Identification and Validation of Hemophilia-Related Outcomes on Japanese Electronic Medical Record Database (Hemophilia-REAL V Study)

Abstract

Purpose: Routinely collected data are useful for epidemiological study in hemophilia, but few studies validated the algorithm accuracy. We aimed to develop and validate algorithms to identify patients with hemophilia A and hemophilia A-related events. Patients and Methods: This validation study compared data from medical chart reviews to a database of routinely collected health data, including claims data and discharge abstracts, and especially electronic medical records (EMR), at a single Japanese hospital (Kurashiki Central Hospital) using a stratified sampling method. Two physicians reviewed the charts for all patients at high risk for hemophilia A, and randomly sampled patients with moderate risk. Diagnostic accuracy was determined based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Results: There were 1,033,845 eligible patients, of whom 31 had a diagnosis of hemophilia A. ICD-10 diagnosis code D66 in the EMR identified hemophilia A with a sensitivity of 93.5% (95% confidence interval: 78.6-99) and PPV of 61.7% (95% confidence interval: 46.4-75.5). The administration of ≥10,000 units/month of factor VIII products, as documented in the EMR, identified 81.3% of patients with prophylactic factor replacement therapy. The ICD-10 diagnosis code for intracranial bleeding in the EMR identified 75.0% of patients with intracranial bleeding, but those of gastrointestinal bleeding and major joint bleeding identified only 11.1% and 1.7%, respectively. Conclusion:We developed and validated algorithms to identify congenital hemophilia A and hemophilia A-related events. Hemophilia A could be identified with high sensitivity and PPV, but it was still challenging to identify hemophilia A-related events.

Burden of congenital hemophilia A requiring treatment in Japan: The HIKOBOSHI study

“…In that study, the ICD‐10 D66 code in the electronic medical records in combination with administration of FVIII products without administration of FIX products had a positive predictive value of 95.2% (95% CI, 76.2–99.9) and sensitivity of 64.5% (95% CI, 45.4–80.8) for identifying HA 20 . The predictive values for identifying ICH and IHD could not be confirmed because of insufficient incidence, and the presence of FVIII inhibitors and FVIII activity levels were not very reliable definitions 20 . Additionally, major joint bleeding or arthropathy could not be accurately identified; the positive predictive values for these outcomes, plus FVIII product prescription, were 27.8% and 42.9%, respectively.…”

“… 20 The predictive values for identifying ICH and IHD could not be confirmed because of insufficient incidence, and the presence of FVIII inhibitors and FVIII activity levels were not very reliable definitions. 20 Additionally, major joint bleeding or arthropathy could not be accurately identified; the positive predictive values for these outcomes, plus FVIII product prescription, were 27.8% and 42.9%, respectively. Nevertheless, it would be difficult to conduct a large‐scale prospective study in this population because of the rarity of the condition; thus, medical information databases offer a valuable means of scrutinizing real‐world disease burden of people with HA to highlight remaining unmet needs.…”

“…20 The predictive values for identifying ICH and IHD could not be confirmed because of insufficient incidence, and the presence of FVIII inhibitors and FVIII activity levels were not very reliable definitions. 20 Additionally, major joint bleeding or arthropathy could not be accurately identified; the positive predictive values for these outcomes, plus FVIII product prescription, were 27.8% and 42.9%, respectively.…”

“…For example, the intended use of the anticoagulants prescribed to four individuals and the results of their use cannot be determined. Moreover, the accuracy of the definitions for the outcome measures may be limited because it has not been possible to validate these using true information, although a validation study using data from a single hospital has been attempted 20 . In that study, the ICD‐10 D66 code in the electronic medical records in combination with administration of FVIII products without administration of FIX products had a positive predictive value of 95.2% (95% CI, 76.2–99.9) and sensitivity of 64.5% (95% CI, 45.4–80.8) for identifying HA 20 .…”

“…Moreover, the accuracy of the definitions for the outcome measures may be limited because it has not been possible to validate these using true information, although a validation study using data from a single hospital has been attempted 20 . In that study, the ICD‐10 D66 code in the electronic medical records in combination with administration of FVIII products without administration of FIX products had a positive predictive value of 95.2% (95% CI, 76.2–99.9) and sensitivity of 64.5% (95% CI, 45.4–80.8) for identifying HA 20 . The predictive values for identifying ICH and IHD could not be confirmed because of insufficient incidence, and the presence of FVIII inhibitors and FVIII activity levels were not very reliable definitions 20 .…”