Forks in the road: Definitions of response, remission, recovery, and other dichotomized outcomes in randomized controlled trials for adolescent depression. A scoping review

Abstract

Background: Definitions of dichotomous outcome terms, such as "response," "remission," and "recovery" are central to the design, interpretation, and clinical application of randomized controlled trials of adolescent depression interventions.Accordingly, this scoping review was conducted to document how these terms have been defined and justified in clinical trials. Method: Bibliographic databases MEDLINE, Embase, APA PsycInfo, and CINAHL were searched from inception to February 2020 for randomized controlled trials evaluating treatments for adolescent depression. Ninety-eight trials were included for data extraction and analysis. Results: Assessment of outcome measurement instruments, metric strategies, methods of aggregation, and measurement timing, yielded 53 unique outcome definitions of "response" across 45 trials that assessed response, 47 unique definitions of "remission" in 29 trials that assessed remission, and 19 unique definitions of "recovery" across 11 trials that assessed recovery. A minority of trials (N = 35) provided a rationale for dichotomous outcomes definitions, often by citing other studies that used a similar definition (N = 11). No rationale included input from youth or families with lived experience. Conclusion:Our review revealed that definitions of "response," "remission," "recovery," and related terms are highly variable, lack clear rationales, and are not informed by key stakeholder input. These limitations impair pooling of trial results and the incorporation of trial findings into pragmatic treatment decisions in clinical practice. Systematic approaches to establishing outcome definitions are needed to enhance the impact of trials examining adolescent depression treatment.

Revisiting the theoretical and methodological foundations of depression measurement

“…An analysis of 350 clinical trials for depression using the MADRS identified that 28 different thresholds were used to determine whether patients have MDD and should therefore be included in a given trial; thresholds ranged from total scores of 5 to 34 points 36 . Similarly, a review of 29 trials for adolescent MDD identified 47 unique definitions of remission, with only a minority of trials providing a rationale for their cut-offs 51 . Overall, this illustrates that the internal structure of the most commonly used depression instruments does not support the use of cut-offs to identify the presence or absence of MDD.…”

Predictors, Moderators, and Mediators Associated With Treatment Outcome in Randomized Clinical Trials Among Adolescents With Depression

“…The most common examples of depression outcomes were continuous outcomes of symptom reduction on a scale score over time or dichotomous outcomes of response or remission. 19 Regardless of treatment exposure, response was most often defined as a specified percentage decrease in depression scale scores (eg, 50% reduction on the CDRS-R) or a rating of much improved or very much improved on the Clinician's Global Impression-Improvement subscale. 26 Remission was most often defined by an end point scale score below a specific cutoff or no longer meeting criteria for major depressive disorder.…”

“…26 Remission was most often defined by an end point scale score below a specific cutoff or no longer meeting criteria for major depressive disorder. 19 Greater reduction in symptom scale scores over time or greater proportions of responders and/or remitters represented favorable outcomes. Predictors, moderators, and mediators associated with other outcomes (eg, suicidal ideation, function) were not extracted in this review.…”

Efficacy and safety of non-invasive brain stimulation in combination with antidepressants in adolescents with depression: a systematic review and meta-analysis

“…3) Outcome: the studies reported one or more of the following outcomes, including changes in depression scores compared to baseline, relief of depressive symptoms, or rate of adverse events. There is currently no unified standard for outcome measurement ( 35 ). Based on the current research status, we have developed the following criteria.…”