Methodology of the IQVIA Dx claims database analysis

A retrospective, longitudinal cohort study was conducted from 1 November 2016 to 31 October 2019.

Female patients with one or more medical claims with a primary or secondary diagnosis code for RTT (ICD-10-CM: F84.2) were included. A record of MECP2 genetic mutation was not required for inclusion in the study. The date of the first observed diagnosis of RTT was defined as the index date. Patients aged one year or older were required to have ≥12 months of continuous enrolment prior to the index date. The 12-month period prior to the index date was defined as the baseline period and served to describe demographics and clinical characteristics. Patients with one or more medical claims for cerebrovascular disease (ICD-10-CM: I60–I69) or brain trauma (ICD-10-CM: S06) were excluded.

The observation period spanned the time from the index date until the end of clinical activity or the end of data availability (whichever occurred first). GI manifestations and healthcare costs were evaluated during the observation period. An overview of the study design is provided in Figure 1.

Key outcomes reported in the study were the prevalence of GI manifestations of RTT and medical costs associated with GI management, including a breakdown of costs by service setting (inpatient, emergency department [ED], outpatient, home/hospice care, therapeutic services, medical supplies, durable medical equipment, other, missing).

The following GI manifestations were evaluated in the analyses: constipation, gall bladder dysfunction (including biliary tract disorders), growth abnormalities (i.e., underweight, short stature), GERD, gastroparesis, vomiting/regurgitation, and diarrhea. The list of specific ICD-10-CM codes used to identify the GI manifestations of RTT is provided in Supplementary Table 1.

Demographics and key baseline characteristics were reported. These included information on MECP2 genetic testing (Supplementary Table 2 for a list of procedure codes used to identify the MECP2 testing), comorbidity burden measured using the Quan-Charlson Comorbidity Index [9] (Supplementary Table 3 for a list of ICD-10-CM codes used to calculate the index), and differential diagnoses received prior to an RTT diagnosis [10,11] (Supplementary Table 4 for a list of ICD-10-CM codes used to identify potential differential diagnoses of RTT).

The prevalence of GI manifestations was described during the observation period as the frequency and proportion of patients with each GI manifestation. Mean medical costs were reported per patient per year (PPPY) to account for varying lengths of follow-up and inflation-adjusted to 2021 US dollars.

Baseline patient characteristics, prevalence of RTT manifestations, and medical costs were described for the overall study sample and for subgroups stratified by age category (pediatric patients aged <18 years vs adults aged ≥18 years). Continuous variables were summarized using means and standard deviations (SDs), and medians and interquartile ranges (IQRs). Categorical variables were summarized using relative frequencies and proportions.

Data were analyzed in SAS Enterprise Guide version 7.1 (SAS Institute, NC, US). All analyses were descriptive and no statistical comparisons between adult and pediatric groups were performed.