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Human Reproduction (Oxford, England) Apr 2019How much statistical power do randomised controlled trials (RCTs) and meta-analyses have to investigate the effectiveness of interventions in reproductive medicine? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
How much statistical power do randomised controlled trials (RCTs) and meta-analyses have to investigate the effectiveness of interventions in reproductive medicine?
SUMMARY ANSWER
The largest trials in reproductive medicine are unlikely to detect plausible improvements in live birth rate (LBR), and meta-analyses do not make up for this shortcoming.
WHAT IS KNOWN ALREADY
Effectiveness of interventions is best evaluated using RCTs. In order to be informative, these trials should be designed to have sufficient power to detect the smallest clinically relevant effect. Similar trials can subsequently be pooled in meta-analyses to more precisely estimate treatment effects.
STUDY DESIGN, SIZE, DURATION
A review of power and precision in 199 RCTs and meta-analyses from 107 Cochrane Reviews was conducted.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Systematic reviews published by Cochrane Gynaecology and Fertility with the primary outcome live birth were identified. For each live birth (or ongoing pregnancy) meta-analysis and for the largest RCT in each, we calculated the power to detect absolute improvements in LBR of varying sizes. Additionally, the 95% CIs of estimated treatment effects from each meta-analysis and RCT were recorded, as these indicate the precision of the result.
MAIN RESULTS AND THE ROLE OF CHANCE
Median (interquartile range) power to detect an improvement in LBR of 5 percentage points (pp) (e.g. 25-30%) was 13% (8-21%) for RCTs and 16% (9-33%) for meta-analyses. No RCTs and only 2% of meta-analyses achieved 80% power to detect an improvement of 5 pp. Median power was high (85% for trials and 93% for meta-analyses) only in relation to 20 pp absolute LBR improvement, although substantial numbers of trials and meta-analyses did not achieve 80% power even for this improbably large effect size. Median width of 95% CIs was 25 pp and 21 pp for RCTs and meta-analyses, respectively. We found that 28% of Cochrane Reviews with LBR as the primary outcome contain no live birth (or ongoing pregnancy) data.
LARGE-SCALE DATA
The data used in this study may be accessed at https://osf.io/852tn/?view_only=90f1579ce72747ccbe572992573197bd.
LIMITATIONS, REASONS FOR CAUTION
The design and analysis decisions used in this study are predicted to overestimate the power of trials and meta-analyses, and the size of the problem is therefore likely understated. For some interventions, it is possible that larger trials not reporting live birth or ongoing pregnancy have been conducted, which were not included in our sample. In relation to meta-analyses, we calculated power as though all participants were included in a single trial. This ignores heterogeneity between trials in a meta-analysis, and will cause us to overestimate power.
WIDER IMPLICATIONS OF THE FINDINGS
Trials capable of detecting realistic improvements in LBR are lacking in reproductive medicine, and meta-analyses are not large enough to overcome this deficiency. This situation will lead to unwarranted pessimism as well as unjustified enthusiasm regarding reproductive interventions, neither of which are consistent with the practice of evidence-based medicine or the idea of informed patient choice. However, RCTs and meta-analyses remain vital to establish the effectiveness of fertility interventions. We discuss strategies to improve the evidence base and call for collaborative studies focusing on the most important research questions.
STUDY FUNDING/COMPETING INTEREST(S)
There was no specific funding for this study. KS and SL declare no conflict of interest. AV consults for the Human Fertilisation and Embryology Authority (HFEA): all fees are paid directly to AV's employer. JW declares that publishing research benefits his career. SR is a Statistical Editor for Human Reproduction. JW and AV are Statistical Editors for Cochrane Gynaecology and Fertility. DRB is funded by the NHS as Scientific Director of a clinical IVF service.
PROSPERO REGISTRATION NUMBER
None.
Topics: Birth Rate; Female; Humans; Infertility; Live Birth; Pregnancy; Randomized Controlled Trials as Topic; Reproductive Medicine; Treatment Outcome
PubMed: 30838395
DOI: 10.1093/humrep/dez017 -
Journal of Psychosomatic Research Dec 2016Depression is common in people with long term conditions, and is associated with worse medical outcomes. Previous research shows perseverative negative thinking (e.g.... (Review)
Review
OBJECTIVE
Depression is common in people with long term conditions, and is associated with worse medical outcomes. Previous research shows perseverative negative thinking (e.g. worry, rumination) predicts subsequent depression and worse medical outcomes, suggesting interventions targeting perseverative negative thinking could improve depression and medical outcomes. Previous studies recruited healthy individuals, however. This review aimed to determine the temporal relationship and strength of prospective association of perseverative negative thinking with depression, anxiety and emotional distress in people with long term conditions.
METHOD
Four electronic databases were searched for studies including standardised measures of perseverative negative thinking and depression, anxiety or emotional distress, and which presented prospective associations. Findings were narratively synthesized.
RESULTS
Thirty studies were identified in a range of long term conditions. Perseverative negative thinking and subsequent depression, anxiety or emotional distress were significantly correlated in the majority of studies (bivariate r=0.23 to r=0.73). 25 studies controlled for confounders, and in 15 perseverative negative thinking predicted subsequent depression, anxiety or emotional distress. Results varied according to condition and study quality. Six of 7 studies found bivariate associations between depression, anxiety or emotional distress and subsequent perseverative negative thinking, though 2 studies controlling for key covariates found no association. Few studies assessed the impact of perseverative negative thinking on medical outcomes.
CONCLUSION
Strongest evidence supported perseverative negative thinking predicting subsequent depression, anxiety and emotional distress in people with long term conditions. Further prospective research is warranted to clarify the association of perseverative negative thinking with subsequent poor medical outcomes.
Topics: Adult; Anxiety; Chronic Disease; Depression; Female; Humans; Male; Pessimism; Stereotyped Behavior; Stress, Psychological; Young Adult
PubMed: 27894469
DOI: 10.1016/j.jpsychores.2016.11.004 -
Digital Health 2016Africa is labelled the world's fastest-growing 'mobile region'. Considering such growth and the fragility of the continent's healthcare, mHealth has flourished. This... (Review)
Review
Exploring the ambivalent evidence base of mobile health (mHealth): A systematic literature review on the use of mobile phones for the improvement of community health in Africa.
BACKGROUND
Africa is labelled the world's fastest-growing 'mobile region'. Considering such growth and the fragility of the continent's healthcare, mHealth has flourished. This review explores mHealth for community health in Africa in order to assess its still ambivalent evidence base.
METHODS
Using PubMed, Web of Science, OvidSP and Google Scholar, a systematic review was conducted of one decade (2005-2015) of peer-reviewed literature on mHealth in Africa. Data analysis focused on qualifications of success and failure. Impact evaluations of project assessments ( = 65) were complemented with general analyses/overviews of mHealth's effectiveness ( = 35).
RESULTS
Review of these texts reveals ambivalence in the appraisal of mHealth; essentially, the critical stance in general analyses/overviews is absent from project assessments. Especially weak evidence concerning sustainability and scalability is stressed in overviews. Project assessments are more optimistic. Their analysis suggests a causal connection between simplicity and success. Effective interventions are thus characterized by straightforward design and modest objectives. Greatest impediments of impact are general technology-related issues and intervention inappropriateness due to insufficient understanding of beneficiaries and specific context of use (circumstantial complications).
CONCLUSION
Distinguishing between these two categories of complications helps to break the deadlock that marks the mHealth debate and add nuance to claims that mHealth's evidence base is weak. Constructive realism - rather than unfounded optimism or pessimism without nuance - should guide the design of interventions. Besides anticipative of technology-related complications, such realism must lead to either basic interventions or to smart mHealth shaped by deep understanding of the context of implementation.
PubMed: 29942576
DOI: 10.1177/2055207616679264 -
Social Science & Medicine (1982) May 2019The criminological "broken windows" theory (BWT) has inspired public health researchers to test the impact of neighborhood disorder on an array of resident health... (Meta-Analysis)
Meta-Analysis
The criminological "broken windows" theory (BWT) has inspired public health researchers to test the impact of neighborhood disorder on an array of resident health behaviors and outcomes. This paper identifies and meta-analyzes the evidence for three mechanisms (pathways) by which neighborhood disorder is argued to impact health, accounting for methodological inconsistencies across studies. A search identified 198 studies (152 with sufficient data for meta-analysis) testing any of the three pathways or downstream, general health outcomes. The meta-analysis found that perceived disorder was consistently associated with mental health outcomes, as well as substance abuse, and measures of overall health. This supported the psychosocial model of disadvantage, in which stressful contexts impact mental health and related sequelae. There was no consistent evidence for disorder's impact on physical health or risky behavior. Further examination revealed that support for BWT-related hypotheses has been overstated owing to data censoring and the failure to consistently include critical covariates, like socioeconomic status and collective efficacy. Even where there is evidence that BWT impacts outcomes, it is driven by studies that measured disorder as the perceptions of the focal individual, potentially conflating pessimism about the neighborhood with mental health.
Topics: Crime; Health Behavior; Humans; Mental Disorders; Outcome Assessment, Health Care; Residence Characteristics; Self Report; Socioeconomic Factors; Substance-Related Disorders
PubMed: 30885673
DOI: 10.1016/j.socscimed.2018.11.015