Working Group Meeting February 7-8, 2011
EGAPP Working Group members present:
Al Berg, MD, MPH, Chair; Ned Calonge, MD, MPH; Doug Campos-Outcalt, MD, MPA; Benjamin Djulbegovic, MD, PhD; Nancy Fisher, RN, MD, MPH; Ted Ganiats, MD; James Haddow, MD; Roger D. Klein, MD, JD; Don Lyman, MD, DTPH; Kenneth Offit MD, MPH; Stephen Pauker, MD, MACP, FACC, ABMH; Margaret Piper, PhD, MPH; Sue Richards, PhD, FACMG; Ora Strickland, PhD; Sean Tunis MD, MSc; and David L. Veenstra, PharmD, PhD
Welcome and Opening Statement
Ned Calonge called the closed session to order. He welcomed the EGAPP Working Group (EWG) to Atlanta, GA and to the February EWG meeting. He asked for introductions for EWG members, CDC Staff and Knowledge Synthesis Center (KSC) members in attendance.
CDC, OPHG, and EGAPP
Muin Khoury presented a plan for downsizing the EGAPP Initiative between now and the end of September 2011.
Starting in October 2011 the OPHG will be focusing on the following functions:
- Performing limited horizon scanning
- Continuing limited stakeholder engagement
- Seeking external support for an independent EGAPP function
- Assessing whether or not a “bare-bones” EGAPP activity by phone/email can be supported until current work is done.
Most of the CDC staff and contract staff will be leaving for other positions, and support for the KSC will be ending in September 2011. Other organizations were approached about funding for EGAPP. No organizations approached wished to take on the EWG and the EGAPP Initiative.
The goal of the meeting is to determine EWG, KSC and OPHG planning for what can be accomplished in the next few months.
Some possibilities could include one or more of the following:
- Several evidence reviews are available or will be available soon
- EWG subcommittee papers in various stages of work, specifically developing methods for “Quick Nos”
- Writing a final report or publication on the EGAPP Initiative
- Developing recommendations from any of the evidence reviews
- Continuing or archiving the web site
- Holding a May/June meeting
- Continuing/Creating subcommittees to develop publications
- Members can apply for independent funding
Do we need EGAPP 2.0? Some possibilities could include:
- Core EWG methods working group that can be supplemented with ad hoc disease-specific expertise
- Implementing “Quick No” methodology
- Pointing out the extent and quality of information for “informed decision making”
- Pointing out knowledge gaps for research
- Full reviews that lead to up or down recommendation to be used sparingly with stakeholder input and collaboration in defining the reviews
CDC, OPHG and EGAPP Working Group Discussion
Ned Calonge opened the floor for discussion on moving EGAPP forward.
What do you think is needed for a home for EGAPP? The EWG needs to have a home to maintain credibility. For OPHG to maintain EGAPP; the function/focus must change in accordance with budget/funding availability. The PCORI project may be able to provide some funding but this has not been officially investigated as a source.
None of the organizations mentioned as a possibility for incorporating EGAPP (CDC, AHRQ, etc.) are private. Can EWG/EGAPP Initiative go private? There may be nothing stopping this move, however, there may be a political piece involved as well. Some proponents of personalized medicine may perceive that evidence-based medicine will slow them down.
- CDC is a neutral home that can house all the focus of EGAPP
- NIH is not specifically used to performing Evidence-based reviews
- AHRQ has the culture and history of evidence-based medicine
- A Cochrane type program for EGAPP might be a feasible process
- There appears to be a perfect marriage between the Genetic Testing Registry and EGAPP
We must be doing something right if we have gotten so many passionate responses. EGAPP is really well respected in terms of methods development and its evidence-based approach. The tempest is the yes and no recommendations which can be seen as slowing down the development of new tests.
The IOM is releasing 2 reports on how to conduct reviews. These reports are going to raise the bar much higher than what EGAPP uses.
The EWG and CDC Staff need to come up with a plan to move the EGAPP Initiative forward.
Status Updates and review of briefing book materials
Dave Dotson welcomed the EWG, CDC Staff and the KSC to the 20th EGAPP Working Group Meeting. The agenda was reviewed for Monday and Tuesday.
EGAPP in the news and on the web primarily focused on the FVL recommendation.
A summary table of reviews in progress was provided. The EWG would like to make recommendations from each of these reviews.
One goal of the CDC Staff is to finalize an EGAPP procedure manual (depending upon how and where this work fits in with EWG priorities that will be developed throughout the present meeting). Volunteers from the EWG to review and provide feedback on such a manual are Doug Campos-Outcalt, Maggie Piper, Jim Haddow & Ted Ganiats. However, later in the meeting, it was decided not to pursue this endeavor.
EGAPP Working Group and Project Planning
The timing of the next meeting should be so that we can have as many of the reviews and draft recommendations done as possible.
The KRAS/BRAF CRC recommendation and Type 2 Diabetes (T2D) recommendations should be made in the same manner as the past. However, the EWG was open to other ideas to make recommendations in other manners. It was suggested that perhaps some recommendations could be made in conjunction with other professional societies that are appropriate for the topic.
A methods procedure manual for a proven method for conducting a review and writing an evidence report would be an ideal product. Once developed, methods to take an existing evidence review and make a bridge/gap process to then make a recommendation could be included in the manual.
KSC might be able to facilitate AHRQ adoption of methods for reviewing genomic tests.
The ”Quick No” process was designed as a method with ongoing support. Dave Veenstra is not sure this is feasible given the funding and staffing for ongoing support. Is there utility to propose moving forward with the methodology?
It would serve us well, to put together the GRADE background material in reference to EGAPP Methods evidence.
An EGAPP Lessons Learned publication in JAMA signed by the full EWG may be an important story to tell including genomics and the future.
Where would you like the staff priorities?
- Updates to the methods paper – could include ”Quick No” theory and portions of topics
- Integrated Procedure manual
- Lessons Learned paper
- 2 recommendations – Type 2 Diabetes and KRAS/BRAF CRC
- Funding possibilities – a preliminary budget is needed
What does the EWG want done by the end of August/September?
- Methods SC people working with KSC to put together one or more methods articles
- EWG members need to determine how they may move forward
- Support for recommendation writing
- EWG web site maintain for archive online
Type 2 Diabetes Report
Glenn Palomaki presented a status report on the current T2D Review. There are two clinical scenarios under investigation:
- Genomic Panel for risk prediction of T2D in the general population
- TCF7L2 testing for risk prediction of T2D in a high risk population.
The methods used for the review were presented including the use of the Venice Criteria (Weak = inadequate = C, C, C; Moderate = adequate = A?? (where zero, one or two A’s exist with the other ratings being B, but not C) ; Strong credibility – convincing evidence A, A, A) to grade the Clinical Validity data.
A model was presented for genetic risk prediction of 4, 8 and 31 genes. ROC curves were generated for each using an assumed lifetime risk for T2D of about 5% and an OR cut-off level of 1.38.
Searches for Clinical Utility in Pubmed were conducted.
Clinical Scenario 2 – risk prediction of type 2 diabetes in high risk populations – was evaluated. A formal search for clinical validity and clinical utility was conducted.
KRAS and Colorectal Cancer Report
Leslie Levin presented a recent review on KRAS and colorectal cancer. A basic history of the Canadian Health system was reviewed and how pharmacogenomic testing (as opposed to drug vs. non-drug technology) is evaluated.
He also discussed stakeholder engagement in relation to the review and recommendations made by Health Canada.
KRAS testing in treatment decision for advanced colorectal cancer
Margie Parthimos presented the analytic framework and AV, CV and CU key questions (similar to those used in the EGAPP methods) for the review conducted by Health Canada on KRAS testing in treatment decision for advanced colorectal cancer. KRAS was the main focus because BRAF and other genes were considered “cusp” genes. A summary of the systematic evidence review was presented.
KRAS Testing Economic Analysis
Lusian Teraci presented the KRAS testing economic analysis done as part of the evidence review. A summary of the evidence and decision on use was presented based on the economic analysis.
EGFR-related pharmacogenetic testing in metastatic colorectal cancer: BRAF and beyond
Jennifer Lin presented a summary of the BRAF and CRC review completed by the KSC. The summary included: a brief summary of introduction and methods, evidence synthesis and a summary of evidence in comparison to body of evidence supporting the use of KRAS testing.
Type 2 Diabetes Recommendation
Glenn Palomaki presented a summary of the T2D review to date. The summary included: a brief summary introduction and methods used for review, a review of the evidence synthesized to date and a summary of modeling exercise. The EWG discussed the evidence for AV, CV and CU and proposed recommendation statement language.
The recommendation writing team will be composed of Jim Haddow, Ora Strickland and Ted Ganiats.
KRAS, BRAF and Beyond Recommendation
Jennifer Lin led a discussion on KRAS and BRAF testing for colorectal cancer treatment with anti-EGFR therapy. The working group decided to use the reviews to make a recommendation on KRAS and BRAF testing. The recommendations will be segmented into 3 parts: KRAS, BRAF, and all other markers (NRAS, PIK3CA, PTEN, ATK). The EWG discussed the evidence for AV, CV and CU and proposed recommendation statement language.
The recommendation writing team will be composed of Ned Calonge, Ken Offit, Roger Klein and Sue Richards.
EGAPP Evaluation Report – Dave Dotson
Dave Dotson presented the final EGAPP Initiative Evaluation Report on behalf of Judy Johnson. The executive summary is in the briefing book along with the full evaluation. A very high level review of data and a call can be scheduled with Judy, if needed.
Ned Calonge led a discussion on transition planning for the EWG. The items discussed were:
- Itemized budget (by function/process)
- Grant writing
- Grant shopping
- AHRQ conference grant
- CER topic submission
- Virtual meetings for EWG
“Lessons Learned” paper
The EWG proposed putting together an EGAPP “Lessons Learned” manuscript to address the EGAPP initiative. The initial group to outline a draft will be composed of Ned Calonge, Al Berg, Ken Offit, Jim Haddow and Muin Khoury. The EWG suggested contact and feedback from emeritus members of the EWG and CDC Staff, as well as, input from Judy Johnson.
Manuscript Rough Outline
- Focus of the manuscript is policy/translation
- EGAPP History
- Products to date
- Controversies/lessons learned (good and bad)
- Stakeholder group
- Liability insurance (FACA, non-FACA)
- Conclusions (spin) – how do we hook the reader?
- Future of EGAPP and evidence-based evaluation
Dave Veenstra led a planning session on updating methods and moving forward. The goal is to further define the EGAPP Methods Development: moving evidence-based medicine into the genomics era. Several opportunities to do this are:
- “Quick Nos”
- Use of existing reviews
- Determining relevance
- Defining the quality criteria
- Staged review process
- Start with clinical validity
- Patient preferences
The methods SC updated the status of their work and provided a timeframe for completion:
- “Quick No”
- Refined methods 1Q 2011; testing 2Q 2011
- Use existing reviews
- Methods developed; testing and implementation 2011-2012
- Staged reviews
- Methods developed; testing 2011-2012
- Risk-benefit modeling
- Methods developed, tested; implementation 2011
- Provide better recommendations
- Develop method in 2011-2012
- Updating analytic frameworks – PICO type
- Refine methods 1Q 2011
Horizon Scanning and Topics Selection
The horizon scanning and process to select topics for review was discussed. This could fit under methods since the original method has a selection process (weighting), but did not have a formal scanning process. The summaries used to aid in the selection process should be made available to the public.
Dave Veenstra, Ted Ganiats, and Ben Djulbegovic will work on a proposed scenario analysis. The topics SC can respond; but the process of topic selection process might not be needed in the methods paper. Sean Tunis will propose the stakeholder involvement/engagement for the topics selection.
Ned thanked the EGAPP Staff and the meeting was adjourned at 1pm eastern.
The next EGAPP Working Group Meeting is scheduled for Monday & Tuesday,
June 27 -28, 2011 in Atlanta, GA.