As you are probably aware, FDA recently announced a public docket entitled “Exposure-Response Analysis in Drug Development and Regulatory Decision Making; Request for Comments” (https://go.usa.gov/xQ4m2) to give interested parties an opportunity to identify areas of scientific policy that may need further clarity or elaboration, as well as any obstacles preventing use of exposure-response analyses in drug development and regulatory review.
The community has been invited to provide detailed information and comments on the use of exposure-response analysis in drug development and regulatory review. Particularly, the following questions have been posed:
- In general, are there any aspects of the 2003 guidance for industry titled “Exposure-Response Relationships–Study Design, Data Analysis, and Regulatory Applications” (https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072109.pdf) that merit further elaboration? Additionally, are there any new topic areas that should be addressed?
- What are best practices for conducting exposure-response analysis that can be generally applied across development programs and regulatory submissions? Input on best practices can include any of the following topic areas:
- Planning and design (e.g., data considerations, assumption setting)
- Analytical approaches (e.g., exposure and response metrics, choice and inclusion of predictors, methods for addressing confounding factors)
- Model evaluation and qualification (e.g., goodness-of-fit, assessment of model risk, impact on regulatory decisions)
- Communication of results and impact on subsequent drug development or regulatory decisions
- What attributes of an exposure-response analysis are critical to effectively inform a drug development or regulatory decision? Additionally, what are the main obstacles preventing widespread acceptance of exposure-response analyses?
- During which stages of drug development would it be most productive to interact with the FDA regarding exposure-response analysis planning? What type of feedback would be useful to inform exposure-response analyses and to reduce uncertainty in regulatory acceptance?
ISoP plans to submit a consensus response which represents the views of our community. If you would like to participate or contribute, please submit your input via the online form at https://insp.memberclicks.net/index.php?option=com_mc&view=mc&mcid=form_254412. You can also access the form from the ISoP information page at http://www.go-isop.org/exposure-response-analysis-in-drug-development-and-regulatory-decision-making--request-for-comments.
We plan to share and discuss the first round of feedback (received by May 25, 2018) face-to-face at the PAGE meeting in the last week of May, and additionally via TC thereafter for those not attending PAGE. We will continue to accept input until June 8, 2018, after which we intend to start work on our final response document, which is due on July 5, 2018. Every contributor will be invited to take part in the crafting and review of the final response, and contributors need not be current ISoP members to participate. Contributors are naturally still free, and are indeed encouraged, to provide their comments on the draft guidance document independently of ISoP, and we welcome discussions and collaboration with other groups working to prepare responses should they be interested.
Feedback need not be provided as a fully-formed document – bullet points are sufficient, although detail is welcome.
This effort will be coordinated through the ISoP Standards and Best Practices Committee, and will be co-led by Al Maloney (firstname.lastname@example.org), who independently broached this topic on NMusers a couple of days ago (thanks for agreeing to help, Al!), and ISoP Board member Jonathan French (email@example.com). Please reach out to them if you have any questions!
We look forward to hearing from you!