In Memoriam: A Tribute to Daniel J. Sargent, Ph.D.

Abstract

Dan Sargent, who died this year at the age of 46, applied innovative approaches to biostatistics and clinical trials. He fostered collaboration among researchers, government agencies, pharmaceutical companies, professional organizations, and academic statisticians from around the world to advance cancer research.

Daniel J. Sargent, Ph.D.

Dan Sargent was 46 years old when he died unexpectedly on September 22, 2016, during a brief hospitalization at the Mayo Clinic. He grew up in Rochester, Minnesota, where his family runs a successful landscaping business, before completing his undergraduate and doctoral degrees at the nearby University of Minnesota. While an undergraduate there, he caught the attention of Don Berry, the Bayesian statistician who works now at MD Anderson Cancer Center. Dan credited Don with luring him away from his childhood ambition to be an astrophysicist and convincing him to dedicate himself to biostatistics. I also credit Don with teaching Dan to love his work and to do it outside the boundaries of the field’s conventions.

Dan returned to Rochester in 1996 as a newly minted Ph.D. assigned to support the gastrointestinal (GI) program at the Mayo Clinic Cancer Center, which we led together. We met on his first day at work. In response to his admission that he knew nothing about GI cancer, we spent our first hour reviewing the American Joint Committee on Cancer staging manual for colorectal cancer. Twenty years later, his knowledge base was such that we worked together as members of the panel charged with revising the staging manual for its eighth edition. Our work together over 20 years has been a highlight of my life and led to 90 coauthored publications and many shared hours poring over databases, performing analyses, writing abstracts and papers, and presenting our work.

Among the many important things that defined Dan were two critical events that occurred in his youth. One was meeting his future wife, Becky, who became a veterinarian as he was getting his doctorate. Despite his early death, they had the good fortune of enjoying a partnership that spanned a few days less than three decades. Becky and their two children, Alec and Paige, were a highlight of Dan’s life to whom he was highly devoted and by whom he never ceased to be amazed and delighted.

Another event that indelibly shaped Dan into the man he became was a diagnosis of Hodgkin’s disease as an 11-year-old, followed by a relapse 6 months later. He survived the disease as a consequence of the multimodality therapy (surgery, radiation, and chemotherapy) that he would spend his adult life evaluating and refining. That experience changed him physically and intellectually. Those of you who are keen observers would have noticed that he did not fill out the collar on his shirt, a consequence of mantle radiation delivered while he was still maturing physically. Invisible to us, his friends, he also endured changes in his cardiopulmonary status that were a subsequent governor on his physical capacity and likely contributed to his early exit. Those of us who worked with him and read his work know that his perspective as a cancer survivor profoundly influenced his research and how he conducted it, just as it did the rest of his life. His brother, Nick, noted at the celebration of Dan’s life that he was not a doctor himself but that he attributed his brother’s early death to that childhood cancer.

An example of how Dan applied both his innovative bent and his personal experience with cancer to his work occurred at the outset of our collaborations in the late 1990s. At that time, we were designing and running trials comparing the activity of irinotecan- and oxaliplatin-based therapies for patients with advanced colorectal cancer. Early in the days of computer monitoring and in the infancy of electronic mail (e-mail), Dan designed a program that monitored in real time grade 3 and higher toxicity events. We both received an automated e-mail every morning updating us on severe side effects among patients being accrued at more than 100 sites in the United States and Canada. With this primitive dashboard, we were able to discern unexpected toxicity, some of which led to fatal outcomes, and to intervene in our own study and other trials being conducted across the world. Subsequently, that trial led to the new indication of treatment of metastatic colorectal cancer with FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) and, together with scores of coauthors, we published more than 35 reports and even more abstracts and presentations spawned by that trial. Reports using that database are still being published almost 2 decades after the trial opened.

This approach is a prototypical case study illustrative of Dan’s passion to be sure that we extracted as much useful information as possible from every patient who was treated in a clinical trial. He discerned the value of collecting information from across studies that led us to pool clinical trial-derived data. He spearheaded this effort long before the term “big data” was born. He initiated the ACCENT group, which pools data from colorectal cancer adjuvant trials, and he became the lead statistician for the ARCAD (Aide de Recherche en Cancerologie Digestive) group, which pools data from studies collected in advanced disease trials, and a formative member of the CEO Roundtable on Cancer’s Project Datasphere. Analyses from these studies led to many insights. Perhaps the most clinically important result convinced Food and Drug Administration officials to accept disease-free survival as an early efficacy endpoint for adjuvant trials in colon cancer (whereas previously, overall survival was the sole acceptable efficacy endpoint in this setting) thus speeding our ability to analyze studies and deliver advances to clinics worldwide.

Dan was a consummate collaborator. He worked with researchers, government agencies, pharmaceutical companies, professional organizations, and academic statisticians from around the world. As a voice of reason, innovation, and collegiality, he was widely sought after and recruited into leadership roles. A few examples of his success as a leader among these groups follow. He was the lead statistician of multiple National Cancer Institute (NCI)-designated cancer clinical trials groups, including the North Central Cancer Treatment Group and the Alliance for Clinical Trials in Oncology. He was so good at this that he was chosen to be the chair of Subcommittee H, the NCI’s group charged with evaluating NCI-designated Clinical Trials Organizations and serving on a host of other committees and working groups. He served as an advisor and data-monitoring committee member for many companies, assisting them in drug development. He became the president of the Society for Clinical Trials and worked on many activities for the American Society of Clinical Oncology and other professional organizations.

Dan also had a passion for identifying and attracting talented statisticians early in their careers to help mold them into the type of professional that he was and to transform them into people that he wanted to have on his team as head of Cancer Center Statistics at Mayo Clinic. He did this both in the classroom and in the office. His publications spanned the gamut from clinical trials to statistical methodology. Because of the relevance of his work, he is one of the most highly cited authors in the field of oncology, indicating the impact of his work. He also was widely sought to give lectures around the world. As a consequence of these exposures, I watched him transform from a man with a perspective drawn from his experience of growing up in Rochester, Minnesota, to one who keenly appreciated the diversity and enjoyed the experiences that world travel afforded him.

Dan was a warm person who reveled in the friendships of his family, friends, and colleagues. He loved to watch his children play tennis and to take his golf clubs on his professional trips so that he could escape and enjoy his travels with a colleague, in addition to getting work done. The week that he died, he had just been named a department chair at Mayo Clinic. His delighted colleagues expected to thrive under his expanded leadership role. His last e-mail to them from his hospital bed was sent to reassure them that he would be back at work in a couple of days.

I have two final anecdotes to convey. Dan told me once that his family’s successful landscaping business competed on quality and not on price. That was a life lesson that Dan learned from his parents and that served him well in the domain of cancer statistics. A Sargent’s work is worth the price. I also had an occasion to write a letter a few years ago recommending Dan for an honor. In the closing paragraph, I noted that I had known a number of Nobel Prize winners but only one person that I considered a true genius, my forever friend and late colleague, Dan Sargent. His contributions to cancer research, the ongoing contributions of the many people whose careers he accelerated, and our memories will remain a lasting source of pride and solace for his family and his many friends.