The principal investigator landscape remains a challenge for clinical trial sponsors
New study sheds light on the factors for high turnover of principal investigators in FDA-regulated clinical trials.
The U.S. biopharmaceutical industry is a global leader in the development of innovative therapeutics. Advances in biotechnology and biomedicine are enabling drug manufacturers to address complex diseases for which there are currently insufficient treatments, like diabetes, cardiovascular conditions, and mental disorders. While these diseases each affect only a small proportion of the general population, they collectively represent an important area of medical need and are thereby a strong focus of new therapeutics development. While the potential of the discovery pipeline is promising and robust, substantial challenges remain in the clinical trial process that is used to evaluate the safety and efficacy of new therapeutics.
Early analysis of the clinical trials landscape in the US showed that the numbers of both industry-sponsored clinical trials and principal investigators (PIs) conducting such studies had declined steadily since 2001. At the same time, turnover rates among PIs sharply rose, as did regional and gender disparities1,2. These first-in-kind studies were conducted by the Boston-based Tufts Center for the Study of Drug Development (Tufts CSDD), which provides strategic information to help drug developers, regulators, and policy makers. Tufts CSDD conducted extensive analyses of a database of more than 100,000 PIs who registered with the U.S. Food and Drug Administration (FDA) between 1977 and 2007. Ken Getz, Director of Sponsored Research Programs at Tufts CSDD and one of the authors of the studies, noted at the time of publication that these trends pose several threats to research sponsors, as the capacity of the market to conduct clinical trials is eroding and efforts to establish well-trained, experienced pools of clinical investigators are becoming more difficult.
A new study from the Duke Clinical Research Institute in Durham has revealed key factors associated with investigator turnover3. The work was based on an online survey that aimed to identify the determinants influencing PIs to cease participation in FDA-regulated clinical drug trials, particularly those who stopped after participating in only one trial (so-called “one-and-done” PIs).
Of the 201 PIs who responded, 54.2% were classified as “one-and-done.” Among them, a third reported having decided not to conduct another trial for personal reasons, while almost half indicated interest in conducting another trial but cited a lack of opportunities to do so. The study identified three categories of barriers that affected a majority of these investigators’ decisions to cease participation in FDA-regulated trials:
1) Work-load balance (balancing trial implementation with other work obligations and opportunities)
2) Time requirements (the time necessary to initiate and implement the trial, or investigator and staff time)
3) Data and safety reporting
These findings confirm the high rate of investigator turnover, as more than half of the respondents in the survey were indeed “one-and-done” PIs. Interestingly, a large portion of respondents expressed an interest in conducting more FDA-regulated trials if there were opportunities, which indicates the need for mechanisms that match interested investigators with research sponsors.
The authors of the study believe the experiences respondents reported can be used to raise awareness of the causes of turnover, to start designing potential interventions encouraging sustained engagement in FDA-regulated clinical trials among one-time PIs, and to devise mechanisms linking PIs with study sponsors. This, combined with addressing the different barriers identified in the study, should encourage continued participation of experienced PIs in clinical research, benefiting the overall clinical research enterprise.
1 Current investigator landscape poses a growing challenge for sponsors. Tufts Center for the Study of Drug Development Impact Report. Volume 11 Number 1 • January/February 2009. http://csdd.tufts.edu/files/uploads/summaryjan-feb09.pdf
3 Contemporary Clinical Trials Communications, Volume 6, June 2017, Pages 31–38. http://www.sciencedirect.com/science/article/pii/S245186541630093X