Working Group Meeting September 25-26, 2006

Sheraton Hotel – Atlanta, GA

MEETING SUMMARY

View Meeting Agenda

Sub-Committee Meetings
Individual meetings of the Methods, Topics and Products Subcommittees (SC) were held from 8:30 – 9:30 am, allowing the subcommittee chairs and members to finalize recommendations and presentations for the full EGAPP Working Group (WG).

Welcome
The EGAPP WG meeting was convened by Al Berg, Chair. Working Group Members participating were Katrina Armstrong, Jeff Botkin, Ned Calonge, James Haddow, Maxine Hayes, Kathryn Phillips, Margaret Piper, Sue Richards, Joan Scott, Ora Strickland, SteveTeutsch, and Celia Kaye (via teleconference).

Consultants present were Siobhan Dolan, Judith Johnson, and Glenn Palomaki. Dr. Berg reported that he and Linda Bradley had reviewed the conflict of interest forms submitted by all the WG members in September 2006. No conflicts of interest were identified for this meeting. Two potential past conflicts of interest were noted in the record; none were determined to require action.

Opening Remarks and Introductions
Dr. Berg called the meeting to order at 9:30 am, welcomed the Working Group (WG), and thanked everyone for their participation.

Welcome and Remarks from Drs. Khoury and Collins
Dr. Muin Khoury, Director of the Office of Public Health Genomics welcomed the WG members and thanked them for their efforts. Dr. Khoury introduced Dr. Janet Collins, Director of the National Center for Chronic Disease Prevention and Health Promotion.

Dr. Janet Collins welcomed the WG members to Atlanta and provided praise for the efforts of the group. She appreciates the contribution of the WG to efforts of NCCDPHP in chronic disease and cancer. Dr. Collins thanked Dr. Khoury for his efforts and offered her support and resources for EGAPP.

Presentation on Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Draft Report
Representatives of the Evidence-based Practice Center (EPC) provided a presentation on the draft report and answered questions from the WG. Details of the presentation and discussion are documented in the EGAPP HNPCC Evidence Report records (information embargoed until completion of the evidence report).

Commentary and Working Group Response to HNPCC Draft Report
Dr. Berg reminded the WG that the objective for this discussion is to look at the content of the report and asked for comments. The WG discussed the analytic validity (AV) section and further discussion included specific concerns with the clinical validity (CV) (e.g., definitions of terms, stratification by methodology, exclusion of specific key papers) and clinical utility (CU) (e.g., separation of outcomes for probands and family members) sections that were described in the comments provided to the EPC.

The group had a general discussion on reasonable expectations for quality of reports and the types of direction the WG needs to provide in order to ensure the needed outcome.

Presentation on UGT1A1 Draft Report
Mr. Palomaki and Dr. Bradley presented a draft evidence report on the Benefits of UGT1A1 Promoter Region Polymorphism Testing in Cancer Patients Treated with Irinotecan and answered questions from the WG. Details of the presentation and discussion are documented in the EGAPP UGT1A1 Evidence Report records (information embargoed until completion of the evidence report).

Commentary and Working Group Response to UGT1A1 Draft Report
Dr. Berg reminded the WG that the objective for this discussion is to look at the content of the report and asked for comments. Overall, the presentation and the document were extremely clear. The WG encouraged emphasis on the final end points – side effects and mortality.

Staff Updates 
Dr. Kolor provided an update on project activities.

• The meeting objectives were presented:
  • Plan for finalization and timeline for:
    • UGT1A1 evidence report
    • HNPCC evidence report
    • CYP450 evidence report & recommendations
    • Ovarian Cancer evidence report and recommendations
  • New project: Gene Expression Profiles
    • TEP Selection
    • Decision on approach to first TEP calls
• Outcomes of interest, Key Contextual issues were presented.
• Specific methodological request/guidance was requested on:
  • New project: Cardiogenomic profiling – how to develop?
  • Plan for website development with or without waiver approval by HHS
  • Individual Subcommittee Objectives
    • Methods – Approval of Recommendation framework
    • Products – Process for finalizing a plan for peer review of recommendations
    • Topics – Plan for formatting the topic list and topic selection criteria for web posting & developing a web page for topic solicitation
• Other topics reviewed included:
  • Current status of evidence reviews and recommendations in progress
  • Key questions and analytic framework for the Gene Expression Profiles in Breast Cancer review, and solicitation of Technical Expert Panel (TEP) Members
  • New EGAPP Steering Committee Members and the Steering Committee meeting tentatively scheduled for January, 2007.
  • Update on plan for publication of EGAPP reviews and recommendations in Genetics in Medicine
  • Evaluation plan
  • University of Michigan Center for Genomics and Public Health Stakeholder Report
  • Recent policy activities related to genetic testing, including the FTC/FDA/CDC consumer Advisory on At-home Genetic Tests, the Senate Hearing on DTC Genetic Tests, and the FDA draft Guidance on In Vitro Diagnostic Multivariate Index Assays.

Topics Subcommittee Report
Ms. Scott presented a report of the Topics SC activities and the morning subcommittee meeting. The recent work focused on: 1) recommendation for posting topics list on the proposed EGAPP website; 2) possibility of a rapid ACCE Review to be done by a OPHG fellow, and 3) possible topics for the EPC review.

It was suggested that the website should have a description of the process for selecting topics, a topics table, and short summaries of topics. The benefits (e.g., transparency of process, feedback) and risks (e.g., incomplete information that could be taken at face value) of posting intermediate products were discussed.

There was further discussion on several models for conducting evidence reviews, and how the models used might affect the impact of evidence reports and recommendations. In general, feedback is that it is beneficial and appreciated that EGAPP will assess different models.

The EGAPP WG decided to conduct the Cardiogenomic Profiles review selected in June 2006 as a targeted review rather than an EPC review. The WG voted on several topics for the EPC review and selected “Screening for CYP450 Polymorphisms to Predict Response to Pain Management with Codeine.”

Products Subcommittee Report
Dr. Botkin presented a report of the Products SC activities and the morning subcommittee meeting. The recent work focused on: 1) peer review of EGAPP recommendations; 2) votes to finalize the recommendations format, authorship recommendations, and peer review process; and 3) involving test manufacturers/developers in the evidence collection and peer review processes.

The WG discussed the peer review of EGAPP recommendations process and how to handle confidentiality. The “Review Process for EGAPP WG Recommendations” document and the “Authorship Recommendations and Review Process” documents were reviewed and accepted by the full WG.

With regard to soliciting input from test developers/proprietary providers on the evidence report, it was considered potentially helpful to identify gaps in literature and reinforce transparency, but there are concerns about confidentiality and inappropriate release before a final decision is made. The WG seems to be in agreement asking for the information in the data collection phase is a reasonable approach, but when and how should be discussed further.

Methods Subcommittee Report
Dr. Teutsch presented a report of the Methods SC activities and the morning subcommittee meeting. The recent work focused on: 1) Developing Recommendations document review/acceptance; 2) development of the Methods Procedure Manual; 3) use of existing reviews and assessment of criteria for quality; 4) use of decision modeling; and 5) refining the process of translating evidence into recommendations.

The “Developing Recommendations” document was reviewed and accepted by the full WG. The WG discussed the Methods Procedure Manual with regard to inclusion of contextual and economic costs, more TEP and EPC interactions, and inclusion of AV search criteria. Also, the WG members discussed the overall review process, the consistency of how methods are being applied to each review, and how to help the EPCs better understand EGAPP objectives.

The WG discussed using existing reviews as a source of data. Reviews such as those done by EPCs, NICE and NHS Reports will be used in the EGAPP review process. Decision modeling was part of the first three reviews. The WG discussed developing a “model process” that would be requested for each review in the future.

The WG discussed refining the process of translating evidence into recommendations:

• Specifying the levels of certainty required for different types of tests, outcomes, and applications?
• Assessing magnitude of effect – How will we do it and how big is big enough?
• Methods for assessing cost, opportunity cost and cost effectiveness.
• Specifying how we will provide guidance when studies are insufficient?

The WG discussed how the recommendations relate to the key questions. The analytic framework (supported by the key questions) provides the evidentiary chain to support or refute the overarching question, ultimately looking for good evidence of improvement in health outcomes (morbidity/mortality) or other intermediate outcomes (e.g., health behavior).

CYP450: Developing Recommendations 
Dr. Bradley presented the principal findings of the CYP450 review. Overall, the WG was pleased with the EPC’s response to comments from the TEP and WG, and thought they were addressed adequately.

The WG used the “Principles of Making Recommendation” document to begin formulating the recommendation and determine if the evidence was sufficient to answer the overarching question, and, if not, is there compelling evidence to answer some key questions. A recommendation writing team was conferred to begin drafting the recommendation.

Ovarian Cancer Recommendations
Dr. Dolan presented the principal findings of the Ovarian Cancer report, emphasizing that this was a horizon scanning report developed in collaboration with CDC’s Division of Cancer Prevention and Control. The WG used the “Principles of Making Recommendation” document to begin formulating the recommendation and determine if the evidence is sufficient to answer the overarching question, and, if not, is there compelling evidence to answer some key questions. A recommendation writing team was conferred to begin drafting one or two recommendations focused on proteomic screening tests and gene expression profiles for management. Additional reports and articles to take advantage of the ideas and findings in the report were proposed by others.

Action Items for the next meeting:

• The Products SC will continue work on the peer review process, continue to review project products and documents, and work with staff on website development.
• The Topics SC will be evaluating additional topics for future consideration and also working on format and content for the EGAPP website (e.g., topic list, topic selection methodology).
• The Methods SC will continue to work on decision modeling in each review, develop assistance for the EPC approach to AV, and work with staff on the Procedure Manual.

Dr. Berg thanked everyone for their participation and attendance.  The meeting was adjourned at 1:30 PM.