Recent Research Highlights
Report offers recommendations for responsible sharing of clinical trial data
October 21, 2013
Boston, MA – A new report by researchers from Harvard University and others in a working group convened by the Multi-Regional Clinical Trials Center (MRCT) at Harvard proposes recommendations for addressing a problem that has vexed drug regulators: how to expand public access to data from clinical trials while protecting patients’ privacy and weighing pharmaceutical companies’ business interests. Recently, the European Medicines Agency (EMA) announced it will provide public access to participant-level data submitted in applications for marketing approval in Europe, prompting questions about whether the U.S. Food and Drug Administration should follow suit. Data releases by the EMA have spurred litigation by drug companies and heated debate about whether clinical trial data should be protected as proprietary information or widely shared.
The report, published online October 21, 2013 in The New England Journal of Medicine, was released to coincide with the first meeting of the Institute of Medicine’s Committee on Strategies for Responsible Sharing of Clinical Trial Data on October 23. The Institute of Medicine convened the committee on an accelerated timetable to develop a framework for expanded public access to clinical trial data. An initial report is expected in January 2014.
“Our experiences with Vioxx, Avandia, and other widely prescribed drugs that were revealed to have serious safety risks show how important it is to give independent scientists access to clinical trial data,” said Michelle Mello, professor of law and public health at the Harvard School of Public Health and lead author of the report. “The question is, how can we achieve the powerful public health benefits of data sharing while protecting research participants’ privacy, avoiding ‘junk science,’ and minimizing burdens on trial sponsors?”
According to the authors, expanding access to participant-level data could both serve as a check on trial sponsors’ characterizations of a product’s safety and effectiveness, as well as open up new avenues of scientific inquiry beyond the scope of the original study. However, there are concerns that research participants’ identities could be discovered, and that competitors and others could use the data to produce flawed analyses. The FDA historically has treated participant-level clinical trial data submitted to the agency as confidential.
The authors recommend that a system of expanded access to clinical trial data apply to trials of all approved prescription drugs, medical devices, and biologics; and treat all trial sponsors and qualified data requesters evenhandedly. It should have mechanisms to ensure that all sponsors and data users adhere to minimum standards—for example, rules should specify what must be shared, and data users should commit to following a scientifically sound analytical plan. If sponsors are permitted to influence which data requests get granted, they should be required to apply explicit decision criteria and publicly explain the reasons for denials. Using an independent intermediary organization to make those decisions, however, may be preferable.
“As in other areas of health care, the push for greater transparency in the area of clinical-trial data appears inexorable,” the authors wrote. “The question is not whether, but how, these data should be broadly shared. The potential risks to research participants and trial sponsors must be thoughtfully addressed in the design of any new data-sharing system but need not block progress toward achieving the promise of ‘big data’ in the clinical trials context.”
“The European Medicines Agency has hastened to impose regulatory mandates for data sharing, which may indeed be needed,” said Mark Barnes, a partner at Ropes & Gray LLP and the Harvard faculty co-director of MRCT, “but such mandates need to be carefully considered, to avoid harms to participants and to preserve commercial incentives for industry to invest in vital research.”
The authors were part of a working group of both academics and pharmaceutical industry experts convened by Harvard’s Multi-Regional Clinical Trials Center, which receives funding from pharmaceutical companies and not-for-profit entities.
“Preparing for Responsible Sharing of Clinical-Trial Data,” Michelle M. Mello, Jeffrey K. Francer, Marc Wilenzick, Patricia Teden, Barbara E. Bierer, and Mark Barnes, online October 21, 2013, DOI: 10.1056/NEJMhle1309073
Survey finds public support for legal interventions to fight obesity, noncommunicable diseases
March 5, 2013
The public is very supportive of government action aimed at changing lifestyle choices that can lead to obesity, diabetes, and other noncommunicable diseases—but they’re less likely to support such interventions if they’re viewed as intrusive or coercive, according to a new Harvard School of Public Health (HSPH) study. The study also found that support was higher for interventions that help people make more healthful choices, such as menu labeling requirements, than for interventions that penalize certain choices or health conditions, such as charging higher insurance premiums for obese individuals.
“Policymakers everywhere are looking for ways to use legal and policy levers to stem the rising tide of health care costs related to obesity and chronic disease,” said Stephanie Morain, a doctoral candidate in health policy at Harvard University, who led the study. “They should be heartened by these findings—the public does see this as an appropriate role for government.” That public support is important, the study authors wrote, because it may affect people’s willingness to comply with the law.
The study appears in the March 2013 issue of Health Affairs.
In recent years, lifestyle choices such as overeating, physical inactivity, and alcohol and tobacco use have led to troubling increases in chronic ailments in the U.S. In response, health departments and legislative bodies have adopted policies aimed at combating the behavioral risk factors that lead to ill health, such as banning trans fats in restaurants, raising taxes on cigarettes, and screening schoolchildren for high body mass index.
But some have criticized such interventions, saying that they impinge on personal choice and exceed the scope of governmental authority. So the HSPH researchers decided to examine which factors play into public support for so-called “new-frontier” public health initiatives.
For the study, co-authors Morain and Michelle Mello, professor of law and public health in the HSPH Department of Health Policy and Management, analyzed the results of an online survey of 1,817 American adults conducted in October 2011 by Knowledge Networks (now part of GfK), a professional survey organization. In the survey, respondents were asked about their support for various types of public health policies, as well as the factors that influenced their support. There were questions about seven noncommunicable health conditions and 14 specific strategies to address them.
The researchers found a high level of support—between 70% and 90%—for government action on each of seven areas: preventing cancer, heart disease, childhood and adult obesity, and tobacco use; helping people control their diabetes; and reducing alcohol consumption.
Support was quite high for interventions that facilitate healthy choices, such as increasing the affordability of fruits and vegetables or requiring more instruction in public schools about the health risks of obesity. However, support waned when government actions were viewed as focusing on penalties or on limiting choices—such as adding insurance surcharges for obese individuals or making it illegal to smoke in private spaces.
The researchers also found that African-Americans and, to a lesser extent, Hispanics, are significantly more likely than whites to support government action to address noncommunicable diseases.
In addition, the survey indicated that people are much more supportive of government public health initiatives if they believe that “people like me” can influence public health priorities and if they think that public health officials understand the public’s values.
“The message for public health officials and legislators is, if you want the public to buy in to these legal interventions, you’ve got to engage them early on,” said Mello. “You’ve also got to communicate about policies in a way that resonates with the public’s values. For example, how does the intervention support healthy choices? Why is it fair?”
The study was supported by a grant from the Greenwall Foundation.
“Survey Finds Public Support for Legal Interventions Directed at Health Behavior to Fight Noncommunicable Disease,” Stephanie Morain and Michelle M. Mello, Health Affairs, March 2013.
Study Reveals Complexities of Disclosing and Compensating for Medical Mistakes
When disclosing a medical error to patients, healthcare providers should follow up with a proactive offer of compensation—but patients’ responses may not be as straightforward as they might expect. According to a study by Harvard School of Public Health (HSPH) researchers and colleagues, two thirds of patients expect compensation following a harmful medical error, and three quarters are likely to accept even modest compensation offers. But offering full compensation can prompt suspicion that the provider is motivated by a desire to avoid a lawsuit, rather than a desire to do the right thing. To preserve trust in physicians, the authors recommend clearly separating disclosure and compensation discussions and leaving physicians out of talks about money. The study appears in the December 2012 issue of Health Affairs (click here for the abstract). The study was conducted by Michelle Mello, JD, PhD, Professor of Law and Public Health in the Department of Health Policy and Management at HSPH; Lindsey Murtagh, JD, MPH, a former HSPH Research Associate who is now an Associate at the law firm Hogan Lovells in Washington, DC; Penny Andrew, MBChB, LLB, a former Commonwealth Fund Harkness Scholar who is currently the clinical lead for quality at Waitemata District Health Board in New Zealand; and Thomas Gallagher, MD, a professor in the Departments of Medicine and Bioethics and Humanities at the University of Washington. The researchers were supported by grants from the Robert Wood Johnson Foundation and the Commonwealth Fund, and in-kind support from the National Science Foundation’s TESS program.
Institute of Medicine Report Discusses Ethical Concerns Surrounding Postmarketing Regulation of New Drugs
The tumult arising from revelations of serious safety risks associated with widely prescribed drugs, including Avandia, Vioxx, and Celebrex, has led to widespread recognition that improvement is needed in our national system of ensuring drug safety. Notwithstanding federal legislation in 2007 that strengthened the authority of the Food and Drug Administration (FDA) in the postmarketing period,critical weaknesses in the national system persist.
Central to these weaknesses are dilemmas surrounding not only the science but also the ethics of drug-safety research, many of which came to the fore in the heated public debate about the Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) trial, which compared the cardiovascular outcomes of long-term treatment with rosiglitazone with those of pioglitazone (Actos, Takeda) in patients with type 2 diabetes. At the request of the FDA, an Institute of Medicine (IOM) committee was convened to examine the ethics and science of FDA-required postmarketing safety research. In an article published in The New England Journal of Medicine in September 2012, 3 members of the IOM committee review the key ethics findings from the committee’s May 1, 2012, report and offer some reflections on the challenges ahead. Read the article here and access the IOM’s full report, “Ethical and Scientific Issues in Studying the Safety of Approved Drugs,” here.