Including Non-inferiority Trials in Contemporary Meta-analyses of Chronic Medical Conditions: a Meta-epidemiological Study.
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ABSTRACT:
SUBMITTER: Wang Z
PROVIDER: S-EPMC7352026 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: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: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.
| S-EPMC4850460 | biostudies-other
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:BACKGROUND:Patients with posttraumatic stress disorder (PTSD) are at increased risk for adverse consequences from comorbid medical conditions. Nonadherence to medications prescribed to treat those comorbid conditions may help explain this increased risk. We sought to determine the association between PTSD and medication nonadherence and whether it varied according to the type of event inducing the PTSD. METHODS:Prospective observational cohort or cross-sectional studies relating PTSD and nonadherence among adults prescribed medications for a chronic medical illness were identified by searching MEDLINE, EMBASE, PsycINFO, the Cochrane Library, CINAHL, SCOPUS, and the PILOTS Database and by hand-searching bibliographies from selected articles. Individual estimates of odds ratios were pooled using random effects meta-analysis with inverse variance weighting. Articles were pooled separately according to whether PTSD was induced by a medical versus non-medical event. OUTCOMES:Sixteen articles comprising 4483 patients met eligibility criteria. The pooled effect size of the risk of PTSD to medication nonadherence was OR 1.22 (95% CI, 1.06-1.41). Among the 6 studies of medical event-induced PTSD, the OR was 2.08 (95% CI, 1.03-4.18); p?=?0.04. Among the 8 studies in which PTSD was not induced by a medical event, the OR was 1.10 (95% CI, 0.99-1.24); p?=?0.09. INTERPRETATION:Patients with PTSD were more likely to be nonadherent to medications prescribed for chronic medical conditions - an association that may exist specifically when PTSD was induced by a medical event. Medications may serve as aversive reminders among survivors of acute medical events, magnifying avoidance behaviors characteristic of PTSD. FUNDING:NHLBI.
| S-EPMC6124486 | biostudies-literature
Project description:We established patient-derived organoids and monolayer culture cells from the salivary gland cancer cases. To compare the RNA profiles of primary culture cells (Organoids and monolayer culture cells) and their parental tumors, we isolated total RNA from 2 cases of the salivary gland cancer and performed transcriptome sequencing for the organoids, monolayer culture cells, and their parental tumors of both cases. Case 6 is a case of adenoid cystic carcinoma and Case 11 is a case of salivary duct carcinoma.
2023-04-27 | GSE223554 | GEO
Project description:AimsThe neutrophil-lymphocyte ratio (NLR) is a readily available inflammatory biomarker that may associate with atherosclerosis and predict cardiovascular (CV) events. The aims of this study are to determine whether the NLR predicts incident major adverse cardiovascular events (MACE) and is modified by anti-inflammatory therapy.Methods and resultsBaseline and on-treatment NLRs were calculated from complete blood counts among 60 087 participants randomized in the CANTOS, JUPITER, SPIRE-1, SPIRE-2, and CIRT trials to receive placebo or canakinumab, rosuvastatin, bococizumab, or methotrexate, respectively, and followed up for MACE. All analyses were performed first in CANTOS, and then externally validated in the other four trials. For the five trials, hazard ratios for major CV events and mortality comparing NLR quartiles were computed using Cox proportional hazards models, and the effect of each randomized intervention on the NLR was evaluated in comparison to placebo. The NLR modestly correlated with interleukin-6, C-reactive protein, and fibrinogen levels but minimally with lipids. In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14-25%, P < 0.0001], 31% in SPIRE-1 (95% CI 14-49%, P = 0.00007), 27% in SPIRE-2 (95% CI 12-43%, P = 0.0002), 9% in CIRT (95% CI 0.2-20%, P = 0.045), and 11% in JUPITER (95% CI 1-22%, P = 0.03). While lipid-lowering agents had no significant impact on the NLR, anti-inflammatory therapy with canakinumab lowered the NLR (P < 0.0001).ConclusionThe NLR, an easily obtained inflammatory biomarker, independently predicts CV risk and all-cause mortality, and is reduced by interleukin-1β blockade with canakinumab.
| S-EPMC7936519 | biostudies-literature
Project description:ObjectivesAdaptive platforms allow for the evaluation of multiple interventions at a lower cost and have been growing in popularity, especially during the COVID-19 pandemic. The objective of this review is to summarize published platform trials, examine specific methodological design features among these studies, and hopefully aid readers in the evaluation and interpretation of platform trial results.MethodsWe performed a systematic review of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov from January 2015 to January 2022 for protocols or results of platform trials. Pairs of reviewers, working independently and in duplicate, collected data on trial characteristics of trial registrations, protocols, and publications of platform trials. We reported our results using total numbers and percentages, as well as medians with interquartile range (IQR) when appropriate.ResultsWe identified 15,277 unique search records and screened 14,403 titles and abstracts after duplicates were removed. We identified 98 unique randomized platform trials. Sixteen platform trials were sourced from a systematic review completed in 2019, which included platform trials reported prior to 2015. Most platform trials (n = 67, 68.3%) were registered between 2020 and 2022, coinciding with the COVID-19 pandemic. The included platform trials primarily recruited or plan to recruit patients from North America or Europe, with most subjects being recruited from the United States (n = 39, 39.7%) and the United Kingdom (n = 31, 31.6%). Bayesian methods were used in 28.6% (n = 28) of platform RCTs and frequentist methods in 66.3% (n = 65) of trials, including 1 (1%) that used methods from both paradigms. Out of the twenty-five trials with peer-reviewed publication of results, seven trials used Bayesian methods (28%), and of those, two (8%) used a predefined sample size calculation while the remainder used pre-specified probabilities of futility, harm, or benefit calculated at (pre-specified) intervals to inform decisions about stopping interventions or the entire trial. Seventeen (68%) peer-reviewed publications used frequentist methods. Out of the seven published Bayesian trials, seven (100%) reported thresholds for benefit. The threshold for benefit ranged from 80% to >99%.ConclusionWe identified and summarized key components of platform trials, including the basics of the methodological and statistical considerations. Ultimately, improving standardization and reporting in platform trials require an understanding of the current landscape. We provide the most updated and rigorous review of platform trials to date.
| S-EPMC9991927 | biostudies-literature
Project description:Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, androgen receptor inhibition, and CYP17 (cytochrome P450 17A1) inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.
| S-EPMC7047549 | biostudies-literature
Project description: Not available
| S-EPMC10902941 | biostudies-literature