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Chimeric antigen receptor (CAR) T-cell therapy is a human gene therapy product where T cells from a patient are genetically modified to enable them to recognize desired target antigen(s) more effectively. In recent years, promising antitumor activity has been seen with autologous CAR T cells. Since 2017, six CAR T-cell therapies for the treatment of hematological malignancies have been approved by the Food and Drug Administration (FDA). Despite the rapid progress of CAR T-cell therapies, considerable statistical challenges still exist for this category of products across all phases of clinical development that need to be addressed. These include (but not limited to) dose finding strategy, implementation of the estimand framework, use of real-world data in contextualizing single-arm CAR T trials, analysis of safety data and long-term follow-up studies. This paper is the first step in summarizing and addressing these statistical hurdles based on the development of the six approved CAR T-cell products., (© 2024. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

Objective: The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) study investigated the use of teriparatide in men and women with osteoporosis in the United States (US) and Puerto Rico (PR). In a sub-analysis, we evaluated whether the baseline characteristics of Latinas differed from those of white women in the study population and whether any patient attributes affected physicians' decisions to prescribe teriparatide., Methods: We assessed 3 patient cohorts treated with teriparatide 20 microg once daily for up to 24 months: 1) PR Latinas, 2) US Latinas, and 3) white women on the US mainland (white women). We analyzed differences related to ethnicity (Latina vs. white) and geography (PR vs. US mainland)., Results: Overall, 302 of the 3243 women (9%) enrolled in DANCE were Latina (205 of these 302 Latinas resided in PR). Significant differences were observed in 7 of 11 baseline characteristics. White women had more prior fragility fractures and family history of hip fracture than Latinas, while PR Latinas were generally older than US Latinas and had more comorbid conditions. A similar proportion of subjects in each cohort had received prior osteoporosis therapy. Physicians prescribed teriparatide more often for Latinas based on multiple risk factors for fracture and intolerance to previous osteoporosis therapy and to white women based on inadequate response to previous therapy or new (incident) fractures. Overall, Latinas were less persistent with teriparatide therapy than white women., Conclusion: We observed significant differences related to ethnicity and geography in the baseline demographics of Latinas enrolled in the DANCE study, criteria cited by physicians for initiating teriparatide therapy, and treatment persistence.