Chimeric antigen receptor — or CAR — T-cell therapy is a new form of immunotherapy that uses specially altered T cells to attack diseased cells. CAR T cells are engineered by removing T cells from the blood, modifying them in a laboratory to increase the immune system’s natural response, and reinjecting them into the patient, where they multiply and attack diseased cells. CAR T-cell therapies have ushered in a new approach in treating cancer and other serious conditions.
As announced in April 2018, CAR T-cell therapies are assessed through the CADTH Health Technology Assessment (HTA) Service for medical devices and clinical interventions. This approach was implemented in direct response to feedback from Canada’s federal, provincial, and territorial Ministries of Health, and the Canadian Association of Provincial Cancer Agencies (CAPCA), and is consistent with several other HTA bodies, including the Institut national d’excellence en santé et en services sociaux (INESSS) in Quebec.
Assessments are led by CADTH, with recommendations from the CADTH Health Technology Expert Review Panel (HTERP). HTERP is a CADTH expert committee, convened to develop recommendations on health technologies to inform a range of stakeholders within the Canadian health care system. For CAR T-cell reviews, the panel is supplemented with individuals who have applicable clinical expertise and who are leading the implementation of CAR T-cell program planning provincially.
Transparency, collaboration, and stakeholder engagement are central to each assessment that CADTH undertakes, and our appraisals of CAR T-cell therapies are no different. Stakeholders, including patient groups and clinicians, have the opportunity to provide their insights and perspectives on these treatments. For indications specific to cancer, CADTH works closely with CAPCA to ensure that operational and implementation issues are effectively addressed.
An overview of the CADTH CAR T-cell assessment process, with approximate time frames, is available here. As with all our review programs, we will be continually revisiting the CADTH CAR T-cell assessment process and adjusting it accordingly. Changes to the process will be reflected in published documentation and communicated through CADTH’s e-alert service. To receive CADTH e-alerts, subscribe here: www.cadth.ca/subscribe.
Considering the Evidence
As per the HTERP review process, a CAR T-cell therapy review begins with CADTH developing a review protocol for the topic being assessed. The research questions and analysis plan in the protocol are based on information gathered during scoping of the topic. The protocol is reviewed by external experts and methodologists, and by HTERP members, and is then posted on the CADTH website and registered with PROSPERO.
Based on the review protocol, CADTH conducts an HTA. The HTA includes a review of the clinical effectiveness, an appraisal of the economic model and budget impact analysis, an assessment of ethical issues, a review of implementation considerations, and a review of patient perspectives and experiences. Feedback on the HTA is sought from external peer reviewers, methodologists, HTERP members, patient groups, and clinicians. The final version of the HTA is posted on the CADTH website.
Development of Recommendations
Following rigorous discussions of the evidence, HTERP develops recommendations using the HTERP deliberative framework, taking into consideration the intended audience for the recommendation, the type of decision required, the evidence, and implementation issues. Recommendations are based on consensus, and evidence gaps are identified in the recommendation to suggest additional areas of primary research.
Draft recommendations are sent to relevant stakeholders for input. Once the feedback is addressed, recommendations are made final and posted on the CADTH website.
Please direct any questions regarding the CAR T-cell therapy review process to firstname.lastname@example.org.