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EGAPP Working Group Meeting August 19-20, 2013


Atlanta, Georgia



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EGAPP Working Group members present:
Jonathan Berg, MD/PhD, FACMG; Ned Calonge, MD, MPH, chair; Doug Campos-Outcalt, MD, MPA; Ben Djulbegovic, MD; Ted Ganiats, MD; Cecile Janssens, PhD; Roger D. Klein, MD, JD; Ken Offit, MD, MPH; Stephen Pauker, MD, MACP, FACC, ABMH; Sue Richards, PhD, FACMG; Ora Strickland, PhD; Sean Tunis, MD, MSc; Marc Williams, MD, FAAP, FACMG; and Doris Zallen, PhD.


Welcome and Opening Statement
Ned Calonge opened the meeting by welcoming the EGAPP Working Group (WG) members, Knowledge Synthesis Center (KSC) Members, and CDC staff.  Each person introduced themselves and provided a brief summary of their involvement.


EGAPP updates
Dave Dotson presented an update and review of the briefing book for the meeting.  He also announced that Michael Douglas will be leaving OPHG and EGAPP Initiative at the end of August.  Michael Marrone (John’s Hopkins) will be wrapping up his work soon on the Breast Cancer Gene Expression Profiling by submitting the evidence review update to Genetics in Medicine.

In other news, the EGAPP “scored” very high in a recent systematic review of Guidelines for guidelines developers.”  Dave reviewed the key points of the systematic review and how EGAPP methods were superior to others.

The EGAPP WG has published the lessons learned manuscript in addition to three recommendations published or in press since the last meeting:  KRAS/BRAF in metastatic CRC, Type 2 Diabetes risk assessment, and PCA3/prostate cancer (in press).

Two new recommendations for CYP2C19/clopidogrel and Prostate cancer SNP panels are underway.  Two additional reviews/recommendations are pending:  Familial Hypercholesterolemia testing and a colorectal cancer modeling project.

Dave Dotson also reviewed the significant web presence of the web site, the citations from EGAPP reviews/recommendations and other publications.

FY2014 projected publications include:


CDC updates
Muin Khoury presented the latest news from the Office of Public Health Genetics.  Since we last met the OPHG has implemented or is close to completing:  Tool kit for high value recommended genetic testing (almost done), A clickable state map for genetic resources (June 2013), Enhanced communication strategies (social media), Surveillance indicators (in progress), and participated in a training course at Emory University on August 15-16, 2013.

OPHG will also be participating in the Disparities Conference, NHGRI Genomic Medicine Federal Meeting, FH Summit September 19, 2013.

OPHG staff members have been advancing the evidence-based classification of genetic testing methodology with a draft of the March 2013 methodology meeting discussions, a Tier 1-3 classification manuscript, and an update to the Tier 1-3 classification of FDA Pharmacogenomic biomakers list on their web site. 

CDC Advanced Molecular Detection Initiative is a FY14 CDC Budget Initiative which focuses on Pathogen Genomics & Bioinformatics, while this will not directly impact OPHG, it is good news that CDC management are funding genomics research.   

He outlined organizational and leadership changes at CDC and the uncertainties in OPHG funding with government budget cuts with the next fiscal cliff of January 2014.

He discussed the future of honest broker role and the EGAPP initiative.   


Cisnet Collaboration Update and Discussion
Ann Zauber presented an update on the CISNET collaboration on behalf of the CRC/CISNET team.  Members of the team were introduced and/or acknowledged. The goals of the discussion were outlined as:  summarize scoping/framing activities since the May meeting; presenting the work plan, modeling strategies, and timeline.

The framing the modeling was outlined:  microsimulation modeling of CRC increased risk, impact of increased risk assumptions on screening benefits, exploratory analyses for polygenic predisposition, and cost-effective analyses.  Each topic was presented in depth and key questions were discussed.  Preliminary conclusions include:


The full presentation is embargoed until the review is published.


CRC Collaboration Update and Discussion
Nora Henrikson presented an update on the CRC collaboration on behalf of the KSC.  Members of the team were introduced and/or acknowledged. The goals of the discussion were outlined as:  summarize activities since May meeting; present work plan, key questions, results to date and timeline.

The framing the key questions, as a systematic review was provided. A summary of the abstract review/full text search and dual independent review was presented.  KSC members have operationalized the histology, natural history events of interest and categorized overlapping populations (eliminated), tiering of study types (population-based vs. screening) and family history.

Initial data abstraction is complete for Key Question 3. The KSC will complete the data abstraction, data synthesis and quality, and begin drafting the evidence review.  Monthly meetings with CISNET partners continue. 

The deliverables were defined as:  Evidence Review, Modeling Results, and Recommendation.
A timeline was proposed.  Key milestones include:

The full presentation is embargoed until the review is published.


5-FU & MSI Status Update and Discussion
Katrina Goddard presented a report on their recent project on MSI status and response to 5FU chemotherapy for the EGAPP WG to consider preparing a recommendation.  The team members were acknowledged. Background information on microsatellite Instability (MSI) in colorectal cancer was presented including information on Lynch Syndrome CRC, a review of clinical guidelines, and evidence of a prognostic effect in which MSI could be predictive of prognosis and a negative predictor of response to 5-fluorouracil (5-FU). 

The key questions and analytic framework, inclusion/exclusion criteria and search strategies were reviewed.



Screening of abstracts, full text and abstraction of data has been completed.  A report on the odd ratios and hazard ratio analyses were presented.  The results of the primary analysis show that treatment with 5FU-based chemotherapy improves DFS and OS in CRC patients but no difference in the effect of treatment based on MSI status.  Results of the sensitivity analyses show that the conclusions depend on the choice of included data.  The final report will be completed in the next month.

The full presentation is embargoed until the review is published.


Familial Hypercholesterolemia
Katrina Goddard presented an update from the KSC on the ongoing Familial Hypercholesterolemia (FH).  The team members were acknowledged. She presented background and existing FH criteria for clinical diagnosis.  There is no one clinical definition for FH.  The clinical criteria vs. molecular criteria for FH were presented, as well as, FH mutations in relation to cholesterol levels.

The search strategy for articles was reviewed and results to date were presented.  The evidence from these articles was presented based on each key question.


The full presentation is embargoed until the review is published.


Muin Khoury and Dave Dotson presented a proposed structure for the EGAPP Initiative moving forward due to budgetary cuts and staffing.  The proposal included all virtual meetings, breaking up the EWG into teams to handle specific items, and elimination of a chair for the group. 


Clinically Relevant Variants Resource
Jonathan Berg presented a brief report on his grant on clinically relevant variants resource.  He outlined the differences between the Clinically Relevant Variant Resource (CRVR) and other resources.  The collaborators to the grant were outlined and what the roles of each would be, as well as, an organizational chart was presented.  Ken Offit will be co-chairing a cancer working group and Cecile Janssens will be co-chairing a common diseases working group.  Sue Richards will be on the Science Advisory Board. 


Breast Cancer Gene Expression Profiling Update
Michael Marrone presented an update on the Breast Cancer Gene Expression Panels review update.  The previous EGAPP recommendation was reviewed.  A review of recent “non-EGAPP” recommendations was presented.  The key questions were reviewed, types of studies and evidence found was presented.

The evidence review found that none of the systematic reviews identified direct evidence of the clinical utility of using Oncotype DX or MammaPrint to direct treatment decisions in women with breast cancer and very low quality, indirect evidence of the clinical utility of Oncotype DX and MammaPrint.

The cost effectiveness of existing studies assuming clinical utility was reviewed.

The full presentation is embargoed until the review is published.


Public comments
There were no public comments.


Wrap-Up and adjorn
Ned Calonge thanked the EGAPP WG members for their time and adjourned the meeting at noon.


The next EGAPP Working Group Meeting is TBA


Historical Document
Page last updated: September 12, 2013
Page last reviewed: September 12, 2013
Content Source: OPHG Staff