Time to Get Going on Involving FITs in Clinical Trials

Formative research experiences during fellowship training are critically important for building the foundation of knowledge and skills necessary to launch a successful academic career. Traditionally, these opportunities have ranged from basic laboratory experiments to retrospective epidemiologic cohort studies. Involvement in clinical trials represents another valuable experience for fellows-in-training (FITs) but is much more challenging to facilitate. The merits of fellow-initiated clinical trials have previously been described in this space¹ and should be supported. However, this model has yet to be embraced on a national level, and a paucity of funding to support fellow-initiated clinical trials limits exposure for the majority of FITs.

In the interim, one alternative model for FITs eager to learn about conducting clinical trials is to serve as a co-investigator alongside faculty mentors in active randomized controlled trials (RCTs). Given the large number of RCTs in cardiology ongoing worldwide, this approach could immediately impact a significant number of trainees across a broad range of training environments. With this in mind, the Principal Investigators (PI) designed the Get Going trial—an international multicenter RCT intended to examine the effect of a wearable accelerometer (which measures step count) on physical activity following a cardiovascular hospitalization among frail older adults.² Unique to this study was the additional key objective of engaging FITs in an RCT experience and subsequently facilitating their career development. Accordingly, the PIs mandated that all participating sites involve an FIT in all key operational aspects under direct supervision from a local faculty mentor.

The Get Going trial launched in January 2016 and included 15 sites across Canada and the United States. Every site included a local faculty mentor and an FIT in either cardiology or geriatrics. The PIs leveraged the American College of Cardiology (ACC) Geriatric Cardiology member section to identify faculty and FITs interested in participating. The study enrolled 65 participants through November 2017 but was ultimately stopped early upon the recommendation of the Data and Safety Monitoring Board (DSMB) based on interim analyses showing futility of the intervention. While the study itself did not meet its primary target, it did successfully introduce a novel mechanism for FIT engagement and career development. At the conclusion of the trial, FITs unanimously agreed that they learned a tremendous amount about the technical aspects of running an RCT. In addition, this unique study design facilitated opportunities for mentorship and network-building; FITs routinely engaged with and learned from like-minded trainees and extramural mentors across the continent who share an interest in Geriatric Cardiology—an emerging field dedicated to the provision of cardiovascular care to meet the specific needs of older adults.³ As 3 of the FITs involved in the Get Going trial, we share the many benefits of this unique experience which most notably included: 1.) acquisition of technical skills related to running a clinical trial, and 2.) increased access to mentorship and networking opportunities beyond our respective institutions.

Technical skills: the nuts and bolts of running a clinical trial

A number of technical skills are necessary to run an RCT, ranging from Institutional Review Board (IRB) management to recruitment and retention of participants to the handling of adverse events. As the study launched, one of our first tasks was to apply for IRB approval. While obtaining IRB approval is not unique to an RCT, the regulatory oversight for an interventional clinical trial is greater than that of an observational or retrospective study. Accordingly, many of us experienced several related challenges. For example, many of us had to engage in lengthy discussions with our local IRBs to provide detailed explanations of the mechanisms in place that would mitigate the risks of recruiting adults aged older than 70 years, a subpopulation that statistically experiences an increased rate of adverse outcomes compared to their younger counterparts; at least one site had to restrict enrollment to age <89 years per their local IRB’s request. Several sites were also required to provide additional layers of regulatory paperwork to engage in international research and Veterans Affairs-based research, while others encountered medico-legal issues related to the language of the protocol and legal responsibility of the institution. Data acquisition from the accelerometer devices and their storage also introduced challenges and further highlighted the variability in local IRB requirements and expectations.

Robust recruitment of participants and subsequent retention over the course of the study represent critical elements of any successful RCT. During our semi-monthly study-specific conference calls, we frequently shared best practices and strategies with one another to maximize recruitment and ensure participant retention across sites. Recruitment strategies employed multidimensional approaches that included screening inpatient charts, engaging the clinicians who provided direct care to potentially eligible participants, presenting at divisional conferences, and posting flyers in opportune locations. Although the study duration was only 30 days, coordinating follow-up visits for older adults offered its own challenges, not surprising given the issue of patient retention in Geriatrics research.⁴ Managing follow-up visits, while also balancing our own clinical duties and fellowship obligations, proved to be an excellent tutorial in time-management and coordination. Facing these various constraints, FITs implemented creative solutions, even conducting house-calls on occasion to collect the 30-day follow-up data of participants. This valuable experience not only reinforced the importance of having specific processes in place to promote retention but also gave us all a greater appreciation for the efforts necessary to conduct a successful large-scale RCT.

During the Get Going trial, we were also expected to detect and report adverse events. Some of the adverse events observed in this trial included hospital readmission, implantable cardioverter-defibrillator (ICD) shocks, and even one death. Although these events were not necessarily related to our accelerometer-based intervention, we learned first-hand of the rigor necessary to properly document and report all potentially adverse events, even if seemingly unrelated. This involved notifying several different regulatory bodies—the IRB, study PIs, and DSMB— further highlighting the personnel and efforts necessary to undertake an RCT.

For most of us, the Get Going trial marked our first exposure to a DSMB. Through the opportunity to observe DSMB meetings, we acquired valuable knowledge regarding the role of a DSMB in providing oversight for a trial. In particular, discussions between the DSMB and PIs regarding premature termination of the study offered unique insight into the real-world challenges of conducting an RCT, including the critical lesson that RCTs have finite resources.

Mentorship and Networking

In addition to the technical skills, the Get Going trial also provided an excellent forum for mentorship and networking. Mentorship is critical to the career development of any junior investigator and comes in many forms. The PIs of the Get Going trial served as mentors to all of us, not only by facilitating our involvement in this unique opportunity, but also by modeling for us how to properly run an RCT (and how to effectively mentor junior investigators). Social learning theory, which states that behavior is learned from the environment through the process of observational learning, represents a major tenet of medical education.⁵ Observing the PIs manage the operational challenges of the study will one day allow us to apply similar principles when we have the opportunity to run our own RCT.

The Get Going trial also enabled us to develop broader networks of faculty and like-minded peers who share an interest in Geriatric Cardiology. Semi-monthly phone calls facilitated our direct interaction with the trial PIs, as well as many of the preeminent leaders in Geriatric Cardiology. Such interactions have since matured into opportunities for interested FITs to serve on committees, co-author manuscripts, and give presentations at national conferences, furthering our own academic careers. Interactions with fellow FITs have also proven fruitful. Many of us remain in touch and have collaborated on other projects, as well as shared experiences and advice on various topics relevant to navigating academia as junior investigators, and more recently as junior faculty.

Conclusion

Since the Get Going trial finished, the three of us have each successfully transitioned into academic faculty positions and have continued to pursue careers within Geriatric Cardiology. Based on this invaluable experience, we are uniquely positioned to thrive as junior investigators and believe that additional formative opportunities for FITs such as our own Get Going experience are greatly needed. Accordingly, it is time to Get Going on involving FITs in clinical trials on a more routine basis. We encourage senior investigators to consider strategies to incorporate FITs into proposed RCTs, potentially leveraging ACC member sections to identify and engage interested FITs, just as the Get Going PIs did. As the three of us can attest, such opportunities can transform careers.