Goodarz Danaei1, Luis Alberto García Rodríguez2, Oscar Fernández Cantero2, Roger W Logan3, Miguel A Hernán4. 1. Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA. Electronic address: gdanaei@hsph.harvard.edu. 2. Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain. 3. Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA. 4. Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
Abstract
OBJECTIVE: To emulate three target trials: single treatment vs. no treatment, joint treatment vs. no treatment, and head-to-head comparison of two treatments, we explain how to estimate the observational analogs of intention-to-treat and per-protocol effects, using hazard ratios and survival curves. For per-protocol effects, we describe two methods for adherence adjustment via inverse-probability weighting. STUDY DESIGN AND SETTING: Prospective observational study using electronic medical records of individuals aged 55-84 with coronary heart disease from >500 practices in the United Kingdom between 2000 and 2010. RESULTS: The intention-to-treat mortality hazard ratio (95% confidence interval) was 0.90 (0.84, 0.97) for statins vs. no treatment, 0.88 (0.73, 1.06) for statins plus antihypertensives vs. no treatment, and 0.91 (0.77, 1.06) for atorvastatin vs. simvastatin. When censoring nonadherent person-times, the per-protocol mortality hazard ratio was 0.74 (0.64, 0.85) for statins vs. no treatment, 0.55 (0.35, 0.87) for statins plus antihypertensives vs. no treatment, and 1.13 (0.88, 1.45) for atorvastatin vs. simvastatin. We estimated per-protocol hazard ratios for a 5-year treatment using different dose-response marginal structural models and standardized survival curves for each target trial using intention-to-treat and per-protocol analyses. CONCLUSION: When randomized trials are not available or feasible, observational analyses can emulate a variety of target trials.
OBJECTIVE: To emulate three target trials: single treatment vs. no treatment, joint treatment vs. no treatment, and head-to-head comparison of two treatments, we explain how to estimate the observational analogs of intention-to-treat and per-protocol effects, using hazard ratios and survival curves. For per-protocol effects, we describe two methods for adherence adjustment via inverse-probability weighting. STUDY DESIGN AND SETTING: Prospective observational study using electronic medical records of individuals aged 55-84 with coronary heart disease from >500 practices in the United Kingdom between 2000 and 2010. RESULTS: The intention-to-treat mortality hazard ratio (95% confidence interval) was 0.90 (0.84, 0.97) for statins vs. no treatment, 0.88 (0.73, 1.06) for statins plus antihypertensives vs. no treatment, and 0.91 (0.77, 1.06) for atorvastatin vs. simvastatin. When censoring nonadherent person-times, the per-protocol mortality hazard ratio was 0.74 (0.64, 0.85) for statins vs. no treatment, 0.55 (0.35, 0.87) for statins plus antihypertensives vs. no treatment, and 1.13 (0.88, 1.45) for atorvastatin vs. simvastatin. We estimated per-protocol hazard ratios for a 5-year treatment using different dose-response marginal structural models and standardized survival curves for each target trial using intention-to-treat and per-protocol analyses. CONCLUSION: When randomized trials are not available or feasible, observational analyses can emulate a variety of target trials.
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