Criteria for use of composite end points for competing risks—a systematic survey of the literature with recommendations

Manja, Veena; Albashir, Siwar; Guyatt, Gordon

doi:10.1016/j.jclinepi.2016.12.001

Cited by 42 publications

(42 citation statements)

References 27 publications

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“…This ambiguity associated with composite outcome measures is consistent with a recent assessment of the cardiology literature (23, 24), which suggested that composite outcomes have a large gradient of importance and that less important endpoints occur more frequently and thus drive effect estimates. For example, a trial of irbesartan versus amlodipine or placebo showed benefit of irbesartan over amlodipine for the composite outcome of doubling of creatinine, onset of end-stage renal disease, or death of any cause (25).…”

Section: Limitations Of Using Failure-free Dayssupporting

confidence: 84%

Reappraisal of Ventilator-Free Days in Critical Care Research

Yehya

Harhay²,

Curley

et al. 2019

Am J Respir Crit Care Med

259

288

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Ventilator-free days (VFDs) are a commonly reported composite outcome measure in acute respiratory distress syndrome trials. VFDs combine survival and duration of ventilation in a manner that summarizes the “net effect” of an intervention on these two outcomes. However, this combining of outcome measures makes VFDs difficult to understand and analyze, which contributes to imprecise interpretations. We discuss the strengths and limitations of VFDs and other “failure-free day” composites, and we provide a framework for when and how to use these outcome measures. We also provide a comprehensive discussion of the different analytic methods for analyzing and interpreting VFDs, including Student’s t tests and rank-sum tests, as well as competing risk regressions treating extubation as the primary outcome and death as the competing risk. Using simulations, we illustrate how the statistical test with optimal power depends on the relative contributions of mortality and ventilator duration on the composite effect size. Finally, we recommend a simple analysis and reporting framework using the competing risk approach, which provides clear information on the effect size of an intervention, a statistical test and measure of confidence with the ability to adjust for baseline factors and allow interim monitoring for trials. We emphasize that any approach to analyzing a composite outcome, including other “failure-free day” constructs, should also be accompanied by an examination of the components.

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Section: Limitations Of Using Failure-free Dayssupporting

confidence: 84%

Reappraisal of Ventilator-Free Days in Critical Care Research

Yehya

Harhay²,

Curley

et al. 2019

Am J Respir Crit Care Med

259

288

View full text Add to dashboard Cite

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“…In these cases, a composite outcome could be an option to deal with the problem of competitive risks. 4 However, a significant BACO could lead to reconsider the necessity of using a composite outcome or to adequately disaggregate the estimations for the component endpoints in both results and conclusions.…”

Section: Discussionmentioning

confidence: 99%

“…1 Moreover, it can be a way of dealing with competitive risks. 4 In other cases, a composite outcome can deliberately integrate events of a different nature that are not expected to be strongly related to each other. For example, it may simultaneously incorporate indicators of effectiveness and safety of an intervention.…”

Section: Introductionmentioning

confidence: 99%

Estimating and testing an index of bias attributable to composite outcomes in comparative studies

Díaz-Quijano

2021

Journal of Clinical Epidemiology

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Background: Little guidance is available on how composite outcomes should be interpreted, especially in situations of varied direction in the association across the event subtypes. I proposed an index to evaluate the bias attributable to composite outcomes (BACO) and applied it in recently published clinical trials.Methods: I defined the BACO index as the ratio between logarithms of the association measures of both a composite outcome and its most relevant component (e.g., any-cause mortality). By using the non-linear combination of parameters, based on the delta method, I calculated the confidence intervals and performed Wald-type tests for the null hypotheses (BACO index = 1). I applied this method in systematically selected clinical trials, and in two other preselected trials which I considered "positive controls". These last trials have been recognized as examples of primary composite outcomes that were disregarded because of inconsistency with the treatment effect on mortality.Results: BACO index values different from one were classified according to whether the use of composite outcomes overestimated (BACO index >1), underestimated (BACO index between zero and <1), or inverted (BACO index <0) the association between exposure and prognosis. In three of 23 clinical trials and the two positive controls, the BACO indices were significantly lower than one (using p <0.005 as a preset cutoff). Conclusion:Based on the BACO index testing, researchers could predefined rules to make impartial decisions about maintaining a composite outcome as the primary endpoint or to state cautions regarding its interpretation.

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“…Many of the authors were from Canadian institutions (n = 12, 38.7%), followed by Japan and USA (n = 4, 12.9% each). Based on the previously defined criteria, we scored ten studies (32.3%) as generalizable [28,30,38,40,49,[51][52][53][54]57]. Only three studies (9.7%, two of which we scored as generalizable) commented on generalizability and reported their own work as generalizable, either to the subject area (e.g., venous ulcer disease), to a clinical area, or in general terms [27,30,38].…”

Section: Characteristics Of Included Methodological Reviewsmentioning

confidence: 99%

Mapping the nomenclature, methodology, and reporting of studies that review methods: a pilot methodological review

Lawson

Leenus

Mbuagbaw

2020

Pilot Feasibility Stud

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Background: A relatively novel method of appraisal, methodological reviews (MRs) are used to synthesize information on the methods used in health research. There are currently no guidelines available to inform the reporting of MRs. Objectives: This pilot review aimed to determine the feasibility of a full review and the need for reporting guidance for methodological reviews. Methods: Search strategy: We conducted a search of PubMed, restricted to 2017 to include the most recently published studies, using different search terms often used to describe methodological reviews: "literature survey" OR "meta-epidemiologic* review" OR "meta-epidemiologic* survey" OR "methodologic* review" OR "methodologic* survey" OR "systematic survey." Data extraction: Study characteristics including country, nomenclature, number of included studies, search strategy, a priori protocol use, and sampling methods were extracted in duplicate and summarized. Outcomes: Primary feasibility outcomes were the sensitivity and specificity of the search terms (criteria for success of feasibility set at sensitivity and specificity of ≥ 70%). Analysis: The estimates are reported as a point estimate (95% confidence interval). Results: Two hundred thirty-six articles were retrieved and 31 were included in the final analysis. The most accurate search term was "meta-epidemiological" (sensitivity [Sn] 48.39; 95% CI 31.97-65.16; specificity [Sp] 97.56; 94.42-98.95). The majority of studies were published by authors from Canada (n = 12, 38.7%), and Japan and USA (n = 4, 12.9% each). The median (interquartile range [IQR]) number of included studies in the MRs was 77 (13-1127). Reporting of a search strategy was done in most studies (n = 23, 74.2%). The use of a pre-published protocol (n = 7, 22.6%) or a justifiable sampling method (n = 5, 16.1%) occurred rarely. Conclusions: Using the MR nomenclature identified, it is feasible to build a comprehensive search strategy and conduct a full review. Given the variation in reporting practices and nomenclature attributed to MRs, there is a need for guidance on standardized and transparent reporting of MRs. Future guideline development would likely include stakeholders from Canada, USA, and Japan.

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Criteria for use of composite end points for competing risks—a systematic survey of the literature with recommendations

Cited by 42 publications

References 27 publications

Reappraisal of Ventilator-Free Days in Critical Care Research

Reappraisal of Ventilator-Free Days in Critical Care Research

Estimating and testing an index of bias attributable to composite outcomes in comparative studies

Mapping the nomenclature, methodology, and reporting of studies that review methods: a pilot methodological review

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