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Adam Feuerstein Interviews Dr. Mark Ratain on How a Clinician Analyzes Clinical Trial Results. We'll talk Red flags, Tools to Spot Issues, and When a Redesign of a Failed Study Might Actually WorkTicker(s): PFE, LLY, AZN.L, NVS, KERX, CPXX
Name: Dr Mark Ratain - MD
Institution: The University of Chicago
- International leader in Phase I clinical trials, pharmacogenomics, and clinical trial methodology, with over 280 original publications, Dr. Ratain is an expert in the use of investigational agents to treat advanced solid tumors.
- In partnership with Adam Feuerstein he developed the well-known Feuerstein-Ratain Rule for investing in Phase 3 oncology trials. His clinical trial design experience, combined with his roles as the first chair of the Steering Committee of the National Institutes of Health Pharmacogenetics Research Network, as well as one of the first co-chairs of the National Cancer Institute Investigational Drug Steering Committee provide the perfect basis to help investors evaluate drugs in clinical development.
- Leads The University of Chicago's Phase I oncology trials program where he is currently a Professor of Medicine. Director of the Center for Personalized Therapeutics and Chief Hospital Pharmacologist. In addition, he serves as the Associate Director for Clinical Sciences in the University’s Comprehensive Cancer Center.
Adam Feuerstein writes for www.TheStreet.com, covering biotech names. One of the best known personalities on Twitter and the biotech landscape, he has spent years spotting red flags and trouble spots in the plans of many biotech managements.
Due to the overwhelming response on this project, an additional
conference line has been added to accommodate additional capacity.
Please dial the primary conference # first.
PRIMARY CONFERENCE LINE:
Dial In: 844-776-1770
- Passcode: 143#
- Dial In: 877-462-0052 (No PIN required)
Some topics that Adam and Dr. Ratain will focus on in no particular order:
- When a company presents subgroup analysis, what kind of follow-up questions should investors be asking themselves or management?
- What investors should be concerned to see missing from a press release.
- Red flag words: Per protocol, retrospective, responder analysis, subgroup.
- How to interpret p values? Is a statistically significant result always clinically meaningful? If not, how do you know?
- What is your feeling about companies which provide limited disclosure of clinical trial results in press releases due in order to preserve full data for presentation at medical meetings or publication? This is a source of tension for investors who often feel like press releases contain the greatest hits from clinical trials without fully disclosing the risks or negative. What’s your view as a clinician?
- Feuerstein-Ratain Rule --- Celator broke the Feuerstein-Ratain Rule. Let’s discuss!
Links/source material to prepare for the call:
Raptor Pharma: Example of bad data-mined subset math in Huntington’s disease
The call format will consist of Adam Feuerstein and Joe McCann interviewing Dr. Ratain for the first 45-50 minutes loosely following the outline above. This will incorporate some of the questions submitted below. With the time remaining we will ask some of the highest rated questions submitted by the community.
Not infrequently we see really good or great Phase 2 results (from relatively large P2 trials) that form the basis of optimism for a successful phase 3, only to see complete failure with P3 hazard ratios close to 1. Examples include CLDX, ZIOP, THLD, OGXI. CYTR boasted incredible P2 results and P3 top line should be reported soon. Can you explain the process of trial arm randomization and any differences in process between P2 & 3. Is there more potential for company or investigator bias/conflict of interest to sneak into P2 vs P3 (intentionally or unintentionally)? If the treatment arm in P2 has "better" patient characteristics, is this just "luck of the draw".
CEO's often spin the participation of famous treatment centers in their trials as evidence the drug must be promising. If the trial investigator is from a famous hospital, some biotechs will leverage that fact as much as they can, quite often having this doctor participate in trial readout conference calls. Should we put any weight on the affiliation of the lead investigator and the reputation of the hospitals that signed on to the trial? Why or why not?
The F-R track record is nothing short of astounding. Over the years Adam Feuerstein has written about his views on the underlying drivers. However, even mid caps not fitting within F-R rule size parameters often see their stock price go down prior to reporting negative trial results. Do you think it's inevitable that, even in double blinded trials, clinicians will have a sense as to whether the treatment arm is receiving added benefit and that it is just too difficult to keep a lid on these impressions in a large, global study? I.e, the word usually gets out?
How reliable are positive/negative signs before clinical trial results are announced? For example, how long does it typically take to get institutional review board (IRB) approval? Does rapid enrollment correlate with success? What is the typical number of weeks between final data collection and announcing results?
What are some tell tale signs that the clinical results from a prior phase have better than usual odds of being replicated at a later phase? Are there particular areas (oncology, CNS, etc.) where these are more or less applicable than others?Added By: rayleigh
Could you address statistical metrics such as p-value, hazard ratio, etc and when those numbers can mislead investors. What does a change in Hazard ratio mean to expectations of results in terms of OS, PFS, or other measures of trial success.
When you read the clinical results press release or listen to the company's call, are there a few well-scripted phases (clinical or legal) that sound alarm bells?Added By: addy
How can investors better avoid a situation like where Clovis touted positive data, then submitted data to FDA based on unconfirmed responses, blindsiding everyone who assumed the data was on confirmed responses. How commonplace is this sort of erroneous data set submission to the FDA with oncology biotechs? http://phx.corporate-ir.net/phoenix.zhtml?c=247187&p=irol-newsArticle&ID=2054589 http://phx.corporate-ir.net/phoenix.zhtml?c=247187&p=irol-newsArticle&ID=2112606
Can you give us a checklist of the most important things you look for when looking at a top-line press release? Abstract? Manuscript?
Retroactive subgroup analyses on clinical data have a bad reputation, and with good reason. But can you comment on when (if ever) a retroactive analysis is likely to be adding some real, meaningful insight?Added By: user6626944a
Recently a very small company Celator broke the Feuerstein-Ratain Rule.
In looking at the Phase 2 data previously disclosed were there clues
this might be the company to do it?
When a company doesn't give details in a PR, is there any way to find them out?Added By: lemongrass
When trials fail companies frequently try and "find a silver lining" to justify further study. What are the important things to think about when evaluating the new path forward?
The Feuerstein-Ratain rule makes has no flexibilty to account for the size of the market of the cancer indication being pursued. Should the rule apply equally to an indication with a market potential of a few hundred million versus a multi billion dollar indication?Added By: wallstreettitan
Discuss why trials run in E Europe etc often produce unreliable results, leading to failures in subsequent "western" studies. Is quality of care in these regions the primary issue, or lack of rigor from these "cheaper" CROs?Added By: kingsly
Can a company have any influence over the Data Monitoring Committee (DMC) in any way? If not HOW the DMC looks at the data, can it influence other aspects such as WHEN the data is reviewed? Can it ask for additional data not initially specified in the original trial specs, prior to reporting results to the FDA and public?
Pharma companies are adept at designing trials to show positive results in a small slice of patients with a particular disease. How can we avoid being bagholders when the CEO and sell siders trumpet the results for a wider patient population?Added By: addy
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