Heterogeneity of outcome measures in depression trials and the relevance of the content of outcome measures to patients: a systematic review.

Research waste occurs when randomised controlled trial (RCT) outcomes are heterogeneous or overlook domains that matter to patients (eg, relating to symptoms or functions). In this systematic review, we reviewed the outcome measures used in 450 RCTs of adult unipolar and bipolar depression registered between 2018 and 2022 and identified 388 different measures. 40% of the RCTs used the same measure (Hamilton Depression Rating Scale [HAMD]). Patients and clinicians matched each item within the 25 most frequently used measures with 80 previously identified domains of depression that matter to patients. Seven (9%) domains were not covered by the 25 most frequently used outcome measures (eg, mental pain and irritability). The HAMD covered a maximum of 47 (59%) of the 80 domains that matter to patients. An interim solution to facilitate evidence synthesis before a core outcome set is developed would be to use the most common measures and choose complementary scales to optimise domain coverage. TRANSLATIONS: For the French and Dutch translations of the abstract see Supplementary Materials section.

How to measure mental pain: a systematic review assessing measures of mental pain.

QUESTION: Although mental pain is present in many mental disorders and is a predictor of suicide, it is rarely investigated in research or treated in care. A valid tool to measure it is a necessary first step towards better understanding, predicting and ultimately relieving this pain. STUDY SELECTION AND ANALYSIS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic review to identify all published standardised measures of mental pain. We used qualitative content analysis to evaluate the similarity of each measure, quantified via Jaccard Index scores ranging from no similarity (0) to full similarity (1). Finally, using the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology, we evaluated each measure's development (assessing 35 features), its content validity (31 features) and if the latter was rated at least adequate, its other psychometric properties. FINDINGS: We identified 10 self-reported scales of mental pain in 2658 screened studies relying on diverse definitions of this construct. The highest average similarity coefficient for any given measure was 0.24, indicative of weak similarity (individual pairwise coefficients from 0 to 0.5). Little to no information was provided regarding the development and the content validity of all 10 scales. Therefore, their development and content validity were rated 'inadequate' or 'doubtful'. CONCLUSIONS AND CLINICAL IMPLICATIONS: There is not enough evidence of validity to recommend using one measure over others in research or clinical practice. Heterogeneous use of disparate measures across studies limits comparison and combination of their results in meta-analyses. Development by all stakeholders (especially patients) of a consensual patient-reported measure for mental pain is needed. PROSPERO REGISTRATION NUMBER: CRD42021242679.

Important adverse events to be evaluated in antidepressant trials and meta-analyses in depression: a large international preference study including patients and healthcare professionals.

BACKGROUND: Non-serious adverse events (NSAEs) should be captured and reported because they can have a significant negative impact on patients and treatment adherence. However, the reporting of NSAEs in randomised controlled trials (RCTs) is limited. OBJECTIVE: To identify the most important NSAEs of antidepressants for patients and clinicians, to be evaluated in RCTs and meta-analyses. METHODS: We conducted online international surveys in English, German and French, including (1) adults prescribed an antidepressant for a depressive episode and (2) healthcare professionals (HCPs) prescribing antidepressants. Participants ranked the 30 most frequent NSAEs reported in the scientific literature. We fitted logit models for sets of ranked items and calculated for each AE the probability to be ranked higher than the least important AE. We also identified additional patient-important AEs not included in the ranking task via open-ended questions. FINDINGS: We included 1631 patients from 44 different countries (1290 (79.1%) women, mean age 39.4 (SD 13), 289 (37.1%) with severe depression (PHQ-9 score ≥20)) and 281 HCPs (224 (79.7%) psychiatrists). The most important NSAEs for patients were insomnia (95.9%, 95% CI 95.2% to 96.5%), anxiety (95.2%, 95% CI 94.3% to 95.9%) and fatigue (94.6%, 95% CI 93.6% to 95.4%). The most important NSAEs for HCPs were sexual dysfunction (99.2%, 95% CI 98.5% to 99.6%), weight gain (98.9%, 95% CI 97.7% to 99.4%) and erectile problems (98.8%, 95% CI 97.7% to 99.4%). Participants reported 66 additional NSAEs, including emotional numbing (8.6%), trouble with concentration (7.6%) and irritability (6%). CONCLUSIONS: These most important NSAEs should be systematically reported in antidepressant trials. CLINICAL IMPLICATIONS: The most important NSAEs should contribute to the core outcome set for harms in depression.

Identifying outcomes for depression that matter to patients, informal caregivers, and health-care professionals: qualitative content analysis of a large international online survey.

BACKGROUND: Many clinical trials have assessed treatments for depressive disorders and bipolar depression. However, whether, and which, assessed outcome domains really matter to patients, informal caregivers, and health-care professionals remains unclear. METHODS: We did an international online survey in French, German, and English. Participants were adult patients with a history of depression, informal caregivers, and health-care professionals, recruited by purposeful sampling. To identify outcome domains, participants answered four open-ended questions about their expectations for depression treatment. We disseminated the survey without restriction via social media, patient and professional associations, and a media campaign. Four researchers independently did qualitative content analyses. We assessed data saturation using mathematical models to ensure the comprehensive identification of outcome domains. FINDINGS: Between April 5, 2018, and Dec 10, 2018, 1912 patients, 464 informal caregivers, and 627 health-care professionals from 52 countries provided 8183 open-ended answers. We identified 80 outcome domains related to symptoms (64 domains), such as mental pain (or psychological or psychic pain, 523 [17%] of 3003 participants) and motivation (384 [13%]), and functioning (16 domains), such as social isolation (541 [18%]). We identified 57 other outcome domains regarding safety of treatment, health care organisation, and social representation, such as stigmatisation (408 [14%]). INTERPRETATION: This study provides a list of outcome domains important to patients, informal caregivers, and health-care professionals. Unfortunately, many of these domains are rarely measured in clinical trials. Results from this study should set the foundation for a core outcome set for depression. FUNDING: Fondation pour la Recherche Medicale and NIHR Oxford Health Biomedical Research Centre.