Clinical Trials最新文献

{"title":"Quality management of a multi-center randomized controlled feeding trial: A prospective observational study.","authors":"Xiayan Chen, Huijuan Li, Lin Feng, Xi Lan, Shuyi Li, Yanfang Zhao, Guo Zeng, Huilian Zhu, Jianqin Sun, Yanfang Wang, Yangfeng Wu","doi":"10.1177/17407745251324653","DOIUrl":"10.1177/17407745251324653","url":null,"abstract":"<p><p>BackgroundNutrition and dietary trials are often prone to bias, leading to inaccurate or questionable estimates of intervention efficacy. However, reports on quality management practices of well-controlled dietary trials are scarce. This study aims to introduce the quality management system of the Diet, ExerCIse and CarDiovascular hEalth-Diet Study and report its performance in ensuring study quality.MethodsThe quality management system consisted of a study coordinating center, trial governance, and quality control measures covering study design, conduct, and data analysis and reporting. Metrics for evaluating the performance of the system were collected throughout the whole trial development and conducted from September 2016 to June 2021, covering major activities at the coordinating center, study sites, and central laboratories, with a focus on the protocol amendments, protocol deviations (eligibility, fidelity, confounders management, loss to follow-up and outside-of-window visits, and blindness success), and measurement accuracy.ResultsThree amendments to the study protocol enhanced feasibility. All participants (265) met the eligibility criteria. Among them, only 3% were lost to the primary outcome follow-up measurement. More than 95% of participants completed the study, they consumed more than 96% of the study meals, and more than 94% of participants consumed more than 18 meals per week, with no between-group differences. Online monitoring of nutrient targets for the intervention diet showed that all targets were achieved except for the fiber intake, which was 4.3 g less on average. Only 3% experienced a body weight change greater than 2.0 kg, and 3% had medication changes which were not allowed by the study. James' blinding index at the end of the study was 0.68. The end digits of both systolic and diastolic blood pressure readings were distributed equally. For laboratory measures, 100% of standard samples, 97% of blood-split samples, and 87% of urine-split samples had test results within the acceptable range. Only 1.4% of data items required queries, for which only 30% needed corrections.DiscussionThe Diet, ExerCIse and CarDiovascular hEalth-Diet Study quality management system provides a framework for conducting a high-quality dietary intervention clinical trial.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"527-537"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a research coordinator workforce: A case study of a hospital and university collaboration.","authors":"April M Crawford, Steven L Arxer, James P LePage","doi":"10.1177/17407745251338574","DOIUrl":"10.1177/17407745251338574","url":null,"abstract":"","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"632-634"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the use of text-message reminders and personalised text-message reminders on the return of participant questionnaires in trials, a systematic review and meta-analysis.","authors":"Laura Doherty, Catherine Arundel, Elizabeth Coleman, Ailish Byrne, Katherine Jones","doi":"10.1177/17407745251320888","DOIUrl":"10.1177/17407745251320888","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Randomised controlled trials are widely accepted as the gold standard research methodology for the evaluation of interventions. However, they often display poor participant retention. To prevent this, various participant interventions have been identified and evaluated through the use of studies within a trial. Two such interventions are participant short message service reminders (also known as text-messages) and personalised participant short message service reminders, designed to encourage a participant to return a study questionnaire. While previous studies within a trial have evaluated the effectiveness of these two retention strategies, trialists continue to spend both time and money on these strategies while the evidence remains inconclusive.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This systematic review and meta-analysis compared the use of short message service reminders with no short message service reminder and personalised short message service reminders with non-personalised short message service reminders, on participant retention. Eligible studies were identified through advanced searches of electronic databases (MEDLINE, EMBASE and Cochrane Library) and hand-searching of alternative information sources. The review primary outcome was the proportion of study questionnaires returned for the individual study within a trial primary analysis time points.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Nine eligible studies within a trial were identified, of which four compared short message service versus no short message service and five compared personalised short message service versus non-personalised short message service. For those that compared personalised short message service versus non-personalised short message service, only three were deemed appropriate for meta-analysis. The primary outcome results for short message service versus no short message service concluded that short message service led to a statistically non-significant increase in the odds of study questionnaire return by 9% (odds ratio = 1.09, 95% confidence interval = 0.92 to 1.30). Similarly, comparison of personalised short message service versus non-personalised short message service concluded that personalised short message service caused a statistically non-significant increase in odds by 22% (odds ratio = 1.22, 95% confidence interval = 0.95 to 1.59).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The effectiveness of both short message service and personalised short message service as retention tools remains inconclusive and further study within a trial evaluations are required. However, as short message services are low in cost, easy to use and generally well accepted by participants, it is suggested that trialists adopt a pragmatic approach and utilise these reminders until further research is conducted. Given both the minimal addition in cost for studies already utilising short message service reminders and some evidence of effect, personalisation shoul","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"607-618"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and mitigation of a systematic analysis error in a multicenter dual-energy x-ray absorptiometry study.","authors":"Gayle M Lorenzi, Barbara H Braffett, Ionut Bebu, Victoria R Trapani, Jye-Yu C Backlund, Kaleigh Farrell, Rose A Gubitosi-Klug, Ann V Schwartz","doi":"10.1177/17407745251328257","DOIUrl":"10.1177/17407745251328257","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Background/AimsData integrity in multicenter and longitudinal studies requires implementation of standardized reproducible methods throughout the data collection, analysis, and reporting process. This requirement is heightened when results are shared with participants that may influence health care decisions. A quality assurance plan provides a framework for ongoing monitoring and mitigation strategies when errors occur.MethodsThe Diabetes Control and Complications Trial (1983-1993) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (1994-present), have characterized risk factors and long-term complications in a type 1 diabetes cohort followed for over 40 years. An ancillary study to assess bone mineral density was implemented across 27 sites, using one of two dual x-ray absorptiometry scanner types. Centrally generated reports were distributed to participants by the sites. A query from a site about results that were incongruent with a single participant's clinical history prompted reevaluation of this scan, revealing a systematic error in the reading of hip scans from one of the two scanner types. A mitigation plan was implemented to correct and communicate the errors to ensure participant safety, particularly among those originally identified as having low bone mineral density scores for whom antiresorptive treatment may have been initiated based on these results.ResultsThe error in the analysis of hip scans from the identified scanner type resulted in lower bone mineral density scores in scans requiring manual deletion of the ischium bone. Hip scans with original T-score ≤ -2.5 (n = 84) acquired on either scanner were reviewed, and reanalyzed if the error was detected. Fourteen scans were susceptible to this error and reanalyzed: nine scans were reclassified from osteoporosis to low bone mineral density, one from low to normal bone mineral density, and four were unchanged. All errors occurred on one scanner type. An integrated communication and intervention plan was implemented. The nine participants whose scans were reclassified from osteoporosis to low bone mineral density were contacted; five were using antiresorptive treatment, all of whom had other risk factors for fracture beyond these scan results. Review of all hip scans with a T-score &gt; -2.5 (n = 371) using this scanner type identified 27 additional hip scans that required reanalysis and potential reclassification: 1 scan was reclassified from osteoporosis to low bone mineral density, 11 from low to normal bone mineral density, and 15 were unchanged.ConclusionThe impact of an analysis error on participant safety, specifically when the initiation of unnecessary treatment may result, necessitated implementation of a coordinated communication and mitigation plan across all clinical centers to ensure consistent messaging and accurate results are provided to participants and their local care providers. This framework may serve as a resource for othe","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"538-546"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized study comparing patient portal and email communications for trial recruitment.","authors":"Jeanette Y Ziegenfuss, Elanadora U Sour, Erica J Roelofs, Jennifer M Vesely, Karen L Margolis, Stephanie A Hooker","doi":"10.1177/17407745251358259","DOIUrl":"10.1177/17407745251358259","url":null,"abstract":"&lt;p&gt;&lt;p&gt;BackgroundRecruitment is a necessary, yet challenging component to clinical trial implementation. Using intentional strategies to meet enrollment goals is important to ensure the recruited sample adequately reflects the intended study population. Outreach via electronic health record (EHR) patient portals is a promising strategy. While identifying potentially eligible individuals in the EHR is largely accepted as effective, little is known about the effectiveness of outreach via EHR compared to outreach via traditional electronic mail (email) communication given equivalent population identification strategies.MethodsThis study was conducted using recruitment data from one of four study locations participating in the LEAP study, a multi-site, double-blind, placebo-controlled trial studying the long-term use of phentermine on weight loss and blood pressure. Between May 2023 and February 2024, 17,989 potentially trial-eligible participants identified using EHR data were randomized to either portal or email recruitment communications. Outreach success was measured at six milestones between starting the self-screener and study randomization. Recruitment rates overall and by demographic subpopulation are reported at each milestone as a percent of total invited and as a percent of previous milestone completers. Multivariate analysis considers the moderating effect of demographics on the relative impact of communication type.ResultsOverall, 6.6% (n = 1191) completed the self-screener and 0.5% (n = 85) were randomized into the LEAP trial. Individuals randomized to patient portal communication were more likely to start the self-screener (Odds Ratio [OR]= 2.4 [2.12, 2.73], p &lt; 0.0001) and complete the subsequent four steps, however there was no significant difference in the percent ultimately randomized into the study (OR = 1.43 [0.93, 2.21], p = 0.10). Moreover, when controlling for completion of the previous step, all subsequent milestone differences were no longer significant. Gender was the only significant moderating factor of all available participant characteristics, with women 2.92 ([2.48, 3.43], p &lt; 0.001) and men 1.72 ([1.41, 2.12], p &lt; 0.001) times more likely to respond to portal messages than email communications.ConclusionsInitial activation in study activities was higher in the patient portal group. Although this impact sustained itself across all but the final study milestone and resulted in absolute larger counts among those randomized to portal messages, there is no evidence that this choice will improve representation in biomedical research or the final study randomization rate overall. Therefore, these findings suggest using the portal strategy may lead to more effort without yield on interim steps by both the research team and the potential participants compared to email. Ultimately, the research team's approach may depend on organizational context and study topic, as some topics do not lend themselves to the less secure nature of","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"597-606"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From RAGs to riches: Utilizing large language models to write documents for clinical trials.","authors":"Nigel Markey, Ilyass El-Mansouri, Gaetan Rensonnet, Casper van Langen, Christoph Meier","doi":"10.1177/17407745251320806","DOIUrl":"10.1177/17407745251320806","url":null,"abstract":"<p><p>Background/AimsClinical trials require numerous documents to be written: Protocols, consent forms, clinical study reports, and many others. Large language models offer the potential to rapidly generate first-draft versions of these documents; however, there are concerns about the quality of their output. Here, we report an evaluation of how good large language models are at generating sections of one such document, clinical trial protocols.MethodsUsing an off-the-shelf large language model, we generated protocol sections for a broad range of diseases and clinical trial phases. Each of these document sections we assessed across four dimensions: <i>Clinical thinking and logic; Transparency and references; Medical and clinical terminology</i>; and <i>Content relevance and suitability</i>. To improve performance, we used the retrieval-augmented generation method to enhance the large language model with accurate up-to-date information, including regulatory guidance documents and data from ClinicalTrials.gov. Using this retrieval-augmented generation large language model, we regenerated the same protocol sections and assessed them across the same four dimensions.ResultsWe find that the off-the-shelf large language model delivers reasonable results, especially when assessing <i>content relevance</i> and the <i>correct use of medical and clinical terminology</i>, with scores of over 80%. However, the off-the-shelf large language model shows limited performance in <i>clinical thinking and logic</i> and <i>transparency and references</i>, with assessment scores of ≈40% or less. The use of retrieval-augmented generation substantially improves the writing quality of the large language model, with <i>clinical thinking and logic</i> and <i>transparency and references</i> scores increasing to ≈80%. The retrieval-augmented generation method thus greatly improves the practical usability of large language models for clinical trial-related writing.DiscussionOur results suggest that hybrid large language model architectures, such as the retrieval-augmented generation method we utilized, offer strong potential for clinical trial-related writing, including a wide variety of documents. This is potentially transformative, since it addresses several major bottlenecks of drug development.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"626-631"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building a professionally recognised clinical trial workforce: Is it time for an education and accreditation strategy?","authors":"Simone Spark, Prudence Perry, Thobekile Mthethwa-Pitt, Dragan Ilic, Anne Woollett, Sophia Zoungas, Marina Skiba","doi":"10.1177/17407745251328287","DOIUrl":"10.1177/17407745251328287","url":null,"abstract":"<p><p>Evidence-based medicine relies heavily on well-conducted clinical trials. Australia lacks a discipline-specific education pathway to provide the specialist skills necessary to conduct clinical trials to the highest standards. Unlike allied health professionals, clinical trialists who currently possess the specialist skills to conduct clinical trials do not receive professional recognition. The National Health and Medical Research Council defines 'clinical trialist' to include site staff as well as investigators. In this perspective piece, we explore the importance of discipline-specific education in creating a job-ready workforce of clinical trialists; the need for recognition of clinical trialists as an allied health profession in concert with their existing medical, nursing and other professional qualifications and outline a proposed specialist education and accreditation strategy.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"511-516"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design considerations for randomized comparisons of neoadjuvant-adjuvant versus adjuvant-only cancer immunotherapy when tumor measurement schedules do not align (SWOG S1801).","authors":"Megan Othus, Elad Sharon, Michael C Wu, Vernon K Sondak, Antoni Ribas, Sapna P Patel","doi":"10.1177/17407745251321371","DOIUrl":"10.1177/17407745251321371","url":null,"abstract":"<p><p>BackgroundIn 2022, SWOG S1801 was the first trial to demonstrate that single-agent anti-PD-1 checkpoint inhibition used as neoadjuvant-adjuvant therapy leads to significantly improved outcomes compared to adjuvant-only therapy. Endpoints in trials comparing neoadjuvant-adjuvant to adjuvant strategies need special consideration to ensure that event measurement timing is appropriately accounted for in analyses to avoid biased comparisons artificially favoring one arm over another.MethodsThe S1801 trial is used a case study to evaluate the issues involved in selecting endpoints for trials comparing neoadjuvant-adjuvant versus adjuvant-only strategies.ResultsDefinitions and timing of measurement of events is provided. Trial scenarios when recurrence-free versus event-free survival should be used are provided.ConclusionsIn randomized trials comparing neoadjuvant-adjuvant to adjuvant-only strategies, event-free survival endpoints measured from randomization are required for unbiased comparison of the arms. The time at which events can be measured on each arm needs to be carefully considered. If measurement of events occurs at different times on the randomized arms, modified definitions of event-free survival must be used to avoid bias.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"571-577"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal inference in randomized trials with partial clustering.","authors":"Joshua R Nugent, Elijah Kakande, Gabriel Chamie, Jane Kabami, Asiphas Owaraganise, Diane V Havlir, Moses Kamya, Laura B Balzer","doi":"10.1177/17407745251333779","DOIUrl":"10.1177/17407745251333779","url":null,"abstract":"<p><strong>Background: </strong>Participant dependence, if present, must be accounted for in the analysis of randomized trials. This dependence, also referred to as \"clustering,\" can occur in one or more trial arms. This dependence may predate randomization or arise after randomization. We examine three trial designs: one \"fully clustered\" (where all participants are dependent within clusters or groups) and two \"partially clustered\" (where some participants are dependent within clusters and some participants are completely independent of all others).</p><p><strong>Methods: </strong>For these three designs, we (1) use causal models to non-parametrically describe the data generating process and formalize the dependence in the observed data distribution; (2) develop a novel implementation of targeted minimum loss-based estimation for analysis; (3) evaluate the finite-sample performance of targeted minimum loss-based estimation and common alternatives via a simulation study; and (4) apply the methods to real-data from the SEARCH-IPT trial.</p><p><strong>Results: </strong>We show that the two randomization schemes resulting in partially clustered trials have the same dependence structure, enabling use of the same statistical methods for estimation and inference of causal effects. Our novel targeted minimum loss-based estimation approach leverages covariate adjustment and machine learning to improve precision and facilitates estimation of a large set of causal effects. In simulations, we demonstrate that targeted minimum loss-based estimation achieves comparable or markedly higher statistical power than common alternatives for these partially clustered designs. Finally, application of targeted minimum loss-based estimation to real data from the SEARCH-IPT trial resulted in 20%-57% efficiency gains, demonstrating the real-world consequences of our proposed approach.ConclusionsPartially clustered trial analysis can be made more efficient by implementing targeted minimum loss-based estimation, assuming care is taken to account for the dependent nature of the observed data.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"547-558"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid sample size calculations for cluster randomised trials using assurance.","authors":"S Faye Williamson, Svetlana V Tishkovskaya, Kevin J Wilson","doi":"10.1177/17407745241312635","DOIUrl":"10.1177/17407745241312635","url":null,"abstract":"<p><strong>Background/aims: </strong>Sample size determination for cluster randomised trials is challenging because it requires robust estimation of the intra-cluster correlation coefficient. Typically, the sample size is chosen to provide a certain level of power to reject the null hypothesis in a two-sample hypothesis test. This relies on the minimal clinically important difference and estimates for the overall standard deviation, the intra-cluster correlation coefficient and, if cluster sizes are assumed to be unequal, the coefficient of variation of the cluster size. Varying any of these parameters can have a strong effect on the required sample size. In particular, it is very sensitive to small differences in the intra-cluster correlation coefficient. A relevant intra-cluster correlation coefficient estimate is often not available, or the available estimate is imprecise due to being based on studies with low numbers of clusters. If the intra-cluster correlation coefficient value used in the power calculation is far from the unknown true value, this could lead to trials which are substantially over- or under-powered.</p><p><strong>Methods: </strong>In this article, we propose a hybrid approach using Bayesian assurance to determine the sample size for a cluster randomised trial in combination with a frequentist analysis. Assurance is an alternative to traditional power, which incorporates the uncertainty on key parameters through a prior distribution. We suggest specifying prior distributions for the overall standard deviation, intra-cluster correlation coefficient and coefficient of variation of the cluster size, while still utilising the minimal clinically important difference. We illustrate the approach through the design of a cluster randomised trial in post-stroke incontinence and compare the results to those obtained from a standard power calculation.</p><p><strong>Results: </strong>We show that assurance can be used to calculate a sample size based on an elicited prior distribution for the intra-cluster correlation coefficient, whereas a power calculation discards all of the information in the prior except for a single point estimate. Results show that this approach can avoid misspecifying sample sizes when the prior medians for the intra-cluster correlation coefficient are very similar, but the underlying prior distributions exhibit quite different behaviour. Incorporating uncertainty on all three of the nuisance parameters, rather than only on the intra-cluster correlation coefficient, does not notably increase the required sample size.</p><p><strong>Conclusion: </strong>Assurance provides a better understanding of the probability of success of a trial given a particular minimal clinically important difference and can be used instead of power to produce sample sizes that are more robust to parameter uncertainty. This is especially useful when there is difficulty obtaining reliable parameter estimates.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"517-526"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}