SS P08 15March2016 Standard Scripts Project 08 Meeting

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Meeting Record

When: 15 March 2016
Place: CSS Face-to-Face Meeting
Facilitator: Mary Nilsson
Scribe: Mary Nilsson
Attendance: Terry Walsh, Mercy Navarro, Karolyn Kracht, Sheryl Treichel, Karin LaPann, Lila Thome, Grace Lu, Alan Shapiro, Nhi Beasley, Janet Fan, Xiaoping Zhang, Kendra Worthy, Mary Doi, Eileen Navarro, others that may have been in and out

  1. Questionnaire Data White Paper
  2. Hepatotoxicity White Paper


  • Questionnaire Data White Paper (Karin LaPann)
    • Discussed what standard displays would generally make sense for questionnaire data. The ADaM team is working on Questionnaire data now, so having a white paper on the displays at this time would be very helpful. The following seem to make sense:
      • Baseline to endpoint change and changes over time (could use boxplots as shown in lab/vital/ECG central tendency white paper). If a key efficacy measure, may need more sophisticated stats methods that what is described in the lab/vital/ECG white paper (e.g., MMRM).
      • If the questionnaire is collected for safety purposes, you would also be interested in "emergent" outcomes (e.g., shift from not having an issue to having an issue). The displays in the lab/vital/ECG outlier/shift white paper might be helpful as a starting point.
    • Discussed whether there's a standard imputation method for missing questionnaires. Some scales have specific methods and those would need to be followed. Otherwise, we should have a default method if the scale itself doesn't define it. Sheryl has experience with methods for handling missing questionnaires and can have follow-up discussions with Karin. (Post-meeting note: We might also need to address a standard imputation method for missing items if the scale doesn’t define a method. Mary can ask internal experts within her company that might be able to lead us to relevant literature.)
    • Discussed that it would be nice if the ADaM team would make the C-SSRS a priority for ADaM specifications. For the C-SSRS, an analysis guide already exists: C-SSRS Scoring and Data Analysis Guide
    • Project team members should share any mocks they have that might be helpful.
  • Hepatotoxicity White Paper (Terry Walsh)
    • Discussed whether we should make sure we incorporate everything outlined in the DILI Guidance. We decided that we should feel free to include what we think makes sense. The FDA representatives on the team will help network with key SMEs to make sure there's alignment on anything different that the DILI guidance. For example, per discussion, we can probably exclude summaries of Alk Phos and replace with R-values.
    • Discussed that there's an annual DILI conference. We currently don't have any project team members that attend this conference. We'll need to recruit or make sure we network really well! For example, there is some discussion about moving toward multiples of a patients' baseline as opposed to multiples of ULN. We'll stick with ULN until we hear otherwise.
    • We discussed the display for 3x/5x/10x/20x ULN. We know we need to show everyone with these regardless of baseline, but also interested in what they were at baseline. Terry will take the feedback and update the draft table. There's also a desire to have all 4 cuts in the same table (as opposed to having 4 separate tables).
    • We discussed the usefulness of a liver-specific patient profile. It would have AEs, conmeds, and all the liver-related labs. Some examples were forwarded to Terry. We decided that we would recommend that these liver-specific profiles be created for patients that have a TEAE from the Hepatic Disorders Comprehensive Search SMQ or have a ALT>=3X or have a AST >=3X. The idea is to have a listing with these patients with a link to their liver-specific patient profile (with indicator on which criteria were met among other things like r-value). If there are a lot of patients meeting one of the criteria, then we're hoping we can incorporate a way of prioritizing (e.g., adding an indicator if the Total Bili was within a certain time period of the ALT/AST increase).
    • Some people were aware of references that we didn't already know about. We'll get them added to the white paper and/or on the wiki. (Mertz Lee, Methods to Assess Liver Safety Data, Drug Safety 2014).
    • Discussed whether we should add summaries that look at 2 consecutive values meeting 3x/5x/10x/20x. We decided this would not be value-added.

    • Last revision by MaryNilsson,04/6/2016