Working Group Meeting December 6-7, 2010

Atlanta, Georgia

 

MEETING SUMMARY

View Agenda

 

EGAPP Working Group members present: 
Al Berg, MD, MPH; Ned Calonge, MD, MPH, chair; Doug Campos-Outcalt, MD, MPA; Ben Djulbegovic, MD; Ted Ganiats, MD; James Haddow, MD; Roger D. Klein, MD, JD; Don Lyman, MD, DTPH; Ken Offit, MD, MPH; Stephen Pauker, MD, MACP, FACC, ABMH; Margaret Piper, PhD, MPH; Sue Richards, PhD, FACMG; Ora Strickland, PhD, RN, FAAN; and Sean Tunis, MD, MSc

 

Welcome and Opening Statement
Ned welcomed everyone to Atlanta and the EGAPP Working Group (EWG) members each introduced themselves.  The CDC Staff and Knowledge Synthesis Center (KSC) staff introduced themselves.

Stephen Thacker presented the welcome and opening of the EWG Meeting.  He presented the Office of Public Health Genomics in context of the organization and by Tom Freiden’s (the CDC Director) priorities.  The role of the office is to cross cut and enable other programs to do things better in the aspect of genomics.

 

CDC Update
Muin Khoury thanked the EWG for the smooth transitioning of chairs, members, and team leaders within the EGAPP program.  EGAPP and OPHG have a performance plan internal to the office, and the goals of the office are matched specifically with the priorities set by the CDC Director.
Muin Khoury outlined the objectives of the office including:

• Knowledge Synthesis Center (KSC)
• Public health implementation with a focus on BRCA, Lynch syndrome and family history
• Comparative Effectiveness Research Stakeholder meeting – January 11, 2011
• Fourth National Conference on Genomics and Public Health  - December 8-10, 2010

The office is working on a “Data to Action Cycle Program” which includes the KSC with whom the EGAPP staff is working closely.  These include efforts to ramp up KSC operations, AHRQ reviews, PLoS EoGT, and GAPPNet.
 
Muin Khoury asked the EWG to consider taking a role in family history evaluation.

 

Staff Status Updates and briefing book materials 
Dave Dotson presented the staff status updates including a review of the agenda, publication pipeline and current ongoing reviews.

The publication pipeline includes the CVD review and recommendation scheduled to be published in the December issue of Genetics in Medicine.  Additionally, the Factor V Leiden recommendation is scheduled to be published in the January issue of Genetics in Medicine. 

The recommendations will be submitted to Guidelines.gov for publication on their web site.

The PCA3 expression review is in need of a TEP.  Roger Klein, Sean Tunis and Ben Djulbegovic volunteered to be on the TEP for the PCA3 expression review.
Strickland volunteered to be an addition to the Age-related Macular Degeneration Review.

 

KSC – CDC Objectives, process for funding announcement
Ralph Coates introduced the KSC personnel:  Evelyn Whitlock, Jennifer Lin, and Katrina Goddard; and described the process for establishing the KSC.  The process included the process for drafting the proposal, review, selection process, and early discussions of KSC activities. 

Basic KSC activities will be to assist in conducting more reviews in order to make more recommendations more quickly.  Additionally, the activities include topic briefs, and assisting the development of methods and other EWG methodology. 

 

KSC – Introduction of KSC
Evelyn Whitlock introduced the Knowledge Synthesis Center representatives and provided some background on each.  The purpose of the presentation is to provide overview of Center for Health Research-Northwest, communicate the breadth of evidence-based medicine activities at CHR (Oregon Evidence-based Practice Center - EPC & others), and review key elements of our proposal to support EGAPP as the first Knowledge Synthesis Center.

The Center for Health Research-Northwest is the recipient or co-recipient of the USPSTF grant for Evidence-based reviews since the inception (1998).  They currently have 21 reviews in progress, with 12 new additions since July 2010. 

Under this award, the primary goal of the Center for Health Research-Northwest is to establish a KSC in collaboration with OPHG.  The second goal is to conduct systematic evidence reviews.  Each of these reviews will have at least 4 calls; at least 3 presentations (depends on the topic), as well as, several planning calls.  The third goal is to conduct targeted reviews and post topic briefs on PLOS EGT on specific topics identified by the CDC OPHG.  The fourth goal is to establish a working relationship with the EWG to assist in developing novel methods for conducting reviews built on EGAPP methods and document the methods.

 

Collaboration Process for EWG, KSC & CDC 
Ned Calonge, Ralph Coates and Evelyn Whitlock led a discussion for the vision of a collaboration process between the EWG, KSC and the CDC – OPHG.  Key participants included KSC, EWG and OPHG Staff.

There particular areas that might be significantly different than from work with USPSTF and OPHG.  There are different iterations of EPC and USPSTF; however, more involvement of people the more time that it takes to complete the individual reviews.  The KSC is proposing more interactions in the beginning to effectively develop the process and be clear on the topic. 

Ultimately, publishing is a big factor from the KSC standpoint and resource allocation on the KSC side is critical to accomplish this.

There is key input needed for the development of the clinical scenario and understanding the key questions/analytic framework.  A key question is the addition of AV from the KSC standpoint.  The KSC understands the need to ask questions regarding this and other aspects of the review.
To quickly develop a preferred format for the summary of evidence is important and having this for the EGAPP evidence reviews would be beneficial to the ability to simplify presentations and documents.
All parties agreed that communication is the most important tool in building a successful working relationship.

 

Initial Topics for KSC & CDC
Ralph Coates presented the initial topics and projects for the KSC.  The primary topics for the KSC Systematic Evidence Reviews are:

• Use of Fecal DNA Screening to Detect Colorectal Cancer and Improve Patient Outcomes
• KRAS and BRAF Testing for use of anti-EGFR Antibody Treatment for Colorectal Cancer
• Genetic Testing for CYP450 Polymorphisms to Predict Response to Clopidogrel (Plavix)
• Analysis of Gene Variants in Adults with Early Stage Age-related Macular Degeneration (AMD) to Identify Patients at Higher than Average Risk to Progress to Wet AMD

Key funding groups and Technical Expert Panels (TEP) have been identified for these reviews.

The CDC & KSC will be supporting the EWG and the methods subcommittee in the development of additional methods and quick no’s reviews.

The KSC will participate in the development of Topic Briefs for PLoS Currents: Evidence on Genomic Tests.  Input from EWG topics and products sub-committees on topics to be completed and formatting will be considered.

 

Type 2 Diabetes update
Michael Douglas presented the current evidence found for the type 2 diabetes (T2D) review for both clinical scenarios. 

Data was presented on the clinical validity and clinical utility on the Use of a multi-gene panel in the general  population to estimate lifetime risk of developing T2D including: 8 markers reviewed in meta-analysis, 14 markers used in available test panels from literature and 9 markers not found in available test but literature exists.  Monte Carlo simulation modeling data was presented for 4, 8 and 31 markers in relation to the use of a multi-gene panel in the general population to estimate lifetime risk of developing T2D.

 

Engaging Stakeholders 
Ralph Coates and Ned Calonge lead a discussion on engaging stakeholders.  The purpose of the stakeholder group is to “get involved in knowledge synthesis and distribution.” As background, the EGAPP Stakeholder Group disbanded after an agreement of roles could not be reached. 

 

EGAPP Audience and Coordination of EGAPP with USPSTF & other advisory groups 
Ralph Coates and Ned Calonge led a discussion on the EGAPP Audience and Coordination of EGAPP with similar advisory groups.  There are number of federally supported or sanctioned evidence based groups with some overlap in mission.  These include SACGHS, IOM, newborn screening, Community Guide, USPSTF and ACIP.

The EWG thought there needs to be some clarification of what the methods for evidence review are for each of these groups.  There is likely to be different methods which could affect whether they should be equivalent groups in terms of products produced. With resources so slim, we should never do anything that overlaps.

There was a suggestion to pursue a meeting among the various groups making evidence based recommendations.   The idea of inviting other federal agencies to our WG meetings is appealing.  It would require a little different format for the meeting, but everyone involved could contribute when needed and would find it useful.  The meeting would need to be convened through the Secretary’s level. 

 

Topics Subcomittee report
Sue Richards presented a report on the morning subcommittee meeting.  The topics included topics briefs from knols, suggested topics for evidence review by the KSC, and a joint Methods/Topics SC call to discuss methods.

The topics briefs from knols were discussed and the main question was should these be used for selecting topics or information purposes to the genetics community.  The type of information in them and the format would be different depending on the purpose.

It was also suggested to expand the existing Lynch syndrome review/recommendation to include endometrial cancer in women. 

A Joint Topics/Methods meeting which can look at nexgen sequencing review process? Michael will schedule back to back calls for methods/topics to discuss this topic.

 

Products SC Report
Doug Campos-Outcalt presented a report on the morning subcommittee meeting.  The topics include translational products, the Lynch syndrome recommendation translation project, and implementation of the translational products.

The previous goal was to have a set of translational products ready to be released at the time of review/recommendation publication.  These were originally to be three different products:

• Two for clinicians
•  One for general public
  • Can’t get on to web site for up to 6 months due to several issues
  • Maybe we need smaller number of products
  • The consumer and clinician product could be the same

Lynch syndrome recommendation

• Is it meant to be implemented through the primary care or through a state health department?
• No translation product for clinicians on how to implement?
• Why wasn’t thought given in the beginning?
• What about a 2 step (recommendation; implementation of the recommendation)?

This is a recurring theme; how to implement and who the audience is.  This is dependant of the individual review.

• Pathologists
• Comprehensive Cancer Centers
• NCCN guidelines
• Going forward
  • Need to interface with different groups
  • What kind of liaison structures do we need in place?
    • Depends on the topic
    • Systematic way
  • Implementation documents need to be generated
    • Brings back to EGAPP WHO the audience is?

There are huge complexities on implementation in the Lynch syndrome recommendation.  The primary question is “My patient’s relative has Lynch syndrome what do I do as a primary care physician?”  This raises questions like:

• Who is the audience then?
• Need to link up with stakeholders
• What is the product?
• Privacy issues with primary care physician to inform the proband; and the proband needs to inform the relative.

Products SC will not be developing translational materials on their own.

 

Methods SC Report
Jim Haddow presented a report on the morning subcommittee meeting.  The report included Quick Nos, Updating reviews and Nuancing the “I’s.”  The report included a short presentation by Steve Pauker on a recent presentation seen on Factor V Leiden at the SMDM meeting.

Extensive discussion about Quick No’s

• Dave Veenstra is the lead
• A summary statement has drafted for consideration by the Methods SC and KSC
  • Will involve input from the KSC
  • Primary topic for the next Methods SC call

Updates

• Obligated to do an update by 2013
• Need to update the CYP450/Depression topic to keep on the National Guidelines Clearinghouse web site
  • Cyp450/depression seems to be dead in practice
  • Do we want to use resources to do this?
  • Can we do a literature scan to from last review to current and make a statement to not change the recommendation statement?
• Graphic display of method updates?

Steve Pauker presented on recent presentation on Factor V Leiden and Anticoagulation duration model from the recent SMDM meeting.  The primary question is has anyone heard of these conclusions of protection genotype?  No one on the EWG had heard of these.

 

Public Comment
There were no public comments

 

Wrap up and action items
The new EWG members selected what subcommittees they wish to be on.  Ben Djulbegovic and Sean Tunis selected the Methods SC, and Don Lyman has selected the Products SC. 

The KSC representatives asked to be added to all the subcommittee calls.

Jim Haddow thanked everyone for their participation and adjourned the meeting at 12:30pm. 

The next EGAPP Working Group Meeting is scheduled for Monday & Tuesday,
February 7 - 8, 2011 in Atlanta, GA.