Working Group Meeting January 29-30, 2007

Hilton Garden Inn Atlanta Airport / Millenium Center – 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, Maxine Hayes, Celia Kaye, Kathryn Phillips, Margaret Piper, Sue Richards, Joan Scott, Ora Strickland, Steve Teutsch, and James Haddow (via teleconference).  Consultants present were Siobhan Dolan, Debra Leonard, 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 December 2006. No conflicts of interest were identified for this meeting.  Two potential past conflicts of interest were noted in the record; neither were determined to require action.

Opening Remarks and Introductions

Dr. Berg welcomed the WG and thanked everyone for their participation.

Welcome and Remarks from Dr. Khoury 

Dr. Khoury, Director of the Office of Public Health Genomics (OPHG) at CDC, welcomed the WG and once again expressed CDC’s appreciation for the amount and effectiveness of their work.  He expects the anticipation of their work to be high and that this will be an important year for EGAPP.  Dr. Khoury expressed the OPHG commitment to the EGAPP process for an additional two years.  He also briefly described the areas of discussion at the EGAPP Steering Committee meeting on January 26, 2007, and that he felt the discussion provided many constructive suggestions for the project.

Presentation on Gene Expression Profiling in Breast Cancer Patients 

Representatives of the Evidence-based Practice Center (EPC) provided a brief review of the work plan for this review and answered questions from the WG.   A draft report is expected at the end of May.

Presentation on UGT1A1 testing for predicting response to irinotecan in patients with colorectal cancer (CRC)

Dr. Bradley presented a brief overview of the findings of the UGT1A1 evidence report and answered questions from the WG.  The final draft and external reviewer comments will be discussed at the next meeting.

Rapid ACCE Review on CYP2C9/VKORC1 and Warfarin Treatment 

Mr. Palomaki presented a brief report on the methods and approach for a recently completed report that will be released by ACMG in the near future.

Breast Cancer Expression Profiling Report – Commentary and Working Group Response

Dr. Armstrong led a WG discussion on the Breast Cancer Expression Profiles presentation by the EPC.  This report is progressing well.

EGAPP Staff Updates

Dr. Katie Kolor presented:

Staff objectives for the meeting:

• Plan for finalization, peer review, and submission of Ovarian Cancer recommendations
• Plan for finalization, peer review, and submission of CYP450 Recommendation Statement
• Plan for finalization and peer review of UGT1A1 evidence report
• Selection of Lead and Writing Team for UGT1A1 Recommendation Statement
• Additional discussion AHRQ HNPCC report and selection of Lead and Writing Team for HNPCC Recommendation Statement
• Determining status of Gene Expression Profiling report
• Kick-off the next two planned reports (Cardiogenomic Profiling and topic to be determined)
• Approval of plans for web site development
• Update to Working Group from EGAPP Steering Committee meeting and briefing from Dr. Khoury and Dr. Bradley on project plans
• Current status of the evaluation plan, the OMB submission, and planned surveys were presented.  Stakeholder surveys have been developed.  After OMB clearance, first surveys will be conducted 6 months after release of the first 2-3 Recommendation Statements.
• Current status of evidence reviews
• Completed/released reports with Recommendation Statements in development are CYP450 Testing in Patients Treated for Depression with SSRIs, and Genomic Tests for Ovarian Cancer Detection and Management
• Final report under review and Recommendation Statement in planning is Testing for HNPCC in Colorectal Cancer Patients and Their Families
• Draft report in review is UGT1A1 Testing in Colorectal Cancer Patients Treated with Irinotecan
• Evidence review in progress is Gene Expression Profiling for Breast Cancer Management and Prognosis
• Evidence reviews in planning are Use of Genomic Profiling to Assess Risk for Cardiovascular Disease and Identify Individualized Prevention Strategies and Screening for CYP450 Polymorphisms to Predict Response to Pain Management with Codeine

Mr. Douglas presented the current status of the recently approved independent www.EGAPPreviews.org web site:

• The mock-up was presented with suggested color scheme and content pages.
• Next steps include resolution of server hosting issues, development time of 1-2 weeks after server space acquired, and transfer of current pages with updates.  Staff will develop additional pages in conjunction with Subcommittees & consultants
• WG will work with Staff to finalize the approval process for web summaries.

The WG expressed interest in revising the color scheme and EGAPP logo.  Dr. Bradley noted that the logo was submitted with the web site waiver and may not be modifiable.  The WG did not identify any particular alternative color scheme; staff will consider with the web team.

Products Subcommittee Report 

Dr. Kaye presented the Products SC report that addressed: 1) the process for internal review and external peer-review of non-EPC reports and WG Recommendation Statements; and 2) the updated list of completed and planned EGAPP products.

A discussion on the review and approval process for topic summaries to be posted on the www.egappreviews web site was conducted in conjunction with the Topics SC (presented by Topics SC).

Topics Subcommittee Report 

Ms. Scott presented the Topics SC report, including: 1) review of a draft narrative on the topic selection process to be posted on the web site; 2) review of a draft topics list for the web site; and 3) review of a draft document on the approval process for Topic Summaries to be posted on the web site.

The draft narrative on topic selection for the web site is intended to describe the EGAPP process for identifying, prioritizing and selecting topics for review.  The topic list will provide web site visitors a regularly updated list of tests under evaluation and under consideration for evaluation.  Summaries of topics in review will also include the Key Criteria and EGAPP considerations upon which selection of the topic by the WG was based.  Each topic summary will have standard disclaimer language to include:

• This information is NOT intended to be a comprehensive review
• This information is NOT a direct or implied endorsement of the test or manufacturer by EGAPP.

The Topics SC will review Topic Summaries for the web site and then send to the full WG for review.  A full Working Group vote will not be needed to approve for posting on the www.EGAPPreviews web site.

Plans for the future direction of the subcommittee include:

• development of more systematic and standardized processes for identifying new topics that includes outreach to organizations, individuals, and the academic/laboratory community, and more systematic horizon scanning.
• determining protocols for updating of topic summaries.

Methods Subcommittee Report

Dr. Teutsch presented the Methods SC report that addressed: 1) decision analysis/modeling as part of an evidence review; and 2) grading of evidence for Clinical Validity and Clinical Utility.  Dr. Piper also presented an update of the Analytical Validity document.

Potential reasons for use of decision analysis/modeling include:

• Assessing magnitude of effect for different intended uses
• Assessing impact of use of the test and subsequent interventions versus current or alternative strategies
• Identifying major determinants of effectiveness

The definition of “model” and the focus of modeling (e.g., effectiveness, cost-effectiveness) was a concern for some WG members.  The definition suggested was: “Simple decision tools to facilitate evaluation and communication, rather than complex, sophisticated models intended as stand-alone scientific products with the purpose of providing estimates of population, rather than individual, effects.”  This type of simple model – similar to the one developed for the UGT1A1 report – would be powerful with the practicing physicians, helping to clearly lay out the benefits vs. harms.

Grading Evidence on Clinical Validity (CV) and Clinical Utility (CU)

Strength of evidence criteria for clinical validity and clinical utility need further development and updating.  The WG suggested a framework for looking at the definitions for Clinical Validity and Clinical Utility by type of test (e.g., diagnostic, predictive, pharmacogenomics).  The methods that one would use to look at the CV and CU may be dependent on test type.  The methods SC was charged with completing a proposed table that has a definition for CV and CU by test categories.  WG members discussed how this framework might change how we are currently evaluating our reviews.

Analytic Validity (AV)

Dr. Piper presented the regulatory requirements and the arguments for including AV in the evidence reviews.  Some key arguments are:

• Laboratory performance (CLIA) regulation – CLIA provides general oversight of lab performance but there is no genetics specialty
• Few proficiency testing programs for genetic testing and no mandate to participate
• Few genetic tests FDA-approved, and recent draft guidance may result in regulation of some, but not all, genetic tests
• Good CV or CU not possible without good AV

Discussion of the HNPCC Report, Hereditary Nonpolyposis Colorectal Cancer:  Accuracy of diagnostic strategies and implications to patients with colorectal cancer and their families.

Mr. Palomaki focused comments on the important estimates expected from the HNPCC report, and some of the questions related to the report results.  The WG discussed the next steps including:

• contacting the EPC to resolve questions prior to release of report;
• WG, Staff and consultants to consider developing and conducting a decision model to help identify critical variables on which to focus; and
• The TEP/writing group to agree on distribution of responsibilities for review.

Recommendation – CYP450 and Depression 

The WG reviewed a brief overview of the findings of the CYP450 Report and the current draft of the Recommendation Statement.

Recommendation Statement – Genetic Testing for Ovarian Cancer

Dr. Siobhan Dolan presented the current draft recommendation that is focused solely on proteomic tests for detection of ovarian cancer.  A number of questions were posed to the WG:

• Currently, there are no clinically available proteomic tests for detection of Ovarian Cancer.  Does EGAPP want to comment on something that is not available to the general public at this time?
• Should any additional analyses be done on the data identified by the EPC?
• What additional data are needed to support our assessment of the harm of screening?
• How should the research gaps be presented?

HNPCC Recommendation – Writing Team & Planning

The WG did not form a team to begin drafting a recommendation statement pending further discussion of the evidence report.

UGT1A1 Final Report and Recommendation Discussion

The recommendation writing team proposed language for the initial recommendation statement the WG discussed the language.

CYP450 Testing for Treatment of Pain with Codeine – Review Status

Dr. Bradley discussed early planning for this review.

Closing Remarks

Dr. Berg thanked everyone for their participation and the meeting was adjourned at 1:05 pm.