Master of the Clinical Trial: 2014 Canada Gairdner Wightman Award Winner Dr
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News Master of the clinical trial: 2014 Canada Gairdner Wightman Award winner Dr. Salim Yusuf he boy was a good student but tended to coast at times. When T he took biology in Grade 9, he barely passed his first exam. Salim, you can do so much better, his teacher told him. You are being lazy. Accepting the implied challenge, the young pupil decided to show his teacher just how much better he could do. He studied hard, and not just the curriculum. He got his hands on univer- sity textbooks and studied them too. On the next test, he received an extraordi- narily good mark. You see, Salim, his teacher said. Just look what you are capable of. What Salim Yusuf also discovered, in addition to that brief glimpse of his © Alan King potential, was that science is fascinat- ing. He continued to read widely, Dr. Salim Yusuf is the 2014 recipient of beyond what was required or expected the Canada Gairdner Wightman Award. of him, and he continued to excel, his coasting days fading into memory. he brought had to last a month, until he When he finished high school in could return home to fetch more. Kochi, a port city on India's west coast, Later in his medical education, dur- Yusuf applied to medical schools. It ing a rural posting in the village of Mal- was his father, a personnel manager for lur, Yusuf conducted his first research an oil refinery, who encouraged him to experiment. “I didn’t call it a research pursue medicine. And it was his project,” he recalls. “I was just curious. father’s heart attack — for which there I saw a problem and tried to solve it.” were no treatments in the early 1970s The problem was very high rates of — that provided the motivation. The diarrheal diseases. Yusuf did a survey of experience had been terrifying, leaving the nine wells in the village, finding that Yusuf and his mother, brother and sister a few were next to cow sheds or in some in a state of bewilderment. other unhygienic location. He shipped The good news was that his father water samples to a public health labora- recovered. The bad news was that none tory, received the bacteria counts, deter- of the medical schools Yusuf applied to mined how much chlorine was required appeared to reciprocate his interest. As for each well and asked the village head- the rejection letters piled up, he almost man if he could treat the water. gave up and considered pursuing He was granted permission but another field of study. Finally, however, asked to perform the task after the an invitation for an interview arrived in women in the village had finished the mail from St. John’s Medical Col- drawing water for the day, to avoid lege in Bangalore. unnecessary worry. So Yusuf waited Carrying a small suitcase and just until evening and, with a dozen or so enough money for a return trip, Yusuf high school students on bicycles, began departed for Bangalore. His expecta- chlorinating the wells. tions were low. But the interview went Just as they were finishing up four better than he expected, and he was not hours later, a group of women came to only accepted — he was to start classes use the final well on the list. Oh no, the right away. The few changes of clothing women said. You’ve spoiled the water. CMAJ, May 13, 2014, 186(8) 573 News In a moment of bravado, Yusuf pulled Yusuf remains particularly good at sity. As a clinical cardiologist, Yusuf has the bucket from the well and drank asking important questions, according seen first-hand the devastating effects of from it. Unfortunately, it still contained to Dr. Jack Hirsh, professor emeritus of cardiovascular disease and is motivated concentrated chlorine, so he spat the hematology and thromboembolism at to find solutions. He is a collaborative water out onto the ground. McMaster University in Hamilton, genius, says Sackett, and will travel all “That set back my public health Ontario. “Salim and his team may over the world to convince respected effort,” says Yusuf, chuckling at the spend six months or even a year dis- researchers and clinicians to participate memory. “The good news is the rates cussing the questions and how best to in international clinical trials. Yusuf is of diarrheal diseases just plummeted answer them,” says Hirsh. “That’s one also a sophisticated methodologist, able after that.” reason so many of the projects that to coordinate very large clinical trials During his next rural posting, in Salim has been involved with have from concept to completion. Munnar, Yusuf learned another valuable been game-changers and have made a “He knows the types of investiga- lesson. He already knew that data were huge difference.” tions that are required to demonstrate important, but came to see that the Two influential concepts that Yusuf that something works,” says Sackett. answer to a health question sometimes helped introduce to the research com- “He is the master of the clinical trial.” lies in the context rather than numbers. munity during his time at Oxford were It was announced Mar. 26 that He wanted to know why the rates of the properly conducted meta-analysis Yusuf would receive the 2014 Canada salpingectomies were so much higher and the large, simple clinical trial. Gairdner Wightman Award for his out- in Munnar than for vasectomies, a At the time, most clinical trials standing career in biomedical research. much simpler procedure. Surveys were weren’t large enough to prove that a In April, he was inducted into the Can - adian Medical Hall of Fame. These are but two of many honours Yusuf has “Large is the key thing; simple is received for his work, which has changed how cardiovascular disease is the vehicle.” prevented, treated and managed. “The thing that probably pushes him conducted and wishy-washy answers treatment worked. A bit of good luck more than anything else is his concern received. Finally, a man in the village made a treatment seem better than it and abiding dismay over the burden of told him the truth. If the wife of a man was. A bit of bad luck made it seem disability and untimely death from car- who had a vasectomy became pregnant worse that is was. So, instead of diovascular disease that he thinks is via an affair, that man would lose face enrolling thousands of people in their potentially preventable,” says Sackett. in the village. clinical trials, Yusuf and Peto enrolled “He is motivated by human suffering.” “No quantitative survey could get us tens of thousands of people. But the Outside of work, Yusuf’s main inter- that information,” says Yusuf. “Of only way to make that feasible, and est is family. He is married and has course, we weren’t going to cure extra- affordable, was to keep the trial simple. three children: one a pediatrician, marital sex.” Pose a good question and focus on another in medical school, the youngest These initial and rudimentary forays measuring only a few outcomes. still “finding herself.” He occasionally into research, Yusuf believes, helped him “Large is the key thing; simple is the finds time to read The Economist or a win a Rhodes Scholarship to study at the vehicle,” says Yusuf. book on history or philosophy, squeez- University of Oxford in the United After completing his training in car- ing in some fiction by Salman Rushdie Kingdom. It was there that he first met diology at Oxford in 1984, Yusuf or V.S. Naipaul now and then. real scientists, including Dr. Richard moved to Bethesda, Maryland, to work Though he no longer plays field Peto, a world-renowned researcher and for the National Institutes of Health, hockey, as in his younger days, he does professor of medical statistics and epi- where he conducted influential trials on play a little golf. “The word ‘play’ may demiology who would become his men- heart failure. In 1992, he became the be giving it a high level of respectabil- tor and collaborator. director of cardiology at McMast er ity that it doesn’t deserve,” he says. Many of the medical research princi- University and, a few years later, “My wife calls it a very inefficient way ples he learned from Peto in the late found ed the Population Health Re - of chopping grass.” — Roger Collier, 1970s still guide Yusuf today, as he con- search Institute. Now 61 years old, CMAJ ducts some of the largest studies in the Yusuf has published hundreds of stud- world on cardiovascular disease. Three ies and is among the top 1% of cited CMAJ 2014. DOI:10.1503/cmaj.109-4771 principles, in particular, stand out. One: medical researchers in the world. look for a disease’s burden and work in There are several reasons why Yusuf the region where that burden is largest. has been so successful in repeatedly More News online Two: you not only have to get the big producing high-impact research, picture right; you also have to get the according to Dr. David Sackett, profes- To read more CMAJ news articles, details right. Three: ask an important sor emeritus of clinical epidemiology visit cmaj.ca/site/home /news.xhtml question and answer it reliably. and biostatistics at McMaster Univer- 574 CMAJ, May 13, 2014, 186(8) © 2014 Canadian Medical Association or its licensors.