How Well Do Various Health Outcome Definitions Identify Appropriate Cases in Observational Studies?
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Observational data can be useful for drug safety research, but accurate measurement of adverse health outcomes is paramount. Best practices for identifying important health outcomes of interest (HOI) are needed.
To evaluate the extent to which health outcome definitions commonly used in observational database studies identify cases that are consistent with expert panel assessment of the underlying data.
Competing HOI definitions were used to identify potential cases of acute liver injury (ALI; n = 208), acute kidney injury (AKI; n = 200), and myocardial infarction (MI; n = 204) in the Truven MarketScan Lab Database (MSLR). Panelists reviewed patient-level data and answered questions about whether they believed the case actually reflected the HOI and their certainty of case classification on a 10-point scale (1 = unlikely to 10 = likely). Each patient was reviewed independently by two panelists. Case disagreements were resolved through consensus meetings. Positive predictive value (PPV) was calculated as the number of cases deemed to be true over the total number of sampled cases. Kappa statistics assessed inter-rater agreement.
PPV ranged from 0 to 52 % across ALI definitions, 12 to 82 % across AKI definitions, and 1 to 56 % across MI definitions. Certainty scores on the 10-point scale paralleled the PPV, with a range of mean values from 1.7 to 4.8 across ALI definitions, 3.1 to 6.0 across AKI definitions, and 2.8 to 5.7 across MI definitions. Inter-rater agreement was low to moderate (Kappa range 0.0–0.6).
Existing HOI definitions had relatively low PPV based on expert panel review. Experts commonly disagreed on case classification. Additional work is needed to refine HOI case definitions if observational data are to be reliably used for health outcome assessment.
KeywordsPositive Predictive Value Acute Liver Injury Case Classification Common Data Model Observational Medical Outcome Partnership
This project was supported by the Foundation for the National Institutes of Health, grant HANSE11OMOP. We thank the following expert panelists: Jon Duke, MD, MS, Regenstrief Institute; Ben Powers, MD, MHS—St Luke’s Health System; Mei Sheng Duh, MPH, SCD, Analysis Group; T. Craig Cheetham, PharmD, MS, Kaiser Permanente; Scott Sanoff, MD, MPH, University of Virginia; Andrew Bomback, MD, MPH, Columbia University; Gregory Hess, MD, MBA, MSc, University of Pennsylvania; Themistocles Assimes, MD, PhD, Stanford University. A preliminary version of this work was presented as a poster at the OMOP Symposium, June 28, 2012, and at the Annual Meeting of the American Pharmacists Association, March 3, 2013. Dr. Hansen has received consulting support from Takeda Pharmaceuticals, Novartis, and Daiichi Sankyo for research unrelated to the content of this paper, and he has provided expert testimony for Allergan. Drs. Gray, Fox, Hollingsworth, and Zeng, as well as Ms. Gao declare no potential conflicts of interest.
This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.
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