All Times EDT
Keywords: joint submission of therapeutic and CDx products, IVD bridging study, CDx, real world evidence
An IVD bridging study is a type of clinical trial design for possibly jointly submitting a therapeutic product and its companion diagnostic (CDx) to prevent the delay of CDx clearance and the drug ready for use in the appropriate intent-to-treat population. The design provides with a methodology to evaluate efficacy of a therapeutic product in the population determined by the marker status of a candidate IVD CDx, when a clinical trial assay (CTA, a prototype of CDx), instead of the CDx, is employed to enroll patients. It’s via the means of assessing concordance and discordance between CTA and CDx resulted from the same samples collected at the trial enrollment, so to bridge the drug efficacy from CTA defined population to CDx defined intent-to-treat population. During the concordance assessment by both positive and negative percent agreement (PPA & NPA), it’s typically recommended that all patients’ samples tested by CTA, resulting in either CTA+ or CTA-, be re-tested by CDx, in order to cover the entire spectrum of the CDx intended use population. In reality, especially due to valuable samples in oncology, if a subject is ineligible (e.g. CTA-) to be enrolled in a clinical trial, the sample may not be available for a CDx re-test. This leads to NPA unable to be computed, in addition to the missingness in CDx+ results probably in CTA- population. Eventually, the efficacy approximation by CDx+ will also be impacted, given the formula proposed in the IVD bridging study design. We hence developed a method to utilize commercially procured real world samples to establish NPA. Meanwhile, the same set of samples can be simultaneously used for both analytical and clinical validation of the candidate CDx, which in turn improves efficient use of patients’ samples. Issues related to the sample size determination, as well as the challenges in tipping point analysis for efficacy approximation will be addressed in the talk.