Use of Patient Reported Outcomes in Registered Drug Studies for Long COVID

OBJECTIVES: Long COVID is a heterogeneous phenomenon that may cause diverse long-term debilitating sequelae that are typically self-reported (e.g., fatigue). This scoping review’s aim is to identify which patient reported outcomes (PROs) are utilized in registered drug studies for long covid.

METHODS: Using a modified PRISMA approach, we reviewed drug studies registered on ClinicalTrials.gov with “condition/disease” related to Long COVID and “intervention/treatment” of drug from 2019 through October 2023. Studies were excluded if their patient recruitment and data collection were not consistent with the World Health Organization’s definition of long covid. Two coders extracted and categorized PROs from all remaining studies.

RESULTS: 204 studies were identified in the search, of which 85 (42%) study designs were not consistent with Long COVID. Of the 119 Long COVID studies, 23 (19%) did not include PROs. Double coding and adjudication have been completed for 50 studies for common Long COVID symptoms. Sleep/exhaustion/fatigue symptoms were identified 42 times and measured by 11 different instruments including Chalder Fatigue Scale (6), Fatigue Severity Scale (6), and Multidimensional Fatigue Inventory (4). Depression symptoms were identified 21 times and captured by 8 measures including Patient Health Questionnaire (8), Beck Depression Inventory (5), and Hospital Anxiety and Depression Scale (2). Pulmonary symptoms were identified 16 times and captured by 4 measures including Modified Medical Research Council Dyspnea Scores (8) and St George's Respiratory Questionnaire (2). Each domain included studies that indicated an intention to collect an outcome category (e.g., fatigue) but did not specify a measure.

CONCLUSIONS: Long COVID drug studies utilize highly variable validated and non-specific patient reported outcome measures (PROMs). This variability will hinder future efforts in accurately comparing study outcomes and performing meta-analyses.