As I was applying for jobs at the end of my fellowship, what I would focus my research program on going forward was unclear, as I had spent 2 years in residency and 1 additional year in my fellowship in a basic science lab, as many aspiring surgical oncologists do. I learned many things, including that I LOVED basic science and also how to ask answerable questions, but I knew that running my own lab was not for me. Fortunately, as we discussed the details of my (current) job, my future partners had a plan. “We want you to reinvigorate the clinical trials program in our group.” Being a good surgical oncology fellow about to take a job at my home institution I said “Sure!” and then slightly panicked because I realized I had no idea how to develop or run a clinical trial. This blog describes a path (my path) and lessons learned along the way for becoming a surgeon clinical-trialist. Although we are currently small in number, I hope this will inspire others to see the reward and importance of surgeons being leaders in clinical trials.
- Identify the need
Like any good research project, the first thing to do is identify the need and knowledge gap. In clinical research, the summit of the evidence hierarchy focuses on clinical trials (and meta-analyses based on these trials). However, the Institute of Medicine estimates that 80-90% of therapies are not supported by high-quality clinical evidence such as that provided by clinical trials. The number of surgical clinical trials pales in comparison to other medical specialties and what compounds the dearth of prospective evidence in surgical care is the lack of well-planned, completed surgical trials. Although >300 surgeon-led trials were registered in clinicaltrials.gov between January 2011-December 2012, almost 75% of these trials were associated with research waste, defined as non-publication, inadequate reporting or presence of avoidable design limitations.1 Recognizing this gap in knowledge in the field (as well as myself), I realized there was an opportunity to make meaningful change for our patients.
- Get educated
Having identified the need (and potential opportunity for me to contribute), I quickly realized I needed to do some serious learning. I recognized that aside from my biostats class in medical school, I had really had no education on how to do good clinical research (let alone clinical trials). Fortunately, within my local area, there was a clinical research program that existed to fulfill my needs. Therefore, I spent the first few years of my faculty appointment obtaining a Masters in Clinical Research. This program was important for several reasons: It was for physicians and taught by physicians (including surgeons such as Lillian Kao, MD) which made it feasible in terms of time commitment (Wednesday afternoons) as well as practical. We learned that although the holy grail of clinical trials were large, phase III double-blind randomized controlled trials, these were not always (and some could argue rarely) feasible but that a well-designed prospective study was better than no study at all. For surgeons, I think this is a particularly important message. Programs such as this are available at many universities and in the current virtual-friendly environment, I imagine online learning opportunities will continue to grow over time.
In addition to advanced degrees, there are many courses offered by societies, including surgical societies to aid in clinical trial development. In oncology, societies such as ASCO and AACR offer annual courses where the participant submits a concept and works through it over several days, with the goal of having a completed protocol at the end of the workshop. The American College of Surgeons recently released a didactic course on developing prospective trials, which can be purchased from the ACS for a small fee. https://learning.facs.org/content/designing-and-running-prospective-surgical-clinical-trial-course.
At my institution, there are similar clinical trials courses offered to faculty. We recognized that there was a need for educating our fellows on clinical trial development and therefore, we developed a Clinical Trials Course for fellows which involves multiple days of lectures as well as clinical trial concept development over the course of several months.2 Hopefully, exposing surgeons to the clinical trial pathway earlier in the careers will inspire more surgeon clinical-trialists.
- Start small, but start something
One major hiccup that all clinical-trialists (especially those just starting out) run into is trying to answer too many questions or too large of a question in the first go-round. In every field of medicine, including surgery there is one BIG question that we would all love to answer. Unfortunately, there are probably several reasons why that question has not been answered: a) it is not an answerable question in the current form, b) it would take too many patients to answer the question in a reasonable time period and c) it would cost too much to complete the trial. But, that does not mean that the question can’t be broken down into smaller parts to get to the answer. Novel clinical trial designs are important for identifying ways to design studies that address problems in answerable ways, sometimes with surrogate outcomes. For example, if you are interested in reducing long-term opioid dependence, instead of designing a large, multi-year trial to look at the long-term use of opioids in surgery patients (which is an important but complicated and multi-factorial questions), try designing a trial evaluating ways to reduce post-operative prescribing with an end-point of 30-day opioid use, as an example.
- Mentors
Like almost everything in academia, having sound mentors is a key to success. The logistics (including regulatory and financial processes) and responsibilities of running clinical trials can be daunting. Identification of mentors in your disease area as well as those that have experience of the nuances of running successful clinical trials is imperative to getting your trial to completion. Many institutions offer support for budgeting as well as regulatory processes including working with the FDA and clinical trial registration.
- Get involved
Finally, there is no better way to become familiar with running clinical trials than getting your hands dirty. One great way to see this process is through the cooperative group network. Most surgical disciplines have cooperative groups for performing multi-institutional trials. These groups are often looking for early-career faculty (and some require it) to be co-PIs on clinical trials. Participation in these groups is invaluable in seeing the process of protocol development and activation which is often a complicated, multi-step process. In addition, participation in your institutional scientific review committee or institutional review board can expose you to examples of clinical trials in other disciplines to learn about novel trial designs, etc.
Well-designed clinical trials can be practice-changing and significantly affect the length and quality of the lives of our patients. Surgeons have a unique perspective and are often the primary team leaders for multidisciplinary care, which gives us the unique opportunity to add to the high-quality evidence that our patients deserve.
References
- Chapman SJ, Aldaffaa M, Downey CL, Jayne DG. Research waste in surgical randomized controlled trials. Br J Surg. 2019;106(11):1464-1471.
- Roland CL, Grubbs EG, Katz MHG, Teshome M, Hunt KK, Tzeng CW. Clinical trials-Designing, implementing, and collaborating. Journal of surgical oncology. 2020;122(1):25-28.