From the New England Journal of Medicine. By Benjamin N. Rome, M.D. and Jerry Avorn, M.D. SUMMARY: This NEJM Perspective by Rome and Avorn examines how the COVID-19 pandemic stress-tested the US drug evaluation and approval infrastructure. Writing in April 2020 as the pandemic's first wave intensified, the authors argue that the pressure to act quickly in a public health crisis creates specific vulnerabilities in the normally rigorous process of evaluating whether drugs work

From the New England Journal of Medicine. By Jerry Avorn, MD; Aaron S. Kesselheim, MD, JD, MPH; Ameet Sarpatwari, JD, PhD. SUMMARY: This NEJM Perspective by Avorn, Kesselheim, and Sarpatwari evaluates the FDA Amendments Act of 2007 (FDAAA) a decade after its enactment. The authors open by situating the FDAAA within the long history of US drug regulation, which has been shaped by crises: Progressive-era concerns about patent medicines led to the 1906 Pure Food and Drug Act; th

From the New England Journal of Medicine. By Jonathan J. Darrow, SJD, JD, MBA; Jerry Avorn, MD; Aaron S. Kesselheim, MD, JD, MPH. SUMMARY: This NEJM review evaluates the FDA breakthrough-therapy designation program, created by Congress in 2012 to accelerate testing and approval of drugs with potential for substantial improvement over existing treatments. Darrow, Avorn, and Kesselheim systematically examine the first four years of the program's operation, assessing which drugs

From the New England Journal of Medicine. By Michael Fralick, MD; Jerry Avorn, MD; Aaron S. Kesselheim, MD, JD, MPH. SUMMARY: This NEJM Perspective examines drug importation from Canada as a potential mechanism for increasing competition and reducing the cost of essential medications in the United States. Fralick, Avorn, and Kesselheim review the state of drug importation policy, including a recently proposed bill addressing the safety of Canadian drugs, and assess both the p

From the New England Journal of Medicine. By Chana A. Sacks, MD; Jerry Avorn, MD; Aaron S. Kesselheim, MD, JD, MPH. SUMMARY: This NEJM Perspective by Sacks, Avorn, and Kesselheim examines the case of solanezumab, a monoclonal antibody developed for Alzheimer's disease that failed to demonstrate meaningful clinical benefit in trials. The authors argue that the FDA's rejection of the drug — despite significant industry and patient-advocate pressure to approve it — served the pu

From JAMA. By Aaron S. Kesselheim; Jerry Avorn, MD; Ameet Sarpatwari, JD, PhD. Importance: The increasing cost of prescription drugs in the United States has become a source of concern for patients, prescribers, payers, and policy makers. Objectives: To review the origins and effects of high drug prices in the US market and to consider policy options that could contain the cost of prescription drugs. Evidence: We reviewed the peer-reviewed medical and health policy literatur

From the New England Journal of Medicine. By Jerry Avorn, MD and Aaron S. Kesselheim, MD, JD, MPH. SUMMARY: This NEJM Perspective by Avorn and Kesselheim offers a critical analysis of the 21st Century Cures Act, then under active congressional debate. The authors argue that the legislation, despite its forward-looking name, would effectively lower FDA approval standards by authorizing the agency to rely on observational data and other forms of real-world evidence in place of

From the New England Journal of Medicine. By Ameet Sarpatwari, JD, PhD; Jerry Avorn, MD; Aaron S. Kesselheim, MD, JD, MPH. SUMMARY: This NEJM Perspective evaluates the early progress of the biosimilar approval pathway created by the 2010 Biologics Price Competition and Innovation Act (BPCIA). Sarpatwari, Avorn, and Kesselheim mark the FDA's first biosimilar approval — filgrastim-sndz — as a milestone, while identifying the significant legal, regulatory, and market obstacles t

From HealthAffairs. By Aaron S. Kesselheim, Yongtian Tina Tan, and Jerry Avorn. Abstract Transformative drugs, defined as pharmaceuticals that are both innovative and have groundbreaking effects on patient care, are the “holy grail” of drug research and development. The sources of drug innovation are often debated, with pharmaceutical manufacturers arguing that high drug prices support innovative output from their sector. We studied the developmental histories of twenty-six d

From the New England Journal of Medicine. By Aaron S. Kesselheim, MD, JD, MPH; Jerry Avorn, MD; Jeremy A. Greene, MD, PhD. SUMMARY: This NEJM Perspective by Kesselheim, Avorn, and Greene examines the legal and regulatory framework governing generic drug safety, with particular focus on the question of who bears responsibility when a generic drug causes harm. The piece engages the then-contested legal question of whether generic manufacturers could be held liable for inadequat

From the New England Journal of Medicine. By Jerry Avorn, MD. SUMMARY: In this NEJM Perspective, Dr. Avorn surveys two centuries of drug risk assessment in the United States, tracing how society's capacity to identify, measure, and respond to the harms caused by medications has evolved from the era of patent medicines to the sophisticated pharmacovigilance infrastructure of the modern FDA. The piece contextualizes contemporary drug safety challenges — including rofecoxib (Vio

From the New England Journal of Medicine. By Alfred B. Engelberg, JD; Aaron S. Kesselheim, MD, JD, MPH; Jerry Avorn, MD. SUMMARY: This NEJM Perspective by Engelberg, Kesselheim, and Avorn examines the debate over how long biologic drugs should enjoy market exclusivity before biosimilar competition is permitted — a policy decision then being shaped by the 2009-2010 health care reform process. The authors use the Hatch-Waxman Act's track record for small-molecule generic drugs

From the New England Journal of Medicine. By Jerry Avorn, MD. SUMMARY: In this NEJM Perspective, Dr. Avorn examines the implications of the FDA's growing reliance on user fees paid by the pharmaceutical industry to fund its drug approval operations. The piece raises structural conflict-of-interest concerns: when the agency regulating an industry derives a significant share of its operating budget from fees paid by that same industry, questions arise about whether the agency's

From the New England Journal of Medicine. By Jerry Avorn, MD. SUMMARY: This NEJM Perspective by Dr. Avorn examines the concealment of adverse drug effect evidence, using the Vioxx withdrawal and the FDA aprotinin (Trasylol) warning as central case studies. Avorn opens with the September 2004 Merck announcement that rofecoxib doubled the risk of myocardial infarction and stroke — leading to its withdrawal after five years of use in more than 20 million patients — and argues th

From Health Affairs. By Jerry Avorn, MD. SUMMARY: This Health Affairs article by Dr. Avorn uses the case of nesiritide (Natrecor) — a drug approved for acute decompensated heart failure that was rapidly adopted into widespread practice before post-market studies raised serious concerns about its safety and efficacy — to illuminate broader problems in the US drug approval and post-market surveillance system. The Natrecor story illustrates the risks of rapid clinical adoption o

From Health Affairs. By Jerry Avorn, MD. SUMMARY: This Health Affairs editorial introduction by Dr. Avorn opens a thematic issue devoted to the relationship between prescription drugs and the elderly population. Avorn, identified as one of very few academically affiliated physicians specializing in this area, provides an overview of the issue's scope, which spans geriatric drug development, elderly participation in clinical trials, pharmaceutical pricing, drug utilization pat