Dr. Abelson credits his undergraduate training in experimental psychology as being invaluable for his career in clinical research. It taught him the fundamentals of writing a protocol, analyzing data, and identifying flaws in a study—skills he directly applied to drug development decades later.

In domains with extreme outcomes (music, startups), success is heavily influenced by luck, making it difficult to replicate. A more effective strategy is to study the common failure modes of the vast majority of talented people who tried. This provides a clearer roadmap of what to avoid than trying to copy a lucky winner.

Clinical trial protocols become overly complex because teams copy and paste from previous studies, accumulating unnecessary data points and criteria. Merck advocates for "protocol lean design," which starts from the core research question and rigorously challenges every data collection point to reduce site and patient burden.

Beyond scientific rigor, designing a truly effective clinical trial protocol is a creative process. It involves artfully controlling for variables, selecting novel endpoints, and structuring the study to answer the core question in the most elegant and precise way possible, much like creating a piece of art.

Novo Nordisk ran a nearly 4,000-patient Phase 3 Alzheimer's trial despite publicly stating it had a low probability of success. This strategy consumes valuable patient resources, raising ethical questions about whether a smaller, definitive Phase 2 study would have been a more responsible approach for the broader research ecosystem.

Foster a culture of experimentation by reframing failure. A test where the hypothesis is disproven is just as valuable as a 'win' because it provides crucial user insights. The program's success should be measured by the quantity of quality tests run, not the percentage of successful hypotheses.

Disagreeing with Peter Thiel, Josh Wolf argues that studying people who made willful mistakes is more valuable than studying success stories. Analyzing failures provides a clear catalog of what to avoid, offering a more practical and robust learning framework based on inversion.

Novo Nordisk's large semaglutide Alzheimer's trial failure highlights a critical design flaw: launching a massive study without first using smaller trials to validate mechanistic biomarkers and confirm central nervous system penetration. This serves as a cautionary tale for all CNS drug developers.

After reacquiring a "failed" ALS drug, Neuvivo's team re-analyzed the 200,000 pages of trial data. They discovered a programming error in the original analysis. Correcting this single mistake was a key step in reversing the trial's outcome from failure to success.