Development Of A Conceptual Model For Early Health Technology Assessment Of Tissue-Engineered Heart Valves.

Objectives: In-situ tissue-engineering provides a promising method to create living heart valves with the potential to grow, repair and last a lifetime. The objective of the present study is to develop a conceptual model (CM) that can be used to investigate the requirements for tissue-engineered heart valves (TEHV) to become cost-effective compared to current surgical and transcatheter heart valve substitutes (HVS). Methods: The development of the CM was based on recommendations from the ISPOR-SMDM Modeling Good Research Practices Task Force-2. After scoping the decision problem, a draft CM was developed based on clinical guidelines and discussion within a small workgroup. This model was compared with existing models for cost-effectiveness of HVS, found by systematic literature search. It was further discussed with a Delphi panel of cardio-thoracic surgeons, cardiologists and a biomedical scientist (n= 10). Delphi panelists were first interviewed individually to discuss the CM structure. Thereafter, they completed online surveys in order to reach consensus between panelists. Results: Health statesincluded in the CM are ‘alive without complications’, cerebrovascular accident, myocardial infarction, vascular complication, bleeding, acute kidney injury, atrial fibrillation, pacemaker implantation, prosthetic valve dysfunction, prosthetic valve thrombosis, prosthetic valve endocarditis, ‘alive after complications’ and dead. Predictors of transition probabilities between the health states are included; age, gender, NYHA functional class, left ventricular function, renal impairment, and diabetes. Relevant outcome measures included health-related quality of life, event occurrence, event-free survival, mortality and costs. Conclusions: The CM provides the foundation of a microsimulation model that will be used to estimate the cost-effectiveness of TEHV compared with current HVS. The results will be used to inform stakeholders about the requirements for TEHV to become cost-effective. This information can help bio-tech companies to decide about further development of TEHV, focus on the most promising target groups, set realistic performance-price goals, and design and manage a reimbursement strategy.