Targeted Review of mITT vs. ITT Data in CAR-T Submissions
Author(s)
Lisanne Brouwer, PharmD, Inge Buiter, MSc, Reva Efe, Msc.
National Health Care Institute, Diemen, Netherlands.
National Health Care Institute, Diemen, Netherlands.
OBJECTIVES: Chimeric antigen receptor T-cell (CAR-T) immunotherapies are innovative treatments within oncology. Delays between leukapheresis, modification and reinfusion steps can cause some patients to progress while awaiting therapy. Within randomized controlled trials, this results in some patients not initiating treatment. Analyzing only those patients that receive therapy (i.e., modified intent-to-treat (mITT) population) can lead to bias. Health Technology Assessment (HTA) submissions CAR-T were explored to evaluate how the use of mITT vs. ITT data was appraised.
METHODS: A targeted review of CAR-T submissions was conducted of the following countries: Canada, Denmark, France, Germany, Ireland, The Netherlands, and United Kingdom. The availability of clinical and economic reports for each submission was assessed, and information/critique on the analyzed population (mITT/ITT) submitted by the manufacturer was collected.
RESULTS: 68 submissions were included (68 clinical; 42 economic). Clinical effectiveness was presented for the ITT (n=40), mITT (n=13), both (n=6) or unclear (n=9). In 27 (40%) reports, arguments from HTA bodies in favor of ITT analysis to mITT were encountered. Reasons included selection bias, overestimation of treatment effect and non-generalizability of mITT data. When arguments in favor of mITT were included (n=3, 4%), the main reasons included the high drop-out discrepancies between the intervention and comparator arms or availability of data. In most submissions, no comments on the use of mITT versus ITT analysis were identified (n=38).
CONCLUSIONS: The use of mITT and ITT varies among and within the different HTA bodies. In most reports there was no discussion about the issue at all. In reports were a discussion on ITT/mITT was identified, more arguments in favor of ITT were found. However, there are also instances where mITT might be more appropriate. It is necessary to deliberate on the analyzed population in the clinical and economic submissions of CAR-T’s, and to provide justification for the analysis.
METHODS: A targeted review of CAR-T submissions was conducted of the following countries: Canada, Denmark, France, Germany, Ireland, The Netherlands, and United Kingdom. The availability of clinical and economic reports for each submission was assessed, and information/critique on the analyzed population (mITT/ITT) submitted by the manufacturer was collected.
RESULTS: 68 submissions were included (68 clinical; 42 economic). Clinical effectiveness was presented for the ITT (n=40), mITT (n=13), both (n=6) or unclear (n=9). In 27 (40%) reports, arguments from HTA bodies in favor of ITT analysis to mITT were encountered. Reasons included selection bias, overestimation of treatment effect and non-generalizability of mITT data. When arguments in favor of mITT were included (n=3, 4%), the main reasons included the high drop-out discrepancies between the intervention and comparator arms or availability of data. In most submissions, no comments on the use of mITT versus ITT analysis were identified (n=38).
CONCLUSIONS: The use of mITT and ITT varies among and within the different HTA bodies. In most reports there was no discussion about the issue at all. In reports were a discussion on ITT/mITT was identified, more arguments in favor of ITT were found. However, there are also instances where mITT might be more appropriate. It is necessary to deliberate on the analyzed population in the clinical and economic submissions of CAR-T’s, and to provide justification for the analysis.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA311
Topic
Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes
Disease
Genetic, Regenerative & Curative Therapies