Dataset Information

Assessing Heterogeneity of Treatment Effects: Are Authors Misinterpreting Their Results?

ABSTRACT:

Objective

To determine whether investigations of heterogeneity of treatment effects (HTE) in randomized-controlled trials (RCTs) are prespecified and whether authors' interpretations of their analyses are consistent with the objective evidence.

Data sources/study setting

Trials published in Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine in 1994, 1999, and 2004.

Study design

We reviewed 87 RCTs that reported formal tests for statistical interaction or heterogeneity (HTE analyses), derived from a probability sample of 541 articles.

Data collection/extraction

We recorded reasons for performing HTE analysis; an objective classification of evidence for HTE (termed "clinicostatistical divergence" [CSD]); and authors' interpretations of findings. Authors' interpretations, compared with CSD, were coded as understated, overstated, or adequately stated.

Principle findings

Fifty-three RCTs (61 percent) claimed prespecified covariates for HTE analyses. Trials showed strong (6), moderate (11), weak (25), or negligible (16) evidence for CSD (29 could not be classified due to inadequate information). Authors stated that evidence for HTE was sufficient to support differential treatment in subgroups (10); warranted more research (31); was absent (21); or provided no interpretation (25). HTE was overstated in 22 trials, adequately stated in 57 trials, and understated in 8 trials.

Conclusions

Inconsistencies in performance and reporting may limit the potential of HTE analysis as a tool for identifying HTE and individualizing care in diverse populations. Recommendations for future studies on the reporting and interpretation of HTE analyses are provided.

SUBMITTER: Fernandez Y Garcia E

PROVIDER: S-EPMC2813449 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Publications

Assessing Heterogeneity of Treatment Effects: Are Authors Misinterpreting Their Results?

Fernandez Y Garcia Erik E Nguyen Hien H Duan Naihua N Gabler Nicole B NB Kravitz Richard L RL

Health services research 20100201 1

<h4>Objective</h4>To determine whether investigations of heterogeneity of treatment effects (HTE) in randomized-controlled trials (RCTs) are prespecified and whether authors' interpretations of their analyses are consistent with the objective evidence.<h4>Data sources/study setting</h4>Trials published in Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine in 1994, 1999, and 2004.<h4>Study design</h4>We re ...[more]

PMID: 19929962

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Project description:BackgroundCluster-randomized trials (CRTs) are being increasingly used to test a range of interventions, including medical interventions commonly used in clinical practice. Policies created by the NIH and the Food and Drug Administration (FDA) require the reporting of demographics and the examination of demographic heterogeneity of treatment effect (HTE) for individually randomized trials. Little is known about how frequent demographics are reported and HTE analyses are conducted in CRTs.ObjectivesWe sought to understand the prevalence of HTE analyses and the statistical methods used to conduct them in CRTs focused on treating cardiovascular disease, cancer, and chronic lower respiratory diseases. Additionally, we also report on the proportion of CRTs that reported on baseline demographics of its populations and conducted demographic HTE analyses.Data sourcesWe searched PubMed and Embase for CRTs published between 1/1/2010 and 3/29/2016 that focused on treating the top 3 Center for Disease Control causes of death (cardiovascular disease, chronic lower respiratory disease, and cancer). Evidence Screening And Review: Of 1,682 unique titles, 117 abstracts were screened. After excluding 53 articles, we included 64 CRT publications and abstracted information on study characteristics and demographic information, statistical analysis, HTE analysis, and study quality.ResultsAge and sex were reported in greater than 95.3% of CRTs, while race and ethnicity were reported in only 20.3% of CRTs. HTE analyses were conducted in 28.1% (n = 18) of included CRTs and 77.8% (n = 12) were prespecified analyses. Four CRTs conducted a demographic subgroup analysis. Only 6/18 CRTs used interaction testing to determine whether HTE existed.ConclusionsBaseline demographic reporting was high for age and sex in CRTs, but was uncommon for race and ethnicity. HTE analyses were uncommon and was rare for demographic subgroups, which limits the ability to examine the extent of benefits or risks for treatments tested with CRT designs.

Project description:To investigate subgroup responses to long-acting injectable (LAI) medications haloperidol decanoate (HD) and paliperidone palmitate (PP) in a randomized controlled trial that found no difference between the treatments on the primary outcome of efficacy failure. A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS) enrolled 311 participants from March 2011 to July 2013 meeting DSM-IV-TR criteria for diagnoses of schizophrenia or schizoaffective disorder at risk of relapse due to medication nonadherence or substance abuse. Participants were randomly assigned to double-blinded treatment with HD or PP and followed for up to 2 years. A committee blinded to treatment assignment adjudicated efficacy failure on the basis of participants' meeting at least 1 of these criteria: psychiatric hospitalization, crisis stabilization, increased outpatient visits, could not discontinue oral antipsychotic, discontinued assigned LAI due to inadequate therapeutic benefit, or ongoing or repeated need for adjunctive oral antipsychotic medication. Survival analyses examined modification of treatment effects on efficacy failure by age, sex, race, substance abuse, baseline symptom severity, and baseline adherence. Mixed-effect linear models and analysis of covariance examined this modification on safety outcomes. An interaction between age and treatment (P = .009) revealed younger participants assigned HD had longer time to efficacy failure than those assigned PP. Interactions were not significant between treatment group and sex, race, substance use disorder, baseline symptom severity, or baseline adherence. An interaction of treatment and age on akathisia (P = .047) found an advantage for PP that was larger among younger persons. An advantage for HD on serum prolactin levels was larger among younger women (P = .033). Among younger persons, HD was associated with lower rates of efficacy failure than PP. Age effects on adverse effects were mixed. Age-related heterogeneity of antipsychotic treatment effects warrants further investigation and consideration in clinical practice. ClinicalTrials.gov identifier: NCT01136772.

Dataset Information

Assessing Heterogeneity of Treatment Effects: Are Authors Misinterpreting Their Results?

Objective

Data sources/study setting

Study design

Data collection/extraction

Principle findings

Conclusions

Publications

Assessing Heterogeneity of Treatment Effects: Are Authors Misinterpreting Their Results?

Similar Datasets

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