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1259 Results

The Long CON: an Empirical Analysis of Pharmaceutical Patent Thickets

Tu SS - University of Pittsburgh Law Review

  • Research Publications
| December 2024
  • Innovation Incentives and Competition
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“Secondary” patents that do not cover a drug’s active ingredient can contribute to patent thickets that can delay or deter competition. These patents often use a continuation application (CON) that allows brand manufacturers to obtain new patents based on a previous patent without disclosing any new information, with firms sometimes filing CONs more than five years after the original patent (“long CONs”).The pharmaceutical industry disproportionately files and litigates long CON patents relative to other industries, with long CONs representing 33% of all small molecule drug patents and 36% of all litigated drug patents between 2000 and 2022.
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Multiple Myeloma Clinical Trials Exclude Patients with the Highest-Risk Disease: A Systematic Review of Trial Exclusion Criteria

Zhukovsky S, White J, Chakraborty R, Costa LJ, Van Oekelen O, Sborov DW, Cliff ERS, Mohyuddin GR - Leukemia & Lymphoma

  • Research Publications
| December 2024
  • Regulation and Clinical Evidence
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Reviewing 80 randomized multiple myeloma trials, the authors find persistent exclusion of patients with high‑risk disease features, limiting both access and generalizability of evidence. They conclude that eligibility criteria have not meaningfully improved over time and call for deliberate inclusion of high‑risk populations in trial design.
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Impact of Priority Review Voucher Eligibility on Research and Development of Medical Countermeasures

Wang S, Hahn G, Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Research Publications
| December 2024
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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Following the creation of the priority review voucher (PRV) program for medical countermeasures, no statistically significant increase in the rate of new medical countermeasure entry into clinical trials was observed. The sunset of PRVs for medical countermeasures in 202 paves the way for more effective policies to incentivize drug research and development.
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Clinical Benefit and Revenues of Drugs Affected By Rare Pediatric Disease Priority Review Vouchers, 2017-2023

Liu ITT, Kesselheim AS - Journal of Pediatrics

  • Research Publications
| December 2024
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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Between 2017 and 2023, drugs for rare pediatric diseases generated similar revenues to other brand-name drugs, suggesting that these the FDA’s pediatric rare disease priority review voucher (PRV) program may not be necessary to incentivize the development of treatments for pediatric rare diseases.
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Association Between Changes in Prices and Out‐of‐Pocket Costs for Brand‐Name Clinician‐Administered Drugs

Lalani HS, Russo M, Desai RJ, Kesselheim AS, Rome BN - Health Services Research

  • Research Publications
| December 2024
  • Price, Value, and Access
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For 52 clinician-administered drugs, no association was found between annual list price changes and changes in patients’ out-of-pocket costs between 2009 and 2018, though both increased during the study period. These findings may be explained by payer reimbursements that exceed drug list prices and complex insurance benefit designs.
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A Comparative Analysis of International Drug Price Negotiation Frameworks: an Interview Study of Key Stakeholders

Syversen ID, Schulman K, Kesselheim AS, Feldman WB - Milbank Quarterly

  • Research Publications
| December 2024
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The authors compare the processes that health systems in seven other countries (Belgium, Canada, France, Germany, Netherlands, Norway, UK) and the US Department of Veterans Affairs use to negotiate brand-name prescription drug prices. Health systems differ across several axes, including how added health benefit is assessed, whether explicit willingness-to-pay thresholds are employed, and how specific approaches for priority disease areas are taken, but they largely coalesce around a set of practices that are absent from Medicare drug price negotiation.
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Azithromycin to Reduce Mortality

Goh M, Kesselheim AS, Outterson K - New England Journal of Medicine

  • Commentary & Opinion
| November 2024
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The authors emphasize the lifesaving benefits of azithromycin demonstrated in the AVENIR trial, which showed a 14% reduction in child mortality in Niger. Concerns about antimicrobial resistance should not hinder access to this critical intervention, and stewardship programs should instead be implemented to monitor resistance without creating barriers to drug availability.
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Strategies to Help Patients Navigate High Prescription Drug Costs

Lalani HS, Hwang CS, Kesselheim AS, Rome BN - JAMA

  • Research Publications
| November 2024
  • Price, Value, and Access
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The authors provide an overview of the tools and resources health care providers can use to help patients afford their medications depending on insurance type, including the use of patient assistance programs, copay cards, and direct-to-consumer pharmacies.
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Medicare’s First Round of Drug-Price Negotiation—Measuring Success

Rome BN, Kesselheim AS, Feldman WB - New England Journal of Medicine

  • Commentary & Opinion
| November 2024
  • Price, Value, and Access
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The authors reflect on the results of the first round of Medicare drug price negotiation, measuring the success based on the potential savings to the federal government, how the negotiated prices compare to prices in other countries, and how the program will lead to lower out-of-pocket costs for patients with Medicare prescription drug coverage.
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How Agencies Should Decide Which Costly Drugs to Target with Government March-In Rights

Ravinthiran J, Kesselheim AS, Knievel S - Health Affairs Forefront

  • Commentary & Opinion
| November 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Federal agencies should consider seven key factors when deciding whether to use march-in rights under the Bayh-Dole Act to address the high cost of prescription drugs with ties to federal funding, including product revenues, excessive prices, remaining non-patent exclusivities, and a product’s broader patent portfolio.
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US Food and Drug Administration’s Directive to Deal with Delayed Confirmatory Trials: Lessons From Pralatrexate and Belinostat for T-Cell Lymphoma

Cliff ERS, Russler-Germain DA, Daval CJR, Kesselheim AS - Journal of Clinical Oncology

  • Research Publications
| November 2024
  • Regulation and Clinical Evidence
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Prolonged delays in confirmatory trials under the FDA’s accelerated approval program expose patients to costly therapies with unproven clinical benefit for many years. FDA should require confirmatory trials to be underway at approval, optimize trial designs to speed up evidence generation, and use stronger incentives and penalties to prevent these “dangling” accelerated approvals.
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Does Policy Uncertainty Boost Vaccine Hesitancy? Political Controversy, the FDA and COVID-19 Vaccine Hesitancy in Fall 2020

Carpenter D, Dardet ME, Bhaskar A, Rand LZG, Feldman WB, Kesselheim AS - Journal of Health Politics, Policy and Law

  • Research Publications
| November 2024
  • Regulation and Clinical Evidence
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Policy uncertainty during the evaluation and rollout of COVID-19 vaccines in the fall of 2020 was associated with a spike in vaccine hesitancy, with the greatest increase among Democrats, Independents, Asian Americans, and Black Americans. Vaccine hesitancy after this spike did not decline uniformly, with Black Americans and college-educated individuals having more persistent hesitancy. These findings highlight the influence political instability may have on public confidence in vaccine safety and trust in federal health agencies.
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Testing of New Drugs Approved From 2015 Through 2021 Under the US Pediatric Research Equity Act

Liu ITT, Hwang TJ, Kesselheim AS - JAMA

  • Research Publications
| November 2024
  • Regulation and Clinical Evidence
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The Pediatric Research Equity Act (PREA), which added pediatric testing requirements for new drugs indicated for adults, applied to only 30% of new drugs approved by the FDA between 2015 and 2021, in part due to exemptions for drugs indicated for rare diseases. Furthermore, more than half of post-marketing pediatric trials were incomplete five years after approval.
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Shortages of Essential Generic Drugs with Limited Competition

Martin MJ, Rome BN, Kesselheim AS, Lalani HS - Journal of General Internal Medicine

  • Research Publications
| November 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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20% of the 117 drugs in shortage in the US as of November 2023 were generic drugs considered essential medicines by the World Health Organization that were nonetheless produced by a small number of manufacturers (< 3). Policymakers and other stakeholders may want to prioritize these essential drugs facing limited competition when developing solutions to address US drug shortages.
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Estimating Costs in Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa (Reply)

Raymakers AJN, Kesselheim AS, Feldman WB - JAMA Dermatology

  • Commentary & Opinion
| November 2024
  • Price, Value, and Access
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The authors agree with comments that the high cost of beremagene geperavec (B-VEC) for dystrophic epidermolysis bullosa may be offset by reductions in other health care costs. However, these offsets are likely to vary by disease subtype. They also reinforce the value of conducting a QALY-based cost-effectiveness analysis of B-VEC to further inform reimbursement decisions.
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Estimated Savings Under the Medicare High-Value Drug List Model

Cai CL, Kesselheim AS, Rome BN - JAMA Internal Medicine

  • Research Publications
| November 2024
  • Price, Value, and Access
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Under the CMS High-Value Drug List Model, a voluntary model under which Medicare Part D plans cap patient out-of-pocket costs for 150 generic drugs at $2 per month, an estimated 4 in 10 Medicare beneficiaries would experience modest savings under this model, with an annual savings of $11 per person.
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Comparing Supplemental Indications for Cancer Drugs Approved in the US and EU

Stoelinga J, Bloem LT, Russo M, Kesselheim AS, Feldman WB - European Journal of Cancer

  • Research Publications
| November 2024
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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Manufacturers obtained supplemental indications for cancer drugs at a substantially higher rate in the US than in the EU, despite drugs often starting with the same number of indications in both jurisdictions. Differences in regulatory processes and incentives, like accelerated approval and rare disease drug designations, may contribute to this variation.
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Patent Claim Scope and Biosimilar Competition in the US and EU

Bloomfield D, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Fall 2024
  • Innovation Incentives and Competition
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In this commentary on an analysis of the patent thicket surrounding adalimumab (Humira), the authors discuss how the findings open interesting avenues for further research. Such analyses, they argue, reinforce the need for policy changes at the USPTO to improve patent quality so as to not hinder biosimilar market entry.
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Invited Commentary on Interventional Pharmacoepidemiology: Origins, Current Status, and Future Possibilities

Avorn J - American Journal of Epidemiology

  • Commentary & Opinion
| October 2024
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The author explores the historical development and future potential of interventional pharmacoepidemiology—using claims data and other patient information to understand and develop interventions to address suboptimal drug use. Use of such methods can improve the quality and cost-effectiveness of medication use.
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Health Technology Assessment in Prescription Drug Coverage and Pricing Decisions: Examples From Other Countries

Rand LZG, Raymakers AJN, Martin MJ, Egilman AC, Kesselheim AS, Rome BN - National Academy for State Health Policy (NASHP)

  • Policy Interactions
| October 2024
  • Price, Value, and Access
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This memo summarizes how five high-income countries—England, Canada, Australia, France, and Germany—use health technology assessment (HTA) to inform drug coverage and price negotiations, including each country’s use of QALYs or alternative outcome measures. It also provides guidance on accessing publicly available HTA and pricing information and includes price comparisons between the US and these countries for ten top-spending drugs.
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The Patent Trial and Appeals Board: A Target for Prescription Drug Patent Reform?

Freilich J, Kesselheim AS - JAMA

  • Commentary & Opinion
| October 2024
  • Innovation Incentives and Competition
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Efforts to reform the US Patent Trial and Appeals Board (PTAB) via the PREVAIL Act threatens to worsen drug patent thickets by impeding efforts to challenge patents as improperly granted. Instead, allowing patent challenges at the PTAB to trigger the 180-day generic exclusivity period and for successful challenges to end the 30-month stay on generic entry would be better solutions to strengthen the PTAB and promote generic competition.
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Confirmatory Trials of Accelerated Approval Drugs—Will Imposing Fines Reduce Delays?

Daval CJR, Kesselheim AS, Cliff ERS - New England Journal of Medicine

  • Commentary & Opinion
| October 2024
  • Regulation and Clinical Evidence
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The authors discuss the need for stronger FDA action to address delays in confirmatory trials of accelerated approval drugs. The agency already has the authority to fine sponsors for failure to complete trials, yet the FDA has chosen not to do so, and in the absence of other reforms to the accelerated approval proces fines could be a worthwhile tool for FDA to ensure timely evidence generation.
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Vaccine Messaging By the FDA: A National Randomized Survey Study

Feldman WB, Rand LZG, Carpenter D, Campbell EG, Darrow JJ, Kesselheim AS - Journal of General Internal Medicine

  • Research Publications
| October 2024
  • Regulation and Clinical Evidence
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In a national survey of public attitudes toward vaccination, respondents were more likely to get a well-tested vaccine with demonstrated safety and efficacy over a vaccine that had been quickly tested, irrespective of whether vaccine development was announced by the FDA or the President. This suggests that political interference may need to be more explicit before it alters public trust in the FDA’s vaccine approval process.
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Use of Omalizumab for Pediatric Asthma After US Food and Drug Administration Expanded Indications

Deshmukh AD, Kesselheim AS, Tsacogianis T, Rome BN - Pharmacoepidemiology and Drug Safety

  • Research Publications
| October 2024
  • Regulation and Clinical Evidence
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An FDA advisory committee’s recommendation against pediatric label expansion for omalizumab (Xolair), a biologic treatment for asthma, did not affect off-label pediatric use, while use increased when the label was evenually expanded in 2016 based on new clinical evidence. These findings emphasize the need for timely testing of drugs in pediatric populations to inform evidence-based prescribing.
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The RACE Act and Pediatric Trials of Adult Cancer Drugs

Liu ITT, Kesselheim AS - Pediatrics

  • Research Publications
| October 2024
  • Regulation and Clinical Evidence
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Expanded pediatric testing requirements for adult cancer drugs under the Research to Accelerate Cures and Equity (RACE) for Children Act. was shown to increase pediatric post-approval testing requirements, yet early pediatric trial rates appear unchanged. As more evidence emerges, policymakers may consider using the RACE for Children Act as a model to ensure the timely completion of pediatric studies.
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Seeking a Better Paper Trail of Federal Research Funding

Bendicksen L, Kesselheim AS, Feldman WB - JAMA

  • Commentary & Opinion
| October 2024
  • Innovation Incentives and Competition
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Stronger reporting and compliance mechanisms are needed to track federal investments in pharmaceutical research and development, as current disclosure of federal funding in drug patents and government databases is inadequate. Developing a more robust system to monitor the government’s pharmaceutical investments would facilitate efforts to quantify federal contributions to drug development—data that would be informative to both federal and state prescription drug programs.
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Sales Revenues for New Therapeutic Agents Approved by the United States Food and Drug Administration from 1995 to 2014

Wouters OJ, Kesselheim AS, Kuha J, Luyten J - Value in Health

  • Research Publications
| October 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Global revenues on 361 new FDA-approved drugs averaged $15 billion per product from 1995 to 2014, with the 25 best-selling products accounting for 38% of total sales. When including production, marketing, and other costs, 2 in 10 drugs recovered R&D and other costs within 5 years of FDA approval, and 1 in 2 within 10 years.
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Patient Assistance Programs-A New Era of Law and Policy

Daval CJR, Kesselheim AS - JAMA

  • Commentary & Opinion
| October 2024
  • Price, Value, and Access
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The authors summarize the legal and policy landscape surrounding the use of patient assistance programs. They discuss the effectiveness of the federal government’s authority under the Anti-Kickback Statute to scrutinize these programs in Medicare and the limitations of this approach in the private market. To address the back-and-forth between manufacturers and private payers, government intervention is necessary to ensure patients are not caught in the middle.
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Estimating New Eligibility and Maximum Costs of Expanded Medicare Coverage of Semaglutide for Cardiovascular Risk Prevention

Chaitoff A, Bendicksen L, Feldman WB, Zheutlin AR, Lalani HS - Annals of Internal Medicine

  • Research Publications
| October 2024
  • Price, Value, and Access
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Under the proposed expansion of Medicare coverage for semaglutide (Wegovy) for patients with elevated body mass index and established cardiovascular disease, an estimated 3.6 million Medicare beneficiaries would likely be newly eligible, with a maximum annual cost to Medicare of $34.4 billion. However, if “established cardiovascular disease” was broadly defined, 15.2 million beneficiaries could be eligible, adding up to $145 billion in annual costs.
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Price and Variability in Hospital Charges for Generic Indomethacin Suppositories

Feder NM, Hernandez I, Feldman WB, Murali M, Kesselheim AS, Elmunzer BJ, Gellad WF - JAMA Network Open

  • Research Publications
| September 2024
  • Price, Value, and Access
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New clinical uses for generic indomethacin suppositories in 2012 fueled a price increase by the drug’s manufacturer from $13 in 2008 to over $720 in 2023, with a median hospital gross charge price over $1800. Medicare patients may be particularly vulnerable to this price increase, as the drug is not covered under Medicare Part B or Part D, suggesting that policy action may be needed.
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Brief of Economists and Scholars of Health Policy in AstraZeneca v. Kennedy

Frank RG, Scott Morton FM, Kesselheim AS, Anderson GF, Conti RM, Cutler DM, Hoadley J - US Court of Appeals for the Third Circuit

  • Policy Interactions
| September 2024
  • Price, Value, and Access
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The amici argue that the prescription drug market does not function as a free market because patents and exclusivity periods grant manufacturers temporary monopolies that allow them to set prices far above production costs, and that AstraZeneca’s claim that the Medicare drug price negotiation program caps prices below “actual market value” misrepresents how drug pricing actually works. The brief further contends that the programs mirrors fair negotiation processes already used by federal agencies like the VA and DoD, and that its safeguards—including eligibility limits and category exemptions—protect innovation while restoring bargaining equity for Medicare.
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Letter on S.2140, The 2024 Patent Eligibility Restoration Act (PERA)

Bock JW, Carrier MA, Contreras JL, Duan C, Ford RA, Ghosh S, Kesselheim AS, Lemley MA, Liebesman YJ, Malone P, Morten CJ, Sandeen SK, Sarnoff JD, Sinha MS, Strandburg KJ, Tu SS, Vertinsky L - 118th Congress, Senate Committee on the Judiciary

  • Policy Interactions
| September 2024
  • Innovation Incentives and Competition
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The commenters urge the Committee to oppose the Patent Eligibility Restoration Act (PERA), arguing it would overturn centuries of jurisprudence preventing patents on scientific discoveries, laws of nature, and abstract ideas that belong in the public domain.They contend PERA would not solve alleged uncertainty problems in patent eligibility doctrine and would instead generate wasteful litigation and harm scientific discovery and health care.
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Brief of Law Scholars in BMS v. Kennedy and Janssen v. Kennedy

Kesselheim AS, Sarpatwari A, Tu SS - US Court of Appeals for the Third Circuit

  • Policy Interactions
| September 2024
  • Price, Value, and Access
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The amici support affirmance of the district court decisions in the challenges to the Medicare drug price negotiation program brought by Bristol Myers Squibb and Janssen. They argue that that the government routinely negotiates contract prices for goods including drugs without implicating the Takings Clause, that Congress has broad authority to directly regulate prices in the heavily-subsidized and highly-regulated pharmaceutical industry, and that ruling for the manufacturers would destabilize Medicare, Medicaid, and Veterans Administration drug programs that depend on negotiated discounts.
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Brief of Economists and Scholars of Health Policy in BMS v. Kennedy and Janssen v. Kennedy

Frank RG, Scott Morton FM, Kesselheim AS, Anderson GF, Conti RM, Cutler DM, Hoadley J - US Court of Appeals for the Third Circuit

  • Policy Interactions
| September 2024
  • Price, Value, and Access
An icon of a bill representing government policy.
The amici argue that the prescription drug market does not function as a free market because patents and exclusivity periods grant manufacturers temporary monopolies that allow them to set prices far above production costs, forcing payors like Medicare to pay exorbitant prices for brand-name drugs without generic alternatives. Thus, they contend that the Medicare drug price negotiation program restores bargaining equity through a fair process that mirrors existing federal drug purchasing programs (such as those used by the VA and DoD), while safeguarding innovation by targeting only drugs that have already recouped their R&D costs many times over.
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Extent of Drug Patents with Terminal Disclaimers and Obviousness-Type Double Patenting Rejections

Tu SS, Kesselheim AS, Chao B - JAMA

  • Research Publications
| September 2024
  • Innovation Incentives and Competition
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The authors investigated the use of terminal disclaimers in drug patents, particularly focusing on the practice of filing secondary patents to extend market exclusivity. 45% of small molecule patents and 33% of biologic patents had obviousness-type double patenting rejections followed by terminal disclaimers, contributing to large patent thickets that can delay generic and biosimilar entry.
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Brief of 14 Professors of Medicine and Law in Teva v. Amneal

Feldman WB, Kesselheim AS, Tu SS, Avorn J, Rome BN - US Court of Appeals for the Federal Circuit

  • Policy Interactions
| September 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
An icon of a bill representing government policy.
Teva’s improper listing of device-only patents in the Orange Book for ProAir HFA is part of a broader pattern of strategies, including dense patent thickets, post-approval patent filings, and “device hops”, that inhaler manufacturers have used for decades to delay generic competition and maintain high prices. The amici contend that because device patents extended market protection on inhalers by a median of 5.5 years and because drug-device combinations represent a large share of top-selling drugs, the Federal Circuit’s decision in Teva v. Amneal could have far-reaching implications for generic competition and patient access across many therapeutic classes.
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The Double-Edged Sword of Extremely High Prices for Gene Therapies in Sickle Cell Disease

Cliff ERS, Tessema FA - JAMA

  • Commentary & Opinion
| September 2024
  • Price, Value, and Access
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Health equity considerations should factor into the pricing of multi-million-dollar gene therapies approved for use in sickle cell disease, as these therapies are a “double-edged sword”—while high prices incentivize therapeutic development for neglected diseases, these prices conversely limit access to treatments for the underserved populations they are intended to benefit. The authors suggest creating federally funded grants targeted at drug development for historically underinvested diseases.
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Trends in Use and Evidence of Adherence to Risk Evaluation and Mitigation Strategy Pregnancy Testing Requirements for Thalidomide, Lenalidomide, and Pomalidomide in the USA, 2000-2020

Mahesri M, Sarpatwari A, Huybrechts KF, Lii J, Lee SB, Toyserkani GA, LaCivita C, Zhou EH, Dal Pan GJ, Kesselheim AS, Bykov K - Drug Safety

  • Research Publications
| September 2024
  • Regulation and Clinical Evidence
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The authors assessed patient use of and adherence to three teratogenic drugs subject to FDA-imposed risk evaluation and mitigation strategies (REMS). Patients who could become pregnant and initiated lenalidomide, thalidomide, and pomalidomide compromised 3% of all patients initiating these drugs. There was no evidence of adherence to pregnancy testing requirements in most patients of childbearing potential, pointing to the need for further research on how often patients do not adhere to REMS pregnancy testing requirements.
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Regulating Laboratory Tests: What Framework Would Best Support Safety and Validity?

Horrow C, Kesselheim AS - Milbank Quarterly

  • Commentary & Opinion
| September 2024
  • Regulation and Clinical Evidence
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The authors discuss the need for a balanced regulatory framework for laboratory-developed tests (LDTs) that protects patients without stifling laboratory innovation. They also discuss the impact and rationale behind proposals like the VALID Act and the FDA’s LDT final rule.
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Patient Perspectives on Evidence Supporting Drug Safety and Effectiveness: “What Does It Mean for Me?”

Rand LZG, McGraw SA, Wang J, Woloshin S, Wang SV, Darrow JJ, Kesselheim AS - Journal of the American Geriatrics Society

  • Research Publications
| September 2024
  • Regulation and Clinical Evidence
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When new drugs are approved, there is often limited evidence from older patient populations, and data from routine clinical care could provide patient population-relevant information. Focus groups with patients 65 years and older who take an anticoagulant were conducted to understand patient perspectives on the evidence of safety and effectiveness from clinical trials or routine clinical use data for similar patients.
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Letter to the Editor Re: “Life Years Gained From the FDA Accelerated Approval Program in Oncology: A Portfolio Model”

Liu ITT, Kesselheim AS - Journal of the National Comprehensive Cancer Network

  • Commentary & Opinion
| September 2024
  • Regulation and Clinical Evidence
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The authors comment on an analysis quantifying the life years gained from the accelerated approval program in oncology. Instead of using 37 months after accelerated approval as the counterfactual date in the authors’ analysis, they recommend using a shorter period between 7 and 19 months to reflect prior research and more accurately assess the benefits of accelerated approval.
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Drug Repurposing Via the Best Pharmaceuticals for Children Act

Liu ITT, Kesselheim AS - JAMA Pediatrics

  • Commentary & Opinion
| September 2024
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Policymakers should consider creating an NIH-sponsored federal program to repurpose off-patent drugs for new indications. An existing piece of legislation, section 409(i) of the Best Pharmaceuticals for Children Act, which is intended to run pediatric clinical trials for off-patent drugs, could act as a model for a federal drug repurposing program.
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Commercial Markups on Pediatric Oncology Drugs at 340B Pediatric Hospitals

Liu ITT, Wang J, Sarpatwari A, Kesselheim AS, Feldman WB - Pediatric Blood & Cancer

  • Research Publications
| September 2024
  • Price, Value, and Access
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Negotiated prices for oncology drugs among pediatric hospitals participating in the 340B program varied across and within hospitals, with median prices ranging between 102% and 630% of the drug’s average sales price.
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Availability and Cost of Expensive and Common Generic Prescription Drugs: A Cross-Sectional Analysis of Direct-To-Consumer Pharmacies

Lalani HS, Tessema FA, Kesselheim AS, Rome BN - Journal of General Internal Medicine

  • Research Publications
| September 2024
  • Price, Value, and Access
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Among five national direct-to-consumer pharmacies, many expensive generic drugs were not available at one or more of these pharmacies, while less expensive commonly-used generics were widely available. Prices varied but were frequently much lower than at traditional retail pharmacies. Patients might need to comparison shop to identify the lowest price for each drug, which could be difficult for many patients.
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Emulating Randomized Trials By Observational Database Studies: The RCT-DUPLICATE Initiative in COPD and Asthma

Suissa S, Schneeweiss SG, Feldman WB, Tesfaye H, Wang SV - American Journal of Epidemiology

  • Research Publications
| August 2024
  • Regulation and Clinical Evidence
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In five observational studies designed to emulate randomized clinical trials (RCTs) of asthma and COPD drugs, the authors were unable to align the study results with their respective RCTs due to the trial requirmeent to discontinue treatment before randomization, which could not be replicated observationally.This outcome highlights the challenge of trial emulation in asthma and COPD and suggests that regulators should take caution in comparing RCT and observational study results in these therapeutic areas until adequately addressed.
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The Origins of “Confidential Commercial Information” at the FDA

Daval CJR, Kesselheim AS - JAMA

  • Commentary & Opinion
| August 2024
  • Regulation and Clinical Evidence
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The authors discuss the FDA’s handling of “confidential commercial information” submitted by drug manufacturers during the drug approval process and outline steps the agency can take to allow greater flexibility to disclose information of public interest.
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Clinical Value of Guideline Recommended Molecular Targets and Genome Targeted Cancer Therapies: Cross Sectional Study

Tibau Martorell A, Hwang TJ, Avorn J, Kesselheim AS - BMJ

  • Research Publications
| August 2024
  • Regulation and Clinical Evidence
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Using the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the Scale for Clinical Actionability of Molecular Targets (ESCAT), only about one-eighth of genome-targeted cancer drugs recommended by the National Comprehensive Cancer Network (NCCN) were likely to provide high clinical benefit, while approximately one-third demonstrated promising but unproven efficacy.
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Revisiting the Potential of “Money Blinds”: Lessons From Lykos’s MDMA Research

Eisenkraft Klein D, Kesselheim AS - Health Affairs Forefront

  • Commentary & Opinion
| August 2024
  • Regulation and Clinical Evidence
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The authors discuss the FDA advisory committee’s decision to recommend against approving Lykos Therapeutics’ MDMA therapy for PTSD, arguing that the case highlights broader issues with companies funding and running their own trials. They propose the implementation of “money blinds,” where an independent intermediary would oversee the funding and selection of investigators, to reduce the impact of sponsors’ financial and ideological biases on trial outcomes.
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Merging Medical and Drug Benefits: Seeing the Whole Picture

Gondi S, Rome BN, Shrank WH - Health Affairs Forefront

  • Commentary & Opinion
| August 2024
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The authors caution against excessive restrictions on insurer-PBM integration, outlining how this integration can facilitate efforts to better manage care and comprehensively view benefit design. Rather, they recommend interventions to ensure the PBM market operates fairly, including greater scrutiny of vertical integration between PBMs and pharmacies, which may have a greater anticompetitive effect.
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Trust in the Food and Drug Administration: A National Survey Study

Feldman WB, Rand LZG, Carpenter D, Russo M, Bhaskar A, Lu Z, Campbell EG, Darrow JJ, Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Research Publications
| August 2024
  • Regulation and Clinical Evidence
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In a survey of more than 2,000 participants, a lack of trust in the FDA was associated with various characteristics, including female sex, rural communities, conservative political views, worse self-reported health, lower health care satisfaction, paying less attention to health and science news, and not having children under 18. These findings underscore the challenges in convincing a heterogeneous American public to trust the FDA.
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Biosimilar Uptake in the US: Patient and Prescriber Factors

Hong D, Kesselheim AS, Sarpatwari A, Rome BN - Health Affairs

  • Research Publications
| August 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Between 2013 and 2022, the proportion of patients who initiated a biosimilar in the US increased from 1% to 34%. Patients were less likely to initiate biosimilars if they were younger than age eighteen or the drug was prescribed by a specialist or administered in a hospital outpatient facility. These findings highlight the need for targeted policy intervention to increase biosimilar use.
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Misaligned Pharmacy Incentives in Value-Based Care

Jain N, Rome BN, Mendu ML - JAMA

  • Commentary & Opinion
| July 2024
  • Price, Value, and Access
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The authors discuss why pharmacy spending poses particular challenges for value-based care contracts between insurers and accountable care organizations, including the lack of transparency around rebates and the high cost of new, clinically effective therapies. Incorporating rebates and new drug approvals into pharmacy spending benchmarks, moving toward value-based formularies, and other strategies can help realign incentives.
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Op-Ed: This Gene Therapy May Not Work. So Why Did the FDA Fully Approve It?

Bendicksen L, Cliff ERS, Kesselheim AS - Washington Post

  • Commentary & Opinion
| July 2024
  • Regulation and Clinical Evidence
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The authors discuss the FDA’s full approval of Elevidys for Duchenne muscular dystrophy, which failed to meet its primary endpoint in a confirmatory trial. They highlight the risks of granting full approval to treatments that have failed to demonstrate significant benefit in clinical trials and caution against the approval of unproven therapies.
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Comments on Draft Policy, “NIH Intramural Research Program: Promoting Equity Through Access Planning”

Gabriele SME, Martin MJ, Kesselheim AS - National Institutes of Health (NIH)

  • Policy Interactions
| July 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The commenters support finalizing NIH’s proposed policy requiring licensees of NIH-developed technologies to submit access plans, recommending the inclusion of reasonable pricing commitments in such access planning. They also urge the agency to require public disclosure of access plans, consider patent type and license exclusivity when evaluating plans, and implement systematic annual reporting to monitor licensee compliance.
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Use of Track One Prioritized Examination for Pharmaceutical Patents

Tu SS, Feldman WB - JAMA Health Forum

  • Research Publications
| July 2024
  • Innovation Incentives and Competition
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In this review of the USPTO “Track One” program which allows companies to pay a fee for prioritized patent examination, brand-name drug manufacturers were found to disproportionately rely on the Track One program to quickly build their patent portfolios, often obtaining patents just as market exclusivity periods expire.
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State Spending Targets for Prescription Drugs

Hwang CS, Lalani HS, Rome BN - JAMA Health Forum

  • Commentary & Opinion
| July 2024
  • Price, Value, and Access
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The authors discuss recent state efforts to set prescription drug spending targets for state-sponsored health insurance plans. They outline the limitations of using this policy to address high drug spending absent a more robust approach to improve affordability.
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Removing the FDA’s Boxed Hepatotoxicity Warning and Liver Function Testing Requirement for Ambrisentan

Feldman WB, Mahesri M, Sarpatwari A, Huybrechts KF, Zhu Y, Hwang CS, Lii J, Lee SB, K Sreedhara S, Toyserkani GA, Zhou EH, Zendel L, LaCivita C, Manzo C, Dal Pan GJ, Kesselheim AS, Bykov K - JAMA Network Open

  • Research Publications
| July 2024
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Two FDA-approved treatments for pulmonary arterial hypertension, bosentan and ambrisentan, initially carried boxed warnings for hepatotoxicity and required monthly liver function tests (LFTs). The FDA later removed the warning and LFT requirement for ambrisentan in 2011, but not for bosentan. This study found an immediate increase in the use of ambrisentan but no change for bosentan after the labelling changes. LFT monitoring decreased for ambrisentan while remaining stable for bosentan.
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Comments on Proposed Rule, “Terminal Disclaimer Practice to Obviate Nonstatutory Double Patenting”

Tu SS, Carrier MA, Chao B, Cook-Deegan RM, Feldman WB, Heled Y, Kesselheim AS, Robertson CT, Sinha MS - US Patent and Trademark Office (USPTO)

  • Policy Interactions
| July 2024
  • Innovation Incentives and Competition
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The commenters support the USPTO’s proposed rule to reform terminal disclaimer practice, presenting evidence that the current system enables brand-name drug manufacturers to build thickets of indistinct continuation patents that delay generic and biosimilar competition and contribute to high drug prices.
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Biosimilar Approval Pathways: Comparing the Roles of Five Medicines Regulators

Knox RP, Desai V, Sarpatwari A - Journal of Law and the Biosciences

  • Research Publications
| July 2024
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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The authors compare the regulatory approval process for biosimilars in five jurisdictions (Australia, Canada, EU, UK, and US), noting differences in biosimilar testing requirements and policies regarding indication extrapolation, exclusivities, and biosimilar substitution. Understanding the impact of these policies on biosimilar approval and uptake is important to strengthen the global biosimilar market.
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The Cost of Drug Patent Expiration Date Errors

Tu SS, Cheian D, Gabriele SME, Rome BN, Kesselheim AS - Nature Biotechnology

  • Research Publications
| July 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The USPTO uses an automated program to calculate patent expiration dates which is subject to errors. Among 200 key drug patents, the program had a 4% error rate that erroneously extended the patent term, potentially resulting in hundreds of millions of dollars in added drug spending.
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Patent Portfolios Protecting 10 Top-Selling Prescription Drugs

Horrow C, Gabriele SME, Tu SS, Sarpatwari A, Kesselheim AS - JAMA Internal Medicine

  • Research Publications
| July 2024
  • Innovation Incentives and Competition
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Nearly 75% of the US patents and patent applications protecting the 10 highest-revenue brand-name drugs in 2021 were filed after FDA approval. These post-approval patents, particularly those on parts of the drug other than the active ingredient, can contribute to dense patent thickets that warrant closer scrutiny by the USPTO to limit delays to generic and biosimilar competition.
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Measuring and Understanding Market Exclusivity Length for New Prescription Drugs in France, Australia, and the USA

Van de Wiele VL, Kesselheim AS, Gleeson D, Lu Z, Tu SS, Rome BN - Pharmaceutical Medicine

  • Research Publications
| July 2024
  • Innovation Incentives and Competition
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The length of market exclusivity obtained by brand-name drug manufacturers was found to be similar in the US, France, and Australia, in part due to various policy differences in the three markets that affect the duration of market exclusivity. Alignment of market exclusivity lengths internationally could better enable timely generic entry to address high prescription drug spending in these countries.
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Quantifying Research and Development Expenditures in the Drug Industry

Wouters OJ, Kesselheim AS - JAMA Network Open

  • Commentary & Opinion
| June 2024
  • Innovation Incentives and Competition
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In this comment on an a new bottom-up estimate of the costs of drug development, the authors highlight the value of these cost estimates to ongoing policy discussions on prescription drug pricing and innovation while also recognizing the methodological limitations of each estimate.
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Federal Trade Commission Actions on Prescription Drugs, 2000-2022

Daval CJR, Egilman AC, Sarpatwari A, Kesselheim AS - JAMA

  • Research Publications
| June 2024
  • Innovation Incentives and Competition
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From 2000-2022, the Federal Trade Commission (FTC) pursued 22 enforcement actions against pharmaceutical firms for alleged anticompetitive practices and challenged 62 mergers, of which 61 were allowed to continue, 58 after divesting drugs to third-party competitors. Congressional action may be necessary to strengthen the FTC’s authority and enforcement capacity related to pharmaceuticals.
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Patient-Level Savings on Generic Drugs Through the Mark Cuban Cost Plus Drug Company

Kouzy R, El Alam MB, Corrigan KL, Lalani HS, Ludmir EB - JAMA Health Forum

  • Research Publications
| June 2024
  • Price, Value, and Access
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In this economic evaluation, patients could have saved on 12% of all prescriptions filled across 124 generic drugs in 2019, with a median savings of $5 per fill, if the drugs were purchased through the Mark Cuban Cost Plus Drug Company’s (MCCDPC) direct-to-consumer pharmacy. Uninsured patients would have benefitted the most from using MCCDPC.
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Comments for Listening Session, “Optimizing FDA’s Use of and Processes for Advisory Committees”

Rand LZG - Food and Drug Administration (FDA)

  • Policy Interactions
| June 2024
  • Regulation and Clinical Evidence
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The FDA should convene advisory committee meetings more frequently with formal votes to promote public trust, provide explanations when agency decisions differ from committee recommendations, and develop guidance on how patient and caregiver testimony should be incorporated into advisory committee decision-making.
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Medicare Negotiation’s Drug Reformulation Problem

Vogel M, Rome BN, Kesselheim AS, Feldman WB - Annals of Internal Medicine

  • Commentary & Opinion
| June 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The authors shed light on a loophole in the Medicare Drug Price Negotiation program: once a generic version of any formulation of a drug is marketed, all formulations of that drug are exempted from negotiation. They detail how this loophole could enable costly gamesmanship, listing expensive drugs that could be excluded through this technicality. Instead, negotiation eligibility should be determined by aggregating Medicare spending on all formulations that do not face bona fide competition.
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How Health Technology Assessment Can Help to Address Challenges in Drug Repurposing: a Conceptual Framework

Abu-Zahra T, Grimm SE, Scholte M, Raymakers AJN, Kesselheim AS, Joore MA - Drug Discovery Today

  • Research Publications
| June 2024
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Drug repurposing can be an efficient way to use existing drugs to treat new indications but is not without challenges, particularly in the early stages of development. This study identifies 20 challenges with drug repurposing, grouped into six categories (data access, research and development, collaboration, business case, regulatory and legal challenges), and outlines a framework for incorporating health technology assessment (HTA) methods to address these challenges.
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How Do Risk Evaluation and Mitigation Strategies Impact Clinical Practice? A National Survey of Physicians

Sarpatwari A, Lu Z, Russo M, Zakoul H, Lee SB, Toyserkani GA, Zhou EH, LaCivita C, Hyatt Hawkins Shaw K, Zendel L, Dal Pan GJ, Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Research Publications
| June 2024
  • Regulation and Clinical Evidence
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Over two-thirds of surveyed physicians thought that the FDA-mandated risk evaluation and mitigation strategies (REMS) certification process for certain drugs provided useful context and information, though roughly the same proportion wanted REMS materials to include additional data on drugs’ benefits. Physicians also indicated that they wanted more information concerning non-REMS-related safety risks and that REMS paperwork should be better integrated into clinical workflows.
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Global Cooperation and Early Access-Clinical Outcomes Matter

Tibau Martorell A, Kesselheim AS - Lancet Oncology

  • Commentary & Opinion
| June 2024
  • Regulation and Clinical Evidence
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In this commentary on two analyses related to cancer drug approvals, the authors highlight that although using surrogate measures may reduce costs and expedite patient access to new treatments, these measures might not accurately predict overall survival benefits. Thus, rigorous post-approval testing and transparent data reporting are critical to ensure patients receive the most effective treatments.
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Estimated Medicare Part D Savings From Generic Drugs with a Skinny Label

Egilman AC, Kesselheim AS, Sarpatwari A, Rome BN - Annals of Internal Medicine

  • Research Publications
| June 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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For 15 brand-name drugs that faced competition from “skinny-label” generics, these generics entered the market a median of 2.5 years earlier than generic competition might otherwise be expected. This earlier competition aved Medicare Part D an estimated $14.6 billion from 2015 to 2021. To reinforce these savings, a safe harbor should be created to protect manufacturers engaged in skinny labeling from induced patent infringement lawsuits.
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Use of Artificial Intelligence in Drug Development

Druedahl LC, Price WN, Minssen T, Sarpatwari A - JAMA Network Open

  • Research Publications
| May 2024
  • Regulation and Clinical Evidence
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Out of more than 100,000 investigational and approved drugs listed in the Pharmaprojects database, developers reported using artificial intelligence (AI) to aid in the development of 164 investigational drugs and 1 approved drug. Thus, the use of AI in drug development has been modest and mostly limited to early-stage applications, such as molecule discovery and screening.
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Medicare Should Cover Weight Loss Drugs as Long as the Prices Are Affordable

Hwang CS, Kesselheim AS, Rome BN - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Spring 2024
  • Price, Value, and Access
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Glucagon-like peptide-1 (GLP-1) receptor agonists are effective for treating obesity, but the high cost of these medications endangers the financial viability of our health care system. To ensure that these drugs are available to Medicare beneficiaries, pharmaceutical manufacturers must lower their prices.
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Testimony: Patent Thickets and Product Hops: How Congress Could Reward Legitimate Innovation While Facilitating More Timely Generic Competition

Feldman WB - 118th Congress, Senate Committee on the Judiciary

  • Policy Interactions
| May 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Feldman outlines how brand-name manufacturers delay generic competition through large patent thickets and product hops. He uses inhalers and GLP-1 receptor agonists as primary case studies, noting that more than half of patents on these drug-device combinations cover devices rather than active ingredients. He endorses four bipartisan patent reform bills currently under consideration and proposes additional reforms, including FDA authority to review Orange Book listings, mandatory USPTO re-examination, limits on patents asserted in infringement litigation, and adjustments to the 180-day generic exclusivity and 30-month stay periods. Read his written testimony.
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Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval

Liu ITT, Kesselheim AS, Cliff ERS - JAMA

  • Research Publications
| May 2024
  • Regulation and Clinical Evidence
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Among a 5-year cohort of cancer drugs approved by the FDA under accelerated approval, only half of approvals demonstrated improvements in overall survival or quality of life in confirmatory trials, with 60% of conversions to full approval relying on clinical endpoints.
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The Value of the Quality-Adjusted Life Years

Willke RJ, Pizzi LT, Rand LZG, Neumann P - Value in Health

  • Commentary & Opinion
| May 2024
  • Price, Value, and Access
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Recent concerns about the quality-adjusted life year (QALY) being discriminatory against selected patient groups have resulted in US legislation and regulation that would ban the use of the QALY in government programs. The authors identify scientific support for the QALY and its usefulness as an input to healthcare decision-making, acknowledge its limitations, and argue that, when appropriately constructed and used, it will not be discriminatory against these patient groups.
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Clinical Value of Molecular Targets and FDA-Approved Genome-Targeted Cancer Therapies

Tibau Martorell A, Hwang TJ, Molto C, Avorn J, Kesselheim AS - JAMA Oncology

  • Research Publications
| May 2024
  • Regulation and Clinical Evidence
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Fewer than a third of genome-targeted oncology drugs approved in the US between 2015 and 2022 were shown to have substantial clinical benefit at the time of approval. Benefit frameworks like the ESMO Magnitude of Clinical Benefit Scale (MCBS) can help identify genome-targeted therapies with demonstrated clinical potential.
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From “Price Controls” to Robust Public Conversation: How CMS Can Move Drug Price Negotiation Into the Light

Ollendorf DA, Rand LZG, Mooney H, Phillips M, Basu A - Health Affairs Forefront

  • Commentary & Opinion
| April 2024
  • Price, Value, and Access
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The authors propose a framework for the Medicare Drug Price Negotiation Program that aims to promote an evidence-based, robust process that includes stakeholders and draws on both cost-effectiveness and open deliberation to reach maximum fair prices.
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The FDA in the Crosshairs-Science, Politics, and Abortion

Fernandez Lynch H, Kesselheim AS - JAMA

  • Commentary & Opinion
| April 2024
  • Regulation and Clinical Evidence
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The authors discuss the implications of the Supreme Court’s decision in FDA v. Alliance for Hippocratic Medicine for abortion access, FDA regulatory discretion, and the extent to which the FDA’s actions preempt conflicting state laws. They urge the Supreme Court to endorse the importance of the FDA’s public health mission and the agency’s authority to take regulatory action under a broad Congressional mandate.
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State Coverage and Reimbursement of Antiobesity Medications in Medicaid

Liu BY, Rome BN - JAMA

  • Research Publications
| April 2024
  • Price, Value, and Access
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In early 2023, 21% of state Medicaid programs covered at least one anti-obesity medication. From 2011 to 2022, the number of prescriptions for anti-obesity medications reimbursed by Medicaid increased by 1300%, driven by use of the glucagon-like peptide-1 (GLP-1) receptor agonists. Considering the cost burden of novel anti-obesity medications and their therapeutic potential, Medicaid beneficiaries’ access to these therapies will depend on negotiating lower prices.
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Changes in Use of Hepatitis C Direct-Acting Antivirals After Access Restrictions Were Eased By State Medicaid Programs

Davey S, Costello K, Russo M, Davies S, Lalani HS, Kesselheim AS, Rome BN - JAMA Health Forum

  • Research Publications
| April 2024
  • Price, Value, and Access
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In a difference-in-differences analysis using Medicaid data from 2015-2019, the use of highly effective direct-acting hepatitis C antivirals increased substantially after states eliminated coverage restrictions based on the severity of liver disease, active substance use, or prescriber specialty. These findings suggest that such restrictions have prevented access to an important and cost-effective public health intervention.
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Spending on Targeted Therapies for Duchenne Muscular Dystrophy

Bendicksen L, Kesselheim AS, Rome BN - JAMA

  • Research Publications
| April 2024
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The US spent an estimated $3 billion on targeted therapies for Duchenne muscular dystrophy from 2016-2023, despite limited evidence of effectiveness and delayed confirmatory trials. More than $1 billion was paid by Medicaid and Medicare. Policymakers should compel the timely completion of confirmatory trials for these therapies and implement alternative payment models to minimize financial risk in case novel interventions prove ineffective.
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We Need to Talk About Values: a Proposed Framework for the Articulation of Normative Reasoning in Health Technology Assessment

Charlton V, DiStefano MJ, Mitchell P, Morrell L, Rand LZG, Badano G, Baker R, Calnan M, Chalkidou K, Culyer A, Howdon D, Hughes D, Lomas J, Max C, McCabe C, O'Mahony JF, Paulden M, Pemberton-Whiteley Z, Rid A, Scuffham P, Sculpher M, Shah K, Weale A, Wester G - Health Economics, Policy and Law

  • Commentary & Opinion
| April 2024
  • Price, Value, and Access
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Health technology assessment (HTA) is an inherently value-based activity, yet variation exists in the description of value-based judgements across HTA organizations and literature. The authors propose a framework that distinguishes between the considerations, claims, and beliefs used in HTA, providing a tool to support decision-makers and improve transparency.
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Use of Efficiency Frontiers to Align Prices and Clinical Benefits of Biologic Therapies for Plaque Psoriasis

Egilman AC, Kesselheim AS, Avorn J, Raymakers AJN, Rome BN - JAMA Dermatology

  • Research Publications
| April 2024
  • Price, Value, and Access
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Using an efficiency frontier approach, the prices for 13 biologic drugs used to treat plaque psoriasis would need to be reduced by a median of 71% in the US to align with prices for the most cost-effective therapeutic alternatives on the frontier. This approach offers policymakers a useful alternative to conventional cost-effectiveness analysis that could be useful for therapeutic classes with multiple drugs.
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Rates and Costs of Drug Testing Practices for Private Payors in the Outpatient Setting in the United States, 2015-2019

Barenie RE, Bateman BT, Connery HS, Tsacogianis T, Kesselheim AS - Journal of Substance Use and Addiction Treatment

  • Research Publications
| April 2024
  • Price, Value, and Access
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The authors assessed the frequency and cost of drug testing for privately insured US patients who were chronically dispensed opioids versus those with substance use disorders. Although a similar proportion of patients in each population underwent drug testing, patients with substance use disorders were tested at much higher rates. Further research is necessary to determine how the costs of drug testing affect patients’ adherence to medications for substance use disorders.
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No Parking Here: A Review of Generic Drug 180-Day Exclusivity and Recent Reform Proposals

Van de Wiele VL, Darrow JJ, Kesselheim AS - Yale Journal of Health Policy, Law and Ethics

  • Research Publications
| April 2024
  • Innovation Incentives and Competition
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Loopholes in the Hatch‑Waxman Act’s 180‑day generic exclusivity enabled “parking” opportunities for drug manufacturers to strategically delay generic competition, though reforms enacted in 2003 and subsequent antitrust scrutiny have largely addressed the most problematic “parking” behaviors. The remaining instances of gaming 180-day exclusivity are rare and often driven by changed in FDA review standards rather than strategic conduct by manufacturers.
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Federal Enforcement of Pharmaceutical Fraud Under the False Claims Act, 2006-2022

Bendicksen L, Kesselheim AS, Daval CJR - Journal of Health Politics, Policy and Law

  • Research Publications
| April 2024
  • Innovation Incentives and Competition
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Between 2006 and 2022, federal antifraud actions involving drug manufacturers under the False Claims Act have resulted in lucrative settlements, but alleged fraud has continued despite the penalties. Additional measures may be necessary to deter fraudulent activity that harms patients and taxpayers.
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Patient Out-Of-Pocket Costs for Biologic Drugs After Biosimilar Competition

Feng K, Russo M, Maini L, Kesselheim AS, Rome BN - JAMA Health Forum

  • Research Publications
| March 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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In this study of commercially insured patients using 1 of 7 biologic drugs facing biosimilar competition between 2009 and 2022, biosimilar competition was not associated with lower patient out-of-pocket spending. These findings emphasize the need for targeted policy intervention to improve the affordability of biologics.
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Direct-To-Consumer Drug Company Pharmacies

Rome BN - JAMA

  • Commentary & Opinion
| March 2024
  • Price, Value, and Access
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The author discusses the potential effects of LillyDirect, the new pharmacy program launched by Eli Lilly to sell the company’s drugs directly to patients. This new direct-to-consumer pharmacy is unlikely to improve access for affordability for most patients but could introduce new complications.
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Patents on Risk Evaluation and Mitigation Strategies for Prescription Drugs and Generic Competition

Sarpatwari A, Kohli S, Tu SS, Kesselheim AS - JAMA

  • Research Publications
| March 2024
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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Five of 21 drugs covered by non-class-wide risk evaluation and mitigation strategies (REMS) had patents on these REMS programs; of these drugs, a median of 10 REMS patents were listed in the Orange Book, which can complicate generic entry. Federal lawmakers shield generic manufacturers from REMS patent infringement lawsuits to ensure timely generic competition.
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The Constitutionality of Medicare Drug-Price Negotiation Under the Takings Clause

Bhargava R, Brown N, Kapczynski A, Kesselheim AS, Lim SY, Morten CJ - Journal of Law, Medicine & Ethics

  • Research Publications
| Spring 2024
  • Price, Value, and Access
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The authors evaluate the claim that Medicare price negotiation under the Inflation Reduction Act amounts to an unconstitutional taking of private property under the Takings Clause. Since selling prescription drugs in the Medicare program is a voluntary act, government action to lower Medicare reimbursement is not an unconstitutional taking and accepting such a contention would invite further challenges to essential government programs.
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Brief of Economists and Scholars of Health Policy in Novartis v. Becerra

Frank RG, Scott Morton FM, Kesselheim AS, Anderson GF, Conti RM, Cutler DM, Hoadley J - US District Court for the District of New Jersey

  • Policy Interactions
| March 2024
  • Price, Value, and Access
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The amici argue that the prescription drug market is not a free market but a highly regulated environment in which government-granted patents and exclusivity periods allow manufacturers to set prices far above competitive levels. Thus, they contend that the Medicare drug price negotiation program restores bargaining equity by targeting only drugs that have already recouped their R&D investments many times over, mirrors longstanding federal price negotiation mechanisms (e.g., VA, DoD, Medicaid), and poses negligible risk to genuine innovation given that higher drug prices do not meaningfully correlate with therapeutically valuable new products.
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Delivery Device Patents on GLP-1 Receptor Agonists

Alhiary R, Gabriele SME, Kesselheim AS, Tu SS, Feldman WB - JAMA

  • Research Publications
| March 2024
  • Innovation Incentives and Competition
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Dozens of delivery device patents were listed in the FDA Orange Book for glucagon like peptide-1 (GLP-1) receptor agonists despite none of these patents mentioning the drugs’ active ingredients, chemical structures, or therapeutic classes. These patents contribute to large patent thickets that serve as a basis for litigation against potential generic GLP-1 manufacturers and their removal would substantially reduce barriers to generic entry.
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Public Returns on Public Investment: Moderna’s Violation of the Social Contract

Sarpatwari A - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Spring 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Moderna’s proposed fourfold price increase for the NIH‑Moderna COVID‑19 vaccine violates the social contract underlying extensive public investment, given that US taxpayers bore much of the risk and cost of the vaccine’s development and manufacturing. The author recommends that Congress use its purchasing power and pricing authorities to ensure affordable access to the vaccine and to prevent price gouging for publicly funded therapeutics in future public health emergencies.
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Promoting Drug and Vaccine Innovation and Managing High Prices: Introducing a Special Symposium

Kesselheim AS, Sarpatwari A, Rome BN - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Spring 2024
  • Price, Value, and Access
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This introduction to a special symposium frames the central policy challenge of promoting meaningful drug and vaccine innovation while preventing high prices from putting new therapies out of reach for patients. Federal policy must better align public and private investment, pricing, and coverage decisions so that government‑supported innovation delivers broad access and real clinical value.
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Government Support of Meaningful Drug and Device Innovation: Pathways and Challenges

Kesselheim AS - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Spring 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The US government is a central driver of transformative drug and device innovation through NIH funding and early‑stage research, but too often ends up paying high prices for products that offer little added clinical benefit. It contends that Congress should strengthen policies that link payment and coverage to meaningful evidence of benefit, while expanding public investment in high‑value innovation, to protect patients and taxpayers from low‑value, high‑cost therapies.
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Addressing High Drug Prices By Reforming Pharmacy Benefit Managers

Rome BN - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Spring 2024
  • Price, Value, and Access
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High US drug prices are driven primarily by manufacturer pricing power and delayed generic competition, while pharmacy benefit managers (PBMs) play a complex but secondary role through formularies, rebates, and consolidation. Congress should pursue targeted PBM reforms while prioritizing policies that curb brand‑name drug prices and promote timely competition, or risk raising costs without addressing the root cause.
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Identifying Therapeutic Alternatives in Medicare Drug Price Negotiation: The Case of Etanercept

Mooney H, Martin MJ, Bendicksen L, Kesselheim AS, Rome BN, Lalani HS - Journal of Managed Care & Specialty Pharmacy

  • Research Publications
| March 2024
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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As part of Medicare drug price negotiation, the Centers for Medicare and Medicaid Services (CMS) must identify the appropriate therapeutic alternatives to which to compare each selected drug. This study outlines a methodology to identify therapeutic alternatives using clinical guidelines, using etanercept (Enbrel) as an example. Up to 22 therapeutic alternatives are identified for the biologic, highlighting the complexity of such a task.
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Estimated Spending on Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa

Raymakers AJN, Kesselheim AS, Mostaghimi A, Feldman WB - JAMA Dermatology

  • Research Publications
| March 2024
  • Price, Value, and Access
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Beremagene geperpavec (B-VEC) is a topical gene therapy FDA-approved in 2023 for both recessive and dominant dystrophic epidermolysis bullosa (DEB). US spending on B-VEC therapy was estimated to reach $805 million in the first three years post-approval, with a lifetime cost of $15 and $17 million per patient with recessive or dominant DEB, respectively.
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Biologic Patent Challenges Under the America Invents Act

Van de Wiele VL, Kesselheim AS, Tu SS - Nature Biotechnology

  • Research Publications
| March 2024
  • Innovation Incentives and Competition
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Of the 42% of patents asserted in administrative review proceedings concerning biologics from 2012 to 2021, most had all patent claims found invalid. These findings indicate that inter partes review (IPR) and post grant review challenges to biologic patents are an effective means of invalidating wrongly granted biologic patents and encouraging timely biosimilar entry.
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Administrative Action on Drug Pricing: Lessons and Opportunities for the Center for Medicare and Medicaid Innovation

Liu ITT, Lalani HS, Kesselheim AS - Journal of Managed Care & Specialty Pharmacy

  • Research Publications
| March 2024
  • Price, Value, and Access
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The Center for Medicare and Medicaid Innovation (CMMI) is a federal agency tasked with developing innovative healthcare payment and delivery models to decrease spending while maintaining or improving patient outcomes. The authors review CMMI interventions targeted to prescription drug spending and prices, identifying lessons for policymakers on the design of future payment interventions.
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Additional Steps for Maintaining Public Trust in the FDA (Reply)

Rand LZG, Carpenter D, Kesselheim AS, Bhaskar A, Darrow JJ, Feldman WB - Hastings Center Report

  • Commentary & Opinion
| March 2024
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
In response to a letter on strategies to improve trust in the FDA, the authors note that, despite calls for greater transparency, the FDA broadly applies the Trade Secrets Act, limiting the information it releases publicly. The “revolving door” of appointees who leave government service for industry also weakens efforts to reduce industry interference in the agency. Though legislation has been proposed to limit lobbying and improve disclosure by former federal employees, these solutions have not yet become law.
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Testimony: Supporting Drug Innovation and Fair Prices for Patients with Rare Diseases

Kesselheim AS - 118th Congress, House Committee on Energy and Commerce, Subcommittee on Health

  • Policy Interactions
| February 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Kesselheim argues that growth in rare disease drug development stems primarily from NIH-funded research, FDA regulatory flexibility, and blockbuster revenue potential rather than Orphan Drug Act incentives, and that the rare disease carve-outs in the Medicare drug price negotiation program should not be expanded. He urges the subcommittee to reject the ORPHAN Cures Act, MINI Act, and Creating Hope Reauthorization Act related to priority review vouchers, while advancing the RARE Act to close a loophole created by Catalyst Pharmaceuticals v. Becerra that allows manufacturers to block timely generic competition for rare disease drugs. Read his written testimony.
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Determining Upper Payment Limits: Considerations for State PDABs

Martin MJ, Rome BN, Mooney H, Rand LZG, Raymakers AJN, Bendicksen L, Hwang CS, Lalani HS - National Academy for State Health Policy (NASHP)

  • Policy Interactions
| February 2024
  • Price, Value, and Access
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This white paper presents three potential strategies state PDABs may use to set upper payment limits (UPLs) for drugs deemed unaffordable: reference pricing, net price benchmarking, and budgetary threshold analyses. It explores the strengths and limitations of each approach and emphasizes that strategies are not mutually exclusive and should be tailored to the underlying drivers of a drug’s unaffordability.
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Identifying Therapeutic Alternatives for State PDAB Affordability Reviews

Mooney H, Martin MJ, Bendicksen L, Kesselheim AS, Rome BN, Lalani HS - National Academy for State Health Policy (NASHP)

  • Policy Interactions
| February 2024
  • Price, Value, and Access
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This memo proposes a methodology for state Prescription Drug Affordability Boards (PDABs) to identify therapeutic alternatives for drugs under affordability review, drawing on clinical practice guidelines from US medical professional associations. It outlines inclusion and exclusion criteria, addresses methodological challenges such as multi-drug regimens and strong guideline recommendations based on low-quality evidence.
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March-In Guidance for Publicly Funded Drugs: A Necessary Safety Net for Patients

Avorn J, Kesselheim AS - Health Affairs Forefront

  • Commentary & Opinion
| February 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The authors discuss the promise and limitations of the Biden administration’s proposed framework to implement march-in rights for prescription drugs under the Bayh-Dole Act. Exercising march-in rights, implementing Medicare drug price negotiation under the Inflation Reduction Act, and operationalizing government patent use under 21 U.S.C. § 841 could collectively help lower drug costs and begin to properly account for the role of federal funding in drug development.
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Comments on Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights

Kesselheim AS, Bhaskar A - National Institute of Standards and Technology (NIST)

  • Policy Interactions
| February 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The commenters support the proposed framework’s recognition that price can be a relevant factor when federal agencies consider exercising Bayh-Dole Act march-in rights on federally funded inventions, arguing this clarification advances the public’s statutory right to reasonable access while preserving incentives for innovation.
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Brief of Law Scholars in Novo Nordisk v. Becerra

Kesselheim AS, Sarpatwari A, Tu SS - US District Court for the District of New Jersey

  • Policy Interactions
| February 2024
  • Price, Value, and Access
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The amici argue that the Medicare drug price negotiation program is constitutional because the federal government has long-settled authority to negotiate prices for goods it purchases and to regulate prices within industries, particularly those (like pharmaceuticals) that benefit from extensive government-granted privileges such as patents, regulatory exclusivities, and research subsidies. They warn that accepting Novo Nordisk’s Fifth Amendment takings theory would destabilize core federal health programs, including Medicaid, the 340B program, the Veterans Health Administration, and EMTALA, all of which rely on similar statutory pricing and discount mechanisms to function.
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Brief of Economists and Scholars of Health Policy in Novo Nordisk v. Becerra

Frank RG, Scott Morton FM, Kesselheim AS, Anderson GF, Conti RM, Cutler DM, Hoadley J - US District Court for the District of New Jersey

  • Policy Interactions
| February 2024
  • Price, Value, and Access
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The amici argue that Novo Nordisk’s challenge to the Medicare drug price negotiation program misrepresents the prescription drug market, which is not a free market because patents and exclusivity periods grant manufacturers temporary monopolies that allow them to set prices far above production costs. They defend CMS’s decision to aggregate products sharing the same active ingredient as a necessary response to “product hopping” tactics explicitly contemplated by Congress, and contend that the negotiation program mirrors other fair federal drug purchasing processes while including safeguards that protect innovation.
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Independent Advice on Drug Approvals: an Investigation of EMA Practices

Daval CJR, Kesselheim AS, Sharpless LK, Sarpatwari A - Journal of General Internal Medicine

  • Research Publications
| February 2024
  • Regulation and Clinical Evidence
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The European Medicines Agency (EMA) consulted independent scientific advisory groups (SAGs) in a minority of drug approval decisions, and these decisions usually aligned with the advisors’ non-binding recommendations. In contrast to the FDA’s declining use of advisory committees, however, EMA’s consultation with SAGs fluctuated annually.
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Op-Ed: How Much Do Physicians Really Know About FDA Drug and Device Regulation?

Dhruva SS, Kesselheim AS, Redberg RF - MedPage Today

  • Commentary & Opinion
| January 2024
  • Regulation and Clinical Evidence
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Recent surveys show that many physicians misunderstand FDA drug and device approval, often assuming that therapeutics are consistently approved based on rigorous evidence despite the growing use of expedited pathways and delayed or incomplete post‑approval studies. Stronger pre‑ and post‑market evidence standards and better physician education are necessary so FDA approval more reliably signals meaningful clinical benefit.
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Characteristics of Patients Receiving Novel Muscular Dystrophy Drugs in Trials vs Routine Care

Hong D, Avorn J, Wyss R, Kesselheim AS - JAMA Network Open

  • Research Publications
| January 2024
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Patients prescribed novel treatments for Duchenne Muscular Dystrophy were older and had more advanced diseases stage than patients enrolled in the pre-market clinical trials. Patients also discontinued these treatments after a median of 7 months. These findings raise questions about the translation of trial findings to routine care settings and the clinical benefit of high-cost drugs.
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Biologic Patent Thickets and Terminal Disclaimers

Tu SS, Goode R, Feldman WB - JAMA

  • Research Publications
| January 2024
  • Innovation Incentives and Competition
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Almost half of biologic patents have terminal disclaimers, with most issued 12-14 years after FDA approval, coinciding with the expiration of FDA market exclusivity. These patents typically do not disclose anything new and cover follow-on features of the drug, instead contributing to patent thickets that can delay biosimilar competition.
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Brief of Law Scholars in Novartis v. Becerra

Kesselheim AS, Sarpatwari A, Tu SS - US District Court for the District of New Jersey

  • Policy Interactions
| January 2024
  • Price, Value, and Access
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The amici argue that the Medicare drug price negotiation program does not effect a Fifth Amendment taking because the government routinely negotiates contract prices in its commercial capacity and may constitutionally regulate prices in highly regulated, privilege-dependent industries like pharmaceuticals. They additionally contend that Novartis’s patent rights do not alter the takings analysis, noting that 28 U.S.C. § 1498 already authorizes the government to use patented inventions (including by procuring generic copies) in exchange for only a reasonable royalty, a far more extreme but clearly constitutional alternative to Medicare negotiation.
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Improving Drug Supply Chain Security

Kannarkat JT, Denham MW, Sarpatwari A - JAMA Health Forum

  • Commentary & Opinion
| January 2024
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The authors discuss the FDA’s progress towards requiring pharmaceutical supply chain actors to develop an interoperable system for tracking and exchanging prescription drugs. In light of recent manufacturing issues related to cancer drugs and diabetes therapies, they recommend regulators impose stronger, more centralized interoperability standards and communicate clearer, more detailed guidance to stakeholders.
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Why Some Patients Overpay for Specialty Generic Drugs

Crosson FJ, Kesselheim AS - JAMA Internal Medicine

  • Commentary & Opinion
| January 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The authors discuss the Hatch-Waxman Act framework for generic drug competition, and the distortions in the pharmaceutical supply chain that can keep generic drug prices high years after the end of market exclusivity for the branded originator.
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Preserving Timely Generic Drug Competition with Legislation on “Skinny Labeling”

Tu SS, Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Commentary & Opinion
| January 2024
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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Recent court decisions, including Federal Circuit’s ruling in GlaxoSmithKline v. Teva, threaten the FDA’s “skinny labeling” pathway by exposing generic manufacturers to patent liability based on required labeling. Congress should act to reverse these decision to preserve skinny labeling as a pathway to facilitate the timely entry of affordable generic drugs.
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Potential Medicare and Medicaid Savings on Anti-CD20 Therapy for Multiple Sclerosis

Kim J, Kesselheim AS, Bove R, Avorn J, Rome BN - JAMA Neurology

  • Research Publications
| January 2024
  • Price, Value, and Access
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The authors discuss the financial repercussions of using ocrelizumab, a more expensive anti-CD20 monoclonal antibody, compared to rituximab for treating multiple sclerosis (MS). Between 2018 and 2021, they estimate that Medicare and Medicaid could have saved $2.5 billion if ocrelizumab were priced similarly to rituximab.
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Physicians’ Perspectives on FDA Regulation of Drugs and Medical Devices: A National Survey

Dhruva SS, Kesselheim AS, Woloshin S, Ji RZ, Lu Z, Darrow JJ, Redberg RF - Health Affairs

  • Research Publications
| January 2024
  • Regulation and Clinical Evidence
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In a national survey of oncologists, internists, and cardiologists, just 41% of those surveyed reported a moderate or better understanding of FDA’s drug approval process. Based on these findings, information about drug and device approval processes should be better integrated into medical school curricula and physicians’ subspecialty education.
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CRISPR-Phage Antibacterials to Address the Antibiotic Resistance Crisis: Scientific, Economic, and Regulatory Considerations

Pacia DM, Brown BL, Minssen T, Darrow JJ - Journal of Law and the Biosciences

  • Research Publications
| January 2024
  • Innovation Incentives and Competition
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CRISPR‑enhanced bacteriophage therapies offer a promising, highly targeted approach to combating antibiotic‑resistant infections but face substantial scientific, economic, and regulatory barriers that could impede development and uptake. Realizing the public health potential of CRISPR‑phage antibacterials will require sustained public investment, clearer and more flexible regulatory pathways for individualized therapies, and incentive structures that address market failures inherent in antibacterial development.
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Cost of Exempting Sole Orphan Drugs From Medicare Negotiation

Vogel M, Zhao O, Feldman WB, Chandra A, Kesselheim AS, Rome BN - JAMA Internal Medicine

  • Research Publications
| January 2024
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The Inflation Reduction Act allows Medicare to negotiate certain high-spending drugs but excludes those that are approved solely for the treatment of a single rare disease. 25 out of 282 drugs with annual Medicare spending over $200 million from 2012-2021 might have qualified for this exemption, and Medicare spent an average of $2.5 biollion annually on these products.
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Complicated Regulatory Decision-Making Following Inconsistent Trial Results: The Issue with Ibrutinib for Mantle Cell Lymphoma

Cliff ERS, Hilal T, Kesselheim AS - Nature Reviews Clinical Oncology

  • Commentary & Opinion
| January 2024
  • Regulation and Clinical Evidence
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The authors discuss the delay in the withdrawal of ibrutinib for mantle cell lymphoma after the release of conflicting confirmatory trial results, and highlight why the FDA needs more regulatory options than “approve” or “withdraw” when reviewing products.
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Building Public Trust in Scientific Decision Making Through Expert Advisory Committees: Lessons From the FDA

Daval CJR, Kesselheim AS - IBM Center for the Business of Government

  • Research Publications
| December 2023
  • Regulation and Clinical Evidence
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FDA drug approval decisions closely align with advisory committee recommendations despite a marked decline in committee use over time. To strengthen trust in the FDA and the agency’s use of expert advisory committees, the authors recommend more consistent referral criteria, clearer and more confirmable voting questions, expanded deliberation time, and explicit procedures for explaining committee disagreements to the public.
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Brief of Law Scholars in Dayton Area Chamber of Commerce v. Becerra

Kesselheim AS, Sarpatwari A, Tu SS - US District Court for the Southern District of Ohio

  • Policy Interactions
| December 2023
  • Price, Value, and Access
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The amici argue that the Medicare drug price negotiation program is constitutional because the federal government has long-established authority to negotiate prices as a market participant and to regulate prices in industries like pharmaceuticals that benefit from extensive government privileges such as patents, regulatory exclusivities, and research subsidies. They further warn that accepting the Chamber’s constitutional challenge would upend not only Medicare but also the Medicaid, 340B, and Veterans Health Administration drug pricing programs, as well as EMTALA, by exposing longstanding cost-containment mechanisms to a flood of takings litigation.
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Brief of Law Scholars in Boehringer Ingelheim v. Becerra

Kesselheim AS, Sarpatwari A, Tu SS - US District Court for the District of Connecticut

  • Policy Interactions
| December 2023
  • Price, Value, and Access
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The amici argue that the Medicare drug price negotiation program is a constitutionally permissible exercise of the government’s long-recognized authority to negotiate prices for goods it purchases and that accepting Boehringer’s takings theory would destabilize Medicare, Medicaid, Veterans Health, and 340B price-containment mechanisms that courts have uniformly upheld. The brief also argues that patents are public franchises likely outside the Takings Clause and that 28 U.S.C. § 1498 already permits the government to procure generic versions of patented drugs like Jardiance for only a reasonable royalty, undermining Boehringer’s coercion argument.
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Brief of Economists and Scholars of Health Policy in Boehringer Ingelheim v. Becerra

Frank RG, Scott Morton FM, Kesselheim AS, Anderson GF, Conti RM, Cutler DM, Hoadley J - US District Court for the District of Connecticut

  • Policy Interactions
| December 2023
  • Price, Value, and Access
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The amici argue that Boehringer Ingelheim’s challenge to the Medicare drug price negotiation program rests on a misleading account of the prescription drug market, which does not function as a free market because patents and exclusivity periods grant manufacturers temporary monopolies that allow them to set prices well above production costs and any true measure of value. They further contend that the program mirrors fair negotiation processes already used by federal agencies like the VA and DoD, and that its safeguards protect innovation while restoring bargaining equity for Medicare.
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Overcoming Challenges to Implementing New Evidence for Low-Dose Anticoagulant Use in Peripheral Artery Disease

Chaitoff A, Kesselheim AS - Circulation

  • Commentary & Opinion
| December 2023
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The authors discuss new evidence informing the use of low-dose anticoagulants in patients with peripheral artery disease, noting that inadequate provider uptake has limited optimal use of this intervention. Further clinical trials, establishing living clinical guidelines, and further government action on anticoagulant drug prices could improve care quality.
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Inequitable Conduct and Invalidation of Patents Related to Food and Drug Administration-Regulated Products

Tu SS, Leadmon C, Daval CJR, Kesselheim AS - JAMA

  • Research Publications
| December 2023
  • Innovation Incentives and Competition
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Patents on FDA-regulated products were more frequently invalidated due to fraud on the USPTO, known as “inequitable conduct,” than patents in any other sector. Although such invalidation is rare, these results suggest that pharmaceutical and medical device companies are caught hiding information or lying to the USPTO more than firms in other industries.
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Ancillary Product Patents to Extend Biologic Patent Life

Goode R, Feldman WB, Tu SS - JAMA

  • Research Publications
| December 2023
  • Innovation Incentives and Competition
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Biologic manufacturers initially use patents to protect their product’s fundamental structure, while often protecting any ancillary features (e.g., post-translational modifications) using trade secret law at the time of FDA approval. Only after a median of 18.3 years do firms seek to patent these ancillary features, effectively extending their patent protection by a median of 10.4 years.
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FDA and Chevron Deference: A Case Review

Bendicksen L, Kesselheim AS, Daval CJR - Food and Drug Law Journal

  • Research Publications
| December 2023
  • Regulation and Clinical Evidence
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Among a case cohort of 26 disputes, the FDA won every case in which federal appellate courts found relevant laws to be ambiguous and applied Chevron deference. The demise of the Chevron regime may threaten the FDA’s product jurisdiction authority and ability to protect public health.
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Outcomes of the 340B Drug Pricing Program: A Scoping Review

Knox RP, Wang J, Feldman WB, Kesselheim AS, Sarpatwari A - JAMA Health Forum

  • Research Publications
| November 2023
  • Price, Value, and Access
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In this literature review of the 340B program, the authors found that while the program does provide benefits to patients, greater transparency is needed to ensure that 340B entities are acting in alignment with the program’s intended purpose.
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Incorporating Information on Therapeutic Alternatives Into the IRA Prescription Drug Negotiations

Anderson GF, Frank RG, Rome BN - The Brookings Institution

  • Commentary & Opinion
| November 2023
  • Price, Value, and Access
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Under the Inflation Reduction Act, Medicare is beginning to negotiate prices for some high-cost drugs. These negotiations will be based on several factors, including how the drug compares to therapeutic alternatives. The authors provide practical considerations for how the Centers for Medicare and Medicaid Services (CMS) can identify therapeutic alternatives to inform price negotiation.
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Patents and Regulatory Exclusivities on FDA-Approved Insulin Products: A Longitudinal Database Study, 1986-2019

Olsen A, Beall RF, Knox RP, Tu SS, Kesselheim AS, Feldman WB - PLOS Medicine

  • Research Publications
| November 2023
  • Innovation Incentives and Competition
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The authors describe how insulin manufacturers have utilized U.S.-granted patents and FDA regulatory exclusivities from 1986 to 2019 to establish long-lasting market protections. Numerous modern insulin products are drug-device combination products, and the device patents associated with these products have played a critical role in extending protections over the past decade.
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National Comprehensive Cancer Network Guideline Recommendations of Cancer Drugs with Accelerated Approval

Cliff ERS, Rome RS, Kesselheim AS, Rome BN - JAMA Network Open

  • Research Publications
| November 2023
  • Regulation and Clinical Evidence
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National Comprehensive Cancer Network (NCCN) committees combine evidence and expert opinion to create oncology treatment guidelines that inform clinical practice and reimbursement. Among 100 drugs and 315 cancer indications, most NCCN recommendations were foudn to be supported by lower-level evidence.
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Modernizing Federal Oversight of Laboratory-Developed Tests—Toward Safety, Validity, and Utility

Singhal U, Horrow C, Kesselheim AS, Morgan TM - New England Journal of Medicine

  • Commentary & Opinion
| November 2023
  • Regulation and Clinical Evidence
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The rapid growth and commercialization of laboratory‑developed tests (LDTs) have outpaced federal oversight, leaving many widely used diagnostics with limited evidence of clinical validity or utility and posing risks of misdiagnosis and patient harm. Congress and the FDA should modernize oversight by establishing a unified, risk‑based regulatory framework that ensures safety, validity, and clinical utility while preserving LDT innovation.
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Brief of Economists and Scholars of Health Policy in AstraZeneca v. Becerra

Frank RG, Scott Morton FM, Kesselheim AS, Anderson GF, Conti RM, Cutler DM, Hoadley J - US District Court for the District of Delaware

  • Policy Interactions
| November 2023
  • Price, Value, and Access
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The amici argue that the prescription drug market does not function as a free market because patents and exclusivity periods grant manufacturers temporary monopolies that allow them to set prices far above production costs, and that AstraZeneca’s claim that the Medicare drug price negotiation program caps prices below “actual market value” misrepresents how drug pricing actually works. The brief further contends that the programs mirrors fair negotiation processes already used by federal agencies like the VA and DoD, and that its safeguards—including eligibility limits and category exemptions—protect innovation while restoring bargaining equity for Medicare.
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The Inflation Reduction Act and Access to High-Cost Cardiovascular Therapies

Kazi DS, Wadhera RK, Rome BN - JAMA

  • Commentary & Opinion
| November 2023
  • Price, Value, and Access
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Seven of the first 10 drugs selected for Medicare price negotiation are indicated for cardiovascular and metabolic conditions, and many older adults with cardiovascular disease will benefit from new out-of-pocket limits in Medicare Part D. Now is the time for action as financial barriers limit patient access to cardiovascular therapies and cardiovascular mortality continues to climb.
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Comments on Proposed Rule, “Discrimination on the Basis of Disability in Health and Human Services Programs or Activities”

Rand LZG, Kesselheim AS, Raymakers AJN - US Department of Health & Human Services (HHS)

  • Policy Interactions
| November 2023
  • Price, Value, and Access
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The commenters support HHS efforts to eliminate disability discrimination in health care but argue that the proposed rule should not preclude the use of value assessment methods like cost-effectiveness analysis and quality-adjusted life years (QALYs), which can promote access to effective treatments and incentivize meaningful therapeutic innovation for people with disabilities.
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Reforming Pharmacy Benefit Managers—A Review of Bipartisan Legislation

Cai CL, Rome BN - New England Journal of Medicine

  • Commentary & Opinion
| November 2023
  • Price, Value, and Access
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As Congress considers several bipartisan proposals to regulate pharmacy benefit managers (PBMs), the authors provide background on the role of PBMs and review the policies unde consideration. While many of these reforms are a step in the right direction, they may do little to lower prescription drug costs for patients and the health care system.
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Confronting High Costs and Clinical Uncertainty: Innovative Payment Models for Gene Therapies

Horrow C, Kesselheim AS - Health Affairs

  • Commentary & Opinion
| November 2023
  • Price, Value, and Access
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The authors offer a taxonomy of alternative payment models that payers can deploy to navigate uncertainty regarding the effectiveness, durability, and budgetary impact of novel cell and gene therapies. They discuss the strengths and limitations of three types of alternative payment model designs: amortization, risk spreading, and performance-based strategies.
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Changes in Induced Medical and Procedural Abortion Rates in a Commercially Insured Population, 2018 to 2022: an Interrupted Time-Series Analysis

Hwang CS, Kesselheim AS, Sarpatwari A, Huybrechts KF, Brill G, Rome BN - Annals of Internal Medicine

  • Research Publications
| November 2023
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The COVID-19 pandemic and regulatory changes to the in-person dispensing requirement for mifepristone resulted in a persistent, decreasing rate of procedural abotions, while the use of teelhealth for medical abortions remained rare. Amid increasing state restrictions of teleprescribing of mifepristone, the authors outline opportunities for commercial payers to improve abortion access.
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Approval and Therapeutic Value of Gene Therapies in the US and Europe

Vokinger KN, Glaus CEG, Kesselheim AS - Gene Therapy

  • Research Publications
| November 2023
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Among gene therapies approved for use in Switzerland, the EU, and the US, two-thirds of these products had high added therapeutic value, and approved indications in Europe tended to be more restrictive than those in the US.
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Characteristics of Post Hoc Subgroup Analyses of Oncology Clinical Trials: A Systematic Review

Alrawabdeh J, Alzu'bi M, Alzyoud M, Odeh N, Hamadneh Y, Mian H, Mohyuddin GR, Kelkar AH, Goodman AM, Chakraborty R, Russler-Germain DA, Mehra N, Baggio D, Cliff ERS, Al Hadidi S - JNCI Cancer Spectrum

  • Research Publications
| October 2023
  • Regulation and Clinical Evidence
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Post hoc subgroup analyses now constitute a large and expanding share of oncology publications, often with industry funding and without clear signals that findings are secondary or exploratory. This practice risks misleading clinicians and regulators, necessitated stronger reporting standards for such studies.
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Will Medicare Price Negotiation Delay Cancer-Drug Launches?

Vogel M, Kesselheim AS, Feldman WB, Rome BN - New England Journal of Medicine

  • Commentary & Opinion
| October 2023
  • Price, Value, and Access
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The authors analyze whether the new Medicare negotiation program will incentivize drug makers to delay launching cancer drugs, as claimed by some in the industry. They show that for several reasons, a strategy of delayed launch would have greater costs than benefits for drugmakers.
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Fairer Returns on Public Investments

Lalani HS, Kesselheim AS - Issues in Science and Technology

  • Commentary & Opinion
| October 2023
  • Innovation Incentives and Competition
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The authors reflect on strategies to ensure fair taxpayer return on the high-risk investments made by the Advanced Research Projects Agency for Health (ARPA-H). Direct patient benefit must be central to the agency’s grant programs, as should a commitment to leverage the agency’s legal authorities to share in the financial benefits of innovative technologies.
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Op-Ed: We Can’t Let Drug Companies Get Out of Negotiating Prices

Daval CJR, Kesselheim AS - Washington Post

  • Commentary & Opinion
| October 2023
  • Price, Value, and Access
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The authors outline and refute some of the most prominent legal claims raised by drug manufacturers in litigation against Medicare drug price negotiation. Each of these claims suggests a concerning belief that some private companies have a right to public funds—a belief that courts should reject as price negotiation litigation moves forward.
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Brief of Law Scholars in BMS v. Becerra and Janssen v. Becerra

Kesselheim AS, Sarpatwari A, Tu SS - US District Court for the District of New Jersey

  • Policy Interactions
| October 2023
  • Price, Value, and Access
An icon of a bill representing government policy.
The amici argue that the Medicare drug price negotiation program does not effectuate an unconstitutional taking because the federal government has long-settled authority to negotiate prices as a market participant and to regulate prices in industries (like pharmaceuticals) that benefit from extensive government privileges such as patents and regulatory exclusivities They also contend that patents are public franchises rather than private property subject to the Takings Clause, and that 28 U.S.C. § 1498 demonstrates the government could lawfully pursue an even more aggressive remedy by procuring generic copies of patented drugs in exchange for only a reasonable royalty.
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Brief of Economists and Scholars of Health Policy in BMS v. Becerra and Janssen v. Becerra

Frank RG, Scott Morton FM, Kesselheim AS, Anderson GF, Conti RM, Cutler DM, Hoadley J - US District Court for the District of New Jersey

  • Policy Interactions
| October 2023
  • Price, Value, and Access
An icon of a bill representing government policy.
The amici argue that the prescription drug market does not function as a free market because patents and exclusivity periods grant manufacturers temporary monopolies that allow them to set prices far above production costs, forcing payors like Medicare to pay exorbitant prices for brand-name drugs without generic alternatives. Thus, they contend that the Medicare drug price negotiation program restores bargaining equity through a fair process that mirrors existing federal drug purchasing programs (such as those used by the VA and DoD), while safeguarding innovation by targeting only drugs that have already recouped their R&D costs many times over.
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Wedding Websites, Free Speech, and Adverse Drug Effects

Avorn J - New England Journal of Medicine

  • Commentary & Opinion
| October 2023
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The Supreme Court decision in 303 Creative LLC v. Elenis, though focused on the First Amendment rights of a website designer, may also have implications for the FDA’s ability to effectively regulate drug manufacturers’ statements on the efficacy and safety of their products.
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Infections Following Bispecific Antibodies in Myeloma: a Systematic Review and Meta-Analysis

Reynolds G, Cliff ERS, Mohyuddin GR, Popat R, Midha S, Ng Liet Hing M, Harrison SJ, Kesselheim AS, Teh BW - Blood Advances

  • Research Publications
| October 2023
  • Regulation and Clinical Evidence
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Bispecific antibodies, a novel immunotherapy, have demonstrated promising efficacy against multiple myeloma yet can increase patient infection risk due to their effectiveness in depleting plasma- and T-cells. In this systematic review and meta-analysis of infections in more than 1600 myeloma patients in 16 clinical trials, the pooled prevalence of all-grade infections and grade 3+ infections were found to be 56% and 24%, respectively.
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The Problem of Limited-Supply Agreements for Medicare Price Negotiation

Gabriele SME, Feldman WB - JAMA

  • Commentary & Opinion
| October 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Limited supply agreements should factor into CMS’ assessment of “bona fide competition” for Medicare drug price negotiation. These agreements, in which a generic manufacturer agrees with a branded drugmaker to release its product at a reduced volume, should be disclosed during price negotiation and should not exempt a drug from negotiation.
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Free Speech Challenges to the Inflation Reduction Act

Tu SS, Tushnet R - JAMA

  • Commentary & Opinion
| October 2023
  • Price, Value, and Access
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Drug manufacturers’ First Amendment arguments against the Medicare drug price neogtiation program fail based on current Supreme Court jurisprudence. Furthermore, drug firms are allowed to challenge the Inflation Reducation Act as violating the First Amendment, this would create a much broader problem for any laws that permit the federal government to negotiate prices.
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Trust and Regulation: Assuring Scientific Independence in the FDA’s Emergency Use Authorization Process

Patel NG, Kesselheim AS, Darrow JJ - Journal of Health Politics, Policy and Law

  • Research Publications
| October 2023
  • Regulation and Clinical Evidence
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Political interference in the FDA’s Emergency Use Authorization (EUA) process can undermine the agency’s scientific independence and public trust in FDA approval decisions. Expanding advisory committee involvement, increasing transparency around agency decision‑making, and better managing internal agency disagreement are all strategies the FDA should consider to improve the EUA process.
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Regulatory Review Duration and Differences in Submission Times of Drugs in the United States and Europe, 2011 to 2020

Vokinger KN, Serra-Burriel M, Glaus CEG, Rohr U, Hwang TJ, Di Sanguinetto SDT, Kesselheim AS - Annals of Internal Medicine

  • Research Publications
| October 2023
  • Regulation and Clinical Evidence
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In this comparison of the FDA, European Medicines Agency (EMA), and Swissmedic, the regulatory review times of drugs submitted to all three agencies were found to be slightly longer in the EU and Switzerland (44 weeks) than in the US (39 weeks). Differences in the agencies’ review procedures that likely drive this variation.
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The 340B Drug Pricing Program: Administration, Litigation, and Reform

Knox RP, Sarpatwari A - Oklahoma Law Review

  • Research Publications
| September 2023
  • Price, Value, and Access
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The 340B Drug Pricing Program is increasingly threatened by the Health Resources and Services Administration’s (HRSA’s) limited statutory authority and a wave of adverse litigation narrowing its ability to regulate and enforce program requirements. Drawing on recent court decisions involving orphan drugs, patient definitions, contract pharmacies, and administrative dispute resolutions in the 340B program, the authors contend that Congress must expand HRSA’s authority to ensure the program continues to function as intended.
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Putting the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act Under the Microscope

Madden J, Minssen T, Kesselheim AS - GARDP Antimicrobial Viewpoints

  • Commentary & Opinion
| September 2023
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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The Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act would provide $6 billion in funding for the creation of a subscription model to incentivize antibiotic research and development. Though the bill’s goals are praiseworthy, improvements are still needed to achieve optimal results in promoting and protecting public health.
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Three Key Ways to Strengthen Proposed Pharmacy Benefit Manager Regulations

Lalani HS, Martin MJ, Kesselheim AS - Health Affairs Forefront

  • Commentary & Opinion
| September 2023
  • Price, Value, and Access
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Congressional efforts to regulate the business practices of pharmacy benefit managers (PBMs), while an important step toward a more transparent pharmaceutical supply chain, could be strengthened in three ways to the legislation’s impact on patients and health care spending.
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Protecting Medicare’s Discretion to Say No to Unproven Therapies

Daval CJR, Bendicksen L, Kesselheim AS - JAMA

  • Commentary & Opinion
| September 2023
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The authors discuss two legislative proposals that would restrict the Center for Medicare & Medicaid Services’ (CMS) coverage discretion for drugs and devices that lack robust evidence. A drug’s FDA approval should not be an automatic qualifier for Medicare coverage given the recognized distinctions in the FDA’s and CMS’ statutory authorities. Thus, CMS’ ability to “say no” is a critical safeguard for public health and Medicare’s financial solvency.
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Testimony: The Inflation Reduction Act of 2022: Reducing Excessive Spending and Support Patient Access to Brand-Name Drugs While Promoting Meaningful Innovation

Kesselheim AS - 118th Congress, House Committee on Energy and Commerce, Subcommittee on Oversight and Investigations

  • Policy Interactions
| September 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Kesselheim defends the IRA’s Medicare drug price negotiation provisions as necessary to address unsustainable US brand-name drug prices, projecting approximately $100 billion in savings over a decade while actually improving incentives for meaningful innovation. He systematically rebuts industry concerns about innovation impacts (including claims about drug launch delays, orphan drug disincentives, and small-molecule drug development) and discusses the main constitutional challenges to the IRA brought by drug manufacturers. Read his written testimony.
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Why Pharmaceutical Patent Thickets Are Unique

Carrier MA, Tu SS - Texas Intellectual Property Law Journal

  • Research Publications
| September 2023
  • Innovation Incentives and Competition
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The authors refute the argument that pharmaceutical companies’ accumulation of patent thickets is analogous to technology companies’ patenting practices. Firms’ litigation of method of use patents and increasing use of continuation patents to block generic entry highlight how pharmaceutical patent thickets, unlike thickets in other industries, are designed to be anti-competitive.
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Brief of Economists and Scholars of Health Policy in Merck v. Becerra

Frank RG, Scott Morton FM, Kesselheim AS, Anderson GF, Conti RM, Cutler DM, Hoadley J - US District Court for the District of Columbia

  • Policy Interactions
| September 2023
  • Price, Value, and Access
An icon of a bill representing government policy.
The amici argue that the prescription drug market does not function like a typical free market, as patents and exclusivity periods grant manufacturers temporary monopolies that allow them to set prices far above production costs and the drugs’ true value to consumers. Thus, they contend that the Medicare drug price negotiation program restores bargaining equity without meaningfully harming innovation, since eligible drugs have already recouped their R&D investments many times over and the law includes multiple safeguards exempting certain categories of drugs.
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The Accelerated Approval Program for Cancer Drugs—Finding the Right Balance

Gyawali B, Kesselheim AS, Ross JS - New England Journal of Medicine

  • Commentary & Opinion
| September 2023
  • Regulation and Clinical Evidence
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FDA should further improve the accelerated approval program for cancer drugs to ensure meaningful patient benefit. Key elements of trial design and endpoint selection, if appropriately defined, can improve the program’s aim to advance access to effective, safe cancer therapies.
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Conducting Drug Affordability Reviews: Considerations for State PDABs

Martin MJ, Rome BN, Hwang CS, Lalani HS, Raymakers AJN, Rand LZG, Bendicksen L, Mooney H, Liu ITT, Avorn J, Kesselheim AS - National Academy for State Health Policy (NASHP)

  • Policy Interactions
| September 2023
  • Price, Value, and Access
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This white paper offers comprehensive guidance for state PDABs on conducting drug affordability reviews, covering how to define affordability across multiple perspectives and how to evaluate drug evidence, pricing and spending, comparative effectiveness, economic analyses, patient access, and market dynamics. It emphasizes the need for holistic, indication-specific assessments that account for statutory constraints, stakeholder engagement, and the complexities of the pharmaceutical supply chain.
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Variation in Endpoints in FDA Medication Approvals: A Review of Acute and Preventive Migraine Medications

Sharpless LK, Kesselheim AS, Orr SL, Darrow JJ - Neurology

  • Research Publications
| September 2023
  • Regulation and Clinical Evidence
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Of the 16 migraine drugs approved by the FDA between 2001-2022, the clinical endpoints measured in the 45 pivotal trials for these therapies significantly varied in both type and timing, complicating comparative effectiveness research intended to guide patients to the optimal migraine medications
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The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence

Bendicksen L, Zuckerman DM, Avorn J, Phillips S, Kesselheim AS - Annals of Internal Medicine

  • Commentary & Opinion
| September 2023
  • Regulation and Clinical Evidence
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The authors review the FDA’s controversial decision to grant accelerated approval to eteplirsen and other antisense oligonucleotides for Duchenne muscular dystrophy. Eteplirsen’s limited evidence of efficacy in pivotal trials, high price, and delays in post-approval testing may have set a problematic precedent for later accelerated approvals.
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Securing the Trustworthiness of the FDA to Build Public Trust in Vaccines

Rand LZG, Carpenter D, Kesselheim AS, Bhaskar A, Darrow JJ, Feldman WB - Hastings Center Report

  • Research Publications
| September 2023
  • Regulation and Clinical Evidence
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In the context of the FDA’s approval of the COVID-19 vaccine in 2020, the authors discuss outline five conditions the FDA should meet to minimize political influence and build public trust and acceptance of public health interventions.
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Physician Perspectives on the Food and Drug Administration’s Decision to Grant Accelerated Approval to Aducanumab for Alzheimer’s Disease

Dhruva SS, Kesselheim AS, Woloshin S, Ji RZ, Lu Z, Darrow JJ, Redberg RF - Clinical Pharmacology & Therapeutics

  • Research Publications
| September 2023
  • Regulation and Clinical Evidence
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In a national survey of 214 physicians familiar with the FDA’s accelerated approval of aducanumab for Alzheimer’s disease, only 14% reported that they would prescribe or recommend the drug, while 86% said they would not. Additionally, 67% of respondents reported reduced trust in other drugs approved through the accelerated approval pathway following the aducanumab decision.
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Battles Over Medication Abortion Threaten the Integrity of Drug Approvals in the US

Bendicksen L, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Fall 2023
  • Regulation and Clinical Evidence
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Legal challenges to the FDA’s approval of mifepristone, such as Alliance for Hippocratic Medicine v. FDA, represent an unprecedented intrusion into the drug approval process that threatens the FDA’s regulatory authority. Allowing courts to second‑guess FDA scientific judgments would destabilize the US drug approval system, deter pharmaceutical innovation, and jeopardize patient access to a wide range of lawful, evidence‑based medications.
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Authority of Medicare to Limit Coverage of FDA-Approved Products: Legal and Policy Considerations

Daval CJR, Kesselheim AS - JAMA Internal Medicine

  • Commentary & Opinion
| September 2023
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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A review of legal precedents and coverage determinations reveals how CMS exercises its legal discretion to shape Medicare coverage of FDA-regulated drugs and devices. As products come to market with limited clinical evidence and narrow risk-benefit profiles, CMS should leverage conditional or limited coverage mechanisms to account for these evidence gaps.
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Ensuring Ethical Postprogression Therapy for Patients in Randomized Trial Control Arms

Cliff ERS, Kesselheim AS, Feldman WB - Journal of Clinical Oncology

  • Commentary & Opinion
| August 2023
  • Regulation and Clinical Evidence
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Randomized oncology trials are ethically and scientifically compromised when patients in control arms are denied timely access to standard‑of‑care therapies after disease progression, particularly when investigational drugs already have known efficacy in later‑line settings. Ensuring post‑progression crossover is essential both to respect trial participants’ contributions and to produce valid overall‑survival evidence, and should be treated as a core requirement of ethical trial design rather than an optional feature.
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Patents and Regulatory Exclusivities on GLP-1 Receptor Agonists

Alhiary R, Kesselheim AS, Gabriele SME, Beall RF, Tu SS, Feldman WB - JAMA

  • Research Publications
| August 2023
  • Innovation Incentives and Competition
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A median of nearly 20 patents were listed in the FDA Orange Book for GLP-1 drugs, leading to a median market exclusivity period of 18.3 years. More than half of these patents were on the drugs’ delivery devices rather than active ingredients, with many filed after FDA approval.
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Gauging the Value of Top-Selling Drugs in Medicare (Reply)

Egilman AC, Rome BN, Kesselheim AS - JAMA

  • Commentary & Opinion
| August 2023
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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In the absence of a US national health technology assessment (HTA) agency to evaluate the clinical benefit of FDA-approved drugs, the authors outline why therapeutic benefit ratings from foreign HTA agencies are a valuable resource for Medicare drug price negotiations.
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340B-Where Do We Go From Here?

Kishore S, Nayak RK, Kesselheim AS - JAMA

  • Commentary & Opinion
| August 2023
  • Price, Value, and Access
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To strengthen the future of the 340B drug discount program, policy reforms that improve program oversight, reimagine program eligibility, and strengthen protections for 340B facilities and pateints can ensure that savings from the program translate into improved clinical care.
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Patenting Strategies on Inhaler Delivery Devices

Demkowicz BJ, Tu SS, Kesselheim AS, Carrier MA, Feldman WB - Chest

  • Research Publications
| August 2023
  • Innovation Incentives and Competition
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Among 53 brand‑name inhalers approved for asthma and COPD between 1986 and 2020, 39 products had device patents listed in the FDA’s Orange Book, accounting for nearly half of all listed patents on inhalers. Most device patents (77%) did not mention the inhaler’s active ingredients, and these patents extended market exclusivity by a median of 5.5 years beyond non‑device patents. These broadly scoped device patents can delay generic competition, and the FDA should take action to better align Orange Book patent listings with genuine drug innovation.
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Moving Naloxone Over the Counter Is Necessary but Not Sufficient

Messinger JC, Beletsky L, Kesselheim AS, Barenie RE - Annals of Internal Medicine

  • Commentary & Opinion
| August 2023
  • Price, Value, and Access
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FDA approval of the first over-the-counter formulation of naloxone has expanded access to the life-saving medication, but action is needed to ensure adequate supply in the face of new demand, including by prioritizing comprehensive distribution methods and investing in harm-reduction strategies.
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Market Dynamics of Authorized Generics in Medicaid From 2014 to 2020

Rome BN, Gunter SJ, Kesselheim AS - Health Services Research

  • Research Publications
| August 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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From 2014 to 2020, authorized generics (AGs) accounted for 4% of all Medicaid prescriptions and 16% of prescriptions among drugs with an AG available. While most AGs entered the market around the same time as independent generics, about one‑third were marketed at least one year before independent generic competition or faced no independent generics at all. These early AG launches may be used to blunt independent generic competition, which should warrant closer scrutiny by regulators.
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Comparative Effectiveness and Safety of Generic Versus Brand-Name Fluticasone-Salmeterol to Treat Chronic Obstructive Pulmonary Disease

Feldman WB, Kesselheim AS, Avorn J, Russo M, Wang SV - Annals of Internal Medicine

  • Research Publications
| August 2023
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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In a response to FDA officials’ comment, the authors agree that the FDA struck an appropriate balance between evidence generation and patient access to lower-cost generics in the case of bioequivalence studies for fluticasone-salmeterol. Post-market studies using real-world data can help the FDA continue to promote the availability of generic inhalers and other drug-device combinations.
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Changes in the Number of Continuation Patents on Drugs Approved By the FDA

Tu SS, Kesselheim AS, Wetherbee K, Feldman WB - JAMA

  • Research Publications
| August 2023
  • Innovation Incentives and Competition
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Between 2000 and 2015, the number of continuation patents on pharmaceuticals increased by 200% and the number of litigated continuation patents increased by 213%. These patents do not disclose any new innovations, and typically cover follow-on features of a drug (e.g., new formulations or methods of use), contributing to patent thickets that can delay generic competition.
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Biosimilar Competition for Humira Is Here: Signs of Hope Despite Early Hiccups

Rome BN, Kesselheim AS - Arthritis & Rheumatology

  • Commentary & Opinion
| August 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The long‑delayed arrival of biosimilar competition for Humira in the US offers a critical test of whether biosimilars can meaningfully lower biologic drug prices, after years of patent thickets, settlements, and regulatory barriers kept competition at bay. While early biosimilar entry shows promise, insurer incentives, product reformulations, and opaque rebate practices may blunt price reductions unless policymakers intervene to promote transparent competition and easier substitution.
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Comments on Discussion Draft of the 2023 Modernizing and Ensuring PBM Accountability Act

Lalani HS, Martin MJ, Rome BN, Kesselheim AS - 118th Congress, Senate Committee on Finance

  • Policy Interactions
| July 2023
  • Price, Value, and Access
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The commenters propose modifications to the Committee’s PBM reform bill to reduce patient out-of-pocket costs by basing Medicare Part D cost-sharing on net rather than list prices and requiring PBMs to remit 100% of rebates to plan sponsors. They also call for increased transparency through data sharing with state Medicaid programs and annual public reporting on drug-level rebates for the highest-spending Medicare and Medicaid drugs.
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Op-Ed: Registry Enrollment for Alzheimer’s Drug Coverage Won’t Help Much

Avorn J, Chaitoff A - MedPage Today

  • Commentary & Opinion
| July 2023
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Medicare’s requirement that patients receiving lecanemab (Leqembi) enroll in a registry will neither meaningfully improve evidence generation nor substantially restrict access to the drug. Given lecanemab’s modest clinical benefit and significant cost, the authors the registry is a largely symbolic policy that does little to address the evidence and value concerns raised by amyloid‑targeting Alzheimer’s treatments.
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Comments on Discussion Draft of 2023 Reauthorization of the Pandemic and All-Hazards Preparedness Act

Kesselheim AS, Martin MJ, Sarpatwari A - 118th Congress, Senate Committee on Health, Education, Labor, and Pensions

  • Policy Interactions
| July 2023
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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The commenters support a proposed reasonable pricing requirement for BARDA- and CDC-supported medical countermeasures tied to G7 prices, citing substantial public investment in pharmaceutical development including the mRNA COVID-19 vaccines. However, the authors oppose extending and expanding the Priority Review Voucher program for medical countermeasures, arguing empirical evidence shows PRVs do not stimulate innovation and instead strain FDA resources while accelerating review of non-innovative drugs.
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Association of Advisory Committee Votes with US Food and Drug Administration Decision-Making on Prescription Drugs, 2010-2021

Daval CJR, Teng TW, Russo M, Kesselheim AS - JAMA Health Forum

  • Research Publications
| July 2023
  • Regulation and Clinical Evidence
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Between 2010 and 2021, FDA drug advisory committees were convened less frequently over time, from a high of 50 in 2012 to a low of 18 in 2020 and 2021. FDA regulatory actions aligned with 88% of advisory committee votes on initial approvals, supplemental approvals, withdrawals of accelerated approvals, and safety actions, suggesting the agency continued to follow committee advice even as committee meetings declined.
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The Impact of Electronic Health Record Discontinuity on Prediction Modeling

Kar S, Bessette LG, Wyss R, Kesselheim AS, Lin KJ - PLOS ONE

  • Research Publications
| July 2023
  • Regulation and Clinical Evidence
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Among patients with cardiovascular (CV) comorbidities, prediction models developed using electronic health record (EHR) data with low continuity consistently performed worse than those with high continuity in the prediction of mortality, major CV events, and bleeding outcomes.
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Physician Experiences with and Perceptions of Risk Evaluation and Mitigation Strategy Programs with Elements to Assure Safe Use

Sarpatwari A, Brown BL, McGraw SA, Dejene SZ, Abdurrob A, Kesselheim AS - PLOS ONE

  • Research Publications
| July 2023
  • Regulation and Clinical Evidence
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Interviewed physicians held mixed views on the impact of FDA risk evaluation and mitigation strategy (REMS) programs for drugs on their clinical practice, with many expressing concerns about the programs’ administrative burden and patient privacy. This suggests that while REMS programs may have positive features, they must be better integrated into clinical workflows.
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Therapeutic Value of First Versus Supplemental Indications of Drugs in US and Europe (2011-20): Retrospective Cohort Study

Vokinger KN, Glaus CEG, Kesselheim AS, Serra-Burriel M, Ross JS, Hwang TJ - BMJ

  • Research Publications
| July 2023
  • Regulation and Clinical Evidence
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As the number of supplemental indications for drugs approved by the FDA and EMA has increased over the last decade, the proportion of approved supplemental indications rated as having high therapeutic value was substantially lower than for approved first indications. Second and third indications were 36-37% and 45-52% less likely, respectively, to receive a high-value rating than the drug’s initial indication.
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The Prevalence of Drug Patent Term Extensions in the United States, 2000-2018

Van de Wiele VL, Kesselheim AS, Nagar SN, Tu SS - Nature Biotechnology

  • Research Publications
| July 2023
  • Innovation Incentives and Competition
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Nearly half of new U.S. drugs approved between 2000 and 2018 received patent term extensions, which frequently prolonged market exclusivity well beyond non‑patent regulatory protections. Patent term extensions were rarely invalidated in litigation and often applied to secondary patents, reinforcing their role in delaying generic or biosimilar entry.
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Chronic Obstructive Pulmonary Disease Exacerbations and Pneumonia Hospitalizations Among New Users of Combination Maintenance Inhalers

Feldman WB, Avorn J, Kesselheim AS, Gagne JJ - JAMA Internal Medicine

  • Research Publications
| July 2023
  • Regulation and Clinical Evidence
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In a large real‑world cohort, initiation of LAMA–LABA inhalers was associated with fewer COPD exacerbations and significantly fewer pneumonia hospitalizations than ICS–LABA therapy. These findings support clinical guidelines favoring LAMA–LABA combinations for most patients with COPD.
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Identifying Drugs for State PDAB Affordability Review

Rome BN, Martin MJ, Kesselheim AS - National Academy for State Health Policy (NASHP)

  • Policy Interactions
| June 2023
  • Price, Value, and Access
An icon of a bill representing government policy.
This memo explains how drugs are defined and categorized under the US regulatory framework—including active ingredients, active moieties, drug products, NDAs/BLAs, and National Drug Codes (NDCs)—and discusses the implications of these definitions for PDAB drug selection. It recommends that PDABs adopt a broad definition of a drug (aggregating by active moiety where feasible) to enable comprehensive affordability review and prevent manufacturer gaming, while acknowledging practical and statutory limitations.
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Congress’ Misguided Plan to Ban QALYs

Rand LZG, Raymakers AJN, Rome BN - JAMA

  • Commentary & Opinion
| June 2023
  • Price, Value, and Access
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Congress’s proposed ban on the use of quality‑adjusted life‑years (QALYs) and “similar measures” in federal health programs is based on a misunderstanding of how these tools are used and would not protect patients from discrimination. Instead, such a ban would undermine comparative‑effectiveness analysis, weaken Medicare drug price negotiations, and ultimately preserve high drug prices that restrict patient access.
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Op-Ed: New Alzheimer’s Drug Is a Problem for FDA’s Pass-Fail Approach

Avorn J - Washington Post

  • Commentary & Opinion
| June 2023
  • Regulation and Clinical Evidence
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FDA’s binary “approve or reject” framework is ill‑suited for drugs like lecanemab (Leqembi) that offer only modest clinical benefit while posing meaningful risks and costs. The agency should adopt a conditional approval pathway that allows limited use of such drugs while stronger evidence is generated, rather than granting full approval that triggers widespread use and spending despite uncertainty.
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The Rise and Fall of the Insulin Pricing Bubble

Feldman WB, Rome BN - JAMA Network Open

  • Commentary & Opinion
| June 2023
  • Price, Value, and Access
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Soaring insulin list prices over the past two decades created a “gross‑to‑net” pricing bubble, in which manufacturers raised prices while insurers and PBMs negotiated ever‑larger confidential rebates that lowered net prices but left patients facing high out‑of‑pocket costs. Recent insulin price cuts were driven largely by looming Medicaid rebate penalties rather than market reform, and without greater pricing transparency and policy intervention, similar pricing bubbles will persist for other brand‑name drugs.
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Medicare Drug Price Negotiation: Few Drugs, Big Impact?

Nagar SN, Kesselheim AS, Rome BN - Health Affairs Forefront

  • Commentary & Opinion
| June 2023
  • Price, Value, and Access
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Although Medicare’s new drug price negotiation authority under the Inflation Reduction Act applies to only a small number of high‑spending drugs, it could affect a much larger share of spending through price “spillover” to competing products. Even limited negotiations may therefore yield substantial savings for patients and taxpayers, though design flaws in Part D and Part B payment rules could blunt these effects without further reform.
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Testimony in Support of S.749: an Act Relative to Pharmaceutical Access, Costs and Transparency

Lalani HS - Massachusetts General Court, Joint Committee on Health Care Financing

  • Policy Interactions
| June 2023
  • Price, Value, and Access
An icon of a bill representing government policy.
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An Empirical Review of Key Glucose Monitoring Devices: Product Iterations and Patent Protection

Darrow JJ, Van de Wiele VL, Beran D, Kesselheim AS - Journal of Diabetes Science and Technology

  • Research Publications
| June 2023
  • Innovation Incentives and Competition
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Manufacturers of blood glucose monitoring systems introduced frequent incremental product changes accompanied by extensive patenting, resulting in thousands of overlapping patents. Many older devices are now off‑patent, suggesting that wider adoption of these technologies could reduce costs without sacrificing clinical effectiveness.
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Op-Ed: How the Makers of Inhalers Keep Prices So High

Feldman WB, Kesselheim AS - Washington Post

  • Commentary & Opinion
| June 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Inhaler manufacturers have kept prices high for decades by exploiting patents and regulatory rules around drug‑device combinations, despite minimal therapeutic innovation. Congress and the FDA should pursue various reforms to patent listings, generic substitution, and approval pathways to break these monopolies and lower costs for patients with asthma and COPD.
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Inflationary Rebates for Generic Drugs Sold Through Medicaid Saved Billions During 2017-20

Rome BN, Patel AN, Kesselheim AS - Health Affairs

  • Research Publications
| June 2023
  • Price, Value, and Access
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Inflationary rebates for generic drugs offset an estimated 2–12% of Medicaid generic drug spending from 2017 to 2020, saving billions of dollars. Despite the policy, many generic manufacturers continued to raise prices above inflation, particularly for higher‑priced and non‑oral drugs.
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High Cost of Chimeric Antigen Receptor T-Cells: Challenges and Solutions

Cliff ERS, Kelkar AH, Russler-Germain DA, Tessema FA, Raymakers AJN, Feldman WB, Kesselheim AS - American Society of Clinical Oncology Educational Book

  • Commentary & Opinion
| June 2023
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
Chimeric antigen receptor (CAR) T-cells are a cellular immunotherapy with remarkable efficacy against hematologic malignancies, yet they come with extremely high prices that are prohibitive for many countries. The authors review the factors that impact the high cost of CAR T therapy and propose reforms to improve affordability and access.
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Health Technology Assessment for Cancer Medicines Across the G7 Countries and Oceania: An International, Cross-Sectional Study

Jenei K, Raymakers AJN, Bayle A, Berger-Thürmel K, Cherla A, Honda K, Jackson CGA, Karikios D, Trapani D, Berry S, Gyawali B - Lancet Oncology

  • Research Publications
| June 2023
  • Price, Value, and Access
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Despite broadly similar HTA criteria, countries reached markedly different reimbursement decisions for the same cancer drugs, particularly those with marginal clinical benefits. Greater transparency and cross‑national HTA learning could help prioritize high‑value care and limit low‑value spending.
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Comments on Draft Guidance, “Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics”

Gyawali B, Kesselheim AS, Ross JS - Food and Drug Administration (FDA)

  • Policy Interactions
| May 2023
  • Regulation and Clinical Evidence
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The commenters support FDA’s proposed shift toward randomized single-trial designs for accelerated approval of cancer drugs, which would address limitations of single-arm trials and delays in confirmatory studies, while offering additional suggestions to improve the guidance to strengthen surrogate endpoint validation and ensure timely confirmation of clinical benefit.
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