This story is part of a series highlighting the research accomplishments of Robert Wood Johnson Foundation (RWJF) grantees from the Human Capital portfolio.

As a physician, patent lawyer and public health policy researcher, Aaron Kesselheim, MD, JD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, uses his unique, multidisciplinary skills to examine the complex world of prescription drug laws and their largely unexplored impact on medicine and public health.

Kesselheim, a 2009 recipient of a RWJF Investigator Award in Health Policy Research, demonstrates a profound understanding of the complicated realm of drug laws, including off-label prescription guidelines and other regulations that play a role in how the medications are used in treatment. He investigates how these issues affect the health care system and what policy initiatives are needed to improve the patient experience.

Protecting Patients

In his two most recent studies, published in the December 2011 issue of Health Affairs, Kesselheim and his colleagues addressed two difficult problems faced by clinicians and patients. One study, “False Claims Act Prosecution Did Not Deter Off-Label Drug Use in the Case of Neurontin,” concluded that, “current enforcement actions targeting illegal, off-label [drug] promotion might not have a substantial deterrent effect on prescription rates, so they should be combined with other efforts to combat off-label promotion. He advised that “additional resources for enforcement and a steep increase in penalties might be needed because settlements have been dwarfed by the financial gains to pharmaceutical companies that engage in improper, off-label marketing.”

In his other study, “Clinical Decision Support Systems Could be Modified to Reduce ‘Alert Fatigue’ While Still Minimizing the Risk of Litigation,” Kesselheim and his collaborators examined the inadequacies of computer systems designed to prevent prescription medication errors. They found that alert fatigue was causing clinicians to ignore computer-generated alarms about potential drug risks. Examining legal concerns from the perspectives of all of the key constituents, Kesselheim and his team determined that the manufacturer’s perceived risk of legal liability was a large part of the problem. They found that more finely tailored warnings could ease alert fatigue without imparting a high risk of litigation for vendors, purchasers and users. Stronger government regulation of clinical decision support systems was also recommended.

“I enjoyed working on these issues," Kesselheim explained, “because both show how the intersection between law and medicine affect health care delivery and how important it is to subject widely held assumptions in this area to empirical study and critical analysis.”

Producing Affordable Drugs

In work supported, in part, by Kesselheim’s RWJF Investigator Award, he scrutinized the patent system and its role in delaying patients’ access to affordable, generic drugs.

In a study published in the October 2011 issue of the New England Journal of Medicine, Kesselheim and his colleagues describe the consequences of “pay-for-delay” legal settlements related to pharmaceutical patents. “These settlements are happening largely under the radar, but they have immense impact on drug costs and access,” Kesselheim said. “One goal of the article was to explain how important the settlement issue is to physicians, patients and policy-makers.”

Pharmaceutical companies hold multiple patents for the drugs they develop. Apart from the active ingredient, secondary patents defend other aspects of the drug, such as the formulation or the coating. Even after the patent on the active ingredient has expired, the generic manufacturer usually has to defend against lawsuits related to these secondary patents before a competing version of that drug can be marketed.

“Ultimately, if the generic company is right, the generic drug can reach the market sooner. Patients benefit because of lower drug costs and it allows patients to get the essential medications that they need and improves adherence,” Kesselheim said. But, these lawsuits can also lead to settlements where the pharmaceutical company pays a generic manufacturer not to release its competing drug. Such settlements benefit the companies involved, but don’t help consumers. “Having a generic version on the market after the active ingredient patent expires is part of the reason for granting that patent in the first place,” he added.

Such settlements affect all types of drugs and conditions. For example, in one such agreement for Cardizem CD, a blood pressure medication, Hoechst Marion Roussel, Inc. paid a generic manufacturer, Andrx Corporation, $40 million each year not to market its generic version of the drug. This particular settlement was found to restrict free trade and was eventually invalidated.

Though patents offer companies incentives that can encourage the development of new drugs, the system doesn’t necessarily support the most critical steps in the process. “Currently, the patent system is a relatively blunt tool as applied to the drug market. It is as likely to protect a small change to an existing drug as to protect a totally new idea that could transform how a disease is treated,” Kesselheim said. “In fact, often times it is the strength of the patent protection, rather than the strength of the science, that determines where investment will occur.”

Kesselheim’s overall goal is to understand what it takes to develop drugs that can enhance patient care. Through his analysis of patents, regulations, interviews with companies, physicians and patients, Kesselheim is attempting to craft policy recommendations that can support start-ups or other companies trying to develop highly innovative medical treatments. At the same time, he wants to make sure that the system appropriately recognizes the role of basic science and the needs of patients.

Kesselheim’s work is also raising awareness among physicians and policy-makers. In addition to publishing his research in scientific journals, he speaks at conferences and stays in contact with people in key Congressional offices and at the Food and Drug Administration. “I’m trying to contribute to policy-making by developing a better, more equitable and more efficient system for drug development and rational drug use,” he said. “Those are the goals and principles that inspire my work. The Investigator Award has been critical in providing support to allow me to pursue these goals and in giving me credibility when I reach out and talk to key stakeholders.”

The Robert Wood Johnson Foundation’s Investigator Awards in Health Policy Research program provides funding to highly qualified individuals undertaking broad studies of the most challenging health, health care and health policy issues facing America. Grants are awarded to Investigators from a wide range of disciplines. Their work reflects thinking that is creative and conceptual and crosses disciplinary boundaries in search of knowledge and innovative solutions to critical health problems and policy issues.

  • For an overview of RWJF scholar and fellow opportunities, visit RWJF Leaders.org