Preclinical Alzheimer Disease Drug Development: Early Considerations Based on Phase 3 Clinical Trials.

The number of people in the United States living with Alzheimer disease (AD) is growing, resulting in significant clinical and economic impact. Substantial research investment has led to drug development in stages of AD before symptomatic dementia, such as preclinical AD. Although there are no treatments approved for preclinical AD, there are currently 6 phase 3 clinical trials for preclinical AD treatments. In this article, we review these clinical trials and highlight considerations for future coverage decisions. In line with the definition of preclinical AD, enrollment in these trials focuses on cognitively unimpaired patients that are at high risk of AD because of family history and then genetic testing or brain imaging. Enrollment in most of these trials also allows for younger patients, including those aged under 65 years. Primary clinical trial endpoints focus on cognition often 4 or more years after treatment. Secondary endpoints include other measures of cognition and function, as well as biomarkers. Review of these trials brings to light a few potential considerations when covering these new medications in the future. First, novel and potentially costly approaches involving genetic testing and/or positron emission tomography imaging may be needed to identify appropriate patients and should be developed efficiently. Second, the long duration of these clinical trials suggest that there may be a need for alternative payment approaches in the United States that encourage early payers to pay for a medication for which the long-term benefits may not be realized until after the beneficiary is no longer with the health plan. Third, the value of AD treatments may differ across populations, creating a potential role for indication-based or population-based contracting. Finally, considering the potentially high budgetary impact and little real-world evidence for a new drug class, payers and manufacturers may want to consider outcomes-based payment approaches and coverage with evidence development to mitigate uncertainty about the value of the treatment demonstrated in well-defined populations in clinical trials versus more heterogeneous real-world settings. DISCLOSURES: This work was funded through a generous gift from the Global CEO Initiative on Alzheimer Disease. Hung reports grants from Agency for Healthcare Research and Quality and Pharmaceutical Research and Manufacturers of America outside the submitted work and past employment at CVS Health and BlueCross BlueShield Association. McClellan is an independent board member on the boards of Johnson & Johnson, Cigna, Alignment Healthcare, and Seer; co-chairs the Accountable Care Learning Collaborative and the Guiding Committee for the Health Care Payment Learning and Action Network; and receives fees for serving as an advisor for Cota and MITRE. Hamilton Lopez and Schneider have nothing to disclose. Part of this work was presented at the 2019 AMCP Nexus Meeting, October 29-November 1, 2019, in National Harbor, MD.

Paying For Value From Costly Medical Technologies: A Framework For Applying Value-Based Payment Reforms.

Innovative medical products offer significant and potentially transformative impacts on health, but they create concerns about rising spending and whether this rise is translating into higher value. The result is increasing pressure to pay for therapies in a way that is tied to their value to stakeholders through improving outcomes, reducing disease complications, and addressing concerns about affordability. Policy responses include the growing application of health technology assessments based on available evidence to determine unit prices, as well as alternatives to volume-based payment that adjust product payments based on predictors or measures of value. Building on existing frameworks for value-based payment for health care providers, we developed an analogous framework for medical products, including drugs, devices, and diagnostic tools. We illustrate each of these types of alternative payment mechanisms and describe the conditions under which each may be useful. We discuss how the use of this framework can help track reforms, improve evidence, and advance policy analysis involving medical product payment.

Implementation of a Market Entry Reward within the United States.

As part of a multifactorial approach to address weak incentives for innovative antimicrobial drug development, market entry rewards (MERs) are an emerging solution. Recently, the Duke-Margolis Center for Health Policy released the Priority Antimicrobial Value and Entry (PAVE) Award proposal, which combines a MER with payment reforms, transitioning from volume-based to "value-based" payments for antimicrobials. Here, the PAVE Award and similar MERs are reviewed, focusing on further refinement and avenues for implementation.