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[NMusers] ISoP Request for Comments: Exposure-Response Analysis in Drug Development and Regulatory Decision Making

From: Justin Wilkins <>
Date: Mon, 14 May 2018 13:22:20 +0000

Dear all,

As you are probably aware, FDA recently announced a public docket entitled =
"Exposure-Response Analysis in Drug Development and Regulatory Decision Mak=
ing; Request for Comments" ( to give interested pa=
rties an opportunity to identify areas of scientific policy that may need f=
urther clarity or elaboration, as well as any obstacles preventing use of e=
xposure-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 regulator=
y review. Particularly, the following questions have been posed:

  1. In general, are there any aspects of the 2003 guidance for industry t=
itled "Exposure-Response Relationships--Study Design, Data Analysis, and Re=
gulatory Applications" (
nceRegulatoryInformation/Guidances/UCM072109.pdf) that merit further elabor=
ation? Additionally, are there any new topic areas that should be addressed=
  2. What are best practices for conducting exposure-response analysis tha=
t can be generally applied across development programs and regulatory submi=
ssions? Input on best practices can include any of the following topic area=
     * 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, assessm=
ent of model risk, impact on regulatory decisions)
     * Communication of results and impact on subsequent drug development=
 or regulatory decisions
  3. What attributes of an exposure-response analysis are critical to effe=
ctively inform a drug development or regulatory decision? Additionally, wha=
t are the main obstacles preventing widespread acceptance of exposure-respo=
nse analyses?
  4. During which stages of drug development would it be most productive t=
o 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 y=
our input via the online form at
tion=com_mc&view=mc&mcid=form_254412. You can also access the form fr=
om the ISoP information page at

We plan to share and discuss the first round of feedback (received by May 2=
5, 2018) face-to-face at the PAGE meeting in the last week of May, and addi=
tionally via TC thereafter for those not attending PAGE. We will continue t=
o accept input until June 8, 2018, after which we intend to start work on o=
ur 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 respo=
nse, and contributors need not be current ISoP members to participate. Cont=
ributors are naturally still free, and are indeed encouraged, to provide th=
eir comments on the draft guidance document independently of ISoP, and we w=
elcome discussions and collaboration with other groups working to prepare r=
esponses should they be interested.

Feedback need not be provided as a fully-formed document - bullet points ar=
e sufficient, although detail is welcome.

This effort will be coordinated through the ISoP Standards and Best Practic=
es Committee, and will be co-led by Al Maloney (, =
who independently broached this topic on this list a couple of days ago (th=
anks for agreeing to help, Al!), and ISoP Board member Jonathan French (jon= Please reach out to them if you have any questions!

We look forward to hearing from you!

Best regards,
Justin Wilkins

on behalf of ISoP

Received on Mon May 14 2018 - 09:22:20 EDT

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