OBJECTIVES: Defining appropriate matched controls is challenging in health economics and outcomes research (HEOR) studies. An HEOR study was conducted in patients with assumed classic congenital adrenal hyperplasia (CAH), a rare and potentially serious autosomal recessive disorder characterized by impaired cortisol synthesis and excess androgen production. Results from this study are presented to illustrate the challenges of selecting appropriate controls.

METHODS: Analyses were based on longitudinal patient-level data from the Decision Resources Group Real World Evidence repository. Pediatric and adults with assumed classic CAH based on International Classification of Diseases 9/10 codes associated with “adrenogenital disorders” and glucocorticoid treatment were matched 1:3 with controls based on age, gender, geographic region, and insurance type. For stabilization, both cohorts were required to have ≥1 medical claim and ≥1 pharmacy claim in 2018 and 2019.

RESULTS: Healthcare resource utilization (HCRU) data indicated that the matched controls were not a “typical” population. Much higher use of mental health resources was found in the control cohort (N=2234) compared to the CAH cohort (N=778), including outpatient visits for mental health (17% vs 5%) and pain (12% vs 4%). Inpatient discharge diagnoses indicated that mood/affective disorders were more prevalent in the controls (12% vs 0%), as was schizophrenia (5% vs 0%). The control cohort also had more emergency room discharge diagnoses for anxiety (38% vs 0%) and major depressive episode (33% vs 0%).

CONCLUSIONS: Due to the difficult-to-manage consequences of CAH (disease impacts and adverse events from chronic glucocorticoid therapy), HCRU was expected to be higher in this patient cohort than in matched controls. The higher psychiatric HCRU among controls was unexpected because the clinical data on neuropsychiatric impact of CAH are mixed, suggesting that the claims criteria used for stabilization/control were too conservative. More discussion is needed about how controls are defined in HEOR studies.