Author + information
- Yan Liu, MD, PhD∗ ( and )
- Xuming Dai, MD, PhD
- Division of Cardiology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- ↵∗Reprint requests and correspondence:
Dr. Yan Liu, Division of Cardiology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7075.
Research during cardiology fellowship is important for fellows-in-training, advancing knowledge on cardiovascular diseases and improving quality of patient care. However, the challenges are real and have been well outlined (1,2). Individualized and systematic strategies to overcome these challenges, including an innovative American College of Cardiology Research Network, have been intensively discussed in recent Fellows-in-Training (FIT) & Early Career (EC) pages (2,3).
An important question is how a young investigator with limited research experience could work around these challenges and produce high-quality data that affect patient care directly. However, fellows have the advantage of being at the front line in cardiovascular care by being in direct contact with a large number of patients. This exposes the clinically important knowledge gaps and reveals the unmet need of clinical research. Funding is an important aspect of research, but there are alternate sources often looking for clinical collaborations actively (4). By taking advantage of the above, we propose that fellow-initiated clinical trials (FiCTs) are not only feasible, but also a fundamental form of research in modern cardiology FIT and EC development.
FiCTs refer to clinical trials that arise from the initiative of a fellow or an EC cardiologist who serves as the principle investigator (PI), while a senior faculty member either supervises or serves as co-PI. FiCTs often focus on a specific but novel clinical question, with a design feasible to complete within the duration of the fellow’s training. Unlike large industry-sponsored trials, which are usually designed to test a new medication or technology (5,6), FiCTs usually focus on highly hypothesis-driven, single-center, smaller studies aiming to identify new ways of using existing, less expensive treatments or technologies with well-known safety profiles; a novel use of a diagnostic test; or a new strategy to improve the efficacy, cost-effectiveness, and quality of patient care.
In this paper, we propose a stepwise strategy of planning and conducting an FiCT, including how to take on the challenges and maximize our opportunities, with a goal to provide a blueprint that a young investigator can use to start his/her first trial.
The 10 steps of FiCTs are as follows:
1. Ask a clinically important and novel question. Identifying a “gap” in the available evidence or an unmet clinical need is the first step leading to important and novel research. The idea has to be unique. A careful and detailed search of the published data will help to verify that the gap truly exists and highlight some of the challenges faced by other investigators working around a relatively similar concept. This will lead to a better understanding of the subject and lead to the design of a better protocol and, ultimately, a more refined study.
2. Find a mentor. Establishing a mutually beneficial mentor–mentee relationship is vital for FiCTs. Discussing the idea with your advisers or experts in the field before proceeding to next steps is essential for a polished hypothesis and will save you a lot of time going forward. A good mentor is one of the key determining factors of successful and productive research during fellowship.
3. Find collaborators, locally or through networking. Equipped with a common interest, the collaborators can be a start-up company, a PhD researcher, a core laboratory facility, a colleague, or a nonprofit organization. Once you have a research question in mind, the next step will be to conduct a search through the published data or networks to find a collaborator of common interest, which will dramatically enhance your chance to get funded and later execute on the trial. For example, a start-up company that is developing a novel clinical assay would be eager to collaborate on a trial testing the clinical utility of the assay.
4. Getting funded. When it comes down to getting funded, FiCTs should focus on state or local sources, instead of competing for federal funding with pure PhD researchers or large trial institutions. There is a national consortium of >60 medical research institutions in >30 states with translational or clinical research funding of variable sizes to support smaller, local clinical studies (7). The industry funding sources, especially start-up companies, are also especially suitable when you are collaborating with them already. The translational institutions often have designated funding to bring local clinical researchers and start-up companies together—a great opportunity for FITs.
5. Institutional review board and clinical trial office process—appropriate expectation and planning. With collaborators and funding in hand, it seems that the rest of the process would be easier. The reality is often quite the opposite, as now the process of working with the institutional review board (IRB)/clinical trial office starts. The IRB and research account set-up processes are time-consuming, and sometimes tedious and frustrating. Planning ahead and having appropriate expectations will make your experience with them more efficient and satisfactory. A reasonable strategy is to work around your rotation schedule, get the proposal done during an easy rotation, and wait for the IRB while you are kept busy anyway with calls and nights.
6. Putting together a good team is essential. The quality of your team determines the fate of your trial. The clinical trial coordinator is responsible for daily patient recruitment and follow-up. Hiring someone who fits the budget, is eager to learn, and is motivated is easier said than done, but college graduates who are interested in pursuing a career in medicine or clinical research are not too difficult to find. Some institutions have coordinators who can help. Regardless, a multidisciplinary team with a physician, coordinator, statistician, nurses, residents, and students—as well as insight and oversight from senior physicians and researchers—is the basis for a successful trial.
7. Supporting environment and resources—improvisation and improvement. Starting a clinical trial as a fellow or an EC does not mean recruiting patients alone, but instead means acting as a physician leader who works with supporting staff. The supporting environment for FiCTs varies among different institutes and is overall not yet optimized; even some prestigious clinical research institutions may not have a good FiCT supporting mechanism. Some institutions have designated coordinators and trial managers working with fellows with a goal to help with trial planning, IRB, funding management, and even hiring and training of new project-specific coordinators, which is a good mechanism to potentially model after. Improvisation in different supporting environments is needed from an FIT standpoint to keep your FiCTs ongoing, but improvement is warranted from an institutional aspect to encourage FiCTs.
8. Balancing between clinical duty and research—for now and for the future as a cardiologist. During the whole process of FiCTs, clinical training and patient care are the more important counterparts. Therefore, balancing between research and patient care is a constant routine for your present and future career. Three important points to remember are: 1) be a planner: set your timetable early, weeks or even months earlier so you are always prepared; 2) be a learner: talk to and learn from experienced senior cardiologists and field experts so that you will save time “staring at the map,” as they will often point you in the right direction; and 3) be a leader: pick the right team members, motivate and organize your team, and trust them to do their job and help them if needed. Good leadership improves team efficiency and saves time for everybody.
9. Aim for meaningful publications—design, execution, and analysis. A meaningful publication is the most effective way for FiCTs to have an effect on patient care. In addition to the novel and important question asked, there are 3 indispensable steps to publication: the appropriate design makes the study powerful; the good execution makes the study of high quality; and the thoughtful data analysis makes the study of significance. Following the stepwise strategies outlined in the previous text may not guarantee but at least will maximize the chance for FiCTs to have meaningful publications in the end.
10. Timing. Fellowship training is limited to 3 to 4 years in most programs. FiCTs require early initiation to recruit adequate patients, complete the designed study, and submit reports. Therefore, it is never too early to start planning for your trial during fellowship.
In summary, FiCTs should be considered as a fundamental form of research training in modern cardiology fellowship. As we discuss the strategies of performing FiCTs as fellows or EC cardiologists, we also call for improvement of the supporting environment for FiCTs from an institutional standpoint. Institutional effort on this aspect will not only stimulate vigorous fellow-initiated clinical research, but also improve health care efficacy and cost-effectiveness as a whole.
RESPONSE: Are We Committed to Training Fellows in Clinical Investigation?
The paper by Drs. Liu and Dai describes the opportunities and value of conducting fellow-initiated clinical trials. It sheds light on the important challenges that we face as cardiovascular leaders in training the next generation of cardiovascular clinical investigators. I commend the authors for comprehensively highlighting the activities that must occur to conduct a successful fellow-initiated clinical trial, but the question may overlook the true problem we will face in the future. Namely, how can we train the next generation of cardiovascular clinical investigators when there is a predicted shortage of clinical cardiologists and research training funds over the next 20 years?
The resources for academic training programs continue to decrease and adversely affect the opportunity to appropriately train cardiologists in clinical research. In contrast, the future is bright for improving cardiovascular human health over the next several decades, because every day new molecules, devices, and biological therapeutics are discovered and enter the arena of human investigation. Yet, if we do not have a national commitment from the U.S. cardiovascular community to train clinical investigators, none of these opportunities will emerge. For example, LCZ696, a drug that the cardiovascular community was committed to test against angiotensin-converting enzyme inhibitors, was found to improve clinical outcomes in heart failure patients. This positive result was due in part to the contributions of many highly experienced and skilled cardiovascular clinical investigators (1).
Today, as I look at training programs across the United States, I am concerned about the reduction in protected time for fellows to take part in clinical investigations. As 1 of the architects of the clinical investigator track in the Duke Heart Failure Fellowship, I felt it was imperative for future clinical investigators to complete a minimum of 1 year and preferably 2 years of protected time for clinical research training with qualified mentorship, didactic coursework, investigative initiatives around retrospective database analyses, prospective design of clinical registries or pilot clinical trials, the development of peer-review grants, participation in a multicenter study team, and conducting site-based research.
The undertaking of a clinical trial by fellows is complex, and it also requires the leadership and endorsement of cardiovascular program directors, division chiefs, and health system administrators to be possible. These trials require significant resources because of the requirements for a data safety monitoring board, institutional review board reviews, adjudication committee, monitoring, and audits, so that our patients can expect the highest level of protection against harm and the greatest likelihood of success. Cardiovascular leaders need to convince their health systems that this is a valued investment. Currently, many health systems rely on fellows, instead of hospitalists, for high-level care at a modest cost. These savings should be returned to the training programs for fellow research. Many of these private clinical trials afford opportunities to improve the value of care in the health systems by reducing length of stay, reducing readmissions, and improving survival. More importantly, in addition, these pilot studies can be the basis for peer-reviewed grants from the National Institute of Health or other institutions, resulting in millions of dollars back to the institution (2–5).
Thus, I applaud the authors for their continued interest to develop as clinical investigators, and yet, they should not believe that conducting a clinical trial would result in them becoming certified clinical investigators. A more comprehensive approach to their education is necessary. They should be the advocates for this, and as leaders, we should endorse this mission.
The authors would like to sincerely thank Dr. Pradeep Yadav for his kind help in the writing and editing of this paper.
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- ↵National Center for Advancing Translational Sciences. Available at: http://www.ncats.nih.gov/research/cts/ctsa/ctsa.html. Accessed May 28, 2015.