scholarly journals Conditional power of antidepressant network meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lisa Holper
Keyword(s):  
Meta Analysis ◽  
Indirect Evidence ◽  
Dropout Rate ◽  
Conclusive Evidence ◽  
Effect Sizes ◽  
Current Evidence ◽  
Hamilton Depression Scale ◽  
Conditional Power ◽  
Sample Sizes ◽  
Antidepressant Treatments

Abstract Background Conditional power of network meta-analysis (NMA) can support the planning of randomized controlled trials (RCTs) assessing medical interventions. Conditional power is the probability that updating existing inconclusive evidence in NMA with additional trial(s) will result in conclusive evidence, given assumptions regarding trial design, anticipated effect sizes, or event probabilities. Methods The present work aimed to estimate conditional power for potential future trials on antidepressant treatments. Existing evidence was based on a published network of 502 RCTs conducted between 1979-2018 assessing acute antidepressant treatment in major depressive disorder (MDD). Primary outcomes were efficacy in terms of the symptom change on the Hamilton Depression Scale (HAMD) and tolerability in terms of the dropout rate due to adverse events. The network compares 21 antidepressants consisting of 231 relative treatment comparisons, 164 (efficacy) and 127 (tolerability) of which are currently assumed to have inconclusive evidence. Results Required sample sizes to achieve new conclusive evidence with at least 80% conditional power were estimated to range between N = 894 - 4190 (efficacy) and N = 521 - 1246 (tolerability). Otherwise, sample sizes ranging between N = 49 - 485 (efficacy) and N = 40 - 320 (tolerability) may require stopping for futility based on a boundary at 20% conditional power. Optimizing trial designs by considering multiple trials that contribute both direct and indirect evidence, anticipating alternative effect sizes or alternative event probabilities, may increase conditional power but required sample sizes remain high. Antidepressants having the greatest conditional power associated with smallest required sample sizes were identified as those on which current evidence is low, i.e., clomipramine, levomilnacipran, milnacipran, nefazodone, and vilazodone, with respect to both outcomes. Conclusions The present results suggest that conditional power to achieve new conclusive evidence in ongoing or future trials on antidepressant treatments is low. Limiting the use of the presented conditional power analysis are primarily due to the estimated large sample sizes which would be required in future trials as well as due to the well-known small effect sizes in antidepressant treatments. These findings may inform researchers and decision-makers regarding the clinical relevance and justification of research in ongoing or future antidepressant RCTs in MDD.

scholarly journals Obesity and Periodontal Disease: A Narrative Review on Current Evidence and Putative Molecular Links

2019 ◽  
Vol 13 (1) ◽  
pp. 526-536
Author(s):  
Federica Di Spirito ◽  
Ludovico Sbordone ◽  
Vincenzo Pilone ◽  
Francesco D’Ambrosio
Keyword(s):  
Periodontal Disease ◽  
Systematic Reviews ◽  
Literature Search ◽  
Meta Analysis ◽  
Indirect Evidence ◽  
Positive Association ◽  
Current Evidence ◽  
Screening Process ◽  
Clinical Criteria ◽  
Comparison Of The Results

Background: Obesity represents one of the main health problems worldwide and is considered a risk factor for several diseases, including periodontitis, which is a microbially-associated inflammatory disease affecting the tooth-supporting structures. Objective: The aim of this review was to report the current direct and indirect evidence concerning the possible association between obesity and periodontitis and their putative molecular links. Methods: A literature search was conducted between January 1999 and September 2019, in PubMed/MEDLINE and Science Direct databases, using pertinent keyword combined by Boolean operators. Through a multi-step screening process (literature search; articles title and abstract evaluation and full-text reading), studies fitting inclusion/exclusion criteria were considered for the review. Results: 35 studies were included in the present review (17 observational studies; 7 systematic reviews; 11 systematic reviews with meta-analysis), focusing on the direct and indirect evidence of the possible association between obesity and periodontitis and their potential etiopathogenic molecular links Conclusion: Although the majority of the studies reported a positive association between obesity and periodontitis, the heterogeneity of the classification criteria and of the clinical parameters employed in the studies for both obesity and periodontitis evaluation, complicated the comparison of the results, thus considered inconclusive. Although several putative molecular pathogenic links between obesity and periodontitis have been highlighted, further studies, with longer follow-ups and with homogeneous clinical criteria, are needed to better understand the putative relation between obesity and periodontal disease.

scholarly journals Specificity of Future Thinking in Depression: A Meta-Analysis

2018 ◽  
Author(s):  
Beau Gamble ◽  
David Moreau ◽  
Lynette J. Tippett ◽  
Donna Rose Addis
Keyword(s):  
Random Effects ◽  
Meta Analysis ◽  
Emotional Valence ◽  
Effect Sizes ◽  
Current Evidence ◽  
Future Research ◽  
Future Thinking ◽  
Moderator Variables ◽  
Search Terms ◽  
The Relationship

Reduced specificity of autobiographical memory has been well established in depression, but whether this ‘overgenerality’ extends to future thinking has not been the focus of a meta-analysis. Following a preregistered protocol, we searched six electronic databases, Google Scholar, personal libraries, and contacted authors in the field for studies matching search terms related to depression, future thinking, and specificity. We reduced an initial 7,332 results to 46 included studies, with 89 effect sizes and 4,813 total participants. Random effects meta-analytic modelling revealed a small but robust correlation between reduced future specificity and higher levels of depression (r = .13, p < .001). Of the 11 moderator variables examined, the most striking effects related to the emotional valence of future thinking (p < .001) and the sex of participants (p = .025). Namely, depression was linked to reduced specificity for positive (but not negative or neutral) future thinking, and the relationship was stronger in samples with a higher proportion of males. This meta-analysis contributes to our understanding of how prospection is altered in depression and dysphoria and, by revealing areas where current evidence is inconclusive, highlights key avenues for future research.

scholarly journals Specificity of Future Thinking in Depression: A Meta-Analysis

2019 ◽  
Vol 14 (5) ◽  
pp. 816-834 ◽  
Author(s):  
Beau Gamble ◽  
David Moreau ◽  
Lynette J. Tippett ◽  
Donna Rose Addis
Keyword(s):  
Random Effects ◽  
Meta Analysis ◽  
Emotional Valence ◽  
Effect Sizes ◽  
Current Evidence ◽  
Future Research ◽  
Future Thinking ◽  
Moderator Variables ◽  
Search Terms ◽  
The Relationship

Reduced specificity of autobiographical memory has been well established in depression, but whether this overgenerality extends to future thinking has not been the focus of a meta-analysis. Following a preregistered protocol, we searched six electronic databases, Google Scholar, and personal libraries and contacted authors in the field for studies matching search terms related to depression, future thinking, and specificity. We reduced an initial 7,332 results to 46 included studies, with 89 effect sizes and 4,813 total participants. Random-effects meta-analytic modeling revealed a small but robust correlation between reduced future specificity and higher levels of depression ( r = −.13, p < .001). Of the 11 moderator variables examined, the most striking effects were related to the emotional valence of future thinking ( p < .001) and the sex of participants ( p = .025). Namely, depression was linked to reduced specificity for positive (but not negative or neutral) future thinking, and the relationship was stronger in samples with a higher proportion of males. This meta-analysis contributes to our understanding of how prospection is altered in depression and dysphoria and, by revealing areas where current evidence is inconclusive, highlights key avenues for future research.

A meta-analysis on pain sensitivity in self-injury

2016 ◽  
Vol 46 (8) ◽  
pp. 1597-1612 ◽  
Author(s):  
J. Koenig ◽  
J. F. Thayer ◽  
M. Kaess
Keyword(s):  
Pain Intensity ◽  
Pain Sensitivity ◽  
Pain Threshold ◽  
Meta Analysis ◽  
Pain Tolerance ◽  
Effect Sizes ◽  
Current Evidence ◽  
Healthy Controls ◽  
Hand Search ◽  
Self Injury

Individuals engaging in self-injurious behavior (SIB) frequently report absence of pain during acts of SIB. While altered pain sensitivity is discussed as a risk factor for the engagement in SIB, results have been mixed with considerable variance across reported effect sizes, in particular with respect to the effect of co-morbid psychopathology. The present meta-analysis aimed to summarize the current evidence on pain sensitivity in individuals engaging in SIB and to identify covariates of altered pain processing. Three databases were searched without restrictions. Additionally a hand search was performed and reference lists of included studies were checked for potential studies eligible for inclusion. Thirty-two studies were identified after screening 720 abstracts by two independent reviewers. Studies were included if they reported (i) an empirical investigation, in (ii) humans, including a sample of individuals engaging in (iii) SIB and a group of (iv) healthy controls, (v) receiving painful stimulation. Random-effects meta-analysis was performed on three pain-related outcomes (pain threshold, pain tolerance, pain intensity) and several population- and study-level covariates (i.e. age, sex, clinical etiology) were subjected to meta-regression. Meta-analysis revealed significant main effects associated with medium to large effect sizes for all included outcomes. Individuals engaging in SIB show greater pain threshold and tolerance and report less pain intensity compared to healthy controls. Clinical etiology and age are significant covariates of pain sensitivity in individuals engaging in SIB, such that pain threshold is further increased in borderline personality disorder compared to non-suicidal self-injury. Mechanisms underlying altered pain sensitivity are discussed.

scholarly journals Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain: A Systematic Review and Meta-Analysis for an Appropriateness Panel

2019 ◽  
Vol 2 (22.2) ◽  
pp. E55-E70 ◽  
Author(s):  
Ian D. Coulter
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Neck Pain ◽  
Meta Analysis ◽  
Chronic Neck Pain ◽  
Risk Of Bias ◽  
Current Evidence ◽  
Sample Sizes ◽  
Serious Adverse Events ◽  
Multiple Treatment

Background: Mobilization and manipulation therapies are widely used by patients with chronic nonspecific neck pain; however, questions remain around efficacy, dosing, and safety, as well as how these approaches compare to other therapies. Objectives: Based on published trials, to determine the efficacy, effectiveness, and safety of various mobilization and manipulation therapies for treatment of chronic nonspecific neck pain. Study Design: A systematic literature review and meta-analysis. Methods: We identified studies published between January 2000 and September 2017, by searching multiple electronic databases, examining reference lists, and communicating with experts. We selected randomized controlled trials comparing manipulation and/or mobilization therapies to sham, no treatment, each other, and other active therapies, or when combined as multimodal therapeutic approaches. We assessed risk of bias by using the Scottish Intercollegiate Guidelines Network criteria. When possible, we pooled data using random-effects meta-analysis. Grading of Recommendations, Assessment, Development, and Evaluation was applied to determine the confidence in effect estimates. This project was funded by the National Center for Complementary and Integrative Health under award number U19AT007912 and ultimately used to inform an appropriateness panel. Results: A total of 47 randomized trials (47 unique trials in 53 publications) were included in the systematic review. These studies were rated as having low risk of bias and included a total of 4,460 patients with nonspecific chronic neck pain who were being treated by a practitioner using various types of manipulation and/or mobilization interventions. A total of 37 trials were categorized as unimodal approaches and involved thrust or nonthrust compared with sham, no treatment, or other active comparators. Of these, only 6 trials with similar intervention styles, comparators, and outcome measures/timepoints were pooled for meta-analysis at 1, 3, and 6 months, showing a small effect in favor of thrust plus exercise compared to an exercise regimen alone for a reduction in pain and disability. Multimodal approaches appeared to be effective at reducing pain and improving function from the 10 studies evaluated. Health-related quality of life was seldom reported. Some 22/47 studies did not report or mention adverse events. Of the 25 that did, either no or minor events occurred. Limitations: The current evidence is heterogeneous, and sample sizes are generally small. Conclusions: Studies published since January 2000 provide low-moderate quality evidence that various types of manipulation and/or mobilization will reduce pain and improve function for chronic nonspecific neck pain compared to other interventions. It appears that multimodal approaches, in which multiple treatment approaches are integrated, might have the greatest potential impact. The studies comparing to no treatment or sham were mostly testing the effect of a single dose, which may or may not be helpful to inform practice. According to the published trials reviewed, manipulation and mobilization appear safe. However, given the low rate of serious adverse events, other types of studies with much larger sample sizes would be required to fully describe the safety of manipulation and/or mobilization for nonspecific chronic neck pain. Key words: Chronic neck pain, nonspecific, chiropractic, manipulation, mobilization, systematic review, meta-analysis, appropriateness

Unsuccessful Treatments of “Writer's Block”: A Meta-Analysis

2014 ◽  
Vol 115 (1) ◽  
pp. 276-278 ◽  
Author(s):  
Derrick C. McLean ◽  
Benjamin R. Thomas
Keyword(s):  
Meta Analysis ◽  
Small Sample ◽  
The Body ◽  
Effect Sizes ◽  
Sample Sizes ◽  
Writer's Block ◽  
Unsuccessful Treatment ◽  
Group Treatments ◽  
Writer’S Block ◽  
Small Sample Sizes

A wide literature of the unsuccessful treatment of writer's block has emerged since the early 1970's. Findings within this literature seem to confer generalizability of this procedure; however, small sample sizes may limit this interpretation. This meta-analysis independently analyzed effect sizes for “self-treatments” and “group-treatments” using number of words in the body of the publication as indication of a failure to treat writer's block. Results of the reported findings suggest that group-treatments tend to be slightly more unsuccessful than self-treatments.

scholarly journals Evidence synthesis and decision modelling to support complex decisions: stockpiling neuraminidase inhibitors for pandemic influenza usage

F1000Research ◽  
2017 ◽  
Vol 5 ◽  
pp. 2293
Author(s):  
Samuel I. Watson ◽  
Yen-Fu Chen ◽  
Jonathan S. Nguyen-Van-Tam ◽  
Puja R. Myles ◽  
Sudhir Venkatesan ◽  
...  
Keyword(s):  
Observational Data ◽  
Pandemic Influenza ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Policy Decision ◽  
Epidemiological Data ◽  
Neuraminidase Inhibitor ◽  
Conclusive Evidence ◽  
Current Evidence ◽  
Net Benefit

Objectives: The stockpiling of neuraminidase inhibitor (NAI) antivirals as a defence against pandemic influenza is a significant public health policy decision that must be made despite a lack of conclusive evidence from randomised controlled trials regarding the effectiveness of NAIs on important clinical end points such as mortality. The objective of this study was to determine whether NAIs should be stockpiled for treatment of pandemic influenza on the basis of current evidence. Methods: A decision model for stockpiling was designed. Data on previous pandemic influenza epidemiology was combined with data on the effectiveness of NAIs in reducing mortality obtained from a recent individual participant meta-analysis using observational data. Evidence synthesis techniques and a bias modelling method for observational data were used to incorporate the evidence into the model. The stockpiling decision was modelled for adults (≥16 years old) and the United Kingdom was used as an example. The main outcome was the expected net benefits of stockpiling in monetary terms. Health benefits were estimated from deaths averted through stockpiling. Results: After adjusting for biases in the estimated effectiveness of NAIs, the expected net benefit of stockpiling in the baseline analysis was £444 million, assuming a willingness to pay of £20,000/QALY ($31,000/QALY). The decision would therefore be to stockpile NAIs. There was a greater probability that the stockpile would not be utilised than utilised. However, the rare but catastrophic losses from a severe pandemic justified the decision to stockpile. Conclusions: Taking into account the available epidemiological data and evidence of effectiveness of NAIs in reducing mortality, including potential biases, a decision maker should stockpile anti-influenza medication in keeping with the postulated decision rule.

scholarly journals Evidence synthesis and decision modelling to support complex decisions: stockpiling neuraminidase inhibitors for pandemic influenza usage

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2293
Author(s):  
Samuel I. Watson ◽  
Yen-Fu Chen ◽  
Jonathan S. Nguyen-Van-Tam ◽  
Puja R. Myles ◽  
Sudhir Venkatesan ◽  
...  
Keyword(s):  
Observational Data ◽  
Pandemic Influenza ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Policy Decision ◽  
Epidemiological Data ◽  
Neuraminidase Inhibitor ◽  
Conclusive Evidence ◽  
Current Evidence ◽  
Net Benefit

Objectives: The stockpiling of neuraminidase inhibitor (NAI) antivirals as a defence against pandemic influenza is a significant public health policy decision that must be made despite a lack of conclusive evidence from randomised controlled trials regarding the effectiveness of NAIs on important clinical end points such as mortality. The objective of this study was to determine whether NAIs should be stockpiled for treatment of pandemic influenza on the basis of current evidence. Methods: A decision model for stockpiling was designed. Data on previous pandemic influenza epidemiology was combined with data on the effectiveness of NAIs in reducing mortality obtained from a recent individual participant meta-analysis using observational data. Evidence synthesis techniques and a bias modelling method for observational data were used to incorporate the evidence into the model. The stockpiling decision was modelled for adults (≥16 years old) and the United Kingdom was used as an example. The main outcome was the expected net benefits of stockpiling in monetary terms. Health benefits were estimated from deaths averted through stockpiling. Results: After adjusting for biases in the estimated effectiveness of NAIs, the expected net benefit of stockpiling in the baseline analysis was £444 million, assuming a willingness to pay of £20,000/QALY ($31,000/QALY). The decision would therefore be to stockpile NAIs. There was a greater probability that the stockpile would not be utilised than utilised. However, the rare but catastrophic losses from a severe pandemic justified the decision to stockpile. Conclusions: Taking into account the available epidemiological data and evidence of effectiveness of NAIs in reducing mortality, including potential biases, a decision maker should stockpile anti-influenza medication in keeping with the postulated decision rule.

Abstract 12138: Angiotensin Blockade Reduces Aortic Dilatation in Patients With Marfan Syndrome: A Meta-Analysis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Partha Sardar ◽  
Amartya Kundu ◽  
Omosalewa Adenikinju ◽  
Gerald Pekler ◽  
Saurav Chatterjee ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Aortic Root ◽  
Meta Analysis ◽  
Conclusive Evidence ◽  
Sensitivity Analyses ◽  
Current Evidence ◽  
Cochrane Central Register ◽  
Aortic Dilatation ◽  
Observation Study ◽  
Aortic Root Dilatation

Introduction: Recently few studies evaluated the effects of ACE/ARB in patients with Marfan syndrome. However, as majority of the studies were small and mainly pilot studies, conclusive evidence of benefit with ACE/ARB in this scenario is still pending. The objective of the present meta-analysis was to evaluate the effect of ACE/ARB on the progression of aortic root dilatation in patients with Marfan syndrome. Hypothesis: Treatment with ACE/ARBs is effective for the prevention of aortic-root enlargement in patients with Marfan syndrome. Methods: We searched PubMed, EMBASE, and Cochrane Central Register of Clinical Trials from the inception to April 30, 2013. The main outcome of the present analysis was the change in aortic root diameter with ACE/ABR therapy compared to control. The random effects model of DerSimonian and Laird was used. Results: Four studies were included in the final analysis; three studies were randomized trial and one was observation study. ACE/ARB significantly reduced enlargement of aortic root diameters compared to control; mean difference of -0.97 (95% confidence interval, -1.42 to -0.52; P<0.0001). Consistent benefit of ACE/ARB was observed in all sub-group and sensitivity analyses; against beta blocker, against placebo, in adult patients, with only ARB, analysis with the results from only RCTs. Conclusions: This is the first meta-analysis indicating a beneficial effect of ACE/ARB treatment on aortic root dilatation in patients with Marfan Syndrome. Current evidence supports the use of ARB, specially losartan for this indication.

Power Statistics for Meta-analysis: Tests for Mean Effects and Homogeneity

2013 ◽  
Author(s):  
Marc J. Lajeunesse
Keyword(s):  
Statistical Power ◽  
Meta Analysis ◽  
Effect Sizes ◽  
Experimental Sample ◽  
Sample Sizes ◽  
Homogeneity Tests ◽  
Sufficient Power ◽  
Experimental Effect ◽  
The Common

The common justification for meta-analysis is the increased statistical power to detect effects over what is obtained from individual studies. For ecologists and evolutionary biologists, the statistical power of meta-analysis is important because effect sizes are usually relatively small in these fields, and experimental sample sizes are often limited for logistic reasons. Consequently, many studies lack sufficient power to detect an experimental effect should it exist. This chapter provides a brief overview of the factors that determine the statistical power of meta-analysis. It presents statistics for calculating the power of pooled effect sizes to evaluate nonzero effects and the power of within- and between-study homogeneity tests. It also surveys ways to improve the statistical power of meta-analysis, and ends with a discussion on the overall utility of power statistics for meta-analysis.

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