scholarly journals A Method to Estimate the Efficacy vs Effectiveness in Meta-Analysis of Clinical Trials with Different Adherence Scenarios: A Monte Carlo Simulation Study in Nutrition

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2352
Author(s):  
Miguel Ángel López-Espinoza ◽  
José Antonio Lozano-Lozano ◽  
David Prieto-Merino
Keyword(s):  
Clinical Trials ◽  
Monte Carlo ◽  
Randomized Clinical Trials ◽  
Expert Knowledge ◽  
Meta Analysis ◽  
Specific Effect ◽  
Cochrane Systematic Review ◽  
Monte Carlo Simulation Study ◽  
Intention To Treat ◽  
Meta Analyses

Randomized clinical trials (RCTs) evaluating the effectiveness of interventions to promote fruit and vegetable (FV) consumption usually report intention-to-treat (ITT) analysis as the main outcome. These analyses compare the randomly assigned groups and accept that some individuals may not follow the recommendations received in their group. The ITT analysis is useful to quantify the global effect of promoting the consumption of FV in a population (effectiveness) but, if non-adherence is significant in the RCT, they cannot estimate the specific effect in the individuals that increased their FV consumption (efficacy). To calculate the efficacy of FV consumption, a per protocol analysis (PP) would have to be carried out, in which groups of individuals are compared according to their actual adherence to FV consumption, regardless of the group to which they were assigned; unfortunately, many RCTs do not report the PP analysis. The objective of this article is to apply a new method to estimate the efficacy of Meta-analysis (MA) PP which include RCTs of effectiveness by ITT, without estimates of adherence. The method is based on generating Monte Carlo simulations of percentages of adherence in each allocation group from prior distributions informed by expert knowledge. We illustrate the method reanalyzing a Cochrane Systematic Review (SR) of RCTs on increased FV consumption reported with ITT, simulating 1000 times the estimation of a PP meta-analyses, and obtaining means and ranges of the potential PP effects. In some cases, the range of estimated PP effects was clearly more favourable than the effect calculated with the original ITT assumption, and therefore this corrected analysis must be considered when estimating the true effect of the consumption of a certain food.

scholarly journals Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Steven Kwasi Korang ◽  
Sophie Juul ◽  
Emil Eik Nielsen ◽  
Joshua Feinberg ◽  
Faiza Siddiqui ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Individual Patient Data ◽  
Viral Vector ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Serious Adverse Events ◽  
Meta Analyses ◽  
Harmful Effects

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19. Methods/design We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; “active placebo;” no intervention; standard care; an “active” intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately. Discussion COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease. Systematic review registration PROSPERO CRD42020196492

scholarly journals Efficacy of Adjunctive Treatments Added to Olanzapine or Clozapine for Weight Control in Patients with Schizophrenia: A Systematic Review and Meta-Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yun-Jung Choi
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Effects ◽  
Weight Reduction ◽  
Weight Control ◽  
Randomized Clinical Trials ◽  
Psychiatric Symptoms ◽  
Meta Analysis ◽  
Cochrane Central Register ◽  
Meta Analyses

Objectives. This study was conducted to review systematically adjunctive treatments for weight reduction in patients with schizophrenia and compare efficacies of clinical trials through meta-analysis, so as to provide effective clinical guideline regarding weight control for patients taking atypical antipsychotics.Methods. Candidate clinical trials were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO. Fourteen randomized clinical trials were included for systematic review and meta-analysis from 132 potential trials. The Comprehensive Meta-Analysis version 2 was used for meta-analysis.Results. Difference in means and significances from meta-analyses regarding weight control by adjunctive treatments showed that topiramate, aripiprazole, or sibutramine was more effective than metformin or reboxetine. Psychiatric evaluations did not show statistically significant changes between treatment groups and placebo groups except topiramate adjunctive treatments. Adverse effects regarding adjunctive therapies were tolerable and showed statistically no significances compared to control groups.Conclusion. Though having several reports related to exacerbation of psychiatric symptoms, topiramate and aripiprazole are more efficacious than other medications in regard to weight reduction and less burden of critical adverse effects as well as being beneficial for clinical improvement.

scholarly journals A Systematic Review and Network Meta-Analysis on the Efficacy of Medications in the Treatment of Chronic Idiopathic Constipation in Japan

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Atsushi Nakajima ◽  
Ayako Shoji ◽  
Kinya Kokubo ◽  
Ataru Igarashi
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Bayesian Network ◽  
Systematic Reviews ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Relative Efficacy ◽  
Idiopathic Constipation ◽  
Chronic Idiopathic Constipation ◽  
Meta Analyses

Background. In the 2010s, medications with new mechanisms were introduced in Japan for the treatment of chronic idiopathic constipation (CIC). A few systematic reviews have compared medications’ relative efficacy, but the reviews included studies on patients from various races, even though the mechanism of CIC is considered to differ between races. The aim of this study was to use a systematic review and network meta-analysis to compare the relative efficacy of these medications in Japanese patients. Methods. We conducted a meta-analysis and report it here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified studies by searching MEDLINE (via the PubMed interface) and the Cochrane Library and ICHUSHI databases and included randomized clinical trials that compared medications for CIC with placebo in Japanese adults. Two reviewers independently screened and assessed articles, abstracted data, and assessed the risk of bias. We pooled data by random-effects meta-analyses and also performed a Bayesian network meta-analysis to indirectly compare data. Results. The present systematic review and meta-analyses included 1460 patients in 6 randomized clinical trials: 2 on linaclotide, 3 on elobixibat, 2 on lubiprostone, and 1 on lactulose. The results of direct comparisons showed that linaclotide, elobixibat, and lubiprostone were superior to placebo in the change of spontaneous bowel movements (SBMs) within 1 week: linaclotide, 1.95 (95% CI, 1.51-2.39); elobixibat, 5.69 (95% CI, 3.31-8.07); and lubiprostone, 2.41 (95% CI, 0.82-4.01). The Bayesian network meta-analysis showed consistent results. Elobixibat 10 mg was ranked first for the increase in SBMs and complete SBMs within 1 week and the time to first SBM. Lubiprostone 48 μg was ranked first for the proportion of patients with SBM within 24 hours. Conclusion. Our direct and indirect meta-analyses revealed that the new CIC medications available in Japan have equal efficacy but that elobixibat and lubiprostone are highly likely to be more efficacious.

Cardiovascular toxicity incidence following immune checkpoint inhibitors in randomized clinical trials: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2636-2636
Author(s):  
Camila Bragança Xavier ◽  
Carlos Diego Holanda Lopes ◽  
Guilherme Harada ◽  
Artur Katz ◽  
Denis Leonardo Fontes Jardim
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Increased Risk ◽  
Meta Analyses

2636 Background: Immune checkpoint inhibitors (ICIs) are widely used in oncology and may be associated with a variety of immune-related toxicities. Cardiovascular (CV) adverse effects (AEs) are underreported in randomized clinical trials (RCTs), and the real risk associated with ICIs use has yet to be defined. Therefore, we aimed to investigate the incidence and risk of cardiovascular toxicities in patients receiving ICIs, using an up-to-date meta-analysis of prospective RCTs. Methods: We conducted a systematic search of the literature from January 1st, 2010 until July 1st, 2020 to identify RCTs testing ICIs for solid tumors, either in monotherapy or in combination between them. Our initial search yielded a total of 21,249 relevant publications. For CV AEs incidence estimation, we included phase III RCTs testing PD-1, PD-L1, CTLA-4 inhibitors or any combination of these agents. For relative risk (RR) assessment, we included phase II or phase III RCTs testing the same agents and with placebo or best supportive care (BSC) as the comparator. Data were extracted by independent reviewers following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. CV AEs were categorized based on the Common Toxicity Criteria (CTCAE) and stratified by ICIs type. Analyses were conducted using random effects model. Results: After screening and eligibility assessment, a total of 21,118 patients (67 cohorts from 57 trials) were available for this meta-analysis. We categorized the cohorts by ICIs regimen as monotherapy with a PD-1 inhibitor (35 cohorts; 10,241 patients), PD-L1 inhibitor (12 cohorts; 3,755 patients), CTLA-4 inhibitor (11 cohorts; 4,135 patients), and combination therapy (9 cohorts; 2,987 patients). Incidence measures are described in the table. Deaths from any CV cause occurred in 0.20% of the patients (95%CI 0.10%; 0.20%). For RR analysis, we included 12 cohorts from 11 RCTs. Risk of experiencing all grade AEs was numerically higher among patients who received ICIs than placebo or BSC (RR 1.16; 95%CI 0.98; 1.37; p=0.09). When only grade 3-5 CV AEs were considered, ICIs were associated with increased risk (RR 1.36; 95%CI 1.06; 1.73; p= 0.01). Additional analyses were conducted to estimate the RR of individual CV AEs including arrhythmia, cardiac arrest, heart failure, stroke, hypertension, myocardial infarction, myocarditis, pericardial events, and thromboembolic events. None of the analysis identified a significant additional risk. Conclusions: This meta-analysis corroborates the preclinical rationale of worsen CV risk related to ICIs use.[Table: see text]

scholarly journals Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials

2020 ◽  
Author(s):  
Cathrine Axfors ◽  
Andreas M. Schmitt ◽  
Perrine Janiaud ◽  
Janneke van ’t Hooft ◽  
Sherief Abd-Elsalam ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Total Sample ◽  
Recruitment Challenges ◽  
Included Patient ◽  
Chloroquine Treatment ◽  
All Cause Mortality ◽  
High Doses ◽  
Meta Analyses

AbstractSubstantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We conducted a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine was 1.11 (95% CI: 1.02, 1.20; I2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine was associated with increased mortality in COVID-19 patients, and there was no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

PP052 Hospital-based Health Technology Assessment Of Prasugrel In Patients With Stent: Outpatient Use

2017 ◽  
Vol 33 (S1) ◽  
pp. 96-96
Author(s):  
Márcia Gisele Costa ◽  
Marisa Santos ◽  
Rafaela Peixoto
Keyword(s):  
Clinical Trials ◽  
Stent Thrombosis ◽  
Major Bleeding ◽  
Stent Implantation ◽  
Randomized Clinical Trials ◽  
New Technologies ◽  
Meta Analysis ◽  
Adherence To Treatment ◽  
Cost Study ◽  
Meta Analyses

INTRODUCTION:A reference hospital, specialized in cardiology, has standardized clopidogrel, ticagrelor and recently the incorporation of prasugrel was approved with an estimate of fifteen patients with stent implantation monthly. Stent thrombosis is a rare but serious complication and it is recommended that patients be treated with antiplatelet therapy. Considering the existing therapeutic options and the low adherence to treatment, a cost study was requested to discuss a disinvestment proposal.METHODS:Perspective of the hospital; Population: patients with myocardial infarction and stent implantation; Intervention: prasugrel; Comparators: clopidogrel and ticagrelor; Outcomes of interest: stent thrombosis and major bleeding; and types of study: meta-analyses and randomized clinical trials. Literature review was performed in the Medline database, via Pubmed and performed meta-analysis. Cost estimates: data collection made in the institution's database.RESULTS:Thirteen articles were selected; there are no differences in the outcomes for prasugrel and ticagrelor; discontinuation of treatment is the most important risk factor for stent thrombosis and major bleeding is an important predictor of nonadherence to treatment. Quantitative analysis: three clinical trials. All showed a superiority of prasugrel and ticagrelor over clopidogrel for outcome of stent thrombosis (Odds Ratio, OR .60 Confidence Interval, CI 95 percent [.40; .90]), which was committed by the heterogeneity of studies (I2 = 64 percent); and favorable outcome for clopidogrel compared to ticagrelor and prasugrel for the outcome of major bleeding (OR 1.28 CI 95 percent [1.10; 1.50]). Annual cost with treatment of the fifteen patients: clopidogrel = USD5,765.86; prasugrel = USD41,047.48; and ticagrelor = USD44,081.30.CONCLUSIONS:The evidences found support the opening of a disinvestment process and suggest to the managers of the institution a reflection on: strategy to optimize adherence to treatment; and especially in the cost of opportunity with new technologies about 10 times more expensive.

scholarly journals Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cathrine Axfors ◽  
Andreas M. Schmitt ◽  
Perrine Janiaud ◽  
Janneke van’t Hooft ◽  
Sherief Abd-Elsalam ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Total Sample ◽  
Recruitment Challenges ◽  
Chloroquine Treatment ◽  
All Cause Mortality ◽  
High Doses ◽  
Meta Analyses ◽  
Clinical Trials Registry

AbstractSubstantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

The Effect of L-Carnitine on Mortality Rate in Septic Patients: A Systematic Review and Meta-Analysis on Randomized Clinical Trials

2020 ◽  
Vol 20 ◽  
Author(s):  
Hamed Abdollahi ◽  
Mina Abdolahi ◽  
Mohsen Sedighiyan ◽  
Arash Jafarieh
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Mortality Rate ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Carnitine Supplementation ◽  
Language Restriction ◽  
One Year ◽  
Meta Analyses

Background: Recent clinical trial studies have reported that L-carnitine supplementation can reduce the mortality rate in patients with sepsis, but there are no definitive results in this context. The current systematic review and metaanalysis aimed to evaluate the effect of L-carnitine supplementation on 28-day and one-year mortality in septic patients. Methods: A systemically search conducted on Pubmed, Scopus and Cochrane Library databases up to June 2019 without any language restriction. The publications were reviewed based on Cochrane handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA). To compare the effects of L-carnitine with placebo, Risk Ratio (RR) with 95% confidence intervals (CI) were pooled according to random effects model. Results: Across five enrolled clinical trials, we found that L-carnitine supplementation reduce one-year mortality in septic patients with SOFA> 12 (RR: 0.68; 95% CI: 0.49 to 0.96; P= 0.03) but had no significant effect on reducing 28-day mortality ((RR: 0.93; 95% CI: 0.68 to 1.28; P= 0.65) compared to placebo. Finally, we observed that based on current trials, Lcarnitine supplementation may not have clinically a significant effect on mortality rate. Conclusions: L-carnitine patients with higher SOFA score can reduce the mortality rate. However, the number of trials, study duration and using dosage of L-carnitine are limited in this context and further large prospective trials are required to clarify the effect of L-carnitine on mortality rate in septic patients.

scholarly journals The effects of adding glucocorticosteroids to standard care for children with sepsis. A systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis

2021 ◽  
Author(s):  
Steven Kwasi Korang ◽  
Sanam Safi ◽  
Christian Gluud ◽  
Janus C Jakobsen
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Standard Care ◽  
Sequential Analysis ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
Serious Adverse Events ◽  
Meta Analyses

Abstract Background: Glucocorticosteroids are widely used to treat severe sepsis in pediatric intensive care units. However, the evidence on the clinical effects is unclear.Objective: To assess the benefits and harms of glucocorticosteroids for children with sepsis. Data Sources: We conducted a systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis (TSA) (PROSPERO CRD42017054341). We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, and more. Study Selection: Randomized clinical trials assessing the effects of adding glucocorticosteroids to standard care for children with sepsis. Data Extraction: Two independent reviewers screened studies and extracted data. Evidence was assessed by GRADE according to our published protocol.Data Synthesis: We included 24 trials randomizing 3073 participants. Meta-analyses showed no evidence of an effect of adding glucocorticosteroids for children with sepsis with a mixed focus for any of our outcomes. Meta-analyses suggested evidence of a beneficial effect of dexamethasone for children with meningitis when assessing serious adverse events (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.53 to 0.86; P = 0.001, very low certainty of evidence) and ototoxicity (RR 0.63, 95% CI 0.45 to 0.88; P = 0.007, low certainty of evidence). TSAs showed that we did not have sufficient data to confirm or reject these results. We found insufficient evidence to confirm or reject an effect on mortality or our other outcomes. No trials reported quality of life or organ failure. Most trials were at high risks of bias. We found high clinical heterogeneity between participants. None of our TSAs showed benefits, harms or futility. Conclusions: Generally, we found no evidence of an effect of glucocorticosteroids for children with sepsis without meningitis. Dexamethasone for sepsis in children due to meningitis may decrease serious adverse events and ototoxicity.

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