More than one million participants worldwide: Population Health Research Institute
May 30, 2016
Four years ago, Bayer Inc. went looking for an international research organization to conduct a huge clinical trial on the use of a new anticoagulant drug for preventing heart attacks and stroke. One group in particular stood out.
The Canadian subsidiary of giant Bayer AG chose the Population Health Research Institute (PHRI)—a joint research institute of McMaster University and Hamilton Health Sciences—to do the trial to evaluate rivaroxaban and compare it with the use of aspirin among patients with coronary or peripheral artery disease.
Based in Hamilton, Ontario, PHRI is a world leader in large clinical trials and population studies, says Dr. Shurjeel Choudhri, Senior Vice-President and Head of Medical and Scientific Affairs for Bayer Inc. He says PHRI is one of the few places in the world which has the capacity, experience, data quality, record of success and global reach to do such work. Moreover, Canada and particularly Ontario present advantages, with both the expertise and the network for such trials to be conducted efficiently.
“We strongly felt the study should be done at PHRI,” recalls Dr. Choudhri, noting that since it began in 2013 the trial, called COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) has evaluated more than 27,000 high-risk patients at more than 1,000 sites in 45 countries, one of Bayer’s largest-ever R&D drug studies.
PHRI is now doing a second trial for Bayer, called ESUS, evaluating the use of rivaroxaban and aspirin in patients with embolic strokes that have an undetermined source. The institute is also starting a further trial, called INVICTUS, focused on using rivaroxaban and other medications to treat rheumatic valvular heart disease.
The Bayer studies are among some 50 clinical studies currently underway at PHRI, says Dr. Salim Yusuf, Executive Director of the institute, which he founded in 1992. To date, PHRI has led over 100 clinical trials and epidemiological studies enrolling more than one million participants worldwide—both investigator-initiated and industry-sponsored. They are particularly focused on pharmaceuticals and medical devices in the area of cardiovascular disease (CVD), including stroke, diabetes and kidney disease, as well as infectious diseases such as influenza, tuberculosis, Chagas disease and rheumatic heart disease.
Dr. Yusuf, a cardiologist and epidemiologist who is President of the World Heart Federation, says that global companies partner with PHRI because “we do high-quality work, both from a clinical trials perspective as well as from a medical and scientific perspective. We’ve always delivered on time and within budget, our data have stood up to scrutiny by the regulators and we have global networks which few others have.”
The institute’s international infrastructure includes experts at 1,500 sites in 86 countries. Dr. Yusuf says PHRI has developed “a broad range of study designs” including trials “that help us answer more than one question.”
The largest study of its kind, the Prospective Urban and Rural Epidemiological (PURE) study, involves 400,000 participants worldwide. It is investigating the impact of modernization, urbanization and globalization on obesity and other risk factors for CVD, diabetes, lung diseases, cancers, injuries and kidney diseases in 30 countries representing different levels of economic development.
Dr. Yusuf says that among PHRI’s most significant clinical trials was the HOPE (Heart Outcomes Prevention Evaluation) study showing that ramipril, a blood pressure medication, reduced death rates from heart attacks and stroke by 25 per cent. Another trial, CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events) showed that adding clopidogrel to aspirin doubled its benefit in patients susceptible to ischemic strokes. A third one, RE-LY (Randomized Evaluation of Long-term anticoagulant therapy) was the first trial to show that the new oral anticoagulants were more effective and safer than warfarin in patients with atrial fibrillation.
The results of a trial that PHRI conducted in 22 countries with AstraZeneca and jointly funded by the Canadian Institutes of Health Research, called HOPE-3 (Heart Outcomes Prevention Evaluation-3), were recently published in three papers in the same issue of the New England Journal of Medicine. It showed that cholesterol-lowering medications are beneficial in reducing heart attack and stroke in a wide range of individuals, but that blood pressure lowering medications were was only beneficial in those with elevated blood pressure.
Other recent and ongoing industry collaborations include clinical trials conducted in collaboration with Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Astra Zeneca and Sanofi, as well as the three studies being done in collaboration with Bayer.
Dr. Yusuf says that PHRI’s collaborations with companies include peer-reviewed and industry studies as well as trials that have joint funding from peer-review organizations and industry. “We’ve got many different models of working with industry which are tailored to the circumstance of the trial and the stage of development of a drug,” he says, noting that most are large Phase III and Phase IV trials.
The institute’s location is important. PHRI gets 15% to 20% of its patients from Canada, and about half to two-thirds of those are in Ontario. It also benefits from the high quality of hospitals in the Hamilton area. They help to “pilot-test” the design of each trial, such as assessing the forms PHRI will use “to see that they actually work.”
PHRI’s success showcases the strengths of Ontario and Canada in doing clinical trials, Dr. Yusuf comments. “We think Canada is a very good place to do trials. There are good rates of follow-up, high adherence, good data quality and good recruitment. Further, Canadian investigators have a high level of skill and expertise.”
He says that conducting clinical trials has become somewhat easier in Ontario, especially with more streamlined systems for ethics approvals and contracting processes.
Dr. Choudhri says that Bayer’s collaboration with PHRI has gone “extremely well.” PHRI is close in distance to Bayer and yet is a global institution and one of the few that can do all aspects of a complex trial such as COMPASS, he explains, including protocol design, data-quality monitoring, data management and analysis.
“They do it very efficiently as well,” he says, noting that Dr. Yusuf has really pushed for simplicity in the design of clinical trials, which makes them easier to do.
PHRI’s ability to complete studies with very high rates of follow up of study participants (>99% in most studies) is especially important, Dr. Choudhri remarks, because if patients leave a study, “then you have missing data, and that can jeopardise the interpretation and validity of your trial.”
The COMPASS trial will finish in early 2018. The results could change the treatment paradigm for preventing acute coronary syndrome, while the ESUS trial could have a benefit in preventing strokes.