Contemporary Clinical Trials Communications最新文献

{"title":"A protocol for modifying progesterone to increase postpartum cigarette smoking abstinence and reduce secondhand smoke exposure in infants","authors":"Nermine Abdelwahab ,&nbsp;Alicia Allen ,&nbsp;Katherine Harrison ,&nbsp;Ashley Petersen ,&nbsp;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}

{"title":"An automated platform trial framework for A/B testing","authors":"Wenru Zhou ,&nbsp;Miranda Kroehl ,&nbsp;Maxene Meier ,&nbsp;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}

{"title":"Personalizing cognitive processing therapy with a case formulation approach to intentionally target impairment in psychosocial functioning associated with PTSD","authors":"T.E. Galovski ,&nbsp;L.B. McSweeney ,&nbsp;R.D.V. Nixon ,&nbsp;J.S. Wachen ,&nbsp;B.N. Smith ,&nbsp;S. Noorbaloochi ,&nbsp;D. Vogt ,&nbsp;B.L. Niles ,&nbsp;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}

{"title":"Personalized tourniquet pressure versus uniform tourniquet pressure in orthopedic trauma surgery of extremities: A prospective randomized controlled study protocol","authors":"Zhi-jian Sun ,&nbsp;Cheng-hui Chen ,&nbsp;Zhe-lun Tan ,&nbsp;Chang-run Li ,&nbsp;Han Fei ,&nbsp;Xiang Yu ,&nbsp;Dong-chen Yao ,&nbsp;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}

{"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 ,&nbsp;Elena Frangou ,&nbsp;Babak Choodari-Oskooei ,&nbsp;James Larkin ,&nbsp;Tom Powles ,&nbsp;Grant D. Stewart ,&nbsp;Laurence Albiges ,&nbsp;Axel Bex ,&nbsp;Toni K. Choueiri ,&nbsp;Ian D. Davis ,&nbsp;Tim Eisen ,&nbsp;Alison Fielding ,&nbsp;Craig Gedye ,&nbsp;David J. Harrison ,&nbsp;Rick Kaplan ,&nbsp;Salena Mulhere ,&nbsp;Paul Nathan ,&nbsp;Grisma Patel ,&nbsp;Jay Patel ,&nbsp;Hannah Plant ,&nbsp;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}

{"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 ,&nbsp;Yaru Huang ,&nbsp;Jielai Xia,&nbsp;Ling Wang,&nbsp;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}

{"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 ,&nbsp;James L. Merle ,&nbsp;Mary Baker-Ericzén ,&nbsp;Kari Sherwood ,&nbsp;Lindsay A. Bornheimer ,&nbsp;Brittany Ross ,&nbsp;Meghan Harrington ,&nbsp;Apara Sharma ,&nbsp;Cheryl Brown ,&nbsp;Timotheus (TJ) Gordon . ,&nbsp;David Telfer ,&nbsp;Jocelyn Reese ,&nbsp;Jennifer Hirst ,&nbsp;Eugene A. Oulvey ,&nbsp;Valerie Dignadice ,&nbsp;Ed-Dee Williams ,&nbsp;Sandra Magaña ,&nbsp;Kara Hume ,&nbsp;Connie Sung ,&nbsp;Jane K. Burke-Miller ,&nbsp;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}

{"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 ,&nbsp;Patrick Hammett ,&nbsp;David Nelson ,&nbsp;Andrew Busch ,&nbsp;Warren McKinney ,&nbsp;Pravesh Sharma ,&nbsp;Christi A. Patten ,&nbsp;Nathalia Gutierrez Sacasa ,&nbsp;Lynn Andreae ,&nbsp;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}

{"title":"Run-in periods and treatment outcomes in asthma trials: A narrative review","authors":"Emilio Pizzichini ,&nbsp;Guy Brusselle ,&nbsp;Dawn Edwards ,&nbsp;Peter G. Gibson ,&nbsp;Huib A. Kerstjens ,&nbsp;Alison Moore ,&nbsp;David Slade ,&nbsp;Robert A. Wise ,&nbsp;Shiyuan Zhang","doi":"10.1016/j.conctc.2024.101382","DOIUrl":"10.1016/j.conctc.2024.101382","url":null,"abstract":"<div><h3>Background</h3><div>The run-in period is an important element of randomized controlled trials, and is often used in respiratory disease trials. The design of the run-in period can greatly impact results and data interpretation, and as such should be designed carefully.</div></div><div><h3>Methods</h3><div>In this review, we describe the design of run-in periods across six phase 3A trials of triple therapy in asthma, and discuss how differences in run-in period design (specifically the duration, treatment, and reporting of run-in results) may have the potential to alter the interpretation of study outcomes.</div></div><div><h3>Results</h3><div>We found that the duration of run-in periods ranged between 2 and 7 weeks, with some studies including a combination of screening, run-in and stabilization periods, and others including a run-in period only. Run-in treatment also varied, with some studies running in patients on their previous inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) therapy, and others harmonizing treatment by switching to the same ICS/LABA combination used in the on-treatment phase, or a different ICS/LABA combination entirely. Most of the studies included did not report any changes to study outcomes seen prior to randomization.</div></div><div><h3>Conclusion</h3><div>We discuss the potential implications associated with the various trial designs, and propose that run-in periods should be consciously designed to meet the goals of the specific study. We also propose that standardized reporting of run-in changes would further allow for differentiation between improvements due to improved adherence and true treatment benefits, and aid with comparing data from different clinical trials.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"Article 101382"},"PeriodicalIF":1.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702693","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}

{"title":"Baseline-dependent improvement in CF studies, plausibility of bias","authors":"Ellen Graham ,&nbsp;Sonya L. Heltshe ,&nbsp;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}