Clinical Trials最新文献

{"title":"Recommendations for the collection and annotation of biosamples for analysis of biomarkers in neurofibromatosis and schwannomatosis clinical trials.","authors":"R Taylor Sundby, Steven D Rhodes, Edina Komlodi-Pasztor, Herb Sarnoff, Vito Grasso, Meena Upadhyaya, AeRang Kim, D Gareth Evans, Jaishri O Blakeley, C Oliver Hanemann, Chetan Bettegowda","doi":"10.1177/17407745231203330","DOIUrl":"10.1177/17407745231203330","url":null,"abstract":"<p><strong>Introduction: </strong>Neurofibromatosis 1 and schwannomatosis are characterized by potential lifelong morbidity and life-threatening complications. To date, however, diagnostic and predictive biomarkers are an unmet need in this patient population. The inclusion of biomarker discovery correlatives in neurofibromatosis 1/schwannomatosis clinical trials enables study of low-incidence disease. The implementation of a common data model would further enhance biomarker discovery by enabling effective concatenation of data from multiple studies.</p><p><strong>Methods: </strong>The Response Evaluation in Neurofibromatosis and Schwannomatosis biomarker working group reviewed published data on emerging trends in neurofibromatosis 1 and schwannomatosis biomarker research and developed recommendations in a series of consensus meetings.</p><p><strong>Results: </strong>Liquid biopsy has emerged as a promising assay for neurofibromatosis 1/schwannomatosis biomarker discovery and validation. In addition, we review recommendations for a range of biomarkers in clinical trials, neurofibromatosis 1/schwannomatosis-specific data annotations, and common data models for data integration.</p><p><strong>Conclusion: </strong>These Response Evaluation in Neurofibromatosis and Schwannomatosis consensus guidelines are intended to provide best practices for the inclusion of biomarker studies in neurofibromatosis 1/schwannomatosis clinical trials, data, and sample annotation and to lay a framework for data harmonization and concatenation between trials.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10922556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411012","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 comparison of two-stage versus traditional one-stage consent for a low-stakes randomized trial.","authors":"Andrew J Vickers, Emily A Vertosick, Mia Austria, Christopher D Gaffney, Sigrid V Carlsson, Scott Yh Kim, Behfar Ehdaie","doi":"10.1177/17407745231185058","DOIUrl":"10.1177/17407745231185058","url":null,"abstract":"<p><strong>Background/aims: </strong>It has been proposed that informed consent for randomized trials should be split into two stages, with the purported advantage of decreased information overload and patient anxiety. We compared patient understanding, anxiety and decisional quality between two-stage and traditional one-stage consent.</p><p><strong>Methods: </strong>We approached patients at an academic cancer center for a low-stakes trial of a mind-body intervention for procedural distress during prostate biopsy. Patients were randomized to hear about the trial by either one- or two-stage consent (n = 66 vs n = 59). Patient-reported outcomes included Quality of Informed Consent (0-100); general and consent-specific anxiety and decisional conflict, burden, and regret.</p><p><strong>Results: </strong>Quality of Informed Consent scores were non-significantly superior for two-stage consent, by 0.9 points (95% confidence interval = -2.3, 4.2, p = 0.6) for objective and 1.1 points (95% CI = -4.8, 7.0, p = 0.7) for subjective understanding. Differences between groups for anxiety and decisional outcomes were similarly small. In a post hoc analysis, consent-related anxiety was lower among two-stage control patients, likely because scores were measured close to the time of biopsy in the two-stage patients receiving the experimental intervention.</p><p><strong>Conclusion: </strong>Two-stage consent maintains patient understanding of randomized trials, with some evidence of lowered patient anxiety. Further research is warranted on two-stage consent in higher-stakes settings.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10128490","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":"Site staff perspectives on communicating trial results to participants: Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial.","authors":"Annabelle South, Julia Bailey, Barbara E Bierer, Eva Burnett, William J Cragg, Carlos Diaz-Montana, Katie Gillies, Talia Isaacs, Nalinie Joharatnam-Hogan, Claire Snowdon, Matthew R Sydes, Andrew J Copas","doi":"10.1177/17407745231186088","DOIUrl":"10.1177/17407745231186088","url":null,"abstract":"<p><strong>Background/aims: </strong>Sharing trial results with participants is an ethical imperative but often does not happen. Show RESPECT (ISRCTN96189403) tested ways of sharing results with participants in an ovarian cancer trial (ISRCTN10356387). Sharing results via a printed summary improved patient satisfaction. Little is known about staff experience and the costs of communicating results with participants. We report the costs of communication approaches used in Show RESPECT and the views of site staff on these approaches.</p><p><strong>Methods: </strong>We allocated 43 hospitals (sites) to share results with trial participants through one of eight intervention combinations (2 × 2 × 2 factorial; enhanced versus basic webpage, printed summary versus no printed summary, email list invitation versus no invitation). Questionnaires elicited data from staff involved in sharing results. Open- and closed-ended questions covered resources used to share results and site staff perspectives on the approaches used. Semi-structured interviews were conducted. Interview and free-text data were analysed thematically. The mean additional site costs per participant from each intervention were estimated jointly as main effects by linear regression.</p><p><strong>Results: </strong>We received questionnaires from 68 staff from 41 sites and interviewed 11 site staff. Sites allocated to the printed summary had mean total site costs of sharing results £13.71/patient higher (95% confidence interval (CI): -3.19, 30.60; p = 0.108) than sites allocated no printed summary. Sites allocated to the enhanced webpage had mean total site costs £1.91/patient higher (95% CI: -14, 18.74; p = 0.819) than sites allocated to the basic webpage. Sites allocated to the email list had costs £2.87/patient lower (95% CI: -19.70, 13.95; p = 0.731) than sites allocated to no email list. Most of these costs were staff time for mailing information and handling patients' queries. Most site staff reported no concerns about how they had shared results (88%) and no challenges (76%). Most (83%) found it easy to answer queries from patients about the results and thought the way they were allocated to share results with participants would be an acceptable standard approach (76%), with 79% saying they would follow the same approach for future trials. There were no significant effects of the randomised interventions on these outcomes. Site staff emphasised the importance of preparing patients to receive the results, including giving opt-in/opt-out options, and the need to offer further support, particularly if the results could confuse or distress some patients.</p><p><strong>Conclusions: </strong>Adding a printed summary to a webpage (which significantly improved participant satisfaction) may increase costs to sites by ~£14/patient, which is modest in relation to the cost of trials. The Show RESPECT communication interventions were feasible to implement. This information could help future trials e","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9916090","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":"The Targeted Agent and Profiling Utilization Registry Study: A pragmatic clinical trial.","authors":"Pam K Mangat, Elizabeth Garrett-Mayer, Jacqueline K Perez, Richard L Schilsky","doi":"10.1177/17407745231182013","DOIUrl":"10.1177/17407745231182013","url":null,"abstract":"<p><p>The conceptual framework of pragmatism in clinical trials is explored using the American Society of Clinical Oncology's pragmatic, non-randomized, phase II, multi-center basket clinical trial, the Targeted Agent and Profiling Utilization Registry Study (NCT02693535) as a model. The Targeted Agent and Profiling Utilization Registry Study aims to identify signals of drug activity when Food and Drug Administration approved drugs are matched to pre-specified genomic targets in patients with advanced cancer outside of their approved indication(s). The objectives of the study are to generate evidence of potential signals of activity in targeted therapies prescribed in an off-label setting as well as to expose and educate community cancer centers to genomic testing and precision medicine through the study protocol. The principles of pragmatic trial design can be applied across a broad spectrum of evidence-generation strategies, from explanatory trials to real-world evidence studies, and are briefly discussed. American Society of Clinical Oncology's Targeted Agent and Profiling Utilization Registry Study falls closer to the pragmatic end of this spectrum as it seeks to assess the efficacy of Food and Drug Administration approved drugs used outside their approved indications under usual care conditions, yielding results generalizable to the population that would likely receive the intervention in practice, while still adhering to rigorous data quality standards. The Targeted Agent and Profiling Utilization Registry Study's pragmatic objectives, characteristics, strengths, and limitations in its implementation are discussed and demonstrate that a large, multi-center, precision medicine basket trial can be mounted in the context of community practice and can generate clinically useful information with minimal burden to patients and clinical trial sites.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9863100","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":"Assessing the use of observational methods and real-world data to emulate ongoing randomized controlled trials.","authors":"Joshua D Wallach, Yihong Deng, Eric C Polley, Sanket S Dhruva, Jeph Herrin, Kenneth Quinto, Charu Gandotra, William Crown, Peter Noseworthy, Xiaoxi Yao, Molly Moore Jeffery, Timothy D Lyon, Joseph S Ross, Rozalina G McCoy","doi":"10.1177/17407745231193137","DOIUrl":"10.1177/17407745231193137","url":null,"abstract":"<p><strong>Background/aims: </strong>There has been growing interest in better understanding the potential of observational research methods in medical product evaluation and regulatory decision-making. Previously, we used linked claims and electronic health record data to emulate two ongoing randomized controlled trials, characterizing the populations and results of each randomized controlled trial prior to publication of its results. Here, our objective was to compare the populations and results from the emulated trials with those of the now-published randomized controlled trials.</p><p><strong>Methods: </strong>This study compared participants' demographic and clinical characteristics and study results between the emulated trials, which used structured data from OptumLabs Data Warehouse, and the published PRONOUNCE and GRADE trials. First, we examined the feasibility of implementing the baseline participant characteristics included in the published PRONOUNCE and GRADE trials' using real-world data and classified each variable as ascertainable, partially ascertainable, or not ascertainable. Second, we compared the emulated trials and published randomized controlled trials for baseline patient characteristics (concordance determined using standardized mean differences <0.20) and results of the primary and secondary endpoints (concordance determined by direction of effect estimates and statistical significance).</p><p><strong>Results: </strong>The PRONOUNCE trial enrolled 544 participants, and the emulated trial included 2226 propensity score-matched participants. In the PRONOUNCE trial publication, one of the 32 baseline participant characteristics was listed as an exclusion criterion on ClinicalTrials.gov but was ultimately not used. Among the remaining 31 characteristics, 9 (29.0%) were ascertainable, 11 (35.5%) were partially ascertainable, and 10 (32.2%) were not ascertainable using structured data from OptumLabs. For one additional variable, the PRONOUNCE trial did not provide sufficient detail to allow its ascertainment. Of the nine variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 6 (66.7%). The primary endpoint of time from randomization to the first major adverse cardiovascular event and secondary endpoints of nonfatal myocardial infarction and stroke were concordant between the emulated trial and published randomized controlled trial. The GRADE trial enrolled 5047 participants, and the emulated trial included 7540 participants. In the GRADE trial publication, 8 of 34 (23.5%) baseline participant characteristics were ascertainable, 14 (41.2%) were partially ascertainable, and 11 (32.4%) were not ascertainable using structured data from OptumLabs. For one variable, the GRADE trial did not provide sufficient detail to allow for ascertainment. Of the eight variables that were ascertainable, values in the emulated trial and published randomized controlled trial were","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10014630","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":"Data-driven strategies for increasing patient diversity in Bristol Myers Squibb-sponsored US oncology clinical trials.","authors":"Lorena Kuri, Sagar Setru, Gengyuan Liu, Diane Moniz Reed, David Weigand, Aparna Surampudi, Susan Berger, David Paulucci, Angshu Rai, Venkat Sethuraman, Blythe Vito, Helen Kellar-Wood, Mariann Micsinai Balan","doi":"10.1177/17407745231180506","DOIUrl":"10.1177/17407745231180506","url":null,"abstract":"<p><strong>Background/aims: </strong>Determining whether clinical trial findings are applicable to diverse, real-world patient populations can be challenging when the full demographic characteristics of enrolled patients are not consistently reported. Here, we present the results of a descriptive analysis of racial and ethnic demographic information for patients in Bristol Myers Squibb (BMS)-sponsored oncology trials in the United States (US) and describe factors associated with increased patient diversity.</p><p><strong>Methods: </strong>BMS-sponsored oncology trials conducted at US sites with study enrollment dates between 1 January 2013 and 31 May 2021 were analyzed. Patient race/ethnicity information was self-reported in case report forms. As principal investigators (PIs) did not report their own race/ethnicity, a deep-learning algorithm (ethnicolr) was used to predict PI race/ethnicity. Trial sites were linked to counties to understand the role of county-level demographics. The impact of working with patient advocacy and community-based organizations to increase diversity in prostate cancer trials was analyzed. The magnitude of associations between patient diversity and PI diversity, US county demographics, and recruitment interventions in prostate cancer trials were assessed by bootstrapping.</p><p><strong>Results: </strong>A total of 108 trials for solid tumors were analyzed, including 15,763 patients with race/ethnicity information and 834 unique PIs. Of the 15,763 patients, 13,968 (89%) self-reported as White, 956 (6%) Black, 466 (3%) Asian, and 373 (2%) Hispanic. Among 834 PIs, 607 (73%) were predicted to be White, 17 (2%) Black, 161 (19%) Asian, and 49 (6%) Hispanic. A positive concordance was observed between Hispanic patients and PIs (mean = 5.9%; 95% confidence interval (CI) = 2.4, 8.9), a less positive concordance between Black patients and PIs (mean = 1.0%; 95% CI = -2.7, 5.5), and no concordance between Asian patients and PIs. Geographic analyses showed that more non-White patients enrolled in study sites in counties with higher proportions of non-White residents (e.g. a county population that was 5%-30% Black had 7%-14% more Black patients enrolled in study sites). Following purposeful recruitment efforts in prostate cancer trials, 11% (95% CI = 7.7, 15.3) more Black men enrolled in prostate cancer trials.</p><p><strong>Conclusion: </strong>Most patients in these clinical trials were White. PI diversity, geographic diversity, and recruitment efforts were related to greater patient diversity. This report constitutes an essential step in benchmarking patient diversity in BMS US oncology trials and enables BMS to understand which initiatives may increase patient diversity. While complete reporting of patient characteristics such as race/ethnicity is critical, identifying diversity improvement tactics with the highest impact is essential. Strategies with the greatest concordance to clinical trial patient diversity should be implemen","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10425799","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":"Data monitoring committees in pediatric randomized controlled trials registered in ClinicalTrials.gov.","authors":"Tiago Machado, Beatrice Mainoli, Daniel Caldeira, Joaquim J Ferreira, Ricardo M Fernandes","doi":"10.1177/17407745231182417","DOIUrl":"10.1177/17407745231182417","url":null,"abstract":"<p><strong>Background: </strong>Data monitoring committees advise on clinical trial conduct through appraisal of emerging data to ensure participant safety and scientific integrity. While consideration of their use is recommended for trials performed with vulnerable populations, previous research has shown that data monitoring committees are reported infrequently in publications of pediatric randomized controlled trials. We aimed to assess the frequency of reported data monitoring committee adoption in ClinicalTrials.gov registry records and to examine the influence of key trial characteristics.</p><p><strong>Methods: </strong>We conducted a cross-sectional data analysis of all randomized controlled trials performed exclusively in a pediatric population and registered in ClinicalTrials.gov between 2008 and 2021. We used the Access to Aggregate Content of ClinicalTrials.gov database to retrieve publicly available information on trial characteristics and data on safety results. Abstracted data included reported trial design and conduct parameters, population and intervention characteristics, reasons for prematurely halting, serious adverse events, and mortality outcomes. We performed descriptive analyses on the collected data and explored the influence of clinical, methodological, and operational trial characteristics on the reported adoption of data monitoring committees.</p><p><strong>Results: </strong>We identified 13,928 pediatric randomized controlled trial records, of which 39.7% reported adopting a data monitoring committee, 49.0% reported not adopting a data monitoring committee, and 11.3% did not answer on this item. While the number of registered pediatric trials has been increasing since 2008, we found no clear time trend in the reported adoption of data monitoring committees. Data monitoring committees were more common in multicenter trials (50.6% vs 36.9% for single-center), multinational trials (60.2% vs 38.7% for single-country), National Institutes of Health-funded (60.3% vs 40.1% for industry-funded or 37.5% for other funders), and placebo-controlled (47.6% vs 37.5% for other types of control groups). Data monitoring committees were also more common among trials enrolling younger participants, trials employing blinding techniques, and larger trials. Data monitoring committees were more common in trials with at least one serious adverse event (52.6% vs 38.4% for those without) as well as for trials with reported deaths (70.3% vs 38.9% for trials without reported deaths). In all, 4.9% were listed as halted prematurely, most often due to low accrual rates. Trials with a data monitoring committee were more often halted for reasons related to scientific data than trials without a data monitoring committee (15.7% vs 7.3%).</p><p><strong>Conclusion: </strong>According to registry records, the use of data monitoring committees in pediatric randomized controlled trials was more frequent than previously reported in reviews of published trial","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743105","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":"Futility monitoring for randomized clinical trials with non-proportional hazards: An optimal conditional power approach.","authors":"Xiaofei Wang, Stephen L George","doi":"10.1177/17407745231181908","DOIUrl":"10.1177/17407745231181908","url":null,"abstract":"<p><strong>Background: </strong>Standard futility analyses designed for a proportional hazards setting may have serious drawbacks when non-proportional hazards are present. One important type of non-proportional hazards occurs when the treatment effect is delayed. That is, there is little or no early treatment effect but a substantial later effect.</p><p><strong>Methods: </strong>We define optimality criteria for futility analyses in this setting and propose simple search procedures for deriving such rules in practice.</p><p><strong>Results: </strong>We demonstrate the advantages of the optimal rules over commonly used rules in reducing the average number of events, the average sample size, or the average study duration under the null hypothesis with minimal power loss under the alternative hypothesis.</p><p><strong>Conclusion: </strong>Optimal futility rules can be derived for a non-proportional hazards setting that control the loss of power under the alternative hypothesis while maximizing the gain in early stopping under the null hypothesis.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10412008","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":"Poor effort on cognitive testing in voluntary research predicts failure in US Army Ranger School: Implications for clinical trial design.","authors":"Travis H Turner, Jill C Newman, Bernadette P Marriott","doi":"10.1177/17407745231178847","DOIUrl":"10.1177/17407745231178847","url":null,"abstract":"<p><strong>Introduction: </strong>Failure to provide effortful performance on cognitive testing is not uncommon for participants in clinical trials and can significantly impact sensitivity to treatment effect. Whether poor effort on cognitive testing might relate to other behaviors of interest is unknown. In the current investigation, we examined whether effort on baseline cognitive testing in a randomized controlled trial to enhance resiliency in US Army Officers predicted subsequent success in Ranger school.</p><p><strong>Methods: </strong>Baseline data on six cognitive tests were obtained from 237 US Army Officers entering a military training program prior to attempting Ranger School. Participation was voluntary and the Army was not informed of test scores. \"Poor effort\" was defined by chance-level accuracy or extreme outlier scores. Logistic regression examined likelihood of Ranger success according to the number of tests with poor effort.</p><p><strong>Results: </strong>Overall, 170 (72%) participants provided good effort on all tests. For these participants, 47% were successful in Ranger, versus 32% with poor effort on one test and 14% with poor effort on two tests. Logistic regression analysis found poor effort on baseline testing predicted reduced likelihood of Ranger success, β =-.486, p = .005.</p><p><strong>Discussion: </strong>A substantial number of participants exhibited poor effort on testing, and poor effort was predictive of failure in Ranger school. Findings highlight the importance of assessing effort in clinical trials involving cognitive outcomes and suggest application of cognitive effort testing in trials where other motivated behavior is targeted.</p><p><strong>Registration: </strong>Clinical Trials.gov NCT02908932.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9618782","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":"Randomized controlled dose-escalation design to evaluate the safety of a novel pharmacological cardiopulmonary resuscitation strategy.","authors":"Sydney Benson, Demetri Yannopoulos, Tom P Aufderheide, Thomas A Murray","doi":"10.1177/17407745231188443","DOIUrl":"10.1177/17407745231188443","url":null,"abstract":"<p><strong>Background/aims: </strong>The motivating randomized controlled phase I trial evaluates three sodium nitroprusside doses in a novel sodium nitroprusside-enhanced cardiopulmonary resuscitation strategy for improved end-organ perfusion relative to local standard of care. Sodium nitroprusside is a vasodilator with an established safety profile in other indications, whereas the local standard of care uses vasoconstrictors, typically epinephrine. The purpose of the proposed trial is to identify the highest safe dose of sodium nitroprusside in this new context as excessive doses may cause severe hypotension with compromised end-organ perfusion.</p><p><strong>Methods: </strong>The proposed phase I trial design expands upon traditional dose-finding designs to include a randomized control arm, which is needed to assess safety through the relative increase in serum lactate on hospital admission. For guiding dose escalation, we propose and compare six Bayesian models which characterize expected serum lactate as a function of sodium nitroprusside dose and randomization group. Each model makes a different assumption about the expected change in serum lactate across control cohorts concurrently randomized with each dose. Model selection aims to minimize the expected number of times that a dose is incorrectly classified as safe or unsafe while sample size selection targets an expected number of incorrectly classified doses. Randomization is 1:1 for the initial cohort, and for subsequent cohorts is chosen to maximize the lower confidence bound.</p><p><strong>Results: </strong>The spike-and-slab model minimizes the expected number of times that a dose is incorrectly classified as safe or unsafe under the most scenarios in the motivating three-dose trial, but all six models exhibit relatively similar performance. A 2:1 randomization ratio for the second and third cohorts maximizes the lower confidence bound when using the spike-and-slab model. With the optimal design, on average, 70 individuals will ensure 1 incorrectly classified dose in 6 opportunities.</p><p><strong>Conclusion: </strong>We recommend that the motivating trial use the spike-and-slab model with a 1:1 randomization ratio for the initial cohort and 2:1 randomization ratio for subsequent cohorts; however, the simpler fixed effects approaches performed similarly well.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9912710","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}