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Avoidable flaws in observational analyses: an application to statins and cancer

Dickerman, BA; Garcia-Albeniz, X; Logan, RW; Denaxas, S; Hernan, MA; (2019) Avoidable flaws in observational analyses: an application to statins and cancer. Nature Medicine , 25 (10) pp. 1601-1605. 10.1038/s41591-019-0597-x. Green open access

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Abstract

The increasing availability of large healthcare databases is fueling an intense debate on whether real-world data should play a role in the assessment of the benefit–risk of medical treatments. In many observational studies, for example, statin users were found to have a substantially lower risk of cancer than in meta-analyses of randomized trials. Although such discrepancies are often attributed to a lack of randomization in the observational studies, they might be explained by flaws that can be avoided by explicitly emulating a target trial (the randomized trial that would answer the question of interest). Using the electronic health records of 733,804 UK adults, we emulated a target trial of statins and cancer and compared our estimates with those obtained using previously applied analytic approaches. Over the 10-yr follow-up, 28,408 individuals developed cancer. Under the target trial approach, estimated observational analogs of intention-to-treat and per-protocol 10-yr cancer-free survival differences were −0.5% (95% confidence interval (CI) −1.0%, 0.0%) and −0.3% (95% CI −1.5%, 0.5%), respectively. By contrast, previous analytic approaches yielded estimates that appeared to be strongly protective. Our findings highlight the importance of explicitly emulating a target trial to reduce bias in the effect estimates derived from observational analyses.

Type: Article
Title: Avoidable flaws in observational analyses: an application to statins and cancer
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41591-019-0597-x
Publisher version: https://doi.org/10.1038/s41591-019-0597-x
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Medicine, Research & Experimental, Research & Experimental Medicine, PROSTATE-CANCER, COLORECTAL-CANCER, RANDOMIZED EXPERIMENTS, TARGET TRIAL, REAL-WORLD, RISK, METAANALYSIS, VALIDATION, PROGESTIN, ESTROGEN
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10084474
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