Harnessing Change Through Research

Reshma Ramachandran, MD, MPP, MHS, wants to ensure that everyone has access to safe and effective medical treatments.

“As clinicians, we need studies done to provide assurance that whatever we’re prescribing or administering is best for our patients,” she says.

An assistant professor of medicine (general medicine) at Yale School of Medicine (YSM), Ramachandran co-directs the Yale Collaboration for Regulatory Rigor, Integrity, and Transparency, an interdisciplinary initiative aligning research on medical product evaluation, approval, and coverage with the goal of advancing policies that improve patient health and health care. She is the recent recipient of a Bernard Lown Award for Social Responsibility and a Reimagine America Fellowship from the Roosevelt Institute, among other honors.

In a Q&A, Ramachandran discusses the inspiration behind her advocacy efforts and her vision for a health care system that prioritizes patients.

At the end of my first year as a fellow in the National Clinician Scholars Program at YSM, the FDA approved a new drug for Alzheimer's disease, for which there is no known cure. That same week, I had patients coming into my office, asking me if I could prescribe it.

I had been following the drug for a while, and the clinical trials didn't show that the drug meaningfully treated Alzheimer's disease or improved patients' lives. And there were serious safety concerns, including brain swelling, brain bleeding, and even deaths among patients.

It was a difficult conversation to have with patients because I didn't have other options to give them. And I was saying no to a drug that had been approved by our national regulator. That's when I realized we need to strengthen FDA approvals so that clinicians and patients have assurance that an FDA-approved drug is safe and effective.

Many new cancer drugs and, increasingly, other drugs are being approved by the FDA based on flexible standards to enable earlier access, measuring efficacy through surrogate markers that show either the tumor size has shrunk or there's a change in a blood test. Our and others’ research has found that those surrogate markers don't necessarily correlate with meaningful clinical outcomes, such as survival or quality of life. There are also safety concerns, which can create a compound effect of potentially serious harms in addition to having concerns around efficacy.

Our work has shown that the level of evidence at the time of approval still leaves a lot of questions for clinicians and patients about safety and efficacy. Sometimes, but not always, the FDA will require additional studies after approval when there is lingering uncertainty around efficacy and safety. But, as our research has shown, this uncertainty can persist because the FDA often will not ensure that meaningful clinical benefit is proven in a timely manner. And there's not a lot of incentive for companies to voluntarily do studies to show that their treatment doesn't really work or might not be safe.

In addition to clinicians and patients, we have many stakeholders in health care, including pharmaceutical, medical device, and insurance companies. Our health care system has become increasingly financialized, shifting priorities away from patients and more towards these private sector actors, who extract as much as possible from the system. This has fostered mistrust not only between patients and physicians but also between patients and public health agencies.

I think about what we can do from the public, nonprofit, and academic sides to protect our patients. Unlike companies, we don’t have a bottom line.

A long-term project of mine is to envision and shape what a research, development, and health care delivery system might look like if we enhanced public capacity to do that work with patients at the center of it.

General Internal Medicine, one of 10 sections in the Yale Department of Internal Medicine, is committed to the core missions of patient care, research, education, and community health from the “generalist” perspective. To learn more, visit General Internal Medicine.