Working Group Meeting September 10-11, 2012
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; Donald O. Lyman, MD, DTPH; Ken Offit, MD, MPH; Stephen Pauker, MD, MACP, FACC, ABMH; Margaret Piper, PhD, MPH; 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.
Status Updates and review of briefing book materials
Dave Dotson presented an update and review of the briefing book for the meeting. In personnel news, Michael Marrone (John’s Hopkins) and Allison Stewart (PGH Foundation) will be joining us part time to work on the Breast Cancer Gene Expression Profiling Update and the CYP2D6/clopidigril recommendation, respectively.
In other news, the EGAPP WG plans to publish new recommendations for Kras/BRAF testing in Colorectal Cancer and Genetic testing for Type 2 Diabetes risk assessment in the final quarter of 2012.
The EGAPP WG is working on other publications including a Whole Genome Sequencing (WGS) binning manuscript, a EGAPP WG lessons learned manuscript and two additional reviews/recommendations: Familial Hypercholesterolemia testing and a colorectal cancer modeling project.
Muin Khoury provided a brief update on CDC and the Office of Public Health Genomics (OPHG). He expects no further reductions relative to FY11 for the upcoming fiscal year and expects the core staff to remain.
OPHG hosted a conference entitled “New Strategies in Public Health Genomics: Actions to save lives now” held on Friday, September 7, 2012.
In regards to updating the existing EGAPP recommendation for Lynch syndrome, the EGAPP WG discussed if endometrial cancer could be added to the existing recommendation. This would require a review of the high quality evidence and a discussion on the feasibility of this task was undertaken. The EGAPP WG members recommended to investigate this in existing health care systems (e.g. Intermountain Health) which could be helpful since they look at evidence for implementation.
Katrina Goddard, from the KSC, presented background information on the Familial Hypercholesterolemia review. Background information on prevalence, under-diagnosis, locus/allelic heterogeneity, variable phenotype and clinical diagnosis for FH were provided. Additional information was provided on the types of assays (sequencing, targeted mutation analysis, chips) and their respective mutation detection rates range from 13 to 55.6%. There is clinical utility for those diagnosed which includes statin drugs.
The context of existing recommendations from National Cholesterol Education Program/Adult Treatment Panel III (ATPIII), USPSTF, NICE, NHLBI/American Academy of Pediatrics (AAP), and National Lipid Association (NLA) were presented.
An analytic framework was presented to include: adults only, risk assessment (high risk and ave. risk), individual interventions and cascade testing in family members, and clinical utility – statins, vs. harms of testing.
The KSC will be requesting EWG assistance in developing key questions.
Whole Genome Sequencing (WGS) Binning
Katrina Goddard provided an update on the KSC’s WGS project. The update included an overview of the stage 1 process (a quick rule out), stage 2 (binning summary), and 3 case studies. Bin 1 consists of test results that are obligated to be returned to patient. Bin 2 consists of those test results that could be helpful for the patient but either do not have established clinical utility or do not directly impact the patient. The KSC developed an explicit evidence based process for bin 1.
The EWG and KSC will be discussing bin 2 and staging tiers of evidence within the stage. The KSC suggested using quality rating source documents (e.g. AMSTAR) as a tie breaker for conflicting evidence at the same bin 2.
Case Studies for binning include FAP, HHC and A1A.
CYP2C19 Testing/Anti-platelet Therapy
Issa Dahabreh (Tufts EPC) presented the results of the CYP2C19/Clopidogrel evidence review. Clopidogrel clinical mechanisms and enzymes were presented leading to clinical outcomes. The presentation included an overview of the variants (e.g. loss of function (*2,*3,*4,*5), gain of function (*17) and normal function(*1)) The key questions were reviewed and the literature search methods and study selection criteria were presented.
A qualitative and quantitative synthesis of available evidence was presented including the strength of evidence. Limitations of the review were outlined.
The full presentation is embargoed until the review is published.
CRC collaboration planning discussion – Karen Kuntz
Karen Kuntz presented a review of the CISNET Colorectal cancer (CRC) collaboration project. A background on colorectal cancer related to this project was presented. Specific aims of the project as the natural history of CRC affords an opportunity to screen. The analytic plan was reviewed.
The KSC work needs to be specifically framed. Currently, the EGAPP WG does not understand the specific analytic framework and key question that would be used in an evidence review process.
Would a recommendation be based only on the model? Is the EWG willing to make a recommendation based solely on modeling? A recommendation needs to be described as “model-based on evidence” or hypothesis generating.
The scopes for each KSC and CISNET were defined as related to the project.
Clinically relevant genetic variants resource
Ned Calonge led the EWG in a discussion on clinically relevant genetic variants resource. The purpose of the discussion was to determine the EGAPP WG interest in partnering with one or more WG members in responding to a RFA. The EGAPP WG could participate in the effort by continuing the EGAPP “binning effort, development of end user products, WG members on individual committees and partnerships on developing methods.
Prostate Cancer/PCA3 review and recommendation
Glenn Palomaki presented on behalf of the BCBSA EPC, who conducted the evidence review on PCA3 testing for Prostate Cancer. Background and rationale for prostate cancer screening were reviewed and the key questions were defined:
- Examine the use of PCA3 in patients at higher risk
- Improving decision making about treatment choices (e.g. active surveillance vs. aggressive therapy)
A summary of the methods used in the evidence review were reviewed including literature search and article selection criteria. The results were reviewed for analytic and clinical validity and clinical utility. Conclusions and gaps in knowledge were presented.
The full presentation is embargoed until the review is published.
Prostate Cancer/SNP panel recommendation
The EGAPP WG discussed the recommendation and a vote on language was approved.
There were no public comments.
Wrap-Up and adjorn
Ned Calonge thanked the EGAPP WG members for their time and adjorned the meeting at noon.
The next EGAPP Working Group Meeting is scheduled for Monday & Tuesday,
February 11 -12, 2013 in Atlanta, GA.