Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials: a meta-epidemiological study.

BACKGROUND: Researchers and decision-makers often use evidence from randomised controlled trials (RCTs) to determine the efficacy or effectiveness of a treatment or intervention. Studies with observational designs are often used to measure the effectiveness of an intervention in 'real world' scenarios. Numerous study designs and their modifications (including both randomised and observational designs) are used for comparative effectiveness research in an attempt to give an unbiased estimate of whether one treatment is more effective or safer than another for a particular population. An up-to-date systematic analysis is needed to identify differences in effect estimates from RCTs and observational studies. This updated review summarises the results of methodological reviews that compared the effect estimates of observational studies with RCTs from evidence syntheses that addressed the same health research question. OBJECTIVES: To assess and compare synthesised effect estimates by study type, contrasting RCTs with observational studies. To explore factors that might explain differences in synthesised effect estimates from RCTs versus observational studies (e.g. heterogeneity, type of observational study design, type of intervention, and use of propensity score adjustment). To identify gaps in the existing research comparing effect estimates across different study types. SEARCH METHODS: We searched MEDLINE, the Cochrane Database of Systematic Reviews, Web of Science databases, and Epistemonikos to May 2022. We checked references, conducted citation searches, and contacted review authors to identify additional reviews. SELECTION CRITERIA: We included systematic methodological reviews that compared quantitative effect estimates measuring the efficacy or effectiveness of interventions tested in RCTs versus in observational studies. The included reviews compared RCTs to observational studies (including retrospective and prospective cohort, case-control and cross-sectional designs). Reviews were not eligible if they compared RCTs with studies that had used some form of concurrent allocation. DATA COLLECTION AND ANALYSIS: Using results from observational studies as the reference group, we examined the relative summary effect estimates (risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), mean differences (MDs), and standardised mean differences (SMDs)) to evaluate whether there was a relatively larger or smaller effect in the ratio of odds ratios (ROR) or ratio of risk ratios (RRR), ratio of hazard ratios (RHR), and difference in (standardised) mean differences (D(S)MD). If an included review did not provide an estimate comparing results from RCTs with observational studies, we generated one by pooling the estimates for observational studies and RCTs, respectively. Across all reviews, we synthesised these ratios to produce a pooled ratio of ratios comparing effect estimates from RCTs with those from observational studies. In overviews of reviews, we estimated the ROR or RRR for each overview using observational studies as the reference category. We appraised the risk of bias in the included reviews (using nine criteria in total). To receive an overall low risk of bias rating, an included review needed: explicit criteria for study selection, a complete sample of studies, and to have controlled for study methodological differences and study heterogeneity. We assessed reviews/overviews not meeting these four criteria as having an overall high risk of bias. We assessed the certainty of the evidence, consisting of multiple evidence syntheses, with the GRADE approach. MAIN RESULTS: We included 39 systematic reviews and eight overviews of reviews, for a total of 47. Thirty-four of these contributed data to our primary analysis. Based on the available data, we found that the reviews/overviews included 2869 RCTs involving 3,882,115 participants, and 3924 observational studies with 19,499,970 participants. We rated 11 reviews/overviews as having an overall low risk of bias, and 36 as having an unclear or high risk of bias. Our main concerns with the included reviews/overviews were that some did not assess the quality of their included studies, and some failed to account appropriately for differences between study designs - for example, they conducted aggregate analyses of all observational studies rather than separate analyses of cohort and case-control studies. When pooling RORs and RRRs, the ratio of ratios indicated no difference or a very small difference between the effect estimates from RCTs versus from observational studies (ratio of ratios 1.08, 95% confidence interval (CI) 1.01 to 1.15). We rated the certainty of the evidence as low. Twenty-three of 34 reviews reported effect estimates of RCTs and observational studies that were on average in agreement. In a number of subgroup analyses, small differences in the effect estimates were detected: - pharmaceutical interventions only (ratio of ratios 1.12, 95% CI 1.04 to 1.21); - RCTs and observational studies with substantial or high heterogeneity; that is, I2 ≥ 50% (ratio of ratios 1.11, 95% CI 1.04 to 1.18); - no use (ratio of ratios 1.07, 95% CI 1.03 to 1.11) or unclear use (ratio of ratios 1.13, 95% CI 1.03 to 1.25) of propensity score adjustment in observational studies; and - observational studies without further specification of the study design (ratio of ratios 1.06, 95% CI 0.96 to 1.18). We detected no clear difference in other subgroup analyses. AUTHORS' CONCLUSIONS: We found no difference or a very small difference between effect estimates from RCTs and observational studies. These findings are largely consistent with findings from recently published research. Factors other than study design need to be considered when exploring reasons for a lack of agreement between results of RCTs and observational studies, such as differences in the population, intervention, comparator, and outcomes investigated in the respective studies. Our results underscore that it is important for review authors to consider not only study design, but the level of heterogeneity in meta-analyses of RCTs or observational studies. A better understanding is needed of how these factors might yield estimates reflective of true effectiveness.

Non-vitamin-K-antagonist oral anticoagulants (NOACs) after acute myocardial infarction: a network meta-analysis.

BACKGROUND: Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging, and the optimal antithrombotic therapy remains uncertain. The potential of non-vitamin K antagonist oral anticoagulants (NOACs) to prevent ischaemic cardiovascular events is promising, but the evidence remains limited. OBJECTIVES: To evaluate the efficacy and safety of non-vitamin-K-antagonist oral anticoagulants (NOACs) in addition to background antiplatelet therapy, compared with placebo, antiplatelet therapy, or both, after acute myocardial infarction (AMI) in people without an indication for anticoagulation (i.e. atrial fibrillation or venous thromboembolism). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science, and two clinical trial registers in September 2022 with no language restrictions. We checked the reference lists of included studies for any additional trials. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that evaluated NOACs plus antiplatelet therapy versus placebo, antiplatelet therapy, or both, in people without an indication for anticoagulation after an AMI. DATA COLLECTION AND ANALYSIS: Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random-effects pairwise analyses using Review Manager Web, and network meta-analysis using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons and allow ranking of treatments on a continuous 0-to-1 scale. MAIN RESULTS: We identified seven eligible RCTs, including an ongoing trial that we could not include in the analysis. Of the six RCTs involving 33,039 participants, three RCTs compared rivaroxaban with placebo, two RCTs compared apixaban with placebo, and one RCT compared dabigatran with placebo. All participants in the six RCTs received concomitant antiplatelet therapy. The available evidence suggests that rivaroxaban compared with placebo reduces the rate of all-cause mortality (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.69 to 0.98; number needed to treat for an additional beneficial outcome (NNTB) 250; 3 studies, 21,870 participants; high certainty) and probably reduces cardiovascular mortality (RR 0.83, 95% CI 0.69 to 1.01; NNTB 250; 3 studies, 21,870 participants; moderate certainty). There is probably little or no difference between apixaban and placebo in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35; number needed to treat for an additional harmful outcome (NNTH) 334; 2 studies, 8638 participants; moderate certainty) and cardiovascular mortality (RR 0.99, 95% CI 0.77 to 1.27; number needed to treat not applicable; 2 studies, 8638 participants; moderate certainty). Dabigatran may reduce the rate of all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06; NNTB 63; 1 study, 1861 participants; low certainty). Dabigatran compared with placebo may have little or no effect on cardiovascular mortality, although the point estimate suggests benefit (RR 0.72, 95% CI 0.34 to 1.52; NNTB 143; 1 study, 1861 participants; low certainty). Two of the investigated NOACs were associated with an increased risk of major bleeding compared to placebo: apixaban (RR 2.41, 95% CI 1.44 to 4.06; NNTH 143; 2 studies, 8544 participants; high certainty) and rivaroxaban (RR 3.31, 95% CI 1.12 to 9.77; NNTH 125; 3 studies, 21,870 participants; high certainty). There may be little or no difference between dabigatran and placebo in the risk of major bleeding (RR 1.74, 95% CI 0.22 to 14.12; NNTH 500; 1 study, 1861 participants; low certainty). The results of the network meta-analysis were inconclusive between the different NOACs at all individual doses for all primary outcomes. However, low-certainty evidence suggests that apixaban (combined dose) may be less effective than rivaroxaban and dabigatran for preventing all-cause mortality after AMI in people without an indication for anticoagulation. AUTHORS' CONCLUSIONS: Compared with placebo, rivaroxaban reduces all-cause mortality and probably reduces cardiovascular mortality after AMI in people without an indication for anticoagulation. Dabigatran may reduce the rate of all-cause mortality and may have little or no effect on cardiovascular mortality. There is probably no meaningful difference in the rate of all-cause mortality and cardiovascular mortality between apixaban and placebo. Moreover, we found no meaningful benefit in efficacy outcomes for specific therapy doses of any investigated NOACs following AMI in people without an indication for anticoagulation. Evidence from the included studies suggests that rivaroxaban and apixaban increase the risk of major bleeding compared with placebo. There may be little or no difference between dabigatran and placebo in the risk of major bleeding. Network meta-analysis did not show any superiority of one NOAC over another for our prespecified primary outcomes. Although the evidence suggests that NOACs reduce mortality, the effect size or impact is small; moreover, NOACs may increase major bleeding. Head-to-head trials, comparing NOACs against each other, are required to provide more solid evidence.

Quality of information in news media reports about the effects of health interventions: Systematic review and meta-analyses.

Background Many studies have assessed the quality of news reports about the effects of health interventions, but there has been no systematic review of such studies or meta-analysis of their results. We aimed to fill this gap (PROSPERO ID: CRD42018095032). Methods We included studies that used at least one explicit, prespecified and generic criterion to assess the quality of news reports in print, broadcast, or online news media, and specified the sampling frame, and the selection criteria and technique. We assessed criteria individually for inclusion in the meta-analyses, excluding ineligible criteria and criteria with inadequately reported results. We mapped and grouped criteria to facilitate evidence synthesis. Where possible, we extracted the proportion of news reports meeting the included criterion. We performed meta-analyses using a random effects model to estimate such proportions for individual criteria and some criteria groups, and to characterise heterogeneity across studies.  Results We included 44 primary studies in the review, and 18 studies and 108 quality criteria in the meta-analyses. Many news reports gave an unbalanced and oversimplified picture of the potential consequences of interventions. A limited number mention or adequately address conflicts of interest (22%; 95% CI 7%-49%) (low certainty), alternative interventions (36%; 95% CI 26%-47%) (moderate certainty), potential harms (40%; 95% CI 23%-61%) (low certainty), or costs (18%; 95% CI 12%-28%) (moderate certainty), or quantify effects (53%; 95% CI 36%-69%) (low certainty) or report absolute effects (17%; 95% CI 4%-49%) (low certainty).  Discussion There is room for improving health news, but it is logically more important to improve the public's ability to critically appraise health information and make judgements for themselves.

Psychological and social consequences of non-invasive prenatal testing (NIPT): a scoping review.

BACKGROUND: Genomics-based noninvasive prenatal tests (NIPT) allow screening for chromosomal anomalies such as Down syndrome (trisomy 21). The technique uses cell-free fetal DNA (cffDNA) that circulates in the maternal blood and is detectable from 5 weeks of gestation onwards. Parents who choose to undergo this relatively new test (introduced in 2011) might be aware of its positive features (i.e. clinical safety and ease of use); however, they might be less aware of the required decisions and accompanying internal conflicts following a potential positive test result. To show the evidence on psychological and social consequences of the use of NIPT, we conducted a scoping review. METHODS: We systematically searched four electronic databases (MEDLINE (Ovid), Cochrane Library (Wiley), CINAHL (EBSCO) and PsychINFO (EBSCO)) for studies that investigated the psychological or social consequences of the use of NIPT by pregnant women or expecting parents. The search was limited to studies published between 2011 and August 8, 2018. We identified 2488 studies and, after removal of duplicates, screened 2007 titles and abstracts, and then assessed 99 articles in full text (both screenings were done independently in duplicate). We included 7 studies in our analysis. RESULTS: Five studies assessed anxiety, psychological distress and/or decisional regret among women with validated psychological tests like the Spielberger State Trait-Anxiety Inventory (STAI), the Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R), the Kessler Psychological Distress Scale (K6) or the Decisional Regret Scale (DRS). Two studies assessed women's experiences with and feelings after NIPT in interviews or focus groups. The included studies were heterogeneous in location, study setting, inclusion criteria, outcome assessment, and other characteristics. CONCLUSIONS: Only few studies on psychological consequences of NIPT have been identified. The studies assessed only short-term psychological consequences of NIPT at baseline and/or after receiving the results or after giving birth. Studies show that short term anxiety decreased when women received negative NIPT results and that decisional regret was generally low. We could not identify studies on long term consequences of NIPT, as well as studies on women's partners' short and long term outcomes, nor on social consequences of NIPT.