Contemporary clinical trials最新文献

{"title":"The Health, Aging, and Later-Life Outcomes Pilot Study: Design, recruitment, and participants' baseline characteristics","authors":"Cynthia L. Stowe ,&nbsp;Kimberly Kennedy ,&nbsp;Shannon S. Emilson ,&nbsp;Rebecca H. Neiberg ,&nbsp;Stephen B. Kritchevsky ,&nbsp;Michael E. Miller ,&nbsp;Denise K. Houston ,&nbsp;Barbara J. Nicklas ,&nbsp;Jason Fanning ,&nbsp;W. Jack Rejeski ,&nbsp;the HALLO-P Investigators","doi":"10.1016/j.cct.2025.108049","DOIUrl":"10.1016/j.cct.2025.108049","url":null,"abstract":"<div><h3>Background</h3><div>Multi-morbidity increases significantly with age, and obesity is a major risk factor for conditions like cardiovascular disease and diabetes, indicating a critical need for effective interventions.</div></div><div><h3>Objective</h3><div>We discuss the study design of the HALLO-Pilot Study that randomized older adults to in-person caloric restriction (CR), remotely delivered CR (RCR), or a time restricted eating (TRE) intervention. In addition, we emphasize inclusion/exclusion criteria, recruitment, and baseline characteristics of randomized participants.</div></div><div><h3>Methods</h3><div>The study randomized 90 participants aged 60+ to one of three 9-month interventions. Eligibility focused on including adults with an indication for weight loss while excluding for safety concerns or factors potentially affecting adherence. Screening involved telephone interviews and in-person visits. Assessments included measures for eligibility, outcomes, adherence, and safety, with data collected at baseline, 6 months, and 9 months. The intervention involved in-person or online group meetings and individual contacts with participants monthly. Interventions included nutritional and behavioral guidance and a targeted increase in steps per day. Remote monitoring technology was used for monitoring diet and weight for CR participants and logging eating times for TRE participants.</div></div><div><h3>Results</h3><div>There were a total of 1753 pre-screening contacts with 678 (39 %) completing telephone screening. Of 139 (∼21 %) who were eligible after the telephone screening and consented, 135 participants attended in-person screening visits. Of those screened in-person, 90 were eligible and randomized for a yield of 13 %.</div></div><div><h3>Conclusion</h3><div>The HALLO-Pilot Study provided valuable insights into eligibility criteria and the recruitment of older adults for future large-scale trials of CR and TRE.</div><div><strong>Clinical Trials.gov</strong>: NCT05424042.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"157 ","pages":"Article 108049"},"PeriodicalIF":1.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893574","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":"Engage: Protocol of a randomized controlled trial of a telehealth-delivered psychosocial intervention to decrease symptom interference in patients with advanced cancer","authors":"Joseph G. Winger ,&nbsp;Sarah A. Kelleher ,&nbsp;Justin A. Yu ,&nbsp;Jessica E. Ma ,&nbsp;Catherine M. Majestic ,&nbsp;Elizabeth B. Martinson ,&nbsp;Maren K. Olsen ,&nbsp;Reginald Lerebours ,&nbsp;Linda M. Sutton ,&nbsp;Tamara J. Somers","doi":"10.1016/j.cct.2025.108053","DOIUrl":"10.1016/j.cct.2025.108053","url":null,"abstract":"<div><h3>Background</h3><div>Pain, fatigue, and distress are highly prevalent co-occurring symptoms in patients with stage IV cancer. Emerging evidence suggests these patients may benefit from Acceptance and Commitment Therapy (ACT), a Cognitive-Behavioral Therapy (CBT) approach that emphasizes acceptance, mindfulness, and engagement in value-guided activity. Our team developed and successfully pilot tested Engage, a psychosocial intervention integrating CBT skills (e.g., activity pacing) and ACT skills (e.g., mindfulness), with the goal of decreasing symptom interference and improving quality of life (QoL).</div></div><div><h3>Method/design</h3><div>This paper describes the protocol of a randomized controlled trial to evaluate Engage's efficacy for reducing symptom interference in patients receiving cancer care in medically underserved areas. We aim to enroll 190 patients with stage IV breast, prostate, lung, or colorectal cancer. Participants will be randomized 1:1 to Engage or Supportive Care control. Both conditions will be delivered by therapists over four, 45-min telehealth sessions. Aim 1 is to determine Engage's efficacy for reducing symptom interference (primary outcome) at 2 months (primary endpoint). Aim 2 is to determine Engage's efficacy for improving secondary outcomes (i.e., self-efficacy for symptom management, acceptance, mindfulness, valued activity engagement, symptom severity, and QoL) at 2 months. Aim 3 is to test the maintenance of Engage's effects at 4 months. An exploratory aim seeks insights for future implementation efforts.</div></div><div><h3>Conclusion</h3><div>This trial is one of the first to evaluate the efficacy of an ACT-based intervention for patients with stage IV cancers, yielding important information about ways to reduce suffering in this patient population.</div><div>Registered on <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> on August 13, 2024, Identifier: <span><span>NCT06555588</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108053"},"PeriodicalIF":1.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885582","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":"Sex differences in clinical trial enrollment in the United States across psychiatric disorders","authors":"Amanda Koire ,&nbsp;Tamar Jacobsohn ,&nbsp;Hadine Joffe ,&nbsp;Janet Rich-Edwards ,&nbsp;Primavera A. Spagnolo","doi":"10.1016/j.cct.2025.108052","DOIUrl":"10.1016/j.cct.2025.108052","url":null,"abstract":"<div><h3>Background</h3><div>Equality in clinical trial enrollment by sex is optimal for detecting sex-specific differences in treatment safety and efficacy. Little is known about how representation may vary among psychiatric disorders under study or interact with other clinical trial features. This study assessed sex differences in enrollment for <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>-registered psychiatric drug clinical trials and identified trial characteristics associated with enrollment disparities.</div></div><div><h3>Methods</h3><div>This cross-sectional study assessed, for ten psychiatric disorders, enrollment by sex for US-based phase 1–3 interventional drug trials open to both sexes in <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> between 2000 and 2024 (441 total trials; 63,254 participants). Enrollment proportions were compared to parity (50 % each sex) and proportionality (sex-specific disease prevalence) expectations using one-sample Wilcoxon signed rank tests. Two-way ANOVA tests with interaction analyzed effects of disorder and trial characteristics on enrollment.</div></div><div><h3>Results</h3><div>Significant (<em>p</em> &lt; 0.01) female underrepresentation by both standards was detected in trials for schizophrenia (26.6 % female vs. 50.0 % sex-specific prevalence), opioid use disorder (29.2 % vs. 49.4 %), and post-traumatic stress disorder (36.2 % vs. 74.2 %). Significant male underrepresentation was noted for eating disorders (18.4 % male vs. 30.9 % sex-specific prevalence). Female enrollment improved significantly in newer trials for attention deficit hyperactivity disorder (female &lt;2015 vs. ≥ 2015: 29.0 % vs. 53.2 %, <em>p</em> &lt; 0.001) and alcohol use disorder (22.0 % vs. 37.7 %, <em>p</em> = 0.04).</div></div><div><h3>Conclusions</h3><div>Enrollment disparities by sex were observed for psychiatric drug clinical trials, with male and female participants underrepresented in different areas of research. Most disorders have not demonstrated progress toward improving representation over time. Psychiatric disorders with unequal and disproportionate enrollment may benefit from support to improve representation.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108052"},"PeriodicalIF":1.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885583","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":"Adaptive phase 2/3 design with dose optimization","authors":"Cong Chen ,&nbsp;Mo Huang ,&nbsp;Xuekui Zhang","doi":"10.1016/j.cct.2025.108048","DOIUrl":"10.1016/j.cct.2025.108048","url":null,"abstract":"<div><div>FDA's Project Optimus initiative for oncology drug development emphasizes selecting a dose that optimizes both efficacy and safety. When an inferentially adaptive Phase 2/3 design with dose selection is implemented to comply with the initiative, the conventional inverse normal combination test is commonly used for Type I error control. However, indiscriminate application of this overly conservative test can lead to substantial increase in sample size and timeline delays, which undermines the appeal of the adaptive approach. This, in turn, frustrates drug developers regarding Project Optimus.</div><div>The inflation of Type I error depends on the probability of selecting a dose with better long-term efficacy outcome at end of the study based on limited follow-up data at dose selection. In this paper, we discuss the estimation of this probability and its impact on Type I error control in realistic settings. Incorporating it explicitly into the two methods we have proposed result in improved designs, potentially motivating drug developers to adhere more closely to an initiative that has the potential to revolutionize oncology drug development.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108048"},"PeriodicalIF":1.9,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882363","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":"Protocol for VetASSIST: A randomized controlled trial to evaluate virtual peer health coaching for veterans with multimorbidity","authors":"Kristen E. Gray ,&nbsp;Jennifer L. Williams ,&nbsp;Andrades Rivera-Remines ,&nbsp;Tiffanie Fennell ,&nbsp;Mayuree Rao ,&nbsp;Tavion Rogers ,&nbsp;Leslie Taylor ,&nbsp;Karin M. Nelson ,&nbsp;Katherine D. Hoerster","doi":"10.1016/j.cct.2025.108045","DOIUrl":"10.1016/j.cct.2025.108045","url":null,"abstract":"<div><h3>Background</h3><div>More than half of Department of Veterans Affairs (VA) patients have multimorbidity, two or more co-occurring chronic conditions. Multimorbidity impairs health-related quality of life and contributes to disability, mortality, and high healthcare costs. Chronic conditions typically require individuals to engage in self-management, which can be especially challenging for those with multimorbidity. We developed a Veteran-led, synchronous video peer health coaching intervention called VetASSIST to help patients with multimorbidity overcome barriers to self-management and improve health-related quality of life. We are conducting a randomized controlled trial to determine the effectiveness of VetASSIST.</div></div><div><h3>Methods</h3><div>Veterans from a single VA healthcare system (<em>N</em> = 294) with at least three chronic conditions in three or more body systems are randomized 1:1 to either usual care (control) or usual care plus Veteran peer health coaching (intervention). Those in the intervention group receive 20 video visits over one year delivered by trained Veteran peers who provide brief health education; assistance with disease self-management, including goal setting and problem-solving; linkages to VA and community resources; and social support. The primary outcome is 12-month change from baseline in physical health-related quality of life, measured by the SF-12. Secondary outcomes include 12-month changes in SF-12 mental health-related quality of life and healthcare utilization.</div></div><div><h3>Discussion</h3><div>This trial will test whether a peer health coaching program can promote health and wellbeing among individuals with multimorbidity. If effective, the VetASSIST program could be implemented within VA and other healthcare systems to support high risk patients with multimorbidity.</div><div>Clinical Trials Registration: <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span> (<span><span>NCT05560451</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"157 ","pages":"Article 108045"},"PeriodicalIF":1.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862187","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":"COVID Prevention Program: Rationale and methodology of a tailored behavioral intervention to prevent household and community spread of COVID-19 among Latinos","authors":"Noe C. Crespo ,&nbsp;Job Godino ,&nbsp;Alma Behar ,&nbsp;Patricia Dionicio ,&nbsp;Carolina Lopez de la Torre ,&nbsp;Kiria Fraga ,&nbsp;Marco Santoscoy ,&nbsp;John P. Elder ,&nbsp;Eyal Oren ,&nbsp;Chii-Dean Lin ,&nbsp;Elva M. Arredondo ,&nbsp;Hala Madanat ,&nbsp;Christian B. Ramers","doi":"10.1016/j.cct.2025.108046","DOIUrl":"10.1016/j.cct.2025.108046","url":null,"abstract":"<div><h3>Background</h3><div>COVID-19 has disproportionately affected underserved communities, such as Latinos living in the U.S. <em>Promotoras</em> (Community Health Workers) may be effective at delivering tailored and culturally relevant strategies to prevent household spread and the burden of SARS-CoV-2 among Latinos and other minority groups.</div></div><div><h3>Purpose</h3><div>To develop, implement, and test the clinic-based <em>promotora</em>-led COVID-19 Prevention Program (CPP) to reduce transmission of SARS-CoV-2 in 256 Latino households and the community.</div></div><div><h3>Design</h3><div>CPP is a two-group randomized controlled trial designed to test the immediate, mid-term, and long-term effectiveness of the <em>promotora-</em>led intervention, as well as test its effectiveness on short- and long-term behavioral, mental, and physical health outcomes. The primary outcome is household infection rate assessed at 6 weeks and 6-, 12-, and 24-months based on a binary indicator (yes vs. no) of evidence of a new infection via antigen, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), or antibody SARS-CoV-2 test results within household members. Patients in the intervention group will receive enhanced standard-of-care, including tailored, real-time text messaging and virtual counseling, delivered by <em>promotoras</em>. Patients in the control group will receive the clinical standard of care. Analyses will test for household-level group differences in new infections related to an identified index case.</div></div><div><h3>Discussion</h3><div>Preventing household spread of SARS-CoV-2 is an important strategy to reduce the overall burden of SARS-CoV-2 among Latinos. The CPP is a scalable and tailored approach that has the potential to serve as a model to address future respiratory disease outbreaks, especially among uninsured, low-income, and medically underserved communities.</div><div>Trial registration: <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span> Identifier <span><span>NCT05697068</span><svg><path></path></svg></span> (1/20/2023).</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108046"},"PeriodicalIF":1.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858969","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":"Implementation of two non-drug pain prescriptions for musculoskeletal pain in primary care clinics","authors":"Carol G.T. Vance ,&nbsp;Dana L. Dailey ,&nbsp;Lynn Nakad ,&nbsp;David A. Katz ,&nbsp;Nicholas R. Butler ,&nbsp;Stacey A. Appenheimer ,&nbsp;Stephanie H. Gilbertson-White ,&nbsp;Jennie Embree ,&nbsp;Sandra E. Daack-Hirsch ,&nbsp;Kathleen A. Sluka ,&nbsp;Barbara A. Rakel","doi":"10.1016/j.cct.2025.108047","DOIUrl":"10.1016/j.cct.2025.108047","url":null,"abstract":"<div><h3>Background</h3><div>Chronic pain affects over 50 million Americans and is the main reason for primary care consultations. Clinical practice guidelines recommend use of non-drug therapies as first-line treatments. However, adoption and implementation of these guidelines are hindered by logistics. Exercise and transcutaneous electrical nerve stimulation (TENS) are effective non-drug strategies for managing chronic musculoskeletal pain, both of which have shown to reduce opioid usage. This study presents the results of implementing the Bundle for Exercises and TENS (BEsT) in primary care to facilitate prescription of non-drug therapy.</div></div><div><h3>Methods</h3><div>We developed an electronic bundle to facilitate prescription of TENS and exercise and trained providers to utilize the bundle. We identified providers who treated chronic pain from three primary care clinics to implement BEsT. Provider behaviors in prescribing TENS, exercise, opioids, non-opioid analgesics, and physical/occupational therapy (PT/OT) referrals were tracked. Surveys and focus groups captured provider perceptions of BEsT.</div></div><div><h3>Results</h3><div>After implementation of BesT, TENS prescription rates increased during training and were maintained in the 6–9 month follow up periods. Exercise prescriptions only increased during training. Across all clinics, opioid prescriptions decreased from 26 % to 14 %. Providers highlighted the auto-populate feature, patient education materials, and reduced opioid use as advantages of BEsT, but also noted increased time and staff burdens and workflow disruptions.</div></div><div><h3>Conclusions</h3><div>Providing decision making tools within provider workflow can increase use of non-drug therapy by primary care providers for chronic pain. However, prescriptions for non-drug therapies are hindered by increased the time and perceived burden to prescribe.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108047"},"PeriodicalIF":1.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844824","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":"Using multiple biomarkers for patient enrichment in two-stage clinical designs","authors":"Fengqing Zhang ,&nbsp;Jiangtao Gou","doi":"10.1016/j.cct.2025.108012","DOIUrl":"10.1016/j.cct.2025.108012","url":null,"abstract":"<div><div>Enrichment strategies play a critical role in modern clinical trial design, especially as precision medicine advances the focus on patient-specific efficacy. By targeting biomarker-defined populations most likely to benefit, these strategies improve efficiency, reduce sample sizes and costs, accelerate timelines, and minimize unnecessary exposure to treatment-related risks and side effects. Recent developments in enrichment design have introduced biomarker randomness and accounted for the correlation structure between treatment effect and biomarker, resulting in a two-stage threshold enrichment design. However, existing methods are limited to a single continuous biomarker. While incorporating multiple biomarkers can improve the accuracy of target population identification, no study has examined how to incorporate multiple continuous biomarkers into enrichment designs due to the challenges in determining multiple thresholds. To fully utilize information from all relevant biomarkers, we propose novel two-stage enrichment designs capable of handling two or more continuous biomarkers. Our framework accommodates two popular treatment effect metrics including average treatment effect (ATE) and the standardized ATE. We illustrate our method using a hypothetical clinical trial involving early-stage Alzheimer’s patients and assess the impact of stage one sample size on threshold estimation through a simulation study. Overall, our proposed two-stage enrichment designs offer researchers greater flexibility in integrating multiple continuous biomarkers. The findings from our study provide valuable insights for the advancement of enrichment trial methodology.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108012"},"PeriodicalIF":1.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816023","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":"Unequal allocation in randomised phase II trials","authors":"R. Jackson,&nbsp;T. Cox","doi":"10.1016/j.cct.2025.108043","DOIUrl":"10.1016/j.cct.2025.108043","url":null,"abstract":"<div><h3>Background</h3><div>Equal allocation is accepted almost universally in the design of randomised clinical trials and it is often assumed that this approach provides the most efficient use of available resources. The design of a phase II study often depend on a binary endpoint with assessments of efficacy made using an odds ratio. In a trial setting however, precision about this odds ratio will only be optimal under equal allocation when there is no difference in the response rates between two treatment arms. A result which typically is of limited clinical interest.</div></div><div><h3>Methodology</h3><div>For a clinical trial with response rates are p_x and p_y in the experimental and control arm respectively, allocation proportions are derived that seek to maximise the precision about an odds ratio in settings where difference between response rates are expected. Sample size calculations are performed and compared to study designs using equal allocation.</div></div><div><h3>Results</h3><div>Sample size calculations based on the exact methods of Jung and Sargent [<span><span>8</span></span>] show that under the same type 1 error rate and power, the required sample sizes using unequal allocation ratios are smaller than those where equal allocation is used. This discrepancy is greater as the control mean response rate tends towards 0 or 1 while the relative treatment effect remain fixed.</div></div><div><h3>Discussion</h3><div>Trialist involved in the design of phase II studies should take account of possible savings in sample size that may be gained by unequal allocation of patients.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108043"},"PeriodicalIF":1.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798426","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":"Strategies to evaluate treatment effects in clinical trials for emerging infectious diseases","authors":"Kentaro Sakamaki ,&nbsp;Yukari Uemura ,&nbsp;Yosuke Shimizu ,&nbsp;Lori E. Dodd","doi":"10.1016/j.cct.2025.108041","DOIUrl":"10.1016/j.cct.2025.108041","url":null,"abstract":"<div><h3>Background</h3><div>Swift regulatory approval of therapeutic interventions is crucial during emerging infectious disease outbreaks. However, variability in treatment effects based on disease severity or subgroups complicates trial design and endpoint selection. Prioritized composite endpoints can capture treatment effects across diverse clinical courses; however, their performance under heterogeneous treatment effects remains uncertain. This study uses simulation to evaluate trial design strategies in such contexts.</div></div><div><h3>Methods</h3><div>This study examines eight combinations of population and endpoint strategies to optimize trial design in emerging infectious diseases: evaluating treatment in the overall population and subgroups, with various endpoint choices including single, multiple, and prioritized composite endpoints. Simulated data was generated using multistate models based on the ACTT-1 study. Eight treatment effect scenarios, some exhibiting heterogeneity, were considered to evaluate ability to demonstrate efficacy.</div></div><div><h3>Results</h3><div>In scenarios without heterogeneous treatment effects, analyses in the overall population generally showed higher power than subgroup analyses. Time to recovery had relatively high power, while prioritized composite and multiple endpoints were comparable. In scenarios with treatment effect heterogeneity by baseline disease severity, power was higher in effective subgroups than in the overall population. Prioritized composite endpoints showed high power in scenarios where the treatment was effective on distinct endpoints in each subgroup.</div></div><div><h3>Conclusions</h3><div>For drug development in emerging infectious diseases with limited information, it is preferable to focus on evaluating prioritized composite or multiple endpoints in the overall population. Stratified analysis can be more powerful than unstratified analysis and should be considered for the primary analysis in the overall population.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108041"},"PeriodicalIF":1.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798423","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}