1 / 6

Biostatistics

Biostatistics. Dr. Larry Rubinstein, National Cancer Institute. Phase 0 Trial Statistics for PD Assay. Endpoints are PD assay, baseline (ideally, just before Tx) vs. post-Tx, in tumor tissue and in blood

emmaline
Download Presentation

Biostatistics

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Biostatistics Dr. Larry Rubinstein, National Cancer Institute

  2. Phase 0 Trial Statistics for PD Assay • Endpoints are PD assay, baseline (ideally, just before Tx) vs. post-Tx, in tumor tissue and in blood • Baseline measures: 1 pre-treatment tumor biopsy measurement and at least 3 pre-treatment blood measurements (ideally, taken over the baseline to post-Tx time span) per patient • 1 post-Tx measurement used as primary endpoint for tumor and blood (at same time post-Tx) • Declare significant Tx-related change, for an individual patient, for observed 2-fold change combined with 90% statistical confidence of a true difference (10% false positive rate) • For blood this is 1.8 x intra-pt pre-Tx SD • For tumor tissue this is 1.8 x inter-pt pre-Tx SD

  3. Minimal Phase 0 Trial Design • Accrue 3 patients to each of the dose levels • For either endpoint, tumor or blood, significant Tx-related response for a dose is defined as significant change for at least 2 patients out of the 3 • For a dose, if there is 80% likelihood of observing change at the patient level, there is 90% power to detect significant response for the dose level • There is an overall 6% false positive rate, for both endpoints combined, for a dose level with no biologic effect (because of the 10% false positive observed change at the patient level)

  4. Enhanced Phase 0 Trial Design • There may be a need to detect a lower rate of response per dose level—use a 2-stage design • Accrue 3-5 patients per dose level, allowing for the expansion of a cohort to 5 patients if the results are not definitive for the initial 3 • Declare significant change, for an individual patient, for an observed 2-fold change combined with 95% statistical confidence of a true difference • For tumor tissue this is 2.3 x inter-patient pre-Tx SD • For blood this is 2.3 x intra-pt pre-Tx SD

  5. Enhanced Phase 0 Trial Design Details • Accrue 3 patients to each dose level • If a significant change is observed for exactly 1 patient, for either endpoint, expand the dose to 5 patients • For either endpoint, significant Tx-related response for a dose, for cohort size 3 or 5, is defined as significant change for at least 2 pts • For a dose, if there is 60% likelihood of observing change at the patient level, there is 89% power to detect significant response for the dose level • There is an overall 4% false-positive rate, for both endpoints combined, for a dose level with no biologic effect (because of the 5% false- positive observed change at the patient level)

  6. The Next Speaker is:Dr. Holly Taylor

More Related