Clinical Trials: Crying Out for Collaborative Innovation
By Brad Smith
Clinical trials, the single largest contributor to the time and cost of medical research, are important, expensive, complicated, and opaque. Making them more efficient and effective is of central concern to all those invested in improving the R&D ecosystem, from investigators to product developers to regulators and, most importantly, to patients. We can’t just improve clinical trials; we need a paradigm shift. One way to find innovation is through new and powerful collaborations.
Clinical trials are essential to determine if a new medical product is safe and effective, and to provide the U.S. Food and Drug Administration (FDA) with the data it needs to approve a product for marketing in the United States. Without these studies, there would be no way to know if a drug or device is truly able to treat a disease and that the benefits of using the product outweigh any harms caused by side effects.
According to one prominent analysis, clinical development of a new drug accounts for 63 percent of the time from first discovery to regulatory approval. In addition, the same analysis found that average out-of-pocket clinical development costs reached $930 million, more than twice the $430 million cost of pre-clinical development.
The reason trials are so expensive and time-consuming is that human biology – and human disease – is exceedingly complex. It is almost impossible to predict whether a new drug or device that may have worked perfectly in a lab setting or in an animal model will behave as expected in humans. Additionally, the genetic and other diversity of humans means that, ideally, a large, diverse population of people needs to be involved in a single trial so that we can confirm who will, and will not, benefit from the product.
Many trials are not able to recruit enough participants to be effective. Surveys have found that as few as 3 percent of adult cancer patients participate in clinical trials. While most trials ultimately enroll enough participants, it can take twice as long as estimated, and as many as 48 percent of the individual sites in a trial under-enroll study volunteers. One analysis found that 19 percent of studies are terminated or closed early due to insufficient enrollment – a waste of resources and patients’ time, and a tragedy in terms of scientific questions left unanswered.
Clinical trials are extremely opaque – both to researchers and to patients. While there is a public database of ongoing trials at ClinicalTrials.gov, a 2015 investigation found significant under-reporting of trials by companies and universities, resulting in a lack of shared knowledge of clinical research being done and its outcomes, as well as the risk of duplication of effort. The U.S. government has issued stronger regulations, and in response to provisions in the 21st Century Cures Act, the National Institutes of Health (NIH) is working to improve ClincialTrials.gov and take other actions to improve the usability, accuracy, and completeness of the database.
Technology and methodologies
With the emergence of innovative tools like real-world evidence, telemedicine, adaptive trial designs, mobile health apps (e.g., Apple’s ResearchKit), novel endpoints, and more[KS(6] , the system has the opportunity to promote a revolution in technologies and methodologies that can lower costs and shorten timelines of clinical development, and – most importantly – deploy the rarest of commodities, patients, much more ethically and efficiently[CW(7] . But neither government[KS(8] nor industry can do this on its own. In addition to NIH’s work, some of these important challenges are being tackled in various ways across the ecosystem. Two prime examples are the private-sector collaboration TransCelerate and the FDA-supported Clinical Trials Transformation Initiative.
Perhaps the greatest opportunity to improve clinical trials will come from the ongoing culture shift that is moving patients to the center of the innovation system and transforming them from the “subjects” of a clinical trial to “participants” in the research and “partners” with the trial’s clinicians and scientists. There are many examples of this shift, but one of the biggest is the NIH’s All of Us research program that is seeking to recruit 1 million people into a long-term, prospective study of their health. The NIH team has explicitly called these people “study participants” (not “subjects”) and has focused on ensuring a diverse population in the study so that all can benefit from the resulting science. Engaging participants early and often can result in more relevant questions being asked, better study designs, improved recruitment, and greater adoption of research findings.
FasterCures and Collaboration 2.0
Clinical trials are inherently collaborative, requiring participation by many players. There are numerous groups focused on improving the execution of clinical trials as they currently exist, to enhance efficiencies and lower costs. [KS(9] Through its new Collaboration 2.0 program, however, the FasterCures team is exploring ways that collaborative innovation and new partners can enable seismic shifts in clinical trials. The goal is to maintain scientific rigor so that FDA can still make its regulatory decisions, but to work with all stakeholders to improve the entire system.
The stakes are high – both in economic and human terms. We must do better, and, through collaboration and innovation from all parties, we will.