Contact

Our Work

  • Reset Filters

  • Topic Areas

  • Content Types

  • Authors / Speakers

  • Date Range

  • Reset Filters

1377 Results

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

The Vexing Voyage of Vasopressin

Bendicksen L, Kesselheim AS, Rome BN - Chest

  • Research Publications
| August 2022
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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.
View Source

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.
View Source

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.
View Source

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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

Promoting Confidence in Cost-Effectiveness Analyses

Raymakers AJN, Kesselheim AS - BMJ

  • Commentary & Opinion
| June 2022
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

Trends in Prescription Drug Launch Prices, 2008-2021

Rome BN, Egilman AC, Kesselheim AS - JAMA

  • Research Publications
| June 2022
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

QALYs in Health Resource Usage Decisions (Reply)

Rand LZG, Kesselheim AS - Health Affairs

  • Commentary & Opinion
| April 2022
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

Aducanumab and Accelerated Approval: Where Do We Go From Here?

Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Commentary & Opinion
| April 2022
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

Litigating Authority for the FDA

Daval, C Joseph Ross - Washington University Law Review

  • Research Publications
| March 2022
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

States, Preemption, and Patented Drug Prices

Wolitz RE - Seton Hall Law Review

  • Research Publications
| November 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

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.
View Source

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
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
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.
View Source

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.
View Source

Mitigating Bias in Machine Learning for Medicine

Vokinger KN, Feuerriegel S, Kesselheim AS - Communications Medicine

  • Commentary & Opinion
| August 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
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.
View Source

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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

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.
View Source

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.
View Source

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.
View Source

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
Talk bubble graphics representing commentary and opinion.
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.
View Source

Frequency of First Generic Drug Approvals with “Skinny Labels” in the United States

Walsh BS, Sarpatwari A, Rome BN, Kesselheim AS - JAMA Internal Medicine

  • Research Publications
| July 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 56 brand-name drugs first facing generic competition from 2015 to 2019, 43% had generics approved with “skinny labels” that carved out patent- or exclusivity-protected indications, with a median of 3.2 years between skinny-label approval and expiration of the carved-out protections. Skinny labeling was particularly common among high-revenue brand-name drugs (median net sales of $852 million vs. $522 million for those with full-label generics), demonstrating its important role in facilitating timely generic entry while navigating secondary patents and exclusivities.
View Source

FDA Approval Standards for Anticancer Agents—Lessons From Two Recent Approvals in Breast Cancer

Gyawali B, Kesselheim AS - Nature Reviews Clinical Oncology

  • Commentary & Opinion
| July 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Two breast cancer drug approvals (neratinib and margetuximab) serve as evidence that FDA approval standards are declining, with one drug delaying radiological progression by only 3 days without improving overall survival or quality of life, while the other showed similarly marginal benefits.
View Source

A Multi-Modal Approach to Evaluate the Impact of Risk Evaluation and Mitigation Strategy (REMS) Programs

Sarpatwari A, Mitra-Majumdar M, Bykov K, Avorn J, Woloshin S, Toyserkani GA, LaCivita C, Manzo C, Zhou EH, Pinnow E, Dal Pan GJ, Gagne JJ, Huybrechts KF, Feldman WB, Chin K, Kesselheim AS - Drug Safety

  • Research Publications
| July 2021
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
A systematic, multi-method study describes a framework for evaluating how FDA Risk Evaluation and Mitigation Strategy (REMS) programs have operated in practice, incorporating insurance claims analyses of drug use and patient outcomes, physician and patient surveys and interviews, and assessments of risk communication effectiveness. The research aims to address the current lack of evidence on REMS program impacts on informed decision-making, medication access, and patient outcomes, with the goal of generating actionable recommendations for program improvement.
View Source

Over-The-Counter Monograph Safety, Innovation, and Reform Act

Gardiner J, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Research Publications
| Summer 2021
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The prior FDA system for establishing over-the-counter (OTC) drug safety and effectiveness relied on a cumbersome rulemaking process that took decades, creating barriers to new OTC market entry and slow responses to emerging safety concerns. The CARES Act of 2020 reformed this system by replacing rulemaking with a more efficient administrative order process and establishing user fees to support FDA review, though the authors note it will be important to monitor how the OTC market evolves under these new regulatory features.
View Source

Op-Ed: The FDA Has Reached a New Low

Kesselheim AS, Avorn J - New York Times

  • Commentary & Opinion
| June 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The FDA’s approval of aducanumab (Adulhelm) for Alzheimer’s represents a dangerous erosion of the agency’s evidence standards. Despite an advisory committee’s near-unanimous finding that the drug failed to demonstrate clinical benefitand caused brain swelling in roughly a third of higher-dose patients, the FDA approved it based on an unvalidated surrogate measure. The authors call for independent oversight of drug approvals to prevent further regulatory decline.
View Source

Association of California’s Prescription Drug Coupon Ban with Generic Drug Use

Rome BN, Gagne JJ, Kesselheim AS - JAMA

  • Research Publications
| June 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
California’s 2018 ban on manufacturer co-payment coupons for drugs with available generics was associated with a nonsignificant 0.42% increase in generic use relative to surrounding states, with generic use already trending upward in both California and comparison states during the study period. The limited observed effect suggests that while coupon bans may theoretically promote generic substitution, their practical impact may be modest when generic adoption is already high and other factors driving brand-name prescribing remain in play.
View Source

Prospects for Enforcing Prohibitions on Off-Label Drug Promotion After United States v. Caronia: An Analysis of Litigated Cases

Liu S, Mello MM, Kesselheim AS - Journal of Health Politics, Policy and Law

  • Research Publications
| June 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 42 litigated cases citing United States v. Caronia from 2012 to 2019, 52% followed the ruling that truthful off-label drug promotion is protected speech, while 48% declined to follow or distinguished it, demonstrating inconsistent judicial application of First Amendment protections to pharmaceutical marketing. The authors conclude that Caronia has significantly weakened FDA enforcement of off-label promotion restrictions, allowing manufacturers greater latitude to market drugs for unapproved uses despite associated public health risks.
View Source

Postmarket Safety Communication for Protection of Public Health: A Comparison of Regulatory Policy in Australia, Canada, the European Union, and the United States

Bhasale AL, Sarpatwari A, De Bruin ML, Lexchin J, Lopert R, Bahri P, Mintzes BJ - Clinical Pharmacology & Therapeutics

  • Research Publications
| June 2021
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The authors compare postmarket safety communication systems across four major regulatory jurisdictions (US, European Union, Canada, and Australia), examining their governance structures, legislative authorities, risk communication capabilities, and transparency mechanisms for issuing safety advisories about emerging drug risks. Regulators’ shift to communicating postmarket safety issues through letters to healthcare professionals, drug safety bulletins, media alerts, and website announcements highlights a part of the “life cycle” approach to medicine regulation adopted in response to the withdrawal of rofecoxib.
View Source

Factors Associated with Generic Drug Uptake in the United States, 2012 to 2017

Rome BN, Lee CC, Gagne JJ, Kesselheim AS - Value in Health

  • Research Publications
| June 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 227 drugs facing new generic competition, mean generic uptake was 66.1% in the first year and 82.7% in the second year, but declined 4.3% annually in year one and 3.2% annually in year two. Uptake was substantially lower for injected drugs compared to oral drugs. The authors recommend implementing policies to encourage generic competition, particularly for injectable drugs administered in hospital or clinic settings, to counteract declining early generic uptake and reduce prescription drug spending.
View Source

Continual Learning in Medical Devices: FDA’s Action Plan and Beyond

Vokinger KN, Feuerriegel S, Kesselheim AS - Lancet Digital Health

  • Commentary & Opinion
| June 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The authors discuss the regulatory challenges of AI/ML medical devices capable of continual learning, noting that no such adaptive device has yet been FDA-approved. Known risks, including dataset shift, bias, and catastrophic forgetting, require novel regulatory frameworks.
View Source

The Wrong Cure: Financial Incentives for Unimpressive New Antibiotics

Sinha MS, Powers JH, Kesselheim AS - Journal of Infectious Diseases

  • Research Publications
| May 2021
  • Innovation Incentives and Competition
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
US policymakers have relied primarily on market-based financial incentives—including extended exclusivity periods and expedited approval pathways—to encourage antibiotic development, but these incentives do not require demonstration of added clinical benefit over existing therapies, contributing to a pattern of commercially unsuccessful approvals like plazomicin. The authors argue that innovation policies should be redesigned to prioritize antibiotics with demonstrated superiority over available treatments, rather than simply rewarding new market entrants regardless of their clinical value.
View Source

Testimony: Addressing Pharmaceutical Patent Abuses Could Lower Drug Spending and Improve Patient Outcomes

Kesselheim AS - 117th Congress, House Committee on Oversight and Reform

  • Policy Interactions
| May 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
An icon of a bill representing government policy.
Kesselheim argues that brand-name drug manufacturers exploit the US market exclusivity system particularly through patent thickets to delay generic and biosimilar competition well beyond reasonable exclusivity periods, citing adalimumab (Humira) as a case study. He documents how these strategies inflate US drug spending and recommends various reforms, including strengthening USPTO resources and patent quality standards, requiring Patent Trial and Appeals Board review of all FDA-listed drug patents, limiting enforcement to a single primary patent per drug, invoking the government’s existing patent use rights, and reforming orphan drug and biologic exclusivity periods to ensure timely competition. Watch his testimony.
View Source

Evaluation of Aducanumab for Alzheimer Disease: Scientific Evidence and Regulatory Review Involving Efficacy, Safety, and Futility

Alexander GC, Emerson SS, Kesselheim AS - JAMA

  • Commentary & Opinion
| May 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The authors critiques the regulatory review of aducanumab, noting that its two pivotal trials were halted for futility and produced conflicting results, with post hoc analyses raising concerns about data-driven endpoint changes. They also question the unusually close FDA-manufacturer collaboration throughout the approval process and argue that the clinical significance of the observed treatment effect was uncertain.
View Source

Correlation Between Changes in Brand-Name Drug Prices and Patient Out-Of-Pocket Costs

Rome BN, Feldman WB, Desai RJ, Kesselheim AS - JAMA Network Open

  • Research Publications
| May 2021
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
From 2015 to 2017, list prices for brand-name drugs increased by a median of 16.7%, net prices increased by 5.4%, and out-of-pocket (OOP) spending increased by 3.5%, with changes in list prices showing weak correlation with overall out-of-pocket spending but moderate correlation among patients with deductibles or coinsurance who experienced a 15.0% median increase in OOP spending. Policies regulating uncontrolled list price increases may be necessary to reduce out-of-pocket spending for patients with high-deductible or coinsurance-based plans, as manufacturer rebates do not appear to translate into reduced patient costs.
View Source

Antibiotic Development Incentives That Reflect Societal Value of Antibiotics (Reply)

Rome BN, Kesselheim AS - Clinical Infectious Diseases

  • Commentary & Opinion
| May 2021
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
In this reply, the authors respond to advocates of transferable market exclusivity vouchers as an incentive for antibiotic development, arguing that the government report used to estimate the societal value of new antibiotics had significant methodological flaws and that most recently approved antibiotics entered saturated markets with limited added clinical benefit. They contend that exclusivity vouchers are inefficient and ethically problematic and propose alternative approaches.
View Source

Frequency of Generic Drug Price Spikes and Impact on Medicaid Spending

Patel AN, Kesselheim AS, Rome BN - Health Affairs

  • Research Publications
| May 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Using Medicaid data from 2014 to 2017, the authors found that one in five generic drugs experienced a price spike (doubling within one year), with the frequency of spikes declining from 7.8% in 2014 to 5.8% in 2017. These spikes cost Medicaid $1.5 billion, or 4.2% of all generic drug spending, from 2014-2016 and particularly affected injected products and drugs with few manufacturers. The authors conclude that while regulatory action may have reduced the frequency of price spikes for generic drugs, additional policies are needed to enhace generic competition and constrain prices.
View Source

Few New Drugs Deserve Expedited Regulatory Treatment

Darrow JJ - Journal of Managed Care & Specialty Pharmacy

  • Commentary & Opinion
| May 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
While expedited FDA approval pathways were originally intended for truly transformative therapies, most new drugs offer only modest incremental benefits over existing treatments, yet the majority now receive some form of expedited designation. The expansion of these programs has distracted from the more fundamental question of whether approved drugs provide meaningful clinical benefit.
View Source

Diabetes Drugs: List Price Increases Were Not Always Reflected in Net Price; Impact of Brand Competition Unclear

Sarpatwari A, Tessema FA, Zakarian M, Najafzadeh MN, Kesselheim AS - Health Affairs

  • Research Publications
| May 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Between 2005 and 2017, list prices for three classes of diabetes drugs (GLP-1 agonists, DPP4 inhibitors, and SGLT2 inhibitors) increased 8-15% despite the introduction of competing brand-name drugs. Net prices showed a more variable pattern, with GLP-1 net prices rising 10% while net prices for other classes declined. These findings suggest that brand-name competition may have a variable impact on net prices, and that list price changes may not always correspond to changes in net price.
View Source

Safeguarding Evidence-Based Decision Making in the FDA for COVID-19 Vaccines

Angelis A, Darrow JJ - Vaccine

  • Commentary & Opinion
| April 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Political pressure, premature government statements about unproven treatments (e.g., hydroxychloroquine, convalescent plasma), and unclear communication about Emergency Use Authorizations eroded public trust in the FDA during the pandemic. The authors propose measures to restore confidence in vaccine decision-making, including greater transparency and research coordination.
View Source

Public Sector and Non-Profit Contributions to Drug Development—Historical Scope, Opportunities, and Challenges

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

  • Research Publications
| Spring 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Per capita US prescription drug spending reached $1,024 million in 2017 (45% more than the next highest country), driven in part by high-priced new therapies like gene treatments priced at up to $2.1 million, many of which benefited from critical public-sector research support, including NIH funding that contributed at some level to all new drugs approved between 2008 and 2017. This introduction to a special journal issue frames the tension between substantial taxpayer-funded contributions to drug discovery and the high prices subsequently charged to US patients, arguing for policies that ensure public investment is reflected in drug accessibility and affordability.
View Source

Characteristics of Clinical Trials Launched Early in the COVID-19 Pandemic in the US and in France

Raimond VC, Mousquès J, Avorn J, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Research Publications
| Spring 2021
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
An analysis of 200 COVID-19 clinical trials registered early in the pandemic found that most evaluated repurposed drugs (73%) and were funded without industry participation (75%), with French trials less often classified as high-rigor (30%) compared to US trials (47%) and industry funding considerably more common in US trials. Despite the registration of a large number of trials, only a minority had design characteristics usually associated with producing robust and relevant evidence, raising concerns about the efficiency and coordination of the pandemic clinical research response.
View Source

A Non-Profit Approach to Address Foreign Dependence of Generic Drugs

Liljenquist D, Bai G, Sarpatwari A, Anderson GF - Journal of Law, Medicine & Ethics

  • Research Publications
| Spring 2021
  • Innovation Incentives and Competition
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The COVID-19 pandemic exposed critical vulnerabilities in the US generic drug supply chain, with approximately 90% of pharmaceutical ingredients for essential generics manufactured in China and production disruptions threatening availability of key medications. The authors argue that nonprofit drug manufacturers like Civica Rx may be better positioned than for-profit companies to support domestic generic drug production, as they can prioritize supply reliability and public health over profit maximization while complementing legislative efforts to reduce foreign dependence.
View Source

Comments on Proposed Rule, “Rights to Federally Funded Inventions and Licensing of Government Owned Inventions”

Sinha MS - National Institute of Standards and Technology (NIST)

  • Policy Interactions
| April 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
An icon of a bill representing government policy.
NIST should clarify processes for exercising Bayh-Dole Act march-in rights on federally funded research and ensure that unreasonable pricing of publicly funded medical products remains a legitimate basis for government action. The commenters point to the substantial federal investment in pharmaceutical development including COVID-19 vaccines and therapeutics as an example of the need for such authority.
View Source

Substitution of Generic Drugs and Biosimilars (Reply)

Sarpatwari A, Kesselheim AS, Sacks CA - JAMA Internal Medicine

  • Commentary & Opinion
| April 2021
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
The authors acknowledge that many biologics bypass pharmacy dispensing, but note that several top-selling biologics accounting for billions in spending are primarily pharmacy-dispensed, meaning meaningful savings can result from optimizing state drug product selection laws. They also note that the profit-margin dynamics favoring generic substitution for small-molecule drugs may not apply to interchangeable biologics given their manufacturing complexity and fewer competitors, and emphasize that state law optimization should be coupled with educational outreach and closer oversight of pharmacy benefits management practices.
View Source

Public Funding and the Importance of Reasonable Pricing for Buprenorphine

Barenie RE, Kesselheim AS - Drug and Alcohol Dependence

  • Commentary & Opinion
| April 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
In this letter, the authors respond to commentary on their research quantifying NIH contributions to buprenorphine’s development as an opioid use disorder treatment, arguing that when public funding meaningfully supports drug development, policymakers should consider mechanisms to ensure the resulting products are available at fair prices.
View Source

International Reference Pricing for Prescription Drugs in the United States: Administrative Limitations and Collateral Effects

Rand LZG, Kesselheim AS - Value in Health

  • Research Publications
| April 2021
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The authors identify four key administrative challenges to implementing international reference pricing in the US: lack of price transparency, delays in market approvals, the frequency of price revisions, and the prevalence of cross-referencing. Failure to address these issues will result in overspending from price overestimation while likely increasing drug prices in other countries. Policymakers should adopt international reference pricing as a supplementary tool alongside other cost-containment strategies such as value-based pricing or volume agreements, rather than as a standalone policy, given these challenges.
View Source

Identifying Potential Prescription Drug Product Hopping

Gowda V, Beall RF, Kesselheim AS, Sarpatwari A - Nature Biotechnology

  • Research Publications
| April 2021
  • Innovation Incentives and Competition
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The authors define and apply a systematic process for prospectively detecting product hopping. They distinguish between “soft” switches (relying on marketing to shift patients) and “hard” switches (discontinuing the original product), and argue that prospective identification of potential product hops could help policymakers and regulators intervene before patients and the health care system incur unnecessary costs.
View Source

Characteristics of Postmarketing Studies for Vaccines Approved By the US Food and Drug Administration, 2006-2020

Moneer O, Lee CC, Avorn J, Kesselheim AS - JAMA Network Open

  • Research Publications
| April 2021
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 35 vaccines approved by the FDA from 2006 to 2020, all but one were issued postmarketing requirements (PMRs) or commitments (PMCs)—128 total studies with a median of 4 per vaccine—but only 48.4% were fulfilled, with a median time to completion of 50 months. Postmarketing commitments, which lack the same enforcement mechanisms as requirements, had a higher fulfillment rate (54.2%) than PMRs (41.1%), raising concerns about the completeness and timeliness of postapproval safety evidence for vaccines as COVID-19 vaccines enter the postmarketing phase.
View Source

Assessment of Coverage in England of Cancer Drugs Qualifying for US Food and Drug Administration Accelerated Approval

Cherla A, Naci H, Kesselheim AS, Gyawali B, Mossialos E - JAMA Internal Medicine

  • Research Publications
| April 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 87 cancer drug indications that received FDA accelerated approval between 1992 and 2017, 30 were not subsequently reviewed by either the EMA or the UK National Institute for Health and Care Excellence (NICE), and 12 drugs were denied authorization or coverage owing to insufficient safety, clinical efficacy, or cost-effectivenes. National Health Service (NHS) coverage of cancer drugs given FDA accelerated approval commonly required additional price concessions, restrictions to approved indications, or review of additional data.
View Source

Testimony: High Drug Prices in the US: What We Can Learn From Other Countries and Some US States

Kesselheim AS - 117th Congress, Senate Committee on Health, Education, Labor, and Pensions

  • Policy Interactions
| March 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
An icon of a bill representing government policy.
Kesselheim argues that US brand-name drug prices are far higher than in peer countries because manufacturers can freely set launch prices, raise prices annually above inflation, and extend market exclusivity through patent thickets, while Medicare and Medicaid are legally constrained from meaningful negotiation. Drawing on approaches used in Germany, France, Canada, Australia, Japan, and several US states, he proposes a three-pronged reform: establishing a publicly-funded body to negotiate drug prices based on health technology assessment; limiting annual price increases to the rate of inflation; and ensuring efficient transition to generic and biosimilar competition by strengthening USPTO patent quality review and expanding PTAB scrutiny of drug patents. Watch his testimony.
View Source

ASHP Foundation Pharmacy Forecast 2021: Strategic Planning Advice for Pharmacy Departments in Hospitals and Health Systems

DiPiro JT, Fox ER, Kesselheim AS, Chisholm-Burns M, Finch CK, Spivey C, Carmichael JM, Meier J, Woller T, Pinto B, Bates DW, Hoffman JM, Armitstead JA, Segovia D, Dodd MA, Scott MA - American Journal of Health-System Pharmacy

  • Research Publications
| March 2021
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The ASHP Foundation’s 9th annual Pharmacy Forecast surveyed 272 pharmacy leaders and experts to identify emerging trends likely to affect health-system pharmacy practice, including the impact of COVID-19 on pharmacy operations, evolving technology and informatics needs, workforce challenges, and changing regulatory and reimbursement landscapes.
View Source

Paying for Prescription Drugs in the New Administration

Kesselheim AS, Hwang TJ, Avorn J - JAMA

  • Commentary & Opinion
| March 2021
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The authors outline drug pricing policy options for the Biden administration, including establishing inflation-based rebates for Medicare, creating a Drug Affordability Commission, implementing international reference pricing, and promoting generic and biosimilar competition to address the fact that US per capita drug spending is more than twice the average of comparable countries.
View Source

Why France Spends Less Than the United States on Drugs: A Comparative Study of Drug Pricing and Pricing Regulation

Raimond VC, Feldman WB, Rome BN, Kesselheim AS - Milbank Quarterly

  • Research Publications
| March 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The US spends significantly more per capita on prescription drugs than France, with Medicare potentially saving $5.1 billion annually on six high-expenditure drugs if it paid French prices. This difference is driven by France’s use of health technology assessment, value-based pricing, price regulation at drug launch, and restrictions on price increases. The authors recommend that the US adopt French regulatory approaches to drug pricing to control prescription drug spending.
View Source

Trends in Medicare Part D Inhaler Spending: 2012-2018

Feldman WB, Gagne JJ, Kesselheim AS - Annals of the American Thoracic Society

  • Research Publications
| March 2021
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Medicare Part D spent $39.7 billion on inhalers between 2012 and 2018, with spending growing 45.2% over the period. 88.4% of this spending was driven by increased utilization of combination long-acting maintenance inhalers rather than rising per-inhaler costs. These findings highlight that limited generic competition for inhalers, combined with growing use of expensive combination products, has been a major driver of Medicare respiratory drug expenditures.
View Source

Preventing Medical-Device-Borne Outbreaks: High-Level Disinfection Policy for Duodenoscopes

Mehrotra P, Weber DJ, Sarpatwari A - Infection Control and Hospital Epidemiology

  • Commentary & Opinion
| March 2021
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The authors examine outbreaks of antibiotic-resistant bacteria traced to contaminated duodenoscopes, describing the regulatory responses including enhanced post-market surveillance and revised reprocessing requirements, and argue that infection prevention must be more centrally integrated into the medical device regulatory framework.
View Source

Non-Warfarin Oral Anticoagulant Copayments and Adherence in Atrial Fibrillation: A Population-Based Cohort Study

Rome BN, Gagne JJ, Avorn J, Kesselheim AS - American Heart Journal

  • Research Publications
| March 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Higher copayments for non-warfarin oral anticoagulants were associated with significantly lower medication adherence and higher discontinuation rates among commercially-insured atrial fibrillation patients over one year of follow-up. Policies to reduce or cap cost-sharing for NOACs may improve medication adherence and clinical outcomes in this population.
View Source

Federal Spending on Off-Patent Drugs That Lack Generic Competition

Rome BN, Kesselheim AS - Journal of General Internal Medicine

  • Research Publications
| March 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 137 off-patent drugs lacking generic competition with available Medicare or Medicaid spending data, total post-rebate federal spending was approximately $1.6 billion in 2018, with the top 20 drugs accounting for 89% of that spending. Policies to increase competition or reduce prices could have saved $328 million to $1.3 billion. While such policies would meaningfully benefit patients who depend on these essential medicines, this cohort represents a relatively small share of the over $100 billion in annual federal drug spending, suggesting these interventions alone are unlikely to curb overall prescription drug expenditures.
View Source

Changes in Erythropoiesis Stimulating Agent Use Under a Risk Evaluation and Mitigation Strategy (REMS) Program

Sarpatwari A, He M, Tessema FA, Gagne JJ, Kesselheim AS - Drug Safety

  • Research Publications
| March 2021
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
This interrupted time-series analysis of commercial insurance claims data found that implementation and enforcement of a REMS program for erythropoiesis stimulating agents did not produce statistically significant changes in initiation rates for darbepoetin alfa or epoetin alfa among cancer patients, nor did it significantly reduce inappropriate use in patients with hemoglobin above 10 g/dL. The findings raise concerns about the effectiveness of this REMS program in improving safe prescribing practices for these drugs.
View Source

Associations Between Copays, Coverage Limits for Opioid Use Disorder Medications, and Prescribing in Medicaid, 2018

Barenie RE, Kesselheim AS, Tsacogianis T, Fischer MA - Medical Care

  • Research Publications
| March 2021
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
This cross-sectional study of 2018 Medicaid data found substantial state-level variation in use of medication for opioid use disorder (mOUD), but no significant associations between mOUD prescribing rates and copay requirements, copay amounts, or coverage limits. Further research is needed to examine other elements of benefit design that may impact access to mOUD treatment in Medicaid.
View Source

Assessing the Legality of Mandates for Vaccines Authorized via an Emergency Use Authorization

Parasidis E, Kesselheim AS - Health Affairs Forefront

  • Commentary & Opinion
| February 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The EUA statute requires that individuals be informed of “the option to accept or refuse” an authorized product and “the consequences, if any, of refusing,” but the most plausible legal interpretation limits “consequences” to health-related disclosures rather than authorizing mandates. Both legal and policy considerations, including the lower evidentiary standard for EUAs compared to full approval and heightened vaccine hesitancy among vulnerable populations, counsel against mandating COVID-19 vaccines until they receive full BLA approval.
View Source

The Future of Drug-Pricing Transparency

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

  • Commentary & Opinion
| February 2021
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
Amid the release of the Trump administration’s “Transparency in Coverage” Final Rule requiring disclosure of drug prices, the authors arguing that while drug-pricing transparency enjoys bipartisan support, key debates remain about whether disclosure of confidential rebates will empower payers to negotiate better prices or allow manufacturers to push net prices higher.
View Source

Market Exclusivity Length for Drugs with New Generic or Biosimilar Competition, 2012-2018

Rome BN, Lee CC, Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Research Publications
| February 2021
  • Innovation Incentives and Competition
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
From 2012-2018, market exclusivity periods were longer for biologic drugs than small molecule drugs (median 21.5 vs. 14.4 years), longer for drugs with annual revenue < $75 million compared with those with revenue ≥ $500 million (16.6 vs. 14.2 years), and shorter in cases for which the first generic was granted 180 days of exclusivity (14.1 vs. 15.9 years). Exceedingly long exclusivity periods, particularly for biologics, delay patient access to lower-priced medications, and the authors recommend that policymakers implement strategies to encourage timely generic and biosimilar competition.
View Source

Factors Affecting Buprenorphine Utilization and Spending in Medicaid, 2002-2018

Barenie RE, Sinha MS, Kesselheim AS - Value in Health

  • Research Publications
| February 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Brand-name buprenorphine-naloxone (Suboxone) formulations accounted for 2.7 times more prescriptions and 4.4 times higher spending than all other buprenorphine formulations combined in Medicaid from 2002-2018, with various market and regulatory factors delaying market entry of generic versions by 6-9 years. Earlier availability of affordable generic alternatives could have expanded access to buprenorphine treatment during the opioid crisis and reduced Medicaid expenditures.
View Source

Buprenorphine for Opioid Use Disorder: The Role of Public Funding in Its Development

Barenie RE, Kesselheim AS - Drug and Alcohol Dependence

  • Research Publications
| February 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Buprenorphine was developed for opioid use disorder over four decades with primarily through government and academic research, with an estimated $62.3 million in NIH awards supporting its development through pivotal studies and a formal government-industry partnership. Despite substantial public sector investment in buprenorphine’s development, the medication remains expensive and inaccessible to many patients, indicating a need to ensure affordable access to this effective, government-funded treatment.
View Source

Beyond the High Prices of Prescription Drugs: A Framework to Assess Costs, Resource Allocation, and Public Funding

Darrow JJ, Light DW - Health Affairs

  • Research Publications
| February 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The authors argue that the total societal cost of prescription drugs extends well beyond list prices, encompassing an accumulation of publicly funded mechanisms—including tax benefits, fee waivers, publicly funded basic and translational research, new exclusivities that delay competition, and government insurance programs that guarantee payment regardless of price. They propose a more comprehensive framework for assessing drug costs and recommend that Congress direct the Government Accountability Office to study public contributions underlying the highest-cost drugs and require manufacturers to periodically report the direct and indirect public funding they receive.
View Source

A Correlation Analysis to Assess Event-Free Survival as a Trial-Level Surrogate for Overall Survival in Early Breast Cancer

Gyawali B, D'Andrea E, Franklin JM, Kesselheim AS - eClinicalMedicine

  • Research Publications
| February 2021
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
This correlation analysis of seven randomized controlled trials found a moderate but non-significant association between treatment effects on event-free survival (EFS) and overall survival (OS) in early breast cancer. The authors conclude that while current evidence is insufficient to support EFS as a surrogate endpoint for traditional approval in early breast cancer, it may still be considered for accelerated approval pathways.
View Source

Op-Ed: Biden Can Lower Drug Prices Without Congress Doing Anything

Bloomfield D, Kesselheim AS - Washington Post

  • Commentary & Opinion
| January 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Talk bubble graphics representing commentary and opinion.
The Biden administration can meaningfully address high drug prices through executive action at the Patent and Trademark Office, without needing legislation. The authors contend that the PTO’s fee structure and time pressures incentivize examiners to grant weak secondary patents that enable brand-name manufacturers to build patent thickets blocking generic competition. They propose giving examiners more time and resources, revising guidance to make it easier to reject ineligible applications, and restructuring fees to eliminate the agency’s bias toward granting patents.
View Source

Repurposing Existing Drugs for New Uses: A Cohort Study of the Frequency of FDA-Granted New Indication Exclusivities Since 1997

Sahragardjoonegani B, Beall RF, Kesselheim AS, Hollis A - Journal of Pharmaceutical Policy and Practice

  • Research Publications
| January 2021
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 197 new drugs that subsequently experienced generic entry between 1997 and 2020, only 32% received at least one new indication added, with the probability of a new indication peaking above 4% at 7-8 years before generic entry and declining to near zero 15 years post-approval. The findings suggest that current indication-specific exclusivity periods are insufficient to incentivize drug repurposing, and policymakers should consider strengthening incentives to encourage clinical investigations for novel uses of existing drugs.
View Source

Public Funding for Transformative Drugs: The Case of Sofosbuvir

Barenie RE, Avorn J, Tessema FA, Kesselheim AS - Drug Discovery Today

  • Research Publications
| January 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The authors identified approximately $60.9 million in NIH funding that directly or indirectly supported the development of sofosbuvir (Sovaldi), with $7.7 million in direct awards and $53.2 million in indirect awards to academic institutions and companies involved in the drug’s creation. These findings demonstrate the key role of public funding in enabling this transformative hepatitis C treatment and the need for affordable access to government-supported therapeutics.
View Source

Generic Competition for Drugs Treating Rare Diseases

Beall RF, Quinn AE, Kesselheim AS, Tessema FA, Sarpatwari A - Journal of Law, Medicine & Ethics

  • Research Publications
| Winter 2021
  • Innovation Incentives and Competition
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 167 drugs approved with a rare disease indication between 1983 and 2017, only 42% of the 57 that were eligible for generic competition had a generic available, and just 50% of those with Orange Book–listed patents had been challenged, with both generic availability and patent challenges significantly associated with higher prescription volume. These findings suggest that drugs treating rare diseases face elevated risk of insufficient generic competition due to small market sizes, leaving patients vulnerable to high and rising prices for older, off-patent medications.
View Source

Ensuring Safe Access to Mifepristone During the Pandemic and Beyond

Brown BL, Wood SF, Sarpatwari A - Annals of Internal Medicine

  • Commentary & Opinion
| January 2021
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The FDA’s REMS program for mifepristone is not justified by the drug’s safety profile and creates access barriers, particularly for low-income and rural patients, that were exacerbated by the COVID-19 pandemic. The authors contend that the REMS requirements may paradoxically push patients toward later surgical abortions that carry greater risk.
View Source

Assessment of Variation in State Regulation of Generic Drug and Interchangeable Biologic Substitutions

Sacks CA, Van de Wiele VL, Fulchino LA, Patel L, Kesselheim AS, Sarpatwari A - JAMA Internal Medicine

  • Research Publications
| January 2021
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
This cross-sectional analysis of state drug product selection laws found substantial variation across US states in generic drug substitution requirements, with only 19 states mandating generic substitution for small-molecule drugs, 7 states requiring patient consent, and 45 states imposing more stringent requirements for interchangeable biologic substitution compared to generic small-molecule drugs. The authors conclude that state drug product selection laws should be optimized to better promote generic and biosimilar substitution in order to improve medication adherence and reduce drug spending.
View Source

An Overview of Vaccine Development, Approval, and Regulation, with Implications for COVID-19

Kesselheim AS, Darrow JJ, Kulldorff M, Brown BL, Mitra-Majumdar M, Lee CC, Moneer O, Avorn J - Health Affairs

  • Research Publications
| January 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.
The FDA approves vaccines through a standard evaluation process that weighs benefits against risks, and has established expedited pathways such as Emergency Use Authorization to accelerate vaccine availability. Among 35 new vaccines approved in the US from 2006 to October 2020, approximately two-thirds relied on surrogate immune response markers rather than actual disease incidence in their pivotal trials. Robust postapproval safety surveillance mechanisms are essential to detect adverse events that may warrant changes in vaccine recommendations or market withdrawal, and regulatory oversight must balance the need for speed with scientific rigor in addressing pandemic threats.
View Source

Social, Cultural and Economic Aspects of Antimicrobial Resistance

Minssen T, Outterson K, Rogers Van Katwyk S, Batista PHD, Chandler CIR, Ciabuschi F, Harbarth S, Kesselheim AS, Laxminarayan R, Liddell K, Osterholm MT, Price L, Hoffman SJ - Bulletin of the World Health Organization

  • Research Publications
| December 2020
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Antimicrobial resistance is an evolutionary challenge accelerated by social, cultural, and economic factors, including misuse of antimicrobials, inadequate sanitation infrastructure, and insufficient innovation incentives, that existing global efforts may be too slow to counter given the lack of political commitment and difficulty in balancing resistance with other priorities. The authors announce the creation of the International Network for Antimicrobial Resistance Social Science (INAMRSS) to champion interdisciplinary social science research as part of a One Health perspective, arguing that sustainable solutions require understanding the human behavioral drivers of resistance rather than relying solely on new antimicrobial discovery.
View Source

Reducing Prescription Drug Costs: Policy Options for a Public Plan

Hwang TJ, Kesselheim AS - Urban Institute

  • Research Publications
| December 2020
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
An analysis of three policy options for reducing prescription drug spending under a proposed Public Plan found that applying the basic Medicaid rebate (23.1%) would reduce net drug spending by 9–15% relative to private insurance, the total Medicaid rebate would achieve 46–49% savings, and the Big 4 agency rebate would yield 28–34% savings. These projections suggest that adopting existing public payer rebate structures could meaningfully lower drug costs for a Public Plan, though each option carries different trade-offs in administrative complexity and potential effects on other payers’ prices.
View Source

Heterogeneity of Antidiabetic Treatment Effect on the Risk of Major Adverse Cardiovascular Events in Type 2 Diabetes: A Systematic Review and Meta-Analysis

D'Andrea E, Kesselheim AS, Franklin JM, Jung EH, Hey SP, Patorno E - Cardiovascular Diabetology

  • Research Publications
| December 2020
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Both GLP-1 receptor agonists and SGLT-2 inhibitors demonstrated a 14% risk reduction in major adverse cardiovascular events among patients with established cardiovascular disease, but showed no significant benefit in at-risk patients without prior cardiovascular events, with trends toward greater benefits in patients with chronic kidney disease or uncontrolled diabetes. These findings suggest that antidiabetic treatment selection should consider baseline cardiovascular disease status, while chronic kidney disease and uncontrolled diabetes warrant further investigation as potential treatment effect modifiers.
View Source

Comparing Onset of Biosimilar Versus Generic Competition in the United States

Beall RF, Ronksley PE, Wick J, Darrow JJ, Sarpatwari A, Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Research Publications
| December 2020
  • Innovation Incentives and Competition
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Expected market exclusivity periods are similar for biologic and small molecule drugs in the US, with median expected entry dates of 12.3 years after FDA approval for biologics and 12.2 years for small molecule drugs, with biosimilar entry occuring in only 12% of cases compared to 65% for generic entry by 2019. Statutory exclusivity was found to play a more substantial role in market exclusivity protection for biologics than for small molecule drugs.
View Source

Efficacy and Costs of Spinal Muscular Atrophy Drugs

Darrow JJ, Sharma M, Shroff M, Wagner AK - Science Translational Medicine

  • Research Publications
| November 2020
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Despite being lauded as “dramatically effective” and “curative,” FDA review documents reveal that the two approved treatments for spinal muscular atrophy—nusinersen (Spinraza, $125,000 per injection for life) and onasemnogene abeparvovec (Zolgensma, $2,125,000 per infusion)—demonstrated benefits more modest than their public reception suggests, with treated patients showing only limited improvements from very low baseline motor function scores. These findings raise broader questions about the pricing and value assessment of rare disease medicines, particularly when clinical benefits are uncertain and costs are extreme.
View Source

A Qualitative Study of Biosimilar Manufacturer and Regulator Perceptions on Intellectual Property and Abbreviated Approval Pathways

Druedahl LC, Almarsdóttir AB, Kälvemark Sporrong S, De Bruin ML, Hoogland H, Minssen T, Van de Weert M, Kesselheim AS, Sarpatwari A - Nature Biotechnology

  • Research Publications
| November 2020
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Qualitative interviews with 25 participants, including EU national medicines regulators and pharmaceutical manufacturer employees, revealed that while trade secrets were generally viewed as surmountable barriers to biosimilar development, patents on manufacturing processes and formulations posed more significant obstacles, and abbreviated regulatory approval pathways have had mixed success in fostering price-lowering competition. Despite the creation of biosimilar pathways in both the US and EU, expected widespread price reductions have not materialized, with scientific, legal, and regulatory challenges continuing to limit biosimilar market entry and uptake.
View Source

Up Is Down—Pharmaceutical Industry Caution vs. Federal Acceleration of COVID-19 Vaccine Approval

Avorn J, Kesselheim AS - New England Journal of Medicine

  • Commentary & Opinion
| October 2020
  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The authors highlight the unusual role reversal in which pharmaceutical companies publicly pledged to wait for adequate trial data before seeking COVID-19 vaccine approval, while the federal government pushed for rapid authorization before the 2020 election. They analyze how conflicting pressures from clinical trial design, regulatory standards, and politics could shape approval decisions.
View Source

Comments on Implementation of Executive Order 13937, “Executive Order on Access to Affordable Life-Saving Medications.”

Bollyky TJ, Kesselheim AS - Health Resources and Services Administration (HRSA)

  • Policy Interactions
| October 2020
  • Price, Value, and Access
An icon of a bill representing government policy.
The commenters outline the history of failed efforts to legalize large-scale prescription drug importation from Canada, arguing that importation could be most effectively used to address generic drug shortages rather than to broadly lower brand-name drug prices.
View Source

Transferrable Market Exclusivity Extensions to Promote Antibiotic Development: An Economic Analysis

Rome BN, Kesselheim AS - Clinical Infectious Diseases

  • Research Publications
| October 2020
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Transferrable market exclusivity vouchers proposed in the 2018 REVAMP Act to encourage antibiotic drug development would result in median excess spending of $187 million per drug extended, totaling approximately $4.5 billion over 10 years, based on analysis of 10 qualifying antimicrobials matched to high-revenue drugs facing generic entry. The authors conclude that while market exclusivity extensions are a politically attractive policy mechanism to incentivize antibiotic development, this approach would impose substantial costs on public and private payers.
View Source

Producing and Using Timely Comparative Evidence on Drugs: Lessons From Clinical Trials for COVID-19

Naci H, Kesselheim AS, Røttingen J, Salanti G, Vandvik PO, Cipriani A - BMJ

  • Research Publications
| October 2020
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The COVID-19 pandemic exposed critical flaws in the evidence ecosystem for evaluating new treatments, with over 1,000 trials registered on ClinicalTrials.gov by mid-2020. Yet most featured fragmented designs, heterogeneous endpoints, disproportionate focus on hyped treatments like hydroxychloroquine, and fewer than one-third using randomized controlled designs. The authors call for greater collaboration among trialists, meta-analysts, and guideline developers to improve coordination, reduce redundancy, and ensure that the rush to produce evidence translates into robust comparative effectiveness data that can reliably guide clinical and regulatory decisions.
View Source

Accounting for US Public Funding in Drug Development: How Can We Better Balance Access, Affordability, and Innovation?

Sarpatwari A, Avorn J, Kesselheim AS - BMJ

  • Research Publications
| October 2020
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Despite industry claims that high drug prices are necessary to sustain innovation, the US government is the world’s largest single funder of biomedical research ($39 billion through NIH in 2019), contributing at some level to all 210 new drugs approved between 2010 and 2016, with approximately a quarter of small-molecule drugs having direct late-stage links to publicly supported institutions. The authors identify policy reforms, including strengthened march-in rights, reasonable pricing clauses, and greater transparency about public contributions, to help ensure that drugs arising from public funding are affordably accessible to patients.
View Source

Association Between FDA and EMA Expedited Approval Programs and Therapeutic Value of New Medicines: Retrospective Cohort Study

Hwang TJ, Ross JS, Vokinger KN, Kesselheim AS - BMJ

  • Research Publications
| October 2020
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 320 FDA-approved and 268 EMA-approved new drugs from 2007-2017, only 31% received high therapeutic value ratings from one of five health technology assessment organizations. Drugs approved under expedited review pathways were more likely to be highly rated than non-expedited drugs, while most expedited drugs approved by the FDA but not the EMA were rated as having low therapeutic value.
View Source

Regulatory Decision-Making on COVID-19 Vaccines During a Public Health Emergency

Avorn J, Kesselheim AS - JAMA

  • Commentary & Opinion
| October 2020
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Political pressure to rush COVID-19 vaccine approval, including through Emergency Use Authorizations, risks undermining both the scientific rigor of the evaluation process and public trust in vaccination. The authors draw parallels to earlier missteps with hydroxychloroquine and convalescent plasma to illustrate the dangers of politicizing regulatory decisions.
View Source

Using Real‐World Safety Data in Regulatory Approval Decisions: Sotagliflozin and the Risk of Diabetic Ketoacidosis

Fralick M, Kesselheim AS - Pharmacoepidemiology and Drug Safety

  • Commentary & Opinion
| October 2020
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The authors use sotagliflozin (a dual SGLT1/SGLT2 inhibitor) to illustrate how real-world safety data from related drugs already on the market can inform regulatory decisions for new medications under review, noting that diabetic ketoacidosis was an unanticipated adverse event with SGLT2 inhibitors that only became apparent through post-marketing surveillance.
View Source

Understanding When Real World Data Can Be Used to Replicate A Clinical Trial: A Cross‐Sectional Study of Medications Approved in 2011

Fralick M, Bartsch E, Darrow JJ, Kesselheim AS - Pharmacoepidemiology and Drug Safety

  • Research Publications
| October 2020
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 28 medications approved by the FDA in 2011, only 2 drugs (ticagrelor and linagliptin) had pre-approval clinical trials that could potentially be replicated using insurance claims databases, primarily because 79% of trials measured outcomes not captured in claims data such as patient-reported symptoms, imaging findings, and laboratory values. The authors conclude that when pre-approval trials meet the criteria for replication in claims databases, such real-world data studies could be valuable for assessing whether they produce concordant results.
View Source

Reputation and Authority: The FDA and the Fight Over U.S. Prescription Drug Importation

Bollyky TJ, Kesselheim AS - Vanderbilt Law Review

  • Research Publications
| October 2020
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
US prescription drug importation requires the FDA to recognize foreign regulatory equivalence, but the FDA has historically resisted making such determinations because it maintains its gatekeeping authority and “gold standard” reputation by oversee drug safety independently rather than relying on foreign regulators. The authors propose that the FDA could successfully use prescription drug importation to address generic drug shortages and identify other contexts where foreign regulatory cooperation would help fulfill the agency’s institutional mandates without compromising its reputation.
View Source

Origins and Ownership of Remdesivir: Implications for Pricing

Lee CC, Darrow JJ, Avorn J, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Research Publications
| Fall 2020
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Remdesivir—the first drug shown in a well-controlled trial to have activity against COVID-19—was developed through extensive public-private collaboration, with key contributions from the US Army Medical Research Institute of Infectious Diseases (USAMRIID), the CDC, NIH-funded institutions, and multiple academic universities, before Gilead Sciences set its price at $3,120 per treatment course for privately insured patients. The authors detail how federal funding and military research infrastructure were instrumental throughout remdesivir’s discovery and development, raising questions about whether the drug’s pricing adequately reflects these substantial public-sector contributions.
View Source

Implementing U.S. COVID-19 Testing: Regulatory and Infrastructural Challenges

Tan YT, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Commentary & Opinion
| Fall 2020
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The authors examine how delays in COVID-19 testing authorization and rollout in the U.S., including the FDA’s initial restriction of testing to CDC-developed assays and slow Emergency Use Authorization process, significantly hampered the pandemic response.
View Source

Drug Shortages and the Defense Production Act

Raunig BL, Kesselheim AS, Darrow JJ - American Journal of Public Health

  • Research Publications
| October 2020
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
During the COVID-19 pandemic, US hospitals faced critical shortages of sedatives, neuromuscular blocking agents, opioids, antibiotics, and bronchodilators needed to treat patients, and while the Trump administration invoked the Defense Production Act (DPA) for ventilators and personal protective equipment, its application to drug shortages presents greater challenges. The authors outline how the DPA’s authorities could be deployed to address pharmaceutical supply chain vulnerabilities, while noting that statutory limitations to domestic industry and the complexity of drug manufacturing require additional government interventions beyond DPA authority alone.
View Source

Clinical Development Times for Biosimilars in the United States

Lee CC, Kesselheim AS, Sarpatwari A - Mayo Clinic Proceedings

  • Research Publications
| October 2020
  • Innovation Incentives and Competition
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Biosimilars approved in the US required a median of 69.9 months from phase I initiation to approval, with most undergoing phase III testing averaging 22 months in length. The extensive clinical development requirements impose a high testing bar that likely restricts market entry and limits the competitive benefits biosimilars could provide in reducing drug spending.
View Source

Clinical Benefit and Cost of Breakthrough Cancer Drugs Approved By the US Food and Drug Administration

Molto C, Hwang TJ, Borrell M, Andres M, Gich I, Barnadas A, Amir E, Kesselheim AS, Tibau Martorell A - Cancer

  • Research Publications
| October 2020
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Among 106 trials supporting 52 cancer drug approvals, breakthrough-designated drugs showed higher odds of clinically meaningful benefit scores on the ASCO Value Framework and NCCN Evidence Blocks but not on the ASCO-CRC or ESMO-MCBS scales, while median costs of breakthrough drugs were significantly higher than nonbreakthrough drugs. The findings suggest that breakthrough designation is inconsistently associated with greater clinical benefit by validated frameworks, with these drugs commanding substantially higher prices despite mixed evidence of superiority.
View Source

An International Review of Health Technology Assessment Approaches to Prescription Drugs and Their Ethical Principles

Rand LZG, Kesselheim AS - Journal of Law, Medicine & Ethics

  • Research Publications
| Fall 2020
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
A review of health technology assessment (HTA) methods across six countries (Australia, Canada, France, Germany, Japan, and the UK) found significant differences in evaluation methodologies, interpretation of findings, and condition-specific exceptions, all of which influence drug pricing and coverage recommendations. The authors argue that US proposals to link domestic drug prices to these countries’ assessments should carefully consider the ethical implications of relying on HTA frameworks shaped by distinct political, social, and cultural values.
View Source

Op-Ed: Increase Transparency at the FDA: We Need Sunlight to Fight the Pandemic

Bendicksen L, Sharfstein JM, Kesselheim AS - STAT

  • Commentary & Opinion
| September 2020
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The FDA’s lack of transparency in its COVID-19 regulatory decisions has eroded public trust at a critical moment. The authors propose four specific reforms: timely public explanations of clinical holds, disclosure of reviews for products that fail to win approval, release of the full scientific basis for emergency authorizations, and sharing of pooled de-identified clinical datasets with qualified researchers to accelerate therapeutic development.
View Source

Getting the Right Evidence After Drug Approval

Vreman RA, Leufkens HGM, Kesselheim AS - Frontiers in Pharmacology

  • Commentary & Opinion
| September 2020
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
Post-approval evidence generation (particularly comparative effectiveness data) should be prospectively planned and linked to value-based pricing and reimbursement decisions, to ensure that drugs approved with limited pre-market evidence are adequately evaluated in real-world settings.
View Source

US Spending Associated with Transition From Daily to 3-Times-Weekly Glatiramer Acetate

Rome BN, Tessema FA, Kesselheim AS - JAMA Internal Medicine

  • Research Publications
| September 2020
  • Innovation Incentives and Competition
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
The 2014 launch of a 3-times-weekly formulation of glatiramer acetate (Copaxone) delayed generic competition for the daily version by 2.5 years, resulting in excess US spending of $4.3 billion to $6.5 billion from 2015 to 2017, as quarterly spending remained around $962 million following this “product hop” despite the entry of generic daily formulations. Extended market exclusivity from introducing a new version of an existing brand-name drug can yield manufacturer returns out of proportion to the level of investment or risk involved; more limited incentives could encourage incremental innovations to existing drugs at a lower societal cost.
View Source

Projected Spending for Brand-Name Drugs in English Primary Care Given US Prices: A Cross-Sectional Study

Liu M, MacKenna B, Feldman WB, Walker AJ, Avorn J, Kesselheim AS, Goldacre B - Journal of the Royal Society of Medicine

  • Research Publications
| September 2020
  • Price, Value, and Access
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
If the National Health Service (NHS) in England had paid US Medicare Part D prices for the 50 most expensive brand-name drugs in primary care, spending would have increased from £1.39 billion to £6.42 billion (a 4.6-fold increase), with US-England price ratios ranging from 1.3 to 9.9. The authors conclude that adopting US drug prices could substantially reduce NHS England’s ability to fund medicines and other health services.
View Source

Need for Transparency and Reliable Evidence in Emergency Use Authorizations for Coronavirus Disease 2019 (COVID-19) Therapies

Zhai MZ, Lye CT, Kesselheim AS - JAMA Internal Medicine

  • Commentary & Opinion
| September 2020
  • Regulation and Clinical Evidence
Talk bubble graphics representing commentary and opinion.
The authors critique the FDA’s Emergency Use Authorization for hydroxychloroquine and chloroquine for COVID-19, noting that unlike the earlier EUA for peramivir during the H1N1 pandemic, the hydroxychloroquine EUA lacked reliable clinical evidence and adequate transparency in the agency’s decision-making.
View Source

Challenging Patents to Promote Timely Generic Drug Entry: The Second Look Act and Other Options

Bendicksen L, Darrow JJ, Kesselheim AS - Health Affairs Forefront

  • Commentary & Opinion
| August 2020
  • Innovation Incentives and Competition
Talk bubble graphics representing commentary and opinion.
The Second Look Act would increase awareness of inter partes review as a faster, cheaper alternative to court litigation for challenging improperly issued drug patents, leveraging a more favorable evidentiary standard and expert patent judges at the PTAB. However, the bill’s impact is likely limited since it does not change existing processes, and more impactful reforms would include reducing the 30-month litigation stay, shifting the burden of proof to patent holders, or restricting which patents trigger automatic stays of generic approval.
View Source

False Negative Tests for SARS-CoV-2 Infection—Challenges and Implications

Woloshin S, Patel NG, Kesselheim AS - New England Journal of Medicine

  • Research Publications
| August 2020
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
While much debate about COVID-19 testing focused on test availability and antibody test accuracy, the authors highlight that false negative results from diagnostic RT-PCR tests may prove a larger long-term problem for containment efforts. The analysis examines how FDA Emergency Use Authorization validation methods, including the use of contrived specimens and known positive samples rather than natural clinical specimens with independent adjudication, may overestimate test sensitivity, with significant implications for public health strategies relying on testing to reopen society.
View Source

Preferences for and Experiences with Pill Appearance Changes: National Surveys of Patients and Pharmacists

Barenie RE, Kesselheim AS, Gagne JJ, Lu Z, Campbell EG, Dutcher SK, Jiang W, Sarpatwari A - American Journal of Managed Care

  • Research Publications
| August 2020
  • Price, Value, and Access
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Surveys of 1,000 patients and 710 pharmacists found that while most patients experienced changes in generic pill appearance and strongly preferred to be notified, fewer than half recalled receiving notification, and 12% of those experiencing a change reported stopping or reducing their medication as a result. A significant perception gap also emerged, with most pharmacists reporting they frequently notify patients about appearance changes, suggesting a disconnect between pharmacist communication efforts and patient recall that represents an important target for improvement.
View Source

Internet Searches for Unproven COVID-19 Therapies in the United States

Liu M, Caputi TL, Dredze M, Kesselheim AS, Ayers JW - JAMA Internal Medicine

  • Research Publications
| August 2020
  • Regulation and Clinical Evidence
Simple graphic of magnifying glass examining papers to signify reviewing research publications.
Following high-profile endorsements of chloroquine and hydroxychloroquine as COVID-19 treatments in March 2020, Google searches indicative of shopping for these drugs surged (442% higher for chloroquine and 1,389% higher for hydroxychloroquine) despite no reliable clinical evidence of efficacy and known cardiovascular toxicity risks. The findings demonstrate how prominent public endorsements of unproven therapies during a pandemic can rapidly drive dangerous consumer behavior, underscoring the need for responsible public health communication.
View Source

Program On Regulation, Therapeutics, And Law (PORTAL)
Division of Pharmacoepidemiology and Pharmacoeconomics
Brigham and Women's Hospital • Harvard Medical School
41 Avenue Louis Pasteur, Suite 0B17, Boston, MA 02115

©2026 Program On Regulation, Therapeutics, And Law (PORTAL). All rights reserved.