Including Non-inferiority Trials in Contemporary Meta-analyses of Chronic Medical Conditions: a Meta-epidemiological Study.
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SUBMITTER: Wang Z
PROVIDER: S-EPMC7352026 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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Including Non-inferiority Trials in Contemporary Meta-analyses of Chronic Medical Conditions: a Meta-epidemiological Study.
Wang Zhen Z Nayfeh Tarek T Sofiyeva Nigar N Ponte Oscar J OJ Rajjoub Rami R Malandris Konstantinos K Seisa Mohamed M Chu Haitao H Murad Mohammad Hassan MH
Journal of general internal medicine 20200421 7
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Project description:It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, particularly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence, using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was undertaken in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses (59 reports yielded from these studies) assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% confidence interval (CI): 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality; however, careful evaluation according to cancer types is critically important and recommended.
| S-EPMC10302100 | biostudies-literature
Project description:BackgroundPilot/feasibility or studies with small sample sizes may be associated with inflated effects. This study explores the vibration of effect sizes (VoE) in meta-analyses when considering different inclusion criteria based upon sample size or pilot/feasibility status.MethodsSearches were to identify systematic reviews that conducted meta-analyses of behavioral interventions on topics related to the prevention/treatment of childhood obesity from January 2016 to October 2019. The computed summary effect sizes (ES) were extracted from each meta-analysis. Individual studies included in the meta-analyses were classified into one of the following four categories: self-identified pilot/feasibility studies or based upon sample size but not a pilot/feasibility study (N ≤ 100, N > 100, and N > 370 the upper 75th of sample size). The VoE was defined as the absolute difference (ABS) between the re-estimations of summary ES restricted to study classifications compared to the originally reported summary ES. Concordance (kappa) of statistical significance of summary ES between the four categories of studies was assessed. Fixed and random effects models and meta-regressions were estimated. Three case studies are presented to illustrate the impact of including pilot/feasibility and N ≤ 100 studies on the estimated summary ES.ResultsA total of 1602 effect sizes, representing 145 reported summary ES, were extracted from 48 meta-analyses containing 603 unique studies (avg. 22 studies per meta-analysis, range 2-108) and included 227,217 participants. Pilot/feasibility and N ≤ 100 studies comprised 22% (0-58%) and 21% (0-83%) of studies included in the meta-analyses. Meta-regression indicated the ABS between the re-estimated and original summary ES where summary ES ranged from 0.20 to 0.46 depending on the proportion of studies comprising the original ES were either mostly small (e.g., N ≤ 100) or mostly large (N > 370). Concordance was low when removing both pilot/feasibility and N ≤ 100 studies (kappa = 0.53) and restricting analyses only to the largest studies (N > 370, kappa = 0.35), with 20% and 26% of the originally reported statistically significant ES rendered non-significant. Reanalysis of the three case study meta-analyses resulted in the re-estimated ES rendered either non-significant or half of the originally reported ES.ConclusionsWhen meta-analyses of behavioral interventions include a substantial proportion of both pilot/feasibility and N ≤ 100 studies, summary ES can be affected markedly and should be interpreted with caution.
| S-EPMC9938611 | biostudies-literature
Project description:BackgroundTo assess the impact of trials with potential financial conflict of interests (FCOIs) on evidence synthesis in meta-analyses (MAs).MethodsA total of 96 MAs from the Cochrane Library about drug trials were investigated. The primary outcomes examined the proportion of conclusions that would change with the exclusion of trials with potential FCOIs. If the proportion of changed conclusions was below the non-inferiority margin of 10%, we considered that it was not inferior to include the trials with potential FCOIs in the MAs.ResultsOnly 54.17% of MAs reported the funding sources of each included trial, and in 21.88% of MAs, the author-industry-related financial ties of each included trial were reported. When trials with FCOIs were excluded, the changed conclusions of effectiveness and major adverse events were 13.16% and 11.11%, respectively, and the I2 decreased by 13.56% and 10.09%, respectively. For serious adverse events, the exclusion of FCOIs trials did not lead to any change in conclusions; however, the I2 decreased by 24.24%. The impact of trials without reported FCOIs was also examined on evidence synthesis, and the results showed that the changed conclusions of effectiveness and major adverse events were 5.26% and 6.25%, respectively, indicating non-inferiority. However, the I2 increased by 13.60% and 12.37%, respectively.ConclusionIn this meta-epidemiological study, we demonstrated that trials with FCOIs may not only influence the final outcome of MAs but may also increase the heterogeneity of results. It is suggested that all MAs fully report the FCOIs involved in evidence-based research and explore the impact of its FCOIs to better provide a more valuable reference for patients, clinicians, and policy-makers.
| S-EPMC9808270 | biostudies-literature
Project description:IntroductionIn trials, subgroup analyses are used to examine whether treatment effects differ by important patient characteristics. However, which subgroups are most commonly reported has not been comprehensively described.Design and settingsUsing a set of trials identified from the US clinical trials register (ClinicalTrials.gov), we describe every reported subgroup for a range of conditions and drug classes.MethodsWe obtained trial characteristics from ClinicalTrials.gov via the Aggregate Analysis of ClinicalTrials.gov database. We subsequently obtained all corresponding PubMed-indexed papers and screened these for subgroup reporting. Tables and text for reported subgroups were extracted and standardised using Medical Subject Headings and WHO Anatomical Therapeutic Chemical codes. Via logistic and Poisson regression models we identified independent predictors of result reporting (any vs none) and subgroup reporting (any vs none and counts). We then summarised subgroup reporting by index condition and presented all subgroups for all trials via a web-based interactive heatmap (https://ihwph-hehta.shinyapps.io/subgroup_reporting_app/).ResultsAmong 2235 eligible trials, 23% (524 trials) reported subgroups. Follow-up time (OR, 95%CI: 1.13, 1.04-1.24), enrolment (per 10-fold increment, 3.48, 2.25-5.47), trial starting year (1.07, 1.03-1.11) and specific index conditions (eg, hypercholesterolaemia, hypertension, taking asthma as the reference, OR ranged from 0.15 to 10.44), predicted reporting, sponsoring source and number of arms did not. Results were similar on modelling any result reporting (except number of arms, 1.42, 1.15-1.74) and the total number of subgroups. Age (51%), gender (45%), racial group (28%) were the most frequently reported subgroups. Characteristics related to the index condition (severity/duration/types etc) were frequently reported (eg, 69% of myocardial infarction trials reported on its severity/duration/types). However, reporting on comorbidity/frailty (five trials) and mental health (four trials) was rare.ConclusionOther than age, sex, race ethnicity or geographic location and characteristics related to the index condition, information on variation in treatment effects is sparse.Prospero registration numberCRD42018048202.
| S-EPMC11328666 | biostudies-literature
Project description:CONTEXT: Older adults are underrepresented in clinical research. To assess therapeutic efficacy in older patients, some randomized controlled trials (RCTs) include older adults only. OBJECTIVE: To compare treatment effects between RCTs including older adults only (elderly RCTs) and RCTs including all adults (adult RCTs) by a meta-epidemiological approach. METHODS: All systematic reviews published in the Cochrane Library (Issue 4, 2011) were screened. Eligible studies were meta-analyses of binary outcomes of pharmacologic treatment including at least one elderly RCT and at least one adult RCT. For each meta-analysis, we compared summary odds ratios for elderly RCTs and adult RCTs by calculating a ratio of odds ratios (ROR). A summary ROR was estimated across all meta-analyses. RESULTS: We selected 55 meta-analyses including 524 RCTs (17% elderly RCTs). The treatment effects differed beyond that expected by chance for 7 (13%) meta-analyses, showing more favourable treatment effects in elderly RCTs in 5 cases and in adult RCTs in 2 cases. The summary ROR was 0.91 (95% CI, 0.77-1.08, p?=?0.28), with substantial heterogeneity (I(2)?=?51% and ?(2)?=?0.14). Sensitivity and subgroup analyses by type-of-age RCT (elderly RCTs vs RCTs excluding older adults and vs RCTs of mixed-age adults), type of outcome (mortality or other) and type of comparator (placebo or active drug) yielded similar results. CONCLUSIONS: The efficacy of pharmacologic treatments did not significantly differ, on average, between RCTs including older adults only and RCTs of all adults. However, clinically important discrepancies may occur and should be considered when generalizing evidence from all adults to older adults.
| S-EPMC3665786 | biostudies-other
Project description:Several studies reported that Tai Chi showed potential effects for chronic pain, but its role remains controversial. This review assessed the evidence regarding the effects of Tai Chi for chronic pain conditions. 18 randomized controlled trials were included in our review. The aggregated results have indicated that Tai Chi showed positive evidence on immediate relief of chronic pain from osteoarthritis (standardized mean difference [SMD], -0.54; 95% confidence intervals [CI], -0.77 to -0.30; P < 0.05). The valid duration of Tai Chi practice for osteoarthritis may be more than 5 weeks. And there were some beneficial evidences regarding the effects of Tai Chi on immediate relief of chronic pain from low back pain (SMD, -0.81; 95% CI, -1.11 to -0.52; P < 0.05) and osteoporosis (SMD, -0.83; 95% CI, -1.37 to -0.28; P = 0.003). Therefore, clinicians may consider Tai Chi as a viable complementary and alternative medicine for chronic pain conditions.
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Project description:To determine the association of socioeconomic disadvantage with the prevalence of childhood disabling chronic conditions in high-income countries.Systematic review and meta-analyses.6 electronic databases, relevant websites, reference lists and experts in the field.160 observational studies conducted in high-income countries with data on socioeconomic status and disabling chronic conditions in childhood, published between 1 January 1991 and 31 December 2013.Abstracts were reviewed, full papers obtained, and papers identified for inclusion by 2 independent reviewers. Inclusion decisions were checked by a third reviewer. Where reported, ORs were extracted for low versus high socioeconomic status. For studies reporting raw data but not ORs, ORs were calculated. Narrative analysis was undertaken for studies without data suitable for meta-analysis.126 studies had data suitable for meta-analysis. ORs for risk estimates were: all-cause disabling chronic conditions 1.72 (95% CI 1.48 to 2.01); psychological disorders 1.88 (95% CI 1.68 to 2.10); intellectual disability 2.41 (95% CI 2.03 to 2.86); activity-limiting asthma 2.20 (95% CI 1.87 to 2.85); cerebral palsy 1.42 (95% CI 1.26 to 1.61); congenital abnormalities 1.41 (95% CI 1.24 to 1.61); epilepsy 1.38 (95% CI 1.20 to 1.59); sensory impairment 1.70 (95% CI 1.39 to 2.07). Heterogeneity was high across most estimates (I(2)>75%). Of the 34 studies without data suitable for meta-analysis, 26 reported results consistent with increased risk associated with low socioeconomic status.The findings indicate that, in high-income countries, childhood disabling chronic conditions are associated with social disadvantage. Although evidence of an association is consistent across different countries, the review provides limited evidence to explain the association; future research, using longitudinal data, will be required to distinguish low socioeconomic status as the cause or consequence of childhood disabling chronic conditions and the aetiological pathways and mechanisms.
| S-EPMC4563224 | biostudies-other
Project description:IntroductionAlthough interest in including non-randomised studies of interventions (NRSIs) in meta-analysis of randomised controlled trials (RCTs) is growing, estimates of effectiveness obtained from NRSIs are vulnerable to greater bias than RCTs. The objectives of this study are to: (1) explore how NRSIs can be integrated into a meta-analysis of RCTs; (2) assess concordance of the evidence from non-randomised and randomised trials and explore factors associated with agreement; and (3) investigate the impact on estimates of pooled bodies of evidence when NRSIs are included.Methods and analysisWe will conduct a systematic survey of 210 systematic reviews that include both RCTs and NRSIs, published from 2017 to 2022. We will randomly select reviews, stratified in a 1:1 ratio by Core vs non-Core clinical journals, as defined by the National Library of Medicine. Teams of paired reviewers will independently determine eligibility and abstract data using standardised, pilot-tested forms. The concordance of the evidence will be assessed by exploring agreement in the relative effect reported by NRSIs and RCT addressing the same clinical question, defined as similarity of the population, intervention/exposure, control and outcomes. We will conduct univariable and multivariable logistic regression analyses to examine the association of prespecified study characteristics with agreement in the estimates between NRSIs and RCTs. We will calculate the ratio of the relative effect estimate from NRSIs over that from RCTs, along with the corresponding 95% CI. We will use a bias-corrected meta-analysis model to investigate the influence on pooled estimates when NRSIs are included in the evidence synthesis.Ethics and disseminationEthics approval is not required. The findings of this study will be disseminated through peer-reviewed publications, conference presentations and condensed summaries for clinicians, health policymakers and guideline developers regarding the design, conduct, analysis, and interpretation of meta-analysis that integrate RCTs and NRSIs.
| S-EPMC10373676 | biostudies-literature
Project description:BackgroundDigital health interventions might extend service provisions for youth with chronic medical conditions (CC) and comorbid mental health symptoms. We aimed to comprehensively evaluate the efficacy of Internet- and mobile-based interventions (IMIs) for different psychological and disease-related outcomes in children and adolescents with CC.MethodStudies were identified by systematic searches in CENTRAL, Embase, MEDLINE/PubMed and PsycINFO, complemented by searches in reference lists of eligible studies and other reviews. We included studies, when they were randomized controlled trials (RCTs) comparing the efficacy of an IMI to control conditions in improving psychological and disease-related outcomes in youth (mean age ≤ 18 years) with CC. Study selection, data extraction and risk of bias assessment were conducted independently by two reviewers. Meta-analyses were performed within a random-effects model, and Hedges' g (with 95% confidence intervals) was calculated as effect size measure. Primary outcomes were comorbid mental health symptoms (i.e., depression, anxiety and stress), as well as quality of life and self-efficacy.ResultsA total of 19 randomized controlled trials (2410 patients) were included in this meta-analysis. IMIs were associated with improvements in self-efficacy (g = 0.38; 95% CI, 0.15 to 0.61; I 2 = 0) and combined disease-related outcomes (g = -0.13; 95% CI, -0.25 to -0.01; I 2 = 21). Meta-analyses on other outcomes were non-significant, and some pre-planned analyses were not feasible because of a shortage of studies.ConclusionThe available evidence on IMIs for improving mental and health-related outcomes in youth with CC is limited. Our findings point to a rather small benefit and limited efficacy. Future research is needed, to comprehensively assess the potential of IMIs to extend collaborative care, and to identify factors contributing to improved user-centered interventions with better treatment outcomes.
| S-EPMC7941178 | biostudies-literature
Project description:Background In chronic coronary syndromes, myocardial ischemia is associated with a greater risk of death and nonfatal myocardial infarction (MI). We sought to compare the effect of initial revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) plus optimal medical therapy (OMT) with OMT alone in patients with chronic coronary syndrome and myocardial ischemia on long-term death and nonfatal MI. Methods and Results Ovid Medline, Embase, Scopus, and Cochrane Library databases were searched for randomized controlled trials of PCI or CABG plus OMT versus OMT alone for patients with chronic coronary syndromes. Studies were screened and data were extracted independently by 2 authors. Random-effects models were used to generate pooled treatment effects. The search yielded 7 randomized controlled trials that randomized 10 797 patients. Median follow-up was 5 years. Death occurred in 640 of the 5413 patients (11.8%) randomized to revascularization and in 647 of the 5384 patients (12%) randomized to OMT (odds ratio [OR], 0.97; 95% CI, 0.86-1.09; P=0.60). Nonfatal MI was reported in 554 of 5413 patients (10.2%) in the revascularization arms compared with 627 of 5384 patients (11.6%) in the OMT arms (OR, 0.75; 95% CI, 0.57-0.99; P=0.04). In subgroup analysis, nonfatal MI was significantly reduced by CABG (OR, 0.35; 95% CI, 0.21-0.59; P<0.001) but was not reduced by PCI (OR, 0.92; 95% CI, 0.75-1.13; P=0.43) (P-interaction <0.001). Conclusions In patients with chronic coronary syndromes and myocardial ischemia, initial revascularization with PCI or CABG plus OMT did not reduce long-term mortality compared with OMT alone. CABG plus OMT reduced nonfatal MI compared with OMT alone, whereas PCI did not.
| S-EPMC7955292 | biostudies-literature