Core Outcomes Set for Trials in People With Coronavirus Disease 2019

Abstract

Objectives: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019. Design: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set. Setting: International. Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). Interventions: None. Measurements: None. Main Results: Six themes were identified. “Responding to the critical and acute health crisis” reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. “Capturing different settings of care” highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. “Encompassing the full trajectory and severity of disease” was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). “Distinguishing overlap, correlation and collinearity” meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). “Recognizing adverse events” refers to the potential harms of new and evolving interventions. “Being cognizant of family and psychosocial wellbeing” reflected the pervasive impacts of coronavirus disease 2019. Conclusions: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials.

Outcomes Evaluated in Controlled Clinical Trials on the Management of COVID-19: A Methodological Systematic Review

“…Two other groups prioritized specific outcomes and measurement instruments, all of which were captured in our analysis, but were not necessarily the most frequently used [ 10 , 11 ]. The last core outcome set prioritized broader domains to be addressed, rather than specific outcomes [ 9 ]. These domains encompass most outcomes identified in this methodological review.…”

“…In view of the multiple available core outcome sets, the authors of this review believe that outcomes selection for future trials should (i) adhere to the recommendations by the WHO and the meta-COS, and (ii) attempt to address all of the domains proposed by Tong et al, a core outcome set that was informed by consensus of >9000 participants [ 9 ]. Undeniably, the objectives of individual trials vary and, accordingly, additional outcomes could be selected to address specific trial objectives.…”

“…Upon the emergence of COVID-19 pandemic, there was an urgent need for the development of a core outcome set. Within a few months, four sets were developed, using an accelerated process [ 9 , 10 , 11 , 12 ]. These were based on methodological systematic reviews of the first registered RCTs, which were limited in number and design, due to the limited knowledge of the nature of COVID-19, at the time.…”

Core Outcome Measures for Trials in People With Coronavirus Disease 2019: Respiratory Failure, Multiorgan Failure, Shortness of Breath, and Recovery

“…During each workshop, we presented the COVID-19-COS process and core outcome domains ( 17 , 22 ), definitions (for respiratory failure [26], multiple organ failure [27–29], shortness of breath [30, 31], and recovery [17, 22, 32]), an overview of the measurement properties and feasibility considerations (24, 33), and a summary of existing measures based on a review of existing core outcome measures (20, 21, 27, 28, 34–38), registered and published trials in COVID-19 (19), and reviews of trials and measures in respiratory disease and critical illness (39–44). Existing measures were assessed using the COMET initiative and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) framework (24, 33) to identify a proposed core outcome measure for discussion.…”

“…The consensus-based definition of recovery as determined by patients and clinicians included the absence of symptoms related to the illness, the ability to do usual daily activities, and a return to a previous state of health and mind (prior to the COVID-19 illness) ( 17 ). No existing measures were found to provide an overall assessment of recovery, which captured all three dimensions of recovery important to patients with COVID-10 ( 17 ); thus, we developed and piloted a new COVID-19-COS recovery measure that was proposed to workshop participants. We adhered to the COMET/COSMIN framework as was feasible.…”