Working Group Meeting May 13-14, 2013

Virtual Meeting

 

MEETING SUMMARY

View Agenda

 

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; Roger D. Klein, MD, JD; Don Lyman, MD, DTPH; Ken Offit, MD, MPH; Stephen Pauker, MD, MACP, FACC, ABMH; Sue Richards, PhD, FACMG; Ora Strickland, PhD; 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.  Michael Marrone (John’s Hopkins) will be wrapping up his work soon on the Breast Cancer Gene Expression Profiling.

In other news, the EGAPP WG has published two new recommendations for Kras/BRAF testing in Colorectal Cancer and Genetic testing for Type 2 Diabetes risk assessment.  Both have been published online in Genetics in Medicine.

The EGAPP WG, in collaboration with the KSC, has published a Whole Genome Sequencing (WGS) binning manuscript, a EGAPP WG lessons learned manuscript is in draft format and two additional reviews/recommendations are pending:  Familial Hypercholesterolemia testing and a colorectal cancer modeling project.

The Prevention, Epidemiology and Population Science of the European Association of Cardiovascular Prevention is about to start a position paper on the importance of genetics in cardiovascular prevention and wanted to invite the EGAPP WG to collaborate.

 

CDC updates 
Muin Khoury presented the latest news from the Office of Public Health Genetics. 

Karen Greendale is leading the implementation of state click map with resources by state for genetic counselors, physicians and the consumer; and is working on a tool kit for distribution to state genetic counselors on key genomic applications.

He reported on several recent manuscripts in development by the OPHG, including one on the tier classification table and classification process.  This report also touched on the recent whole genome sequencing publications by several groups.

He also gave the EWG a brief report of the outcomes of the Methods meeting held in March 2013 in Bethesda, MD and some EWG members are invited. 

He outlined organizational changes at CDC and the uncertainties in OPHG funding with government budget cuts. 

He expressed his support for the amount of production of writing/manuscripts from the EWG is outstanding since the last meeting with several pending publications.

 

CRC collaboration update 
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 scoping/framing activities since February meeting; present work plan, key questions, and timeline; and discuss the potential products of collaboration.

The framing the key questions, as a systematic review was provided. A summary of the abstract review/full text search was presented.  The modeling approach fits much better.  The work plan including the analytic framework and key questions were discussed.

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

• Data synthesis and evidence review preparation – July 2013
• Final Evidence Review – September 2013

The full presentation is embargoed until the review is published.

 

CRC CISNET collaboration update 
Iris Lansdorp-Vogelaar 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 February meeting; presenting the work plan, modeling strategies, and timeline.

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

• Manifestation of higher CRC risk slightly alters age-specific pattern of CRC incidence and effectiveness of screening
• CRC risk needs to be 90% lower than average before not screening can be considered
• CRC risk needs to be 50% higher than average before intensifying screening is considered
• To determine optimal colonoscopy screening by different levels of increased colorectal cancer (CRC) risk because of family history of CRC or polygenic predisposition
• Focus on family history

 

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).  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 number of articles included narrowed down to 54.  The evidence from these articles was presented based on each key question.

• Key Question 1: In the absence of a gold standard, how well do each of the seven diagnostic criteria for FH predict intermediate or patient-relevant health outcomes?
• Key Question 2a: What is the concordance of FH diagnosis between the seven diagnostic criteria in FH index cases?
• Key Question 2b:  What is the concordance of FH diagnosis between the seven diagnostic criteria in first degree relatives?

 

The full presentation is embargoed until the review is published.

 

MSI testing for 5-FU chemotherapy
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.  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.

• Key Question 1: In patients with colorectal cancer, does determination of MSI status to guide 5FU-based treatment selection/decisions improve patient outcomes (i.e., reduced morbidity, mortality, improved health related quality of life), or lead to non-inferior patient outcomes compared to no determination of MSI status? 

 

• Key Question 2: How well does MSI status predict treatment effectiveness of 5FU-based chemotherapy (i.e., by tumor response [or non-response] by radiographic criteria)?

• Key Question 3: How well does MSI status predict health outcomes (i.e., morbidity, mortality or health related quality of life) in patients undergoing 5FU-based chemotherapy?

 

Preliminary screening of abstracts and full text articles resulted in 46 qualitative synthesis articles and 30 meta-analyses.

The next steps include:

• Finish data abstraction for OR analysis in KQ3 (~40% complete)
• Finalize dual review of data abstraction (~75% complete)
• Complete dual review for quality rating (~50% complete)
• Complete Meta-Analysis for KQ3 (HR and OR analyses)
• Final Report: July 31st, 2013

The full presentation is embargoed until the review is published.

Clinically Relevant Variants Resource
Jonathan Berg presented a brief report on his grant proposal on clinically relevant variants resource.  The grantor is meeting next week to decide on the final funding.  Recipients are expected to get approximately 60% of their proposed budget.

PCA3 testing for prostate cancer recommendation – Michael
Michael Douglas presented the latest PCA3 testing for prostate cancer recommendation.  The final draft has been submitted to peer-reviewers for comment.  Comments are requested to be returned by the end of May and submission to GIM following that week. 

Prostate Cancer SNP Panel recommendation update
Dave Dotson gave a status update and the prostate cancer SNP panel recommendation statement is almost ready for peer review.  Suggestions for peer reviewers were requested.

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 scheduled for Monday & Tuesday,
August 19 -20, 2013 in Atlanta.