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BACKGROUND: The novel coronavirus disease 2019 (COVID-19) infected over 5 million United States (US) residents resulting in more than 180,000 deaths by August 2020. To mitigate transmission, most states ordered shelter-in-place orders in March and reopening strategies varied. OBJECTIVE: To estimate excess COVID-19 cases and deaths after reopening compared with trends prior to reopening for two groups of states: (1) states with an evidence-based reopening strategy, defined as reopening indoor dining after implementing a statewide mask mandate, and (2) states reopening indoor dining rooms before implementing a statewide mask mandate. DESIGN: Interrupted time series quasi-experimental study design applied to publicly available secondary data. PARTICIPANTS: Fifty United States and the District of Columbia. INTERVENTIONS: Reopening indoor dining rooms before or after implementing a statewide mask mandate. MAIN MEASURES: Outcomes included daily cumulative COVID-19 cases and deaths for each state. KEY RESULTS: On average, the number of excess cases per 100,000 residents in states reopening without masks is ten times the number in states reopening with masks after 8 weeks (643.1 cases; 95% confidence interval (CI) = 406.9, 879.2 and 62.9 cases; CI = 12.6, 113.1, respectively). Excess cases after 6 weeks could have been reduced by 90% from 576,371 to 63,062 and excess deaths reduced by 80% from 22,851 to 4858 had states implemented mask mandates prior to reopening. Over 50,000 excess deaths were prevented within 6 weeks in 13 states that implemented mask mandates prior to reopening. CONCLUSIONS: Additional mitigation measures such as mask use counteract the potential growth in COVID-19 cases and deaths due to reopening businesses. This study contributes to the growing evidence that mask usage is essential for mitigating community transmission of COVID-19. States should delay further reopening until mask mandates are fully implemented, and enforcement by local businesses will be critical for preventing potential future closures.

RWE has potential to provide efficient and relevant information on the effectiveness of medical products, complementing the data generated in clinical trials; however, how RWE can support regulatory decision-making is unclear, potentially limiting its use. The objective of this study was to identify and characterize instances where RWE was included in the evidence package to support the effectiveness of a medical product regulated by U.S. Food and Drug Administration. A retrospective landscape analysis was conducted to identify instances where RWE was submitted to support effectiveness through targeted review of white and gray literature and publicly available FDA reviews of medical products. Trained evaluators examined FDA reviews to determine if and how RWE contributed to regulatory decision-making regarding effectiveness. Evaluators identified 34 instances of RWE submitted between 1954 and 2020, where 26% of instances were for oncology, 18% for hematology, and 12% for neurology. Over 50% of the products were indicated for use in rare disease or pediatric populations. 82% of products where RWE was submitted received an orphan designation. RWE was included in the product label in 59% of instances. Stated reasons indicating why submitted RWE did not significantly contribute to regulatory decision-making included lack of prespecification of study design and analysis as well as data reliability and relevancy concerns. While there is historical use of RWE to support medical product effectiveness for oncology and rare diseases, potential exists to leverage the strengths of RWE to support other therapeutic areas and capture outcomes that are most relevant to patients.

IMPORTANCE Patient-reported outcomes (PROs) can inform health care decisions, regulatory decisions, and health care policy. They also can be used for audit/benchmarking and monitoring symptoms to provide timely care tailored to individual needs. However, several ethical issues have been raised in relation to PRO use. OBJECTIVE To develop international, consensus-based, PRO-specific ethical guidelines for clinical research. EVIDENCE REVIEWThe PRO ethics guidelines were developed following the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network's guideline development framework. This included a systematic review of the ethical implications of PROs in clinical research. The databases MEDLINE (Ovid), Embase, AMED, and CINAHL were searched from inception until March 2020. The keywords patient reported outcome* and ethic* were used to search the databases. Two reviewers independently conducted title and abstract screening before full-text screening to determine eligibility. The review was supplemented by the SPIRIT-PRO Extension recommendations for trial protocol. Subsequently, a 2-round international Delphi process (n = 96 participants; May and August 2021) and a consensus meeting (n = 25 international participants; October 2021) were held. Prior to voting, consensus meeting participants were provided with a summary of the Delphi process results and information on whether the items aligned with existing ethical guidance.FINDINGS Twenty-three items were considered in the first round of the Delphi process: 6 relevant candidate items from the systematic review and 17 additional items drawn from the SPIRIT-PRO Extension. Ninety-six international participants voted on the relevant importance of each item for inclusion in ethical guidelines and 12 additional items were recommended for inclusion in round 2 of the Delphi (35 items in total). Fourteen items were recommended for inclusion at the consensus meeting (n = 25 participants). The final wording of the PRO ethical guidelines was agreed on by consensus meeting participants with input from 6 additional individuals. Included items focused on PRO-specific ethical issues relating to research rationale, objectives, eligibility requirements, PRO concepts and domains, PRO assessment schedules, sample size, PRO data monitoring, barriers to PRO completion, participant acceptability and burden, administration of PRO questionnaires for participants who are unable to self-report PRO data, input on PRO strategy by patient partners or members of the public, avoiding missing data, and dissemination plans. CONCLUSIONS AND RELEVANCEThe PRO ethics guidelines provide recommendations for ethical issues that should be addressed in PRO clinical research. Addressing ethical issues of PRO clinical research has the potential to ensure high-quality PRO data while minimizing participant risk, burden, and harm and protecting participant and researcher welfare.