Cohort Definition Name : Earliest event of Pulmonary arterial hypertension (PAH)
Contributor name : Joel Swerdel’
Contributor OrcId : 0000-0002-6976-2594’
Logic Description : Earliest occurrence of Pulmonary Arterial Hypertension (PAH) indexed on occurrence of PAH condition requiring right heart catheterization or echocardiogram 30 days before or 30 days after diagnosis/index. Cohort exit is the end of continuous observation.
Recommended study application : target
Assertion statement : This cohort definition was executed on at least one real person-level observational health data source and resulted in a cohort with at least 1 person.
Target Clinical Description : Pulmonary Arterial Hypertension (PAH) is a rare, progressive and life-threatening disorder that may lead to an untimely death if undiagnosed or left untreated (Montani et al. 2013, Brown et al. 2011). Elevated blood pressure induced by thickening and narrowing of the small pulmonary arteries over time causes vascular and cardiac remodelling, which ultimately may lead to right heart failure if left without proper disease management (Montani et al. 2013). A recent critical appraisal of the literature reported epidemiology estimates of approximately 5.8 adult patients per million for PAH incidence and 47.6 to 54.7 per million for PAH prevalence (Leber 2021) using recent (<5 years) national systematic registry data from centralized healthcare systems (NHS Digital 2021, Kjellström 2020). Pulmonary arterial hypertension can be further classified into subtypes according to etiology. These are idiopathic PAH (IPAH), heritable PAH, PAH induced by exposure to drugs and toxins, or PAH associated with other conditions, such as connective tissue disease (CTD-PAH) and congenital heart disease (CHD-PAH). For the most common PAH subtypes, incidences and prevalences per million population are reported in systematic national registries: for IPAH 2.6 to 7.6 and 9.0 to 18.3; CTDPAH 2.8 and 10.0 to 13.0; and CHD-PAH 2.2 and 7.0 to 19.0, respectively (Peacock 2007, Skride 2018, NHS Digital
"Evaluation conclusion : We developed a prevalent cohort definition for Pulmonary Arterial Hypertension (PAH) using a concept set of 2 concepts which incorporated all those found from the literature review, the analysis of PHOEBE, and orphan concepts in cohort diagnostics. The algorithm requires either a procedure code for right heart catheterization or echocardiography prior to or within 30 days after the diagnosis of PAH.
We performed the evaluation across a network of claim data sources and 1 EHR US data source. The data sources are: IBM® MarketScan® Commercial Database (CCAE), Optum’s longitudinal EHR repository (Optum EHR), Optum’s Clinformatics® Data Mart (DOD), IBM® MarketScan® Multi-State Medicaid Database (MDCD), IBM® MarketScan® Medicare Supplemental Database (MDCR), Japan Claims Database (JMDC), Clinical Practice Research Datalink (CPRD) , IQVIA® Australia Longitudinal Patient Data (LPD) database (Australia), IQVIA® Disease Analyzer (DA) France database (France), QVIA® Disease Analyzer (DA) Germany database (Germany), IQVIA® Adjudicated Health Plan Claims Data (formerly PharMetrics Plus) - US database (PharMetrics), IQVIA® Ambulatory EMR (EMR). The algorithm retrieves subjects from 7 databases tested. Although there were indications of possible index date misclassification, due to the possibility of multiple forms of PH being present prior to a PAH diagnosis, we chose not to alter the index date. We developed a more specific cohort requiring a second diagnosis code for PAH in the time period 31-365 days after index. This cohort improves the specificity of the algorithm albeit at the expense of sensitivity as determined by PheValuator. As the principal analysis in ASSURE will pair a prior diagnosis of PAH with a PAH treatment, it should be acceptable to use single diagnosis code algorithm for ASSURE. Although the two-code algorithm increases the mean PPV, the significant loss in sensitivity will likely reduce its value in our intended analytical use case as a target population with high preference to maximize sensitivity. It should be noted that the subject counts and sensitivity (as determined by PheValuator) showed high variability across the databases. These differences should be taken into consideration when comparing results across databases. The sensitivity was also low across all databases other than MDCR. This may be an issue when considering the generalizability of results for each of the datasets.
Performance characteristics were determined for 6 of the 7 databases. The remaining database did not contain enough subjects to produce an accurate diagnostic model. Using one code (the submitted cohort deffinition), sensitivity ranged from about 3% in MDCD to about 79% in MDCR while positive predictive value ranged from about 50% in CCAE to about 69% in Optum EHR. Using two codes, sensitivity decreased, ranging from about 1% in MDCD to about 27% in MDCR while positive predictive value increased, ranging from 91% in Pharmetrics to 98% in all databases except for Optum EHR and SES.