Health Economics and Market Access
The potential of cell and gene therapies is to have long term “curative” effects of chronic or life-threatening conditions. This is a substantial difference compared to conventional pharmaceutical medicines with repeated, sometimes daily, administration to control the associated symptoms of illnesses. This and multiple other differences between cell, gene and other types of advanced therapies mean developing robust pricing and reimbursement strategies demands additional considerations to those of conventional pharmaceuticals. These considerations also need to be addressed earlier in development given the higher commercial risk cell and gene therapies present.
An example of the work we are doing in this area to understand how the benefits, revenue and uptake of advanced therapies can be maximised is recent research by the Cell and Gene Therapy Catapult Health Economics and Market Access team on establishing the cost of implementing a performance-based, managed entry agreement for a hypothetical CAR T-cell therapy. You can view this and other recent case studies here.
The Midlands-Wales ATTC (MW-ATTC) is developing tools to determine the true costs of patient treatment in chronic conditions that will incorporate all elements of patient care. This data will help provide an improved comparison for reimbursement of advanced therapies against the current standard of care. The iMATCH ATTC alongside the MW-ATTC will evaluate the costs of cancer treatment with an autologous cell therapy for ovarian cancer. The Northern Alliance ATTC (NA-ATTC) will develop a health economics framework to assist ATMP (Advanced Therapy Medicinal Products) companies in identifying parameters they need to consider as part of data submission to regulatory bodies.
Industry advisory group
The ATTC Industry Advisory Group (IAG) was established to bring developers of advanced therapies and supporting industry together to tackle the key challenges and advise the ATTC programme. The core focus of the group is to enable early traction of new advanced therapies by engagement with ATTCs and developing standards and best practices across the industry in the UK and internationally. Recently, the group has been joined by representatives from NHS England to ensure alignment for clinical adoption.
In preparation for an increased number of ATMP products being adopted into clinical practice, sharing knowledge across the ATTC network has been identified as a key strategic activity.
Information generated by the ATTCs and CGTC will be disseminated via our knowledge hub has been built. Examples of the resources we have developed are:
A briefing document for pharmacists on CAR-T treatments (https://www.theattcnetwork.co.uk/wp-content/uploads/2019/06/SPS-CAR-T-briefing-for-Chief-Pharmacists-2.pdf)
Introducing an educational programme to ensure CRF readiness for ATMP trials (https://www.theattcnetwork.co.uk/wp-content/uploads/2019/07/An-educational-program-for-ATMPs-in-clincal-trials.pdf)
We are also developing several networks of experts across the centres. Visits from one centre to another are also a central element to effectively sharing best practice, building relationships and understanding local challenges.
If you have something that you think is worth sharing on this website, then please get in touch via ATTC@ct.catapult.org.uk
Never has the performance of the supply chain been so integral to the safe and effective treatment of patients. From the beginning of the patients’ journey, we are working with supply chain specialists to track and trace both the patient starting material going to and medicine returning from manufacture. The electronic capture of the data and tracking of the cells throughout their journey ensures the patients’ safety at point of delivery. Many of these treatments are time-critical and success relies on an integrated and transparent supply chain, keeping everyone fully informed so they may schedule their activities to deliver the best patient care. We are looking carefully at the supply chain and what good practice could look like This will be exemplified by:
- Supporting the development and integration of electronic systems for tracking and tracing ATMPs meeting the reimbursement and regulatory requirements of therapy developers and, healthcare providers.
- Producing documents defining best practice outline for hospitals and mapping logistical challenges encountered when running ATMP trials.
- The provision of an end-to-end cryochain solution using hardware systems that ensures cell viability and preservation of ATMP products.
- Supporting the development of an electronic supply chain orchestration system and its testing.
Patient and Public involvement and engagement (PPI/E)
Listening to and obtaining feedback from patients and carers, particularly around the language and communication tools used with participants in clinical trials is an essential component of developing safe medicines within a trusted healthcare system. The purpose of good PPI/E within clinical trials is to advance a culture where clinical research is carried out ‘with’ patients, carers and members of the public rather than ‘to’, ‘about’ or ‘for’ them.
ATMPs are significantly different to conventional medicines and some of the key differences can impact both patients and their families. Notably for some advanced therapies, this can include ‘curative’ potential, possible side-effects, and use of the patient’s own biological material. Ensuring the public understands both the benefits and risks associated with developing and delivering ATMPs is imperative.
Through a literature review and a series of patient and public involvement workshops, the MW-ATTC has reviewed the current understanding of ATMPs within the UK population. We found that even individuals who identify themselves as patient experts are unlikely to have come across these therapies and therefore how these therapies work but are very interested in gaining understanding as well as being thoroughly informed on risks and side effects.
Building upon this information, the CGTC and the ATTCs are developing a suite of materials for use by healthcare providers, developers of these new medicines and charity groups to provide accessible, objective and realistic information about these novel therapies. In this initiative we are collaborating with important and trusted stakeholders such as the UK Clinical Research Network (NIHR) and key charity groups to develop these communication tools and disseminate them as part of planned PPI/E activities.
ATMPs have substantially different pathways through patient care compared to conventional medications. These products may be manufactured for specific patients following harvest of a patient’s blood elements or bone marrow and may be only usable for that particular patient (autologous). The manufacturing and treatment pathway for these autologous products is totally patient focussed and provides challenges for coordinating care. Other ATMPs are made on a larger scale, allowing many patients to be treated from the same manufacturing batch (allogeneic). These allogeneic products are commonly frozen to allow long term storage and shipping; however, they require special handling before and after thawing before they can be administered to a patient. Other ATMPs require close coordination within hospital stem cell laboratories in the final preparation of products. All ATMPs have specific storage, handling and dispensing instructions that have to be followed exactly to ensure that the products maintain their potency. Pharmacists are responsible for ensuring that the ordering, storage, reconstitution and dispensing of ATMPs are in line with their product specifications.
The Pan-UK Pharmacy Working Group (PWG) is acting as an expert and informed body to support the activities of the three ATTCs in the administration of ATMPs. The group consists of pharmacists from across the UK that specialise in the governance, prescribing, administration and monitoring of ATMPs and is an excellent example of collaboration across the NHS. The aims of the group are to promote good practice, identify and resolve pharmacy issues to maximise the effectiveness and development of services for hospitals to administer advanced therapies. It has developed guidance and checklist documents in the handling of ATMPs to provide consistency in pharmacies across the country. The PWG is becoming an important partner to the NHS in the administration and commissioning of ATMPs and will continue to develop best practice and guidance for this class of medication.
The overarching goal of the processing network stream is to develop and disseminate shared learnings in relation to consistent and reproducible manufacturing, and quality control of an ATMP. The purpose is to provide confidence that an individual product manufactured in any distributed manufacturing centre meets the appropriate quality criteria and is fully equivalent. Demonstrating consistency of product development is critical for scale-up and/or adoption. As patient numbers increase, it is vital that manufacturing of products can be distributed across the UK and beyond to meet demand. This is particularly critical to ensure equitable access for fresh autologous product.
Using an exemplar product, we shall undertake relevant proof of principle studies (e.g. stability studies, release criteria) to pilot distributed manufacturing, and roll out learnings.
A highly skilled workforce is key to the successful adoption of ATMPs into mainstream clinical practice; the combination of these education resources that we are creating will equip our NHS and industry with the knowledge they need to be able to carry out their roles effectively. In preparation for the change in working practices that will be experienced for those treating patients with advanced therapies across the NHS, we are creating educational resources. We have a network of experienced and passionate professionals from across the network to create training materials which will prepare the UK healthcare workforce for the introduction of novel treatments. As a priority, the group are currently delivering a high-quality introduction to ATMPs for nursing staff. This will be used to bring all staff up to the same level of knowledge across the country. This includes a CAR-T cell therapy syllabus for pharmacists. The group also organised a conference in November 2019, aimed at healthcare professionals, to raise the profile of advanced therapies in development and the impact they are going to have on clinical practice in the very near future.
To deliver this we are:
- Running a survey and producing a report determining the current level of training available for NHS staff in advanced therapies.
- Aiming to develop an online syllabus of training materials catering to the needs of NHS staff involved in the delivery ATMP treatments.
- Hosting a conference for key professionals discussing the state-of-the-art trial design and clinical delivery
As patient demand for access to new ATMPs increases, either due to a growing number of clinical trials and/or commissioned services, it is essential to identify and address potential bottlenecks in the supply chain. One such bottleneck that could arise, unique to ATMPs as a class of medicines, is the capacity within the healthcare system to ‘procure’ starting material from an increasing number of patients. This is because tissue procurement is time consuming and it requires specialist staff and specialist equipment. Each ATMP has its own specific requirements and the impact of limited space and safe cryopreservation technologies on large scale storage.
From the UKRI’s Industry Strategy Challenge Fund, we have secured £2.5 million funding from Innovate UK to drive standardisation for collection of both blood or surgical tissue thereby improving efficiency in tissue collection and increasing capacity within the service for ATMP delivery.
Apheresis is the procedure used to collect blood tissue. Within this project we aim to reduce unnecessary complexity and variation in apheresis tissue collection. This will be achieved by forming a working group of key opinion leaders across clinical apheresis, equipment manufacturers and product developers to:
- Assembling a community of practice amongst all those involved in apheresis procurement of starting materials for ATMP manufacture.
- Identification of key quality attributes and the impact of operational variation on these.
- Development and publication of a consensus set of guidelines and standards.
Additionally, clinic-friendly cryopreservation techniques will be tested and validated to improve apheresis automation. We will improve critical quality attributes of apheresis cryopreservation protocols to increase produce an optimal ATMP starting material for ATMP developers
For surgical tissue, an aseptic fresh-frozen workflow suitable for ATMP manufacture will be developed. Expertise from UK-Blood services, tissue banks, clinical teams and biobanks will be gathered to ensure quality and safety of tissue procurement in a robust, efficient and compliant manner.
Part of the assessment of the values ATMPs by health care agencies is to assess the impact of these new therapies. A single administration of an ATMP may improve a patient’s health over a period of years, however there is a need to show a substantial difference to quality of life. This assessment needs to occur both at the point of receiving therapy and over the longer-term once the patient has been discharged. It can be difficult to monitor patients once they have returned home and stop seeing medical teams on a regular basis.
The Industrial Strategy Challenge Fund and Innovate UK grant funded project: ‘Patient-reported Outcomes assessment to support accelerated access to advanced cell and gene therapies: PROmics’, focuses on the development of an electronic capture system to assess patient symptoms and quality of life when they receive these new therapies. The Centre for Patient Reported Outcomes Research (CPROR) are leading experts in Patient Recorded Outcomes (PRO) methodology. The digital healthcare company Dignio Ltd, have established a cloud based tele-health platform that has been successfully used to support patients with chronic conditions.
The PROmics project will develop a Class IIa device to allow real-time identification of side effects following therapy and how it has impacted on patient’s quality of life. This should facilitate clinical intervention and ensure patient safety in the adoption of advanced therapies within the NHS. Patients will be able to report how they feel on the treatment by using electronic devices. This data will also be used to assess the effectiveness of the treatment and be used as an evidence base for regulators and policy makers to support uptake in the NHS. Patients have been directly involved in development of the project and will provide direct input into the system development to ensure that it meets their needs.
The project will also develop a technology enabled consultancy to advise on the use of patient-reported outcomes and quality of life in testing ATMPs in clinical trials. This data will help ATMP manufacturers and biotechnology companies develop a better understanding of the efficacy of their products with clinical use.