Maarten J IJzerman1,2,3, Julie A Simpson4, Robert K Mahar5,6,7, Myra B McGuinness4,8, Bibhas Chakraborty9,10,11, John B Carlin4,12. 1. Cancer Health Services Research Unit, University of Melbourne Centre for Cancer Research and Centre for Health Policy, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia. 2. Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia. 3. Peter MacCallum Cancer Centre, Parkville, Victoria, Australia. 4. Biostatistics Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia. 5. Biostatistics Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia. robert.mahar@unimelb.edu.au. 6. Cancer Health Services Research Unit, University of Melbourne Centre for Cancer Research and Centre for Health Policy, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia. robert.mahar@unimelb.edu.au. 7. Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia. robert.mahar@unimelb.edu.au. 8. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. 9. Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore. 10. Department of Statistics and Applied Probability, Faculty of Science, National University of Singapore, Singapore, Singapore. 11. Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA. 12. Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Abstract
BACKGROUND: Dynamic treatment regimens (DTRs) formalise the multi-stage and dynamic decision problems that clinicians often face when treating chronic or progressive medical conditions. Compared to randomised controlled trials, using observational data to optimise DTRs may allow a wider range of treatments to be evaluated at a lower cost. This review aimed to provide an overview of how DTRs are optimised with observational data in practice. METHODS: Using the PubMed database, a scoping review of studies in which DTRs were optimised using observational data was performed in October 2020. Data extracted from eligible articles included target medical condition, source and type of data, statistical methods, and translational relevance of the included studies. RESULTS: From 209 PubMed abstracts, 37 full-text articles were identified, and a further 26 were screened from the reference lists, totalling 63 articles for inclusion in a narrative data synthesis. Observational DTR models are a recent development and their application has been concentrated in a few medical areas, primarily HIV/AIDS (27, 43%), followed by cancer (8, 13%), and diabetes (6, 10%). There was substantial variation in the scope, intent, complexity, and quality between the included studies. Statistical methods that were used included inverse-probability weighting (26, 41%), the parametric G-formula (16, 25%), Q-learning (10, 16%), G-estimation (4, 6%), targeted maximum likelihood/minimum loss-based estimation (4, 6%), regret regression (3, 5%), and other less common approaches (10, 16%). Notably, studies that were primarily intended to address real-world clinical questions (18, 29%) tended to use inverse-probability weighting and the parametric G-formula, relatively well-established methods, along with a large amount of data. Studies focused on methodological developments (45, 71%) tended to be more complicated and included a demonstrative real-world application only. CONCLUSIONS: As chronic and progressive conditions become more common, the need will grow for personalised treatments and methods to estimate the effects of DTRs. Observational DTR studies will be necessary, but so far their use to inform clinical practice has been limited. Focusing on simple DTRs, collecting large and rich clinical datasets, and fostering tight partnerships between content experts and data analysts may result in more clinically relevant observational DTR studies.
BACKGROUND: Dynamic treatment regimens (DTRs) formalise the multi-stage and dynamic decision problems that clinicians often face when treating chronic or progressive medical conditions. Compared to randomised controlled trials, using observational data to optimise DTRs may allow a wider range of treatments to be evaluated at a lower cost. This review aimed to provide an overview of how DTRs are optimised with observational data in practice. METHODS: Using the PubMed database, a scoping review of studies in which DTRs were optimised using observational data was performed in October 2020. Data extracted from eligible articles included target medical condition, source and type of data, statistical methods, and translational relevance of the included studies. RESULTS: From 209 PubMed abstracts, 37 full-text articles were identified, and a further 26 were screened from the reference lists, totalling 63 articles for inclusion in a narrative data synthesis. Observational DTR models are a recent development and their application has been concentrated in a few medical areas, primarily HIV/AIDS (27, 43%), followed by cancer (8, 13%), and diabetes (6, 10%). There was substantial variation in the scope, intent, complexity, and quality between the included studies. Statistical methods that were used included inverse-probability weighting (26, 41%), the parametric G-formula (16, 25%), Q-learning (10, 16%), G-estimation (4, 6%), targeted maximum likelihood/minimum loss-based estimation (4, 6%), regret regression (3, 5%), and other less common approaches (10, 16%). Notably, studies that were primarily intended to address real-world clinical questions (18, 29%) tended to use inverse-probability weighting and the parametric G-formula, relatively well-established methods, along with a large amount of data. Studies focused on methodological developments (45, 71%) tended to be more complicated and included a demonstrative real-world application only. CONCLUSIONS: As chronic and progressive conditions become more common, the need will grow for personalised treatments and methods to estimate the effects of DTRs. Observational DTR studies will be necessary, but so far their use to inform clinical practice has been limited. Focusing on simple DTRs, collecting large and rich clinical datasets, and fostering tight partnerships between content experts and data analysts may result in more clinically relevant observational DTR studies.
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Authors: Andrea C Tricco; Erin Lillie; Wasifa Zarin; Kelly K O'Brien; Heather Colquhoun; Danielle Levac; David Moher; Micah D J Peters; Tanya Horsley; Laura Weeks; Susanne Hempel; Elie A Akl; Christine Chang; Jessie McGowan; Lesley Stewart; Lisa Hartling; Adrian Aldcroft; Michael G Wilson; Chantelle Garritty; Simon Lewin; Christina M Godfrey; Marilyn T Macdonald; Etienne V Langlois; Karla Soares-Weiser; Jo Moriarty; Tammy Clifford; Özge Tunçalp; Sharon E Straus Journal: Ann Intern Med Date: 2018-09-04 Impact factor: 25.391