Katrina Mott1,2, David J Graham1, Sengwee Toh3, Joshua J Gagne4, Mark Levenson5, Yong Ma5, Marsha E Reichman1. 1. CDER Office of Surveillance and Epidemiology, U.S. Food and Drug Administration, Silver Spring, MD, USA. 2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 3. Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA. 4. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. 5. CDER Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Abstract
PURPOSE: Several factors limit the statistical power of drug safety surveillance during the early post-approval period, including uptake of the drug and lag in data availability. This study characterized new drug uptake in the Mini-Sentinel Distributed Database and determined statistical power to detect levels of risk in post-launch safety assessments. METHODS: The cumulative exposure among initiators of 46 new molecular entities approved from 2008 to 2011 was assessed. Using a Poisson estimation method, minimum incidence rate ratios (IRRs) detectable, with 80% power, were calculated under varying background incidence rates. RESULTS: Twelve products (26.1%) had more than 15 000 new users after 2 years. With comparator group incidence rate of 1/1000 person-years, 16 (33.3%) products had enough exposure to detect an IRR of 5 with 24 months of data collected that would be available for assessment at 33 months post-launch. With an incidence rate of 5/1000 person-years, 23 (50%) products had enough exposure to detect an IRR of ≥3 with 2 years of data collected. At 33 months post-launch, only two (4.3%) of the drugs examined had enough data availability to detect IRR of <2, and eight (17.4%) of <3, with a background rate of 1/1000 person-years. CONCLUSION: This study highlights the importance of drug uptake and data availability in early post-approval drug safety surveillance in Mini-Sentinel. There is limited ability to detect rate ratios below three for events with background rates of 1/1000 person-years or lower. This is largely due to low product uptake.
PURPOSE: Several factors limit the statistical power of drug safety surveillance during the early post-approval period, including uptake of the drug and lag in data availability. This study characterized new drug uptake in the Mini-Sentinel Distributed Database and determined statistical power to detect levels of risk in post-launch safety assessments. METHODS: The cumulative exposure among initiators of 46 new molecular entities approved from 2008 to 2011 was assessed. Using a Poisson estimation method, minimum incidence rate ratios (IRRs) detectable, with 80% power, were calculated under varying background incidence rates. RESULTS: Twelve products (26.1%) had more than 15 000 new users after 2 years. With comparator group incidence rate of 1/1000 person-years, 16 (33.3%) products had enough exposure to detect an IRR of 5 with 24 months of data collected that would be available for assessment at 33 months post-launch. With an incidence rate of 5/1000 person-years, 23 (50%) products had enough exposure to detect an IRR of ≥3 with 2 years of data collected. At 33 months post-launch, only two (4.3%) of the drugs examined had enough data availability to detect IRR of <2, and eight (17.4%) of <3, with a background rate of 1/1000 person-years. CONCLUSION: This study highlights the importance of drug uptake and data availability in early post-approval drug safety surveillance in Mini-Sentinel. There is limited ability to detect rate ratios below three for events with background rates of 1/1000 person-years or lower. This is largely due to low product uptake.
Authors: Krista F Huybrechts; Rishi J Desai; Moa Park; Joshua J Gagne; Mehdi Najafzadeh; Jerry Avorn Journal: Med Care Date: 2017-06 Impact factor: 2.983
Authors: Jonathan Bates; Craig S Parzynski; Sanket S Dhruva; Andreas Coppi; Richard Kuntz; Shu-Xia Li; Danica Marinac-Dabic; Frederick A Masoudi; Richard E Shaw; Frederick Warner; Harlan M Krumholz; Joseph S Ross Journal: Pharmacoepidemiol Drug Saf Date: 2018-06-12 Impact factor: 2.890
Authors: Nicholas S Downing; Nilay D Shah; Jenerius A Aminawung; Alison M Pease; Jean-David Zeitoun; Harlan M Krumholz; Joseph S Ross Journal: JAMA Date: 2017-05-09 Impact factor: 56.272