4. Discussion
fits, ASD, DukeACT, intellectual disability, improves adaptive behavior, neurodevelopmental disorders
SAID, VBP
In this modeling study we estimated the long-term clinical and economic effects of a potential and novel therapy for children with ASD. We developed and validated a simulation model that incorporates VABS scores to track adaptive behavior development, and costs of ASD. Our results showed that even a modestly effective future intervention that improves adaptive behavior can be cost-effective over a lifetime. CB remained cost-effective (<$100,000/QALY) when the intervention cost was <$15,000. In sensitivity analyses, we found that the cost-effectiveness results were most sensitive to variations in intervention cost, intervention efficacy, and changes in the QOL mapping equation. Of note, this analysis does not project the cost-effectiveness of cord blood therapy as trialed in DukeACT that did not have clinical efficacy, but rather a potential future intervention that is found efficacious in a well-conducted clinical trial.Our results might be used as a preliminary guide to future clinical trial VABS-3 communication subscale score endpoints that may be cost-effective. We showed that future interventions with costs <$15,000 and efficacies on VABS-3 communication subscale score ≥2.0 might be cost-effective with an ICER<$150,000/QALY. This modeling framework may further be used for value-of-information analysis to help inform study design and sample size for these future trials [We also find that providing such an intervention to every child 2–7 years old with ASD (without intellectual disability) in the US would be costly. Assuming an intervention cost of $15,000, and 100% uptake, the 5-year budget impact on the healthcare sector of providing the intervention was upwards of $3.8B. That said, uptake is likely to be much less than 100% and a one-time CB treatment might be less costly than providing intensive behavioral interventions.The high cost of the CB intervention simulated in this study must be taken into context with the high costs and healthcare system burden of alternative effective therapies in ASD [We understand that–once an intervention is proven efficacious–there will remain questions about long-term effectiveness relative to upfront costs. In our current volume-based, fee-for-service healthcare reimbursement system, these concerns could lead to payment and coverage challenges and barriers to access. To address these concerns, a decision modeling framework such as ours might inform value-based payment (VBP) models for proven efficacious therapies. Such a payment model would need to align payer evidentiary demands; identify, capture (and link payments to) improved outcomes that matter to participants and payers and incentivizes better long-term evidence.This is among the first microsimulation models of ASD over the lifetime that incorporates adaptive behavior scores to track developmental trajectories in ASD. Many previously published decision modeling and cost-effectiveness analyses in ASD use IQ strata (i.e. IQ≥70 and IQ<70) to determine future outcomes [The CB intervention efficacy on VABS assumed in our basecase, and factored into QALY calculations, analysis fits well within the range of minimally important clinical difference estimates, which range between 2.01–3.75 [The population simulated in our analysis was based on the participants in DukeACT, however, we note this population is not representative of the general US population [Our study has several limitations. First, we recognize the uncertainties in our underlying input data and the assumptions that are inherent in simulation modeling analyses. We presented sensitivity analysis to test these assumptions. Modeling developmental trajectories in ASD, like many neurodevelopmental disorders, requires simplification of individual heterogeneity. In simulating the VABS trajectory, we used literature estimates to simulate individual trajectories yearly from ages 2–7 years [Second, in the basecase, we incorporated DukeACT 6-month efficacy data to inform our basecase intervention and assumed CB intervention efficacy lasted throughout childhood (for quality of life) and adulthood (for economic productivity). While it is likely that the adaptive behavioral skills acquired 6-months post intervention in DukeACT are not lost, long-term similar follow-up data for the intervention are not available. DukeACT collected 12-month data, however these data were collected remotely and are not comparable to the 6-month data. We addressed this limitation in sensitivity analyses where we lowered the efficacy of the CB intervention to 0, and where we reduced the productivity benefits in adulthood to 0. Third, our total adult ASD costs were an overestimate given inconsistencies in the published literature, however these costs did not affect cost-effectiveness or budget impact estimates as seen in sensitivity analysis [Overall, we find that a novel cord blood intervention in ASD with modest efficacy may be cost-effective under certain circumstances. Our projections may guide researchers and policymakers in their consideration of future novel therapeutics in ASD.