4 Ways Linking CAR-T Therapy Patients to Real-world Data Is Future-proofing Clinical Development

Chimeric antigen receptor T-cell (CAR-T) therapies have demonstrated significant promise in treating hematological and other malignancies.[1] But there are several areas that require a deeper understanding for the development, approval, and sale of CAR-T therapies; these include the long-term therapeutic benefits, risk of serious adverse events, and healthcare resource utilization (HCRU).

Due to the risks these key evidence gaps pose to patients, current regulatory guidelines recommend a 15+ year post-trial follow-up period[2] to monitor long-term effectiveness and potential delayed adverse events. Since CAR T-cell treatments are individualized[3] and have a significant cost per treatment,[4] payors often need data on long-term benefits of these treatments and potential downstream cost savings to justify coverage.

For sponsors looking to develop CAR-T therapies, it’s critical to leverage additional data sources in their study design to fulfill these regulatory and payor expectations. Linking clinical trial data (CTD) with real-world data (RWD) gives sponsors a comprehensive view of the patient journey—including trial patients' routine interactions with the healthcare system before, during, and after trial completion.

Through the process of data linkage and with patients’ permission, novel tokenization techniques leverage personal identifiable information to pair RWD—which include electronic health records, insurance claims, disease registry data, vital statistics, labs, and genomic data—to CTD in a HIPAA-compliant manner.

Below are four ways linking clinical trial data with real-world data supports CAR-T therapy development.

1) Limits Risk of Loss to Follow-up During a Trial

Given that CAR T-cell therapy clinical trials often have a small sample size, loss to follow-up can compromise a sponsor’s ability to meet study end-points with sufficient statistical power. WIth linkage, if a patient can no longer be contacted during the trial, sponsors can use the patient’s RWD to gather valuable information that serves as an alternative way to establish clinical outcomes and therapy effectiveness. For example, data collected through routine provider visits can inform a sponsor on a patient’s overall survival—often a critical study end-point.

2) Efficient Monitoring of Long-term Effectiveness and Safety

Since clinical trial data capture ends with the trial, sponsors traditionally rely on burdensome and costly methods to track therapy effectiveness and patient safety outcomes post-trial. Because of the lengthy post-trial follow up recommended for CAR-T trials, linkage to RWD lets sponsors track metrics like overall survival, rate of remission, and long-term, unexpected, delayed adverse events years beyond trial completion at a fraction of the usual costs.

3) Measures the Effect on Healthcare Resource Utilization and Cost

Payors often require evidence of a therapy’s impact on HCRU and overall cost of care to assess its value and cost-effectiveness when making coverage decisions. But trials collect data solely on clinical outcomes and not HCRU, presenting a challenge when articulating to payors that the therapeutic benefit of CAR-T and potential downstream savings outweigh the high costs.

By linking clinical trial patients to their claims data, sponsors gather a wide range of data both during and after the trial that provides substantive evidence on the impact of treatment on HCRU and cost of care for clinical trial patients. This data informs payor decision-making and value-based contracts and facilitates market access immediately at market entry.

4) Identifies Patient Subgroups with Differential Effects

Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)[5] are examples of life threatening conditions that can develop in response to CAR-T therapy, but whose risk factors are not well understood.

CTD to RWD linkage provides additional information on patients’ total clinical histories—including variables that weren’t included in the original study design—that help researchers learn more about disease pathways, prior treatments, and comorbidities that are risk factors for side effects. This also helps sponsors identify variables that correlate with differential long-term treatment outcomes, as well as the effect of other treatments post-CAR-T therapy on health.

Medidata Link: How Sponsors Can Start Data Linking

Despite the complexity and the high financial risk to sponsors developing CAR T-cell treatments, the promise of this therapy has led to it becoming one of the most congested areas of clinical development.[6] Many organizations are vying for modest populations of highly complex, often comorbid patients. Linking clinical trial data to real-world data provides a passive and cost-effective way to collect the information needed for regulators and payors. Implementing this technology costs a fraction—typically less than 0.1%, of the total cost per patient.

Medidata Link, awarded the 2022 Innovations in Regulatory Science Award from the Reagan-Udall Foundation for the FDA, provides a path forward for sponsors to link clinical trial data with real-world data at the patient level to cost-effectively capture information on long-term efficacy, safety, and healthcare resource utilization.

Download our eBook for more data linkage use cases to future-proof your clinical trials.

References

[1] Emily Whitehead, First Pediatric Patient to Receive CAR T-Cell Therapy, Celebrates Cure 10 Years Later. https://www.chop.edu/news/emily-whitehead-first-pediatric-patient-receive-car-t-cell-therapy-celebrates-cure-10-years

[2] Long Term Follow-Up After Administration of Human Gene Therapy Products Guidance for Industry. https://www.fda.gov/media/113768/download

[3] Lin X, Lee S, Sharma P, George B, Scott J. Summary of US Food and Drug Administration chimeric antigen receptor (CAR) T-cell biologics license application approvals from a statistical perspective. Journal of Clinical Oncology. 2022 Oct 20;40(30):3501-9. https://www.ingentaconnect.com/content/wk/jco/2022/00000040/00000030/art00004

[4] Fiorenza S, Ritchie DS, Ramsey SD, Turtle CJ, Roth JA. Value and affordability of CAR T-cell therapy in the United States. Bone marrow transplantation. 2020 Sep;55(9):1706-15. https://www.nature.com/articles/s41409-020-0956-8

[5] Sengsayadeth S, Savani BN, Oluwole O, Dholaria B. Overview of approved CAR‐T therapies, ongoing clinical trials, and its impact on clinical practice. EJHaem. 2022 Jan;3:6-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175669/

[6] Ivica NA, Young CM. Tracking the CAR-T Revolution: Analysis of Clinical Trials of CAR-T and TCR-T Therapies for the Treatment of Cancer (1997-2020). Healthcare (Basel). 2021 Aug 19;9(8):1062. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392279/