Spending on Targeted Therapies for Duchenne Muscular Dystrophy.

This study estimates public and private spending on genetically targeted treatments for Duchenne muscular dystrophy during years in which the drugs were marketed without completed confirmatory studies.

Identifying therapeutic alternatives in Medicare drug price negotiation: The case of etanercept.

As the Centers for Medicare & Medicaid Services (CMS) navigates the process of negotiating drug prices, it plans to compare the cost, safety, and effectiveness of each drug with its therapeutic alternatives. How CMS selects therapeutic alternatives is a consequential decision, and there remains uncertainty about their methodology. To understand the challenges CMS will face in selecting therapeutic alternatives, we developed a methodology that leverages clinical guidelines by US medical professional associations to identify potential therapeutic alternatives for etanercept, one of the first 10 drugs selected for Medicare price negotiation. For each of etanercept's 5 US Food and Drug Administration-approved indications, we identified all drugs with the same mechanism of action as etanercept and considered drugs with different mechanisms if they were recommended in place of etanercept at the same treatment stage, or if there was no strong comparative safety or effectiveness evidence that the drug differed from etanercept. We identified 22 potential therapeutic alternatives to etanercept, including 4 drugs with the same mechanism, 10 biologics with different mechanisms, and 8 small-molecule drugs. We faced several challenges in selecting therapeutic alternatives using clinical guidelines, such as how to reconcile strong recommendations that were based on weak evidence and how to consider combination therapies. This exercise demonstrates the complex considerations that CMS will face as it negotiates drug prices based on therapies' cost, safety, and effectiveness relative to therapeutic alternatives.

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.

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.

Battles Over Medication Abortion Threaten the Integrity of Drug Approvals in the U.S.

Legal challenges to the FDA's approval of mifepristone have destabilized patients' ability to access controversial medicines like medication abortion. We argue that federal courts' receptiveness to this litigation undermines the coherence and integrity of prescription drug regulation in the U.S.

The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence.

The U.S. Food and Drug Administration (FDA) approved eteplirsen (Exondys 51) for Duchenne muscular dystrophy in 2016 via its accelerated approval program on the basis of a study of 12 boys. After a contentious review process and a high-profile meeting of an external advisory committee, FDA leaders concluded that very small increases in treated patients' levels of dystrophin, a muscle protein, were reasonably likely to predict clinical benefit. The eteplirsen approval, which was followed by approvals of other drugs in the same class via the same pathway, has been controversial because of the questionable evidence underlying these decisions, delays in mandated postapproval testing, and high U.S. prices. Questions remain about the effectiveness and long-term safety of these products. Although the FDA initially set a November 2020 deadline for eteplirsen's manufacturer to complete a clinical trial determining whether the drug has clinical benefit, the company will not complete the trial until 2024 or later. The relationship between levels of truncated dystrophin, the muscle protein studied in eteplirsen's pivotal trial, and clinical outcomes remains uncertain. Despite recent legislative and regulatory changes to the FDA's accelerated approval pathway, the history of eteplirsen and similar drugs points to the need for additional reforms to better balance evidence generation with patient safety and access to promising medications. Lawmakers and regulators should take further action to limit excessive spending on unproven therapies and ensure that drug sponsors conduct robust and timely confirmatory trials after receiving accelerated approval.

Anticipated efficiencies, real costs: Medicaid managed care organizations and the pharmacy benefit.

The Affordable Care Act led an additional 15 states to begin contracting with comprehensive, risk-based managed care organizations (MCOs) to administer pharmacy benefits for Medicaid beneficiaries between 2010 and 2017. Reasons for this shift included concerns about administering complex benefits for an influx of new beneficiaries, assumptions about the cost-saving potential of privately run managed care, and a desire for budget predictability. As drug prices increased during the past decade, the way that state pharmacy benefits were administered via MCOs affected the ability of states to meet the needs of their Medicaid beneficiaries. Here, we review the advantages and limitations of 2 strategies that give states more centralized control over management of the pharmacy benefit: excluding the pharmacy benefit from MCO contracts and aligning preferred drug lists across beneficiary types. We propose that centralizing utilization management tools, aligning incentives for managed care payers with the needs of patients and Medicaid programs, and the ability to implement formulary exclusions may enable states to achieve savings and better meet the needs of beneficiaries. DISCLOSURES: No funding supported the writing of this Viewpoints article. Kesselheim is supported by grants from Arnold Ventures. Bendicksen has nothing to disclose.

Pursuing Value-Based Prices for Drugs: A Comprehensive Comparison of State Prescription Drug-Pricing Boards.

Policy Points In the absence of federal action on rising prescription drug costs, we reviewed the details of five states that have enacted prescription drug-pricing boards seeking to lower drug prices based on products' value. Within these states, six such boards are currently authorized; they have similarities but vary in terms of structure, authority, scope, and leverage. As of June 2021, only one of the boards in our sample has conducted pricing reviews; legislators in other states can learn from the successes and challenges of existing boards. Prescription drug-pricing boards represent a novel and promising way to curb state spending and pay for value in prescription drugs but face legal and political barriers in implementation. CONTEXT: Rising prescription drug costs are consuming a growing proportion of state and private budgets. In response, lawmakers have experimented with a variety of policies to contain spending and achieve value in prescription drugs. As part of this series of reforms, some state legislatures have recently authorized prescription drug-pricing boards to address the high prices of brand-name prescription drugs and assess the value of those drugs. METHODS: We identified state prescription drug-pricing boards in the United States, defined as any agency authorized by a state legislature to review specific drugs and pursue value-based drug prices. To describe the characteristics of the boards, we obtained public records of authorizing legislation, guidance documents, and board meeting minutes. We compared the boards' powers and responsibilities and analyzed completed pricing reviews. FINDINGS: Six state drug-pricing boards in five states met our definition; their design varied substantially. Two of the boards (New York Medicaid and Massachusetts) have authority over drug rebates paid by state Medicaid programs, one (New York Drug Accountability Board) has jurisdiction over state-regulated commercial insurance, and another three (Maine, Maryland, and New Hampshire) oversee non-Medicaid, state-funded insurance. Three boards are authorized to require manufacturers to confidentially submit information related to the pricing and clinical effectiveness of reviewed drugs to inform value determinations. Only one board (New York Medicaid) had completed pricing reviews as of June 3, 2021. CONCLUSIONS: Boards' structure, scope, and statutory leverages to compel manufacturers to negotiate lower net costs are key factors that influence whether and to what extent boards can achieve cost savings for states. Though legal constraints may limit the effective reach of prescription drug-pricing boards, these agencies can enable states to address rising prescription drug costs, in part by virtue of their very existence. To overcome practical limitations, states seeking to implement similar policies can build on the experiences and designs of current boards.