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At least 235 records · Page 13Linked to original sources

PubMed2026

Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. OBJECTIVE: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the I² statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] -4.52, 95% CI -8.38 to -0.67, PI -9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%-2.11%, PI 1.85%-2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98-35.24, PI -16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (R²=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (P=.07). Certainty of evidence ranged from moderate to high. CONCLUSIONS: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base.

Humans↗

PubMed1992

Subliminal psychodynamic activation: updated comprehensive list of experimental results and comments on previous lists.

A comprehensive list of results from visual subliminal psychodynamic activation experiments is presented. This list includes results reported since the publication of the last comprehensive list by Weinberger and Hardaway in 1990 and several results not found on that list. On the present list, SPA results are categorized according to criteria that we contend are more objective than those used previously. In contrast to conclusions drawn from previous lists prepared by Silverman in 1980 and 1983, by Weinberger and Hardaway in 1990, and by Weinberger and Silverman in 1987, the present list indicates that the results of a majority of experiments do not clearly support hypotheses tested by the subliminal psychodynamic activation method. Aspects of Hardaway's meta-analyses from 1987 and 1990 for major areas of research on subliminal psychodynamic activation are discussed in terms of suggestions for further research.

Arousal↗

PubMed1992

Oral contraceptives and cancer of the cervix uteri. A meta-analysis.

AIM AND OBJECTIVE: Because the findings of epidemiologic studies of the relationship between oral contraceptive use and cervical cancer have not been consistent, we reanalyzed the relationship. DESIGN: Meta-analysis of studies published to date. SETTING AND SUBJECTS: Papers were located by searching the MEDLINE data base, supplemented by a hand search of all the references in the articles recovered. MEASUREMENTS: Studies were graded as to quality. Two meta-analyses were performed: one including all the studies gathered and one including methodologically acceptable studies only. The method of Woolf was used to combine relative risks. Heterogeneity of the effect was assessed. MAIN RESULTS: Fifty-one published studies were collected: 21 case-control, 18 cross-sectional, and 12 cohort designs. Twenty-one of these were considered as methodologically acceptable, but only 18 could be pooled. The main results observed were: relative risks was 1.52 (1.3-1.8) for dysplasia, 1.52 (1.3-1.8) for carcinoma in situ, and 1.21 (1.1-1.4) for invasive cancer. A significant linear dose-response effect was observed in dysplasia, carcinoma in situ, and invasive cervical cancer. Heterogeneity of the effect was present in some of the former estimates. CONCLUSIONS: Oral contraceptive use may be a risk factor for all stages of the natural history of cervical cancer, which may imply an initiator effect. Limitations to this research are discussed.

Carcinoma in Situ↗

PubMed1992

Oral contraceptives and breast cancer. A review with some comments on mathematical models.

The relationship between oral contraceptive use and breast cancer is discussed on the basis of information given in review articles, meta-analyses and editorials emphasizing methodological problems related to bias and confounding. Over the last few years a shift in opinion has taken place. Most reviewers now consider that long-term use of oral contraceptives is associated with an increased risk of premenopausal breast cancer and no effect among postmenopausal breast cancer. This result is compatible with an additive effect (in rate measure scale) of oral contraceptive use on breast cancer risk.

Breast Neoplasms↗

PubMed2026

Evaluation of population-specific polygenic risk scores for blood lipids: insights from Taiwanese cohorts and multiancestry meta-analysis.

BACKGROUND: Blood lipids are heritable risk factors for cardiovascular disease (CVD), a leading cause of mortality worldwide. However, the genetic architecture of lipid traits and the performance of polygenic risk scores (PRSs) remain underexplored in East Asian (EAS) populations, including Taiwanese Han individuals. METHODS: We conducted genome-wide association studies and PRS analyses for five lipid traits: total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the ratio of low-density lipoprotein cholesterol to total cholesterol. Lipid profile data were obtained from the China Medical University Hospital cohort. PRSs were evaluated on the basis of their correlations with measured lipid levels. To evaluate trans-ancestry PRS transferability, localized models were systematically compared against models derived from discovery-stage GWAS meta-analyses incorporating five ancestry groups from the Global Lipids Genetics Consortium. The performance of the PRS models in predicting lipid-related diseases was evaluated through receiver operating characteristic curve analyses. RESULTS: The population-specific PRS models explained 11%-40% of the variance in lipid levels within the target cohort. Models leveraging global multiancestry GWAS meta-analysis weights revealed limited predictive performance (r 2 = 0.04-0.19), whereas analyses incorporating EAS-specific data yielded higher correlations (r 2 = 0.13-0.30), although these correlations did not exceed those derived from the hospital-based cohort alone. When combined with age and sex, the PRS models demonstrated strong predictive performance for coronary artery disease, atherosclerosis, and ischemic stroke, with area under the curve values of 0.910, 0.926, and 0.854, respectively. CONCLUSION: Population-specific PRS models derived from a Taiwanese population outperformed meta-analysis-derived frameworks in predicting lipid levels and demonstrated substantial potential for predicting CVD risk, indicating the importance of ancestry-matched genetic studies in precision medicine.

LDL-C/TC ratio↗

PubMed2026

Genetic associations in sepsis and ARDS.

Critical illness syndromes, such as sepsis and acute respiratory distress syndrome (ARDS), are characterized by substantial clinical heterogeneity and remain major causes of morbidity and mortality worldwide. Increasing evidence suggests that genetic variation contributes to susceptibility, disease severity, and clinical outcomes in critically ill patients. However, the molecular mechanisms linking genetic predisposition to the pathophysiology of sepsis and ARDS remain incompletely understood. In this review, we evaluated genetic associations reported in sepsis and ARDS, including 13 genome-wide studies identifying 19 unique single-nucleotide polymorphisms (SNPs) across 17 distinct genomic loci, as well as 21 meta-analyses of candidate-gene studies identifying 21 SNPs across 16 genes. The identified variants were primarily associated with pathways involved in pathogen recognition, immune and inflammatory signaling, leukocyte recruitment, and endothelial dysfunction. Collectively, these findings support a polygenic basis for susceptibility to critical illness and highlight several biologically relevant pathways that may contribute to sepsis and ARDS pathogenesis. Improved understanding of the functional consequences of these variants may facilitate the identification of potential therapeutic targets and support the development of precision-guided approaches to critical care.

ARDS↗

PubMed2021

Genetic Relationship Between Endometriosis and Melanoma.

Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma. Summary statistics from genome-wide association meta-analyses (GWAS) for endometriosis and melanoma were used to estimate the genetic correlation between the traits and Mendelian randomization was used to test for a causal association. When using summary statistics from separate female and male melanoma cohorts we identified a significant positive genetic correlation between melanoma in females and endometriosis (r g = 0.144, se = 0.065, p = 0.025). However, we find no evidence of a correlation between endometriosis and melanoma in males or a combined melanoma dataset. Endometriosis was not genetically correlated with skin color, red hair, childhood sunburn occasions, ease of skin tanning, or nevus count suggesting that the correlation between endometriosis and melanoma in females is unlikely to be influenced by pigmentary traits. Mendelian Randomization analyses also provided evidence for a relationship between the genetic risk of melanoma in females and endometriosis. Colocalization analysis identified 27 genomic loci jointly associated with the two diseases regions that contain different causal variants influencing each trait independently. This study provides evidence of a small genetic correlation and relationship between the genetic risk of melanoma in females and endometriosis. Genetic risk does not equate to disease occurrence and differences in the pathogenesis and age of onset of both diseases means it is unlikely that occurrence of melanoma causes endometriosis. This study instead provides evidence that having an increased genetic risk for melanoma in females is related to increased risk of endometriosis. Larger GWAS studies with increased power will be required to further investigate these associations.

endometriosis↗

PubMed2026

SARS-CoV-2-related immune dysregulation and biologically plausible pathways to lymphomagenesis: a PRISMA-ScR-based scoping review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related immune dysregulation has generated interest in diagnostic pathology because infection-related inflammation, long coronavirus disease (COVID)-related immune disturbance, and post-vaccination lymphoid reactions may overlap with lymphoid-biological mechanisms and complicate the distinction between reactive lymphoid proliferations and lymphoid neoplasia. AIM: This scoping review aimed to map biologically plausible pathways through which SARS-CoV-2-associated immune perturbation may intersect with lymphomagenesis-related mechanisms, emphasizing diagnostic implications rather than causality. MATERIALS AND METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). PubMed∕MEDLINE, Scopus, and Web of Science were searched from January 2020 to March 2026, with selected pre-2020 sources retained for mechanistic or diagnostic relevance. Sources were charted across mechanistic, immunological, virological, clinicopathological, and diagnostic domains. RESULTS: After screening and eligibility assessment, 63 sources were retained for thematic synthesis. Evidence clustered around lymphoma-relevant but non-specific mechanisms, including inflammatory signaling, impaired immune surveillance, latent oncogenic viral reactivation, prolonged germinal-center activity with activation-induced cytidine deaminase (AID)-related genomic vulnerability, and lymphoid microenvironment remodeling. These mechanisms appear most relevant in predisposed hosts with chronic immune dysregulation, latent viral infection, defective deoxyribonucleic acid (DNA) repair, or occult abnormal lymphoid clones. Infection and vaccination are distinct contexts, because infection may produce broader immune disruption, whereas most post-vaccination nodal events are reactive and self-limited. CONCLUSIONS: Current evidence supports biological plausibility rather than a direct or generalizable causal relationship. The main diagnostic implication is careful clinicopathological correlation and distinction between reactive lymphoid proliferations and lymphoid neoplasia in post-COVID-19 and post-vaccination settings.

Humans↗

PubMed2026

Multi-Ancestry Survival GWAS of Substance Use Initiation in the ABCD Study.

BACKGROUND: Substance use initiation in adolescence is influenced by both genetic and environmental factors; however, large-scale genetic studies often treat initiation as a binary outcome and underuse longitudinal timing information. METHODS: We conducted time-to-event (survival) genome-wide association analyses (GWAS) of initiation for four outcomes-alcohol, nicotine, cannabis, and any substance use-using longitudinal follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study. We performed ancestry-stratified GWAS within European (EUR), African (AFR), and Hispanic (HISP) groups, applying consistent quality control and covariate adjustment. Summary statistics were harmonized across ancestries and meta-analyzed using inverse-variance weighted fixed-effects and DerSimonian-Laird random-effects models. We evaluated genomic inflation and heterogeneity (Cochran's Q and I 2), identified independent lead variants at genome-wide and suggestive significance thresholds, and assessed cross-trait overlap of associated loci. RESULTS: In the multi-ancestry meta-analysis, we observed suggestive association signals across traits (minimum p-values: alcohol ~ 1 × 10-7, any ~ 1 × 10-7, cannabis ~ 5 × 10-8, nicotine ~ 1 × 10-8). Nicotine initiation showed one genome-wide significant variant in both fixed- and random-effects meta-analyses (p < 5 × 10-8). Across traits, suggestive loci demonstrated limited overlap, with the strongest concordance between alcohol and any substance use, consistent with shared liability. Heterogeneity statistics indicated that some loci exhibited cross-ancestry variation in effect estimates. CONCLUSIONS: Survival GWAS leveraging initiation timing can identify genetic signals that may be missed by binary designs and enables principled multi-ancestry synthesis. Our results highlight both shared and trait-specific genetic contributions to early substance initiation and provide a foundation for downstream functional annotation and integrative modeling with environmental risk factors. These findings demonstrate the value of incorporating developmental timing into genetic discovery and provide a framework for integrating longitudinal risk modeling with genomic analyses.

ABCD↗

PubMed2026

Systematic common and rare variant association testing in 392,030 whole genomes in All of Us.

Large-scale genome-wide association studies (GWAS) and rare variant association studies (RVAS) from population biobanks provide valuable resources for gene discovery in complex human traits. We present an analysis of the All of Us Research Program v8 release, which includes whole genome sequencing data and harmonized phenotypic information of 392,030 participants after quality control, enabling a unified investigation of rare and common variants across a spectrum of human traits and diseases. We build an extensive phenome- and genome-wide ("All by All") computational framework to perform GWAS and RVAS on 3,602 phenotypes and identify 49,863 approximately independent, high-quality single-variant and gene-level associations. Meta-analyses of All of Us and UK Biobank, with sample sizes as large as 786,871 participants, further enhance statistical power and find 193 pLoF gene-phenotype associations that are not significant in either cohort alone, including 22 associations not highlighted by previous studies. We also present a public interactive browser that integrates association results for common and rare variants to facilitate interpretation and rapid querying of summary statistics, along with supporting documentation, and a Featured Workspace in the All of Us Researcher Workbench. Our framework will apply to iterative data releases as All of Us grows, empowering researchers worldwide to uncover insights into the functional effects of genetic components on complex traits and diseases.

Journal Article↗

PubMed2026

The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration.

Rare coding variants can have large effects on disease risk and provide direct routes from human genetics to disease mechanisms and therapeutic targets, but their discovery is constrained by sample size, particularly for low-prevalence diseases. Here we establish the Biobank Rare Variant Analysis (BRaVa) consortium, a global rare variant association resource that integrates sequencing and linked health-record data from ten biobanks and cohorts comprising over 1.2 million individuals across diverse ancestries. We performed gene-based meta-analyses of rare coding variation across 33 clinical endpoints and 11 quantitative traits. Aggregating evidence across biobanks and ancestries identified 514 gene-trait associations, including 31 not previously reported in prior studies or curated association resources following systematic literature review. Notably, 36.1% of gene-level associations were undetectable in any individual biobank, and 91 emerged only through cross-ancestry meta-analysis, demonstrating that federated integration enables discovery beyond the reach of single cohorts. Similar gains were observed at the variant level, where 25.0% of phenotype-locus associations were detectable only through meta-analysis. Effect size estimates were correlated across ancestries with concordant directions of effect, supporting the generalizability of rare variant associations. The identified signals implicate pathways involved in transcriptional and epigenetic regulation, metabolism, vascular and epithelial biology, and immune function, highlighting rare coding variation as an engine for biological discovery across medical record phenotypes. For example, damaging variation in ANKRD12 implicates inflammatory transcriptional dysregulation in asthma and chronic obstructive pulmonary disease, and ultra-rare predicted loss-of-function variants in NAA15 link protein acetylation processes to type 2 diabetes risk. BRaVa establishes a scalable framework and freely available community resource for rare variant meta-analysis across global biobanks. Public release of gene- and variant-level association summary statistics provides a reference map of rare coding variant associations to support disease gene discovery, biological interpretation, and therapeutic target prioritization as sequencing-linked health-record resources continue to expand.

Journal Article↗

PubMed1992

A consumer's guide to subgroup analyses.

The extent to which a clinician should believe and act on the results of subgroup analyses of data from randomized trials or meta-analyses is controversial. Guidelines are provided in this paper for making these decisions. The strength of inference regarding a proposed difference in treatment effect among subgroups is dependent on the magnitude of the difference, the statistical significance of the difference, whether the hypothesis preceded or followed the analysis, whether the subgroup analysis was one of a small number of hypotheses tested, whether the difference was suggested by comparisons within or between studies, the consistency of the difference, and the existence of indirect evidence that supports the difference. Application of these guidelines will assist clinicians in making decisions regarding whether to base a treatment decision on overall results or on the results of a subgroup analysis.

Causality↗

PubMed2026

Evolving Role of Immunotherapy in Advanced Esophageal Squamous Cell Carcinoma: Are Programmed Death-Ligand 1 (PD-L1) Cutoffs Still Relevant?

Immune checkpoint inhibitors have transformed the management of advanced esophageal squamous cell carcinoma (ESCC) across first-line, second-line, and perioperative settings. Programmed death-ligand 1 (PD-L1) expression has served as the principal biomarker guiding patient selection for these agents, yet it is measured inconsistently across trials and antibody platforms, and its predictive value has come under renewed scrutiny as follow-up data have matured. This review synthesizes the pivotal randomized trials that established anti-programmed cell death protein-1 therapy in ESCC, critically appraises the pooled and patient-level meta-analyses that have re-examined outcomes across biomarker subgroups, and situates recent regulatory reassessment of PD-L1 thresholds within this broader evidence base. Assay heterogeneity between scoring systems, discordance across antibody clones, and the biological distinction between PD-L1 as a prognostic versus a predictive marker are examined as sources of continued uncertainty. The review concludes by considering emerging genomic and microenvironmental biomarkers that may eventually complement or refine PD-L1-based patient selection, and offers a framework for interpreting a single expression threshold as an approximate, assay-dependent stratifier rather than a precise biological boundary.

combined positive score↗

PubMed1992

[Mishaps with anti-arrhythmic agents used to reduce mortality after infarction].

The presence of isolated and/or repetitive ventricular arrhythmias following myocardial infarction identifies a group of patients at increased risk of death. The availability of anti-arrhythmic drugs, noticeably drugs with class I activity, efficient at suppressing arrhythmias has led to the hope that their administration could reduce post-myocardial infarction mortality. However, this hypothesis has not been confirmed. The Cardiac Arrhythmia Suppression Trial, which was designed to have the power to test the hypothesis that suppression of ventricular arrhythmias is associated with a decrease in mortality following myocardial infarction, even showed an increase in mortality with two drugs with class I activity. Several meta-analyses have confirmed that administration of class I antiarrhythmic drugs is of no clinical benefit in patients with non sustained ventricular arrhythmias following myocardial infarction. Ongoings studies are testing the hypothesis that such benefit could exist with amiodarone. The clinical benefit of beta-blockers, in terms of reduction of both total and sudden death post-myocardial infarction, has been clearly documented and mandates their administration in this setting. Futures studies of anti-arrhythmic drugs will have to focus on groups of patients at increased risk of arrhythmic death.

Amiodarone↗

PubMed1992

Review articles and publication bias.

Publication bias occurs if the results from studies which have not been published are different from the published ones. From a Bayesian viewpoint, it also concerns non-publication of studies with similar results as the published ones because the strength of the evidence will be influenced. Publication bias complicates the interpretation of reviews and meta-analyses. If favourable results are published more often there will be an overestimation of the effects of a treatment. There have been several attempts to assess the magnitude of publication bias. Unpublished trials could be identified by means of a survey among researchers, and the results could subsequently be compared with the outcomes of published trials. Also, the results from published trials could be compared with trials from a registry. Furthermore, the results from registered but unpublished trials could be compared with those of registered and subsequently published trials. Studies addressing publication bias have shown that it is a serious problem which complicates the interpretation of reviews. In assessments of publication bias other factors must be taken into account. These include the mode of publication: refereed journals, other journals, books, etc. Differences could also be related to the quality of trials. Finally, the source of funding may influence both the results and subsequent publication. Publication bias can only be avoided by registration of all trials before data collection is started; several of such registries have already been installed. Perhaps, if more of such registries exist, reviewers could only use registered trials for their main conclusions. All other information could then be considered sensitive to publication bias.

Meta-Analysis as Topic↗

PubMed1992

Paroxetine in the treatment of melancholia and severe depression.

Meta-analyses of the worldwide paroxetine database assessed the efficacy of this compound in the treatment of both DSM-III defined melancholia and hospitalised patients with severe depression (HAMD > or = 25). The analysis for melancholia included 178 paroxetine treated patients and 66 patients treated with placebo. Paroxetine was significantly superior to placebo in the treatment of melancholia and a clear dose-response relationship was established. The meta-analysis for severely depressed hospitalised patients included 109 paroxetine treated patients and 107 patients treated with a tricyclic/tetracyclic control. Paroxetine and active controls showed comparable efficacy in the treatment of severely depressed hospitalised patients.

Adult↗

PubMed1992

The exclusion of the elderly and women from clinical trials in acute myocardial infarction.

OBJECTIVE: To determine the extent to which the elderly have been excluded from trials of drug therapies used in the treatment of acute myocardial infarction, to identify factors associated with such exclusions, and to explore the relationship between the exclusion of elderly and the representation of women. DATA SOURCES: We conducted a systematic search of the English-language literature from January 1960 through September 1991 to identify all relevant studies of specific pharmacotherapies employed in the treatment of acute myocardial infarction. To accomplish this, we searched MEDLINE, major cardiology textbooks, meta-analyses, reviews, editorials, and the bibliographies of all identified articles. STUDY SELECTION: Only trials in which patients were randomly allocated to receive a specific therapeutic regimen or a placebo or nonplacebo control regimen were included for review. DATA EXTRACTION: Studies were abstracted for year of publication, source of support, performance location, drug therapies to which patients were randomized, use of invasive diagnostic tests or therapeutic procedures, exclusion criteria, size and demographic characteristics of the randomized study population, and principal outcome measures. DATA SYNTHESIS: A total of 214 trials met inclusion criteria, involving 150,920 study subjects. Over 60% of trials excluded persons over the age of 75 years. Studies published after 1980 were more likely to have age-based exclusions compared with studies published before 1980 (adjusted odds ratio, 4.92; 95% confidence interval, 2.33 to 10.54). Trials of thrombolytic therapy involving an invasive procedure were more likely to exclude elderly patients compared with other studies (adjusted odds ratio, 2.45; 95% confidence interval, 1.10 to 5.47). Studies with age-based exclusions had a smaller percentage of women compared with those without such exclusions (18% vs 23%; P = .0002), with the mean age of the study population significantly associated with the proportion of women participants (P = .0001, R2 = .29). CONCLUSIONS: Age-based exclusions are frequently used in clinical trials of medications used in the treatment of acute myocardial infarction. Such exclusions limit the ability to generalize study findings to the patient population that experiences the most morbidity and mortality from acute myocardial infarction.

Age Factors↗

PubMed1992

The impact of stopping rules on heterogeneity of results in overviews of clinical trials.

This paper explores the extent to which application of statistical stopping rules in clinical trials can create an artificial heterogeneity of treatment effects in overviews (meta-analyses) of related trials. For illustration, we concentrate on overviews of identically designed group sequential trials, using either fixed nominal or O'Brien and Fleming two-sided boundaries. Some analytic results are obtained for two-group designs and simulation studies are otherwise used, with the following overall findings. The use of stopping rules leads to biased estimates of treatment effect so that the assessment of heterogeneity of results in an overview of trials, some of which have used stopping rules, is confounded by this bias. If the true treatment effect being studied is small, as is often the case, then artificial heterogeneity is introduced, thus increasing the Type I error rate in the test of homogeneity. This could lead to erroneous use of a random effects model, producing exaggerated estimates and confidence intervals. However, if the true mean effect is large, then between-trial heterogeneity may be underestimated. When undertaking or interpreting overviews, one should ascertain whether stopping rules have been used (either formally or informally) and should consider whether their use might account for any heterogeneity found.

Analysis of Variance↗