Pub Date : 2024-11-09DOI: 10.1016/j.conctc.2024.101392
Maureen M. Churipuy , Shirin Golchi , Marie Hudson , Sabrina Hoa
It is important for researchers to carefully assess the feasibility of a clinical trial prior to the launch of the study. One feasibility aspect that needs to be considered includes whether investigators can expect to successfully achieve the sample size needed for their trial. In this manuscript, we present a Bayesian design in which data collected during a pilot study is used to predict the feasibility of a planned phase III trial. Specifically, we outline a model that predicts a target sample size obtained from the Gamma-Poisson distribution. In a simulation study, we showcase the utility of the proposed design by applying it to a phase III trial designed to assess the efficacy of mycophenolate mofetil in individuals with mild systemic sclerosis. We demonstrate that the predictive nature of the proposed design is particularly useful for rare disease clinical trials and has the potential to greatly increase their efficiency.
对于研究人员来说，在启动研究之前仔细评估临床试验的可行性非常重要。需要考虑的一个可行性方面包括研究人员是否有望成功达到试验所需的样本量。在本手稿中，我们介绍了一种贝叶斯设计，利用试验研究期间收集的数据来预测计划中的 III 期试验的可行性。具体来说，我们概述了一个模型，该模型可预测从伽马-泊松分布中获得的目标样本量。在一项模拟研究中，我们将所提出的设计应用于一项 III 期试验，以评估霉酚酸酯对轻度系统性硬化症患者的疗效，从而展示了该设计的实用性。我们证明，所提设计的预测性对罕见病临床试验特别有用，并有可能大大提高其效率。
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Pub Date : 2024-11-06DOI: 10.1016/j.conctc.2024.101389
Nermine Abdelwahab , Alicia Allen , Katherine Harrison , Ashley Petersen , Sharon Allen
New interventions are necessary to increase postpartum abstinence from cigarette smoking. Sex hormones, specifically progesterone, have been found to be protective against drug-taking behaviors. Our pilot double-blind, randomized, controlled trial, although underpowered, suggested a trend toward a higher prevalence of smoking abstinence among postpartum participants receiving exogenous progesterone compared to those receiving placebo. This paper outlines the protocol used in our study to evaluate the efficacy of modifying progesterone to increase postpartum smoking abstinence and, subsequently, decrease secondhand smoke exposure in infants. In the intervention arm, participants will receive open-label exogenous oral progesterone (200 mg twice daily). Using a concurrent control group that does not receive progesterone treatment, we hypothesize that progesterone treatment will increase postpartum smoking abstinence as measured using a 7-day point prevalence at six months post-treatment allocation, as well as reduce smoking-related risk factors. Secondary objectives include examining the impact of this maternal smoking intervention on infant health. In addition to describing the protocol, we also discuss the protocol changes made due to the COVID-19 pandemic. Upon completion, this study will provide new information on how sex hormones may influence smoking cessation in postpartum populations, which can have broad public health implications.
{"title":"A protocol for modifying progesterone to increase postpartum cigarette smoking abstinence and reduce secondhand smoke exposure in infants","authors":"Nermine Abdelwahab , Alicia Allen , Katherine Harrison , Ashley Petersen , Sharon Allen","doi":"10.1016/j.conctc.2024.101389","DOIUrl":"10.1016/j.conctc.2024.101389","url":null,"abstract":"<div><div>New interventions are necessary to increase postpartum abstinence from cigarette smoking. Sex hormones, specifically progesterone, have been found to be protective against drug-taking behaviors. Our pilot double-blind, randomized, controlled trial, although underpowered, suggested a trend toward a higher prevalence of smoking abstinence among postpartum participants receiving exogenous progesterone compared to those receiving placebo. This paper outlines the protocol used in our study to evaluate the efficacy of modifying progesterone to increase postpartum smoking abstinence and, subsequently, decrease secondhand smoke exposure in infants. In the intervention arm, participants will receive open-label exogenous oral progesterone (200 mg twice daily). Using a concurrent control group that does not receive progesterone treatment, we hypothesize that progesterone treatment will increase postpartum smoking abstinence as measured using a 7-day point prevalence at six months post-treatment allocation, as well as reduce smoking-related risk factors. Secondary objectives include examining the impact of this maternal smoking intervention on infant health. In addition to describing the protocol, we also discuss the protocol changes made due to the COVID-19 pandemic. Upon completion, this study will provide new information on how sex hormones may influence smoking cessation in postpartum populations, which can have broad public health implications.</div></div><div><h3>Clinical trials registration #</h3><div>NCT04783857.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101389"},"PeriodicalIF":1.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142652496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-04DOI: 10.1016/j.conctc.2024.101388
Wenru Zhou , Miranda Kroehl , Maxene Meier , Alexander Kaizer
This paper proposes a platform trial for conducting A/B tests with multiple arms and interim monitoring to investigate the impact of several factors on the expected sample size and probability of early stopping. We examined the performance of three stopping boundaries: O’Brien Fleming (OBF) stopping for either futility or difference (both), Pocock stopping for futility only, and fixed sample size design. We simulated twelve scenarios of different orders of arms based on various effect sizes, as well as considered 1 or 3 interim looks. The overall findings are summarizing in a flowchart to provide intuitive guidance for the design of the platform based on the simulation. We found that it is better to use OBF stopping for both if there is any effective variant and the trial is sufficiently powered to detect the expected effect size. If the study is underpowered to detect a difference, we recommend fixed sample size design to gather as much information as possible, however if the expected sample size is important to minimize, we recommend using Pocock boundaries with futility monitoring. Our results aimed at helping high-tech companies conduct their own studies without requiring extensive knowledge of clinical trial design and statistical methodology.
{"title":"An automated platform trial framework for A/B testing","authors":"Wenru Zhou , Miranda Kroehl , Maxene Meier , Alexander Kaizer","doi":"10.1016/j.conctc.2024.101388","DOIUrl":"10.1016/j.conctc.2024.101388","url":null,"abstract":"<div><div>This paper proposes a platform trial for conducting A/B tests with multiple arms and interim monitoring to investigate the impact of several factors on the expected sample size and probability of early stopping. We examined the performance of three stopping boundaries: O’Brien Fleming (OBF) stopping for either futility or difference (both), Pocock stopping for futility only, and fixed sample size design. We simulated twelve scenarios of different orders of arms based on various effect sizes, as well as considered 1 or 3 interim looks. The overall findings are summarizing in a flowchart to provide intuitive guidance for the design of the platform based on the simulation. We found that it is better to use OBF stopping for both if there is any effective variant and the trial is sufficiently powered to detect the expected effect size. If the study is underpowered to detect a difference, we recommend fixed sample size design to gather as much information as possible, however if the expected sample size is important to minimize, we recommend using Pocock boundaries with futility monitoring. Our results aimed at helping high-tech companies conduct their own studies without requiring extensive knowledge of clinical trial design and statistical methodology.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101388"},"PeriodicalIF":1.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142652493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.conctc.2024.101385
T.E. Galovski , L.B. McSweeney , R.D.V. Nixon , J.S. Wachen , B.N. Smith , S. Noorbaloochi , D. Vogt , B.L. Niles , S.M. Kehle-Forbes
Posttraumatic stress disorder (PTSD) is a debilitating condition often accompanied by significant functional impairments affecting quality of life and well-being. While Cognitive Processing Therapy (CPT) is a leading, evidence-based psychotherapy for PTSD, demonstrating substantial efficacy in core symptom reduction, its impact on psychosocial functioning is less well-established. The Personalizing Cognitive Processing Therapy with a Case Formulation Approach (Personalizing Approaches to Therapy: PATh) study aims to enhance CPT by explicitly targeting functional impairments and idiosyncratic challenges to optimal therapy outcomes (COTOs), comparing its efficacy against standard CPT in improving psychosocial functioning, quality of life, well-being, and core PTSD and depression symptoms. This randomized controlled trial involves 200 Veterans across eight Veterans Health Administration clinical sites, assigned to either Case Formulation CPT (CF-CPT) or standard CPT. Providers will deliver up to 20 sessions per patient, with assessments at baseline, mid-treatment, post-treatment, and three months follow-up. It is hypothesized that Veterans receiving CF-CPT will show greater improvements in functioning, quality of life, well-being, and symptom reduction, alongside higher treatment completion rates compared to standard CPT. Secondary outcomes will examine specific clinical challenges and their influence on treatment outcomes. This study investigates whether a personalized, flexible CPT protocol can enhance functional recovery in PTSD treatment without compromising the efficacy of the traditional approach, potentially impacting clinical practices and patient outcomes by promoting holistic recovery for veterans with PTSD.
{"title":"Personalizing cognitive processing therapy with a case formulation approach to intentionally target impairment in psychosocial functioning associated with PTSD","authors":"T.E. Galovski , L.B. McSweeney , R.D.V. Nixon , J.S. Wachen , B.N. Smith , S. Noorbaloochi , D. Vogt , B.L. Niles , S.M. Kehle-Forbes","doi":"10.1016/j.conctc.2024.101385","DOIUrl":"10.1016/j.conctc.2024.101385","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD) is a debilitating condition often accompanied by significant functional impairments affecting quality of life and well-being. While Cognitive Processing Therapy (CPT) is a leading, evidence-based psychotherapy for PTSD, demonstrating substantial efficacy in core symptom reduction, its impact on psychosocial functioning is less well-established. The Personalizing Cognitive Processing Therapy with a Case Formulation Approach (Personalizing Approaches to Therapy: PATh) study aims to enhance CPT by explicitly targeting functional impairments and idiosyncratic challenges to optimal therapy outcomes (COTOs), comparing its efficacy against standard CPT in improving psychosocial functioning, quality of life, well-being, and core PTSD and depression symptoms. This randomized controlled trial involves 200 Veterans across eight Veterans Health Administration clinical sites, assigned to either Case Formulation CPT (CF-CPT) or standard CPT. Providers will deliver up to 20 sessions per patient, with assessments at baseline, mid-treatment, post-treatment, and three months follow-up. It is hypothesized that Veterans receiving CF-CPT will show greater improvements in functioning, quality of life, well-being, and symptom reduction, alongside higher treatment completion rates compared to standard CPT. Secondary outcomes will examine specific clinical challenges and their influence on treatment outcomes. This study investigates whether a personalized, flexible CPT protocol can enhance functional recovery in PTSD treatment without compromising the efficacy of the traditional approach, potentially impacting clinical practices and patient outcomes by promoting holistic recovery for veterans with PTSD.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101385"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142652495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-26DOI: 10.1016/j.conctc.2024.101376
Zhi-jian Sun , Cheng-hui Chen , Zhe-lun Tan , Chang-run Li , Han Fei , Xiang Yu , Dong-chen Yao , Ting Li
Background
In the field of orthopedic surgery, tourniquets are often used to achieve a clear operative field, expedite operations, and minimize hemorrhagic events. However, determining the optimal tourniquet inflation pressure is a topic of debate. The current approach involves using a constant tourniquet pressure, although this is associated with the potential to augment the risk of tourniquet-associated complications. The Association of Surgical Technologists recommends a tourniquet pressure of systolic blood pressure plus 50 mm Hg for the upper limb and 100 mm Hg for the lower limb. Nevertheless, this method lacks robust support from high-quality medical literature. Therefore, the study aimed to compare the hemostatic efficacy and disparities in tourniquet pressure settings based on systolic blood pressure versus those using the constant-pressure method. The findings might outline the theoretical framework necessary for advocating for tourniquet pressure setups guided by systolic blood pressure.
Methods/design
This randomized controlled study classified the tourniquet pressure regimen into two groups: one based on the patient's systolic blood pressure (the study group) and the other using a constant pressure (the control group). The study included patients aged between 16 and 70 who presented with fresh fractures (less than 3 weeks) of the lower and upper limbs. All the included patients required surgical treatment involving the intraoperative use of a tourniquet and had no contraindications to this surgery. Our primary outcome was to assess the surgeon's satisfaction with the hemostasis achieved in the operative field. We also examined the changes in the circumference of the limb where the tourniquet was applied and tracked any postoperative complications and their incidence. The study ultimately encompassed 144 patients.
Discussion
Despite the prevalent use of tourniquets in surgical operations related to limb fractures, conflicting viewpoints persist concerning the adjustments in pressure and other elements. The study aimed to compare the hemostatic efficacy and disparities in tourniquet pressure settings based on systolic blood pressure versus those using the constant-pressure method.
Study registration
The study was duly recorded in the Chinese Clinical Trial Registry on May 13, 2022 (Registration number: ChiCTR2200059867).
背景在骨科手术领域，止血带常用来获得清晰的手术视野、加快手术进程并最大限度地减少出血事件。然而，如何确定最佳止血带充气压力一直是个争论不休的话题。目前的方法是使用恒定的止血带压力，但这有可能增加止血带相关并发症的风险。外科技师协会建议上肢使用收缩压加 50 mm Hg 的止血带压力，下肢使用 100 mm Hg 的止血带压力。然而，这种方法缺乏高质量医学文献的有力支持。因此，本研究旨在比较根据收缩压设定止血带压力与使用恒压法设定止血带压力的止血效果和差异。方法/设计这项随机对照研究将止血带压力方案分为两组：一组基于患者的收缩压（研究组），另一组使用恒定压力（对照组）。研究对象包括年龄在 16 岁至 70 岁之间、上下肢有新鲜骨折（不足 3 周）的患者。所有患者都需要进行手术治疗，包括术中使用止血带，并且没有手术禁忌症。我们的主要结果是评估外科医生对术野止血效果的满意度。我们还检查了使用止血带的肢体周长的变化，并跟踪了术后并发症及其发生率。讨论尽管止血带在与四肢骨折相关的外科手术中得到了普遍使用，但关于压力和其他因素的调整仍存在相互矛盾的观点。该研究旨在比较基于收缩压的止血带压力设置与恒压法止血带压力设置的止血效果和差异。研究注册该研究于2022年5月13日在中国临床试验注册中心正式注册（注册号：ChiCTR2200059867）。注册网站https://www.chictr.org.cn/showproj.aspx?proj=162504。
{"title":"Personalized tourniquet pressure versus uniform tourniquet pressure in orthopedic trauma surgery of extremities: A prospective randomized controlled study protocol","authors":"Zhi-jian Sun , Cheng-hui Chen , Zhe-lun Tan , Chang-run Li , Han Fei , Xiang Yu , Dong-chen Yao , Ting Li","doi":"10.1016/j.conctc.2024.101376","DOIUrl":"10.1016/j.conctc.2024.101376","url":null,"abstract":"<div><h3>Background</h3><div>In the field of orthopedic surgery, tourniquets are often used to achieve a clear operative field, expedite operations, and minimize hemorrhagic events. However, determining the optimal tourniquet inflation pressure is a topic of debate. The current approach involves using a constant tourniquet pressure, although this is associated with the potential to augment the risk of tourniquet-associated complications. The Association of Surgical Technologists recommends a tourniquet pressure of systolic blood pressure plus 50 mm Hg for the upper limb and 100 mm Hg for the lower limb. Nevertheless, this method lacks robust support from high-quality medical literature. Therefore, the study aimed to compare the hemostatic efficacy and disparities in tourniquet pressure settings based on systolic blood pressure versus those using the constant-pressure method. The findings might outline the theoretical framework necessary for advocating for tourniquet pressure setups guided by systolic blood pressure.</div></div><div><h3>Methods/design</h3><div>This randomized controlled study classified the tourniquet pressure regimen into two groups: one based on the patient's systolic blood pressure (the study group) and the other using a constant pressure (the control group). The study included patients aged between 16 and 70 who presented with fresh fractures (less than 3 weeks) of the lower and upper limbs. All the included patients required surgical treatment involving the intraoperative use of a tourniquet and had no contraindications to this surgery. Our primary outcome was to assess the surgeon's satisfaction with the hemostasis achieved in the operative field. We also examined the changes in the circumference of the limb where the tourniquet was applied and tracked any postoperative complications and their incidence. The study ultimately encompassed 144 patients.</div></div><div><h3>Discussion</h3><div>Despite the prevalent use of tourniquets in surgical operations related to limb fractures, conflicting viewpoints persist concerning the adjustments in pressure and other elements. The study aimed to compare the hemostatic efficacy and disparities in tourniquet pressure settings based on systolic blood pressure versus those using the constant-pressure method.</div></div><div><h3>Study registration</h3><div>The study was duly recorded in the Chinese Clinical Trial Registry on May 13, 2022 (Registration number: ChiCTR2200059867).</div></div><div><h3>Registration website</h3><div><span><span>https://www.chictr.org.cn/showproj.aspx?proj=162504</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101376"},"PeriodicalIF":1.4,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.conctc.2024.101381
Angela Meade , Elena Frangou , Babak Choodari-Oskooei , James Larkin , Tom Powles , Grant D. Stewart , Laurence Albiges , Axel Bex , Toni K. Choueiri , Ian D. Davis , Tim Eisen , Alison Fielding , Craig Gedye , David J. Harrison , Rick Kaplan , Salena Mulhere , Paul Nathan , Grisma Patel , Jay Patel , Hannah Plant , Mahesh K.B. Parmar
Clinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period.
In this paper we describe how we modified the design of the RAMPART trial (NCT03288532) which was set up to investigate immune checkpoint inhibitor therapy in the adjuvant renal cancer setting. The trial had been initiated when no globally accepted adjuvant strategy after nephrectomy existed. A subsequent change in the standard of care for many patients with early renal cancer meant it was no longer feasible to continue to recruit. We needed to find a way to maximise the contribution that RAMPART participants could make to the evidence base for immune checkpoint inhibitor therapy without introducing bias or detriment to the integrity of the trial results. We describe how we agreed and incorporated all design and timeline changes while remaining blinded to accumulating data within the trial, thus protecting the reliability of the future results. We share details of our design modifications to guide others who may have similar experiences, particularly as more agents and combinations of agents are developed and investigated in similar adjuvant settings.
{"title":"Adapting the design of the ongoing RAMPART trial in response to external evidence: An example for trials which take many years to run and report","authors":"Angela Meade , Elena Frangou , Babak Choodari-Oskooei , James Larkin , Tom Powles , Grant D. Stewart , Laurence Albiges , Axel Bex , Toni K. Choueiri , Ian D. Davis , Tim Eisen , Alison Fielding , Craig Gedye , David J. Harrison , Rick Kaplan , Salena Mulhere , Paul Nathan , Grisma Patel , Jay Patel , Hannah Plant , Mahesh K.B. Parmar","doi":"10.1016/j.conctc.2024.101381","DOIUrl":"10.1016/j.conctc.2024.101381","url":null,"abstract":"<div><div>Clinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period.</div><div>In this paper we describe how we modified the design of the RAMPART trial (<span><span>NCT03288532</span><svg><path></path></svg></span>) which was set up to investigate immune checkpoint inhibitor therapy in the adjuvant renal cancer setting. The trial had been initiated when no globally accepted adjuvant strategy after nephrectomy existed. A subsequent change in the standard of care for many patients with early renal cancer meant it was no longer feasible to continue to recruit. We needed to find a way to maximise the contribution that RAMPART participants could make to the evidence base for immune checkpoint inhibitor therapy without introducing bias or detriment to the integrity of the trial results. We describe how we agreed and incorporated all design and timeline changes while remaining blinded to accumulating data within the trial, thus protecting the reliability of the future results. We share details of our design modifications to guide others who may have similar experiences, particularly as more agents and combinations of agents are developed and investigated in similar adjuvant settings.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101381"},"PeriodicalIF":1.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.conctc.2024.101383
Wenwen Wang , Yaru Huang , Jielai Xia, Ling Wang, Chen Li
Although the risk difference (RD) is the most common and well explored functional form for testing efficacy with dichotomous endpoint, odds ratio (OR) is also suggested and well applied measure for non-inferiority (NI) trials. Since the construction and interpretation of these function forms are quite different, this study aims to provide detailed discussions and comprehensive comparisons on the design and testing approach for RD and OR scales for the fixed and group sequential three-arm NI trials under various of situations. The sample size determinations and testing approaches for assessing NI of a new treatment in three-arm clinical trials for RD and OR scales were reviewed comprehensively. Simulation studies are conducted for hundreds of scenarios with parameter configurations of the response rates, randomized allocations, NI margins and interim analysis. The operating characteristic (OC) of RD and OR scales based on the MLE and RMLE methods were thoroughly investigated. A trial example was designed and analyzed to demonstrate the methodologies. It is found that sample size determination on OR scale gives smaller sample size and robust procedure compared to RD scale in the majority of situations. When evaluating the behaviors of the attained power, the RMLE methods based on OR scale outperforms the MLE method and tend to have more power to reject the null hypothesis especially under the small sample size situations. Compared to the fixed design, the group sequential design has better OC, which provides a comparable power while needing smaller total average sample sizes for all cases. In addition, we suggest a lower significance level with a higher power for the sample size determination in the superiority test stage in the group sequential design, which can significantly reduce the total sample sizes while the number of subjects in the placebo group does not increase much. It can offer some recommendations for the investigators to choose the optimal endpoints and parameter configurations to design a three-arm NI trial under certain situations.
虽然风险差异（RD）是二分终点疗效测试中最常见、最受关注的函数形式，但在非劣效性（NI）试验中，几率比（OR）也是被建议和广泛应用的测量方法。由于这些函数形式的构建和解释有很大不同，本研究旨在详细讨论和全面比较在各种情况下固定和分组顺序三臂非劣效性试验中，RD 和 OR 的设计和测试方法。全面回顾了三臂临床试验中RD量表和OR量表评估新疗法NI的样本量确定和测试方法。通过对反应率、随机分配、净住院率和中期分析的参数配置，对数百种情况进行了模拟研究。深入研究了基于 MLE 和 RMLE 方法的 RD 和 OR 量表的运行特征（OC）。设计并分析了一个试验示例来演示这些方法。结果发现，在大多数情况下，与 RD 量表相比，用 OR 量表确定样本量的样本量更小，程序更稳健。在评估获得功率的行为时，基于 OR 标度的 RMLE 方法优于 MLE 方法，尤其是在样本量较小的情况下，往往具有更强的拒绝零假设的能力。与固定设计相比，分组序列设计具有更好的 OC，在所有情况下都需要较小的总平均样本量，但却能提供相当的功率。此外，我们还建议在分组序列设计中，在优效性检验阶段用较低的显著性水平和较高的功率来确定样本量，这样可以显著减少总样本量，而安慰剂组的受试者人数不会增加太多。这为研究者在特定情况下选择最佳终点和参数配置设计三臂 NI 试验提供了一些建议。
{"title":"Optimization the design of fixed and group sequential three-arm non-inferiority trials with dichotomous endpoints of risk difference and odds ratio","authors":"Wenwen Wang , Yaru Huang , Jielai Xia, Ling Wang, Chen Li","doi":"10.1016/j.conctc.2024.101383","DOIUrl":"10.1016/j.conctc.2024.101383","url":null,"abstract":"<div><div>Although the risk difference (RD) is the most common and well explored functional form for testing efficacy with dichotomous endpoint, odds ratio (OR) is also suggested and well applied measure for non-inferiority (NI) trials. Since the construction and interpretation of these function forms are quite different, this study aims to provide detailed discussions and comprehensive comparisons on the design and testing approach for RD and OR scales for the fixed and group sequential three-arm NI trials under various of situations. The sample size determinations and testing approaches for assessing NI of a new treatment in three-arm clinical trials for RD and OR scales were reviewed comprehensively. Simulation studies are conducted for hundreds of scenarios with parameter configurations of the response rates, randomized allocations, NI margins and interim analysis. The operating characteristic (OC) of RD and OR scales based on the MLE and RMLE methods were thoroughly investigated. A trial example was designed and analyzed to demonstrate the methodologies. It is found that sample size determination on OR scale gives smaller sample size and robust procedure compared to RD scale in the majority of situations. When evaluating the behaviors of the attained power, the RMLE methods based on OR scale outperforms the MLE method and tend to have more power to reject the null hypothesis especially under the small sample size situations. Compared to the fixed design, the group sequential design has better OC, which provides a comparable power while needing smaller total average sample sizes for all cases. In addition, we suggest a lower significance level with a higher power for the sample size determination in the superiority test stage in the group sequential design, which can significantly reduce the total sample sizes while the number of subjects in the placebo group does not increase much. It can offer some recommendations for the investigators to choose the optimal endpoints and parameter configurations to design a three-arm NI trial under certain situations.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101383"},"PeriodicalIF":1.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.conctc.2024.101384
Matthew J. Smith , James L. Merle , Mary Baker-Ericzén , Kari Sherwood , Lindsay A. Bornheimer , Brittany Ross , Meghan Harrington , Apara Sharma , Cheryl Brown , Timotheus (TJ) Gordon . , David Telfer , Jocelyn Reese , Jennifer Hirst , Eugene A. Oulvey , Valerie Dignadice , Ed-Dee Williams , Sandra Magaña , Kara Hume , Connie Sung , Jane K. Burke-Miller , Justin D. Smith
A number of policies mandate that autistic transition-age youth receive employment services to prepare for the workforce before high school graduation. A key limitation to these services is the job interview component, which relies on non-standardized, resource-intensive, staff-led role-plays to help autistic transition-age youth improve their interview skills. The autism community has called for better job interview preparation. To address this gap in services, our team, collaborated with the autism community to adapt the intervention, Virtual Reality Job Interview Training (VR-JIT; effective among adults with serious mental illness), into Virtual Interview Training for Transition Age Youth (VIT-TAY). This adapted intervention was tailored to meet the needs of autistic transition age youth while maintaining the core components of VR-JIT (i.e., an online job interview simulator with four levels of automated feedback and e-learning content). A pilot randomized controlled trial (RCT) demonstrated VIT-TAY's feasibility and initial effectiveness at improving job interview skills, reducing anxiety, and increasing employment rates within six months when added to transition services or pre-employment transition services (Pre-ETS). Thus, the overarching goal of this Hybrid Type 1 effectiveness-implementation study protocol is to conduct a fully-powered RCT of VIT-TAY across 16 schools in various geographical locations. Our specific aims are to 1) Evaluate whether Pre-ETS (or transition services) with VIT-TAY, as compared to Pre-ETS (or transition services) with an active control intervention (i.e., job interview didactics/e-learning with a series of 3–5 min videos of employed autistic adults talking about their career pathways) enhances employment outcomes; 2) Evaluate mechanisms of employment by nine months post-randomization; and 3) Conduct a multilevel, mixed-method process evaluation of the initial implementation of VIT-TAY across settings (e.g., acceptability, feasibility, and barriers and facilitators of implementation).
{"title":"A type 1 hybrid multi-site randomized controlled trial protocol for evaluating virtual interview training among autistic transition-age youth","authors":"Matthew J. Smith , James L. Merle , Mary Baker-Ericzén , Kari Sherwood , Lindsay A. Bornheimer , Brittany Ross , Meghan Harrington , Apara Sharma , Cheryl Brown , Timotheus (TJ) Gordon . , David Telfer , Jocelyn Reese , Jennifer Hirst , Eugene A. Oulvey , Valerie Dignadice , Ed-Dee Williams , Sandra Magaña , Kara Hume , Connie Sung , Jane K. Burke-Miller , Justin D. Smith","doi":"10.1016/j.conctc.2024.101384","DOIUrl":"10.1016/j.conctc.2024.101384","url":null,"abstract":"<div><div>A number of policies mandate that autistic transition-age youth receive employment services to prepare for the workforce before high school graduation. A key limitation to these services is the job interview component, which relies on non-standardized, resource-intensive, staff-led role-plays to help autistic transition-age youth improve their interview skills. The autism community has called for better job interview preparation. To address this gap in services, our team, collaborated with the autism community to adapt the intervention, Virtual Reality Job Interview Training (<em>VR-JIT</em>; effective among adults with serious mental illness), into Virtual Interview Training for Transition Age Youth (<em>VIT-TAY</em>). This adapted intervention was tailored to meet the needs of autistic transition age youth while maintaining the core components of <em>VR-JIT</em> (i.e., an online job interview simulator with four levels of automated feedback and e-learning content). A pilot randomized controlled trial (RCT) demonstrated <em>VIT-TAY</em>'s feasibility and initial effectiveness at improving job interview skills, reducing anxiety, and increasing employment rates within six months when added to transition services or pre-employment transition services (Pre-ETS). Thus, the overarching goal of this Hybrid Type 1 effectiveness-implementation study protocol is to conduct a fully-powered RCT of VIT-TAY across 16 schools in various geographical locations. Our specific aims are to 1) Evaluate whether Pre-ETS (or transition services) with <em>VIT-TAY</em>, as compared to Pre-ETS (or transition services) with an active control intervention (i.e., job interview didactics/e-learning with a series of 3–5 min videos of employed autistic adults talking about their career pathways) enhances employment outcomes; 2) Evaluate mechanisms of employment by nine months post-randomization; and 3) Conduct a multilevel, mixed-method process evaluation of the initial implementation of <em>VIT-TAY</em> across settings (e.g., acceptability, feasibility, and barriers and facilitators of implementation).</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101384"},"PeriodicalIF":1.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.conctc.2024.101380
Steven S. Fu , Patrick Hammett , David Nelson , Andrew Busch , Warren McKinney , Pravesh Sharma , Christi A. Patten , Nathalia Gutierrez Sacasa , Lynn Andreae , Sandra Japuntich
Background
Black, Indigenous, and People of Color (BIPOC) communities experience higher prevalence of cardiovascular disease and related chronic conditions compared to White communities due to disparities in tobacco exposure. Smoking can be effectively treated but evidence-based treatments are less likely to be offered to or used by BIPOC patients. We present the study protocol of the Smoking Cessation Outreach for Racial Equity (SCORE) trial that tests the effect of adding longitudinal care coordination to current standard of care for smoking cessation to promote health equity among BIPOC patients.
Methods
Longitudinal Proactive Outreach (LPO; 4 culturally tailored outreach call cycles over one year by motivational interviewing trained counselors to connect patients to cessation counseling and medication) will be added to the current standard of care, Ask-Advise-Connect (AAC; primary care providers asking all patients if they smoke, and if smoking, advising to quit and connecting to treatment). We will conduct a hybrid type 1 implementation-effectiveness trial to examine the direct effect of AAC + LPO (a multilevel health system intervention) vs. AAC on population-level combustible tobacco abstinence at 18 months and treatment utilization among 2000 BIPOC adults who smoke across two healthcare systems in Minnesota. Participants will be surveyed at 6, 12, and, 18 months post-enrollment to assess outcomes. The primary outcome is biochemically confirmed combustible cigarette abstinence at 18 months.
Discussion
LPO has potential to promote health equity by addressing barriers caused by structural racism, including access to care, care fragmentation, and provider racism, by systematically reaching out to all BIPOC patients who smoke.
{"title":"Evaluating chronic disease approaches to ameliorate tobacco-related health disparities: Study protocol of a hybrid type 1 implementation-effectiveness trial","authors":"Steven S. Fu , Patrick Hammett , David Nelson , Andrew Busch , Warren McKinney , Pravesh Sharma , Christi A. Patten , Nathalia Gutierrez Sacasa , Lynn Andreae , Sandra Japuntich","doi":"10.1016/j.conctc.2024.101380","DOIUrl":"10.1016/j.conctc.2024.101380","url":null,"abstract":"<div><h3>Background</h3><div>Black, Indigenous, and People of Color (BIPOC) communities experience higher prevalence of cardiovascular disease and related chronic conditions compared to White communities due to disparities in tobacco exposure. Smoking can be effectively treated but evidence-based treatments are less likely to be offered to or used by BIPOC patients. We present the study protocol of the Smoking Cessation Outreach for Racial Equity (SCORE) trial that tests the effect of adding longitudinal care coordination to current standard of care for smoking cessation to promote health equity among BIPOC patients.</div></div><div><h3>Methods</h3><div>Longitudinal Proactive Outreach (LPO; 4 culturally tailored outreach call cycles over one year by motivational interviewing trained counselors to connect patients to cessation counseling and medication) will be added to the current standard of care, Ask-Advise-Connect (AAC; primary care providers asking all patients if they smoke, and if smoking, advising to quit and connecting to treatment). We will conduct a hybrid type 1 implementation-effectiveness trial to examine the direct effect of AAC + LPO (a multilevel health system intervention) vs. AAC on population-level combustible tobacco abstinence at 18 months and treatment utilization among 2000 BIPOC adults who smoke across two healthcare systems in Minnesota. Participants will be surveyed at 6, 12, and, 18 months post-enrollment to assess outcomes. The primary outcome is biochemically confirmed combustible cigarette abstinence at 18 months.</div></div><div><h3>Discussion</h3><div>LPO has potential to promote health equity by addressing barriers caused by structural racism, including access to care, care fragmentation, and provider racism, by systematically reaching out to all BIPOC patients who smoke.</div></div><div><h3>Clinicaltrialsgov</h3><div>NCT05671380.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101380"},"PeriodicalIF":1.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1016/j.conctc.2024.101378
Ellen Graham , Sonya L. Heltshe , Amalia S. Magaret
Background:
It has been commonly reported that therapeutic treatments in cystic fibrosis (CF) have ceiling effects, such that their efficacy is diminished for persons with high pre-treatment health (Montgomery et al., 2012 and Newsome et al., 2019). Floor effects have also been reported where decline is of lower magnitude in those with below-average pre-treatment health (Harun et al., 2016; Konstan et al., 2012 and Szczesniak et al., 2017). When measurement error is present, the statistical literature has warned of exaggerated or spurious associations between pre-treatment measures and subsequent change (Chambless and Davis, 2003 and Yanez et al., 1998). Measurement error, equivalently described as day-to-day variation, has been described to occur in CF outcome measurements such as forced expiratory volume in 1 s taken by spirometry (FEVpp) (Magaret et al., 2024; Stanojevic et al., 2020 and Thornton et al., 2023).
Methods:
We conducted a simulation study to assess the potential for spurious floor or ceiling effects in studies of CF therapeutics. We considered uncontrolled or single-arm studies, and evaluated estimated association between pre-treatment FEVpp and treatment-induced change: post-versus pre-treatment.
Results:
When day-to-day variation was present in FEVpp, at levels equivalent to those reported in large studies measuring spirometry both at home and in clinic, naive analytic approaches found spurious associations of change with baseline (Paynter et al., 2022 and Saiman et al., 2003). Type I error ranged from 31.9% to 98.3% for day-to-day variation as high as 3% to 15% relative to biological variation. Incorporating known day-to-day variation, the regression calibration approach corrected bias and controlled type I error (Chambless and Davis, 2003).
Conclusion:
Exaggerated ceiling effects are possible. Further studies could provide meaningful confirmation of ceiling effects in CF, perhaps reducing day-to-day variation by incorporating multiple pre- and post-treatment measurements.
{"title":"Baseline-dependent improvement in CF studies, plausibility of bias","authors":"Ellen Graham , Sonya L. Heltshe , Amalia S. Magaret","doi":"10.1016/j.conctc.2024.101378","DOIUrl":"10.1016/j.conctc.2024.101378","url":null,"abstract":"<div><h3>Background:</h3><div>It has been commonly reported that therapeutic treatments in cystic fibrosis (CF) have ceiling effects, such that their efficacy is diminished for persons with high pre-treatment health (Montgomery et al., 2012 and Newsome et al., 2019). Floor effects have also been reported where decline is of lower magnitude in those with below-average pre-treatment health (Harun et al., 2016; Konstan et al., 2012 and Szczesniak et al., 2017). When measurement error is present, the statistical literature has warned of exaggerated or spurious associations between pre-treatment measures and subsequent change (Chambless and Davis, 2003 and Yanez et al., 1998). Measurement error, equivalently described as day-to-day variation, has been described to occur in CF outcome measurements such as forced expiratory volume in 1 s taken by spirometry (FEV<span><math><msub><mrow></mrow><mrow><mn>1</mn></mrow></msub></math></span>pp) (Magaret et al., 2024; Stanojevic et al., 2020 and Thornton et al., 2023).</div></div><div><h3>Methods:</h3><div>We conducted a simulation study to assess the potential for spurious floor or ceiling effects in studies of CF therapeutics. We considered uncontrolled or single-arm studies, and evaluated estimated association between pre-treatment FEV<span><math><msub><mrow></mrow><mrow><mn>1</mn></mrow></msub></math></span>pp and treatment-induced change: post-versus pre-treatment.</div></div><div><h3>Results:</h3><div>When day-to-day variation was present in FEV<span><math><msub><mrow></mrow><mrow><mn>1</mn></mrow></msub></math></span>pp, at levels equivalent to those reported in large studies measuring spirometry both at home and in clinic, naive analytic approaches found spurious associations of change with baseline (Paynter et al., 2022 and Saiman et al., 2003). Type I error ranged from 31.9% to 98.3% for day-to-day variation as high as 3% to 15% relative to biological variation. Incorporating known day-to-day variation, the regression calibration approach corrected bias and controlled type I error (Chambless and Davis, 2003).</div></div><div><h3>Conclusion:</h3><div>Exaggerated ceiling effects are possible. Further studies could provide meaningful confirmation of ceiling effects in CF, perhaps reducing day-to-day variation by incorporating multiple pre- and post-treatment measurements.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101378"},"PeriodicalIF":1.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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