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Purpose Clinical research is widely sponsored by drug and device companies. We investigated whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship. This review is an update of a previous Cochrane review. Methods In this update we searched MEDLINE and Embase (2010 to February 2015), Cochrane Methodology Register (2015, Issue 2) and Web of Science (June 2015). We included empirical studies that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. Two assessors included papers, extracted data and assessed risk of bias. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether conclusions agreed with results. Results We included 27 additional papers in this update (review now includes 75 papers). Industry sponsored studies more often had favorable efficacy results, RR: 1.27 (95% CI 1.17-1.37), no difference in harms results RR: 1.37 (95% CI 0.64-2.93) and more often favorable conclusions RR: 1.34 (95% CI 1.19-1.51) compared with non-industry sponsored studies. Nineteen papers reported on sponsorship and efficacy effect size, but could not be pooled due to differences in reporting of data and heterogeneity of results. Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment, follow-up and selective outcome reporting. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.25 (95% CI 1.05-1.50), compared with non-industry sponsored studies. Conclusions Drug and device studies sponsored by manufacturing companies have more favorable efficacy results and conclusions than studies sponsored by other sources., Author(s): Andreas Lundh [sup.1] [sup.2] [sup.3] [sup.4], Joel Lexchin [sup.5], Barbara Mintzes [sup.6], Jeppe B. Schroll [sup.7], Lisa Bero [sup.6] Author Affiliations: (1) 0000 0004 0512 5013, grid.7143.1, Centre for [...]

Abstract Background Dealing with heterogeneity in meta-analyses is often tricky, and there is only limited advice for authors on what to do. We investigated how authors addressed different degrees of heterogeneity, in particular whether they used a fixed effect model, which assumes that all the included studies are estimating the same true effect, or a random effects model where this is not assumed. Methods We sampled randomly 60 Cochrane reviews from 2008, which presented a result in its first meta-analysis with substantial heterogeneity (I2 greater than 50%, i.e. more than 50% of the variation is due to heterogeneity rather than chance). We extracted information on choice of statistical model, how the authors had handled the heterogeneity, and assessed the methodological quality of the reviews in relation to this. Results The distribution of heterogeneity was rather uniform in the whole I2 interval, 50-100%. A fixed effect model was used in 33 reviews (55%), but there was no correlation between I2 and choice of model (P = 0.79). We considered that 20 reviews (33%), 16 of which had used a fixed effect model, had major problems. The most common problems were: use of a fixed effect model and lack of rationale for choice of that model, lack of comment on even severe heterogeneity and of reservations and explanations of its likely causes. The problematic reviews had significantly fewer included trials than other reviews (4.3 vs. 8.0, P = 0.024). The problems became less pronounced with time, as those reviews that were most recently updated more often used a random effects model. Conclusion One-third of Cochrane reviews with substantial heterogeneity had major problems in relation to their handling of heterogeneity. More attention is needed to this issue, as the problems we identified can be essential for the conclusions of the reviews.

Background: Guidelines recommend metformin as the first-line oral treatment for type 2 diabetes. We conducted a systematic review to assess whether the use of second- and third-generation sulfonylurea agents is associated with benefits and harms in terms of patient-important outcomes compared with metformin. Methods: We searched several electronic databases and other sources for randomized clinical trials published to August 2011. We included trials that compared sulfonylurea versus metformin monotherapy among patients 18 years or older with type 2 diabetes and that had an intervention period of at least 24 weeks. We assessed risk of bias and extracted data related to interventions and outcomes. The risk of random errors was assessed by trial sequential analysis. Results: We included 14 trials (4560 participants). All trials were judged to be at high risk of bias. Data on patient-important outcomes were sparse. Compared with metformin, sulfonylurea did not significantly affect all-cause mortality (relative risk [RR] 0.98, 95% confidence interval [CI] 0.61 to 1.58) or cardiovascular mortality (RR 1.47, 95% CI 0.54 to 4.01). Sulfonylurea significantly decreased the risk of nonfatal macrovascular outcomes (RR 0.67, 95% CI 0.48 to 0.93). However, the definition of this outcome varied among trials, and trial sequential analysis showed that more trials are needed before reliable conclusions can be drawn. No differences between sulfonylurea and metformin were found for change in fasting blood glucose level or glycosylated hemoglobin concentration in the random-effects model. Sulfonylurea resulted in greater weight gain compared with metformin, a finding confirmed in the trial sequential analysis. Significantly more patients in the sulfonylurea arm than in the metformin arm had mild hypoglycemia (RR 2.95, 95% CI 2.13 to 4.07) and severe hypoglycemia (RR 5.64, 95% CI 1.22 to 26.00). Interpretation: Some evidence suggests that, compared with metformin, second- and third-generation sulfonylureas may not affect all-cause or cardiovascular mortality but may decrease the risk of nonfatal macrovascular outcomes among patients with type 2 diabetes. They may also increase the risk of hypoglycemia. In general, the available data were too few and inconsistent to provide firm evidence concerning patient-important outcomes in relation to the benefits and harms of sulfonylurea versus metformin monotherapy. [ABSTRACT FROM AUTHOR]

Background: Premenstrual syndrome (PMS) is a combination of physical, psychological and social symptoms in women of reproductive age, and premenstrual dysphoric disorder (PMDD) is a severe type of the syndrome, previously known as late luteal phase dysphoric disorder (LLPDD). Both syndromes cause symptoms during the two weeks leading up to menstruation (the luteal phase). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as a treatment for PMS and PMDD, either administered in the luteal phase or continuously. We undertook a systematic review to assess the evidence of the positive effects and the harms of SSRIs in the management of PMS and PMDD., Objectives: To evaluate the benefits and harms of SSRIs in treating women diagnosed with PMS and PMDD., Search Methods: We searched the Cochrane Gynaecology and Fertility (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase and PsycINFO for randomised controlled trials (RCTs) in November 2023. We checked reference lists of relevant studies, searched trial registers and contacted experts in the field for any additional trials. This is an update of a review last published in 2013., Selection Criteria: We considered studies in which women with a prospective diagnosis of PMS, PMDD or LLPDD were randomised to receive SSRIs or placebo., Data Collection and Analysis: We used standard Cochrane methods. We pooled data using a random-effects model. We calculated standardised mean differences (SMDs) with 95% confidence intervals (CIs) for premenstrual symptom scores, using 'post-treatment' scores for continuous data. We calculated odds ratios (ORs) with 95% CIs for dichotomous outcomes. We stratified analyses by type of administration (luteal phase or continuous). We calculated absolute risks and the number of women who would need to be taking SSRIs in order to cause one additional adverse event (i.e. the number needed to treat for an additional harmful outcome (NNTH)). We rated the overall certainty of the evidence for the main findings using GRADE., Main Results: We included 34 RCTs in the review. The studies compared SSRIs (i.e. fluoxetine, paroxetine, sertraline, escitalopram and citalopram) to placebo. SSRIs probably reduce overall self-rated premenstrual symptoms in women with PMS and PMDD (SMD -0.57, 95% CI -0.72 to -0.42; I 2 = 51%; 12 studies, 1742 participants; moderate-certainty evidence). SSRI treatment was probably more effective when administered continuously than when administered only in the luteal phase (P = 0.03 for subgroup difference; luteal phase group: SMD -0.39, 95% CI -0.58 to -0.21; 6 studies, 687 participants; moderate-certainty evidence; continuous group: SMD -0.69, 95% CI -0.88 to -0.51; 7 studies, 1055 participants; moderate-certainty evidence). The adverse effects associated with SSRIs were nausea (OR 3.30, 95% CI 2.58 to 4.21; I 2 = 0%; 18 studies, 3664 women), insomnia (OR 1.99, 95% CI 1.51 to 2.63; I 2 = 0%; 18 studies, 3722 women), sexual dysfunction or decreased libido (OR 2.32, 95% CI 1.57 to 3.42; I 2 = 0%; 14 studies, 2781 women), fatigue or sedation (OR 1.52, 95% CI 1.05 to 2.20; I 2 = 0%; 10 studies, 1230 women), dizziness or vertigo (OR 1.96, 95% CI 1.36 to 2.83; I 2 = 0%; 13 studies, 2633 women), tremor (OR 5.38, 95% CI 2.20 to 13.16; I 2 = 0%; 4 studies, 1352 women), somnolence and decreased concentration (OR 3.26, 95% CI 2.01 to 5.30; I 2 = 0%; 8 studies, 2050 women), sweating (OR 2.17, 95% CI 1.36 to 3.47; I 2 = 0%; 10 studies, 2304 women), dry mouth (OR 2.70, 95% CI 1.75 to 4.17; I 2 = 0%; 11 studies, 1753 women), asthenia or decreased energy (OR 3.28, 95% CI 2.16 to 4.98; I 2 = 0%; 7 studies, 1704 women), diarrhoea (OR 2.06, 95% CI 1.37 to 3.08; I 2 = 0%; 12 studies, 2681 women), and constipation (OR 2.39, 95% CI 1.09 to 5.26; I 2 = 0%; 7 studies, 1022 women). There was moderate-certainty evidence for all adverse effects other than somnolence/decreased concentration, which was low-certainty evidence. Overall, the certainty of the evidence was moderate. The main weakness was poor reporting of study methodology. Heterogeneity was low or absent for most outcomes, although there was moderate heterogeneity in the analysis of overall self-rated premenstrual symptoms. Based on the meta-analysis of response rate (the outcome with the most included studies), there was suspected publication bias. In total, 68% of the included studies were funded by pharmaceutical companies. This stresses the importance of interpreting the review findings with caution., Authors' Conclusions: SSRIs probably reduce premenstrual symptoms in women with PMS and PMDD and are probably more effective when taken continuously compared to luteal phase administration. SSRI treatment probably increases the risk of adverse events, with the most common being nausea, asthenia and somnolence., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)