1. CALGB Fall Committee Meeting October 2006 Correlative Science Protocol Development Paula N. Friedman, PhD Director, Biospecimen & Correlative Science Operations

2. CALGB Fall Committee Meeting October 2006 Where in the protocol should there be information about CS? Introduction Objectives Sample Submission CS Methods* Statistical Considerations Model Consent Form

3. CALGB Fall Committee Meeting October 2006 When in the process does CS need to be considered? Right from the start!!

4. CALGB Fall Committee Meeting October 2006 Things that should be included in the concept/protocol The biologic rationale for studying the proposed marker(s). –Why are the markers relevant to study and how are they related to the therapy? The specific hypotheses behind the proposed correlative studies. –What is it you are expecting to find and why?

5. CALGB Fall Committee Meeting October 2006 Things that should be included in the concept/protocol Preclinical data that supports the proposal to look at the markers* Preliminary data from other clinical trials that have looked at the markers* Statistical considerations The proposed contributions that this study will make to the field Future plans for analysis of the markers if this study accomplishes its goals *references should be provided

6. CALGB Fall Committee Meeting October 2006 Things that should be included in the protocol A detailed description of the types of samples to be collected and the timepoints (Table). Any information about the stability of the marker under the collection conditions proposed A description of the assay method and the reason for selecting it. A summary table that includes assay type, sample type, key contact and institution

7. CALGB Fall Committee Meeting October 2006

8. CALGB Fall Committee Meeting October 2006 Correlative Science Table

9. CALGB Fall Committee Meeting October 2006

10. CALGB Fall Committee Meeting October 2006 Things that should be included in the protocol The technical performance of the assay –Qualitative vs. quantitative –Accuracy (Sens, Spec, PPV, NPV) –Reproducibility (day and user) –Sources of variability and how variability will be minimized A description of the positive and negative controls to be used Method of scoring that will be used. The certification of the testing lab –CLIA and/or CAP –If not, how the QA/QC will be handled

11. CALGB Fall Committee Meeting October 2006 Why is this so important? If the sample collection is not accurately described then the appropriate samples will not be collected. –Example: CALGB 80101- The companion study, CALGB 150205, calls for analysis of IGF-1, IGF-2 and IGFBP-3 in serum but the protocol is not clear as to the collection of serum samples. –We collected plasma at the bank from the blood tube designated for PET and some markers can be done on plasma but not all While going to all the trouble of collecting these valuable samples we need to make sure that they are being utilized fully. –We need to consider using the sample for proteomics (discovery)

12. CALGB Fall Committee Meeting October 2006 Why is this all so important? If the protocol text is not clear then a patient may not be registered to the companion, samples may not be collected appropriately and sent to the bank and consent may not be obtained or correctly recorded. –Example: CALGB 60401 - PET companion to CALGB 80303

13. CALGB Fall Committee Meeting October 2006 The Reality Patients accrued to the clinical trial 601 Patients that consented to the companion and have a high quality sample banked 362 Patients that consented to the companion and have a poor quality sample banked 13 Patients that consented to the companion and have no sample banked 85 Patients that did not consent to the companion and have a high quality sample banked 17 Patients that did not consent to the companion and have no sample banked 124

14. CALGB Fall Committee Meeting October 2006 The Reality Patients accrued to the clinical trial 601 Patients that consented to the companion and have a high quality sample banked 362 Patients that consented to the companion and have a poor quality sample banked 13 Patients that consented to the companion and have no sample banked 85 Patients that did not consent to the companion and have a high quality sample banked 17 Patients that did not consent to the companion and have no sample banked 124

15. CALGB Fall Committee Meeting October 2006 What we are doing to make the system work better Summary tables in protocols SOPs for sample collection Standardized consent questions “Real-time” monitoring of sample submission Patient brochures on the importance of sample donation New committee - Biospecimen & CS Advisory Reference labs that are CLIA/CAP certified

16. CALGB Fall Committee Meeting October 2006 Contact Information Paula N. Friedman, PhD CALGB Central Office (773)702-4694 pfriedman@calgb.org