Conflicts of interest in randomized controlled trials reported in neurosurgical journals

OBJECTIVERandomized controlled trials (RCTs) form the basis of today’s evidence-based approach to medicine, and play a critical role in guidelines and the drug and device approval process. Conflicts of interest (COIs) are commonplace in medical research, but little is known about their influence. The authors aimed to evaluate the extent and influence of COIs in recent RCTs published in core neurosurgical journals using a cross-sectional analysis.METHODSThrough review of 6 general neurosurgical journals, all interventional RCTs published from January 2009 to January 2019 were identified. Because it is difficult to objectively assess study outcome, the authors opted for a strict rating approach based on the statistical significance of unambiguously reported primary endpoints, and the reported statistical protocol.RESULTSA total of 129 RCTs met the inclusion criteria. During the study period, the Journal of Neurosurgery published the largest number of RCTs (n = 40, 31%). Any potential COI was disclosed by 57%, and a mean of 12% of authors had a personal COI. Nonfinancial industry involvement was reported in 10%, while 31% and 20% received external support and sponsoring, respectively. Study registration was reported by 56%, while 51% of studies were blinded. Registration showed an increasing trend from 17% to 76% (p < 0.001). The median randomized sample size was 92 (interquartile range 50–153), and 8% were designed to investigate noninferiority or equality. Sixty-three RCTs (49%) unambiguously reported a primary endpoint, of which 13% were composite primary endpoints. In 43%, study outcome was positive, which was associated with a noninferiority design (31% vs 3%, p = 0.007) and a composite primary endpoint (46% vs 9%, p = 0.002). Potential COIs were not significantly associated with study positivity (69% vs 59%, p = 0.433). In the multivariate analysis, only a composite primary endpoint remained predictive of a positive study outcome (odds ratio 6.34, 95% confidence interval 1.51–33.61, p = 0.017).CONCLUSIONSThis analysis provides an overview of COIs and their potential influence on recent trials published in core neurosurgical journals. Reporting of primary endpoints, study registration, and uniform disclosure of COIs are crucial to ensure the quality of future neurosurgical randomized trials. COIs do not appear to significantly influence the outcome of randomized neurosurgical trials.

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Effects of Diet, Aerobic Exercise, or Both on Non-HDL-C in Adults: A Meta-Analysis of Randomized Controlled Trials

Cholesterol ◽

10.1155/2012/840935 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 11

Author(s):

George A. Kelley ◽

Kristi S. Kelley

Keyword(s):

Aerobic Exercise ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Statistical Significance ◽

Density Lipoprotein ◽

Control Group ◽

Controlled Trials ◽

Mixed Effect ◽

Randomized Controlled ◽

Effect Model

Purpose. To use the meta-analytic approach to examine the effects of diet (D), aerobic exercise (E), or both (DE) on non-high-density lipoprotein cholesterol (non-HDL-C) in adults. Methods. Randomized controlled trials in adults ≥18 years of age were included. A mixed-effect model was used to combine effect size (ES) results within each subgroup and to compare subgroups (Qb). Heterogeneity was examined using the Q and I2 statistics, and 95% confidence intervals (CI) were also calculated. Statistical significance was set at P≤0.05, while a trend for statistical significance was set between P>0.05, and ≤0.10. Results. A statistically significant exercise minus control group decrease in non-HDL-C was found for DE (7 ESs, 389 participants, x¯=-11.1 mg/dL, 95% CI=−21.7 to −0.6, P=0.04, Q=2.4, P=0.88, I2=0%), a trend for the D group (7 ESs, 402 participants, x¯=−8.5 mg/dL, 95% CI=−18.6 to 1.6, P=0.10, Q=0.76, P=0.99, I2=0%), and no change for the E group (7 ESs, 387 participants, x¯=3.0 mg/dL, 95% CI=−7.1 to 13.1, P=0.56, Q=0.78, P=0.99, I2=0%). Overall, no statistically significant between-group differences were found (Qb=4.1, P=0.12). Conclusions. Diet combined with aerobic exercise may reduce non-HDL-C among adults in some settings.

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COVID-19 and Vitamin D (Co-VIVID Study): a systematic review and meta-analysis of randomized controlled trials

10.1101/2021.08.22.21262216 ◽

2021 ◽

Author(s):

Seshadri Reddy Varikasuvu ◽

Balachandar Thangappazham ◽

Hemanth Raj

Keyword(s):

Vitamin D ◽

Randomized Controlled Trials ◽

Literature Search ◽

Meta Analysis ◽

Statistical Significance ◽

Cochrane Library ◽

Controlled Trials ◽

Randomized Controlled ◽

Individual Outcomes ◽

Vitamin D Levels

Background: Vitamin D levels have been reported to be associated with COVID-19 susceptibility, severity and mortality events.. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the use of vitamin D intervention on COVID-19 outcomes. Methods: Literature search was conducted using PubMed, Cochrane library, and ClinicalTrials.gov databases (latest search on August 5, 2021). We included RCTs reporting the use of vitamin D intervention to control/placebo group in COVID-19. Two independent researchers did literature search, abstracted data, and the risk of bias assessment. Results: A total of 6 RCTs with 551 COVID-19 patients were included. The overall collective evidence pooling all the outcomes across all RCTs indicated the beneficial use of vitamin D intervention in COVID-19 (relative risk, RR = 0.60, 95% CI 0.40 to 0.92, Z=2.33, p=0.02, I2 = 48%). However, no statistical significance was observed for individual outcomes of ICU care (RR = 0.11, 95% CI 0.15 to 1.30, Z=1.48, p=0.14, I2 = 66%) and mortality (RR = 0.78, 95% CI 0.25 to 2.40, Z=0.66, p=0.02, I2 = 33%), though decreased rates were noted. The rates of RT-CR positivity was significantly decreased in the intervention group as compared to the non-vitamin D groups (RR = 0.46, 95% CI 0.24 to 0.89, Z=2.31, p=0.02, I2 = 0%). Conclusion: COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events and RT-PCR positivity. However, no statistical significance has been achieved for individual outcomes of ICU and deaths. More RCTs and completion of ongoing trials largely needed to precisely establish the association between vitamin D use and COVID-19.

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Analyzing Spin in Abstracts of Orthopaedic Randomized Controlled Trials With Statistically Insignificant Primary Endpoints

Arthroscopy The Journal of Arthroscopic and Related Surgery ◽

10.1016/j.arthro.2019.12.025 ◽

2020 ◽

Vol 36 (5) ◽

pp. 1443-1450.e1 ◽

Cited By ~ 3

Author(s):

Wade Arthur ◽

Zachariah Zaaza ◽

Jake X. Checketts ◽

Austin L. Johnson ◽

Kevin Middlemist ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Controlled Trials ◽

Randomized Controlled ◽

Primary Endpoints

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Effects of a proposal to alter the statistical significance threshold on previously published orthopaedic trauma randomized controlled trials

Injury ◽

10.1016/j.injury.2019.08.012 ◽

2019 ◽

Vol 50 (11) ◽

pp. 1934-1937 ◽

Cited By ~ 2

Author(s):

Austin L. Johnson ◽

Sheridan Evans ◽

Jake X. Checketts ◽

Jared T. Scott ◽

Cole Wayant ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Statistical Significance ◽

Controlled Trials ◽

Orthopaedic Trauma ◽

Randomized Controlled ◽

Significance Threshold

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Association of author’s financial conflict of interest with characteristics and outcome of rheumatoid arthritis randomized controlled trials

Rheumatology ◽

10.1093/rheumatology/key368 ◽

2018 ◽

Vol 58 (5) ◽

pp. 776-785 ◽

Cited By ~ 5

Author(s):

Nasim Ahmed Khan ◽

Chau L Nguyen ◽

Talha Khawar ◽

Horace Spencer ◽

Karina D Torralba

Keyword(s):

Drug Therapy ◽

Randomized Controlled Trials ◽

Conflicts Of Interest ◽

Phase 1 ◽

Temporal Trends ◽

Positive Outcome ◽

Stock Ownership ◽

Controlled Trials ◽

Randomized Controlled ◽

Research Grant

Abstract Objective To examine the prevalence, types and temporal trends of reported financial conflicts of interest (FCOIs) among authors of drug therapy randomized controlled trials (RCTs) for RA and their association with study outcomes. Methods We identified original, non–phase 1, parallel-group, drug therapy RA RCTs published in the years 2002–03, 2006–07, and 2010–11. Two investigators independently obtained trial characteristics data. Authors’ FCOIs were classified as honoraria/consultation fees receipt, employee status, research grant, and stock ownership. Multivariable logistic regression was performed to identify whether FCOIs were independently associated with study outcome. Results A total of 146 eligible RCTs were identified. Of these, 83 (58.4%) RCTs had at least one author with an FCOI [employee status: 63 (43.2%), honoraria/consultation fees receipt: 49 (33.6%), research grant: 30 (20.5%), and stock ownership: 28 (19.2%)]. A remarkable temporal increase in reporting of honoraria/consultation fees receipt, research grant, and stock ownership was seen. The reporting of any FCOI itself was not associated with positive outcome [50/73 (68.5%) with author FCOI vs 36/52 (69.2%) without author FCOI, P = 0.93]. However, honoraria/consulting fees receipt was independently associated with increased likelihood of a positive outcome [adjusted odds ratio (95% CI) of 3.24 (1.06–9.88)]. In general, trials with FCOIs were significantly more likely to be multicentre, have larger enrolment, use biologic or a small molecule as the experimental intervention, and have better reporting of some methodological quality measures. Conclusion FCOI reporting in RA drug RCT authors is common and temporally increasing. Receipt of honoraria/consulting fees was independently associated with a positive study outcome.

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Multivessel versus culprit-only PCI in STEMI patients with multivessel disease: meta-analysis of randomized controlled trials

Clinical Research in Cardiology ◽

10.1007/s00392-020-01637-6 ◽

2020 ◽

Vol 109 (11) ◽

pp. 1381-1391 ◽

Cited By ~ 3

Author(s):

Hans-Josef Feistritzer ◽

Alexander Jobs ◽

Suzanne de Waha-Thiele ◽

Ingo Eitel ◽

Anne Freund ◽

...

Keyword(s):

Cardiogenic Shock ◽

Randomized Controlled Trials ◽

Primary Endpoint ◽

Meta Analysis ◽

Random Effect ◽

Final Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Risk Of Death ◽

Randomized Controlled

Abstract Aims To perform a pairwise meta-analysis of randomized controlled trials (RCTs) comparing multivessel percutaneous coronary intervention (PCI) and culprit vessel-only PCI in ST-elevation myocardial infarction (STEMI) patients without cardiogenic shock. Methods We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for RCTs comparing multivessel PCI with culprit vessel-only PCI in STEMI patients without cardiogenic shock and multivessel coronary artery disease. Only RCTs reporting mortality or myocardial reinfarction after at least 6 months following randomization were included. Hazard ratios (HRs) were pooled using random-effect models. Results Nine RCTs were included in the final analysis. In total, 523 (8.3%) of 6314 patients suffered the combined primary endpoint of death or non-fatal reinfarction. This primary endpoint was significantly reduced with multivessel PCI compared to culprit vessel-only PCI (HR 0.63, 95% confidence interval [CI] 0.43–0.93; p = 0.03). This finding was driven by a reduction of non-fatal reinfarction (HR 0.64, 95% CI 0.52–0.79; p = 0.001), whereas no significant reduction of all-cause death (HR 0.77, 95% CI 0.44–1.35; p = 0.28) or cardiovascular death (HR 0.64, 95% CI 0.37–1.11; p = 0.09) was observed. Conclusions In STEMI patients without cardiogenic shock multivessel PCI reduced the risk of death or non-fatal reinfarction compared to culprit vessel-only PCI.

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Short Dental Implants (≤7mm) Versus Longer Implants in Augmented Bone Area: A Meta-Analysis of Randomized Controlled Trials

The Open Dentistry Journal ◽

10.2174/1874210601812010354 ◽

2018 ◽

Vol 12 (1) ◽

pp. 354-365 ◽

Cited By ~ 7

Author(s):

Priscila N. Uehara ◽

Victor Haruo Matsubara ◽

Fernando Igai ◽

Newton Sesma ◽

Marcio K. Mukai ◽

...

Keyword(s):

Survival Rate ◽

Bone Loss ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Statistical Significance ◽

Controlled Trials ◽

Bone Area ◽

Marginal Bone Loss ◽

Randomized Controlled ◽

Short Implants

Aim: The aim of this systematic review was to compare the survival rate and the marginal bone loss between short implants (≤7 mm) placed in the atrophic area and longer implants placed in the augmented bone area of posterior regions of maxillaries. Methods: Electronic search using three databases was performed up to May 2017 to identify Randomized Controlled Trials (RCT) assessing short implants survival with a minimal follow-up of 12 months post-loading. For the meta-analysis, a Risk Difference (RD) with the 95% Confidence Interval (CI) was used to pool the results of implant failure rate for each treatment group. For the marginal bone changes, Mean Differences (MD) with 95% CI were calculated. Results: Seven randomized controlled trials met the inclusion criteria, being included in qualitative and quantitative analyses. The RD between the short implant group and the control group was -0.02 (95% CI: -0.04 to 0.00), I2=0 and Chi2=3.14, indicating a favorable survival rate for short implant, but with no statistical significance (p=0.09). Discussion: For marginal bone loss, the mean difference was -0,13 (95%CI: -0.22 to -0.05), favoring the test group with statistical significance (p=0.002). The studies showed more heterogeneity for bone loss compared to survival rate. Short and longer implants showed similar survival rates after one year of loading, however the marginal bone loss around short implants was lower than in longer implants sites. Conclusion: Placement of implants ≤7 mm of length was found to be a predictable alternative for the rehabilitation of atrophic posterior regions, avoiding all the disadvantages intrinsic to bone augmentation procedures.

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Pridopidine for the Improvement of Motor Function in Patients With Huntington's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Frontiers in Neurology ◽

10.3389/fneur.2021.658123 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shujun Chen ◽

Tianyu Liang ◽

Tao Xue ◽

Shouru Xue ◽

Qun Xue

Keyword(s):

Adverse Events ◽

Randomized Controlled Trials ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Meta Analysis ◽

Statistical Significance ◽

Controlled Trials ◽

Efficacy And Safety ◽

Motor Score ◽

Randomized Controlled

Background: Huntington's disease (HD) is a progressive neurodegenerative disorder. Generally, it is characterized by deficits in cognition, behavior, and movement. Recent studies have shown that pridopidine is a potential and effective drug candidate for the treatment of HD. In the present study, we performed a meta-analysis to evaluate the efficacy and safety of pridopidine in HD.Methods: The MEDLINE, EMBASE, CENTRAL, and Clinicaltrials.gov databases were searched for randomized controlled trials (RCTs) which had that evaluated pridopidine therapy in HD patients.Results: We pooled data from 1,119 patients across four RCTs. Patients in the pridopidine group had a significantly lower Unified Huntington's Disease Rating Scale (UHDRS)-modified Motor Score (mMS) (MD −0.79, 95% CI = −1.46 to −0.11, p = 0.02) than those in the placebo group. Additionally, no differences were observed in the UHDRS-Total Motor Score (TMS) (MD −0.91. 95% CI = −2.03 to 0.21, p = 0.11) or adverse events (RR 1.06, 95% CI = 0.96 to 1.16, p = 0.24) in the pridopidine and placebo groups. In the subgroup analysis, the short-term (≤12 weeks) and long-term (>12 weeks) subgroups exhibited similar efficacy and safety with no statistical significance in TMS, mMS, or adverse events. However, TMS (MD −1.50, 95% CI = −2.87 to −0.12, p = 0.03) and mMS (MD −1.03, 95% CI = −1.87 to −0.19, p = 0.02) were observed to be improved significantly when the dosage of pridopidine ≥90 mg/day. Additionally, pridopidine (≥90 mg/day) increased total adverse events (RR 1.11, 95% CI = 1.00 to 1.22, p = 0.04) compared with placebo. On this basis, we analyzed the incidence of various adverse events when the dosage was ≥90 mg/day. Nonetheless, these results were within the acceptable threshold, although patients developed symptoms, such as nasopharyngitis and insomnia.Conclusion: Pridopidine improved mMS and had no statistical significance in association with TMS or adverse events. Pridopidine (≥90 mg/day) improved TMS and mMS but increased adverse events, such as nasopharyngitis and insomnia. More RCTs were expected to assess pridopidine in HD.

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Critical and Comprehensive Ethical Analysis on Pragmatic Randomized Controlled Trials

10.31124/advance.12401960.v1 ◽

2020 ◽

Author(s):

Soaad Hossain

Keyword(s):

Medical Ethics ◽

Randomized Controlled Trials ◽

Ethical Issues ◽

Conflicts Of Interest ◽

Ethical Analysis ◽

Ethical Framework ◽

Controlled Trials ◽

Research Practice ◽

Randomized Controlled ◽

Regulatory Frameworks

The interest of pragmatic randomized controlled trials continues to increase as they are much better suited for studies of how to get medical and health services out into wider practice. However, despite the advantage that such trials have, there are several ethical issues and medical ethics issues that persist with the trial. The ethical and medical ethics issues involve research-practice distinction, consent, disclosure, vulnerable populations, oversight, ethical principles, ethical framework, regulatory frameworks, and conflicts of interest. Through performing an elaborate literature review and analyzing claims and arguments made within the literature, we will provide a critical and comprehensive ethical analysis on pragmatic randomized controlled trials, and we will begin the discussion on conflicts of interest in pragmatic RCTs, arguing that conflicts of interest occur in pragmatic RCTs.

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What Keeps Older People out of Nursing Homes? A Meta-Analysis

Innovation in Aging ◽

10.1093/geroni/igab046.1958 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 510-510

Author(s):

Joseph Gaugler ◽

Rachel Zmora ◽

Colleen Peterson ◽

Lauren Mitchell ◽

Robyn Birkeland ◽

...

Keyword(s):

Nursing Home ◽

Older People ◽

Randomized Controlled Trials ◽

Older Persons ◽

Meta Analysis ◽

Statistical Significance ◽

Nursing Home Admission ◽

Controlled Trials ◽

Fee For Service ◽

Randomized Controlled

Abstract Perhaps one of the most examined, and costly, health transitions older people experience is nursing home admission. In addition to the financial costs nursing home admission poses to older people, their families, and other payers (e.g., the public), institutionalization is linked with a range of negative outcomes and represents a loss of independence and quality of life to many older persons. The current meta-analysis attempted to synthesize all available randomized controlled trials available to ascertain which intervention approaches appeared to prevent nursing home entry for older adults. The MEDLINE, PsycInfo, CINAHL, Cochrane, and EMBASE databases were searched to August, 2020. Abstracts were screened (N = 28,120) to identify randomized controlled trials of interventions to prevent or delay nursing home admission as well as systematic reviews. Identified studies were cross-referenced until the point of saturation, resulting in 1,786 studies for additional inclusion/exclusion screening. Following a consensus-based review among the authors that included risk of bias, 323 randomized controlled trials were included in the meta analysis. Although several intervention modalities appeared protective against nursing home admission and approached statistical significance, preliminary results suggest that comprehensive geriatrics assessment (pooled OR = .69, 95% CI: .50, .95) and specialized, inpatient geriatrics care (pooled OR: .77, 95% CI: .59, .99) were most consistent in helping to prevent institutionalization among older persons. The findings emphasize the importance of geriatrics when delivering optimal care to older persons. Integrating such approaches more effectively into a largely fee-for-service healthcare paradigm remain a critical challenge.

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