Clinical Trials最新文献

{"title":"Adjudication of cause of death in older adults: Learnings for death certification from the ASPirin in Reducing Events in the Elderly study.","authors":"Mark R Nelson, John J McNeil, Nigel Stocks, Sameer Panjwani, Raj C Shah","doi":"10.1177/17407745251368001","DOIUrl":"10.1177/17407745251368001","url":null,"abstract":"<p><strong>Background: </strong>Death certificates are a legal requirement for a body to be buried or cremated. Many randomised clinical trials utilise disease-specific causes of death as key outcomes informed by these documents. Determination of cause of death is commonly assigned to an adjudication committee, a time- and resource-intensive process which becomes more difficult in trials of older individuals. We sought to assess whether a simple transcription from a death certificate would be adequate to meet trial requirements and whether the certification process itself can be improved to meet public health and research requirements.</p><p><strong>Methods: </strong>Random audit of 100 death certificates from ASpirin in Reducing Endpoints in the Elderly, a randomised controlled trial conducted in Australian general practice and US community research centres. Participants were Australians (aged 70+ years) and Americans (65+) living in the community and without life-limiting medical conditions at baseline, recruited between 1 March 2010 and 31 December 2014 for the ASpirin in Reducing Endpoints in the Elderly trial. Outcome of interest was misclassification of death rate.</p><p><strong>Results: </strong>There were 2757 deaths in the 19,114 study population. In a random sample of 100 of these deaths, misclassification of cause of death was identified through the trial adjudication process in 9% of death certificates.</p><p><strong>Conclusion: </strong>In trials without the resources of ASpirin in Reducing Endpoints in the Elderly, a coding method can be accepted. Based on our experience, we recommend changes to the structure and process of death certification to better serve both clinical research and public health needs, particularly in older, multimorbid populations.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"695-700"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12614313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224993","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":"Estimating treatment effects in trials with outcome data truncated by death: A case study on aligning estimators with estimands.","authors":"Tra My Pham, Brennan C Kahan, Andre Lopes, Memuna Rashid, Peter J Hoskin, Ian R White","doi":"10.1177/17407745251360645","DOIUrl":"10.1177/17407745251360645","url":null,"abstract":"<p><strong>Background/aims: </strong>Randomised clinical trials assessing treatment effects on health outcomes (e.g. quality of life) can be affected by data truncation by death, where some patients die before their outcome measure is assessed and their data become undefined after death. The ICH E9(R1) addendum on estimands discusses four strategies for handling such terminal intercurrent events: hypothetical, composite, while-alive, and principal stratum. While the addendum emphasises the importance of aligning statistical methods of analysis (i.e. estimators) with estimands, it does not provide specific guidance and consideration on the choice of estimators in practice. We aim to (1) demonstrate how some statistical methods commonly used in trials can be used to estimate different intercurrent event strategies for handling data truncation by death; and (2) describe how missing outcome data (e.g. due to missed assessments or loss to follow-up) can be handled for each estimator.</p><p><strong>Method: </strong>We use data from SCORAD, a non-inferiority randomised trial comparing single-fraction versus multifraction radiotherapy on ambulatory status at 8 weeks (primary outcome) among patients with spinal canal compression from metastatic cancer. Here, we estimate the effect of radiotherapy on quality of life (secondary outcome), quantified by the difference in mean global health status between the two groups at 8 weeks. We outline the strategies for handling death and describe a selection of commonly used estimators corresponding to each strategy. The handling of missing data is considered and demonstrated as part of the estimation process.</p><p><strong>Results: </strong>The hypothetical strategy, targeting a treatment effect assuming patients had not died, can be estimated using linear mixed models (a likelihood approach) or multiple imputation (a method commonly used for handling missing data). The composite and while-alive strategies relate to the 'outcome' attribute of the estimand; the former incorporates death into the definition of the primary outcome, the latter only uses outcome data before death. These can be estimated by re-defining the outcome, for example, assigning a value reflecting poor global health status post-death, or using the last global health status observed before death. The principal stratum strategy, targeting a treatment effect among patients who would not die under either treatment, can be estimated by an analysis of survivors under specific assumptions. Missing data can be handled with linear mixed models or multiple imputation.</p><p><strong>Conclusions: </strong>Regarding death as an intercurrent event in the process of defining the estimand for the trial will help clarify the choice of suitable estimators. When choosing the estimators, it is important to consider the assumptions required by the estimators as well as their plausibility given the setting of the trial.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"676-686"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224979","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":"Scoping review of family caregiver roles in cancer clinical trial decision-making.","authors":"Eric C Blackstone, Barbara J Daly, Mark P Aulisio, Jennifer A Dorth, Sana Loue","doi":"10.1177/17407745251366317","DOIUrl":"10.1177/17407745251366317","url":null,"abstract":"<p><p>BackgroundCancer clinical trials are vital for improving treatments. Clinical trial decision-making has been examined from the perspectives of patients and oncologists, but caregiver perspectives on clinical trials and roles in patient enrollment decisions remain understudied.MethodsThis scoping review assessed the state of current research on caregiver roles in cancer trial enrollment decision-making. A review of empirical literature was conducted in January 2024 using PubMed and Embase. Articles were evaluated using a review instrument to determine the aspect of decision-making evaluated, the roles of caregivers in clinical trial enrollment decision-making, and recommendations based on study results.ResultsA total of 23 articles were included in the review. Studies focused on awareness and attitudes about clinical trials (7 articles), hypothetical willingness to participate in a trial (6 articles), and experiences with decision-making (10 articles). Caregiver roles included supporting and deferring to patient autonomy, communicating with clinicians, and taking on burden to facilitate participation in the trial. Researchers recommended including caregivers in clinical trial enrollment discussions and educational outreach, developing interventions to reduce caregiver burden, and future research on caregiver clinical trial decision-making using the framework of relational autonomy.ConclusionEmpirical research on caregiver roles in clinical trial enrollment decision-making is limited. Findings of this review suggest that caregivers experience tension between their perceived role of supporting the patient's autonomy and their own well-being. More research is needed to understand how caregivers navigate these challenges and identify best practices for their inclusion in clinical trial consent.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"745-756"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991636","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":"Training the next generation of clinical trial biostatisticians.","authors":"Sameer Parpia, Jacquelyn Dobinson, Anna Heath, Hubert Wong, Kevin Thorpe, Tolulope Sajobi, Shirin Golchi, Lawrence Mbuagbaw, Shun Fu Lee, Thi Ho, Valerie Bishop","doi":"10.1177/17407745251361741","DOIUrl":"10.1177/17407745251361741","url":null,"abstract":"<p><p>BackgroundThere is a critical shortage of biostatistics expertise and targeted training programs in clinical trials across Canada.MethodsThe Canadian Network for Statistical Training in Trials (CANSTAT), a pan-Canadian, multi-institutional training platform for biostatisticians in clinical trials, was developed to increase clinical trial biostatistics capacity in Canada.ResultsCANSTAT's training program integrates experiential learning through mentorship and placements at clinical trial sites, online workshops, and capacity-building meetings. The curriculum is designed to equip fellows with essential knowledge of clinical trials, technical skills, and practical experience necessary for their growth into professional trial biostatisticians, with several specific and measurable objectives set to achieve this goal. Educational materials, including CANSTAT competencies, reflective exercises, and individual development plans, are provided to monitor progress and ensure that fellows are meeting their academic and professional goals. Currently, CANSTAT has enrolled 19 fellows.ConclusionCANSTAT has developed a training program that equips fellows with essential skills in clinical trial design, conduct and analysis, and interprofessional communication, preparing them to effectively lead biostatistical efforts in clinical trials. By training a new generation of clinical trial biostatisticians, CANSTAT is strengthening Canada's clinical trial enterprise and improving health outcomes.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"687-694"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798429","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":"Approaches to ensure quality of information provision and consent processes for vaccine clinical trial participation in Sub-Saharan Africa: A scoping review.","authors":"Aitana Juan-Giner, Elena Carrillo-Alvarez, Cristina Enguita-Fernàndez","doi":"10.1177/17407745251346134","DOIUrl":"10.1177/17407745251346134","url":null,"abstract":"<p><p>Background/AimsTo respect the rights and wellbeing of research participants, these should receive information at all stages of the trial, and procedures should be put in place to ensure a valid consent that promotes an informed, autonomous and voluntary decision-making. This review focuses on the extent and type of evidence available in relation to best practices in the information provision and consent processes for vaccine trials conducted in Sub-Saharan Africa.MethodsAncillary studies or evaluations assessing the information and/or consent processes used in vaccine trials implemented in Sub-Saharan Africa were eligible. The databases PubMed, CINAHL, Scopus, Web of Science, African Index Medicus Google Scholar and ProQuest dissertations and thesis citation index and Open Access Theses and Dissertations were searched, without time limits. Following a deductive approach, relevant data were extracted using an extraction tool and categorised into themes.ResultsThe review included 46 sources reporting results from 37 studies implemented in 13 Sub-Saharan African countries. The studies covered: community engagement (n = 8); informants (n = 7); messages (n = 7); communication tools (n = 3); community groups (n = 4); consent process (n = 11); comprehension (n = 19) and dissemination of results (n = 4). They mostly represented the views of participants or parents of trial participants; researchers and trial site personnel; and community members and representatives, including those with formal informational roles. The studies showed gaps in information and consent processes leading to a lack of understanding and confusion or suspicion. The involvement of community members in information giving was essential. These were able to communicate in culturally-appropriate ways and also increase trust in the trial.ConclusionsThe studies highlight complexities involved in the information and consent processes for vaccine trials implemented in Sub-Saharan Africa. These processes would benefit from a stronger consideration to the context where research takes place, including culture, language, non-biomedical conceptions and power imbalances. The views from ethics review boards were mostly absent.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"701-727"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505001","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":"Evaluating re-identification risks scores in publicly available clinical trial datasets: Insights and implications.","authors":"Aryelly Rodriguez, Linda J Williams, Stephanie C Lewis, Pamela Sinclair, Sandra Eldridge, Tracy Jackson, Christopher J Weir","doi":"10.1177/17407745251356423","DOIUrl":"10.1177/17407745251356423","url":null,"abstract":"<p><p>BackgroundThe motivations to share anonymised datasets from clinical trials within the scientific community are increasing. Many anonymised datasets are now publicly available for secondary research. However, it is uncertain whether they pose a privacy risk to the involved participants.MethodsWe located a broad sample of publicly available, de-identified/anonymised randomised clinical trial datasets from human participants and contacted their owners to request access, following their local procedures. We classified personal data within these datasets, including unique direct identifiers such as date of birth and other personal data that, on their own, does not identify an individual but may do so when combined with each other, such as sex, age and race (indirect identifiers). Combining indirect identifiers forms strata, and adding more identifiers increases granularity by dividing the data into a larger number of smaller strata. The re-identification risk score equations evaluate membership in these strata in three ways: first, by measuring the proportions of participants in strata above predetermined risk threshold levels (Ra); second, by locating the smallest stratum (Rb); third, by estimating the average membership across all strata in a dataset (Rc). The risk scores range from 0 (lowest risk) to 1 (highest risk); they do not aim to re-identify individuals in the datasets and are used for routinely collected health records. If a dataset contained a direct identifier, it automatically scored 1 in all metrics. Conversely, if a dataset contained no direct or up to one indirect identifier, it automatically scored 0 in all metrics. Finally, we explored which characteristics of the datasets were associated with the risk scores and compared the risk scores and their usability.ResultsSeventy datasets from 14 data sources were analysed. Thirty-one datasets were shared with minimal restrictions (open access), while 39 were shared with varying levels of restrictions before access was granted (controlled access). Datasets had, on average, four identifiers and mean risk scores ranging from 0.47 to 0.91. The most common pieces of information present in the datasets that, when combined, may indirectly identify a participant were sex (80%) and age (72.9%).ConclusionsThis study confirms that clinical trial datasets are rich in personal details and that using re-identification risk scores as a measure of this richness is feasible. These scores could inform the anonymisation process of clinical trials datasets regarding their level of granularity prior to releasing them for secondary research. We propose a strategy for employing these scores in the decision-making process for releasing clinical trials datasets.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"649-666"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945762","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":"Policy recommendations for implementing registries to minimize over-volunteering in Phase I clinical trials.","authors":"Roberto Abadie, Jill A Fisher, Shadreck Mwale, François Bompart, François Hirsch","doi":"10.1177/17407745251360649","DOIUrl":"10.1177/17407745251360649","url":null,"abstract":"<p><p>Thousands of healthy volunteers enroll in Phase I clinical trials annually, often motivated by financial gain. Some engage in \"over-volunteering\"-participating in multiple studies simultaneously or ignoring washout periods. While serious adverse effects are rare, the experimental nature of Phase I trials, which for \"first-in-human\" studies are designed to trigger adverse events under controlled conditions, makes risks uncertain and unpredictable-a concern that might be compounded by concealed trial participation, which may further increase the likelihood of adverse events. Over-volunteering may also distort trial results through undetected drug interactions. To address this, France, Malaysia, and the UK have implemented national registries to track enrollments and enforce washout periods. Private, for-profit registries, like India's biometric-based system and the US-based Verified Clinical Trials, are used by some clinical research units, mostly private contract research organizations, but their use is not universal and mandatory within countries. Overall, most countries still lack mandatory systems, highlighting the need for broader oversight to protect volunteers and ensure reliable research outcomes. This article discusses the need for and barriers to implementing effective registries and argues that widespread adoption of such registries is critical to protect healthy volunteers from risk of harm while also enhancing trial results' transparency, reliability, and integrity, thereby contributing to developing safer and more effective drugs.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"757-760"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728482","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":"Characterization of studies considered and required under Medicare's coverage with evidence development program.","authors":"Maryam Mooghali, Osman Moneer, Guneet Janda, Joseph S Ross, Sanket S Dhruva, Reshma Ramachandran","doi":"10.1177/17407745251313979","DOIUrl":"10.1177/17407745251313979","url":null,"abstract":"&lt;p&gt;&lt;p&gt;IntroductionIn 2005, the Centers for Medicare and Medicaid Services introduced the Coverage with Evidence Development program for items and services with limited evidence of benefit and harm for Medicare beneficiaries, aiming to generate evidence to determine whether they meet the statutory \"reasonable and necessary\" criteria for coverage. Coverage with Evidence Development requires participation in clinical studies approved by the Centers for Medicare and Medicaid Services (i.e. Coverage with Evidence Development-approved studies) as a condition of coverage. We examined the quality of evidence generated by Coverage with Evidence Development-approved studies compared with those that informed Centers for Medicare and Medicaid Services' initial Coverage with Evidence Development decisions (i.e. National Coverage Determination studies).MethodsUsing Centers for Medicare and Medicaid Services' webpage, we identified all items and services covered under Coverage with Evidence Development and their Coverage with Evidence Development-approved studies. Through searching PubMed and Google Scholar, we identified original research articles that reported results for primary endpoints of Coverage with Evidence Development-approved studies. We then reviewed the initial Coverage with Evidence Development decision memos and identified National Coverage Determination studies that were original research.We characterized and compared Coverage with Evidence Development-approved studies and National Coverage Determination studies.ResultsFrom 2005 to 2023, 26 items and services were covered under the Coverage with Evidence Development program, associated with 196 National Coverage Determination studies (170 (86.7%) clinical trials and 26 (13.3%) registries) and 116 unique Coverage with Evidence Development-approved studies (86 (74.1%) clinical trials, 23 (19.8%) registries, 4 (3.4%) claims-based studies, and 3 (2.6%) expanded access studies). Among clinical trial studies, National Coverage Determination studies and Coverage with Evidence Development-approved studies did not differ with respect to multi-arm design (59.4% vs 68.6%; &lt;i&gt;p&lt;/i&gt; = 0.15). However, among multi-arm clinical trial studies, National Coverage Determination studies were less likely than Coverage with Evidence Development-approved studies to be randomized (52.5% vs 93.2%; &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Overall, National Coverage Determination studies less frequently had ≥ 1 primary endpoint focused on a clinical outcome measure (65.8% vs 87.9%; &lt;i&gt;p&lt;/i&gt; = 0.006) and less frequently exclusively enrolled Medicare beneficiaries (3.1% vs 25.9%; &lt;i&gt;p&lt;/i&gt; &lt; 0.001). In addition, National Coverage Determination studies had smaller population sizes than Coverage with Evidence Development-approved studies (median 100 (interquartile range, 45-414) vs 302 (interquartile range, 93-1000) patients; &lt;i&gt;p&lt;/i&gt; = 0.002). Among Coverage with Evidence Development-approved studies, 59 (50.9%) had not yet publicly reported resul","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"619-625"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374119","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":"Precision medicine evaluation of heterogeneity of treatment effect for a time-to-event outcome with application in a trial of Initial treatment for people living with HIV.","authors":"Yu Zheng, Judy S Currier, Michael D Hughes","doi":"10.1177/17407745251338558","DOIUrl":"10.1177/17407745251338558","url":null,"abstract":"<p><p>BackgroundEvaluation of heterogeneity of treatment effect among participants in large randomized clinical trials may provide insights as to the value of individualizing clinical decisions. The effect modeling approach to predictive heterogeneity of treatment effect analysis offers a promising framework for heterogeneity of treatment effect estimation by simultaneously considering multiple patient characteristics and their interactions with treatment to predict differences in outcomes between randomized treatments. However, its implementation in clinical research remains limited and so we provide a detailed example of its application in a randomized trial that compared raltegravir-based vs darunavir/ritonavir-based therapy as initial antiretroviral treatments for people living with HIV.MethodsThe heterogeneity of treatment effect analysis used a two-step procedure, in which a working proportional hazards model was first selected to construct an index score for ranking the treatment difference for individuals, and then a second calibration step used a non-parametric kernel approach to estimate the true treatment difference for participants with similar index scores. Sensitivity and supplemental analyses were conducted to evaluate the robustness of the results. We further explored the impact of covariates on heterogeneity of treatment effect and the choice between treatments.ResultsThe heterogeneity of treatment effect analysis showed that while there is a clear trend favoring raltegravir-based therapy over darunavir/ritonavir-based therapy for the vast majority of the target population, there were a small subset of patients, characterized by more advanced HIV disease status, for whom the choice between the two treatments might be equivocal.ConclusionsThrough this example, we illustrate how an exploratory heterogeneity of treatment effect analysis might provide further insights into the comparative efficacy of treatments evaluated in a randomized trial. We also highlight some of the issues in implementing and interpreting effect modeling analyses in randomized trials.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"559-570"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119117","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":"Standardising management of consent withdrawal and other clinical trial participation changes: The UKCRC Registered Clinical Trials Unit Network's PeRSEVERE project.","authors":"William J Cragg, Laura Clifton-Hadley, Jeremy Dearling, Susan J Dutton, Katie Gillies, Pollyanna Hardy, Daniel Hind, Søren Holm, Kerenza Hood, Anna Kearney, Rebecca Lewis, Sarah Markham, Lauren Moreau, Tra My Pham, Amanda Roberts, Sharon Ruddock, Mirjana Sirovica, Ratna Sohanpal, Puvan Tharmanathan, Rejina Verghis","doi":"10.1177/17407745251344524","DOIUrl":"10.1177/17407745251344524","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background/aims: &lt;/strong&gt;Existing regulatory and ethical guidance does not address real-life complexities in how clinical trial participants' level of participation may change. If these complexities are inappropriately managed, there may be negative consequences for trial participants and the integrity of trials they participate in. These concerns have been highlighted over many years, but there remains no single, comprehensive guidance for managing participation changes in ways that address real-life complexities while maximally promoting participant interests and trial integrity. Motivated by the lack of agreed standards, and observed variability in practice, representatives from academic clinical trials units and linked organisations in the United Kingdom initiated the PeRSEVERE project (PRincipleS for handling end-of-participation EVEnts in clinical trials REsearch) to agree on guiding principles and explore how these principles should be implemented.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We developed the PeRSEVERE principles through discussion and debate within a large, multidisciplinary collaboration, including research professionals and public contributors. We took an inclusive approach to drafting the principles, incorporating new ideas if they were within project scope. Our draft principles were scrutinised through an international consultation survey which focussed on the principles' clarity, feasibility, novelty and acceptability. Survey responses were analysed descriptively (for category questions) and using a combination of deductive and inductive analysis (for open questions). We used predefined rules to guide feedback handling. After finalising the principles, we developed accompanying implementation guidance from several sources.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 280 people from 9 countries took part in the consultation survey. Feedback showed strong support for the principles with 96% of respondents agreeing with the principles' key messages. Based on our predefined rules, it was not necessary to amend our draft principles, but comments were nonetheless used to enhance the final project outputs. Our 17 finalised principles comprise 7 fundamental, 'overarching' principles, 6 about trial design and setup, 2 covering data collection and monitoring, and 2 on trial analysis and reporting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;We devised a comprehensive set of guiding principles, with detailed practical recommendations, to aid the management of clinical trial participation changes, building on existing ethical and regulatory texts. Our outputs reflect the contributions of a substantial number of individuals, including public contributors and research professionals with various specialisms. This lends weight to our recommendations, which have implications for everyone who designs, funds, conducts, oversees or participates in trials. We suggest our principles could lead to improved standards in clinical trials and better exper","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"578-596"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559362","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}