NONMEM Users Network Archive

Hosted by Cognigen

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

From: Justin Wilkins <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" (https://go.usa.gov/xQ4m2) 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" (https://www.fda.gov/downloads/Drugs/GuidanceComplia=
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=
s:
     * 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 https://insp.memberclicks.net/index.php?op=
tion=com_mc&view=mc&mcid=form_254412. You can also access the form fr=
om the ISoP information page at http://www.go-isop.org/exposure-response-an=
alysis-in-drug-development-and-regulatory-decision-making--request-for-comm=
ents.

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 (al_in_sweden
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=
athanf

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

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.