TY - JOUR
T1 - Externally Controlled Studies Using Real-World Data in Patients with Hematological Cancers
T2 - A Systematic Review
AU - Hermans, Sjoerd J.F.
AU - Van Der Maas, Niek G.
AU - Van Norden, Yvette
AU - Dinmohamed, Avinash G.
AU - Berkx, Elizabeth
AU - Huijgens, Peter C.
AU - Rivera, Donna R.
AU - De Claro, R. Angelo
AU - Pignatti, Francesco
AU - Versluis, Jurjen
AU - Cornelissen, Jan J.
N1 - Publisher Copyright:
© 2024 American Medical Association. All rights reserved.
PY - 2024/8/29
Y1 - 2024/8/29
N2 - Importance: The use of real-world data (RWD) external control arms in prospective studies is increasing. The advantages, including the immediate availability of a control population, must be balanced with the requirements of meeting evidentiary standards. Objective: To address the question of whether and to what extent the methods of RWD studies compare to standard methods used in randomized clinical trials. Evidence Review: A systematic search across 4 electronic databases and Google Scholar was conducted from January 1, 2000, to October 23, 2023. Studies were included in the systematic review if they compared an intervention arm in a clinical trial to an RWD control arm in patients with hematological cancers and if they were published between 2000 and 2023. Findings: Thirty-two prospective intervention studies incorporating external control data from RWD sources of patients with hematological cancers were identified. A total of 4306 patients from intervention arms and 10594 from RWD control arms were included across all studies. Only 2 studies (6%) included prospectively collected RWD. The complete trial inclusion criteria were applied to the RWD cohort in 7 studies (22%). Four studies (13%) published the statistical analysis plan and prespecified use of RWD. A total of 23 studies (72%) applied matching algorithms for trial and RWD cohorts, including matching for demographic, disease, and/or therapy-related characteristics. The end point criteria were the same as the trial in 8 studies (25%). In contrast, 12 studies (38%) used different end points, and 12 (38%) did not provide an end point definition for the RWD. Twelve studies (38%) had a median follow-up difference of less than a year between arms. Eight studies (25%) reported toxic effect data for the trial arm, of which 5 studies reported toxic effect data for the RWD arm. Conclusions and Relevance: In this systematic review, limitations were observed in the application of clinical trial eligibility criteria to RWD, statistical rigor and application of matching methods, the definition of end points, follow-up, and reporting of adverse events, which may challenge the conclusions reported in studies using RWD.
AB - Importance: The use of real-world data (RWD) external control arms in prospective studies is increasing. The advantages, including the immediate availability of a control population, must be balanced with the requirements of meeting evidentiary standards. Objective: To address the question of whether and to what extent the methods of RWD studies compare to standard methods used in randomized clinical trials. Evidence Review: A systematic search across 4 electronic databases and Google Scholar was conducted from January 1, 2000, to October 23, 2023. Studies were included in the systematic review if they compared an intervention arm in a clinical trial to an RWD control arm in patients with hematological cancers and if they were published between 2000 and 2023. Findings: Thirty-two prospective intervention studies incorporating external control data from RWD sources of patients with hematological cancers were identified. A total of 4306 patients from intervention arms and 10594 from RWD control arms were included across all studies. Only 2 studies (6%) included prospectively collected RWD. The complete trial inclusion criteria were applied to the RWD cohort in 7 studies (22%). Four studies (13%) published the statistical analysis plan and prespecified use of RWD. A total of 23 studies (72%) applied matching algorithms for trial and RWD cohorts, including matching for demographic, disease, and/or therapy-related characteristics. The end point criteria were the same as the trial in 8 studies (25%). In contrast, 12 studies (38%) used different end points, and 12 (38%) did not provide an end point definition for the RWD. Twelve studies (38%) had a median follow-up difference of less than a year between arms. Eight studies (25%) reported toxic effect data for the trial arm, of which 5 studies reported toxic effect data for the RWD arm. Conclusions and Relevance: In this systematic review, limitations were observed in the application of clinical trial eligibility criteria to RWD, statistical rigor and application of matching methods, the definition of end points, follow-up, and reporting of adverse events, which may challenge the conclusions reported in studies using RWD.
UR - http://www.scopus.com/inward/record.url?scp=85203182200&partnerID=8YFLogxK
U2 - 10.1001/jamaoncol.2024.3466
DO - 10.1001/jamaoncol.2024.3466
M3 - Review article
C2 - 39207765
AN - SCOPUS:85203182200
SN - 2374-2437
VL - 10
SP - 1426
EP - 1436
JO - JAMA Oncology
JF - JAMA Oncology
IS - 10
ER -