boards play an essential role in our clinical research process, providing independent oversight, review, and reporting of deviations from and violations of our code of conduct. But who reviews the Review Boards? Even though we require our consent forms to be written at an eighth-grade reading level, what eighth grader can read and retain the content of a 35-page document, especially one without visuals? Although these documents rightly refrain from making any persuasive arguments regarding the unproven benefits to the participant of taking part in clinical research, to what extent has our ambitious display of every possible complication dissuaded our underrepresented populations from trusting the process enough to participate? Perhaps we need to examine the unintended consequences of unabridged transparency without meaningful context.
Undoubtedly, these complexities have contributed to the overall rise in clinical research costs. Oversight from third-party clinical research organizations, increased institutional overhead and oversight, the extra time needed to conduct patient assessments, and a larger number of staff needed to operationalize these trials have all contributed to a 5- to 10-fold increase in the cost of conducting clinical research over my career. Although these costs are justified, they are not sustainable. More and more centers, both community and academic, are cutting back on or discontinuing clinical research. What will be the breaking point to force a reboot of the system? I don’t know, but from my perspective, it cannot come soon enough.
Daniel J. George, MD