Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study

Nüesch, Eveline; Trelle, Sven; Reichenbach, Stephan; Rutjes, Anne W S; Tschannen, Beatrice; Altman, Douglas G.; Egger, Matthias; Jüni, Peter

doi:10.1136/bmj.c3515

Cited by 481 publications

(290 citation statements)

References 52 publications

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“…However, most of the trials had small sample sizes and this could have distorted our meta-analytic results. 51 Our results showed that curcuminoids are ineffective at alleviating stiffness. Knee stiffness has important clinical implications in OA; its presence indicates an increased risk of progression of the disease over time.…”

Section: Discussionmentioning

confidence: 63%

Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta‐analysis of randomized clinical trials

et al. 2017

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Aim: To critically appraise and evaluate the evidence for effectiveness of curcuminoids in the treatment of osteoarthritis (OA) in adults. Methods:We conducted electronic searches in Medline, Embase, AMED, Cinahl and the Cochrane library. We included randomized controlled trials (RCTs) that investigated the effectiveness of orally-administered curcuminoids in OA in adults, and assessed risk of bias using the Cochrane risk of bias criteria. We used a random-effect model for meta-analysis. Results:We included seven studies with a total of 797 participants with primarily knee OA. All studies were conducted in Asia. The overall risk of bias was moderate. Compared with placebo, curcuminoids significantly reduced knee pain (visual analogue scale): (standardized mean difference: À3.45; 95% CI: À5.52 to À1.38; I 2 = 95% P = 0.001), and improved quality of life (Lequesne pain-function index): (mean difference: À2.69; 95% CI: À3.48 to À1.90; I 2 = 0% P < 0.00001). There were significantly fewer effects on pain relief, knee stiffness and physical function with curcuminoids compared with ibuprofen. Significant improvements in Western Ontario and McMaster Universities Arthritis Index total scores, with significant reductions in the use of rescue medication were also observed with curcuminoids. No serious adverse events were reported.Conclusions: Curcuminoids may have some beneficial effects on knee pain and quality of life in patients with knee OA. However, they are less effective at relieving pain compared with ibuprofen. Curcuminoids appear safe on the short-term, and may reduce the need for rescue medication. Published RCTs vary in reporting quality, are characterized by small sample sizes, and have all been conducted in Asia. Further clinical trials are therefore warranted.

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Section: Discussionmentioning

confidence: 63%

Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta‐analysis of randomized clinical trials

et al. 2017

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“…First, the majority of the included studies had relatively small sample sizes, potentially leading to unstable estimates of treatment effects, because smaller trials might be methodologically less robust and are prone to report larger effect sizes 75, 76. Therefore, the present meta‐analysis may have been underpowered to detect a true effect.…”

Section: Discussionmentioning

confidence: 97%

Effect of Sodium‐Glucose Cotransport‐2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis of 43 Randomized Control Trials With 22 528 Patients

Mazidi

Rezaie

Gao

et al. 2017

JAHA

245

174

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BackgroundThe sodium‐glucose cotransporter 2 (SGLT2) inhibitors are a class of oral hypoglycemic agents. We undertake a systematic review and meta‐analysis of prospective studies to determine the effect of SGLT2 on blood pressure (BP) among individuals with type 2 diabetes mellitus.Methods and ResultsPubMed‐Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched to identify trial registries evaluating the impact of SGLT2 on BP. Random‐effects models meta‐analysis was used for quantitative data synthesis. The meta‐analysis indicated a significant reduction in systolic BP following treatment with SGLT2 (weighted mean difference −2.46 mm Hg [95% CI −2.86 to −2.06]). The weighted mean differences for the effect on diastolic BP was −1.46 mm Hg (95% CI −1.82 to −1.09). In these subjects the weighted mean difference effects on serum triglycerides and total cholesterol were −2.08 mg/dL (95% CI −2.51 to −1.64) and 0.77 mg/dL (95% CI 0.33‐1.21), respectively. The weighted mean differences for the effect of SGLT2 on body weight was −1.88 kg (95% CI −2.11 to −1.66) across all studies. These findings were robust in sensitivity analyses.ConclusionsTreatment with SGLT2 glucose cotransporter inhibitors therefore has beneficial off‐target effects on BP in patients with type 2 diabetes mellitus and may also be of value in improving other cardiometabolic parameters including lipid profile and body weight in addition to their expected effects on glycemic control. However, our findings should be interpreted with consideration for the moderate statistical heterogeneity across the included studies.

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“…The assessment of risk of bias in the included studies [13][14][15], the magnitude and determinants of heterogeneity [16][17][18], the relative advantages of different methods to evaluate publication bias and small-study effects, [19][20][21] and the importance of a comprehensive search for relevant studies [22] are examples of meta-epidemiological studies that have guided the choice of optimal methods. We are aware of only three such metaepidemiological studies in NMA: Song et al evaluated the prevalence of inconsistency in networks with three treatments [23,24], Veroniki et al studied the prevalence of inconsistency in complex NMAs that included at least four treatments using two alternative methods [25] while Chaimani et al have provided empirical evidence about the impact of risk of bias and small study effects [26].…”

Section: Introduction Introduction Introductionmentioning

confidence: 99%

Bibliographic study showed improving statistical methodology of network meta-analyses published between 1999 and 2015

Πετροπούλου

Nikolakopoulou

Veroniki

et al. 2017

Journal of Clinical Epidemiology

110

147

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Objective: To assess the characteristics and core statistical methodology specific to network meta-analyses (NMAs) in clinical research articles. Study Design and What is new?Key findings Although the amount of evidence (the number of treatments and studies) included in published NMAs remains stable, the undertaking and reporting of statistical methods have significantly improved over the years. The assumptions underlying NMA are increasingly discussed and evaluated using appropriate methods. Less than 10% of NMAs published in 2014 and 2015 failed to evaluate the assumptions of the joint synthesis. What this adds to what is knownThis meta-epidemiological study presents the largest collection of published NMAs over the past 16 years. It provides an overview of the structural characteristics and statistical methodology of 456 published networks of interventions. It shows that the statistical methods in NMA have considerably improved in all aspects and some, such as the use of appropriate methods to evaluate the plausibility of the assumptions, are now routinely performed. We conclude that the increasingly populous community of NMA methodologists is quickly advancing through the learning curve of statistical methods employed in NMA. What is the implication, what should change nowThe updated description of the structural characteristics of the published NMAs can be used to inform pragmatic simulations studies and the development of methods that are relevant to the type of networks typically found in the medical literature. Future tutorials and training should be focused on improving the methodology and reporting on items that, although they have improved, their prevalence remains low, such as the formal exploration of heterogeneity and inconsistency and the presentation of all pairwise treatment effects.

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Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study

Cited by 481 publications

References 52 publications

Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta‐analysis of randomized clinical trials

Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta‐analysis of randomized clinical trials

Effect of Sodium‐Glucose Cotransport‐2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis of 43 Randomized Control Trials With 22 528 Patients

Bibliographic study showed improving statistical methodology of network meta-analyses published between 1999 and 2015

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