1 / 14

All Is Not Well in the World of Translational Research

All Is Not Well in the World of Translational Research. Ellis F. Unger, M.D. Office of Drug Evaluation-I Office of New Drugs Center for Drug Evaluation and Research U.S. Food and Drug Administration June 21, 2012. All Is Not Well in the World of Translational Research. Disclaimer:

jirair
Download Presentation

All Is Not Well in the World of Translational Research

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. All Is Not Well in the World of Translational Research Ellis F. Unger, M.D. Office of Drug Evaluation-I Office of New Drugs Center for Drug Evaluation and Research U.S. Food and Drug Administration June 21, 2012

  2. All Is Not Well in the World of Translational Research Disclaimer: The views expressed herein are mine, and do not necessarily represent the views/position of the U.S. Food and Drug Administration.

  3. 1985 – 1997: • Translational research, Cardiology Branch, NHLBI, NIH • 1988 – 1997: • Member (chair), Animal Care and Use Committee, NHLBI, NIH • 1995 – 1997: • Clinical Investigator (IND Sponsor), NHLBI, NIH • 1997 – present: • Medical Officer (CBER)  (acting) Office Director (CDER), FDA My Interest in the Topic:

  4. What’s the Problem with Translational Research? • Bias • Lack of knowledge • Lack of oversight • Lack of rigor • Lack of standards • Standards for investigators • Standards for journal editors

  5. Bias – always present: • Positive results: • Publications • Research grants • Speaking engagements • Consulting arrangements • Patents; licensing arrangements • Career advancement

  6. Bias – always present: • Positive results: • Publications • Research grants • Speaking engagements • Consulting arrangements • Patents; licensing arrangements • Career advancement • Negative results: • Mostly wasted time

  7. Remediable Limitations of Pre-clinical POF Studies • Protocol may not exist; may exist but be amended without any record or chain of accountability • Studies not universally randomized • Studies not universally blinded • Randomization code and/or blocking strategy may be known (or available) to investigator • Primary endpoint often not identified; most endpoints are exploratory • Just because an endpoint measure is objective, doesn’t mean it isn’t susceptible to bias!

  8. Remediable Limitations of Pre-clinical POF Studies • No statistical plan; or • Rudimentary and/or flawed statistical plan: • Statistical test not fit for purpose • Typically no plan to deal with multiplicity (multiple end points, multiple time points, or both) • Typically no plan to control Type-I error • Missing data are common; prospective plan to deal with missing data is not common • Exclusion of “outliers” is common; prospective plan to define and exclude “outliers” is not common

  9. Example 1

  10. Example 1

  11. Example 2 No statistical comparison between treatment groups:

  12. Do Editors of Journals Play a Role? • Editors/referees often do not demand an accounting of the details of the study – the study plan or the results • Limitations section is disingenuous: writers typically ignore the REAL limitations; write about limitations of the model to predict human disease (dah!), or point out a limitation they are already addressing in a new study, “setting the table” for the subsequent study

  13. What Should be Done?

  14. Fix these problems!Questions?

More Related