The Reporting Recommendations Intended for Pharmaceutical Risk Minimization Evaluation Studies: Standards for Reporting of Implementation Studies Extension (RIMES-SE).

INTRODUCTION: The Reporting recommendations Intended for pharmaceutical risk Minimization Evaluation Studies (RIMES) was developed to improve the quality of reporting of risk minimization program evaluations. In light of continued inadequacies in study reporting, and high-profile program implementation failures, we updated the RIMES Checklist to incorporate additional concepts from the Standards for Reporting of Implementation studies (StaRI). METHODS: The development of the updated checklist, the RIMES-StaRI Extension (RIMES-SE), entailed developing a study protocol and drafting an initial pool of items based on a mapping of the RIMES against the StaRI checklist. A modified e-Delphi exercise was then conducted to determine the importance and understandability of items for checklist inclusion. An expert workshop and an online commentary period for additional feedback followed. RESULTS: The RIMES-SE contains 27 items. It includes two signature features of the StaRI Checklist: 1) a dual strand of items (represented in two columns) describing the risk minimization program (the 'intervention') and the corresponding implementation strategy; and 2) applicable to an array of different research methodologies. CONCLUSIONS: The RIMES-SE Statement and Checklist extends the reporting guidelines set forth in the original RIMES Checklist via inclusion of key implementation science concepts. It is intended to improve the quality and transparency of reporting of risk minimization evaluation studies so as to advance drug safety science.

Patient and Caregiver Experiences With and Perceptions of Risk Evaluation and Mitigation Strategy Programs With Elements to Assure Safe Use.

Importance: The US Food and Drug Administration (FDA) Amendments Act of 2007 authorized the FDA to impose safety requirements on drugs with important risks, such as prescriber certification or routine laboratory testing, to ensure that the benefits of use outweighed the risks. However, little is known about patient and caregiver experiences with these Risk Evaluation and Mitigation Strategy (REMS) programs with Elements to Assure Safe Use (ETASU). Objective: To understand patient and caregiver experiences with and perceptions of REMS programs with ETASU. Design, Setting, and Participants: This qualitative study included semistructured qualitative phone interviews conducted between 2016 and 2017, with initial analysis performed in 2017 and reanalysis performed in 2021. Adult patients prescribed natalizumab or sodium oxybate, adult patients or caregivers of adult patients prescribed vigabatrin, and adult female patients of reproductive age prescribed riociguat were included. Main Outcomes and Measures: Assessment of knowledge, decision-making, medication access, and perceptions of medical privacy. Results: Among 63 participants, 46 (73%) were female. Twenty-five participants (40%) had taken natalizumab, 10 (16%) riociguat, 15 (24%) sodium oxybate, and 10 (16%) vigabatrin. One participant had taken both natalizumab and vigabatrin; 4 (6%) were caregivers of patients using vigabatrin. Most participants expressed knowledge of REMS program requirements, but many lacked the insight that these requirements were part of an FDA-mandated special safety program and expressed difficulty understanding program education materials. REMS requirements made some participants more likely to initiate treatment. However, many reported burdens accessing medication, including the need to travel to certified prescribers or pharmacies. Manufacturer access to personal health information was also controversial, although some participants expressed an altruistic desire to assist others. Conclusions and Relevance: This qualitative study found that REMS programs with ETASU reassured patients and their caregivers about drug safety and helped support medication initiation. However, steps are needed to improve the quality of REMS educational materials, promote efficient medication access, and protect patient privacy.

Public Health Interventions with Harms and Benefits: A Graphical Framework for Evaluating Tradeoffs.

BACKGROUND: Evaluations of public health interventions typically report benefits and harms aggregated over the population. However, benefits and harms are not always evenly distributed. Examining disaggregated outcomes enables decision makers to consider health benefits and harms accruing to both intended intervention recipients and others in the population. METHODS: We provide a graphical framework for categorizing and comparing public health interventions that examines the distribution of benefit and harm between and within population subgroups for a single intervention and compares distributions of harm and benefit for multiple interventions. We demonstrate the framework through a case study of a hypothetical increase in the price of meat (5%, 10%, 25%, or 50%) that, via elasticity of demand, reduces consumption and consequently reduces body mass index. We examine how inequalities in benefits and harms (measured by quality-adjusted life-years) are distributed across a population of white and black males and females. RESULTS: A 50% meat price increase would yield the greatest net benefit to the population. However, because of reduced consumption among low-weight individuals, black males would bear disproportionate harm relative to the benefit they receive. With increasing meat price, the distribution of harm relative to benefit becomes less "internal" to those receiving benefit and more "distributed" to those not receiving commensurate benefit. When we segment the population by sex only, this result does not hold. CONCLUSIONS: Disaggregating harms and benefits to understand their differential impact on subgroups can strongly affect which decision alternative is deemed optimal, as can the approach to segmenting the population. Our framework provides a useful tool for illuminating key tradeoffs relevant to harm-averse decision makers and those concerned with both equity and efficiency.