{
  "abstract": "Background Despite significant investment in clinical research, a large portion of the learning is siloed by publication bias and restricted data access. Much of this stems from fragmented efforts and failure to build on existing evidence due to a lack of collaboration. Recent examples of historical clinical trial re-use have illustrated the ways have been transformative in the development of life-saving immuno-oncology therapies.Methods Estimate the impact of utilizing historical clinical trial data through three examples in the regulatory setting.Validating Surrogate Endpoints1 In partnership with Bristol Myers Squibb, Medidata analyzed data from 1,600 patients to validate complete response and remission with incomplete hematologic recovery at 12 months as surrogate endpoints for progression-free survival in chronic and small lymphocytic lymphoma. The findings supported the FDA’s March 2024 Accelerated Approval of Breyanzi, the first CAR-T treatment approved for CLL/SLL,2 showing how historical trial data can support novel endpoints when traditional measures are not feasible.External Controls for Single Arm Trials for regulatory decision makingKite was able to observe that their drug demonstrated improved efficacy around a few key endpoints including overall complete remission rate at week 24 (OCR24) and overall survival (OS). Overall, this study highlighted the significant improvement in both OCR24 and OS in adult patients with R/R B-ALL when treated with the sponsor’s drug compared to current standards of care. Insights were used to support EMA regulatory submissions, and analyses were customized to specific populations of interest to EU payor authorities and ultimately supported those submissions as well.An external control created from observed historical trial data, allowed researchers to contextualize clinically relevant improvements in response and event free survival (CR/CRi and EFS) in adult patients following investigational therapy as part of a single arm trial versus available therapies. This provided strong evidence for the investigational therapy’s use in this patient population and supported a positive recommendation from the EMA Committee for Medicinal Products for Human Use.Results Application of advanced analytic methods with robust historical clinical data has helped developers:Prioritize product portfoliosReduce time and cost to marketOptimize evidence for regulators and payorsIncrease patient centricityConclusions Bringing new treatments to market for aggressive and rare diseases is challenging, emphasizing the need for the most advanced and efficient clinical trial designs to maximize success. There is increasing evidence that illustrates regulatory adoption when robust data and analyses are applied to regulatory acceptable use cases.References Jennifer Ann Woyach, et al. Association between treatment (tx) response and PFS and OS in R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): a 12-month landmark (LM) meta-analysis. 2024;JCO 42:7047-7047. DOI:10.1200/JCO.2024.42.16_suppl.70472 U.S. FDA approves Bristol Myers Squibb’s 2. Breyanzi® as the first and only CAR T-cell therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) [Internet]. Bristol Myers Squibb; 2024.",
  "authors": [
    {
      "affiliations": [
        "Medidata, New York, NY, USA"
      ],
      "name": "Bryant Fields"
    },
    {
      "affiliations": [
        "Medidata, New York, NY, USA"
      ],
      "name": "Ruthie Davi"
    }
  ],
  "title": "717 Transforming access to regulatory grade evidence re-using historical clinical trials",
  "uid": "a5884fac-64e5-5740-be34-3c0f8f7be594"
}