Rebecca A Miksad1, Mithat Gönen, Thomas J Lynch, Thomas G Roberts. 1. Department of Medicine, Division of Hematology and Oncology, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA 02215, USA. rmiksad@bidmc.harvard.edu
Abstract
PURPOSE: When successive randomized trials contradict prior evidence, clinicians may be unsure how to evaluate them: Does accumulating evidence warrant changing practice? An increasingly popular solution, Bayesian statistics quantitatively evaluate new results in context. This study provides a clinically relevant example of Bayesian methods. METHODS: Three recent non-small-cell lung cancer adjuvant chemotherapy trials were evaluated in light of prior conflicting data. Results were used from International Adjuvant Lung Trial (IALT), JBR.10, and Adjuvant Navelbine International Trialist Association (ANITA). Prior evidence was sequentially updated to calculate the probability of each survival benefit level (overall and by stage) and variance. Sensitivity analysis was performed using expert opinion and uninformed estimates of survival benefit prior probability. RESULTS: The probability of a 4% survival benefit increased from 33% before IALT to 64% after IALT. After sequential updating with JBR.10 and ANITA, this probability was 82% (hazard ratio = 0.84; 95% CI, 0.77 to 0.91). IALT produced the largest decrease in variance (61%) and decreased the chance of survival decrement to 0%. Sensitivity analysis did not support a survival benefit after IALT. However, sequential updating substantiated a 4% survival benefit and, for stage II and III, more than 90% probability of a 6% benefit and 50% probability of a 12% benefit. CONCLUSION: When evaluated in context with prior data, IALT did not support a 4% survival benefit. However, sequential updating with JBR.10 and ANITA did. A model for future assessments, this study demonstrates the unique ability of Bayesian analysis to evaluate results that contradict prior evidence.
PURPOSE: When successive randomized trials contradict prior evidence, clinicians may be unsure how to evaluate them: Does accumulating evidence warrant changing practice? An increasingly popular solution, Bayesian statistics quantitatively evaluate new results in context. This study provides a clinically relevant example of Bayesian methods. METHODS: Three recent non-small-cell lung cancer adjuvant chemotherapy trials were evaluated in light of prior conflicting data. Results were used from International Adjuvant Lung Trial (IALT), JBR.10, and Adjuvant Navelbine International Trialist Association (ANITA). Prior evidence was sequentially updated to calculate the probability of each survival benefit level (overall and by stage) and variance. Sensitivity analysis was performed using expert opinion and uninformed estimates of survival benefit prior probability. RESULTS: The probability of a 4% survival benefit increased from 33% before IALT to 64% after IALT. After sequential updating with JBR.10 and ANITA, this probability was 82% (hazard ratio = 0.84; 95% CI, 0.77 to 0.91). IALT produced the largest decrease in variance (61%) and decreased the chance of survival decrement to 0%. Sensitivity analysis did not support a survival benefit after IALT. However, sequential updating substantiated a 4% survival benefit and, for stage II and III, more than 90% probability of a 6% benefit and 50% probability of a 12% benefit. CONCLUSION: When evaluated in context with prior data, IALT did not support a 4% survival benefit. However, sequential updating with JBR.10 and ANITA did. A model for future assessments, this study demonstrates the unique ability of Bayesian analysis to evaluate results that contradict prior evidence.
Authors: Pamela M McMahon; Alan M Zaslavsky; Milton C Weinstein; Karen M Kuntz; Jane C Weeks; G Scott Gazelle Journal: Med Decis Making Date: 2006 Sep-Oct Impact factor: 2.583
Authors: Donald A Berry; Lurdes Inoue; Yu Shen; John Venier; Debbie Cohen; Melissa Bondy; Richard Theriault; Mark F Munsell Journal: J Natl Cancer Inst Monogr Date: 2006
Authors: Laura Bojke; Marta Soares; Karl Claxton; Abigail Colson; Aimée Fox; Christopher Jackson; Dina Jankovic; Alec Morton; Linda Sharples; Andrea Taylor Journal: Health Technol Assess Date: 2021-06 Impact factor: 4.014
Authors: Edward J Mills; Nick Bansback; Isabella Ghement; Kristian Thorlund; Steven Kelly; Milo A Puhan; James Wright Journal: Clin Epidemiol Date: 2011-05-27 Impact factor: 4.790
Authors: Maria Bonomi; Sara Pilotto; Michele Milella; Francesco Massari; Sara Cingarlini; Matteo Brunelli; Marco Chilosi; Giampaolo Tortora; Emilio Bria Journal: J Exp Clin Cancer Res Date: 2011-12-29