Early Health Technology Assessment of Tissue-Engineered Heart Valves

One of the most promising developments to limit or eliminate the disadvantages of existing heart valve prostheses is the creation of a living heart valve. In situ tissue-engineering provides a promising method where a synthetic biodegradable scaffold in the shape of a valve will be implanted in the patient. The scaffold recruits endogenous cells from the bloodstream and surrounding tissues, the cells form new tissue and gradually transform into a valve. Tissue-engineered heart valves (TEHV) are in the development phase and not used in clinical practice yet. This thesis describes the early Health Technology Assessment (HTA) of TEHV. The conceptual model of the decision-analytic model used for the early HTA was based on a systematic review of model-based economic evaluations of heart valve implantations and a Delphi panel. The input parameters were based on systematic reviews and meta-analyses, results from a patient-reported questionnaire, and cost-analysis of health insurance claims database, reported in this thesis. The early cost-effectiveness of TEHV was assessed in elderly patients in need of aortic valve implantation and children in need of pulmonary valve implantations. The results can inform various stakeholders. First, it informs biomedical companies developing TEHV about minimum performance requirements and maximum additional costs of TEHV in different target populations, which can guide priority setting of further research initiatives. Developers of TEHV should especially focus on improving durability of TEHV compared to existing heart valve substitutes, since this was the largest driver of quality adjusted life year gains and cost savings. However, it was noted that the potential improvement in thrombogenicity of TEHV compared to existing heart valve substitutes is expected to result in larger benefits in other patient populations than discussed in this thesis (i.e. young adults or middle aged patients eligible for mechanical heart valve substitutes). Moreover, the headroom was sufficiently large for TEHV to be economically viable. Second, it provides patients and clinicians with the first estimates of potential improvements in clinical outcomes with TEHV, which may result in faster adoption of TEHV in clinical practice. Finally, it informs healthcare payers about the possible entrance of TEHV to the market, the promising potential cost-effectiveness of TEHV and the expected large cost savings for the national healthcare budget, which may result in more timely decisions about reimbursement

Benefits of early highly effective versus escalation treatment strategies in relapsing multiple sclerosis estimated using a treatment-sequence model

BACKGROUND: Uncertainty about disproportionate impact on health care budgets limits implementation of early highly effective treatment (EHT) in multiple sclerosis (MS).OBJECTIVE: To estimate cost-effectiveness of escalation versus EHT disease-modifying treatment (DMT) sequences.METHODS: Using a health-economic approach, we analysed health benefits (relapse rate reduction, disability prevention), direct/indirect DMT and societal costs of escalation versus EHT DMT sequences. In scenario analyses, we allowed (1) earlier use of alemtuzumab (ALE) and (2) a single retreatment with cladribine (CLA).RESULTS: In our model, we showed that the ratio between costs and quality-adjusted life years (QALYs) for the most cost-effective EHT and escalation sequence results into a similar net health benefit with higher costs and also higher QALYs associated with an EHT versus escalation strategy. Earlier use of ALE is more cost-effective than in later lines, even when aggravating the impact of its side-effects tenfold. Retreatment with CLA was more cost-effective in both escalation and EHT sequences.CONCLUSIONS: Certain EHT sequences are equally cost-effective to escalation sequences and are likely to result in more health at uncertain additional costs. The favourable cost-benefit ratio of CLA and ALE suggests that a wider application of affordable highly effective therapies could promote the cost-effectiveness both EHT and escalation approaches.</p

Benefits of early highly effective versus escalation treatment strategies in relapsing multiple sclerosis estimated using a treatment-sequence model

BACKGROUND: Uncertainty about disproportionate impact on health care budgets limits implementation of early highly effective treatment (EHT) in multiple sclerosis (MS).OBJECTIVE: To estimate cost-effectiveness of escalation versus EHT disease-modifying treatment (DMT) sequences.METHODS: Using a health-economic approach, we analysed health benefits (relapse rate reduction, disability prevention), direct/indirect DMT and societal costs of escalation versus EHT DMT sequences. In scenario analyses, we allowed (1) earlier use of alemtuzumab (ALE) and (2) a single retreatment with cladribine (CLA).RESULTS: In our model, we showed that the ratio between costs and quality-adjusted life years (QALYs) for the most cost-effective EHT and escalation sequence results into a similar net health benefit with higher costs and also higher QALYs associated with an EHT versus escalation strategy. Earlier use of ALE is more cost-effective than in later lines, even when aggravating the impact of its side-effects tenfold. Retreatment with CLA was more cost-effective in both escalation and EHT sequences.CONCLUSIONS: Certain EHT sequences are equally cost-effective to escalation sequences and are likely to result in more health at uncertain additional costs. The favourable cost-benefit ratio of CLA and ALE suggests that a wider application of affordable highly effective therapies could promote the cost-effectiveness both EHT and escalation approaches.</p

Benefits of sphingosine-1-phosphate receptor modulators in relapsing MS estimated with a treatment sequence model

BackgroundThree sphingosine-1-phosphate receptor (S1PR) modulators are currently available as disease-modifying therapies (DMTs) for relapsing MS in the Netherlands (i.e. fingolimod, ozanimod and ponesimod). We aimed to identify which S1PR modulator yields the highest benefit from a health-economic and societal perspective during a patient's lifespan.MethodsIncorporating Dutch DMT list prices, we used the ErasmusMC/iMTA MS model to compare DMT sequences, including S1PR modulators and eight other DMT classes, for treatment-naïve patients with relapsing MS in terms of health outcomes (number of lifetime relapses, time to Expanded Disability Status Scale (EDSS) 6, lifetime quality-adjusted life years (QALYs)) and cost-effectiveness (net health benefit (NHB)). We estimated the influence of list price and EDSS progression on cost-effectiveness outcomes.ResultsIn deterministic and probabilistic analysis, DMT sequences with ponesimod have lower lifetime costs and higher QALYs resulting in a higher average NHB compared to sequences with other S1PR modulators. Ponesimod remains the most cost-effective S1PR modulator when EDSS progression is class-averaged. Given the variable effects on disability progression, list price reductions could make fingolimod but not ozanimod more cost-effective than ponesimod.ConclusionOur model favours ponesimod among the S1PR modulators for the treatment of relapsing MS. This implies that prioritizing ponesimod over other S1PR modulators translates into a more efficacious spending of national healthcare budget without reducing benefit for people with MS. Prioritizing cost-effective choices when counselling patients contributes to affordable and accessible MS care

Health-economic benefits of anti-CD20 treatments in relapsing multiple sclerosis estimated using a treatment-sequence model

Background: In high-income countries, four anti-CD20 monoclonal antibodies (mAbs) are used or in thepipeline for relapsing MS: ocrelizumab, ofatumumab (both registered), ublituximab (awaiting registration)and rituximab (off-label). List prices differ significantly between registered and off-label drugs.Objective: Comparing differences in benefits between anti-CD20 mAbs from a health-economic and societal perspective.Methods: To reflect lifetime use of DMTs, we used a treatment-sequence model to compare ocrelizumab/ofatumumab and eight other drug classes in terms of health (lifetime relapses, time to Expanded DisabilityStatus Scale [EDSS] 6, lifetime quality-adjusted life years) and cost-effectiveness (net health benefit). Tobecome cost-effective compared to ocrelizumab, we modelled the list price of ublituximab and desiredeffect on EDSS progression of rituximab.Results: Although drug sequences with ocrelizumab in first- and second-line were more cost-effective thanofatumumab, our probabilistic analysis suggests this outcome was very uncertain. To be more cost-effective than ocrelizumab, ublituximab needs to be about 25% cheaper whilst rituximab needs to equal theeffect on disability progression seen with first-line treatments.Conclusions: Our model showed no clear difference in cost-effectiveness between ocrelizumab and ofatumumab. Hence, prescribing the least costly anti-CD20 mAb can democratise MS care without a loss inhealth benefits

Costs of Persons with Dementia Living in Nursing Homes in The Netherlands

BACKGROUND: Disease modifying treatments (DMTs) currently under development for Alzheimer's disease, have the potential to prevent or postpone institutionalization and more expensive care and might delay institutionalization of persons with dementia. OBJECTIVE: The current study estimates costs of living in a nursing home for persons with dementia in the Netherlands to help inform economic evaluations of future DMTs. METHODS: Data were collected during semi-structured interviews with healthcare professionals and from the financial administration of a healthcare organization with several nursing homes. Personnel costs were calculated using a bottom-up approach by valuing the time estimates. Non-personnel costs were calculated using information from the financial administration of the healthcare organization. RESULTS: Total costs of a person with dementia per 24 hours, including both care staff and other healthcare providers, were € 151 for small-scale living wards and € 147 for independent living wards. Non-personnel costs were € 37 per day. CONCLUSION: This study provides Dutch estimates for total healthcare costs per day for institutionalized persons with dementia. These cost estimates can be used in cost-effectiveness analyses for future DMTs in dementia.</p