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1259 Results

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
Talk bubble graphics representing commentary and opinion.
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
An icon of a bill representing government policy.
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. Read his written 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
Talk bubble graphics representing commentary and opinion.
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. Read his written 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. Read his written 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
Talk bubble graphics representing commentary and opinion.
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
Talk bubble graphics representing commentary and opinion.
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
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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
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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
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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
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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
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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
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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
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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
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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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Brand-Name Market Exclusivity for Nebulizer Therapy to Treat Asthma and COPD

Feldman WB, Bloomfield D, Beall RF, Kesselheim AS - Nature Biotechnology

  • Research Publications
| September 2022
  • Innovation Incentives and Competition
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The authors analyzed patents and regulatory exclusivities for brand-name nebulizer solutions for asthma and COPD from 1986 to 2020 and found that nebulizers had a median protection period of 7 years from generic competition compared to 14 years for inhalers, with nebulizers facing generic competition for 62% of the study follow-up time versus 0.5% for inhalers. The authors conclude that regulatory reform is needed to improve patient access to affordable inhaled medications.
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Assessment of Prices for Cardiovascular Tests and Procedures at Top-Ranked US Hospitals

Oseran AS, Ati S, Feldman WB, Gondi S, Yeh RW, Wadhera RK - JAMA Internal Medicine

  • Research Publications
| September 2022
  • Price, Value, and Access
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Leveraging data from the 2021 Hospital Price Transparency Final Rule, this cross-sectional study examined payer-specific negotiated prices for common cardiovascular tests and procedures across top-ranked US hospitals, revealing significant price variation both between and within institutions. These findings represent a novel characterization of cardiovascular pricing variation made possible by newly available transparency data, highlighting the extent of price inconsistency in routine cardiac care.
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Antibody Patent Evolution

Teng TW, Kesselheim AS, Tu SS - IEEE Pulse

  • Commentary & Opinion
| September 2022
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
The therapeutic antibody market has grown substantially, with monoclonal antibodies comprising four of the top six selling prescription drugs in 2021 and generating over $67 billion in revenue, This reality makes patent rules governing antibodies increasingly significant so drug companies, healthcare providers, and consumers can better understand how intellectual property protections affect access to and development of these important therapies.
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Improving the Use of FDA Advisory Committees

Daval CJR, Kesselheim AS, Sarpatwari A - New England Journal of Medicine

  • Commentary & Opinion
| August 2022
  • Regulation and Clinical Evidence
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The authors examine the FDA’s use of advisory committees in regulatory decision-making, highlighting concerns about instances where the FDA has disregarded advisory committee recommendations—most notably in the approval of aducanumab for Alzheimer’s disease despite unanimous committee opposition. The authors propose reforms to strengthen the role and independence of these expert panels.
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Therapeutic Value of Drugs Granted Accelerated Approval or Conditional Marketing Authorization in the US and Europe From 2007 to 2021

Vokinger KN, Kesselheim AS, Glaus CEG, Hwang TJ - JAMA Health Forum

  • Research Publications
| August 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Between 2007 and 2021, only 38.9% of drug indications granted accelerated approval in the US and 37.5% of those granted conditional marketing authorization in the EU demonstrated high added therapeutic value at the time of approval, with cancer indications showing substantially lower therapeutic value compared to noncancer indications. Policymakers and regulators should strengthen enforcement of timely confirmatory studies for drugs approved through these expedited pathways.
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Implications of Oncology Trial Design and Uncertainties in Efficacy-Safety Data on Health Technology Assessments

Trapani D, Tay-Teo K, Tesch ME, Roitberg F, Sengar M, Altuna SC, Hassett MJ, Genazzani AA, Kesselheim AS, Curigliano G - Current Oncology

  • Research Publications
| August 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The increased use of expedited approval pathways and surrogate endpoints in oncology trials has created significant uncertainty in translating efficacy-safety data into clinically and economically meaningful patient outcomes, challenging health technology assessments (HTA) and potentially leading to misallocation of healthcare resources. The authors emphasize the need for policy harmonization between regulatory and HTA authorities, generation of robust post-marketing data, and the use of value frameworks that address these evidence uncertaintyies to imrpove reimbursement decisionmaking for cancer drugs.
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What to Know About the Alzheimer Drug Aducanumab (Aduhelm)

Woloshin S, Kesselheim AS - JAMA Internal Medicine

  • Commentary & Opinion
| August 2022
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
This patient-facing summary explains that while aducanumab reduced brain amyloid plaque (a surrogate outcome), it did not demonstrate noticeable improvement in patient-relevant outcomes like symptoms or quality of life, and its FDA approval remains controversial.
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The Vexing Voyage of Vasopressin

Bendicksen L, Kesselheim AS, Rome BN - Chest

  • Research Publications
| August 2022
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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After the FDA approved Par Pharmaceutical’s version of vasopressin (Vasostrict) in 2014 under the Unapproved Drugs Initiative without requiring new clinical trials, the company raised the price of this century-old critical care drug by 5,400% from 2010 to 2020 and built a patent thicket of 14 patents extending through 2035 to block competition. Par Pharmaceutical’s 8-year market monopoly, which coincided with surging COVID-19-related demand, illustrates the perils of granting market exclusivity under the UDI and highlights the need for reform of both the initiative and US drug patent standards.
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Government Patent Use to Promote Public Health in the United States: Overcoming Nonpatent Exclusivities

Wolitz RE, Kesselheim AS, Darrow JJ - American Journal of Public Health

  • Commentary & Opinion
| August 2022
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
The authors analyze four potential legal pathways for the federal government to use its patent authority to promote public health by enabling generic manufacturing of patented drugs, while addressing the challenge that nonpatent exclusivities may present additional barriers.
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Characteristics of Key Patents Covering Recent FDA-Approved Drugs:

Van de Wiele VL, Torrance AW, Kesselheim AS - Health Affairs

  • Research Publications
| August 2022
  • Innovation Incentives and Competition
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Among 78 FDA-approved drugs in 2019 and 2020, 68 were protected by a median of 4 patents each (322 total), with chemical compound patents being most common (62%), followed by method of use (61%). The median time to final patent expiration was 10.3 years, and approximately 20% of patents had no counterparts in other major non-US jurisdictions. These findings highlight how patent reform, rather than modifications to nonpatent exclusivities, is essential for enabling timely generic drug entry.
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The History of Health Law in the United States

Fuse Brown EC, Kesselheim AS - New England Journal of Medicine

  • Commentary & Opinion
| July 2022
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Health law has fundamentally shaped American health care delivery across four distinct historical eras, each characterized by its own dominant philosophy and approach. Understanding this historical evolution provides essential context for comprehending how legal frameworks have structured and influenced health care systems and policy over time.
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High-Priced Sickle Cell Gene Therapies Threaten to Exacerbate US Health Disparities and Establish New Pricing Precedents for Molecular Medicine

Tessema FA, Sarpatwari A, Rand LZG, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Summer 2022
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
Gene therapies for sickle cell disease are expected to have high costs and will face substantial budget challenges given the large eligible population alongside risks of exacerbating existing healt disparities. Policymakers must establish pricing frameworks and coverage mechanisms that ensure equitable access to these therapies and prevent the perpetuation of health inequities in sickle cell treatment availability.
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Over-The-Counter Availability of Rescue Inhalers for Asthma (Reply)

Feldman WB, Avorn J, Kesselheim AS - JAMA

  • Commentary & Opinion
| July 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Responding to concerns about OTC rescue inhalers, the authors clarify that they advocated for OTC ICS-FABA combination inhalers (not albuterol alone) as the preferred option, consistent with recent Global Initiative for Asthma guidelines. With millions of Americans lacking health insurance, ensuring access to a safer and more effective OTC inhaler option is warranted alongside broader policy reforms.
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Op-Ed: Medicare Could Have Saved $3 Billion Buying Drugs the Mark Cuban Way

Lalani HS, Rome BN, Kesselheim AS - Washington Post

  • Commentary & Opinion
| July 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The authors highlight their research finding that Medicare could have saved over $3 billion in 2020 by purchasing 77 generic drugs at the transparent prices offered by Mark Cuban’s Cost Plus Drugs Company. However, they argue the model has significant limitations: patients must pay out of pocket, savings don’t apply to expensive brand-name drugs, and comparison shopping is burdensome. Meaningful drug prices reform still requires congressional action to allow Medicare price negotiation, cap out-of-pocket costs, and limit price increases.
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Institutionalizing Misinformation—the Dietary Supplement Listing Act of 2022

Cohen PA, Avorn J, Kesselheim AS - New England Journal of Medicine

  • Commentary & Opinion
| July 2022
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Proposed bipartisan legislation requiring supplement manufacturers to list products with the FDA would create an illusion of regulatory oversight while leaving the current lax framework untouched. The authors propose revisions including giving the FDA authority to reject registrations with unlawful ingredients or claims, requiring certificates of analysis, and restricting public posting of health claims to those supported by clinical trials.
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Reforms to Accelerated Approval of New Medicines: Long Overdue

Hwang TJ, Trinh Q, Tibau Martorell A, Vokinger KN - Lancet

  • Commentary & Opinion
| July 2022
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The authors welcome the first legislative reforms to the FDA’s accelerated approval pathway since its 1992 creation, arguing that the program’s expansion has been accompanied by growing controversy over inadequate confirmatory trials and the need for stronger enforcement mechanisms.
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Potential Medicare Part D Savings on Generic Drugs From the Mark Cuban Cost Plus Drug Company

Lalani HS, Kesselheim AS, Rome BN - Annals of Internal Medicine

  • Research Publications
| July 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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A comparison of prices for 89 generic drugs found that Medicare could have saved an estimated $3.3 billion (36%) in 2020 by purchasing at Mark Cuban Cost Plus Drug Company prices,with the largest potential savings on rosuvastatin ($241 million). These findings suggest that Medicare is substantially overpaying for many generic drugs and highlight inefficiencies in the existing pharmaceutical distribution and reimbursement system involving wholesalers, pharmacy benefit managers, and pharmacies.
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Mifepristone, Preemption, and Public Health Federalism

Zettler PJ, Beckmeyer A, Brown BL, Sarpatwari A - Journal of Law and the Biosciences

  • Research Publications
| July 2022
  • Regulation and Clinical Evidence
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State restrictions on FDA-approved pregnancy termination drugs can be challenged on federal preemption grounds, and courts have compelling legal reasons to conclude many such restrictions are preempted by federal authority. Simultaneously, successful preemption challenges in the abortion context need not undermine the benefits of public health federalism in other areas of state drug regulation.
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Communication of Drug Efficacy Information Via a Popular Online Platform

Darrow JJ, Borisova E - Journal of the American Board of Family Medicine

  • Research Publications
| July 2022
  • Regulation and Clinical Evidence
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A significant majority of FDA-approved drugs from 1982 to 2020 have Wikipedia pages that provide information about drug indications (98%) and mechanisms of action (86%), yet only 21% of these pages include quantitative efficacy data. The widespread absence of efficacy information on Wikipedia drug pages limits public understanding of actual drug benefits and represents a missed opportunity to improve pharmaceutical literacy among the general population.
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Promoting Confidence in Cost-Effectiveness Analyses

Raymakers AJN, Kesselheim AS - BMJ

  • Commentary & Opinion
| June 2022
  • Price, Value, and Access
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The authors discuss findings that industry-sponsored cost-effectiveness analyses are twice as likely to report favorable results, and call for greater transparency in model construction, open-source economic models, and standardized reporting to promote confidence in these increasingly important analyses.
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Reference Check: A Simple Strategy to Improve Drug Patent Quality

Tu SS, Crouch D, Kesselheim AS - Health Affairs Forefront

  • Commentary & Opinion
| June 2022
  • Innovation Incentives and Competition
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Brand-name drug manufacturers increasingly inundate patent examiners with hundreds or thousands of references—averaging 218 for small-molecule and 378 for biologic drug patents—far exceeding what examiners can review in their allotted 18 hours, yet these unexamined references strengthen the patent’s legal presumption of validity. The PTO should require claim charts for applications citing more than 50 references and increase filing fees for excessive citations, making it harder for manufacturers to use reference overload to obtain poor-quality patents that delay generic competition.
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Op-Ed: Prices for New Drugs Are Rising 20 Percent a Year. Congress Needs to Act

Rome BN, Egilman AC, Kesselheim AS - New York Times

  • Commentary & Opinion
| June 2022
  • Price, Value, and Access
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Citing their research showing that average launch prices for new drugs grew roughly tenfold from 2008 to 2021, the authors argue that congressional drug pricing reforms must go beyond limiting price increases on existing drugs and allow Medicare to negotiate prices for newly marketed medications. They point to international models demonstrating that price negotiation need not impair access or innovation, and that unchecked pricing incentivizes development of marginally innovative products over meaningful therapeutic advances.
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Trends in Prescription Drug Launch Prices, 2008-2021

Rome BN, Egilman AC, Kesselheim AS - JAMA

  • Research Publications
| June 2022
  • Price, Value, and Access
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Among 548 drugs first marketed from 2008 to 2021, median launch prices increased from $2,115 per year in 2008 to $180,007 in 2021, with unadjusted mean prices rising exponentially by 20% per year and adjusted prices (accounting for drug characteristics like biologics, orphan drugs, and oncology products) still increasing by 13% per year. By 2020-2021, 47% of new drugs were priced above $150,000 per year, with the highest prices among drugs for rare diseases and oncology drugs, with net prices after manufacturer discounts showing similar upward trends.
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Strategies to Manage Drugs and Devices Approved Based on Limited Evidence: Results of a Modified Delphi Panel

Dhruva SS, Darrow JJ, Kesselheim AS, Redberg RF - Clinical Pharmacology & Therapeutics

  • Research Publications
| June 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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In consultation with 13 experts from academia, government, industry, and patient advocacy, the authors identified four priority interventions to address physician-patient decision-making about drugs and devices approved with limited evidence: strengthening FDA post-approval study requirements, creating simplified patient-centered product information labels, implementing conditional pricing for surrogate endpoint-approved products, and improving clinician education about FDA regulation. These consensus-based strategies aim to better manage the inherent uncertainties associated with expedited FDA approval pathways while supporting informed clinical decision-making.
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Patents and Regulatory Exclusivities on Inhalers for Asthma and COPD, 1986-2020

Feldman WB, Bloomfield D, Beall RF, Kesselheim AS - Health Affairs

  • Research Publications
| June 2022
  • Innovation Incentives and Competition
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An analysis of patents and exclusivities for 62 FDA-approved inhalers (1986–2020) found that brand-name products enjoyed a median of 16 years of protection from generic competition, with over 50% of all patents covering the device rather than the active ingredient. Manufacturers extended exclusivity through “device hops” that yielded a median of 28 years of protection across product lines, despite only 1 inhaler containing a genuinely novel mechanism of action. These findings suggest that current patent and regulatory frameworks disproportionately reward device modifications over true therapeutic innovation, underscoring the need for reform to improve generic inhaler competition and reduce costs.
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Hydroxyzine Initiation Following Drug Safety Advisories on Cardiac Arrhythmias in the UK and Canada: A Longitudinal Cohort Study

Morrow RL, Mintzes BJ, Souverein PC, Hallgreen CE, Ahmed B, Roughead EE, De Bruin ML, Kristiansen SB, Lexchin J, Kemp-Casey A, Sketris I, Mangin D, Pearson S, Puil L, Lopert R, Bero L, Gnjidic D, Sarpatwari A, Dormuth CR - Drug Safety

  • Research Publications
| June 2022
  • Regulation and Clinical Evidence
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Following drug safety advisories on hydroxyzine and cardiac arrhythmia risk, hydroxyzine initiation decreased by 21% in the UK but did not change in British Columbia, Canada, during the 12-month post-advisory period. The observed decrease in hydroxyzine initiation in the UK was not significantly differentbetween patients with and without risk factors for QT prolongation and Torsade de pointes, suggesting the advisory’s impact was not appropriately targeted to high-risk populations.
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Direct-To-Consumer Generic Drugs: A Maverick Approach or Another Exposure of Market Failures?

Lalani HS, Kesselheim AS, Rome BN - Annals of Internal Medicine

  • Commentary & Opinion
| June 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
Though the Mark Cuban Cost Plus Drug Company and similar direct-to-consumer generic drug ventures highlight failures in the generic drug market structural policy reforms are needed to ensure all patients have access to low-cost generics.
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Coverage of New Drugs in Medicare Part D

Naci H, Kyriopoulos I, Feldman WB, Hwang TJ, Kesselheim AS, Chandra A - Milbank Quarterly

  • Research Publications
| June 2022
  • Price, Value, and Access
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Only a small minority of newly approved drugs in nonprotected classes achieve widespread coverage across Medicare Part D plans in the first year after FDA approval, with most drugs subject to utilization management restrictions such as prior authorization. Drug price was shown to be the primary driver of formulary coverage decisions over therapeutic value, highlighting the need for value-based formulary design to maximize patient benefit.
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Making the Case for Accelerated Withdrawal of Aducanumab

Whitehouse P, Gandy S, Saini V, George DR, Larson EB, Alexander GC, Avorn J, Brownlee S, Camp C, Chertkow H, Fugh-Berman A, Howard R, Kesselheim AS, Langa KM, Perry G, Richard E, Schneider L - Journal of Alzheimer’s Disease

  • Commentary & Opinion
| May 2022
  • Regulation and Clinical Evidence
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An international group of clinicians, researchers, and dementia advocates unanimously recommended that the FDA withdraw its approval of aducanumab (Aduhelm) due to insufficient evidence of clinical efficacy, safety concerns, and cost considerations. The group supported filing a formal Citizen Petition calling for the reversal of the drug’s controversial June 2021 approval, citing significant problems with the approval process.
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Generating Evidence From Expanded Access Use of Rare Disease Medicines: Challenges and Recommendations

Polak TB, Cucchi DGJ, Van Rosmalen J, Uyl-de Groot CA, Darrow JJ - Frontiers in Pharmacology

  • Commentary & Opinion
| May 2022
  • Regulation and Clinical Evidence
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The authors present examples of clinical data generated from expanded access programs for rare disease medicines and discuss the ethical and regulatory considerations for using such data to inform regulator and payer decisions in the European Union and the US. They recommend that regulators issue new guidance on data collection during expanded access and update existing compassionate use guidance to better balance evidence generation with patient access.
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Improving the Quality of US Drug Patents Through International Awareness

Bloomfield D, Lu Z, Kesselheim AS - BMJ

  • Research Publications
| May 2022
  • Innovation Incentives and Competition
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Brand-name drug manufacturers frequently use secondary patents to create “patent thickets” that delay generic competition, and the USPTO sometimes erroneously issues invalid patents due to time constraints and the difficulty of assessing novelty across a wide scientific literature. The authors propose a novel approach to improving US patent quality by flagging patent applications for additional scrutiny when matching applications have been discontinued abroad, leveraging international patent office decisions to help identify potentially invalid claims.
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Analysis of Supportive Evidence for US Food and Drug Administration Approvals of Novel Drugs in 2020

Mitra-Majumdar M, Gunter SJ, Kesselheim AS, Brown BL, Joyce KW, Ross M, Pham C, Avorn J, Darrow JJ - JAMA Network Open

  • Research Publications
| May 2022
  • Regulation and Clinical Evidence
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The 49 novel drugs approved by the FDA in 2020 were supported by 75 pivotal trials, with 57.1% supported by only a single trial and trial sizes ranging from 19 to 2,230 participants. 45.3%of trials used surrogate endpoints as primary outcomes, and oncology drugs were significantly more likely to rely on historical controls and surrogate measures compared to nononcology drugs. While increased flexibility in preapproval evidence partly reflects constraints in clinical trial recruiment, the FDA and consumers would benefit from a revised approach that better balances expedited market access with robust evidence of drug efficacy.
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Risks to the 340B Drug Pricing Program Related to Manufacturer Restrictions on Drug Availability

Knox RP, Kesselheim AS, Sarpatwari A - JAMA

  • Commentary & Opinion
| May 2022
  • Price, Value, and Access
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As of 2022, 16 pharmaceutical manufacturers have restricted delivery of discounted drugs to 340B-covered safety-net hospitals and clinics, threatening the program that subsidizes care for underserved patients. The authors analyze the legal disputes and policy implications of these restrictions.
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Unwanted Advice? Frequency, Characteristics, and Outcomes of Negative Advisory Committee Votes for FDA-Approved Drugs

Daval CJR, Sarpatwari A, Kesselheim AS - Health Affairs

  • Research Publications
| May 2022
  • Regulation and Clinical Evidence
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Between 2010-2021, the FDA approved drugs against negative advisory committee recommendations approximately once per year, with the proportion of approved drugs referred to advisory committees declining from 55% to 6% annually, and qualitative analysis revealing inconsistent voting question wording across committees. The authors recommend implementing transparent criteria for advisory committee referrals, standardizing voting question language, and establishing clear regulatory responses to negative recommendations to strengthen public confidence in the FDA approval process.
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Use of Extrapolation in New Drug Approvals By the US Food and Drug Administration

Feldman D, Avorn J, Kesselheim AS - JAMA Network Open

  • Research Publications
| April 2022
  • Regulation and Clinical Evidence
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Among 105 novel drug approvals from 2015 to 2017, extrapolation of pivotal trial data to broader patient populations occurred in 21 drugs (20%), with disease severity being the most common basis for extrapolation, followed by disease subtype and concomitant medication use. While such extrapolations may be clinically reasonable, they reduce indication generalizability and necessitate enhanced postapproval monitoring by the FDA to detect unanticipated safety issues or effectiveness differences in real-world use.
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Therapeutic Value Assessments of Novel Medicines in the US and Europe, 2018-2019

Vokinger KN, Hwang TJ, Glaus CEG, Kesselheim AS - JAMA Network Open

  • Research Publications
| April 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Among 67 novel drugs approved by both the FDA and EMA in 2018-2019, only 32% were assessed as having high added therapeutic value by German and French health technology assessment agencies, with none of the 8 accelerated approval drugs achieving a high rating. These findings are consistent with earlier research and support the need for greater scrutiny of which drugs qualify for expedited regulatory programs and rare disease designations, given that so few of these products demonstrate substantial clinical improvement over existing therapies.
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Patient Assistance Programs and the Anti-Kickback Statute: Charting a Pathway Forward

Sinha MS, Kesselheim AS, Robertson CT - JAMA

  • Commentary & Opinion
| April 2022
  • Price, Value, and Access
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Pharmaceutical manufacturer-funded patient assistance programs can circumvent the anti-kickback statute by subsidizing patients’ out-of-pocket costs for expensive drugs through ostensibly independent charities, effectively incentivizing use of high-cost medications at federal program expense.
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QALYs in Health Resource Usage Decisions (Reply)

Rand LZG, Kesselheim AS - Health Affairs

  • Commentary & Opinion
| April 2022
  • Price, Value, and Access
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In this reply, the authors defend the quality-adjusted life-year (QALY) as a rigorous tool for health resource allocation while acknowledging it should be one component of decision-making, and argue that rarity alone should not warrant higher drug prices when public incentives already subsidize rare disease drug development.
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Price Changes and Within-Class Competition of Cancer Drugs in the USA and Europe: A Comparative Analysis

Vokinger KN, Hwang TJ, Carl DL, Laube Y, Ludwig W, Naci H, Kesselheim AS - Lancet Oncology

  • Research Publications
| April 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Cancer drug prices in the US increased substantially over time (median 6.07% at 2 years and 15.31% at 4 years after market entry), while prices in Germany and Switzerland with national price negotiation mechanisms generally decreased or remained stable with inflation. The findings suggest that within-class competition did not effectively constrain US cancer drug prices, and the authors recommend that price negotiation mechanisms similar to those used in Germany and Switzerland could help address high cancer drug prices in the US.
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New Drug Postmarketing Requirements and Commitments in the US: A Systematic Review of the Evidence

Moneer O, Brown BL, Avorn J, Darrow JJ, Mitra-Majumdar M, Joyce KW, Ross M, Pham C, Kesselheim AS - Drug Safety

  • Research Publications
| April 2022
  • Regulation and Clinical Evidence
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A systematic review of postmarketing requirements (PMRs) and postmarketing commitments (PMCs) found that while a majority of new drugs are approved with at least one PMR or PMC, completion rates for neither exceed two-thirds, delays are common, and over half produce novel information leading to regulatory action or changes in clinical practice. These findings suggest that although PMRs and PMCs can yield worthwhile outcomes, greater attention is needed to ensure timely completion and to optimize the utility of this evidence for prescribers and patients.
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Indication-Specific Generic Uptake of Imatinib Demonstrates the Impact of Skinny Labeling

Walsh BS, Kesselheim AS, Sarpatwari A, Rome BN - Journal of Clinical Oncology

  • Research Publications
| April 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Generic imatinib was initiated in 88% of chronic myelogenous leukemia (CML) patients and 85% of gastrointestinal stromal tumor (GIST) patients within 3 years of market entry, despite skinny labeling that excluded GIST from generic versions due to patent protections. Although skinny labeling allowed generic competition to proceed for CML while patents remained on GIST treatment, both indications achieved high generic utilization rates, demonstrating the pathway’s effectiveness in facilitating lower drug prices despite incomplete label coverage.
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Incremental Benefits of Novel Pharmaceuticals in the UK: a Cross-Sectional Analysis of NICE Technology Appraisals From 2010 to 2020

Polak TB, Cucchi DGJ, Darrow JJ, Versteegh MM - BMJ Open

  • Research Publications
| April 2022
  • Price, Value, and Access
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Between 2010 and 2020, NICE approved 129 drugs with a median incremental benefit of 0.27 QALYs, with substantial variation across disease areas, and 25% of drug-indication pairs providing less than one month of incremental benefit. This objective evaluation of therapeutic value can help calibrate patient and physician expectations for new drugs and identify disease areas where pharmaceutical innovation is the most impactful.
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Characteristics of Clinical Trials Evaluating Biosimilars in the Treatment of Cancer: A Systematic Review and Meta-Analysis

Bloomfield D, D'Andrea E, Nagar SN, Kesselheim AS - JAMA Oncology

  • Research Publications
| April 2022
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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This systematic review and meta-analysis of 31 cancer biosimilar studies found that biosimilars were statistically indistinguishable from their reference drugs across all seven drug-cancer type subgroups examined, with biosimilar trials using more rigorous designs than reference drug trials. The findings suggest that cancer biosimilars have undergone sufficiently rigorous clinical evaluation to support their approval and market entry as competitive alternatives to originator biologics.
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Biosimilar Competition: Early Learning

Frank RG, Shahzad M, Kesselheim AS, Feldman WB - Health Economics

  • Research Publications
| April 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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This study examines the early impact of biosimilar competition on biological drug pricing following the implementation of the Biologics Price Competition and Innovation Act (BPCIA) in 2010, finding that each additional biosimilar entrant reduces weighted average market prices by 5.4% to 7% through both originator price reductions and demand shifts to biosimilars. The authors conclude that while biosimilar competition has achieved measurable price reductions, these savings remain below initial expectations for moderating drug price growth in the biologic market.
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Aducanumab and Accelerated Approval: Where Do We Go From Here?

Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Commentary & Opinion
| April 2022
  • Regulation and Clinical Evidence
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The reviews the fallout from the aducanumab approval, arguing that the decision was problematic because amyloid plaque reduction has never been validated as a clinical trial surrogate for Alzheimer’s disease, the FDA’s own statisticians found no patient-level correlation between the surrogate and clinical outcomes, and the approval undermined the credibility of the accelerated approval pathway.
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Preventing Medical Device-Borne Outbreaks: The Case of High-Level Disinfection Policy for Duodenoscopes

Mehrotra P, Weber DJ, Sarpatwari A - The Future of Medical Device Regulation: Innovation and Protection

  • Commentary & Opinion
| March 2022
  • Regulation and Clinical Evidence
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This book chapter examines the regulatory failures and infection control challenges exposed by outbreaks of antibiotic-resistant bacteria linked to contaminated duodenoscopes, tracing how gaps in manufacturer reporting, unclear reprocessing instructions, and the limitations of high-level disinfection contributed to ongoing patient harm. The authors argue for reclassifying scopes as critical devices requiring sterilization, updating industry standards, and embedding infection prevention and environmental sustainability perspectives into the FDA’s medical device regulatory framework.
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Lifecycle Regulation and Evaluation of Artificial Intelligence and Machine Learning-Based Medical Devices

Vokinger KN, Hwang TJ, Kesselheim AS - The Future of Medical Device Regulation: Innovation and Protection

  • Commentary & Opinion
| March 2022
  • Regulation and Clinical Evidence
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Between 2017-2018, the FDA cleared fourteen AI and ML-based software products as devices, yet the evidence for safety and effectiveness at market entry remains limited, prompting the need for a lifecycle-based regulatory framework. Manufacturers and the FDA should establish pre-approved “safe harbor” modifications for real-time software adaptation, implement guardrails to monitor cumulative changes, and require heightened transparency standards to address the inherent opacity of AI/ML systems and enable informed decision-making by patients and clinicians.
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Ensuring Patient Safety and Benefit in Use of Medical Devices Granted Expedited Approval

Dhruva SS, Darrow JJ, Kesselheim AS, Redberg RF - The Future of Medical Device Regulation: Innovation and Protection

  • Commentary & Opinion
| March 2022
  • Regulation and Clinical Evidence
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This book chapter examines how legislative and regulatory efforts to streamline medical device approval in the United States — including the Breakthrough Devices Program and 510(k) pathway — have increased uncertainty about device safety and effectiveness. The authors recommend that expedited device approvals be made contingent on timely completion of mandatory postmarket studies demonstrating safety and effectiveness, with automatic lapse of approval if milestones are not met, alongside improved patient disclosure to support informed consent.
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A New Way to Contain Unaffordable Medication Costs—Exercising the Government’s Existing Rights

Engelberg AB, Avorn J, Kesselheim AS - New England Journal of Medicine

  • Commentary & Opinion
| March 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The federal government has two underutilized legal tools to address high drug prices: the Bayh-Dole Act’s royalty-free license for federally funded inventions (march-in rights) and Section 1498 patent immunity allowing government purchase of generic alternatives. The authors contend that the NIH’s repeated refusal to exercise these rights, despite escalating drug costs, represents a missed opportunity to ensure publicly funded medicines remain affordable.
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Switching to Over-The-Counter Availability of Rescue Inhalers for Asthma

Feldman WB, Avorn J, Kesselheim AS - JAMA

  • Commentary & Opinion
| March 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The authors propose making inhaled albuterol available over-the-counter (OTC), arguing that since the FDA already allows OTC sale of a less effective and less safe epinephrine inhaler, making the superior and widely prescribed albuterol available without a prescription would improve access for uninsured and underinsured asthma patients.
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Updating the Bayh-Dole Act: March-In Rights and Transparency

Cook-Deegan RM, Kesselheim AS, Sarpatwari A - JAMA

  • Commentary & Opinion
| March 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The authors examine the Bayh-Dole Act’s march-in rights provision and argue that these rights should be exercised more actively in light of escalating drug prices. They advocate for greater transparency around federally funded inventions and propose that high prices for publicly funded drugs could justify march-in action.
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US Taxpayers Heavily Funded the Discovery of COVID‐19 Vaccines

Lalani HS, Avorn J, Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Research Publications
| March 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The foundational innovations enabling COVID-19 mRNA vaccines trace directly to publicly funded research—including $2.3 million in NIAID grants supporting Karikó and Weissman’s seminal 2005 nucleoside modification discovery, over $8.4 million in NIAID funding for Barney Graham’s spike protein work, $25 million from DARPA to Moderna, and $33.1 million from DARPA to CureVac—with an additional $18+ billion in public funds invested through Operation Warp Speed and the NIH’s joint ownership of key Moderna vaccine patents. The authors argue that this substantial taxpayer investment creates a moral obligation for the US government to leverage its position and patent rights to negotiate fair vaccine prices domestically and accelerate global vaccine equity.
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Medicaid Spending on Drugs Marketed Without US Food and Drug Administration Approval in 2020

Gunter SJ, Kesselheim AS, Rome BN - JAMA Internal Medicine

  • Research Publications
| March 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Of 31,293 drug codes with Medicaid use in 2020, 327 (1.0%) were unapproved products representing 134 distinct drugs, with 64.9% marketed by a single manufacturer and only 15.7% having similar FDA-approved versions available. The findings come amid ongoing controversy over the FDA’s Unapproved Drugs Initiative and raise concerns about competition, pricing, and regulatory oversight of these legacy products within Medicaid.
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Litigating Authority for the FDA

Daval, C Joseph Ross - Washington University Law Review

  • Research Publications
| March 2022
  • Regulation and Clinical Evidence
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Drawing on 20 semi-structured interviews with former DOJ and FDA attorneys, the author provides a qualitative empirical account of how the interagency relationship between FDA and DOJ shapes federal enforcement policy, identifying three key tensions: DOJ’s authority to decline or delay FDA referrals, the agencies’ distinct but overlapping enforcement priorities, and instances in which DOJ pursues cases without or over FDA’s objection. The author proposes that Congress grant FDA independent authority over civil (but not criminal) litigation, arguing that this reallocation would better align enforcement with FDA’s institutional expertise and mission.
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Influence of Drug Safety Advisories on Drug Utilisation: an International Interrupted Time Series and Meta-Analysis

Morrow RL, Mintzes BJ, Souverein PC, De Bruin ML, Roughead EE, Lexchin J, Kemp-Casey A, Puil L, Sketris I, Mangin D, Hallgreen CE, Pearson S, Lopert R, Bero L, Ofori-Asenso R, Gnjidic D, Sarpatwari A, Perry LT, Dormuth CR - BMJ Quality & Safety

  • Research Publications
| March 2022
  • Regulation and Clinical Evidence
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Drug safety advisories without dose-related guidance were associated with a modest decrease in drug utilization of nearly 6%, while advisories with dose-related advice showed no statistically significant impact on prescribing patterns across Canada, Denmark, the UK, and the US. These observations suggest that regulatory safety advisories have limited effectiveness in changing prescribing behavior, warranting consideration of additional or alternative strategies to ensure appropriate medication use in response to safety concerns.
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Extending Drug Monopolies By Patenting Safe Drug Use

Bloomfield D, Walsh BS, Kesselheim AS - JAMA Internal Medicine

  • Commentary & Opinion
| March 2022
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
The authors show how brand-name pharmaceutical manufacturers use patents on drug safety labeling information, such as drug interaction warnings and dosing strategies, to block generic competition well beyond the expiration of their original patents.
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Anticipated Efficiencies, Real Costs: Medicaid Managed Care Organizations and the Pharmacy Benefit

Bendicksen L, Kesselheim AS - Journal of Managed Care & Specialty Pharmacy

  • Research Publications
| March 2022
  • Price, Value, and Access
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Between 2010 and 2017, 15 states contracted with managed care organizations to administer Medicaid pharmacy benefits based on anticipated cost savings and budget predictability, but this shift has complicated states’ ability to manage rising drug prices and meet beneficiary needs. The authors discuss the advantages and limitations of two proposed solutions: centralizing pharmacy benefit management outside MCO contracts, and aligning preferred drug lists across beneficiary types.
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State Restrictions on Mifepristone Access—The Case for Federal Preemption

Zettler PJ, Sarpatwari A - New England Journal of Medicine

  • Commentary & Opinion
| February 2022
  • Price, Value, and Access
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State-level restrictions on mifepristone access should be preempted by federal law because they conflict with the FDA’s evidence-based determination of the drug’s safety profile, as while states can regulate medical practice, they cannot impose requirements that contradict FDA oversight.
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Regulatory Authority and Clinical Acceptability: Physicians’ Responses to Regulatory Drug Safety Warnings

Bhasale AL, Sarpatwari A, Lipworth W, Møllebæk M, McEwin EJ, Gautam N, Santiago Ortiz AJ, Mintzes BJ - British Journal of Clinical Pharmacology

  • Research Publications
| February 2022
  • Regulation and Clinical Evidence
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Interviewed physicians indicated that their response to drug safety warnings was influenced by uncertainty, trust, and clinical authority, with specialists relying on specialized literature and primary care physicians depending on accessible sources like media and clinical colleagues. Regualtors were perceived as authoritative but lacking clinical credibility, emphaiszing the need to enhace the clinical relevance and accessibility of safety warnings to improve physician communications to patients.
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Recent Orange and Purple Book Legislation Suggests a Need to Bridge Drug and Biologic Patent Regimes

Walsh BS, Darrow JJ, Kesselheim AS - Nature Biotechnology

  • Commentary & Opinion
| February 2022
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
Recent legislation addressing the FDA’s Orange Book and Purple Book patent registries are an important step, but additional reforms are needed to ensure these registries promote rather than hinder generic and biosimilar competition.
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New Treatments for Migraine: Therapeutic Ratings and Comparative Coverage in the US, Canada, and Europe

Hwang TJ, Vokinger KN, Kesselheim AS - JAMA Internal Medicine

  • Research Publications
| February 2022
  • Price, Value, and Access
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Although the FDA and EMA broadly approved 3 CGRP-targeted migraine therapies (erenumab, fremanezumab, galcanezumab) for preventive treatment, French and German health technology assessment agencies rated all 3 as providing no added benefit over existing treatments for their general indications, rating the therapies as providing “considerable added benefit” only for patients who had failed all other prophylactic therapies. Comparator countries and the US VA have also restricted coverage far more narrowly than the FDA indication, consistent with evolving clinical guidelines and cost-effectiveness analyses suggesting price reductions of 23-46% would be needed for these drugs to meet standard value thresholds.
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COVID-19 Vaccine Boosters for All Adults: An Optimal U.S. Approach?

Sarpatwari A, Pandya A, Hyle EP, Persad G - Annals of Internal Medicine

  • Commentary & Opinion
| February 2022
  • Regulation and Clinical Evidence
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The authors question whether universal adult COVID-19 booster doses represent the optimal allocation of limited resources, suggesting that expanding initial vaccine uptake among the unvaccinated, vaccinating children, and donating vaccines globally might achieve greater public health benefit.
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Premarket Development Times for Innovative Vaccines–To What Extent Are the Coronavirus Disease 2019 (COVID-19) Vaccines Outliers?

Beall RF, Kesselheim AS, Hollis A - Clinical Infectious Diseases

  • Research Publications
| January 2022
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
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Using patent filing dates as a marker of commercial development initiation, the authors found that the BioNTech/Pfizer COVID-19 vaccine had a 10-year development timeline from key patent filings to regulatory authorization, which aligns with the established pattern of shortening vaccine development timelines since the 1980s and does not represent an outlier compared to other recently approved vaccines. The findings suggest that COVID-19 vaccine development timelines are comparable to other modern vaccines and drugs, indicating that vaccine hesitancy concerns about rapid development may not be supported by objective measures of drug development time.
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Patient and Caregiver 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, Santiago Ortiz AJ, Kesselheim AS - JAMA Network Open

  • Research Publications
| January 2022
  • Regulation and Clinical Evidence
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Qualitative interviews with 63 patients and caregivers enrolled in four FDA Risk Evaluation and Mitigation Strategy (REMS) programs with Elements to Assure Safe Use (ETASU) found that while most participants understood the program requirements and some were actually reassured about drug safety, many lacked awareness that requirements were part of a formal FDA-mandated program, struggled with educational materials, and faced access burdens such as needing to travel to certified prescribers or pharmacies. The findings suggest that REMS programs with ETASU can support informed treatment decisions but need improvements in educational quality, medication access efficiency, and patient privacy protections.
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Reporting Bias in Clinical Trials: Progress Toward Transparency and Next Steps

Mitra-Majumdar M, Kesselheim AS - PLOS Medicine

  • Commentary & Opinion
| January 2022
  • Regulation and Clinical Evidence
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The authors assess progress in addressing reporting bias in clinical trials noting that while regulatory requirements like ClinicalTrials.gov have improved transparency, studies still find that published literature overstates drug efficacy compared with FDA analyses.
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Differences in Diabetic Prescription Drug Utilization and Costs Among Patients with Diabetes Enrolled in Colorado Marketplace and Medicaid Plans, 2014-2015

Khorrami P, Sinha MS, Bhanja A, Allen HL, Kesselheim AS, Sommers BD - JAMA Network Open

  • Research Publications
| January 2022
  • Price, Value, and Access
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Among low-income diabetic adults in Colorado between 2014 and 2015, Medicaid-enrolled patients had significantly lower out-of-pocket costs and total costs compared to Marketplace-enrolled patients, despite similar rates of medication coverage and insulin use across both groups. These findings suggest that Medicaid provides substantially better drug cost protection for diabetic patients compared to subsidized Marketplace plans, with implications for affordability and access to antidiabetic medications among low-income populations.
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Promoting Competition in Drug Pricing: A Review of Recent Congressional Legislation

Nagar SN, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Research Publications
| Winter 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Brand-name drug manufacturers employ various strategies to delay generic or biosimilar competition—including reverse payment settlements, product hopping, sham petitions, and manipulation of the patent dance—prompting Congressional legislation in October 2021 targeting each of these 4 tactics. The authors analyze these legislative proposals and assess their likely effectiveness in promoting timely competition in the US drug market, using examples like the esomeprazole/omeprazole product hop and the buprenorphine/naloxone reformulation to illustrate how these tactics operate in practice.
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Value-Based Pricing of Drugs with Multiple Indications or in Combinations—Lessons From Europe

Vokinger KN, Kesselheim AS - Nature Reviews Clinical Oncology

  • Commentary & Opinion
| January 2022
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The authors discuss two key complexities of implementing value-based drug pricing: how to price drugs approved for multiple indications with varying levels of clinical benefit, and how to price drugs used in combination regimens, drawing on European experience to inform US reform efforts.
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The Characteristics of Patents Impacting Availability of Biosimilars

Van de Wiele VL, Beall RF, Kesselheim AS, Sarpatwari A - Nature Biotechnology

  • Research Publications
| January 2022
  • Innovation Incentives and Competition
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An examination of 179 patents litigated under the Biologics Price Competition and Innovation Act found that only 6% covered the biologic’s active ingredient, while the vast majority protected peripheral features such as manufacturing processes, formulations, and methods of use, with a median filing date more than a decade after the originator biologic’s approval. One-fifth of litigated patents had no equivalents in the EU, Canada, or Japan, suggesting that a substantial portion of US biologic patent thickets may reflect weaker patent standards rather than genuine innovation, contributing to delays in biosimilar availability.
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Performance-Linked Reimbursement and the Uncertainty of Novel Drugs

Rand LZG, Kesselheim AS - Circulation: Cardiovascular Quality and Outcomes

  • Commentary & Opinion
| January 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The growing uncertainty about new drug effectiveness,exemplified by aducanumab, complicates value-based pricing. The authors propose performance-linked reimbursement as a potential solution where payments are tied to demonstrated real-world outcomes.
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Payer-Specific Negotiated Prices for Prescription Drugs at Top-Performing US Hospitals

Feldman WB, Rome BN, Brown BL, Kesselheim AS - JAMA Internal Medicine

  • Research Publications
| January 2022
  • Price, Value, and Access
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An analysis of newly required price transparency data from 17 of the 20 top-ranked US hospitals found that these institutions routinely charge commercial insurers prices far in excess of Medicare payment limits for clinician-administered drugs, with substantial variation in negotiated prices across payers and self-pay cash prices. The findings reveal considerable hospital markups on pharmaceuticals, with particularly wide gaps at 340B-eligible entities, raising questions about how hospitals generate revenue from drug resale and how proposed 340B program changes may affect care for vulnerable populations.
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COVID-19 Antivirals Must Not Affect HIV Drug Supply

Barber M, Sarpatwari A, Cepuch C - Lancet HIV

  • Commentary & Opinion
| January 2022
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The global scale-up of COVID-19 antiviral treatments risks disrupting supply chains for HIV medications, particularly in low- and middle-income countries that rely on the same manufacturing infrastructure. The authors call for coordinated planning to ensure that pandemic responses do not undermine ongoing HIV treatment programs.
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Competition Law and Pricing Among Biologic Drugs: The Case of VEGF Therapy for Retinal Diseases

Van de Wiele VL, Hammer M, Parikh R, Feldman WB, Sarpatwari A, Kesselheim AS - Journal of Law and the Biosciences

  • Research Publications
| January 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Medicare spending on biologic treatments for neovascular age-related macular degeneration consistently exceeded $4 billion annually from 2015 to 2019, driven by high prices for approved therapies despite the availability of substantially cheaper off-label bevacizumab. Using AMD therapies as a case study, the authors propose legal reforms to improve biologic market competitio, including mechanisms to facilitate biosimilar market entry and empowering Medicare to negotiate drug prices, to lower spending and increase patient access as a large biosimilar pipeline nears approval.
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Associations Between Copays, Coverage Limits for Naloxone, and Prescribing in Medicaid

Messinger JC, Kesselheim AS, Vine SM, Fischer MA, Barenie RE - Substance Abuse: Research and Treatment

  • Research Publications
| January 2022
  • Price, Value, and Access
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This cross-sectional study of Medicaid fee-for-service naloxone dispensing found substantial variation across states in naloxone prescription rates, with a positive relationship between copays and generic naloxone dispensing in the primary analysis, though this relationship was not confirmed in sensitivity analyses, and no other meaningful associations between plan design features and naloxone dispensing were identified. The authors conclude that further evaluation is needed to determine whether Medicaid drug benefit designs influence naloxone use before implementing plan design changes that could limit access to this life-saving medication.
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An Orange Book Landscape: Drugs, Patents, and Generic Competition

Darrow JJ, Mai DTC - Food and Drug Law Journal

  • Research Publications
| January 2022
  • Innovation Incentives and Competition
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An analysis of all prescription drugs in the FDA’s Orange Book as of February 2021 found that only 31-39% retained any patent protection, and that the relationship between patents and competition was weaker than commonly assumed—generics were approved despite existing patents in 28% of cases, while 32% of patent expirations were not followed by generic entry. These findings challenge conventional narratives about patents as the primary barrier to drug competition and suggest policymakers should look beyond patents and regulatory exclusivities to understand the full range of factors influencing generic availability and drug pricing.
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A Global Intellectual Property Waiver Is Still Needed to Address the Inequities of COVID-19 and Future Pandemic Preparedness

Amin T, Kesselheim AS - Inquiry

  • Research Publications
| January 2022
  • Innovation Incentives and Competition
  • Price, Value, and Access
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The World Trade Organization’s (WTO) October 2021 decision on a intellectual property waiver for COVID-19 therapies was insufficient, having substantially narrowed India and South Africa’s original proposal to suspend IP protections on all COVID-19 vaccines, therapeutics, and diagnostics. A comprehensive IP waiver as originally proposed is still necessary to address ongoing COVID-19 inequities, increase manufacturing capacity in low- and middle-income countries, and establish an equitable precedent for future pandemic preparedness.
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Op-Ed: Drugs Should Be Labelled to Say How Well They Work

Darrow JJ - Daily Mail

  • Commentary & Opinion
| December 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Drug labeling fails to communicate the degree of benefit a medication provides in terms patients can understand, analogous to a sunscreen’s SPF rating. The authors calls for standardized, comparative effectiveness information on drug labels that would enable patients and physicians to make informed decisions about whether a drug’s benefits justify its costs and side effects.
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Medicare Spending on Drugs with Accelerated Approval, 2015-2019

Rome BN, Feldman WB, Kesselheim AS - JAMA Health Forum

  • Research Publications
| December 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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Annual Medicare spending on drugs with at least one accelerated approval indication grew from $4.8 billion in 2015 to $9.1 billion in 2019 across Parts B and D, with the highest-spending drugs including nivolumab ($6.8 billion), pembrolizumab ($6.1 billion), and ibrutinib ($6.6 billion) over the 5-year period. These accelerated approval drugs, 74% of which were for oncology, represented 2.5% of total net Part D spending and 16% of Part B spending in 2019, despite having no confirmed clinical benefit at the time of initial approval, underscoring the budgetary implications of high-priced drugs approved on the basis of surrogate endpoints.
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Raising Medicaid Rebates for Drugs with Accelerated Approval

Rome BN, Kesselheim AS - Health Affairs

  • Research Publications
| December 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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An analysis of Medicaid spending on 89 accelerated approval drugs during 2015–2020 found that the program spent an estimated $6.7 billion on these products after existing rebates, and that a proposed policy raising manufacturer rebates until confirmatory efficacy is demonstrated could have saved Medicaid between $0.6 billion and $5.2 billion over that period depending on the rebate level applied. While accelerated approval drugs represent a small but growing share of Medicaid drug spending, implementation of such a policy would need to account for drugs that also hold regular FDA approval for other indications.
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Pursuing Value-Based Prices for Drugs: A Comprehensive Comparison of State Prescription Drug-Pricing Boards

Bendicksen L, Rome BN, Avorn J, Kesselheim AS - Milbank Quarterly

  • Research Publications
| December 2021
  • Price, Value, and Access
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State prescription drug-pricing boards have been established in five states, varying substantially in structure, authority, and scope, with only one board (New York Medicaid) having completed pricing reviews as of June 2021. To overcome implementation challenges and maximize cost savings, states should design boards with clear statutory leverage to compel manufacturer negotiation and learn from the experiences of existing boards, though legal constraints may limit their effectiveness.
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Patient and Payer Incentives to Use Patented Brand-Name Drugs vs Authorized Generic Drugs in Medicare Part D

Dusetzina SB, Sarpatwari A, Carrier MA, Hansen RA, Keating NL, Huskamp HA - JAMA Internal Medicine

  • Research Publications
| December 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
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This study of Medicare Part D formularies in 2020 found that authorized generic versions of insulin and hepatitis C antivirals had list prices 50-67% lower than brand-name equivalents and could save individual beneficiaries $270-$2,974 annually, yet 97% of beneficiaries were in plans covering the brand-name drugs only or both formulations. This suggests that Part D plans lack financial incentives to promote authorized generic use because manufacturer rebates on brand-name drugs likely exceed the savings available through authorized generics, indicating that these lower-priced alternatives may reduce patient out-of-pocket costs without delivering meaningful savings for Medicare.
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Characteristics of US Patients and Prescribers Using Hydroxychloroquine During the COVID-19 Pandemic

Rome BN, Avorn J, Kesselheim AS - Journal of General Internal Medicine

  • Research Publications
| December 2021
  • Regulation and Clinical Evidence
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Following President Trump’s March 2020 promotion of hydroxychloroquine, weekly new users increased 2.9-fold, with the largest spike immediately after his first endorsement. 51.4% of pandemic-period prescriptions came from clinicians with no prior hydroxychloroquine prescribing history. The surge was disproportionately concentrated among men, Asian Americans, and Northeastern states, and use remained 1.7 times above pre-pandemic levels even after the FDA revoked its Emergency Use Authorization in June 2020.
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States, Preemption, and Patented Drug Prices

Wolitz RE - Seton Hall Law Review

  • Research Publications
| November 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
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States face severe budget pressures from patented brand-name drug costs, with single treatments sometimes exceeding half a billion dollars, forcing difficult trade-offs between medication access and funding for other critical services. The authors examine whether states can implement cost-containment and fair-pricing measures for patented drugs despite patent preemption doctrine, which limits state regulatory authority over federally-granted patent rights.
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Views from Academia, Industry, Regulatory Agencies, and the Legal System (3rd Ed)

Gagne JJ, Avorn J, Gatto NM, Mo J, Dal Pan GJ, Raine J, Uzu S, Kesselheim AS, Vokinger KN - Textbook of Pharmacoepidemiology, 3rd Edition

  • Commentary & Opinion
| November 2021
  • Regulation and Clinical Evidence
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This textbook chapter presents four complementary perspectives on the role of pharmacoepidemiology across the drug lifecycle, covering its use in academia, industry, and regulatory agencies. The final section examines the legal system’s intersection with pharmacoepidemiology.
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Simplify Drug Labelling to Show Benefits Clearly

Darrow JJ - Nature

  • Commentary & Opinion
| November 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
FDA drug labeling fails to clearly communicate how well drugs actually work, as though detailed safety warnings are required, there is no mandate to include understandable efficacy information. Drug labels should include meaningful, patient-relevant benefit metrics to help physicians and patients make more informed treatment decisions.
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Public-Sector Contributions to Novel Biologic Drugs

Nayak RK, Lee CC, Avorn J, Kesselheim AS - JAMA Internal Medicine

  • Research Publications
| November 2021
  • Innovation Incentives and Competition
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Among 69 new biologic drugs approved by the FDA between 2008 and 2017, 42% showed evidence of late-stage development contributions from public-sector institutions or their spin-offs—a higher proportion than the 25% found for small-molecule drugs during the same period. These publicly supported biologics were significantly more likely to receive expedited FDA review (90% vs. 55%) and Orphan Drug Act designation (76% vs. 38%). The findings underscore the substantial role of US taxpayer-funded research in developing therapeutically important biologic drugs and support calls for policies ensuring these products are available to patients at reasonable prices.
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Promoting Biosimilar Competition By Revising Medicare Reimbursement Rules

Rome BN, Sarpatwari A - JAMA Network Open

  • Commentary & Opinion
| November 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Current Medicare Part B reimbursement rules inadvertently discourage biosimilar competition by not creating sufficient financial incentives for providers to switch from originator biologics. The authors propose revisions that could save the government billions while promoting uptake.
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Influenza Vaccine Uptake in the Year After Concurrent vs Separate Influenza and Zoster Immunization

Rome BN, Feldman WB, Fischer MA, Desai RJ, Avorn J - JAMA Network Open

  • Research Publications
| November 2021
  • Price, Value, and Access
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Among 89,237 adults aged 50 years or older, influenza vaccine uptake in the subsequent year was significantly lower among those who received concurrent influenza and zoster vaccines compared to those who received them separately (87.3% vs 91.3%). The findings suggest that patients may have misattributed systemic side effects from the zoster vaccine to the influenza vaccine, and the authors recommend either administering these vaccines on separate days or enhancing patient counseling about expected side effects.
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Discovery and Development of Pregabalin (Lyrica): The Role of Public Funding

Barenie RE, Darrow JJ, Avorn J, Kesselheim AS - Neurology

  • Research Publications
| October 2021
  • Innovation Incentives and Competition
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Pregabalin (Lyrica) was discovered primarily through publicly funded research at Northwestern University before being licensed to Parke-Davis in 1990 for further development through its 2004 FDA approval. The study identified $13.8 million in related NIH funding across 37 awards during the drug’s preapproval period, underscoring the significant public-sector contribution to the development of this blockbuster medication.
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A Court Decision on Skinny Labeling: Another Challenge for Less Expensive Drugs

Walsh BS, Bloomfield D, Kesselheim AS - JAMA

  • Commentary & Opinion
| October 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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The Federal Circuit’s decision in GSK v. Teva regarding “skinny labeling” threatens generic drug entry by potentially expanding brand-name manufacturers’ ability to claim patent infringement.
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Variations in Generic Combination Opioid Use Across State Medicaid Programs

Lee CC, Kesselheim AS, Avorn J - Journal of General Internal Medicine

  • Research Publications
| October 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Despite the availability of inexpensive generic oxycodone-acetaminophen since the 1980s, it took over 30 years to reach a 90% generic dispensing rate in Medicaid, with substantial state-level variation.Continued brand-name use cost Medicaid an estimated $239 million ($108 million after rebates) for oxycodone-acetaminophen alone from 1998 to 2018. These findings highlight missed opportunities for cost savings through more timely and consistent generic substitution of commonly prescribed combination opioids across state Medicaid programs.
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The Perils of Increasing Medicaid Rebates for Drugs with Accelerated Approval

Darrow JJ - JAMA Health Forum

  • Commentary & Opinion
| October 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The author cautions that proposals to increase Medicaid rebates for drugs with accelerated approval could have unintended consequences, including incentivizing manufacturers to raise baseline prices, introduce drugs at higher starting prices, or forgo the accelerated pathway altogether. If rebates outweigh the financial benefits of earlier market entry, manufacturers may opt for traditional approval, undermining the program’s purpose of accelerating patient access.
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Fulfilling the Mandate of the US Food and Drug Administration’s Accelerated Approval Pathway: The Need for Reforms

Gyawali B, Ross JS, Kesselheim AS - JAMA Internal Medicine

  • Commentary & Opinion
| October 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The accelerated approval program needs reform because of inadequate surrogate marker validation (exemplified by the aducanumab decision), long delays in completing mandatory confirmatory trials, and instances where the FDA has converted accelerated approvals to regular approvals despite negative confirmatory studies.
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Cost to Medicare of Delayed Adalimumab Biosimilar Availability

Lee CC, Najafzadeh MN, Kesselheim AS, Sarpatwari A - Clinical Pharmacology & Therapeutics

  • Research Publications
| October 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
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Between 2016 and 2019, delayed market entry of five FDA-approved adalimumab biosimilars due to patent settlements cost Medicare an estimated $2.19 billion in cumulative spending, with actual total adalimumab spending reaching $12.11 billion compared to a projected $8.98 billion had biosimilars launched upon approval. Policy reforms are needed to expedite biosimilar market entry following FDA approval in order to maximize cost savings.
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Changing FDA Approval Standards: Ethical Implications for Patient Consent

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

  • Research Publications
| October 2021
  • Regulation and Clinical Evidence
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The FDA has progressively relaxed premarket evidence requirements for drugs and devices over several decades, through programs like accelerated approval, breakthrough therapy designation, and real-world evidence provisions, resulting in a growing number of products reaching patients with limited clinical data. The authors argue that the informed consent process has not kept pace with these changes, creating ethical challenges as patients and physicians make treatment decisions about products with increasingly uncertain benefit-risk profiles.
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Assessing the Impact of US Food and Drug Administration Breakthrough Therapy Designation Timing on Trial Characteristics and Development Speed

Pregelj L, Hine DC, Kesselheim AS, Darrow JJ - Clinical Pharmacology & Therapeutics

  • Research Publications
| October 2021
  • Regulation and Clinical Evidence
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Among pivotal trials supporting approved drugs granted breakthrough therapy designation by the FDA between 2013 and 2018, 83% were already underway when the designation was granted. Trials that began after the designation showed no differences in design characteristics compared to non-designated trials, suggesting that trial design features were driven by disease category rather than the designation itself. However, trials that commenced after the designation was granted were more than 8 months shorter than non-designated trials, indicating that early designations may reduce development timelines through mechanisms other than trial design, such as earlier and more frequent interaction with the FDA.
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To Incentivize COVID-19 Vaccination, Give Vaccinated Individuals A Discount on Their Insurance Premiums

Liu ITT, Darrow JJ - Health Affairs Forefront

  • Commentary & Opinion
| September 2021
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
With over 36% of the US population unvaccinated and vaccinations estimated to have averted $25 billion in hospitalization costs in the first half of 2021, insurers could pass along savings as premium discounts of up to $96 per vaccinated individual. Such benefit-sharing aligns with existing ACA wellness program frameworks and better respects patient autonomy than vaccine mandates, while more equitably distributing the financial costs of the pandemic between vaccinated and unvaccinated populations.
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President Biden Already Has the COVID Vaccine Recipe. He Should Share It

Morten CJ, Rizvi Z, Sarpatwari A - Health Affairs Forefront

  • Commentary & Opinion
| September 2021
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The US government holds detailed manufacturing information for Moderna’s COVID-19 vaccine—co-invented by NIH scientists and developed with over $1 billion in federal funding—and likely has contractual “unlimited rights” to share it. President Biden should disclose this recipe to the WHO and qualified manufacturers worldwide to address the severe vaccine inequity in low-income countries, where only 1.5 doses per 100 people had been administered.
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Op-Ed: Letting the Government Negotiate Drug Prices Won’t Hurt Innovation

Kesselheim AS, Avorn J - Washington Post

  • Commentary & Opinion
| September 2021
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The pharmaceutical industry’s claim that allowing Medicare to negotiate drug prices would devastate innovationis contradicted by evidence showing that publicly funded research drives most transformative drug discoveries, that large manufacturers spend far more on marketing and buybacks than R&D, and that unconstrained pricing actually incentivizes development of low-risk, minimally innovative products. The authors contend that value-based price negotiation would reward genuinely beneficial drugs while discouraging therapeutically marginal ones, and warn that pharmaceutical lobbying and campaign contributions are the real forces behind congressional opposition to reform.
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Analysis of Launch and Postapproval Cancer Drug Pricing, Clinical Benefit, and Policy Implications in the US and Europe

Vokinger KN, Hwang TJ, Daniore P, Lee CC, Tibau Martorell A, Grischott T, Rosemann TJ, Kesselheim AS - JAMA Oncology

  • Research Publications
| September 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
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US cancer drug launch prices are substantially higher than in England, Germany, and Switzerland, with 74% of US drugs experiencing price increases exceeding inflation between 2009-2019 compared to only 2% in England, 0% in Germany, and 13% in Switzerland. Price changes in all countries showed no correlation with clinical benefit. These findings indicate a need for policy reforms that tie US cancer drug prices to demonstrated clinical benefit.
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Regulatory and Clinical Consequences of Negative Confirmatory Trials of Accelerated Approval Cancer Drugs: Retrospective Observational Study

Gyawali B, Rome BN, Kesselheim AS - BMJ (Clinical research ed.)

  • Research Publications
| September 2021
  • Regulation and Clinical Evidence
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Among 18 indications for 10 cancer drugs granted accelerated approval by the FDA that subsequently failed their confirmatory trials, 61% were voluntarily withdrawn by manufacturers and one was revoked by the FDA, while 33% remained on the label. Notably, the NCCN guidelines continued to provide high-level endorsements for many of these drugs even after withdrawal or revocation, demonstrating a need for clinical guidelines to better incorporate negative confirmatiory trial results for accelerated approval cancer drugs to prevent continued use of ineffective treatments.
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The Timing of 30-Month Stay Expirations and Generic Entry: A Cohort Study of First Generics, 2013-2020

Kannappan S, Darrow JJ, Kesselheim AS, Beall RF - Clinical and Translational Science

  • Research Publications
| September 2021
  • Innovation Incentives and Competition
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This cohort study of 46 first-generic drugs found that Paragraph IV certifications were filed a median of 5.2 years after brand-drug approval. There was a median 3.2-year gap between 30-month stay period expiration and generic launch, indicating that 30-month stays are unlikely to delay actual generic entry timing. The authors recommend allowing generic drug applications to be submitted immediately following brand-drug FDA approval to facilitate earlier patent dispute resolution and prevent unnecessary delays in generic launches.
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The Implications of Industry-Funded Disease Awareness Campaigns in the Rare Disease Setting

Gill J, Sarpatwari A, Prasad V - Mayo Clinic Proceedings

  • Commentary & Opinion
| September 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Industry-funded disease awareness campaigns following orphan drug approvals can expand diagnostic criteria and increase diagnostic vigilance, potentially leading to treatment of a broader population than that studied in the pivotal trials. The authors use tafamidis for transthyretin amyloid cardiomyopathy as a case study to illustrate how post-approval screening expansion, funded by the drug’s manufacturer, may alter the patient population in ways that reduce the drug’s real-world efficacy.
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Reimagining Pharmaceutical Market Exclusivities: Should the Duration of Guaranteed Monopoly Periods Be Value Based?

Beall RF, Hollis A, Kesselheim AS, Spackman E - Value in Health

  • Research Publications
| September 2021
  • Innovation Incentives and Competition
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The authors propose a value-based pharmaceutical market exclusivity framework where regulatory exclusivity duration is tied to a drug’s anticipated health impact and price, with reassessment three years post-launch based on real-world effectiveness. This approach would incentivize drug developers to create high-impact, affordable products by granting longer monopoly periods to drugs that offer greater public health value at lower prices.
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International Reference Pricing for Prescription Drugs: A Landscape Analysis

Rand LZG, Kesselheim AS - Journal of Managed Care & Specialty Pharmacy

  • Research Publications
| September 2021
  • Price, Value, and Access
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Nearly two-thirds of comparator countries currently use international reference pricing (IRP) but combine it with additional price negotiation strategies, similar to those proposed for Medicare in Congress.The analysis suggests that aligning US IRP implementation with complementary pricing strategies like price negotiation would be more consistent with how peer nations have structured their drug pricing frameworks.
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How Should Clinicians and Organizations Assess Risks and Benefits of First-In-Human Implantation of Investigational Devices?

Brown BL, Kesselheim AS - AMA Journal of Ethics

  • Commentary & Opinion
| September 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Numerous safety risks associated with FDA 510(k)-cleared medical devices warrant heightened caution with newly cleared 510(k) products pending postmarket surveillance data, enhanced informed consent through better provider and patient education about the 510(k) pathway, and individual risk assessments while maintaining equitable access to these devices.
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Government Pharmaceutical Development to Address High Prices: Challenges Ahead

Darrow JJ - Therapeutic Innovation & Regulatory Science

  • Commentary & Opinion
| September 2021
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The author examines proposals for government drug development as a means of lowering prices, concluding that while some costs (e.g., marketing costs) could be reduced, most development costs would remain unchanged and inefficiencies could worsen with greater government involvement. He argues that government manufacturing is unlikely to substantially improve drug development or lower costs in the long term.
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Controversy Over Using Quality-Adjusted Life-Years in Cost-Effectiveness Analyses: A Systematic Literature Review

Rand LZG, Kesselheim AS - Health Affairs

  • Research Publications
| September 2021
  • Price, Value, and Access
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This systematic literature review identifies and categorizes criticisms of quality-adjusted life-years (QALYs), distinguishing between methods-based criticisms that require technical refinement and ethical criticisms that reflect broader societal value judgments. Understanding and overcoming criticisms of the QALY to enable its use as part of health technology assessment and value-based pricing will be crucial as US policy makers seek to address high drug costs and health care spending.
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Revisiting FDA Approval of Aducanumab

Alexander GC, Knopman DS, Emerson SS, Ovbiagele B, Kryscio RJ, Perlmutter JS, Kesselheim AS - New England Journal of Medicine

  • Commentary & Opinion
| August 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The authors challenge the FDA’s accelerated approval of aducanumab based on beta-amyloid reduction as a surrogate endpoint, arguing that amyloid plaque reduction has not been validated as a reliable predictor of clinical benefit in Alzheimer’s disease. They review principles governing surrogate measures and cite numerous examples of failed surrogates that initially appeared promising.
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Mitigating Bias in Machine Learning for Medicine

Vokinger KN, Feuerriegel S, Kesselheim AS - Communications Medicine

  • Commentary & Opinion
| August 2021
  • Regulation and Clinical Evidence
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Machine learning systems used in medical applications are vulnerable to multiple sources of bias that can degrade performance and affect clinical outcomes. The authors propose mitigation strategies that address bias throughout the entire development pipeline of medical machine learning systems.
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FDA Regulation and Approval of Medical Devices: 1976-2020

Darrow JJ, Avorn J, Kesselheim AS - JAMA

  • Research Publications
| August 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
In this review of FDA regulation of medical devices from 1976 to 2020, the authors outline how the system has evolved to include multiple accelerated review pathways and flexible evidence requirements. The increasing complexity of medical device regulation reflects an ongoing tension between facilitating timely patient access to innovative products and ensuring adequate evidence of safety and effectiveness, with recent adverse events from certain devices raising questions about whether current requirements provide sufficient assurance of patient benefit.
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Will Ending the Medicaid Drug Rebate Cap Lower Drug Prices?

Rome BN, Kesselheim AS - JAMA Internal Medicine

  • Commentary & Opinion
| August 2021
  • Price, Value, and Access
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The authors analyze the American Rescue Plan’s elimination of the Medicaid drug rebate cap, explaining that this change could save billions by allowing rebates to exceed the drug’s price for products with years of price increases exceeding inflation, while potentially discouraging future price hikes by manufacturers.
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Market Exclusivity and Changes in Competition and Prices Associated with the US Food and Drug Administration Unapproved Drug Initiative

Gunter SJ, Kesselheim AS, Rome BN - JAMA Internal Medicine

  • Research Publications
| August 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 21 drugs approved through the FDA’s Unapproved Drugs Initiative from 2008 to 2017, median market exclusivity lasted 3.42 years, and among the 8 self-administered drugs with available pricing data, the number of manufacturers declined for 6 and prices increased for 5, with a median price increase of 157% over 5 years. These findings demonstrate that the UDI’s grant of market exclusivity to manufacturers of legacy drugs, most of which were approved without new clinical data, led to reduced competition and price increases that support the concerns that prompted the program’s brief discontinuation.
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CAAP Rule and Prescription Drug Prices

Walsh BS, Kesselheim AS - American Journal of Managed Care

  • Commentary & Opinion
| August 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
Co-pay accumulator adjustment programs (CAAPs) allow insurers to exclude manufacturer co-pay assistance from patient out-of-pocket maximums, intended to drive beneficiaries to lower-priced generic alternatives. A July 2020 rule permitting CAAPs does not require transparency from payers about the existence of such programs, and may have meaningful impacts on prescription drug spending.
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Barriers to US Biosimilar Market Growth: Lessons From Biosimilar Patent Litigation

Van de Wiele VL, Kesselheim AS, Sarpatwari A - Health Affairs

  • Research Publications
| August 2021
  • Innovation Incentives and Competition
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The authors’ analysis of BPCIA-related litigation from 2010 to 2020 identified two primary barriers to biosimilar market competition: noncompliance with the statutory litigation process by parties and originator manufacturers’ enforcement of large patent portfolios, both resulting in confidential settlements that delay biosimilar market entry. Policymakers should consider implementing limits on patent prosecution, requiring public patent listing, and strengthening antitrust enforcement to accelerate biosimilar availability and address high biologic drug prices.
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Integrating New Effectiveness Data Into US Food and Drug Administration-Approved Drug Labeling

Gyawali B, Darrow JJ, Kesselheim AS - JAMA Internal Medicine

  • Commentary & Opinion
| July 2021
  • Regulation and Clinical Evidence
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The authors identify a gap in how new effectiveness data, particularly for generic drugs tested for new indications, is integrated into FDA-approved drug labeling, since generic manufacturers have little financial incentive to seek FDA approval for new uses that competitors could share freely.
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