Site Principal Investigators in Multicenter Clinical Trials: Appropriately Recognizing Key Contributors.

Correspondence to: Robert J. Mentz, MD, Duke Clinical Research Institute, P.O. Box 17969, Durham, NC 27715. E-mail [email protected] Robert J. Mentz, MD Eric D. Peterson, MD, MPH The success or failure of multicenter clinical trials will remain dependent in large part on the engagement of the site principal investigator (PI). Site PIs play an important role in trial selection, site activation, and study execution, including the development and implementation of a strategy to maximize enrollment, optimize data quality, and ensure patient retention. It is notable that the legal, regulatory, financial, and workload burden for site PIs has grown considerably over time (Figure).1 In contrast, the benefits for serving as a site PI have become less evident. As a result, increasing dissatisfaction exists among physicians involved as site PIs in multicenter trials and there is less interest in trial participation. In this article, we outline current responsibilities and challenges faced by the site PI and propose new strategies to improve the engagement and recognition of site investigators moving forward. The roles and responsibilities of site PIs in a large clinical trial relative to those of the trial’s overall study leadership can be likened to the stage crew and principle actors in a theater production. The stage crew spends hours with set preparation and the logistics of production, which ultimately the actors will benefit from and receive recognition for. Similarly, the site PIs and their research team identify and recruit patients, conduct study procedures, complete necessary study documentation/reporting, and retain patients for outcomes assessments. However, the overall trial leadership most commonly reports the major trial results and receives national and international recognition. Specific examples of the workload of the clinical investigator include assisting with the screening process, discussing trial participation with patients and families, conducting study-specific patient visits, and participating in monitoring and regulatory visits—the end result being interruption in clinical workflow.2 Site PIs are also routinely held responsible for recruitment challenges (and subsequent financial struggles for unprofitable studies) despite having no role in developing the trial’s protocol. These experiences may be compounded by investigator stress related to the perceived complexity of clinical trials, a lack of training in trial concepts (eg, equipoise, allocation, informed consent), and difficulty in conveying these concepts to potential participants.2 Although a passion for trial participation may support continued involvement of some site PIs, we suggest that additional value may be required to support enhanced engagement and contribution from PIs. At present, the incentives for site PIs to invest time and efforts into clinical trial participation (beyond a desire to participate in the scientific process) are relatively limited. Despite the challenges of the site PI role, some investigators express motives involving altruism related to providing patients with access to clinical trial opportunities.3 Conversely, self-interested motives have also been documented, including enhancement of reputation.3 Moreover, participation in trials provides access to new technologies, devices, and medications that can enhance and promote the local clinical practice. Depending on a site’s payment structure, circumstances may exist where an individual investigator can translate clinical trial enrollment into a financially Site Principal Investigators in Multicenter Clinical Trials