Families caring for children and adolescents with rare disease: a health economic evaluation of face-to-face and online psychosocial support intervention of the randomized controlled CARE-FAM-NET study

Abstract Background Parents caring for children with rare diseases often experience a reduced Health-Related Quality of Life (HRQoL). This study addresses the growing need for therapeutic support by evaluating two innovative forms of care: CARE-FAM (CF) and a web-based program (WEP) WEP-CARE (WC). CF is a psychodynamic-psychosocial intervention with eight sessions per family over six months, aiming to improve mental health, HRQoL, and satisfaction of all family members. WC is an online intervention leveraging cognitive-behavioral writing therapy principles to achieve the same objectives. The aim of this study was to evaluate the incremental cost per quality-adjusted life year (QALY) gained for CF, WC and their combination (CF + WC) compared with the control group (CG), on a per-parent basis, over an 18-month time horizon from the German statutory health insurance (SHI) payer perspective. Methods Children Affected by Rare disease and Their Families – Research Network (CARE-FAM-Net) is a 2 × 2 factorial, multicenter randomized controlled study conducted across 17 psychiatric hospitals in Germany with three intervention groups (CF, WC, CF + WC) and a control group. Cost evaluations utilized claims data from seven SHI funds, reflecting the SHI payer perspective, while QALYs were calculated using the EQ-5D-3 L score at four points over an 18-month time horizon. The unit of analysis was the individual parent, therefore all costs and QALYs were estimated on a per-parent basis. The primary analysis used the intention-to-treat statutory health insurance (ITT-SHI) population. Missing data were addressed through multiple imputation by chained equations with predictive mean matching, generating 20 imputed datasets that were combined using Rubin’s rules. Within-family correlation was accounted for in the statistical analyses. Numerical incremental cost-effectiveness ratios (ICERs) were reported where appropriate, and non-parametric family-cluster bootstrapping was performed to estimate statistical uncertainty. The sensitivity analysis used a restricted population. Costs and QALYs were discounted at a rate of 3%. Results The primary ITT-SHI analysis included 653 participants, with a mean age of 39.4 years (SD 7.2), and 396 (60.6%) were female. Unadjusted mean annual discounted costs per parent were €4476 (SE €631) for CG, €3539 (SE €755) for CF, €3970 (SE €1249) for WC and €5518 (SE €1850) for CF + WC. Unadjusted mean annual discounted QALYs per parent were 0.9144 (SE 0.0079) for CG, 0.9215 (SE 0.0097) for CF, 0.9287 (SE 0.0074) for WC and 0.9313 (SE 0.0075) for CF + WC. Based on the incremental mean costs and baseline-adjusted QALY differences, CF and WC dominated CG, whereas CF + WC had an ICER of €109,371 per QALY gained. However, none of the between-group differences in costs or baseline-adjusted QALYs were statistically significant. At a willingness-to-pay (WTP) of €50,000 per QALY, the probabilities of cost-effectiveness in pairwise comparisons with CG were 84.2% for CF, 79.9% for WC, and 43.0% for CF + WC. When all strategies were compared simultaneously, WC had the highest probability of being the most cost-effective strategy (48.2%), followed by CF (37.6%), CF + WC (10.4%) and CG (3.8%). The sensitivity analysis yielded comparable results for CF and WC, whereas CF + WC also dominated CG. Leave-one-out analyses demonstrated sensitivity to individual extreme cost observations. Conclusions In the primary analysis, CF and WC were associated with lower mean costs and positive baseline-adjusted QALY differences relative to CG, whereas CF + WC was associated with higher mean costs and a positive baseline-adjusted QALY difference. None of the differences in costs or baseline-adjusted QALYs were statistically significant. The sensitivity analysis yielded broadly comparable findings for CF and WC, whereas results differed for CF + WC. Given the study limitations, particularly the relatively small sample size, the current evidence is insufficient to support a definitive recommendation for implementation into routine care from a health economic perspective. Trial registration The study was registered at 18th December 2018 at the German clinical trials register (Deutsches Register Klinischer Studien, DRKS, nr: DRKS00015859).