Journal of Clinical Epidemiology最新文献

{"title":"What makes a good guideline? - A systematic review and analysis of 120 clinical practice guidelines using the AGREE II tool.","authors":"Marina L Fotteler, Thomas D Kocar, Jana Willems, Sebastian Voigt-Radloff, Christoph Leinert, Dhayana Dallmeier, Clara Hertneck, Michael Denkinger","doi":"10.1016/j.jclinepi.2025.111830","DOIUrl":"https://doi.org/10.1016/j.jclinepi.2025.111830","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical practice guidelines (CPGs) translate evidence into actionable recommendations to enhance care quality, improve clinical outcomes, reduce treatment variations, and make healthcare delivery more cost-effective. CPGs primarily aid healthcare practitioners but are also used by patients, policymakers, and organizations. The study aim was to assess CPG quality using the AGREE II instrument and to identify AGREE II items and domains that influence the overall assessment.</p><p><strong>Methods: </strong>Medline and eight CPG databases were searched for guidelines applicable to older patients (≥60 years, frail, or with dementia/delirium) in acute orthopedic/traumatological settings, published in English or German since January 1st, 2016, and employing an evidence appraisal. Titles, abstracts, and full texts were independently screened by two reviewers using Covidence. AGREE II assessments were conducted across all 23 items in six domains by three reviewers with different professional backgrounds. Data were analyzed using descriptive statistics, Mann-Whitney U test, Pearson's r correlation matrix, variance inflation factor (VIF), univariable and multivariable regression (non-negative least squares), and intraclass correlation coefficient (ICC). Significance was set at p<0.05.</p><p><strong>Results: </strong>A total of 120 CPGs have been appraised, reaching a mean overall rating of 4.35 (±1.13). Most guidelines received an overall rating of five (n=40, 33.33%), one guideline received an overall rating of one (0.8%). Using a standardized evidence rating framework (e.g. GRADE) is significantly associated with a better overall rating (p<0.001). The multivariable analysis showed that items 9, 12, and 15 had the highest influence on the overall AGREE II rating. Domain 6 (editorial independence) did not have an influence on the overall rating in a multivariable analysis.</p><p><strong>Conclusion: </strong>Methodological rigor, particularly the use of a standardized evidence rating framework, is essential for a good overall AGREE II rating and thus for high-quality CPGs. The results from this analysis can assist different stakeholders who also conduct AGREE II appraisals, develop CPGs, or are charged with implementing CPG recommendations.</p>","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":" ","pages":"111830"},"PeriodicalIF":7.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying predictors of early trial termination: A meta-epidemiologic study utilising elements of the research ethics committee evaluation.","authors":"Marieke S Jansen, Lodewijk A Pet, Jeroen T Buijs, Bob Siegerink, Rolf H H Groenwold, Olaf M Dekkers","doi":"10.1016/j.jclinepi.2025.111832","DOIUrl":"https://doi.org/10.1016/j.jclinepi.2025.111832","url":null,"abstract":"<p><strong>Objectives: </strong>Early trial termination remains frequent. Research ethics committees (RECs) could play a role in reducing the probability of early termination. Their review process provides a window for both identifying trials at high risk of terminating prematurely and imposing preventive measures, such as design modifications. This study aimed to explore whether characteristics of ethics review, alongside trial characteristics, are related to subsequent early trial termination.</p><p><strong>Study design and setting: </strong>This meta-epidemiologic cohort study assessed 198 clinical trials approved by a Dutch REC between 2015 - 2018. Data from archived trial protocols, related study documents and correspondence between the REC and investigators were analysed to identify predictors of early termination during ethics review.</p><p><strong>Results: </strong>Of the 198 trials, 69 (34.8%) terminated early, most often due to recruitment failure (n = 31, 35.2%). Several characteristics were associated with early termination, such as multicentre design (vs. single centre, RR: 1.89, 95% CI: 1.24-3.14), number of comments raised during ethics review (per comment, RR: 1.02, 95% CI: 1.00-1.05), and specific comments regarding privacy and confidentiality (RR: 1.21, 95% CI: 1.05-1.41) and participant information sheets (RR: 1.05, 95% CI: 1.02-1.08). Investigator sponsorship, longer review durations, and comments raised regarding privacy and confidentiality and subject selection were associated with an increased likelihood of recruitment failure, specifically.</p><p><strong>Conclusion: </strong>This exploratory study showed that various characteristics of ethics review have the potential to predict early trial termination. Further studies are needed to validate and expand upon these findings.</p>","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":" ","pages":"111832"},"PeriodicalIF":7.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An umbrella review reveals that control variables are rarely considered as a source of heterogeneity in systematic reviews of observational studies.","authors":"Judith J M Rijnhart, Ava Rabbers, Santina Rizzuto, Allison M Howard, Matthew J Valente","doi":"10.1016/j.jclinepi.2025.111826","DOIUrl":"https://doi.org/10.1016/j.jclinepi.2025.111826","url":null,"abstract":"<p><strong>Objectives: </strong>The effect estimates in systematic reviews of observational studies often exhibit high heterogeneity. A potentially important source of heterogeneity are differences in the control variables across observational studies. However, it remains unclear how often this source of heterogeneity is considered in practice. The objective of this umbrella review is to determine how often control for different sets of variables across primary studies was considered as a source of heterogeneity in published systematic reviews of observational epidemiologic studies.</p><p><strong>Study design and setting: </strong>We systematically searched for systematic reviews of observational studies published in a quartile 1 Web of Science or Scopus indexed epidemiology journal between January 1, 2023, and December 31, 2023. Eligibility screening, data extraction, and quality appraisal were performed by two independent reviewers. Data was summarized using descriptive statistics.</p><p><strong>Results: </strong>Eligibility criteria were met by 297 systematic reviews, of which a random sample of 50 systematic reviews were included in this umbrella review. Differences in confounder sets were mentioned as a potential source of heterogeneity in 5/50 reviews (10.0%), differences in covariate sets in 4/50 reviews (8.0%), control for mediators in 0/50 reviews (0.0%), and control for colliders in 0/50 reviews (0.0%).</p><p><strong>Conclusion: </strong>While differences in control for confounders, mediators, and colliders may explain heterogeneity in systematic reviews of observational studies, these sources of heterogeneity are rarely considered in practice. To avoid invalid pooled effect estimates, it is important that future systematic reviews of observational studies assess these potential sources of heterogeneity.</p>","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":" ","pages":"111826"},"PeriodicalIF":7.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Permissibility & Necessity in the Ethical Justification of RCTs: The Four Quadrants Framework and the Case of Endovascular Thrombectomy Trials for Acute Ischemic Stroke.","authors":"Michel Shamy, Rashi Ramchandani, Brian Dewar, Vignan Yogendrakumar, Victoria Shepherd, Mark Fedyk","doi":"10.1016/j.jclinepi.2025.111831","DOIUrl":"https://doi.org/10.1016/j.jclinepi.2025.111831","url":null,"abstract":"<p><strong>Objective: </strong>This study seeks to propose a novel framework for the ethical justification of randomized controlled trials (RCTs).</p><p><strong>Study design and setting: </strong>This paper develops a novel framework to the ethical evaluation of RCTs, explored through the example of trials of endovascular thrombectomy for acute ischemic stroke. We propose that RCTs can be categorized into four quadrants, where justification in each quadrant relates to different thresholds for permissibility (the ethical defensibility of the trial) and necessity (the social and scientific importance of conducting the trial).</p><p><strong>Results: </strong>Trials can be situated within four quadrants based on the interventions being compared: standard vs standard treatment in the alpha quadrant, standard vs novel treatment in the beta quadrant, standard vs no treatment in the gamma quadrant, and no treatment vs novel treatment in the delta quadrant. In each quadrant, the thresholds to establish permissibility and necessity will differ. The controversies that surrounded trials of thrombectomy for acute stroke can be understood as representing differing points of view about whether those trials should have been situated in the beta or delta quadrant. These differing conclusions highlight the importance of using a quadrant-based analysis in assessing ethical permissibility and necessity of RCTs.</p><p><strong>Conclusion: </strong>The proposed four quadrants framework provides a comprehensive and preise approach to assessing the ethical justification of RCTs. Implementing this framework could improve regulatory evaluations of RCTs and reduce unnecessary harm to trial participants while balancing the objectives of scientific advancement.</p>","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":" ","pages":"111831"},"PeriodicalIF":7.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"There is no upper limit on the maximum effect that can be detected in randomized trials","authors":"Benjamin Djulbegovic ,&nbsp;Iztok Hozo ,&nbsp;Renata Iskander ,&nbsp;Austin J. Parish ,&nbsp;Jonathan Kimmelman ,&nbsp;John P.A. Ioannidis","doi":"10.1016/j.jclinepi.2025.111828","DOIUrl":"10.1016/j.jclinepi.2025.111828","url":null,"abstract":"<div><h3>Background and Objectives</h3><div>Randomized controlled trials (RCTs) are commonly viewed as essential for detecting small treatment benefits, yet they also identify large (“dramatic”) effects. Forecasting the likelihood of future large effects helps guide resource allocation for conducting clinical trials.</div></div><div><h3>Methods</h3><div>We included consecutive cancer RCTs from 5 cohorts identified by funders or trial registries, minimizing publication bias. Between 1955 and 2018 (and published by 2022), 716 RCTs compared 984 experimental vs standard treatments in approximately 350,000 patients. We applied a generalized Pareto distribution (GPD) under Extreme Value Theory to predict future maximum treatment effects using data spanning 65 years.</div></div><div><h3>Results</h3><div>The GPD's positive shape parameter implies no upper limit on maximum treatment effects. Historically, the largest observed effect had an odds ratio (OR) of 45 (95% CI: 2–1008). If current patterns hold, the largest effect over the next 50 years is projected at OR = 23 (95% CI: 13–106). We estimated 20% probability of detecting new treatments with OR &gt;50 within the same time frame. Increasing the number of RCTs from about 20 to 40 or 60 per year would double or triple the likelihood of detecting breakthrough treatments with dramatic effects.</div></div><div><h3>Conclusion</h3><div>Our findings suggest there may be no absolute upper bound on discoverable treatment effects in cancer RCTs, although estimates will likely remain in the range observed between 1955 and 2022. Conducting more RCTs would boost the probability of identifying treatments with large effects, underscoring the importance of sustained or expanded trial activity to accelerate breakthrough discoveries.</div></div><div><h3>Plain Language Summary</h3><div>New treatments cannot be discovered without individuals volunteering to participate in clinical studies. Among all types of human clinical studies, RCTs are considered the most reliable method for evaluating new medical treatments and are especially effective at detecting small beneficial effects. This study also demonstrates that conducting more RCTs would accelerate the discovery of treatments with both small and large effects. By increasing public participation in RCTs, we can drive faster advances in therapeutics and influence policy decisions to allocate more resources toward the conduct of these trials.</div></div>","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":"184 ","pages":"Article 111828"},"PeriodicalIF":7.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAPTING WHO COVID-19 LIVING GUIDELINES BALANCING METHODOLOGICAL RIGOUR WITH EFFICIENCY AND FLEXIBILITY: A CASE STUDY FROM ARGENTINA.","authors":"Carlos Zaror, Maura Klenner, Yang Song, Thomas Agoritsas, Giselle Balaciano, Verónica Sanguine, Débora Lev, Fernando Tortosa, Agustín Bengolea, Ariel Izcovich, Stijn van de Velde, Ludovic Reveiz, Per Vandvik, Romina Brignardello-Petersen","doi":"10.1016/j.jclinepi.2025.111823","DOIUrl":"https://doi.org/10.1016/j.jclinepi.2025.111823","url":null,"abstract":"<p><strong>Objective: </strong>We assessed the perceptions about a new methodological process to translate and adapt World Health Organization living guidelines for COVID-19 (WLGC-19) recommendations for therapeutics in Argentina from the guideline development group's (GDG) perspective.</p><p><strong>Methods: </strong>A tailored adaptation process, linked to a prototype tool and created as part of the GATEWAY project by the MAGIC Evidence Ecosystem Foundation, starts by assessing the recommendation and justification and then examining evidence to decision factors. We focused our evaluation on the adaptation process steps carried out from December 2022 to June 2023. We collected information through 1) observations of the panel meeting, 2) focus group with methods team, 3) semi-structured interviews with panel members, 4) post-panel meeting survey, and 5) a satisfaction survey. We carried out descriptive analyses of surveys and content analysis of focus groups and interviews.</p><p><strong>Results: </strong>GDG adapted four recommendations, of which two were modified in direction or strength, and elaborated one de novo. The survey showed that most GDG found the training session (89%) and pre-panel meeting survey (100%) facilitated adaptation. Focus groups and interviews showed that GDG agreed that the process considered the relevant local factors to adapt the recommendations and that it was transparent and easy to understand, allowing it to reach a consensus efficiently. GDG valued the process's flexibility and time optimization. They considered the pre-meeting survey analysis crucial in facilitating the consensus.</p><p><strong>Conclusion: </strong>From the GDG perspective, this case study demonstrated that this tailored approach provides a transparent, efficient and rigorous methodology for translating and adapting the WLGC-19.</p>","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":" ","pages":"111823"},"PeriodicalIF":7.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics, design, and statistical methods in platform trials: a systematic review","authors":"Clément R. Massonnaud ,&nbsp;Christof Manuel Schönenberger ,&nbsp;Malena Chiaborelli ,&nbsp;Selina Ehrenzeller ,&nbsp;Alexandra Griessbach ,&nbsp;André Gillibert ,&nbsp;Matthias Briel ,&nbsp;Cédric Laouénan","doi":"10.1016/j.jclinepi.2025.111827","DOIUrl":"10.1016/j.jclinepi.2025.111827","url":null,"abstract":"<div><h3>Background and Objective</h3><div>Platform trials (PTs) are gaining popularity in clinical research due to their innovative and flexible methodologies. The objective was to determine the characteristics, methodological, and statistical practices in PTs.</div></div><div><h3>Methods</h3><div>We identified PTs from trial registries and bibliographic databases up to August 2024. Eligible PTs were randomized controlled trials studying multiple interventions within a single population, with flexibility to add or drop arms. Data were extracted on trial status, design, statistical methods, and reporting practices.</div></div><div><h3>Results</h3><div>We identified 189 PTs. Most focused on infectious diseases (77, including 57 for COVID-19) and oncology (68). PT initiation peaked during the COVID-19 pandemic but has since stabilized at 84 active PTs, with 25 in planning. A complete master protocol was available for 47% (89/189) of PTs. Bayesian designs featured in 58/189 PTs vs. 56/189 frequentist trials, 20/189 trials utilizing both (unclear in 55/189 PTs). Overall, 25/111 trials (23%) were designed without a predetermined target sample size, all of which were Bayesian. Among these, 16 were explicitly reported as “perpetual” trials. The number of interim analyses was predetermined in 18% (10/57) of Bayesian trials vs. 58% (28/48) of frequentist trials. Simulations to evaluate operating characteristics were used in 93% (39/42) of Bayesian trials. Simulation reports were available in 67% (26/39) of cases, and the procedures were detailed for 62% (24/39) of trials. Only two trials shared the simulation code.</div></div><div><h3>Conclusion</h3><div>PTs remain popular and increasingly diverse. Efforts to enhance transparency and reporting, especially in complex Bayesian PTs, are essential to ensure reliability and broader acceptance.</div></div>","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":"184 ","pages":"Article 111827"},"PeriodicalIF":7.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-research on patient-reported outcomes in trial protocols and results publications suggested large outcome reporting bias.","authors":"Ala Taji Heravi, Dmitry Gryaznov, Jason W Busse, Christof Manuel Schönenberger, Belinda von Niederhäusern, Lena Hausheer, Manuela Covino, Johannes M Schwenke, Selina Epp, Alexandra Griessbach, Malena Chiaborelli, Arnav Agarwal, Szimonetta Lohner, Julian Hirt, Stefan Schandelmaier, Simon B Egli, Moshao Amos Makhele, Alain Amstutz, Dominik Mertz, Anette Blümle, Erik von Elm, Ramon Saccilotto, Ayodele Odutayo, Sally Hopewell, Benjamin Speich, Matthias Briel","doi":"10.1016/j.jclinepi.2025.111822","DOIUrl":"https://doi.org/10.1016/j.jclinepi.2025.111822","url":null,"abstract":"<p><strong>Objective: </strong>Patient-reported outcomes (PROs) provide crucial information for evaluating healthcare interventions, but previous research in specific disease areas suggested infrequent use and incomplete reporting of PROs. We examined the prevalence and characteristics of PROs in randomized clinical trial (RCT) protocols across medical fields, their reporting quality, and the consistency between PROs specified in trial protocols and subsequent reporting in trial publications.</p><p><strong>Study design and setting: </strong>We included 237 RCT protocols approved in 2012, and 251 approved in 2016, by ethics committees in Switzerland, Germany, and Canada. We systematically searched for corresponding peer-reviewed results publications and results on trial registries. Pairs of reviewers independently extracted characteristics of RCT protocols, PROs specified in protocols and reported in corresponding results publications, and assessed the reporting quality of RCTs with a PRO as the primary outcome using the Consolidated Standards of Reporting Trials-PRO extension (CONSORT-PRO).</p><p><strong>Results: </strong>Out of 488 included RCT protocols, 147 (30%) did not report use of a PRO; 97 (20%) specified a PRO as the primary outcome and an additional 244 (50%) as a secondary outcome. The prevalence of PROs varied substantially across medical fields, ranging from 100% in rheumatology and psychiatry to about one third in cardiology and anesthesiology. At 8-10 years after RCT approval, 264 of the 341 (77%) trial protocols that pre-specified PROs, had available results. Forty-four percent of the published trials (115/264) reported all PROs as defined in the protocol, 21% (55/264) did not report any pre-specified PROs, and 36% (94/264) reported more, less, or different PROs than pre-specified in the protocol. These findings were consistent between trial protocols approved in 2012 and 2016. Among 63 peer-reviewed RCT publications that reported a PRO as their primary outcome, reporting quality was often inadequate with 7 of 13 CONSORT-PRO items met by less than half of trials.</p><p><strong>Conclusion: </strong>Less than half of RCT protocols with planned PROs reported them as specified in corresponding published results, suggesting outcome reporting bias, and PRO reporting quality was often deficient. These limitations complicate informed decision-making between patients and healthcare providers, as well as the development of evidence-based clinical practice guidelines.</p>","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":" ","pages":"111822"},"PeriodicalIF":7.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomization procedures in parallel-arm cluster randomized trials in low- and middle-income countries: a review of 300 trials published between 2017 and 2022","authors":"Julia F. Shaw ,&nbsp;Cory E. Goldstein ,&nbsp;Thais Mazzetti ,&nbsp;Anna Catharina Vieira Armond ,&nbsp;Yacine Marouf ,&nbsp;Kyle Lamprecht ,&nbsp;Eric Tran ,&nbsp;Sami Abdul ,&nbsp;Alex John London ,&nbsp;Charles Weijer ,&nbsp;Karla Hemming ,&nbsp;Lawrence Mbuagbaw ,&nbsp;Mira Johri ,&nbsp;Rashida Ferrand ,&nbsp;Shaun Treweek ,&nbsp;Stuart G. Nicholls ,&nbsp;Monica Taljaard","doi":"10.1016/j.jclinepi.2025.111825","DOIUrl":"10.1016/j.jclinepi.2025.111825","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;Cluster randomized trials (CRTs) are frequently used to evaluate interventions in low- and middle-income countries (LMICs). Robust execution and transparent reporting of randomization procedures are essential for successful implementation and accurate interpretation of CRTs. Our objectives were to review the quality of reporting and implementation of randomization procedures in a sample of parallel-arm CRTs conducted in LMICs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study Design and Setting&lt;/h3&gt;&lt;div&gt;We selected a random sample of 300 primary reports of parallel-arm CRTs from a database of 800 CRTs conducted in LMICs between 2017 and 2022. Data were extracted by two reviewers per trial and summarized using descriptive statistics.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among 300 trials, 192 (64%) reported the method of sequence generation, 213 (71%) reported the type of randomization procedure used, 146 (49%) reported who generated the sequence, 136 (45%) reported whether randomization was implemented by an independent person, and 75 (25%) reported a method of allocation concealment. Among those reporting the methods used, suboptimal randomization procedures were common: 28% did not use a computer, 21% did not use restricted randomization, 58% did not use a statistician to generate the sequence, in 53% the person was not independent from the trial, and 80% did not use central randomization. Public randomization ceremonies were used in 10% of trials as an alternative method of allocation concealment and to reassure participants of fair allocation procedures.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The conduct and reporting of randomization procedures of CRTs in LMICs is suboptimal. Dissemination of guidance to promote robust implementation of randomization in LMICs is required, and future research on the implementation of public randomization ceremonies is warranted.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Plain Language Summary&lt;/h3&gt;&lt;div&gt;Cluster randomized trials (CRTs) are trials where entire groups, rather than individuals, are randomly assigned to different treatments (eg, intervention or usual care). This randomization process can be challenging in CRTs; clear reporting and proper execution are important to ensure fairness and accurate results. In this study, we reviewed how well randomization procedures were reported and carried out in 300 CRTs, selected from a larger database of 800 CRTs, conducted in low- and middle-income countries (LMICs), and published between 2017 and 2022. We found that reporting on key aspects of randomization was often incomplete: 64% reported how they created the random allocation sequence, 71% reported the type of randomization method used, 49% reported who generated the sequence, 45% reported whether a person independent from the trial handled the randomization, and 25% reported how they kept group assignments hidden until the intervention was ready to begin. Even when trials did reported these methods, many did not follow best ","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":"184 ","pages":"Article 111825"},"PeriodicalIF":7.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the feasibility and impact of clinical trial trustworthiness checks via an application to Cochrane Reviews: Stage 2 of the INSPECT-SR project.","authors":"Jack Wilkinson, Calvin Heal, Georgios A Antoniou, Ella Flemyng, Love Ahnström, Alessandra Alteri, Alison Avenell, Timothy Hugh Barker, David N Borg, Nicholas Jl Brown, Rob Buhmann, Jose A Calvache, Rickard Carlsson, Lesley-Anne Carter, Aidan G Cashin, Sarah Cotterill, Kenneth Färnqvist, Michael C Ferraro, Steph Grohmann, Lyle C Gurrin, Jill A Hayden, Kylie E Hunter, Natalie Hyltse, Lukas Jung, Ashma Krishan, Silvy Laporte, Toby J Lasserson, David Rt Laursen, Sarah Lensen, Wentao Li, Tianjing Li, Jianping Liu, Clara Locher, Zewen Lu, Andreas Lundh, Antonia Marsden, Gideon Meyerowitz-Katz, Ben W Mol, Zachary Munn, Florian Naudet, David Nunan, Neil E O'Connell, Natasha Olsson, Lisa Parker, Eleftheria Patetsini, Barbara Redman, Sarah Rhodes, Rachel Richardson, Martin Ringsten, Ewelina Rogozińska, Anna Lene Seidler, Kyle Sheldrick, Katie Stocking, Emma Sydenham, Hugh Thomas, Sofia Tsokani, Constant Vinatier, Colby J Vorland, Rui Wang, Bassel H Al Wattar, Florencia Weber, Stephanie Weibel, Madelon van Wely, Chang Xu, Lisa Bero, Jamie J Kirkham","doi":"10.1016/j.jclinepi.2025.111824","DOIUrl":"https://doi.org/10.1016/j.jclinepi.2025.111824","url":null,"abstract":"<p><strong>Background: </strong>The aim of the INSPECT-SR project is to develop a tool to identify problematic RCTs in systematic reviews. In Stage 1 of the project, a list of potential trustworthiness checks was created. The checks on this list must be evaluated to determine which should be included in the INSPECT-SR tool.</p><p><strong>Methods: </strong>We attempted to apply 72 trustworthiness checks to RCTs in 50 Cochrane Reviews. For each, we recorded whether the check was passed, failed or possibly failed, or whether it was not feasible to complete the check. Following application of the checks, we recorded whether we had concerns about the authenticity of each RCT. We repeated each meta-analysis after removing RCTs flagged by each check, and again after removing RCTs where we had concerns about authenticity, to estimate the impact of trustworthiness assessment. Trustworthiness assessments were compared to Risk of Bias and GRADE assessments in the reviews.</p><p><strong>Results: </strong>95 RCTs were assessed. Following application of the checks, assessors had some or serious concerns about the authenticity of 25% and 6% of the RCTs, respectively. Removing RCTs with either some or serious concerns resulted in 22% of meta-analyses having no remaining RCTs. However, many checks proved difficult to understand or implement, which may have led to unwarranted scepticism in some instances. Furthermore, we restricted assessment to meta-analyses with no more than 5 RCTs (54% contained only 1 RCT), which will distort the impact on results. No relationship was identified between trustworthiness assessment and Risk of Bias or GRADE.</p><p><strong>Conclusions: </strong>This study supports the case for routine trustworthiness assessment in systematic reviews, as problematic studies do not appear to be flagged by Risk of Bias assessment. The study produced evidence on the feasibility and impact of trustworthiness checks. These results will be used, in conjunction with those from a subsequent Delphi process, to determine which checks should be included in the INSPECT-SR tool.</p>","PeriodicalId":51079,"journal":{"name":"Journal of Clinical Epidemiology","volume":" ","pages":"111824"},"PeriodicalIF":7.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}