Patient Assistance Programs-A New Era of Law and Policy.

This Viewpoint from authors at PORTAL discusses the importance of patient assistance programs in covering the cost of prescription drugs, highlights 2 recent rulings that illustrate the substantial barriers to regulating these programs, and calls for continued evaluation of these programs' effectiveness and costs.

US Food and Drug Administration's Directive to Deal With Delayed Confirmatory Trials: Lessons From Pralatrexate and Belinostat for T-Cell Lymphoma.

The FDA's directive to deal with delayed confirmatory trials: lessons from pralatrexate and belinostat for T-cell lymphoma.

The Origins of "Confidential Commercial Information" at the FDA.

This Viewpoint reviews regulations regarding FDA's handing of confidential commercial information, explains how these regulations serve as a barrier to disclosure of information in the interest of public health, and suggests how information could be carefully shared to improve health outcomes and advance research.

Federal Trade Commission Actions on Prescription Drugs, 2000-2022.

Importance: The Federal Trade Commission's (FTC) oversight role in the pharmaceutical market is critical to the health of patients and the health care system. This study characterized the FTC's policy on the pharmaceutical market in recent decades, identifying the types of actions it has favored, barriers it has faced, and authorities that remain untested. Objective: To review FTC legal actions in the pharmaceutical market from 2000-2022. Evidence Review: Legal actions were determined through manual review of search results from the FTC's online Legal Library as well as a 2023 FTC report on pharmaceutical actions. The alleged misconduct, type of legal action taken, timing, and outcome were collected from press releases, complaints, orders, and other legal documents. Findings: From 2000-2022, the FTC challenged 62 mergers, brought 22 enforcement actions against allegedly unlawful business practices, and made 1 rule related to pharmaceuticals. Alleged misconduct in enforcement actions involved anticompetitive settlements in patent litigation (n = 11), unilateral actions by brand manufacturers to delay generic competition (n = 6), noncompete agreements (n = 4), and monopolization (n = 3), with 10 outcomes involving monetary payment, totaling $1.6 billion. Of the 62 mergers the FTC challenged, 61 were allowed to continue, 58 after divesting certain drugs to third-party competitors. The FTC's reliance on drug divestitures decreased from 18 drugs per year from 2000-2017 to 4.3 per year from 2017-2023. Conclusions and Relevance: The FTC brought about 1 enforcement action and 3 merger actions per year against pharmaceutical manufacturers from 2000-2022, pursuing a small fraction of the estimated misconduct and consolidation in the pharmaceutical marketplace. Although the FTC faces substantial legal and practical limitations, important tools remain untested, including a rule defining "unfair methods of competition," that may allow it to more effectively prevent repetitive patterns of anticompetitive behavior.

Federal Enforcement of Pharmaceutical Fraud under the False Claims Act, 2006-2022.

CONTEXT: The False Claims Act is the US federal government's primary tool for identifying and penalizing pharmaceutical fraud. The Department of Justice uses the False Claims Act to bring civil cases against drug manufacturers that allegedly obtain improper payment from federal programs. METHODS: The authors searched the Department of Justice website for press releases published between 2006 and 2022 that announced fraud actions brought against drug companies. They then used the World Health Organization's Anatomical Therapeutic Classification index to identify the classes of prescription drugs implicated in fraud actions. FINDINGS: During fiscal years 2006-2022, payments by six manufacturers amounted to more than 28% of total payments made as a result of federal False Claims Act actions. Nervous system and cardiovascular drugs were the classes of medications most commonly implicated in alleged fraud. Federal officials most frequently alleged that companies improperly promoted nervous system drugs and paid kickbacks to increase revenues from cardiovascular, antineoplastic and immunomodulating, and alimentary tract and metabolism drugs. CONCLUSIONS: Despite frequent pharmaceutical fraud settlements and penalties, incidence of alleged fraud among drug companies remains high. Alternative methods for preventing and deterring fraud could help safeguard our health systems and promote public health, and policy makers should ensure that effective fraud enforcement complements preventive public health regulation.

Inequitable Conduct and Invalidation of Patents Related to Food and Drug Administration-Regulated Products.

This study examines the frequency of drug patent invalidations based on inequitable conduct.

Protecting Medicare's Discretion to Say No to Unproven Therapies.

In this Viewpoint, Kesselheim and coauthors discuss 2 bills in Congress that would curtail Medicare's ability to decline, limit, or conditionally cover medical products that lack robust evidence and argue that officials should distinguish between better and worse therapies when determining reimbursement.

Authority of Medicare to Limit Coverage of FDA-Approved Products: Legal and Policy Considerations.

Importance: When the US Food and Drug Administration (FDA) approves a drug or medical device on the basis of limited clinical evidence, the Centers for Medicare & Medicaid Services (CMS) must decide whether the therapy is "reasonable and necessary" for coverage among Medicare beneficiaries. However, the legal underpinnings of CMS's authority to shape coverage of FDA-regulated products under Medicare Part B are controversial. To clarify this area, we reviewed relevant legal precedents on CMS's approaches to limit coverage and recent decisions Medicare has issued affecting coverage for FDA-regulated products. Observations: The CMS continues to exercise considerable legal discretion to limit coverage of FDA-authorized products to only uses it determines are reasonable and necessary for patients with Medicare. Courts have upheld this discretion repeatedly, emphasizing the difference between Medicare's coverage criteria and the FDA's review standards. As more new drugs and devices come to market without solid evidence of efficacy on clinical outcomes, or have narrow benefit-risk considerations, CMS may increasingly rely on forms of limited or conditional coverage, including coverage with evidence development (CED), which provides reimbursement only in the context of a clinical trial or registry. Conclusions and Relevance: The ability of CMS to condition or limit coverage of FDA-approved products is a commonsense necessity for this crucial taxpayer-funded program. Although courts have thus far deferred to the authority of CMS to make such decisions on the basis of its clear statutory discretion and public health expertise, Congress may want to act to reaffirm statutory language giving CMS sufficient flexibility to craft coverage determinations that reflect the evidence for a product's use.

Association of Advisory Committee Votes With US Food and Drug Administration Decision-Making on Prescription Drugs, 2010-2021.

Importance: The US Food and Drug Administration (FDA) often relies on independent advisory committees when making decisions about the approval of prescription drugs or their withdrawal from the market. These committees provide the FDA with valuable insight and an opportunity to build public trust through transparent deliberation, but recent controversies have raised questions about the optimal use of FDA advisory committees. Objective: To assess the frequency, purposes, and voting outcomes of human drug advisory committees convened from 2010 to 2021 and the FDA's corresponding actions. Design, Setting, and Participants: This qualitative study used a manual review of meeting summaries prepared by FDA staff for the 18 human drug advisory committees active at any time from January 1, 2010, to December 31, 2021, as well as FDA announcements and press releases, drug labels and approval data, industry publications, and company press releases. Main Outcomes and Measures: Outcomes of votes on regulatory questions were recorded using meeting minutes. Alignment of FDA action with advisory votes for new drugs and indications was judged as of 1 year after the vote was held and as of November 30, 2022. Results: The FDA held 409 human drug advisory committee meetings from 2010 to 2021. Committees were convened less frequently over time, from a high of 50 in 2012 to a low of 18 in 2020 and 2021. Much of this decrease occurred at committee meetings involving votes on initial approvals, which declined from a high of 26 in 2012 to a low of 8 in 2021. Overall, FDA regulatory actions aligned with 262 of 298 advisory committee votes on initial approvals, supplemental approvals, withdrawals of approval, and safety actions (88%). Approval followed 142 of 147 positive votes for initial approvals (97%) and 33 of 36 positive votes for supplemental indications (92%), while nonapproval followed 40 of 60 negative votes on initial approvals (67%) and 18 of 21 negative votes on supplemental indications (86%). Conclusions and Relevance: In this qualitative study, there was consistent alignment between advisory votes and FDA action across years and subject areas, but the number of meetings decreased over time. Discordance between FDA actions and advisory committee votes was most frequently an approval after a negative vote. This study demonstrated that these committees have played a key role in the FDA's decision-making process but that the FDA sought independent expert advice less frequently over time even as it continued to follow it. The role of advisory committees in the current regulatory landscape should be more clearly and publicly defined.

Holding Pharmaceutical and Medical Device Executives Accountable as Responsible Corporate Officers.

Importance: When a drug or medical device company violates federal law, the government has a powerful tool to use: the Park doctrine. The aim of the doctrine is to protect patients from the harms of an unsafe or fraudulent medical marketplace by targeting the executives who run the companies that make revenues on these products while violating federal law, rather than have that risk borne by patients or impersonal corporate entities; however, public reports of drug and device company executives being prosecuted in Park doctrine cases are uncommon. Objective: To identify Park prosecutions and characterize their role in US Department of Justice (DOJ) enforcement efforts related to misconduct in the drug and medical device industry. Evidence Review: A systematic search of Westlaw, Google Scholar, DOJ press releases, and the legal literature was conducted. Findings: Thirteen cases of executives from 6 drug and medical device companies prosecuted under the Park doctrine since 2000 were identified. The prosecutions resulted in 11 guilty pleas and 2 jury trials, leading to 2 convictions. Of the 6 companies, 3 were drug manufacturers, 2 were medical device manufacturers, and 1 was a compounding pharmacy. All 3 drug manufacturers were opioid manufacturers, of which 2 executives were charged for unlawful promotion, and 1 was charged for manufacturing errors. Both device manufacturer executives were charged with unlawful promotion. All but 3 prosecutions alleged the defendants' complicity or personal involvement in the misconduct, which Park does not require. By contrast, most large settlements with the DOJ over alleged misconduct in the past 2 decades did not result in individual liability for executives. Conclusions and Relevance: These findings suggest that the government has not exercised the full scope of its authority to prosecute corporate officials responsible for the illegal behavior of the drug and device companies they run. Enforcement under a reinvigorated Park doctrine could better promote the doctrine's goal of protecting patients.

Immigration Law, Public Health, and the Future of Public Charge Policymaking.

U.S. immigration law has excluded noncitizens likely to become a "public charge" since 1882. When the Trump administration proposed a new Rule expanding the interpretation of that exclusion in 2018, over 55,000 people wrote public comments. These comments, overwhelmingly opposed to the change, are the subject of Rachel Fabi and Lauren Zahn's insightful article in this issue of The Journal of Law, Medicine, and Ethics. The themes they identify resonate with the history of the public charge exclusion, which has always reflected a tension between two aims of American governance - to provide for those in need of assistance, and to shape the nation's citizenry according to ideals of self-sufficiency.

Unwanted Advice? Frequency, Characteristics, And Outcomes Of Negative Advisory Committee Votes For FDA-Approved Drugs.

Substantial controversy arose in 2021 when the Food and Drug Administration (FDA) approved the Alzheimer's disease drug aducanumab (Aduhelm) under its accelerated approval program despite a nearly unanimous negative advisory committee vote. Advisory committees are convened before some FDA decisions to provide insight for the agency's decision-making process. To understand the frequency, characteristics, and outcomes of cases in which the FDA authorizes a drug against the recommendations of an advisory committee, we reviewed all FDA advisory committee referrals for new drugs approved during the period 2010-21. The fraction of approved drugs that had been referred to an advisory committee decreased from 55 percent to 6 percent annually, with FDA approvals of negatively reviewed drugs occurring about once a year. Qualitative analysis of committee meetings revealed variability in the substance and wording of key voting questions. Reforms such as transparent criteria for when a drug should be subject to external scrutiny, consistent wording of voting questions, and clear regulatory responses to negative recommendations can better ensure public confidence in the FDA approval process.