{"title":"基于基线的 CF 研究改进,偏差的合理性","authors":"","doi":"10.1016/j.conctc.2024.101378","DOIUrl":null,"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":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Baseline-dependent improvement in CF studies, plausibility of bias\",\"authors\":\"\",\"doi\":\"10.1016/j.conctc.2024.101378\",\"DOIUrl\":null,\"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\":null,\"pages\":null},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-10-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Contemporary Clinical Trials Communications\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S245186542400125X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Contemporary Clinical Trials Communications","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S245186542400125X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Baseline-dependent improvement in CF studies, plausibility of bias
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.
期刊介绍:
Contemporary Clinical Trials Communications is an international peer reviewed open access journal that publishes articles pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from a wide range of disciplines including medicine, life science, pharmaceutical science, biostatistics, epidemiology, computer science, management science, behavioral science, and bioethics. Contemporary Clinical Trials Communications is unique in that it is outside the confines of disease specifications, and it strives to increase the transparency of medical research and reduce publication bias by publishing scientifically valid original research findings irrespective of their perceived importance, significance or impact. Both randomized and non-randomized trials are within the scope of the Journal. Some common topics include trial design rationale and methods, operational methodologies and challenges, and positive and negative trial results. In addition to original research, the Journal also welcomes other types of communications including, but are not limited to, methodology reviews, perspectives and discussions. Through timely dissemination of advances in clinical trials, the goal of Contemporary Clinical Trials Communications is to serve as a platform to enhance the communication and collaboration within the global clinical trials community that ultimately advances this field of research for the benefit of patients.