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Trade-dress protections in trademark law grant drug manufacturers legal exclusivity over pill characteristics such as size, shape, and color, which the authors identify as creating potential adverse public health effects. The authors propose strategies to mitigate these negative consequences of trade-dress protection in the pharmaceutical industry.

Orphan cancer drugs approved between 2004 and 2010 had pivotal trials with significantly smaller sample sizes compared to trials for non-orphan drugs, were less likely to be randomized or double-blinded, and more frequently reported serious adverse events. These findings suggest that the regulatory pathway for orphan drugs relies on less rigorous trial designs and surrogate endpoints, raising questions about the adequacy of evidence supporting their approval relative to nonorphan cancer drugs.

Off-label drug use accounts for approximately 21% of prescriptions overall, yet 73% of off-label uses lack evidence of clinical efficacy. The FDA’s blanket prohibition on manufacturer promotion of these unapproved uses faces growing legal challenge under the commercial speech doctrine, as courts have increasingly applied the Central Hudson test to side with manufacturers’ First Amendment claims. The author proposes a “scaled oversight” framework that would replace the current all-or-nothing approach by categorizing off-label uses into subtypes (genotypic, phenotypic, and dosing variants) and providing expedited FDA review for biologically plausible extensions while maintaining stricter requirements for more substantial departures from approved uses.

This systematic review of 32 studies found that 40%-100% of medical students are exposed to pharmaceutical industry marketing, with 13%-69% believing such gifts influence prescribing, and Substantial pharmaceutical marketing exposure during medical education is associated with positive attitudes toward these interactions, and the authors recommend further research into the factors that shape students’ attitudes of the pharmaceutical industry during their training.

The US Supreme Court’s 2011 ruling in Bruesewitz v. Wyeth granted vaccine manufacturers immunity from design defect lawsuits, a decision supported by physicians and public health organizations who argue it ensures vaccine availability and appropriate use, while critics raise concerns about patient rights and accountability. The case highlights the tension between protecting vaccine supply and addressing the market position of vaccines as essential public health products subject to different liability standards than other consumer goods.

The authors highlight the pervasive problem of off-label drug prescribing unsupported by evidence, using recombinant factor VIIa as a case study. They argue that the gap between FDA approval requirements and the freedom physicians have to prescribe off-label creates significant safety and cost concerns.

Analysis of 41 whistleblower complaints from US federal fraud cases revealed that pharmaceutical off-label marketing schemes most commonly sought to expand drug use to unapproved diseases (85%), unapproved disease subtypes (54%), and unapproved doses (34%), relying heavily on prescriber-targeted practices such as financial incentives to physicians (85%) and self-serving literature presentations (76%). The findings suggest that off-label marketing pervades multiple areas of the health care system, with the most prevalent practices also being the hardest to regulate through external oversight.

This appendix to a National Academies report reviews the regulatory and clinical characteristics of 279 drugs approved under the Orphan Drug Act from 1983 to 2009, finding that most were approved for oncology-related conditions, roughly a third were truly novel molecular entities, and many were approved on the basis of small, sometimes unblinded trials using surrogate endpoints. The analysis also found that orphan drug designation often occurred late in clinical development and that a substantial share of approved orphan drugs targeted conditions for which alternative therapies already existed.

An analysis of 5.6 million prescriptions found that 2.7% were designated dispense as written (DAW) by physicians and 2.0% by patients, with significant variation by medication class, patient and physician age, geographic region, and specialty. Specialists had 78.5% greater odds of requesting DAW than generalists. Both physician and patient DAW requests were associated with significantly higher odds of patients not filling their prescriptions, suggesting that reducing DAW rates could both lower costs and improve medication adherence.

The authors examine the challenges facing antibiotic markets, where the unique dynamics of antimicrobial resistance combined with the need for stewardship that limits the volume of new antibiotic prescriptions create commercial disincentives for development that standard market-based approaches fail to address. They propose reforms to improve antibiotic market sustainability through mechanisms that delink revenues from sales volume, ensuring adequate returns for innovative products while preserving their long-term effectiveness through appropriate use.

Among 546 hypertrophic cardiomyopathy patients surveyed, only 46% had completed advance directives and 51% had healthcare proxies, with Cardiac Implantable Electrical Devices (CIEDs) rarely addressed in either document. Additionally, 29% of respondents characterized pacemaker deactivation as euthanasia and over 50% expressed uncertainty about the legality of device deactivation. The authors conclude that patients with CIEDs require improved advance care planning and education regarding the ethical and legal options for managing these devices at end of life.

The author discusses the role of free “controlled-circulation” medical journals, funded entirely by advertising revenue and distributed without subscription, as potential vehicles for covert pharmaceutical promotion, arguing that their business model creates vulnerability to biased content that may inappropriately influence prescribing behavior.

The authors discuss whether Medicare and Medicaid should reimburse phosphodiesterase inhibitor drugs for erectile dysfunction, which cost over $1 billion annually worldwide, by analyzing the justifications and arguments for and against coverage as case studies. They conclude that coverage decisions should be based primarily on clinical effectiveness and cost considerations rather than moral attitudes toward sexual performance.

Pharmaceutical companies are using social media platforms like Facebook and Twitter for drug marketing, raising concerns that existing FDA regulations governing drug promotion are inadequate to address the unique challenges of digital and social media marketing, including user-generated content and the blurring of promotional and educational messaging.

The traditional pharmaceutical business model—which incentivizes companies to maximize antibiotic sales before patents expire—accelerates the development of drug-resistant infections. The authors propose restructuring antibiotic economics by pricing new antibiotics higher to reflect their true societal value, but conditioning continued marketing exclusivity on meeting government-set conservation and resistance targets, thereby aligning manufacturers’ financial incentives with public health goals of antibiotic stewardship. They also advocate for a Strategic Antibiotic Reserve to preserve the most valuable new antibiotics for future use.

The author examines how federal laws offering extended market exclusivity have been used to incentivize pharmaceutical innovation, while identifying the unintended consequences of these policy mechanisms. More carefully designed regulations are necessary to effectively balance the goal of promoting drug development with the need for affordable, accessible medications.

A survey of 185 internal medicine physicians found they were significantly less experienced with and less comfortable discussing withdrawal of pacemakers and defibrillators compared to other life-sustaining therapies. Only 34% had participated in device withdrawal versus 86% for mechanical ventilation and 74% for feeding tubes, and many mischaracterized the practice, with 19% labeling pacemaker deactivation as physician-assisted suicide and 9% as euthanasia. Compounding these gaps, only 65% correctly identified the legal status of euthanasia and just 20% accurately reported the legal status of physician-assisted suicide in the US, underscoring a significant need for education on end-of-life device management.

An analysis of prior comparative effectiveness research identified key methodological challenges in 3 areas that have limited the clinical applicability of such studies: choice of comparison treatments, study time frames, and generalizability of results. The authors recommend strategies to improve future research, including the use of surrogate endpoints that meet specific validity thresholds, to maximize the potential of comparative effectiveness studies to improve patient outcomes.

The authors question the feasibility and cost-effectiveness of the proposal to develop 10 new antibiotics by 2020, arguing that without reforms to clinical trial design and post-approval stewardship, simply incentivizing new antibiotic development could cost billions while failing to address resistance.

Traditional financial incentives for antibiotic development, such as patent extensions, conflict with the critical need to reduce unnecessary antibiotic prescriptions and may actually increase inappropriate use. The authors recommend a two-pronged strategy that ties increased reimbursement to both appropriate, evidence-based antibiotic use and achievement of specific public health goals, including reducing disease burden while limiting risk of antimicrobial resistance.

States with generic substitution policies requiring patient consent prior to switching from brand-name to generic medications experienced 25 percent lower substitution rates, while eliminating such consent requirements could save state Medicaid programs more than $100 million in coverage for three major medications approaching patent expiration. Policymakers should weigh concerns of patient choice against the substantial cost savings that could be achieved by removing consent requirements for generic substitution.

The authors identify various types of financial and nonfinancial conflicts of interest that arise in healthcare delivery and examine policy options designed to address these conflicts while balancing transparency, patient safety, and the benefits of industry-provider relationships. Effective conflicts of interest policies must account for both the need to protect patients through disclosure mechanisms and the recognition that some industry relationships are important to medical product development.

The authors describe how colchicine—a 3,000-year-old gout treatment that had never been formally FDA-approved—received market exclusivity after a manufacturer conducted modest confirmatory studies, leading to dramatic price increases that paradoxically punished patients who had been using the drug safely for decades.

The author analyzes the Supreme Court’s contrasting rulings on federal preemption for drugs (Wyeth v. Levine) versus devices (Riegel v. Medtronic), arguing that allowing product liability litigation for FDA-approved products serves important public health functions by uncovering safety data, correcting manufacturer behavior, and complementing the FDA’s limited post-market surveillance authority.

The authors discuss the evolving legal landscape around gene patenting, examining a district court ruling that challenged the patentability of human genes and analyzing whether this represented a shift in the courts’ approach to intellectual property protections for genetic discoveries.

Whistle-blowers who initiated successful qui tam cases against pharmaceutical companies for health care fraud experienced substantial personal hardships throughout litigation that averaged 5 years in duration, despite receiving a median settlement of $3 million. The findings suggest that while financial compensation is substantial, the personal costs of whistleblowing in pharmaceutical fraud cases warrant consideration in future policy discussions on whistleblower protections.

A meta-analysis of seven randomized controlled trials found no significant difference in seizure control between patients taking brand-name antiepileptic drugs and those taking generic alternatives, though observational studies suggested possible utilization changes were attributable to patient or physician concerns about generic effectiveness. Physicians should consider intensive monitoring of high-risk patients when switching antiepileptic drugs, but the available evidence does not support the superiority of brand-name formulations over bioequivalent generics.

The author discusses the implications of the Supreme Court’s decision in Bilski v. Kappos for process patents in the pharmaceutical context, examining how patent law intersects with medical innovation and drug development policy.

The authors argue that proposed legislation granting 12 years of market exclusivity for biologic drugs—far longer than the 5 years provided for small-molecule drugs under the Hatch-Waxman Act—is excessive and would delay competition from biosimilar products while generating substantial costs for patients and the healthcare system.

Despite the pharmaceutical industry’s claims that its research is primarily responsible for new medicines, an analysis of drug innovation found that while industry generates a greater volume of drug-related patents, those originating from non-profit research institutions appear to hold greater importance, underscoring the significant role of publicly funded research in driving drug development. This finding emerged amid concerns about declining FDA approvals, which fell to just 22 new molecular entities and biologics in 2007 (the lowest in 24 years), even as industry revenues continued to rise and regulatory review times remained stable.

The FDA should adopt a presumption that safety and efficacy data submitted in drug applications should be made publicly available at the earliest possible time, including clinical study reports and FDA reviewer analyses, to enable independent scientific evaluation and strengthen the quality of agency decisions.

The priority review voucher program—designed to incentivize development of neglected-disease drugs by rewarding manufacturers with expedited FDA review for a subsequent product—is cost-ineffective, unlikely to yield meaningful results, and potentially dangerous because it accelerates review of drugs that may not warrant expedited treatment.

Avorn argues that physicians and patients lack the comparative information needed to choose among treatments because FDA approval only requires a drug to beat placebo, not to demonstrate superiority over existing alternatives, and manufacturers have the incentive to suppress unfavorable findings. He calls for government-funded comparative effectiveness research as a public good and proposes pairing it with academic detailing, citing programs he established in Pennsylvania, Massachusetts, and DC.

The authors outline the Supreme Court’s ruling in Wyeth v. Levine, examining whether FDA approval of a drug’s labeling should preempt state product liability lawsuits, and discussing the implications for patient safety and manufacturer accountability.

The authors examine alternative policy mechanisms to reduce Medicare prescription drug costs beyond direct government price negotiation, including value-based pricing, generic substitution expansion, formulary diversity, drug importation, and limited antitrust waivers. These alternative approaches could potentially reduce federal spending on Part D drugs without requiring changes to the current noninterference provision that restricts Medicare’s negotiating authority.

As developing countries implement pharmaceutical patent laws required by the WTO’s TRIPS agreement, engaging outside experts in the patent review process is critical to prevent the granting of unmerited patents that can sustain high prices for essential medicines, as demonstrated by case studies including the antiretroviral tenofovir disoproxil fumarate. The authors argue that patent review systems in resource-poor countries require information-sharing among developing nations and active consultation with local public health authorities to balance legitimate intellectual property protection with access to affordable drugs.

A systematic review and meta-analysis of 47 articles found clinical equivalence between generic and brand-name cardiovascular drugs across multiple drug classes, indicating no superiority of brand-name drugs. The findings support the clinical interchangeability of generic and brand-name cardiovascular medications, suggesting that generic drugs can be safely used to reduce prescription drug spending without compromising clinical outcomes.

The FDA’s priority review voucher program provides expedited review to companies that develop drugs for neglected tropical diseases (NTDs), but this mechanism is an inefficient and potentially dangerous approach to incentivizing research in this area. The program’s current design fails to adequately address the underlying challenges in NTD drug development and may pose risks to the integrity of the FDA’s review process.

Between 1996 and 2005, 379 unsealed federal qui tam cases recovered $9.3 billion in health care fraud settlements, with whistleblowers receiving over $1.0 billion and pharmaceutical companies accounting for disproportionately large recoveries ($3.6 billion across 13 cases). The findings demonstrate that whistleblower-initiated enforcement actions are a critical mechanism for detecting and prosecuting health care fraud.

The amici argue that state failure-to-warn litigation plays a critical role in promoting drug safety by supplementing the FDA’s limited post-market surveillance capabilities, deterring manufacturers from downplaying safety risks, and facilitating the diffusion of new information about drug effects. They rebuts petitioner’s claims that the FDA is overly cautious in drug labeling, contending instead that empirical evidence shows the FDA faces significant pressures for faster approvals and that state tort liability complements, rather than distorts, the federal regulatory regime.

Global disparities in access to essential medicines stem from multiple factors including high product costs, inadequate government and aid agency cooperation, rigid intellectual property protections, and weak local health leadership, while pharmaceutical innovation has disproportionately focused on developed country health problems. The US can help address these disparities by working with international organizations like the WHO and Médecins Sans Frontières to strengthen pharmaceutical delivery systems in low- and middle-income countries.

Kesselheim argues against federal preemption of failure-to-warn lawsuits against drug manufacturers, explaining that FDA approval cannot fully certify ongoing drug safety and that manufacturers face inherent conflicts of interest in collecting and reporting post-market safety data. Citing Vioxx and Baycol as examples where manufacturers misrepresented safety findings and delayed reporting adverse signals, he contends that litigation plays an essential oversight role by bringing data to light, deterring improper conduct, and revealing gaps in FDA regulation. Read his written testimony.

Legal restrictions on off-label drug promotion, which are being challenged as First Amendment violations, are justified because pharmaceutical promotion presents unique public health concerns that distinguish it from other commercial speech. Courts should permit more stringent regulation of pharmaceutical promotion despite First Amendment protections for commercial speech.

The authors discuss the feasability of US importation of prescription drugs from foreign markets. While individual importation of essential medicines from certain regulated international markets may be reasonable, they recommend that the most effective domestic strategy for reducing prescription drug costs is increased use of available generic drugs rather than large-scale importation of branded products.

The authors challenge three common arguments used to explain inadequate vaccine access in low-income countries—the primacy of infrastructure, insufficient funding, and the need for prior approval in wealthy nations—arguing that each can be overcome with targeted policy interventions. They contend that vaccination programs can themselves strengthen health infrastructure and that mechanisms like advance market commitments and tiered pricing can address funding and access gaps.

Avorn describes how pharmaceutical sales representatives dominate physicians’ drug information environment, driving prescribing toward heavily promoted and expensive products rather than the safest or most cost-effective options, as seen with Vioxx, Avandia, and Vytorin. He advocates for academic detailing as an alternative, citing randomized trial evidence and analysis of Pennsylvania’s PACE program showing that such programs improve prescribing and save roughly $2 for every $1 invested. Read his written testimony.

With recombinant protein drugs (biologics) costing $15,000-$150,000 per year and patents expiring on products representing over $15 billion in annual costs, no general mechanism existed under US federal law for approving “follow-on” protein products, unlike the established pathway for small-molecule generics, allowing manufacturers to sustain high prices even after patent expiration. The authors evaluate the scientific feasibility and policy considerations for creating a follow-on biologics approval pathway, noting that alternative versions could offer savings of at least 10-30% while maintaining high standards of safety.

While HPV vaccines hold great promise for preventing cervical cancer, 93% of related mortality occurs in low- and middle-income countries where high costs limit access, and existing mechanisms like differential pricing and advance market commitments have had only partial success. The authors propose a new licensing model that would leverage generic competition to lower prices in these countries while still ensuring pharmaceutical manufacturers receive appropriate returns on their research and development investments.

This book chapter examines the intersection of patent law and public health, analyzing how patents affect health care costs, access to therapeutics, medical practice, and the direction of medical research. The authors propose a range of regulatory, legislative, and market-based reforms to better balance the promotion of innovation with the protection of public health.

This quantitative study of 85 medication container labels from pharmacies across four cities found that label formatting prioritizes pharmacy identification over medication instructions and warnings, with substantial variability in warning and instruction stickers across pharmacy types. The authors conclude that current labeling practices inadequately emphasize patient safety information and recommend reformatting labels to prioritize use instructions and warnings while standardizing sticker content across pharmacies.

While patents promote pharmaceutical innovation, inappropriate patents that stretch statutory requirements and legal extensions of market exclusivity create monopolistic control that limits patient options, increases healthcare costs, and hinders collaborative research. Government and market-based interventions are necessary to develop more equitable patent policies that balance innovation incentives with broader dissemination of ideas and more affordable healthcare delivery.

Pharmaceutical manufacturers classify clinical trial results as confidential trade secrets even after FDA submission, and courts have limited Freedom of Information Act access to this data, yet cases of approved drugs later found to have serious side effects demonstrate the critical need for complete safety information disclosure. The authors recommend regulatory and legislative policy changes to how the FDA manages confidential information in order to enhance public understanding of prescription drug risks.

Product liability litigation plays a valuable role in the drug safety system by uncovering previously unavailable data about adverse effects through the discovery process, filling gaps left by the FDA’s limited post-market surveillance authority and correcting misleading manufacturer communications about risks and benefits.

Medical-process patents—which claim proprietary rights over methods of diagnosis or treatment, such as a patent on diagnosing vitamin deficiency based on homocysteine levels at issue in the Supreme Court case LabCorp v. Metabolite Laboratories—threaten to complicate medical practice, increase costs, and restrict access to procedures, with the AMA declaring that they compromise patient access. The authors examine the growing controversy over medical-process patents, noting that while US law allows them unlike nearly 80 other countries, Congress curtailed enforcement consequences for physicians in 1996, and the LabCorp case highlighted ongoing tensions between intellectual property rights and the delivery of health care.

Extensions of intellectual property rights, elevated generic drug prices, and low substitution rates delayed generic adoption by an average of twenty-six months for amoxicillin/clavulanate, metformin, and omeprazole, costing Medicaid $1.5 billion between 2000 and 2004. Policymakers should consider reforms to intellectual property protections and strategies to accelerate generic substitution to reduce unnecessary Medicaid expenditures on prescription drugs.

Using nesiritide (Natrecor) for congestive heart failure as a case study, this article examines how FDA approval standards, pharmaceutical marketing practices, and physicians’ prescribing decisions can shape the risk-benefit profile of widely used drugs. The authors draw policy lessons from the Natrecor experience and propose reforms to drug approval, postmarketing surveillance, and drug utilization to better protect patient safety.

The authors explore whether the legal concept of eminent domain could be applied to biomedical patents when restrictive patent management threatens public health, citing historical examples including wartime vitamin D patents, ciprofloxacin during the anthrax scare, and HIV drug pricing.

University-based biomedical innovation relies on patents to allocate ownership and control, but excessive upstream patenting of genes and molecular targets can hinder follow-on research through costly cross-licensing, while limiting such patents risks allowing private firms to commercialize publicly funded discoveries without compensating academic innovators. Drawing on recent court cases, the article examines this tension and proposes mechanisms such as basic science patent pools and mandatory arbitration to balance rewards for foundational discoveries in the public sector with incentives for continued biomedical innovation.

The authors analyze how the Supreme Court reversed its prior expansive interpretation of ERISA preemption of state-law claims against managed care organizations, marking a significant shift in the legal landscape governing patients’ ability to sue health plans for denials of care. This jurisprudential reversal has important implications for the balance between federal uniformity in employee benefit plan regulation and state-level protections for patients in managed care settings.