Emily M Damone, Jiawen Zhu, Herbert Pang, Xiao Li, Yinqi Zhao, Evan Kwiatkowski, Lisa A Carey, Joseph G Ibrahim
{"title":"在随机临床试验设计中纳入外部控制:实体瘤案例研究。","authors":"Emily M Damone, Jiawen Zhu, Herbert Pang, Xiao Li, Yinqi Zhao, Evan Kwiatkowski, Lisa A Carey, Joseph G Ibrahim","doi":"10.1186/s12874-024-02383-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The use of historical external control data in clinical trials has grown in interest and needs when considering the design of future trials. Hybrid control designs can be more efficient to achieve the same power with fewer patients and limited resources. The literature is sparse on appropriate statistical methods which can account for the differences between historical external controls and the control patients in a study. In this article, we illustrate the analysis framework of a clinical trial if a hybrid control design was used after determining an RCT may not be feasible.</p><p><strong>Methods: </strong>We utilize two previously completed RCTs in nonsquamous NSCLC and a nationwide electronic health record derived de-identified database as examples and compare 5 analysis methods on each trial, as well as a set of simulations to determine operating characteristics of such designs.</p><p><strong>Results: </strong>In single trial estimation, the Case Weighted Adaptive Power Prior provided estimated treatment hazard ratios consistent with the original trial's conclusions with narrower confidence intervals. The simulation studies showed that the Case Weighted Adaptive Power Prior achieved the highest power (and well controlled type-1 error) across all 5 methods with consistent study sample size.</p><p><strong>Conclusions: </strong>By following the proposed hybrid control framework, one can design a hybrid control trial transparently and accounting for differences between control groups while controlling type-1 error and still achieving efficiency gains from the additional contribution from external controls.</p>","PeriodicalId":9114,"journal":{"name":"BMC Medical Research Methodology","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529009/pdf/","citationCount":"0","resultStr":"{\"title\":\"Incorporating external controls in the design of randomized clinical trials: a case study in solid tumors.\",\"authors\":\"Emily M Damone, Jiawen Zhu, Herbert Pang, Xiao Li, Yinqi Zhao, Evan Kwiatkowski, Lisa A Carey, Joseph G Ibrahim\",\"doi\":\"10.1186/s12874-024-02383-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The use of historical external control data in clinical trials has grown in interest and needs when considering the design of future trials. Hybrid control designs can be more efficient to achieve the same power with fewer patients and limited resources. The literature is sparse on appropriate statistical methods which can account for the differences between historical external controls and the control patients in a study. In this article, we illustrate the analysis framework of a clinical trial if a hybrid control design was used after determining an RCT may not be feasible.</p><p><strong>Methods: </strong>We utilize two previously completed RCTs in nonsquamous NSCLC and a nationwide electronic health record derived de-identified database as examples and compare 5 analysis methods on each trial, as well as a set of simulations to determine operating characteristics of such designs.</p><p><strong>Results: </strong>In single trial estimation, the Case Weighted Adaptive Power Prior provided estimated treatment hazard ratios consistent with the original trial's conclusions with narrower confidence intervals. The simulation studies showed that the Case Weighted Adaptive Power Prior achieved the highest power (and well controlled type-1 error) across all 5 methods with consistent study sample size.</p><p><strong>Conclusions: </strong>By following the proposed hybrid control framework, one can design a hybrid control trial transparently and accounting for differences between control groups while controlling type-1 error and still achieving efficiency gains from the additional contribution from external controls.</p>\",\"PeriodicalId\":9114,\"journal\":{\"name\":\"BMC Medical Research Methodology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529009/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Medical Research Methodology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12874-024-02383-3\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEALTH CARE SCIENCES & SERVICES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Medical Research Methodology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12874-024-02383-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEALTH CARE SCIENCES & SERVICES","Score":null,"Total":0}
Incorporating external controls in the design of randomized clinical trials: a case study in solid tumors.
Background: The use of historical external control data in clinical trials has grown in interest and needs when considering the design of future trials. Hybrid control designs can be more efficient to achieve the same power with fewer patients and limited resources. The literature is sparse on appropriate statistical methods which can account for the differences between historical external controls and the control patients in a study. In this article, we illustrate the analysis framework of a clinical trial if a hybrid control design was used after determining an RCT may not be feasible.
Methods: We utilize two previously completed RCTs in nonsquamous NSCLC and a nationwide electronic health record derived de-identified database as examples and compare 5 analysis methods on each trial, as well as a set of simulations to determine operating characteristics of such designs.
Results: In single trial estimation, the Case Weighted Adaptive Power Prior provided estimated treatment hazard ratios consistent with the original trial's conclusions with narrower confidence intervals. The simulation studies showed that the Case Weighted Adaptive Power Prior achieved the highest power (and well controlled type-1 error) across all 5 methods with consistent study sample size.
Conclusions: By following the proposed hybrid control framework, one can design a hybrid control trial transparently and accounting for differences between control groups while controlling type-1 error and still achieving efficiency gains from the additional contribution from external controls.
期刊介绍:
BMC Medical Research Methodology is an open access journal publishing original peer-reviewed research articles in methodological approaches to healthcare research. Articles on the methodology of epidemiological research, clinical trials and meta-analysis/systematic review are particularly encouraged, as are empirical studies of the associations between choice of methodology and study outcomes. BMC Medical Research Methodology does not aim to publish articles describing scientific methods or techniques: these should be directed to the BMC journal covering the relevant biomedical subject area.