Randomised trial of Haploidentical Transplantation compared to standard of care for Adults with Sickle Cell Disease

Background: Sickle cell disease (SCD) is an inherited disease associated with shortened life expectancy, life-long intermittent severe acute and chronic pain and chronic multi-organ damage. SCD has negative impacts on quality of life, causes significant burden to the NHS due to high health-care utilisation and frequent hospitalisation. Haematopoietic stem cell transplantation (SCT) offers potentially curative treatment.

The NHS has now routinely commissioned sibling SCT for patients with severe SCD, but most do not have a sibling donor. In recent years research has led to development of haploidentical (haplo) SCT which results in high initial rates of success (60-90%) and appears safe.

Design: Multi-centre phase 3 randomised trial planned to evaluate both clinical, quality of life and cost efficacy when compared to current standard of care for adults with SCD. Setting: JACIE accredited hospital haematology departments with sickle cell and transplant physician expertise. Target Population: Adult patients (>/=18-years) with severe SCD

Health Technology Being Assessed: SCT is a procedure where a preparative protocol of chemotherapy and immunosuppressive drugs are given followed by stem cell infusion. This results in replacement of the recipient’s haematopoietic system (blood cell production) with the donor’s resulting in cure of the abnormal sickle cell production.

Measurement of Costs and Outcomes: We will undertake a model-based health economic analysis to compare haploidentical SCT versus current non-curative therapies for the treatment of severe SCD. The analysis will provide important information for decision-makers to determine whether haplo SCT for SCD represents good value for money for the NHS. The economic analysis will be undertaken from the perspective of the NHS and Personal Social Services over a lifetime horizon.

Cost-effectiveness will be assessed in terms of the incremental cost per quality-adjusted life year (QALY) gained. Health outcomes and costs will be discounted at 3.5% per annum. Costs will be valued at current prices.

The economic analysis will characterise trade-offs between potential improvements in longer term outcomes (e.g. survival and health-related quality of life [HRQoL]) and the potential for adverse effects with SCT. Sample Size: 120 patients (60 haplo SCT, 60 controls).

Project timetable: The project will last for 64 months with planned recruitment start in month 7. An internal pilot to determine the feasibility to proceed is planned in month 19. Recruitment will be completed by month 37, all patients will be followed up for 2-years until completion, last participant last visit is due in month 61. Data analysis and grant end will be by month 64.

Patient and Public Involvement: Patient involvement is critical to ensure an important question for patients is successfully addressed. Ongoing patient involvement will allow us to adapt our protocol responsively and increase publicity and recruitment. We have identified a patient representative from the Sickle Cell Society (SCS), who has agreed to join the trial steering committee and is a co-applicant of the awarded grant.

We will devise a patient advisory group to meet with investigators periodically throughout the trial. The chair of this group will be invited to attend the monthly trial management group meetings. The advisory group will assist with writing and review of patient material.

Expenses incurred including travel, will be covered. We plan future public involvement events with the SCS to maintain patient awareness.