PDDI Info Model Task Force - CONTENT Sub-team minutes for 8/25

Hi Team,

The minutes and link to meeting recording for the August 25th meeting of 
the *content sub-team* of the PDDI Info Model Task Force are pasted below.

The next meeting for the content sub-team is scheduled for 9/21 at 1pm 
Eastern


Kind regards, -R



    Minutes for 8/25/2016 (Content Meeting)

In Attendance:  Evan Draper, Brian LeBaron, Rich Boyce, John Horn, 
Serkan Ayvaz, Michel Dumontier, Dan Malone

Meeting recording:  None (accidental)

Meeting:


  *

    Brief updates

      o

        Progress on writing, expect draft introductory note to circulate
        toward the end of September. Current draft sections linked from
        here:
        http://dbmi-icode-01.dbmi.pitt.edu/dikb-evidence/w3c-ddi/index.html

      o

        One more day to provide feedback on the user-centered definition
        for “Contextual Info-Modifying Factors”:
        https://pitt.co1.qualtrics.com/SE/?SID=SV_ekQnaeXRSwYICPz

      o

        Next qualtrics to be sent Monday - “Frequency of harm /
        frequency of exposure”

  *

    Decision tree status

      o

        Evan

          +

            Tyrosine kinase inhibitors + proton pump inhibitors: draft
            pending - Deadline 9/23

          +

            Warfarin + etoposide/ifosfamide: draft pending - Deadline 9/23

      o

        Dan

          +

            Tamoxifen + paroxetine: draft received and discussed in detail:

              #

                Decisions

                  *

                    The concept of weak, intermediate, and strong enzyme
                    inhibitors was discussed and it was decided that
                    those distinctions would not apply well to tamoxifen

                      o

                        The FDA Guidance that provides definitions for
                        these distinctions is designed for PDDI study
                        protocol design, not clinical decision support:
                        (Table 3)
                        http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm292362.pdf

                      o

                        “Strength” of inhibition depends on the dose of
                        the inhibitor and the PK of the object drug
                        (e.g., Fm, Fm_enz)

              #

                Issues to be addressed

                  *

                    We need to establish a reasonable inhibition
                    threshold for SSRIs and CYP2D6. After much
                    discussion, it was agreed to 1) identify the change
                    in AUC of the active metabolite in 2D6 poor
                    metabolizers and use this concentration change as
                    the criterion for identifying potential interacting
                    drugs, and 2) identify if tamoxifen has a high Fm
                    (close to 1.0).

                  *

                    SSRIs that decrease the active metabolites AUC
                    roughly the same magnitude as being a 2D6 PM would
                    be included as risk increasing drugs for 2D6 EMs

                  *

                    If Fm is close to 1.0 for tamoxifen, than other
                    SSRIs that inhibit 2D6 substrates in vivo would also
                    be included


          +

            MAOIs + indirect acting sympathomimetics: (last meeting)
            stimulants changed to + indirect acting sympathomimetics;
            draft pending

      o

        John

          +

            Amiodarone + simvastatin: draft received - to discuss at the
            next meeting

          + Fluconazole + simvastatin: draft received - to discuss at
            the next meeting



-- 
Richard D Boyce, PhD
Assistant Professor of Biomedical Informatics
Faculty, Center for Pharmaceutical Policy and Prescribing
Faculty, Geriatric Pharmaceutical Outcomes and Gero-Informatics Research and Training Program
University of Pittsburgh
rdb20@pitt.edu
Office: 412-648-9219
Twitter: @bhaapgh