gms | German Medical Science

Brücken bauen – von der Evidenz zum Patientenwohl: 19. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin e. V.

Deutsches Netzwerk Evidenzbasierte Medizin e. V.

08.03. - 10.03.2018, Graz

Guidance for a Causal Comparative Effectiveness Analysis Using “Big” Real World Data: the Case of When to Start Statin Treatment

Meeting Abstract

  • author presenting/speaker Felicitas Kühne - Department of Public Health, Health Services Research and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
  • author Beate Jahn - Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
  • author Annette Conrads-Frank - Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
  • author Christoph Urach - DEXHELPP, Vienna, Austria
  • author Niki Popper - dwh GmbH, simulation services / Technical University, Institute for Analysis and Scientific Computing, Vienna, Austria
  • author Uwe Siebert - Department of Public Health, Health Services Research and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria; Division of Health Technology Assessment and Bioinformatics, ONCOTYROL - Center for Personalized Cancer Medicine, Innsbruck, Austria; Center for Health Decision Science, Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Brücken bauen – von der Evidenz zum Patientenwohl. 19. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin. Graz, Österreich, 08.-10.03.2018. Düsseldorf: German Medical Science GMS Publishing House; 2018. Doc18ebmP3-11

doi: 10.3205/18ebm093, urn:nbn:de:0183-18ebm0931

Published: March 6, 2018

© 2018 Kühne et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Purpose: Within DEXHELPP, a large FFG-funded project on decision support tools for health-policy planning, causal relations are estimated from routine data as source to gain information outside the artificial setting of clinical trials. Common challenges occurring with real world evidence (RWE) are confounding, missing/misclassified data, no explicit treatment assignment, multiple dynamic treatment regimens, and switching. Graphical, structural and statistical techniques exist to estimate causal relations using RWE. The aim of this project is to describe a causal (counterfactual) approach for analyzing such datasets using the case of when to start statin treatment to prevent cardiovascular disease (CVD).

Methods: We determined three comparative strategies, starting statin treatment when the ESC-SCORE exceeds specific thresholds, e.g. 1%, 5%, 10%. We adjust for potential time-independent and time-dependent confounding and protect against selection bias using directed acyclic graphs (DAGs) representing assumptions. We generate a study protocol following the “target trial” approach, describe data structures needed for the causal assessment, and provide potential solutions where necessity and availability of data deviate.

Results: Individuals between 40 and 75 years of age with no history of diagnosed stroke or myocardial infarction (MI) within the last month enter the target trial study at the time they first exceed the risk-threshold of 1% and are followed up for 5 years. Counterfactual “replicates” of all patients are assigned to each treatment strategy. A causal per protocol analysis is applied: individuals not following the assigned treatment protocol are censored at time of protocol violation. As censoring is informative and time-dependent confounding is present, inverse probability of censoring weighting is used to derive unbiased causal estimates. The Austrian GAP-DRG database contains ICD9/ICD10 codes from 2006-2013. As the ESC-SCORE requires continuously measured values that do not exist for all variables, rules are designed to estimate the risk score.

Conclusions: DAGs and a protocol following the “target trial” approach are important tools to guide the database structure, data assessment, and the choice of the analytic strategy in deriving causal effects from big data. Causal analytic methods are needed to provide valid estimates. Techniques using replicates can overcome the problem of missing explicit treatment assignment in secondary RWE data sets.