Andrew J. Cowan, MD, is an associate professor in the Clinical Research Division of Fred Hutchinson Cancer Center in Seattle.
When I was an oncology fellow, a senior faculty member likened the career of a clinical trialist to “being in a straitjacket for the rest of your professional career.” These are hardly words of encouragement for junior faculty who are both excited about this career and looking for direction! Determined not to let others repeat my mistakes, I want to share the pearls I’ve acquired from developing and conducting clinical trials over the last several years. To help illustrate these points, I’ve imbued my nuggets of wisdom with pop culture references in the grand tradition of the legendary “top 10” lists by former ASH Clinical News Associate Editor Joseph Mikhael, MD.
- “With great power comes great responsibility” — Ben Parker, Spider-Man (1972). When leading a clinical trial, you have great power and are responsible for everything, including the things you have no direct control over. This means that any protocol deviation or mistake is ultimately your responsibility! It can be frustrating when a major deviation occurs that was not your fault but is still your responsibility. However, you must take ownership for your team — that’s the mark of a good leader.
- “Alone we can do so little, together we can do so much” — Hellen Keller (1920s). As Helen Keller points out, it is imperative to have a good team. Being the principal investigator (PI) comes with great responsibility, but that responsibility shouldn’t be a barrier to trusting your regulatory staff, clinical research coordinators, research managers, and data coordinators. Maintain good relationships with all of them — your success in conducting a trial according to best practices is dependent on the strength of the team!
- “Is that what you think? IT DOESN’T MATTER WHAT YOU THINK!” — The Rock (2011). PIs are highly trained, well-meaning physician-researchers who want to advance medical science while offering new therapies to patients. In some cases, however, our desire to do what we THINK is best for a patient conflicts with trial protocol. Although common, eligibility criteria violations should be a “never” event. Clinical trial eligibility criteria are not flexible — the reality is that it really doesn’t matter what YOU think, it only matters whether patients meet the criteria.
- “It’s Groundhog Day!” — Phil, Groundhog Day (1993). In the movie, Bill Murray’s character wakes up reliving Groundhog Day over and over again until he gets it right. So much of clinical research is repetitive, iterative, and tedious — signing off on clinical research forms, signing off in the online electronic data capture system, completing dose modification sheets, and so on. However, these monotonous tasks are so important to get right, so just like Phil in Groundhog Day, you must do them repeatedly.
- “Be like water making its way through the cracks” — Bruce Lee (1971). Bruce Lee applied many of the lessons he learned in martial arts to everyday life. In the context of clinical research, his advice to “be like water” means you must be flexible and fluid. Your patient in a phase I trial has a serious adverse event (AE) on the weekend? You need to be ready to address and report it in a timely manner. Your patient receiving cellular therapy has severe immune-related toxicities on trial or an unexpected treatment-related event? You must be flexible and fluid when dealing with unexpected outcomes, and Bruce Lee’s advice to “be like water” could not be more germane!
- “You can observe a lot just by watching” — Yogi Berra (1963). Becoming a skilled PI takes more than just intellect. You need to pay attention to your entire team. From the beginning, observe and learn what all of your team members do. How do they interact? What role does regulatory have in your team? If you have clinical research nurses, what are they doing and how can they best contribute to your team? Meet with your research coordinators regularly; they appreciate getting to know you, and open communication will facilitate better patient care on trials.
- “I gave my blood, sweat, and tears for this” — Taylor Swift, “You’re On Your Own, Kid” (2022). Although clinical trials offer a lifeline to patients — giving hope and providing disease control — don’t forget that they must go through a lot of blood (literally), sweat, and tears to be a trial participant, especially with phase I trials. The burden of testing can be tough on patients who are already dealing with the weight of a blood disease. Be mindful of this — and more important, when writing your investigator-initiated trials, try to think of how you can make the patient experience better.
- “Now you’re just somebody that I used to know” — Gotye, “Somebody That I Used to Know” (2011). Everyone knows the feeling of being ghosted or left hanging when an important email goes unanswered. You feel disrespected and frustrated by the lack of communication. One of the most common complaints from colleagues who left academia for industry is the lack of responsiveness among PIs. When you see an email from someone on the sponsor’s side, or even from your own staff, about a trial-related concern, be prompt with your responses. I stick to the 48-hour rule for email responses when it comes to clinical trials.
- “Higher. Further. Faster” — Captain Marvel, The Marvels (2023). Sometimes it’s easy to get lost in the weeds of patient enrollments, investigator calls, and AEs. Therefore, always remember why we do this: answering the call to go higher, further, and faster than we have before. Why do we have such dramatic advances in immune-based therapies in hematologic malignancies? Why are we now successfully applying gene therapy in sickle cell disease? It’s because of clinical trials, the patients who participated, the whole research team — including you, the PI — and the trial sponsors. Try to remember your mission to advance care for hematologic diseases.
- “Stay on target!” — Gold leader, Star Wars: Episode IV — A New Hope (1977). In the heat of battle, PIs on clinical trials should resist veering off protocol due to personal biases. Only medically justified reasons or patient decisions should lead to patient withdrawal, thereby ensuring the mission’s success. Safety and autonomy are paramount, but so too is the integrity of our collective quest for the knowledge that comes from a clinical trial.
Andrew J. Cowan, MD
Associate Editor
The content of the Editor’s Corner is the opinion of the author and does not represent the official position of the American Society of Hematology unless so stated.
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