Whole organ bioengineering is paving a way to clinic slowly, but confidently. Such bioengineered hollow organs as blood vessels and trachea have entered the clinical stage few years ago. This year, the first UK-based company Videregen has gotten an approval to conduct clinical trial for transplantation of bioengineered trachea. Recently, a team from UK published the first cost analysis of manufacturing and transplant of bioengineered trachea. Since access to the study is paywalled, I’d highlight some important points here.
The case series study, authored by Emily Culme-Seymour, describes 3 cases of tissue engineered trachea implantation in UK. All 3 patients (including 2 pediatric cases) were treated under UK Compassionate Use legislation. One of three patients had good long–term outcome. The manufacturing procedure was performed in GMP facility.
Manufacturing cost was calculated as follows:
The laboratory-based work to generate the stem cell-engineered airway transplants was costed separately using information in Batch Manufacturing Records (BMRs) collected from the UCL Biobank. Where possible we calculated the costs from procurement of the donor trachea, its decellularization and subsequent recellularization, including laboratory equipment, consumables, staff, and laboratory overheads. Laboratory equipment costs and running costs were calculated by taking into account the required staffing, the initial costs for the equipment, and the estimated number of products able to be produced per year.
The authors calculated max manufacturing cost as $27,490 per organ. It includes purchasing of donor trachea, decellularization and recell- procedure with auto epithelial cells and MSC. For the first patient recell process was not included, because cells were not cultured, but fresh bone marrow was applied ntra-operatively. For the 2nd patient, cost of decellularization was not included, since synthetic trachea was used. The cost of synthetic trachea was ~ $1,000. The cost of donor trachea was $3,730. The cost of decellularization and recellularization were ~$9,000 and $14,800 respectively.
Of course, the biggest part of total cost is a clinical care. In this study the cost of clinical care was very high, because patients were severely ill, had co-morbidities, multiple complications and required multiple complex procedures in follow-up. The clinical cost for all 3 patients significantly varied and was $540,450; $697,210 and $146,930 respectively. It depended on many factors – length of follow-up (4 years in first patient), length of hospital stay (only 21 days in 3rd patient), number of graft/ procedures (2 trachea grafts were subsequently transplanted in patient 2) and others. Overall, the manufacturing cost was ~2.3% – 15.8% of total procedure cost.
In discussion, the authors pointed out that cost of bioengineered trachea transplant is comparable with existent current slide tracheoplasty (currently available surgical option), also with typical cost of such procedures as kidney transplant and pancreatic islet transplant in UK. Even though, it is too early to estimate potential cost-effectiveness and healthcare savings, based on 3 cases, the authors seem optimistic. Their hope is to enroll less severely ill patients (in earlier stages of diseases) in the future trials and, therefore, save on clinical care cost. Unlike manufacturing cost, clinical care has much more rooms for improvement. Some estimated calculations from the study:
Estimated clinical costs for a future patient treated within a formal early-stage clinical trial setting are in the region of $105,650 to $116,690 (data not shown). This cost is based on a 5-7 day stay on pediatric intensive care unit followed by a 2-4 week stay on an open pediatric ward (both at GOSH), an identical implantation procedure to those used for both our pediatric patients, CT scans, bronchoscopies, and a bone marrow aspiration and airway biopsy ahead of transplant in order to obtain the autologous cells. With the same laboratory costs as for patient 2 (second transplant) and patient 3, the total cost for a future patient within a formal clinical trial setting can be estimated to be in the range $133,140 to $144,180.
The authors also indicate that if total cost of bioengineered trachea transplant ~$140,000 might be deemed as cost-effective and affordable in UK (based on NICE metrics) only in case of significant improvement in length of life and/or quality of life. In this study, only the first patient demonstrated significant improvement of quality of life. Here is a figure from the study, which demonstrates decreasing clinical cost in 4-years follow-up:
… for patients suffering from congenital abnormalities, where there is a high degree of complexity and concurrent co-morbidities, the health gains upon restoration of the airway with the engineered trachea may be insufficient for the treatment to be considered as cost-effective. Whereas, for an oncology patient, where long-term remission and hence restoration to full health may be achievable, for a UK NHS cost consideration, the treatment may fall under the threshold and become feasible. Affordability for new treatments such as these tracheal replacement grafts, where the same technology is applicable in treating a number of indications, may well thus depend on that indication treated.
This study is the first attempt to analyze the cost of bioengineered organ transplantation. I’d highly recommend to read it to all developers of bioengineered organs. Despite some limitations, the benchmark for the future trials and studies was provided:
The data presented in this paper should act as a base-line to enable researchers to better design future clinical trials for tissue-engineered airways.