(303) Estimation of period-based costs associated with individual chronic complications of rare inherited diseases, in the context of multimorbidity, using real-world data.

Background: Patients with rare inherited diseases e.g., cystic fibrosis or sickle cell disease (SCD) often develop chronic multisystemic complications which can occur earlier than in the general population. Differences in the timing of complication onset complicates estimation of costs associated with individual complications.

Objectives: To estimate the incremental all-cause direct healthcare cost (ACC) associated with individual chronic complications of SCD in the context of multimorbidity.

Methods: We used a retrospective cohort study design of linked English data from Clinical Practice Research Datalink and Hospital Episode Statistics for 01/04/2007 – 31/03/2019. We included patients ≥12 years with ≥1 record of SCD and ≥12 months follow up time (FUT). 10 complications were included as exposures and the outcome was primary and secondary care ACC. Costs were applied from Unit Costs of Health and Social Care and National Tariff Payment Costs and were adjusted to 2020/2021 pounds sterling.
To estimate incremental ACC for each complication we performed a multiple regression analysis using generalised linear methods with gamma distribution and identity link. We accounted for differences in complication onset timing by including the proportion (0 to 1) of FUT for which each patient had a given complication instead of the complication itself. The model was adjusted for age, gender, ethnicity, deprivation, and FUT centred on its median to provide the period cost. Confidence intervals were bootstrapped.

Results: We included 7,265 patients with median FUT of 9.75 years. Most patients were female (61%, n=4,453), of black ethnicities (76%, n=5,508), with mean age of 30 years at index. 25% of patients (n=1814) had ≥1 chronic complication before or during the study.
In the fully-adjusted model, mean ACC for patients with SCD without complications was estimated to be £15,218 (95%CI 13,424 – 17,001) over 9.75 years. Renal failure (RF) had the highest mean incremental ACC of £474,954 (437,289 – 507,290); equivalent to an annual total ACC of £50,274. Followed by sickle hepatopathy at £63,450 (45,881 – 78,696), and osteonecrosis at £60,071 (45,311 – 74,832). Retinopathy was estimated to have the lowest mean incremental cost of £5,459 (1,746 to 9,264). When compared to non-mutually exclusive calculations of mean annualised ACC amongst patients with each complication, costs for RF were consistent (£50,274 vs £49,308); whereas annualised ACC for all other conditions overestimated cost by approximately four times.

Conclusions: This method provides initial estimates of ACC associated with individual complications of rare inherited disease, correcting for overestimation in the context of multimorbidity. Extensions may include weighting the cost model by survival probability to account for censoring.