1. Phase 0 & Patients From the Patient Side of the Desk September 5, 2007 NCI Phase O Workshop Deborah Collyar PAIR: Patient Advocates In Research

2. Patient Advocate Comments HOPES  Promising idea, could eliminate guesswork  New approaches are good  ‘Same old ways’ don’t cut it  Changing status quo  Tied to specific targets  PK/PD = good for patients  Like possibility to screen multiple agents, doses  Holy grail if drug + imaging agent = same thing  How likely? CONCERNS  Multiple biopsies not good  Imaging helps, but not a panacea  Need known/validated markers  Limits to short list of drugs/agents  Biomarkers: must correlate with disease outcome  Getting to tumor isn’t enough  No benefit to participant  Not like phase I, II, III, or IV trials  Will patients really understand?  Opportunity cost  Stage IV may choose phase I for slight benefit potential over none  Quick poll of PAIR, SPORE, and CALGB patient advocates  Overall: too new for many opinions (N=11)

3. Phase 0 = Preclinical Testing in People  Language is very important  This is truly experimental… we need to say so  Exploratory research v. ‘phase 0 clinical trial’  “Biomarker “: what kind? Validated? How to tie to outcome?  There is still time to differentiate terms!  Be a broken record: NO treatment benefit possible  What ramification/price for patient to wait?  Mental, physical, social, logistical, performance status?  Which patients are actually available in a 7-day window?  Does the body react the same way to microdose v. regular dose?  What collateral damage is possible (e.g. ‘nuclear’ fallout)?  ‘Cool’ science is only possible if people agree to it  Could save $ + animals, but what does Aunt Sally get?  Consider assuming costs for participant’s future treatment

4. Words Matter: Cancer Terms 101 © PAIR: Patient Advocates In Research

5. Not ready for ‘prime time’ yet  NCI is the right place to pilot exploratory studies  New findings that may help everyone (e.g. WBCs)  How to analyze, what technology needed, who should be on team, etc.  How to screen multiple agents, doses, etc.  Careful procedures + dedicated team of specialists  e.g. terrific imaging resources, careful assay development  Motivated patients, shorter wait time for new trial  Full financial coverage for studies  VERY important: clear standards for exploratory research  The Assay is the KEY to success before launching an exploratory study  Use only with a KNOWN target  Not for ‘me too’ drugs  Not for non-biologics  What happens if it doesn’t work?  How is a go/no go decision made?  Was it the imaging probe, technology, assay, sample, pharmacogenetics, agent, or what?

6. Wary of ‘for benefit of science’  Is it another band aid or systemic change?  We now have phases 0, I, I/II, II, II/III, III, IV…  How can we truly improve this system?  Efforts to date = disappointing  Will a whole phase 0 dept be next?  Where is Office of Human Research Protections (OHRP)?  People tire of promises  Is this about drugs or patients?  Does this reduce or substitute steps?  Need solid progress vs. policies based on enthusiasm  How to we measure success?  Does ‘success’ involve people? All for improving the process/speeding up clinical trials, but… Are we re-stacking blocks or designing a new structure?

7. In Summary…  Exciting new method: approach cautiously  Share knowledge gained at NCI, develop standards  Suggestions  Conduct these types of exploratory studies ONLY at NCI until utility is validated  Especially for assays and validation  Consider training teams at NIH; certification?  Need stringent adherence to (yet to be established) firm standards/guidelines  Improve methods for entire clinical trial system  Don’t create more Tuskegees, Gelsingers, etc.  Call it ‘exploratory research’, not a clinical trial  Stress no benefit; study impact to patients  Focus on benefit for PATIENTS, not just drugs To garner enduring support… Explain how this gets to end goal of better answers more quickly for PEOPLE