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1377 Results

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
Talk bubble graphics representing commentary and opinion.
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
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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. Watch his 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
An icon of a bill representing government policy.
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
An icon of a bill representing government policy.
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
An icon of a bill representing government policy.
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
Talk bubble graphics representing commentary and opinion.
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
Talk bubble graphics representing commentary and opinion.
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
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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
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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, 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
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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. Watch his 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
Talk bubble graphics representing commentary and opinion.
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
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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
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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
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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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Transferable Exclusivity Vouchers and Incentives for Antimicrobial Development in the European Union

Van de Wiele VL, Raymakers AJN, Kesselheim AS, Rome BN - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Spring 2023
  • Innovation Incentives and Competition
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The European Commission’s proposal for transferable exclusivity vouchers would impose substantial societal costs while offering weak and poorly targeted incentives for antimicrobial innovation. Alternative funding mechanisms, such as direct public investment or advance market commitments, would better support antibiotic development.
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Testimony: Causes of Unaffordable Prescription Drugs: Monopolies, Rebates, and Misaligned Incentives

Rome BN - 118th Congress, House Committee on Ways and Means, Subcommittee on Health

  • Policy Interactions
| May 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Rome explains that while pharmacy benefit managers (PBMs) use tiered formularies and utilization management to negotiate rebates that partially offset rising list prices, these rebates often fail to reach patients whose out-of-pocket costs remain tied to list prices, and practices like spread pricing and vertical integration with pharmacies may be inflating costs particularly for generics. His recommendations for PBM reform include delinking patient cost-sharing from list prices, requiring PBMs to pass 100% of rebates to plan sponsors, prohibiting spread pricing, and investigating PBM-pharmacy vertical consolidation. However, he also notes that the primary driver of high US drug prices as manufacturers’ ability to freely set and raise prices during government-granted monopoly periods, and urges Congress to prioritize policies targeting brand-name pricing and timely generic competition over PBM-focused reforms alone. Watch his testimony.
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Broad Patent Claims Come Before the Supreme Court in Amgen v. Sanofi

Tu SS, Nagar SN, Van de Wiele VL - JAMA

  • Commentary & Opinion
| May 2023
  • Innovation Incentives and Competition
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The Supreme Court case Amgen v. Sanofi threatens to upend long‑standing patent law by potentially allowing broad, inadequately enabled antibody patent claims that could block follow‑on innovation. Upholding such functional genus patents would reduce competition, limit therapeutic choice, and delay incremental improvements in antibody‑based drugs to the detriment of patients.
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Testimony: How the US Government Supports Meaningful Drug and Device Innovation: Funding Development of Transformative Therapies and Avoiding Excessing Prices for New Products with Limited Benefits

Kesselheim AS - 118th Congress, House Committee on Ways and Means, Subcommittee on Health

  • Policy Interactions
| May 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Kesselheim argues that the US government plays an essential role in pharmaceutical innovation through NIH funding while also bearing responsibility as the largest drug purchaser to avoid overpaying for low-value products. He defends recent government efforts to distinguish meaningful from low-value innovation, including CMS’s national coverage determination restricting aducanumab reimbursement, CMMI’s proposed payment models tying reimbursement to clinical benefit for accelerated approval drugs and cell/gene therapies, and the withdrawal of the MCIT rule for breakthrough devices. Kesselheim recommends that Congress increase the NIH budget, expand Medicare’s drug price negotiation authority to cover more drugs sooner after approval, and establish a national health technology assessment body to issue evidence-based reports on new drugs’ added clinical value. Watch his testimony.
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Five-Year Sales for Newly Marketed Prescription Drugs with and Without Initial Orphan Drug Act Designation

Tu SS, Nagar SN, Kesselheim AS, Lu Z, Rome BN - JAMA

  • Research Publications
| May 2023
  • Innovation Incentives and Competition
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Drugs initially approved for orphan indications generated five‑year revenues comparable to non‑orphan drugs, undermining claims that orphan incentives primarily support commercially marginal products. These findings suggest that current orphan drug incentives may over‑reward manufacturers without clear justification.
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Medicare Price Negotiation: The Example of Ibrutinib

Raymakers AJN, Kesselheim AS, Rome BN - Health Affairs Forefront

  • Research Publications
| May 2023
  • Price, Value, and Access
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Using ibrutinib (Imbruvica) as a case study, the authors show how Medicare’s new drug price negotiation authority under the Inflation Reduction Act could generate meaningful savings by benchmarking prices against therapeutic alternatives. They also highlight key limitations of the current framework, especially restrictions on using cost‑effectiveness tools like the QALY, that may constrain Medicare’s ability to fully align prices with clinical value.
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Persistence of Resistance: A Panel Data Analysis of the Effect of Antibiotic Usage on the Prevalence of Resistance

Rahman S, Kesselheim AS, Hollis A - Journal of Antibiotics

  • Research Publications
| May 2023
  • Regulation and Clinical Evidence
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Increases in national antibiotic use were followed by immediate and persistent rises in resistance lasting at least four years, while reductions in use showed little short‑term reversal. Antibiotic use in neighboring countries also increased domestic resistance, highlighting the limits of national‑only stewardship policies.
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Melflufen: Post-Hoc Subgroup Analyses and the US FDA Oncologic Drugs Advisory Committee

Cliff ERS, Janakiram M, Kesselheim AS - Lancet Haematology

  • Commentary & Opinion
| May 2023
  • Regulation and Clinical Evidence
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Reliance on post‑hoc subgroup analyses to rescue melflufen after a failed confirmatory trial undermines the integrity of the FDA’s accelerated approval pathway. Allowing such retrospective justifications risks keeping ineffective or harmful drugs on the market and sets a dangerous precedent for oncology drug regulation.
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Federal Funding for Discovery and Development of Costly HIV Drugs Was Far More Than Previously Estimated

Tessema FA, Barenie RE, Avorn J, Kesselheim AS - Health Affairs

  • Research Publications
| May 2023
  • Innovation Incentives and Competition
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The US government contributed at least $143 million in direct NIH funding to the development of tenofovir disoproxil fumarate-emtricitabine (Truvada) for HIV prevention, substantially more than previously estimated. This extensive public investment contrasts sharply with the drug’s high US prices during years when access to PrEP remained limited.
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Concerns About Climate Activism in Clinical Practice (Reply)

Richie C, Kesselheim AS, Jones DS - Lancet

  • Commentary & Opinion
| May 2023
  • Regulation and Clinical Evidence
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In this reply, the authors argue that addressing climate change falls within the ethical obligations of clinical medicine because environmental harms directly affect patient health. They contend that incorporating climate considerations into prescribing decisions can improve care without compromising patient trust or clinical priorities.
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Surrogate Measures of Drug Efficacy—A Finger Pointing at the Moon

Avorn J - JAMA Network Open

  • Commentary & Opinion
| April 2023
  • Regulation and Clinical Evidence
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The author criticizes the widespread reliance on surrogate endpoints to approve cancer drugs, noting that many such approvals fail to translate into real survival benefits. Stronger post‑approval reassessment and conditional approval frameworks are needed to prioritize meaningful clinical outcomes over early but unreliable signals.
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Added Therapeutic Benefit of Top-Selling Brand-Name Drugs in Medicare

Egilman AC, Rome BN, Kesselheim AS - JAMA

  • Research Publications
| April 2023
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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More than half of the top‑selling brand‑name drugs in Medicare provided little or no added therapeutic benefit compared with existing treatments, yet accounted for a large share of Medicare spending. These findings support using comparative effectiveness evidence in Medicare price negotiations.
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Comments on Initial Guidance for the Medicare Drug Price Negotiation Program, IPAY 2026

Rome BN, Gabriele SME, Lalani HS, Cliff ERS, Daval CJR, Feldman WB, Sarpatwari A, Kesselheim AS - Centers for Medicare and Medicaid Services (CMS)

  • Policy Interactions
| April 2023
  • Price, Value, and Access
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The commenters provide feedback on CMS’s initial guidance for implementing Medicare drug price negotiation under the Inflation Reduction Act, raising concerns about loopholes involving fixed-dose combinations, orphan drug exclusions, and plasma-derived product definitions. They recommend greater transparency in the negotiation process, consideration of international prices as reference points, and safeguards against limited-supply agreements being treated as bona fide generic competition.
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Trends in Medicare Spending on Oral Drugs for Chronic Lymphocytic Leukemia From 2014 to 2020

Cliff ERS, Kesselheim AS, Rome BN, Feldman WB - JAMA Network Open

  • Research Publications
| April 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Despite the introduction of multiple competing therapies for the treatment of chronic lymphocytic leukemia, Medicare spending and per‑unit prices for ibrutinib (Imbruvica) rose substantially between 2014 and 2020. Brand‑to‑brand competition failed to constrain prices, even as newer drugs with improved clinical profiles entered the market.
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Two Views of Cancer Medicines: Imagery Versus Evidence

Darrow JJ - Health Marketing Quarterly

  • Commentary & Opinion
| April 2023
  • Regulation and Clinical Evidence
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Cancer drug advertising routinely exaggerates expected clinical benefits relative to the modest gains demonstrated in clinical trials, prompting the need for greater advertising restrictions, such as requirements to more clearly describe a drug’s efficacy, alongside payment reforms to better align drug manufacturer incentives with patient benefit.
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Alternatives to the Quality‐Adjusted Life Year: How Well Do They Address Common Criticisms?

Rand LZG, Melendez‐Torres GJ, Kesselheim AS - Health Services Research

  • Research Publications
| April 2023
  • Price, Value, and Access
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No alternative outcome measure used in health technology assessment resolves the ethical and methodological critiques of quality-adjusted life years (QALYs) while preserving their core advantage of cross‑disease comparability. As a result, banning QALYs does not eliminate value judgments and risks replacing a transparent metric with less consistent, less accountable ones.
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Acknowledging Infection Risk in Bispecific Antibody Trials in the Treatment of Multiple Myeloma

Cliff ERS, Reynolds G, Popat R, Teh BW, Kesselheim AS, Mohyuddin GR - Journal of Clinical Oncology

  • Commentary & Opinion
| April 2023
  • Regulation and Clinical Evidence
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The authors raise concern that early trials of bispecific antibodies for multiple myeloma may underreport or misattribute serious infection risks despite high response rates. More rigorous and transparent reporting of infectious adverse events is necessary to better inform patient care, trial design, and regulatory decisions.
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Timing of Confirmatory Trials for Drugs Granted Accelerated Approval Based on Surrogate Measures From 2012 to 2021

Deshmukh AD, Kesselheim AS, Rome BN - JAMA Health Forum

  • Research Publications
| March 2023
  • Regulation and Clinical Evidence
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More than half of FDA‑required confirmatory trials for drugs granted accelerated approval were completed late or remained unfinished past their deadlines. These delays prolonged use of expensive drugs with uncertain clinical benefit, highlighting weaknesses in the FDA’s post-approval enforcement of confirmatory trials.
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Op-Ed: Is It Business as Usual for the Drug Industry?

Egilman AC, Kesselheim AS, Rome BN - MedPage Today

  • Commentary & Opinion
| March 2023
  • Price, Value, and Access
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Despite passage of the Inflation Reduction Act, drug manufacturers continue to raise prices, exploiting periods of high inflation and the law’s delayed application to newly launched drugs. While inflation‑based rebates may eventually restrain price growth and spill over beyond Medicare, additional reforms are needed to meaningfully curb excessive drug costs.
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Testimony: Taxpayers Paid Billions for It: So Why Would Moderna Consider Quadrupling the Price of the COVID Vaccine?

Sarpatwari A - 118th Congress, Senate Committee on Health, Education, Labor, and Pensions

  • Policy Interactions
| March 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Sarpatwari argues that Moderna’s proposed 400% price increase of the NIH-Moderna COVID-19 vaccine is unwarranted given the extensive federal role in its development. He contends that Moderna’s justification that higher revenues are needed for R&D is weak given the company’s $37 billion in revenue and $20 billion in profit over two years and notes a broader pattern of opportunism including prior price increases, patent disputes with NIH, breaking its pandemic patent pledge, and failing to supply low-income countries. Sarpatwari recommends that Congress pressure Moderna to reverse the increase, resume federal bulk purchasing to leverage government buying power, and authorize CMS to set prices for the vaccine using IRA-style negotiation factors, while expanding this framework to cover future emergency therapeutics. Watch his testimony.
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Op-Ed: Not So Fast on COVID Vaccine Price Hike

Lalani HS, Nagar SN, Avorn J, Kesselheim AS - Boston Globe

  • Commentary & Opinion
| March 2023
  • Price, Value, and Access
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The authors critcize plans by Pfizer‑BioNTech and Moderna to dramatically raise COVID‑19 vaccine prices after the public health emergency, despite extensive public investment in the vaccines’ development and manufacturing.
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Eroding Judicial Deference to the FDA—Consequences for Public Health

Daval CJR, Bendicksen L, Kesselheim AS - New England Journal of Medicine

  • Commentary & Opinion
| March 2023
  • Regulation and Clinical Evidence
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Supreme Court decisions weakening judicial deference to federal agencies threaten the FDA’s ability to regulate drugs and medical devices in the public interest. Curtailing deference will make nuanced, science‑based regulation more difficult, increase litigation risk, and ultimately undermine patient safety unless Congress provides more explicit statutory authority.
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A Methodology for Estimating Medicaid and Non-Medicaid Net Prices Using Top Brand-Name Drugs, 2015-2019

Epstein M, Clemans-Cope L, Banthin J, Kesselheim AS, Hwang TJ - Urban Institute

  • Research Publications
| March 2023
  • Price, Value, and Access
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The authors present a methodology for estimating Medicaid and non‑Medicaid net drug prices by more accurately accounting for statutory rebates, including the Medicaid “best price” provision. Applying this approach shows that commonly used pricing datasets misattribute costs across payers, overstating Medicaid spending and understating the burden borne by Medicare and commercial insurers.
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The Right to Repair Software-Dependent Medical Devices

Lindgren L, Kesselheim AS, Kramer DB - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Spring 2023
  • Innovation Incentives and Competition
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Manufacturer restrictions on repairing software‑dependent medical devices inflate health care costs and undermine system resilience, especially during public health emergencies. Expanding right‑to‑repair protections through copyright, antitrust, and legislative reform could increase competition, reduce costs, and improve access to essential medical technology.
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The $5 Billion Hop: Glatiramer Acetate and the US Patent System

Patel NG, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Research Publications
| Spring 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Teva’s reformulation of glatiramer acetate (Copaxone) delayed generic competition despite minimal clinical improvement, costing US payers an estimated ~$5 billion. The case illustrates how weak patent scrutiny enables product hopping that sustains high prices without corresponding patient benefit.
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Analysis of Risk Evaluation and Mitigation Strategies for Teratogenic Drugs: Variation in Primary and Secondary Prevention Measures

Brown BL, Kesselheim AS, Sarpatwari A - PLOS Medicine

  • Research Publications
| March 2023
  • Regulation and Clinical Evidence
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FDA risk evaluation and mitigation strategies (REMS) requirements for teratogenic drugs vary widely and are often misaligned with the actual strength of teratogenic evidence. Overly restrictive or inconsistent safeguards can undermine patient autonomy and access without proportionate safety gains.
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Medicaid Spending on Antiretrovirals From 2007 Through 2019

Walsh BS, Kesselheim AS, Rome BN - Clinical Infectious Diseases

  • Research Publications
| March 2023
  • Price, Value, and Access
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Medicaid spending on antiretrovirals nearly tripled from 2007–2019 due to shifts toward newer, higher‑priced drugs, despite inflation‑linked rebates holding down prices of individual products. The findings show that rebate mechanisms fail when manufacturers serially replace drugs with incrementally modified versions.
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Using Multiple Authorized Generics to Maintain High Prices: The Example of Entacapone

Rome BN, Egilman AC, Patel NG, Kesselheim AS - Value in Health

  • Research Publications
| March 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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This case study shows that licensing multiple authorized generics in place of independent generic competition delayed robust price declines for entacapone (Comtan). Medicare spending could have been hundreds of millions lower under typical independent generic entry, highlighting how authorized generics can blunt competition.
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US Public Investment in Development of mRNA COVID-19 Vaccines: Retrospective Cohort Study

Lalani HS, Nagar SN, Sarpatwari A, Barenie RE, Avorn J, Rome BN, Kesselheim AS - BMJ

  • Research Publications
| March 2023
  • Innovation Incentives and Competition
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The US government invested at least $31.9 billion in the development, testing, and purchase of mRNA COVID‑19 vaccines, including decades of foundational research before the pandemic. This scale of public investment strengthens the case for tying pricing and access conditions to intellectual property negotiations for publicly funded health technologies.
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Trends in the Global Antibiotics Market

Madden J, Outterson K - Nature Reviews Drug Discovery

  • Research Publications
| March 2023
  • Innovation Incentives and Competition
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Global revenues for branded antibiotics have steadily declined over two decades as low-priced generics dominate, leaving antibiotic markets financially unattractive for innovation. The findings underscore why stewardship-compatible antibiotics require new public “push and pull” incentives rather than reliance on traditional market sales.
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Patent Challenges and Litigation on Inhalers for Asthma and COPD

Reddy S, Beall RF, Tu SS, Kesselheim AS, Feldman WB - Health Affairs

  • Research Publications
| March 2023
  • Innovation Incentives and Competition
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Generic competition for inhalers is rare and delayed, largely due to device‑focused patent thickets and weak incentives for patent challenges under the Hatch‑Waxman Act. As a result, essential asthma and COPD medicines remain expensive long after initial approval.
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Estimated Medicaid Spending on Original and Citrate-Free Adalimumab From 2014 Through 2021

Wang J, Lee CC, Kesselheim AS, Rome BN - JAMA Internal Medicine

  • Research Publications
| March 2023
  • Price, Value, and Access
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After citrate‑free adalimumab (Humira) entered the US market in 2018, it captured 85% of Medicaid prescriptions by 2021 despite similar list prices to the original formulation. Lower inflationary rebates on the citrate-free version led to an estimated $4.4 billion in excess Medicaid spending, demonstrating how product modifications can circumvent statutory rebate protections.
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Characteristics of Prior Authorization Policies for New Drugs in Medicare Part D

Naci H, Forrest R, Zhai MZ, Stofesky AR, Kesselheim AS - JAMA Health Forum

  • Research Publications
| February 2023
  • Price, Value, and Access
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Among 109 new drugs eligible for Medicare Part D, 66% were subject to prior authorization (PA) and 40% had restrictions more stringent than FDA labeling. Across 638 PA policies, requirements varied widely, adding administrative burden without clear evidence of improved appropriateness.
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Recent Patent Reform Bills and Their Implications for Prescription Drugs

Tu SS, Nagar SN, Kesselheim AS - JAMA

  • Commentary & Opinion
| February 2023
  • Innovation Incentives and Competition
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This viewpoint analyzes three patent reform bills, the Patent Eligibility Restoration Act, the Interagency Patent Coordination and Improvement Act, and the Patent Examination and Quality Improvement Act, and assesses their implications for drug pricing, patent quality, and competition. Patent reforms such as these should preserve incentives for innovation while limiting patent practices that unnecessarily delay generic entry.
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Brief of Arnold Ventures, the National Center for Health Research, and Certain Medical Doctors in Amgen v. Sanofi

Kesselheim AS, Avorn J - US Supreme Court

  • Policy Interactions
| February 2023
  • Innovation Incentives and Competition
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Filed in support of Sanofi, the amici argue that the Federal Circuit correctly applied the Wands factors to find Amgen’s broad functional genus claims covering PCSK9-inhibiting antibodies not enabled. Amgen’s proposed “partial enablement” standard would allow overbroad genus claims to proliferate in pharmaceuticals, harming patients by delaying competition, limiting opportunities to improve on first-in-class drugs, and keeping brand-name drug prices artificially high.
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A “Method of Use” to Prevent Generic and Biosimilar Market Entry

Tu SS, Sarpatwari A - New England Journal of Medicine

  • Commentary & Opinion
| February 2023
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
Brand‑name manufacturers are increasingly using method‑of‑use patents and FDA labeling requirements to undermine the skinny labeling pathway for generics and biosimilars. Focusing on the Federal Circuit’s decision in GlaxoSmithKline v. Teva, the authors warn that the ruling threatens timely generic entry and could enable manufacturers to extend exclusivity well beyond what Congress intended.
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Insulin Products and Patents in the USA in 2004, 2014, and 2020: A Cross-Sectional Study

Van de Wiele VL, Kesselheim AS, Beran D, Darrow JJ - Lancet Diabetes & Endocrinology

  • Research Publications
| February 2023
  • Innovation Incentives and Competition
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The number of FDA‑approved insulin products increased from 18 in 2004 to 43 in 2020, while listed patents grew from 11 to 100 over the same period. Median time to last patent expiration rose from ~16 years to ~24 years, driven largely by device‑related patents rather than new active ingredients.
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Comments on Notice, “USPTO Initiatives to Ensure the Robustness and Reliability of Patent Rights”

Chao B, Heled Y, Lemley MA, Robertson CT, Sinha MS, Tu SS, Vertinsky L, Van de Wiele VL - US Patent and Trademark Office (USPTO)

  • Policy Interactions
| February 2023
  • Innovation Incentives and Competition
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The commenters summarize evidence that pharmaceutical patent thickets—dense webs of overlapping patents linked by terminal disclaimers—delay biosimilar market entry in the United States compared to Canada and the United Kingdom, and urge the USPTO to reform double patenting and terminal disclaimer practices to reduce these barriers to drug price competition.
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Simulated Medicare Drug Price Negotiation Under the Inflation Reduction Act of 2022

Rome BN, Nagar SN, Egilman AC, Wang J, Feldman WB, Kesselheim AS - JAMA Health Forum

  • Research Publications
| January 2023
  • Price, Value, and Access
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Simulating IRA price negotiation from 2018 to 2020 shows Medicare would have saved about $26.5 billion, or roughly 5% of total Part B and Part D drug spending. Savings were concentrated among 37 high‑spending drugs, many receiving ceiling‑price discounts exceeding existing rebates.
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Sources of Innovation in Gene Therapies—Approaches to Achieving Affordable Prices

Vokinger KN, Avorn J, Kesselheim AS - New England Journal of Medicine

  • Research Publications
| January 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Most approved gene therapies originated in publicly funded academic research, with pharmaceutical companies typically entering later in development, despite charging extraordinarily high prices. Recognizing these public contributions should justify policy reforms, such as nonexclusive licensing, value‑based pricing, and broader price negotiation, to improve access and affordability.
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Variation in Use of Lung Cancer Targeted Therapies Across State Medicaid Programs, 2020-2021

Roberts TJ, Kesselheim AS, Avorn J - JAMA Network Open

  • Research Publications
| January 2023
  • Price, Value, and Access
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Use of targeted lung cancer therapies among Medicaid patients varied widely by state, with most states falling below expected treatment levels. Differences were associated with Medicaid policies, oncologist availability, and state economic factors, suggesting access barriers rather than clinical appropriateness.
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Comments for Listening Session, “Joint USPTO-FDA Collaboration Initiatives” (Van de Wiele)

Van de Wiele VL - US Patent and Trademark Office (USPTO)

  • Policy Interactions
| January 2023
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
An icon of a bill representing government policy.
Pharmaceutical patent term extensions and the broader patent framework under the Hatch-Waxman Act and Biologics Price Competition and Innovation Act can form barriers to timely market entry for generic and biosimilar drugs. The commenters offer policy recommendations for USPTO-FDA collaboration to reduce these burdens on health care spending.
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Comments for Listening Session, “Joint USPTO-FDA Collaboration Initiatives” (Tu)

Tu SS - US Patent and Trademark Office (USPTO)

  • Policy Interactions
| January 2023
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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Pharmaceutical patent thickets and continuation patent practice allow brand-name companies to build large portfolios of overlapping patents that delay generic and biosimilar market entry, driving up drug costs for patients, employers, and taxpayers. Greater USPTO-FDA collaboration is necessary to address these barriers.
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Therapeutic Value of Drugs Frequently Marketed Using Direct-To-Consumer Television Advertising, 2015 to 2021

Patel NG, Hwang TJ, Woloshin S, Kesselheim AS - JAMA Network Open

  • Research Publications
| January 2023
  • Regulation and Clinical Evidence
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Fewer than one-third of heavily advertised drugs in the US were rated as having high therapeutic value by independent health technology assessment agencies. Roughly $15.9 billion (71%) of TV advertising spending promoted drugs with low added clinical benefit, raising concerns about misaligned marketing incentives.
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Estimates of Medicaid and Non-Medicaid Net Prices of Top-Selling Brand-Name Drugs Incorporating Best Price Rebates, 2015 to 2019

Clemans-Cope L, Epstein M, Banthin J, Kesselheim AS, Hwang TJ - JAMA Health Forum

  • Research Publications
| January 2023
  • Price, Value, and Access
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This study presents a methodology for more accurately estimating Medicaid net drug prices by incorporating inflationary and “best price” rebates. Applying the method shows Medicaid prices fell while non‑Medicaid prices rose, contradicting conclusions drawn from incomplete pricing datasets.
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Op-Ed: Use Opioid Settlement Funds to Educate Doctors

Avorn J - Boston Globe

  • Commentary & Opinion
| January 2023
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
Opioid settlement funds should be used not only for treatment and remediation, but also to support evidence‑based education for clinicians on safer prescribing and addiction treatment. Investing in academic detailing and physician outreach could correct misinformation driven by past pharmaceutical marketing and help prevent future harms.
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Manufacturer Revenue on Inhalers After Expiration of Primary Patents, 2000-2021

Feldman WB, Tu SS, Alhiary R, Kesselheim AS, Wouters OJ - JAMA

  • Research Publications
| January 2023
  • Innovation Incentives and Competition
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From 2000 to 2021, inhaler manufacturers earned about $178 billion, with 62% of revenue accruing after primary patents expired but secondary patents remained. Less than 1% of revenue occurred after all patents expired, illustrating how device patents sustain long‑term market power.
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Estimated Medicare Part B Savings From Inflationary Rebates

Egilman AC, Kesselheim AS, Rome BN - JAMA

  • Research Publications
| January 2023
  • Price, Value, and Access
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If Medicare inflationary rebates had applied from 2018 to 2020, Medicare Part B drug spending would have been reduced by roughly 3%. The largest savings came from biologics and rare-disease drugs with prices rising faster than inflation.
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Patient Out‐of‐Pocket Costs Following the Availability of Biosimilar Versions of Infliximab

Feng K, Kesselheim AS, Russo M, Rome BN - Clinical Pharmacology & Therapeutics

  • Research Publications
| January 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
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From 2014 to 2018, biosimilar infliximab showed no significant reduction in patient out‑of‑pocket costs compared with the originator (Remicade). Even after biosimilar entry, median patient costs remained around $500 per infusion, showing that payer savings from biosimilars does not automatically translate into patient affordability.
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Frequency of Approval and Marketing of Biosimilars with a Skinny Label and Associated Medicare Savings

Egilman AC, Van de Wiele VL, Rome BN, Darrow JJ, Tu SS, Kesselheim AS, Sarpatwari A - JAMA Internal Medicine

  • Research Publications
| January 2023
  • Innovation Incentives and Competition
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Between 2015 and 2021, 67% of biosimilars were approved with skinny labels, enabling earlier competition before all patents expired on the originator biologic expired. This pathway generated an estimated $1.5 billion in Medicare savings, highlight the value of this pathway amid increasing legal threats.
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Climate Change and the Prescription Pad

Richie C, Kesselheim AS, Jones DS - Lancet

  • Commentary & Opinion
| January 2023
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Pharmaceuticals are a major and underrecognized contributor to health care’s carbon footprint. Physicians can meaningfully reduce emissions and improve patient care with ractical steps, such as reducing low‑value prescriptions, addressing medication non‑adherence, and incorporating climate considerations into shared decision‑making.
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Trends in the Quality of Evidence Supporting FDA Drug Approvals: Results From a Literature Review

Brown BL, Mitra-Majumdar M, Joyce KW, Ross M, Pham C, Darrow JJ, Avorn J, Kesselheim AS - Journal of Health Politics, Policy and Law

  • Research Publications
| December 2022
  • Regulation and Clinical Evidence
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A systematic review of 48 studies finds that clinical trials supporting FDA drug approvals have increasingly relied on less rigorous designs, with declines in randomization, double‑blinding, and active comparators, alongside growing use of surrogate endpoints that are often poorly correlated with clinical outcomes. Drugs approved through expedited regulatory pathways were especially likely to be supported by weaker evidence, highlighting the need for policy changes to ensure high‑quality data collection before and after FDA approval.
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The Bayh-Dole Act at 40: Accomplishments, Challenges, and Possible Reforms

Sarpatwari A, Kesselheim AS, Cook-Deegan RM - Journal of Health Politics, Policy and Law

  • Research Publications
| December 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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This article reviews the history and impact of the Bayh-Dole Act, which allows institutions to patent inventions arising from federally funded research, and examines ongoing debates about its role in drug pricing and access, including controversies surrounding COVID‑19 therapeutics developed with public support. The authors assess the Act’s strengths and limitations and propose reforms, such as clarifying march‑in rights, increasing licensing transparency, and testing alternative innovation models, to better align publicly funded research with public health goals.
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Industry Payments to Physicians Are Kickbacks. How Should Stakeholders Respond?

Mitchell AP, Sarpatwari A, Bach PB - Journal of Health Politics, Policy and Law

  • Research Publications
| December 2022
  • Price, Value, and Access
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In a review of the literature on the impact pharmaceutical industry payments on physician prescribing and the legality of such relationships, the authors conclude that many such payments may meet the definition of illegal kickbacks under the Anti‑Kickback Statute, despite existing compliance guidance. Industry, providers, regulators, and payers all have a range of available actions to curb the effect of these payments on health care spending and prescribing decisions.
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Getting the Price Right: Lessons for Medicare Price Negotiation From Peer Countries

Rand LZG, Kesselheim AS - PharmacoEconomics

  • Research Publications
| December 2022
  • Price, Value, and Access
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As Medicare prepares to exercise its authority to negotiate drug prices beginning in 2026, the authors review how peer countries, Australia, Canada, France, Germany, and the United Kingdom, negotiate brand‑name drug prices using statutory rebates, price ceilings, and arbitration mechanisms. Each approach could reduce Medicare spending even without a closed formulary, and US policymakers should draw on these international models when implementing the new negotiation framework.
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Experts’ Views on FDA Regulatory Standards for Drug and High-Risk Medical Devices: Implications for Patient Care

Dhruva SS, Darrow JJ, Kesselheim AS, Redberg RF - Journal of General Internal Medicine

  • Research Publications
| December 2022
  • Regulation and Clinical Evidence
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Interviewed experts reported that increased use of FDA expedited approval pathways has led to greater reliance on surrogate endpoints with uncertain clinical significance and that many physicians are unaware when drugs or high‑risk devices are approved through these pathways. Participants expressed concern that evidentiary uncertainty is not adequately communicated to patients and emphasized the need to incorporate explanations of expedited review and its limitations into informed treatment consent.
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Evidence at Time of Regulatory Approval and Cost of New Antibiotics in 2016-19: Cohort Study of FDA Approved Drugs

Mitra-Majumdar M, Powers JH, Brown BL, Kesselheim AS - BMJ Medicine

  • Research Publications
| December 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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In a cohort study of 15 antibiotics approved by the FDA between 2016 and 2019, most drugs were authorized based on a median of two pivotal trials, frequently using non‑inferiority designs and surrogate outcomes, with numerous postmarketing requirements still pending years later. This limited preapproval evidence highlights the tension between efforts to incentivize antibiotic development and the need for clinically meaningful evidence of patient benefit.
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Patent “Evergreening” of Medicine-Device Combination Products: A Global Perspective

Beall RF, Glazer T, Ahmad H, Buell M, Hahn S, Houston A, Kesselheim AS, Nickerson J, Kaplan W - Healthcare Policy | Politiques de Santé

  • Research Publications
| November 2022
  • Innovation Incentives and Competition
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Among a cohort 88 drug-device combination products, device patents were found to be widely used to extend market exclusivity globally. Canada was particularly affected, with 90% of product patent portfolios included at least one device patent and 35% consisting solely of device patents. The findings suggest that delivery‑device patenting contributes to global “evergreening” practices and highlight the need for international consensus on which device modifications deliver meaningful clinical value.
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Accumulators and Maximizers: A New Front in the Battle Over Drug Costs (Part 2)

Brennan TA, Kesselheim AS - Health Affairs Forefront

  • Commentary & Opinion
| November 2022
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
This two-part article examines the escalating conflict between pharmaceutical manufacturers and pharmacy benefit managers over patient drug costs. Part 2 explains PBMs’ countermeasures—accumulator programs that prevent copay coupons from counting toward deductibles, and maximizer programs that strategically extract the full value of manufacturers’ assistance to reduce costs for employers—and reviews the resulting litigation. The authors conclude that the entire cycle of price-setting, assistance programs, and counter-programs reveals a fundamentally irrational drug pricing system that will ultimately require government intervention to determine what level of prices the U.S. can afford.
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Accumulators and Maximizers: A New Front in the Battle Over Drug Costs (Part 1)

Brennan TA, Kesselheim AS - Health Affairs Forefront

  • Commentary & Opinion
| November 2022
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
This two-part article examines the escalating conflict between pharmaceutical manufacturers and pharmacy benefit managers over patient drug costs. Part 1 documents growing evidence that out-of-pocket drug costs drive medication non-adherence and serious health consequences, and describes how manufacturers developed copayment assistance programs that simultaneously help patients and sustain high drug prices by undermining insurers’ cost-sharing incentives.
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Variations in Use of Diabetes Drugs with Cardiovascular Benefits Among Medicaid Patients

Zhai MZ, Avorn J, Liu J, Kesselheim AS - JAMA Network Open

  • Research Publications
| November 2022
  • Price, Value, and Access
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Across US Medicaid programs from 2014 to 2019, use of glucose‑lowering drugs with proven cardiovascular benefit increased but varied widely by state, with 2019 use ratios ranging from 0.14 to 1.58. Lower use was associated with larger Medicaid populations, higher diabetes prevalence, and greater managed care enrollment, suggesting persistent structural barriers to adoption of these potentially life‑saving therapies.
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Reforming the World Health Organization’s Essential Medicines List: Essential but Unaffordable

Hwang TJ, Kesselheim AS, Vokinger KN - JAMA

  • Commentary & Opinion
| November 2022
  • Price, Value, and Access
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The WHO Essential Medicines List increasingly faces tension between including clinically effective but expensive drugs (such as PD-1/PD-L1 checkpoint inhibitors) and its original goal of identifying affordable, widely accessible medicines. The authors argue for methodological reforms to address cost considerations more systematically.
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What Should US Policymakers Learn From International Drug Pricing Transparency Strategies?

Nagar SN, Rand LZG, Kesselheim AS - AMA Journal of Ethics

  • Research Publications
| November 2022
  • Price, Value, and Access
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An analysis of prescription drug pricing transparency practices in the UK, Germany, and Canada reveals that while transparency can be a powerful tool for competition and payer negotiation, it can also weaken certain payers’ negotiating positions by preventing manufacturers from offering confidential rebates or discounts. The authors argue that US policymakers should learn from these international approaches as they consider transparency reforms, recognizing that the design of such policie, particularly regarding list versus net price disclosure and international reference pricing, will significantly affect both domestic drug prices and negotiating dynamics.
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Medicaid Expenditures and Estimated Rebates on Line Extension Drugs, 2010-2018

Hwang TJ, Feng J, Maini L, Kesselheim AS - Journal of General Internal Medicine

  • Research Publications
| November 2022
  • Price, Value, and Access
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Total Medicaid spending on line extension drugs (new formulations or minor modifications of existing brand-name products)doubled from $3.7 billion in 2010 to $7.6 billion in 2018, with nearly two-thirds of spending concentrated in the top 10 product families and the share from new non-oral formulations growing from 6% to 22%. The estimated potential savings from applying CMS’s finalized line extension rebate rule would have reduced pre-rebate line extension spending by 9.6% in 2018, suggesting meaningful but modest savings from closing this longstanding loophole in Medicaid drug rebate requirements.
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Holding Pharmaceutical and Medical Device Executives Accountable as Responsible Corporate Officers

Daval CJR, Avorn J, Kesselheim AS - JAMA Internal Medicine

  • Research Publications
| November 2022
  • Regulation and Clinical Evidence
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The authors identified 13 Park doctrine prosecutions of pharmaceutical and medical device executives since 2000 across 6 companies, resulting in 11 guilty pleas and 2 convictions, while most large DOJ settlements over misconduct in the same period did not result in individual executive liability. The authors conclude that the government has underutilized its authority under the Park doctrine to hold executives accountable and that reinvigorated enforcement could better protect patients from unsafe or fraudulent medical products.
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Gastrointestinal Prophylaxis for COVID-19: An Illustration of Severe Bias Arising From Inappropriate Comparators in Observational Studies

Lin KJ, Feldman WB, Wang SV, Pramod Umarje S, D'Andrea E, Tesfaye H, Zabotka LE, Liu J, Desai RJ - Journal of Clinical Epidemiology

  • Research Publications
| November 2022
  • Regulation and Clinical Evidence
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The study found no clinical benefit of any gastrointestinal prophylaxis agent (famotidine, omeprazole, or pantoprazole) for hospitalized COVID-19 patients when using appropriate comparisons, while inappropriate comparisons of users versus nonusers showed spurious associations. The findings demonstrate that improper comparator selection in observational studies of critically ill patients can generate severely biased results and highlight the importance of setting-appropriate study design.
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Fulfillment of Postmarket Commitments and Requirements for New Drugs Approved By the FDA, 2013-2016

Brown BL, Mitra-Majumdar M, Darrow JJ, Moneer O, Pham C, Avorn J, Kesselheim AS - JAMA Internal Medicine

  • Research Publications
| November 2022
  • Regulation and Clinical Evidence
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Among 474 postmarket requirements and commitments issued for 135 new drugs approved by the FDA from 2013 to 2016, 72.1% of those due by Q4 2020 were completed late, with a median delay of 2 quarters, including 83% of Pediatric Research Equity Act studies and 71.3% of FDA Amendments Act requirements. These findings underscore persistent delays in the generation of postapproval safety and efficacy evidence at a time when the FDA is increasingly relying on expedited approval pathways with less preapproval data.
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Op-Ed: Makena Is Just the Latest in Accelerated Approval Mayhem

Bendicksen L, Rome BN - MedPage Today

  • Commentary & Opinion
| October 2022
  • Regulation and Clinical Evidence
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The authors use the case of Makena (17-OHPC), a drug for preterm birth that remained on the market years after a confirmatory trial showed it was ineffective, to illustrate systemic failures in the FDA’s accelerated approval program. They identify three core problems: manufacturers take years to complete required follow-up trials, drugs can be priced exorbitantly before efficacy is confirmed, and the FDA lacks practical authority to withdraw approvals when confirmatory evidence falls short.
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Recent Trends in Prescription Drug Launch Prices (Reply)

Rome BN, Egilman AC, Kesselheim AS - JAMA

  • Commentary & Opinion
| October 2022
  • Price, Value, and Access
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In this exchange, industry representatives argue that net drug spending growth has been modest, while the authors counter that escalating launch prices remain a fundamental problem despite rebates and discounts.
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Limitations on the Capability of the FDA to Advise

Rand LZG, Kesselheim AS - American Journal of Bioethics

  • Commentary & Opinion
| October 2022
  • Regulation and Clinical Evidence
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The authors discuss the FDA’s evolving role beyond setting quality standards to serving as a purveyor of public health advice, examining how population-level health considerations, including external effects of drug use like opioid diversion and antimicrobial resistance, should factor into regulatory decisions.
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Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease—Estimating the True Value

Cliff ERS, Kelkar AH - JAMA Neurology

  • Commentary & Opinion
| October 2022
  • Price, Value, and Access
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Conducting cost-effectiveness analyses of aducanumab and donanemab is premature given that these drugs have not demonstrated clear clinical effectiveness, and publishing such analyses lends undue legitimacy to an unproven drug class. The authors note that the clinical outcomes from the aducanumab trials are discordant and statistically insignificant by meta-analysis.
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State Laws and Generic Substitution in the Year After New Generic Competition

Rome BN, Sarpatwari A, Kesselheim AS - Value in Health

  • Research Publications
| October 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Among more than 500,000, individuals who initiated one of 34 drugs after new generic competition entered the market, 81.6% received a generic version, with generic use significantly lower in states with laws requiring patient consent or notification of generic substitutioncompared to states without such requirements. The findings suggest that state laws requiring patient consent or provider notification for generic substitution create barriers to generic drug use, and policymakers should consider amending these requirements to increase access to affordable and effective generic medications.
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Reforming Patient Cost Sharing for Cancer Medications in Medicare Part D

Hwang TJ, Kesselheim AS, Dusetzina SB - JAMA Oncology

  • Commentary & Opinion
| October 2022
  • Price, Value, and Access
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Medicare Part D’s cost-sharing structure—with no out-of-pocket cap and coinsurance tied to list prices—imposes unsustainable financial burdens on cancer patients. The authors call for an annual out-of-pocket cap coupled with policies addressing underlying drug list prices.
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Post‐marketing Requirements for Cancer Drugs Approved By the European Medicines Agency, 2004-2014

Cherla A, Mossialos E, Salcher-Konrad M, Kesselheim AS, Naci H - Clinical Pharmacology & Therapeutics

  • Research Publications
| October 2022
  • Regulation and Clinical Evidence
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From 2004-2014, 79% of cancer drugs approved by the European Medicines Agency had postmarketing requirements, with pivotal trials for these drugs less likely to be randomized, have active comparators, and use overall survival endpoints. After 5 years, only 60% of postmarketing requirements were completed, 30% were delayed, and most drugs still received permanent marketing authorization despite incomplete data collection, indicating a need for stronger EMA enforcement of confirmatory trial completion.
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Payments for Research Participation: Don’t Tax the Guinea Pig

Rand LZG, Kesselheim AS - Clinical Trials

  • Commentary & Opinion
| October 2022
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Current US tax law treats payments to research participants as taxable income, resulting in participants receiving less compensation than intended by researchers and institutional review boards, while other entities in the research enterprise receive tax exemptions and similar socially valuable activities are not taxed. Research participation payments should be exempted from taxation to ensure fair and adequate compensation for participants.
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Product Hopping in the Drug Industry—Lessons From Albuterol

Wouters OJ, Feldman WB, Tu SS - New England Journal of Medicine

  • Commentary & Opinion
| September 2022
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
Pharmaceutical companies’ transition of albuterol inhalers from chlorofluorocarbon to hydrofluoroalkane formulations, a “product hop” strategy, has cost payers and patients billions of dollars. Without reforms to patent and regulatory systems, similar product hopping strategies will likely continue in the future.
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Op-Ed: Prevent a Legal Catch-22 That Could Push Thousands of Generic Drugs Off the Market

Carrier MA, Duan C, Tu SS - Los Angeles Times

  • Commentary & Opinion
| September 2022
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
A federal court ruling in GSK v. Teva case has effectively gutted the “skinny labeling” pathway Congress created to allow generics to coexist with method-of-use patents. The decision creates a catch-22 in which generic makers must either violate patent law or drug safety regulations—potentially threatening thousands of existing generics and restoring monopoly pricing on long-off-patent drugs. The authors urge the Supreme Court to take the case and call on the FDA and PTO to jointly address how patents interact with drug labeling requirements.
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Risks to the 340B Drug Pricing Program (Reply)

Knox RP, Sarpatwari A - JAMA

  • Commentary & Opinion
| September 2022
  • Price, Value, and Access
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In this reply, the authors respond to a pharmaceutical industry critique of their viewpoint on the 340B program, clarifying that manufacturer restrictions on drug availability to 340B contract pharmacies threaten patient access and that disputes center on HRSA guidance rather than formal rules.
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New Reforms to Prescription Drug Pricing in the US: Opportunities and Challenges

Hwang TJ, Kesselheim AS, Rome BN - JAMA

  • Commentary & Opinion
| September 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The authors provide an overview of the Inflation Reduction Act’s drug pricing provisions—including Medicare price negotiation, inflation-based rebate penalties, and out-of-pocket caps for Part D beneficiaries—calling them the most significant reforms since Medicare Part D was created in 2003 while noting limitations such as the narrow scope of drugs eligible for negotiation.
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Inflation Reduction Act and US Drug Pricing

Sarpatwari A - BMJ

  • Commentary & Opinion
| September 2022
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The author provides an overview of the three major Medicare drug pricing reforms in the Inflation Reduction Act: government price negotiation for selected high-spend drugs, inflation-based rebate penalties for manufacturers raising prices above inflation, and a $2,000 annual out-of-pocket cap for beneficiaries. These reforms are a landmark but incomplete victory over the pharmaceutical industry’s $187 million lobbying campaign, and he argues further reform is needed to address the high cost of prescription drugs in the US.
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Variability in Global Drug Prices

Kesselheim AS - Clinical Advances in Hematology & Oncology

  • Commentary & Opinion
| September 2022
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
US brand-name drug prices are 2-4 times higher than in other industrialized countries because the US lacks the comparative effectiveness assessments and government price negotiations used elsewhere. The Inflation Reduction Act’s limited Medicare negotiation authority and generic/biosimilar competition represent the most promising approaches to reducing costs.
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Overall Survival as a Primary End Point in Multiple Myeloma Trials

Cliff ERS, Mohyuddin GR - Nature Reviews Clinical Oncology

  • Commentary & Opinion
| September 2022
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
While progression-free survival may be a reasonable endpoint for first-line multiple myeloma trials given the disease’s long median survival, there are important scenarios—such as trials in penta-refractory patients with short life expectancies or those testing maintenance therapies that add toxicity—where overall survival and quality of life should remain the primary endpoints.
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Clinical Benefit and Expedited Approval of Cancer Drugs in the United States, European Union, Switzerland, Japan, Canada, and Australia

Hwang TJ, Kesselheim AS, Tibau Martorell A, Lee CC, Vokinger KN - JCO Oncology Practice

  • Research Publications
| September 2022
  • Regulation and Clinical Evidence
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Among 128 new cancer drugs approved across six major regulatory jurisdictions from 2007 to 2020, the FDA was first to approve 80% of them, with delays in manufacturer submission, rather than regulatory review, accounting for most of the lag in approval by other countries’ agencies. Notably, there was no association between high clinical benefit and shorter review times, suggesting regulators should prioritize expedited review for therapies with the greatest demonstrated clinical value.
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Civil Commitment for Opioid Misuse: Do Short-Term Benefits Outweigh Long-Term Harms?

Messinger JC, Ikeda DJ, Sarpatwari A - Journal of Medical Ethics

  • Research Publications
| September 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Civil commitment for opioid misuse can provide short-term overdose protection but emerging evidence suggests it is associated with long-term harms including increased risk of severe withdrawal, relapse, and mortality. States should collect more robust long-term outcome data, decriminalize civil commitment proceedings, decriminalize proceedings, ensure access to medications for opioid use disorder, and strengthen post-release community-based treatment coordination to mitigate these harms.
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