Pub Date : 2025-12-17DOI: 10.1016/j.cct.2025.108181
Rachel C. Whooten , Gracia M. Kwete , Haley Farrar-Muir , Rachel N. Cournoyer , Elizabeth A. Barth , Milton Kotelchuck , Elsie M. Taveras
{"title":"Corrigendum to “Engaging fathers in the first 1000 days to improve perinatal outcomes and prevent obesity: Rationale and design of the First Heroes randomized trial,” [Contemp Clin Trials 101 (2021) 106253]","authors":"Rachel C. Whooten , Gracia M. Kwete , Haley Farrar-Muir , Rachel N. Cournoyer , Elizabeth A. Barth , Milton Kotelchuck , Elsie M. Taveras","doi":"10.1016/j.cct.2025.108181","DOIUrl":"10.1016/j.cct.2025.108181","url":null,"abstract":"","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108181"},"PeriodicalIF":1.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780456","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}
Pub Date : 2025-12-16DOI: 10.1016/j.cct.2025.108188
Shivan J. Mehta , Pamela A. Shaw , Catherine Reitz , Caitlin Brophy , Evelyn Okorie , Keyirah Williams , Abraham Segura , Jinming Tao , Christopher K. Snider , Colin Wollack , Sadie Friday , Katharine A. Rendle , Tamar Klaiman , Karen Glanz , Corinne Rhodes , David A. Asch
Background
Colorectal cancer (CRC) screening rates remain limited, and effective methods for offering the choice of colonoscopy or stool testing through outreach have not been identified. We evaluate the effect of sequential choice compared to colonoscopy outreach on screening completion, and further evaluate behavioral nudges in the electronic health record (EHR).
Methods
In this pragmatic randomized clinical trial, patients were randomly allocated in a 1:2:2 ratio to 1) usual care (no outreach), 2) colonoscopy only, or 3) sequential choice of colonoscopy, then fecal immunochemical testing (FIT). Patients in arms 2 and 3 were additionally randomized to receive either (a) usual care, or (b) a visit-based, clinician-directed nudge facilitated by the EHR with follow-up texting to the patient. The primary outcome is CRC screening completion within 3 years by either colonoscopy, 2 negative fecal immunochemical tests (FIT), or 1 positive FIT followed by colonoscopy within one year.
Analysis
For the patient-directed analysis, the primary outcome will be evaluated by comparing CRC screening completion among patients randomized to either outreach arm (2 or 3) to the no outreach arm (1). We will also compare completion between the colonoscopy only arm (1) and the sequential choice arm (2). For the visit-based analysis, we will compare CRC screening completion among patients between the usual care arms (2a and 3a) and the nudge arms (2b and 3b).
Conclusion
This trial is unique in evaluating the long-term effectiveness of offering sequential choice to colonoscopy alone through a multi-level, centralized outreach and visit-based design.
{"title":"Sequential choice vs colonoscopy outreach for colorectal cancer screening: Design and rationale of a pragmatic randomized clinical trial","authors":"Shivan J. Mehta , Pamela A. Shaw , Catherine Reitz , Caitlin Brophy , Evelyn Okorie , Keyirah Williams , Abraham Segura , Jinming Tao , Christopher K. Snider , Colin Wollack , Sadie Friday , Katharine A. Rendle , Tamar Klaiman , Karen Glanz , Corinne Rhodes , David A. Asch","doi":"10.1016/j.cct.2025.108188","DOIUrl":"10.1016/j.cct.2025.108188","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) screening rates remain limited, and effective methods for offering the choice of colonoscopy or stool testing through outreach have not been identified. We evaluate the effect of sequential choice compared to colonoscopy outreach on screening completion, and further evaluate behavioral nudges in the electronic health record (EHR).</div></div><div><h3>Methods</h3><div>In this pragmatic randomized clinical trial, patients were randomly allocated in a 1:2:2 ratio to 1) usual care (no outreach), 2) colonoscopy only, or 3) sequential choice of colonoscopy, then fecal immunochemical testing (FIT). Patients in arms 2 and 3 were additionally randomized to receive either (a) usual care, or (b) a visit-based, clinician-directed nudge facilitated by the EHR with follow-up texting to the patient. The primary outcome is CRC screening completion within 3 years by either colonoscopy, 2 negative fecal immunochemical tests (FIT), or 1 positive FIT followed by colonoscopy within one year.</div></div><div><h3>Analysis</h3><div>For the patient-directed analysis, the primary outcome will be evaluated by comparing CRC screening completion among patients randomized to either outreach arm (2 or 3) to the no outreach arm (1). We will also compare completion between the colonoscopy only arm (1) and the sequential choice arm (2). For the visit-based analysis, we will compare CRC screening completion among patients between the usual care arms (2a and 3a) and the nudge arms (2b and 3b).</div></div><div><h3>Conclusion</h3><div>This trial is unique in evaluating the long-term effectiveness of offering sequential choice to colonoscopy alone through a multi-level, centralized outreach and visit-based design.</div><div><em>Clinical Trials Identifier:</em> <span><span>NCT05693649</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108188"},"PeriodicalIF":1.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780538","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}
Pub Date : 2025-12-16DOI: 10.1016/j.cct.2025.108191
Kerri N. Boutelle , Dawn M. Eichen , Michael Manzano , Noe C. Crespo , Ingrid Rivera-Iñiguez , Eduardo Castro , David R. Strong , Isabella Newell , Kristie Reed , Becky Marquez , Kyung E. Rhee
Latino children are disproportionally affected by overweight and obesity (OW/OB). Family-based behavioral treatment (FBT) is the most empirically supported treatment for children with OW/OB and traditionally includes a child and a caregiver. Very few FBT programs have been tested among Latino families, and to date, outcomes are inconsistent and/or show small effects. Familismo is a core value in Latino culture highlighting the importance of family functioning over any individual members, and it is possible that by adapting the treatment and including other family members, FBT outcomes could be enhanced for Latino families. Randomized trials show that parent-only FBT programs (PBT) are similarly effective to FBT and can be easier to disseminate and cost less. The current trial is a two-arm randomized controlled trial comparing the effect of a telehealth PBT program tailored to Latino families (PBT-LC) with a health education (HE) comparator on the child's weight over the 18 months of the study. We randomized 167 Latino families with a child with OW/OB to either six-months of telehealth PBT-LC or HE treatment delivered to the parent and additional caregiver in English or Spanish with 12-months of follow-up. This ongoing study may provide a translatable evidence-based cost-effective program tailored for Latino families with a child with OW/OB.
{"title":"Design of the FRESH-LC study: Caregivers as the agent of change for childhood obesity and chronic disease risk among Latino families","authors":"Kerri N. Boutelle , Dawn M. Eichen , Michael Manzano , Noe C. Crespo , Ingrid Rivera-Iñiguez , Eduardo Castro , David R. Strong , Isabella Newell , Kristie Reed , Becky Marquez , Kyung E. Rhee","doi":"10.1016/j.cct.2025.108191","DOIUrl":"10.1016/j.cct.2025.108191","url":null,"abstract":"<div><div>Latino children are disproportionally affected by overweight and obesity (OW/OB). Family-based behavioral treatment (FBT) is the most empirically supported treatment for children with OW/OB and traditionally includes a child and a caregiver. Very few FBT programs have been tested among Latino families, and to date, outcomes are inconsistent and/or show small effects. Familismo is a core value in Latino culture highlighting the importance of family functioning over any individual members, and it is possible that by adapting the treatment and including other family members, FBT outcomes could be enhanced for Latino families. Randomized trials show that parent-only FBT programs (PBT) are similarly effective to FBT and can be easier to disseminate and cost less. The current trial is a two-arm randomized controlled trial comparing the effect of a telehealth PBT program tailored to Latino families (PBT-LC) with a health education (HE) comparator on the child's weight over the 18 months of the study. We randomized 167 Latino families with a child with OW/OB to either six-months of telehealth PBT-LC or HE treatment delivered to the parent and additional caregiver in English or Spanish with 12-months of follow-up. This ongoing study may provide a translatable evidence-based cost-effective program tailored for Latino families with a child with OW/OB.</div><div>Clinical trials # <span><span>NCT05437406</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108191"},"PeriodicalIF":1.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780530","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}
Pub Date : 2025-12-15DOI: 10.1016/j.cct.2025.108184
Diane M. Wisnieski , Rebecca C. Rossom , Lauren M. Weinstock , Jennifer Johnson , Kathleen Miley , Brandon A. Gaudiano , Madeline B. Benz , Caitlin Borgert-Spaniol , Hannah R. Graves , Rachael Norwood , Rowyda Kazan , Colleen Starkey , Hanmin Kim , Linda Fletcher , Sheryl Kane , Yong Hu , Zachary Farrell , Sarah Strong , Hsueh-Han Yeh , Ted Miller , Brian K. Ahmedani
Background
Over 20 % of all adult suicide deaths in the U.S. occur within one year following jail release. Individuals may have increased access to lethal means, be faced with numerous financial, legal, and social stressors, and encounter a resurgence of legal problems. Suicide prevention interventions have demonstrated effects. Widespread implementation of these interventions for individuals leaving jail detention could have a significant impact on national suicide rates.
Methods
The 5S Study (Syncing, Screening, and Services for Suicide Prevention among Health & Jail Systems) aims to prevent suicide attempts among adults aged 18+ who are recently released from jail. Data from public jail release reports are synced with electronic health record (EHR) systems to enable proactive health system outreach. Those randomized to the intervention are contacted and consented, undergo a suicide risk screening and create a safety plan. Care Coordinators connect participants to health services. High risk participants, identified by the Patient Health Questionnaire (PHQ-9), are offered the Coping Long Term with Active Suicide Program (CLASP), an evidence-based suicide prevention intervention. Those randomized to control are never contacted and receive usual care. There is a waiver of consent for the control condition and a waiver of written consent for the intervention condition.
Discussion
The 5S Study uses data linkage between EHRs and jails to identify and connect with those recently released from jail, a population historically at high risk. Trial results will highlight best practices for syncing these data and offering support during the transition back to the community.
{"title":"Study protocol for a type I hybrid effectiveness trial of strategies to prevent suicide attempts among adults recently released from jail","authors":"Diane M. Wisnieski , Rebecca C. Rossom , Lauren M. Weinstock , Jennifer Johnson , Kathleen Miley , Brandon A. Gaudiano , Madeline B. Benz , Caitlin Borgert-Spaniol , Hannah R. Graves , Rachael Norwood , Rowyda Kazan , Colleen Starkey , Hanmin Kim , Linda Fletcher , Sheryl Kane , Yong Hu , Zachary Farrell , Sarah Strong , Hsueh-Han Yeh , Ted Miller , Brian K. Ahmedani","doi":"10.1016/j.cct.2025.108184","DOIUrl":"10.1016/j.cct.2025.108184","url":null,"abstract":"<div><h3>Background</h3><div>Over 20 % of all adult suicide deaths in the U.S. occur within one year following jail release. Individuals may have increased access to lethal means, be faced with numerous financial, legal, and social stressors, and encounter a resurgence of legal problems. Suicide prevention interventions have demonstrated effects. Widespread implementation of these interventions for individuals leaving jail detention could have a significant impact on national suicide rates.</div></div><div><h3>Methods</h3><div>The 5S Study (Syncing, Screening, and Services for Suicide Prevention among Health & Jail Systems) aims to prevent suicide attempts among adults aged 18+ who are recently released from jail. Data from public jail release reports are synced with electronic health record (EHR) systems to enable proactive health system outreach. Those randomized to the intervention are contacted and consented, undergo a suicide risk screening and create a safety plan. Care Coordinators connect participants to health services. High risk participants, identified by the Patient Health Questionnaire (PHQ-9), are offered the Coping Long Term with Active Suicide Program (CLASP), an evidence-based suicide prevention intervention. Those randomized to control are never contacted and receive usual care. There is a waiver of consent for the control condition and a waiver of written consent for the intervention condition.</div></div><div><h3>Discussion</h3><div>The 5S Study uses data linkage between EHRs and jails to identify and connect with those recently released from jail, a population historically at high risk. Trial results will highlight best practices for syncing these data and offering support during the transition back to the community.</div><div><strong>Trial Registration</strong>: <span><span>https://clinicaltrials.gov/study/NCT06506344</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108184"},"PeriodicalIF":1.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760862","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}
Pub Date : 2025-12-15DOI: 10.1016/j.cct.2025.108187
Danielle M. McCarthy , Lisa B. VanWagner , Miriam R. Rafferty , Kenzie A. Cameron , Jungwha Lee , Siyuan Dong , Anuva Fellner , Amy V. Kontrick
Background
Up to a quarter of emergency department (ED) patients have incidental hepatic steatosis (fatty liver) noted on imaging studies; however, patients are infrequently notified about this new finding. This lack of communication may have consequences including delayed diagnosis of metabolic associated steatotic liver disease (MASLD) and disease progression.
Methods
This type-2 hybrid effectiveness-implementation study uses a Stepped Wedge-Cluster Randomized Trial design across 11 EDs to evaluate an electronic health record (EHR) delivered intervention. The STeatosis Identification, Risk stratification, and Referral pathway in the ED (STIRRED) clinical decision support system leverages the EHR to identify cases of hepatic steatosis and deliver risk-stratified communication to clinicians supporting patient notification about hepatic steatosis in the ED. The primary effectiveness outcome will be receipt of a new steatotic liver disease-related diagnosis among high-risk patients within 120 days post-ED discharge; the primary implementation outcome is fidelity, defined as the degree to which STIRRED was delivered as intended. Over the study period, ∼4700 patients with incidental hepatic steatosis will be analyzed, including 616 high-risk patients, providing 80 % power to detect a risk difference of 5.6 % (odds ratio of 3.5) between STIRRED and usual care in the receipt of a new steatotic liver disease-related diagnosis.
Discussion
This trial uses the electronic health record to deliver an evidence-based risk stratification score and referral recommendation to the bedside clinician in patients with incidentally noted hepatic steatosis. Rigorous implementation science methodology used in both the intervention development and assessment will increase the usability of the intervention and future scalability.
Trial Registration: This trial was prospectively registered on 10/9/2024 with ClinicalTrials.gov (# NCT06944353).
{"title":"Improving diagnostic safety through steatosis identification, risk stratification, and referral pathway in the ED (STIRRED): Protocol for an effectiveness implementation trial","authors":"Danielle M. McCarthy , Lisa B. VanWagner , Miriam R. Rafferty , Kenzie A. Cameron , Jungwha Lee , Siyuan Dong , Anuva Fellner , Amy V. Kontrick","doi":"10.1016/j.cct.2025.108187","DOIUrl":"10.1016/j.cct.2025.108187","url":null,"abstract":"<div><h3>Background</h3><div>Up to a quarter of emergency department (ED) patients have incidental hepatic steatosis (fatty liver) noted on imaging studies; however, patients are infrequently notified about this new finding. This lack of communication may have consequences including delayed diagnosis of metabolic associated steatotic liver disease (MASLD) and disease progression.</div></div><div><h3>Methods</h3><div>This type-2 hybrid effectiveness-implementation study uses a Stepped Wedge-Cluster Randomized Trial design across 11 EDs to evaluate an electronic health record (EHR) delivered intervention. The STeatosis Identification, Risk stratification, and Referral pathway in the ED (STIRRED) clinical decision support system leverages the EHR to identify cases of hepatic steatosis and deliver risk-stratified communication to clinicians supporting patient notification about hepatic steatosis in the ED. The primary effectiveness outcome will be receipt of a new steatotic liver disease-related diagnosis among high-risk patients within 120 days post-ED discharge; the primary implementation outcome is fidelity, defined as the degree to which STIRRED was delivered as intended. Over the study period, ∼4700 patients with incidental hepatic steatosis will be analyzed, including 616 high-risk patients, providing 80 % power to detect a risk difference of 5.6 % (odds ratio of 3.5) between STIRRED and usual care in the receipt of a new steatotic liver disease-related diagnosis.</div></div><div><h3>Discussion</h3><div>This trial uses the electronic health record to deliver an evidence-based risk stratification score and referral recommendation to the bedside clinician in patients with incidentally noted hepatic steatosis. Rigorous implementation science methodology used in both the intervention development and assessment will increase the usability of the intervention and future scalability.</div><div>Trial Registration: This trial was prospectively registered on 10/9/2024 with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (# <span><span>NCT06944353</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108187"},"PeriodicalIF":1.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773884","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}
Pub Date : 2025-12-15DOI: 10.1016/j.cct.2025.108185
Nickola D. Pallin , Naomi Algeo , Mary Eileen O'Connor , Hayley Connolly , Michelle Lowry , Kathleen Bennett , Patrick Gillespie , Anna Hobbins , Pamela Gallagher , Louise Mullen , Kathleen D. Lyons , Sheena M. McHugh , Deirdre Connolly
Introduction
Women living with and beyond breast cancer (LWBBC) often experience challenges in returning to work (RTW) because of disease and treatment-related side effects. Therefore, interventions to enhance RTW for those LWBBC are a recommended component of cancer survivorship care. CanWork is a six-week, self-management support programme designed to facilitate women LWBBC in developing knowledge and skills to manage cancer-related symptoms that interfere with RTW. This paper presents the protocol for a cluster randomised controlled trial that will test the effectiveness and cost effectiveness of CanWork in supporting women LWBBC in RTW following completion of cancer treatment.
Methods
A cluster-randomised controlled trial will be conducted through community cancer support centres in the Republic of Ireland. Centres will be assigned to the control or intervention arms by randomisation and the aim is to recruit 248 women. The two primary outcomes are changes in RTW (yes: returned to work; no: not returned to work) and self-efficacy to manage physical, psychological and emotional demands of work at 12 months follow up post-intervention. Secondary outcomes are readiness to return to work, self-efficacy for managing cancer-related symptoms that interfere with work, health related quality of life and absence from work for cancer-related reasons at 12 months follow up post-intervention. Cost effectiveness will also be measured. Follow-up will occur up to 12-months post-intervention using self-reported questionnaires.
Discussion
Findings will determine whether CanWork is an effective and cost-effective intervention in supporting women with breast cancer to return to work.
{"title":"A cluster randomised controlled trial to test the effectiveness and cost-effectiveness of a self-management intervention to support women with breast cancer to return to work: A study protocol","authors":"Nickola D. Pallin , Naomi Algeo , Mary Eileen O'Connor , Hayley Connolly , Michelle Lowry , Kathleen Bennett , Patrick Gillespie , Anna Hobbins , Pamela Gallagher , Louise Mullen , Kathleen D. Lyons , Sheena M. McHugh , Deirdre Connolly","doi":"10.1016/j.cct.2025.108185","DOIUrl":"10.1016/j.cct.2025.108185","url":null,"abstract":"<div><h3>Introduction</h3><div>Women living with and beyond breast cancer (LWBBC) often experience challenges in returning to work (RTW) because of disease and treatment-related side effects. Therefore, interventions to enhance RTW for those LWBBC are a recommended component of cancer survivorship care. CanWork is a six-week, self-management support programme designed to facilitate women LWBBC in developing knowledge and skills to manage cancer-related symptoms that interfere with RTW. This paper presents the protocol for a cluster randomised controlled trial that will test the effectiveness and cost effectiveness of CanWork in supporting women LWBBC in RTW following completion of cancer treatment.</div></div><div><h3>Methods</h3><div>A cluster-randomised controlled trial will be conducted through community cancer support centres in the Republic of Ireland. Centres will be assigned to the control or intervention arms by randomisation and the aim is to recruit 248 women. The two primary outcomes are changes in RTW (yes: returned to work; no: not returned to work) and self-efficacy to manage physical, psychological and emotional demands of work at 12 months follow up post-intervention. Secondary outcomes are readiness to return to work, self-efficacy for managing cancer-related symptoms that interfere with work, health related quality of life and absence from work for cancer-related reasons at 12 months follow up post-intervention. Cost effectiveness will also be measured. Follow-up will occur up to 12-months post-intervention using self-reported questionnaires.</div></div><div><h3>Discussion</h3><div>Findings will determine whether CanWork is an effective and cost-effective intervention in supporting women with breast cancer to return to work.</div><div><strong>Trial registration number:</strong> <span><span>NCT06723899</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108185"},"PeriodicalIF":1.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773816","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}
Pub Date : 2025-12-15DOI: 10.1016/j.cct.2025.108186
Ellie Medcalf , Robin M. Turner , David Espinoza , Lin Zhu , Katy J.L. Bell
Background
Complete case analysis (CCA) is the most common method used to handle missing outcome data in trials but may often lead to biased estimates. Newer methods that address missing not at random data are infrequently used.
Objective
We evaluated six missing data methods in a simulation study based on a melanoma surveillance trial.
Methods
We used the MEL-SELF pilot of patient-led surveillance for patients with early-stage melanoma as the empirical basis of our simulated study. We evaluated three commonly used methods (CCA, mixed models for repeated measurements (MMRM), multiple imputation (MI)), and three recently developed methods (retrieved dropout (RD) imputation, jump to reference (J2R) imputation and trimmed means (TM)), under 48 scenarios where treatment effect size, missingness percentage and missingness assumptions were varied.
Results
Under scenarios with small or small-moderate treatment effects and missing not at random outcome data, all methods produced some bias, with TM and CCA the most biased towards and away from the null, respectively. Both also had low precision and power. J2R performed best of methods that were biased towards the null (JR, TM), with small bias for small and small-moderate treatment effects, high precision and high coverage. RD performed best of methods that were biased away from the null (RD, CCA, MMRM, MI) with small bias, good precision and good coverage.
Conclusion
In this simulation of a melanoma surveillance trial with non-random missing outcomes, RD produced the least bias away from the null and J2R produced the least bias towards the null.
背景：完整病例分析（CCA）是最常用的方法，用于处理试验中缺失的结果数据，但可能经常导致有偏估计。解决非随机数据丢失的新方法很少使用。目的：我们在一项基于黑色素瘤监测试验的模拟研究中评估了六种缺失的数据方法。方法：我们采用患者主导的早期黑色素瘤患者监测MEL-SELF试点作为我们模拟研究的经验基础。我们评估了三种常用的方法（CCA，重复测量混合模型（MMRM），多重imputation (MI)）和三种最近开发的方法(检索dropout (RD) imputation, jump to reference （J2R) imputation和修剪均值（TM）），在48种不同的治疗效应大小，缺失率和缺失假设的情况下。结果：在治疗效果较小或较小的情况下，所有方法都存在一定的偏倚，其中TM和CCA分别最偏向零值和远离零值。两者的精度和功率都很低。J2R在偏零（JR， TM）的方法中表现最好，对小、中治疗效果的偏倚较小，精度高，覆盖率高。RD在偏离零值的方法（RD、CCA、MMRM、MI）中表现最好，偏差小，精度好，覆盖范围好。结论：在这个具有非随机缺失结果的黑色素瘤监测试验模拟中，RD产生的偏离零值的偏倚最小，而J2R产生的偏倚最小。
{"title":"Evaluating missing outcome data methods for the analysis of the MEL-SELF trial of patient-led surveillance for early-stage melanoma: A simulation study","authors":"Ellie Medcalf , Robin M. Turner , David Espinoza , Lin Zhu , Katy J.L. Bell","doi":"10.1016/j.cct.2025.108186","DOIUrl":"10.1016/j.cct.2025.108186","url":null,"abstract":"<div><h3>Background</h3><div>Complete case analysis (CCA) is the most common method used to handle missing outcome data in trials but may often lead to biased estimates. Newer methods that address missing not at random data are infrequently used.</div></div><div><h3>Objective</h3><div>We evaluated six missing data methods in a simulation study based on a melanoma surveillance trial.</div></div><div><h3>Methods</h3><div>We used the MEL-SELF pilot of patient-led surveillance for patients with early-stage melanoma as the empirical basis of our simulated study. We evaluated three commonly used methods (CCA, mixed models for repeated measurements (MMRM), multiple imputation (MI)), and three recently developed methods (retrieved dropout (RD) imputation, jump to reference (J2R) imputation and trimmed means (TM)), under 48 scenarios where treatment effect size, missingness percentage and missingness assumptions were varied.</div></div><div><h3>Results</h3><div>Under scenarios with small or small-moderate treatment effects and missing not at random outcome data, all methods produced some bias, with TM and CCA the most biased towards and away from the null, respectively. Both also had low precision and power. J2R performed best of methods that were biased towards the null (JR, TM), with small bias for small and small-moderate treatment effects, high precision and high coverage. RD performed best of methods that were biased away from the null (RD, CCA, MMRM, MI) with small bias, good precision and good coverage.</div></div><div><h3>Conclusion</h3><div>In this simulation of a melanoma surveillance trial with non-random missing outcomes, RD produced the least bias away from the null and J2R produced the least bias towards the null.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108186"},"PeriodicalIF":1.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773939","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}
Pub Date : 2025-12-15DOI: 10.1016/j.cct.2025.108182
Paulo Henrique Leite Souza , Fernanda Marciano Consolim-Colombo , Bruno Paulino Venancio , Katia de Angelis , João Carlos Ferrari Corrêa , Márcio Gonçalves de Sousa , Raphael Mendes Ritti Dias , Fernanda Ishida Corrêa
Introduction
Hypertensive individuals experience chronic inflammation, higher sympathetic nervous system activity, and decreased functional capacity. While Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) and aerobic training have shown benefits for hypertension, their combined effects have not been explored.
Objective
To evaluate the effects of taVNS combined with aerobic training on blood pressure, cardiac autonomic modulation, inflammation, oxidative stress, and functional capacity in individuals with hypertension.
Methods
This protocol outlines a randomized, controlled, single-blind clinical trial involving hypertensive adults. Participants will be randomly assigned to one of three groups: aerobic training with taVNS, aerobic training alone, or taVNS alone. Aerobic training will consist of 50 min of stationary cycling, while taVNS will be applied using a neuromuscular stimulator with an electrode placed on the left ear for 30 min. The intervention will be administered three times per week for 8 weeks, totaling 24 sessions. The primary outcome is blood pressure measurement, while secondary outcomes include heart rate variability, functional capacity, serum inflammatory mediators, and biomarkers of systemic oxidative stress. Assessments will be conducted before the intervention, after 24 sessions, and 30 days of post-treatment.
Results
The groups will be compared to the outcome measures to determine the taVNS benefits combined with aerobic training for hypertensive individuals.
Conclusion
This is the first clinical trial to assess the taVNS effects combined with physical exercise in hypertensive individuals. The study will provide data on this approach's efficacy for improving blood pressure, cardiac autonomic modulation, oxidative stress, and functional capacity in hypertensive people.
{"title":"Effects of auricular vagus nerve stimulation and aerobic training in individuals with hypertension – Protocol for a controlled, randomized, and blind clinical trial","authors":"Paulo Henrique Leite Souza , Fernanda Marciano Consolim-Colombo , Bruno Paulino Venancio , Katia de Angelis , João Carlos Ferrari Corrêa , Márcio Gonçalves de Sousa , Raphael Mendes Ritti Dias , Fernanda Ishida Corrêa","doi":"10.1016/j.cct.2025.108182","DOIUrl":"10.1016/j.cct.2025.108182","url":null,"abstract":"<div><h3>Introduction</h3><div>Hypertensive individuals experience chronic inflammation, higher sympathetic nervous system activity, and decreased functional capacity. While Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) and aerobic training have shown benefits for hypertension, their combined effects have not been explored.</div></div><div><h3>Objective</h3><div>To evaluate the effects of taVNS combined with aerobic training on blood pressure, cardiac autonomic modulation, inflammation, oxidative stress, and functional capacity in individuals with hypertension.</div></div><div><h3>Methods</h3><div>This protocol outlines a randomized, controlled, single-blind clinical trial involving hypertensive adults. Participants will be randomly assigned to one of three groups: aerobic training with taVNS, aerobic training alone, or taVNS alone. Aerobic training will consist of 50 min of stationary cycling, while taVNS will be applied using a neuromuscular stimulator with an electrode placed on the left ear for 30 min. The intervention will be administered three times per week for 8 weeks, totaling 24 sessions. The primary outcome is blood pressure measurement, while secondary outcomes include heart rate variability, functional capacity, serum inflammatory mediators, and biomarkers of systemic oxidative stress. Assessments will be conducted before the intervention, after 24 sessions, and 30 days of post-treatment.</div></div><div><h3>Results</h3><div>The groups will be compared to the outcome measures to determine the taVNS benefits combined with aerobic training for hypertensive individuals.</div></div><div><h3>Conclusion</h3><div>This is the first clinical trial to assess the taVNS effects combined with physical exercise in hypertensive individuals. The study will provide data on this approach's efficacy for improving blood pressure, cardiac autonomic modulation, oxidative stress, and functional capacity in hypertensive people.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108182"},"PeriodicalIF":1.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773894","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}
Pub Date : 2025-12-09DOI: 10.1016/j.cct.2025.108175
Marcus R. Johnson , Merritt Raitt , Aliya Asghar , Danielle Beck , Grant D. Huang
Participant enrollment remains a leading indicator of the validity and generalizability of clinical trial results in the population at large. Establishing standardized and structured enrollment metrics can offer valuable information on clinical research performance (site and network level).
The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) Network of Dedicated Enrollment Sites (NODES) evaluated its performance against standardized study and network enrollment metrics over a 6-year timeframe from implementation of the metrics (VA Fiscal Year (FY) 2019) through FY 2024. Our findings demonstrate a positive trend in the ability of network sites to achieve NODES-specific enrollment metrics, comparing FY 2019 (55 %) to FY 2024 (73 %). Additionally, we identified improvement in study participant enrollment more broadly based on CSP study-specific enrollment metrics, as evidenced by an increase in the percentage that Node sites achieved ≥50 % of their expected enrollment targets in FY 2019 (64.7 %) on average compared to FY 2024 (69.5 %), and sustained performance as it relates to the percentage that network sites were in the “Top 1/3 of Study Sites Overall” comparing FY 2019 (36.9 %) to FY 2024 (36.1 %). Lastly, CSP Node sites enrolled study participants at a higher percentage than non-Node CSP study sites when comparing enrollment (actual/expected) by margins of 28.4 % (FY 2019) and 21.6 % (FY 2024), respectively. It is our hope that our experiences of navigating challenges associated with this effort, understanding lessons learned, and achieving successes might serve as a useful template for other clinical research consortiums that aim to evaluate their performance.
{"title":"Development and implementation of standardized study enrollment metrics for a VA healthcare system clinical research consortium: A 6-year follow-up assessment","authors":"Marcus R. Johnson , Merritt Raitt , Aliya Asghar , Danielle Beck , Grant D. Huang","doi":"10.1016/j.cct.2025.108175","DOIUrl":"10.1016/j.cct.2025.108175","url":null,"abstract":"<div><div>Participant enrollment remains a leading indicator of the validity and generalizability of clinical trial results in the population at large. Establishing standardized and structured enrollment metrics can offer valuable information on clinical research performance (site and network level).</div><div>The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) Network of Dedicated Enrollment Sites (NODES) evaluated its performance against standardized study and network enrollment metrics over a 6-year timeframe from implementation of the metrics (VA Fiscal Year (FY) 2019) through FY 2024. Our findings demonstrate a positive trend in the ability of network sites to achieve NODES-specific enrollment metrics, comparing FY 2019 (55 %) to FY 2024 (73 %). Additionally, we identified improvement in study participant enrollment more broadly based on CSP study-specific enrollment metrics, as evidenced by an increase in the percentage that Node sites achieved ≥50 % of their expected enrollment targets in FY 2019 (64.7 %) on average compared to FY 2024 (69.5 %), and sustained performance as it relates to the percentage that network sites were in the “Top 1/3 of Study Sites Overall” comparing FY 2019 (36.9 %) to FY 2024 (36.1 %). Lastly, CSP Node sites enrolled study participants at a higher percentage than non-Node CSP study sites when comparing enrollment (actual/expected) by margins of 28.4 % (FY 2019) and 21.6 % (FY 2024), respectively. It is our hope that our experiences of navigating challenges associated with this effort, understanding lessons learned, and achieving successes might serve as a useful template for other clinical research consortiums that aim to evaluate their performance.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108175"},"PeriodicalIF":1.9,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741246","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}
Pub Date : 2025-12-05DOI: 10.1016/j.cct.2025.108173
Aseel El Zein , Vishnu Garla , Michael E. Hall , Tanjila Nawshin , Druss Hays , Tejossy John , Erin Delaney , Eric Wallace , Larry Hearld , Andrea L. Cherrington , Tapan Mehta
Background
In the U.S. Deep South, Black adults experience disproportionate rates of type 2 diabetes (T2D) and associated complications, driven in part by adverse social determinants of health (SDoH). Addressing these disparities requires multilevel interventions that can be optimized for both effectiveness and cost. The Food Delivery, Remote Monitoring, & Coaching-Enhanced Education for Optimized Diabetes Management (FREEDOM) trial aims to identify an optimized, scalable intervention package that improves glycemic control among Black adults with T2D.
Methods
FREEDOM is a multicenter, hybrid type 1 optimization-implementation trial uses a 2 × 2 × 2 factorial design to test three intervention components—digital health coaching, food box delivery, and remote patient monitoring (RPM)—among 304 adults recruited from three health systems in Alabama and Mississippi. Interventions are delivered over six months with follow-up assessments through 12 months. The primary clinical outcome is change in HbA1c at 12 months. Secondary outcomes include within-trial cost-utility using net monetary benefit, RE-AIM outcomes, and CFIR-guided qualitative assessment of contextual determinants. Mixed methods will evaluate fidelity and context. Optimization will be determined using the net monetary benefit framework based on quality-adjusted life years (QALYs).
Discussion
This protocol describes the design and methods of the FREEDOM trial, which seeks to address key gaps in optimizing multilevel interventions for adults with T2D in underserved regions of the Deep South. Findings will guide the selection of scalable, cost-effective intervention strategies to improve glycemic control among adults with T2D.
Registration
ClinicalTrials.gov identifier: NCT05288452; first posted December 29, 2022.
{"title":"Rationale and design of the FREEDOM study: A hybrid type 1 optimization-implementation trial to improve type 2 diabetes management in primary care","authors":"Aseel El Zein , Vishnu Garla , Michael E. Hall , Tanjila Nawshin , Druss Hays , Tejossy John , Erin Delaney , Eric Wallace , Larry Hearld , Andrea L. Cherrington , Tapan Mehta","doi":"10.1016/j.cct.2025.108173","DOIUrl":"10.1016/j.cct.2025.108173","url":null,"abstract":"<div><h3>Background</h3><div>In the U.S. Deep South, Black adults experience disproportionate rates of type 2 diabetes (T2D) and associated complications, driven in part by adverse social determinants of health (SDoH). Addressing these disparities requires multilevel interventions that can be optimized for both effectiveness and cost. The Food Delivery, Remote Monitoring, & Coaching-Enhanced Education for Optimized Diabetes Management (FREEDOM) trial aims to identify an optimized, scalable intervention package that improves glycemic control among Black adults with T2D.</div></div><div><h3>Methods</h3><div>FREEDOM is a multicenter, hybrid type 1 optimization-implementation trial uses a 2 × 2 × 2 factorial design to test three intervention components—digital health coaching, food box delivery, and remote patient monitoring (RPM)—among 304 adults recruited from three health systems in Alabama and Mississippi. Interventions are delivered over six months with follow-up assessments through 12 months. The primary clinical outcome is change in HbA1c at 12 months. Secondary outcomes include within-trial cost-utility using net monetary benefit, RE-AIM outcomes, and CFIR-guided qualitative assessment of contextual determinants. Mixed methods will evaluate fidelity and context. Optimization will be determined using the net monetary benefit framework based on quality-adjusted life years (QALYs).</div></div><div><h3>Discussion</h3><div>This protocol describes the design and methods of the FREEDOM trial, which seeks to address key gaps in optimizing multilevel interventions for adults with T2D in underserved regions of the Deep South. Findings will guide the selection of scalable, cost-effective intervention strategies to improve glycemic control among adults with T2D.</div></div><div><h3>Registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier: <span><span>NCT05288452</span><svg><path></path></svg></span>; first posted December 29, 2022.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108173"},"PeriodicalIF":1.9,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700010","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}
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