Overcoming False Starts, Difficult Strategic Decisions and Regulatory Hurdles to Secure Your First Trial

Connor Brenna, MD

The most engaging clinical trials will often appear deceptively simple. They ask an elegant question, present seamless methods, and report findings with so much clarity that it can look as though success was inevitable from the outset. Of course, the polished final product that we see in published trials seldom captures some of the most important but least visible elements of the process: false starts, difficult strategic decisions, regulatory hurdles, attempts (and reattempts) to secure funding, and various other setbacks and decisions that shape a trial. The complexity of these steps can be further multiplied when trials extend across multiple institutions or are conducted in partnership with industry, because coordination, competing priorities, and operational scale introduce additional layers of difficulty. Two of the leading trialists in our community demystified some of these challenges in “Directors Cut: Trials and Tribulations of Your First Trial,” a session cosponsored by the Early-Stage Anesthesiology Scholars (eSAS) and delivered on May 2, as part of the Scholars’ Day at the 2026 Annual Meeting, presented by IARS and SOCCA.

In “Leading Your First Multicenter Trial: Perspectives and Lessons Learned,” Jessica Spence, MD, PhD, an assistant professor at McMaster University, an investigator at the Population Health Research Institute, and an anesthesiologist and intensivist at Hamilton Health Sciences, spoke to some of the many unique challenges of large, multicentered trials. Dr. Spence’s team recently completed B-Free, a pragmatic, multiple-period, cluster randomized crossover trial conducted in 20 North American cardiac surgical centers. B-Free randomized an impressive 19,768 patients to liberal or restrictive intraoperative benzodiazepine administration protocols, and found that restricting benzodiazepines did not significantly reduce the incidence of postoperative delirium. Drawing on this experience, Dr. Spence distilled her insights into ten discrete pieces of advice for those designing their first trial:

1. Find the right mentors (and many of them).
2. Start with a question you really care about—you must believe in it, and it cannot just be your mentor’s project.
3. Keep it simple. This is especially true for multi-center trials, when you will be asking other sites to follow the protocol you have designed.
4. Take feedback: not just from your mentors, but from your research team and from your patients.
5. Build a team with both formal expertise and practical experience.
6. Choose your partner sites carefully, and make sure you choose sites with genuine buy-in to your idea.
7. Do not take delays or rejection personally, because they are just part of the process.
8. Like research broadly, multi-center trials are necessarily a team sport.
9. Write (a lot). Practice writing clearly and succinctly and, with all the writing you do, consider publishing your steps (e.g., a study protocol) as well as the final product.
10. Set aside and protect your time for deep work.

The second presentation, “Leading Your First Industry-Funded Trial: Perspectives and Lessons Learned” was delivered by Ashish Khanna, MD, MS, professor of anesthesiology and vice-chair of research with the department of anesthesiology, section on critical care medicine at the Wake Forest University School of Medicine, and inaugural director for the Perioperative Outcomes and Informatics Collaborative (POIC). Dr. Khanna spoke about his first industry-supported trial, ATHOS-3, which was funded by La Jolla Pharmaceutical Company. The trial—published in NEJM—demonstrated that angiotensin II increases blood pressure in patients with vasodilatory shock, in whom other conventional therapies fail. The story of his leadership in ATHOS-3 was defined by persistence, mentorship, and the fortitude to weather many obstacles: not least of all the considerable challenges in recruitment for a trial studying critically ill patients requiring vasopressors for septic shock. Dr. Khanna described ATHOS-3 as the study that began a translational journey that has since led to numerous other trials borne out of industry partnership. Dr. Khanna’s lessons for the emerging trialist:

1. Be nimble. Industry-funded trials can move quickly and rarely wait for ideal conditions.
2. Pre-empt the problems your trial will face.
3. Aim to be #1 in the things that you do. An excellent trial will not happen by accident.
4. Own the data in your trial (and not just the results).
5. Follow a “plan-grant-next” cycle. Each trial should be a step within a larger scientific program. For Dr. Khanna, ATHOS-3 was a launching pad into sustained industry partnership and an ever-growing body of work.

A common theme across both sessions was that good clinical trials require more than a brilliant idea. They require intention, leadership, judgment, and perseverance. Importantly, the trials and tribulations of coordinating independent sites or forging industry partnerships are not incidental to the process; they are the process. Fortunately, with sessions like this, trainees and early-stage investigators can anticipate at least some of these challenges before they arrive.

Editor’s Note: Connor Brenna, MD, a research fellow in the Perioperative Brain Health Centre (PBHC) at Sunnybrook Health Sciences Centre, as well as a trainee in the University of Toronto’s Clinician Investigator Program, moderated this session.