Jose G Monzon1, Annette E Hay2, Gail T McDonald2, Joseph L Pater2, Ralph M Meyer3, Eric Chen4, Bingshu E Chen2, Janet E Dancey2. 1. Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, Canada. Electronic address: jose.monzon@albertahealthservices.ca. 2. NCIC Clinical Trials Group, Queen's University, Kingston, Canada. 3. Department of Oncology, Juravinski Hospital and Cancer Centre and McMaster University, 711 Concession St., Hamilton, Ontario L8V 1C3, Canada. 4. Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
Abstract
BACKGROUND AND AIM: The primary aim of this study was to determine whether randomised phase 2 (RP2) trials predict phase 3 trial outcome better than single arm phase 2 (SAP2) studies. Although theoretical superiority of RP2 trials has been postulated, no empiric studies have been conducted. METHODS: Published phase 3 trials testing systemic cancer therapy were identified through a Medline search. Those of superiority design, which cited phase 2 trials supporting the experimental arm, were included. Trial design and outcome details were extracted. Statistical analysis was performed using the Generalized Estimating Equation method correlating phase 2 features with phase 3 outcome, accounting for any phase 3 duplication. RESULTS: Of 189 eligible phase 3 trials, 18.5% were in haematological malignancies and 81.5% in solid tumors. The primary outcome was positive in 79 (41.8%). These were supported by 336 phase 2 trials (range 1-9 per phase 3 trial) including 66 RP2 trials. Positive phase 2 outcome, randomised or not, correlated with positive phase 3 outcome (p=0.03). RP2 studies were not superior to SAP2 studies at predicting phase 3 study success. Phase 2 trial features not predictive of phase 3 outcome included primary endpoint, sponsorship, sample size, similarity in patient population and therapy. CONCLUSIONS: RP2 studies were not superior to SAP2 trials at predicting phase 3 study success. Further research into phase 2 trial design is required given the added resources required to conduct RP2 studies and the lack of empiric evidence supporting superiority over single arm studies.
BACKGROUND AND AIM: The primary aim of this study was to determine whether randomised phase 2 (RP2) trials predict phase 3 trial outcome better than single arm phase 2 (SAP2) studies. Although theoretical superiority of RP2 trials has been postulated, no empiric studies have been conducted. METHODS: Published phase 3 trials testing systemic cancer therapy were identified through a Medline search. Those of superiority design, which cited phase 2 trials supporting the experimental arm, were included. Trial design and outcome details were extracted. Statistical analysis was performed using the Generalized Estimating Equation method correlating phase 2 features with phase 3 outcome, accounting for any phase 3 duplication. RESULTS: Of 189 eligible phase 3 trials, 18.5% were in haematological malignancies and 81.5% in solid tumors. The primary outcome was positive in 79 (41.8%). These were supported by 336 phase 2 trials (range 1-9 per phase 3 trial) including 66 RP2 trials. Positive phase 2 outcome, randomised or not, correlated with positive phase 3 outcome (p=0.03). RP2 studies were not superior to SAP2 studies at predicting phase 3 study success. Phase 2 trial features not predictive of phase 3 outcome included primary endpoint, sponsorship, sample size, similarity in patient population and therapy. CONCLUSIONS: RP2 studies were not superior to SAP2 trials at predicting phase 3 study success. Further research into phase 2 trial design is required given the added resources required to conduct RP2 studies and the lack of empiric evidence supporting superiority over single arm studies.
Authors: Ali A Mokdad; Hao Zhu; Muhammad S Beg; Yull Arriaga; Jonathan E Dowell; Amit G Singal; Adam C Yopp Journal: Target Oncol Date: 2019-10 Impact factor: 4.493
Authors: Miguel Sampayo-Cordero; Bernat Miguel-Huguet; Almudena Pardo-Mateos; Andrea Malfettone; José Pérez-García; Antonio Llombart-Cussac; Javier Cortés; Marc Moltó-Abad; Cecilia Muñoz-Delgado; Marta Pérez-Quintana; Jordi Pérez-López Journal: Orphanet J Rare Dis Date: 2019-10-21 Impact factor: 4.123
Authors: Miguel Sampayo-Cordero; Bernat Miguel-Huguet; José Pérez-García; David Páez; Ángel L Guerrero-Zotano; Javier Garde-Noguera; Elena Aguirre; Esther Holgado; Elena López-Miranda; Xin Huang; Andrea Malfettone; Antonio Llombart-Cussac; Javier Cortés Journal: Contemp Clin Trials Commun Date: 2020-11-28