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EGAPP Working Group Meeting, July 18-19, 2005


Crowne Plaza Hotel - Atlanta, GA



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Topics Chosen for Review at the July 18-19, 2005 Working Group Meeting

Screening for Hereditary Nonpolyposis Colorectal Cancer (HNPCC) in Newly Diagnosed Colorectal Cancer Patients - The evidence report will evaluate the efficacy and effectiveness of screening strategies for identifying HNPCC mutations in an identified high risk subset of individuals with newly diagnosed colorectal cancer. The review will include preliminary evaluations such as clinical and family history, immunohistochemical staining of fixed tumor tissue, or genetic testing for microsatellite instability (MSI) in tumor tissue that are used to select a subgroup of colorectal cancer patients for HNPCC mutation testing.

Testing for Cytochrome P450 Polymorphisms in Adults with Non-Psychotic Depression Prior to Treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) - The evidence report will evaluate what is known about the analytic and clinical validity of this testing, and its efficacy and effectiveness in improving outcomes of drug treatment for non-psychotic depression.


Subcommittee Meetings
Individual meetings of the Methods, Outcomes and Topics subcommittees were held from 8:30 - 10:00 am, allowing the subcommittee chairs and members to finalize recommendations and presentations for the full Working Group.


Welcome and Introductions
The EGAPP Working Group (WG) meeting was convened by Al Berg, Chair. Working Group members participating were Katrina Armstrong, Ned Calonge, James Haddow, Maxine Hayes, Celia Kaye, Kathryn Phillips (by teleconference), Margaret Piper, Sue Richards, Joan Scott, Ora Strickland and Steve Teutsch. Consultants present were Dr. Debra Leonard and Glenn Palomaki. The Chair introduced two members who were not able to attend the May meeting, James Haddow and Maxine Hayes, as well as a new member, Ora Strickland. Nedra Whitehead reported that she and Al Berg had reviewed all the conflict of interest forms from the Working Group members and determined that there were no conflicts for this meeting.


Outcomes Subcommittee Report and Discussion
Steve Teutsch presented a preliminary list of direct and indirect outcomes developed by the Outcomes subcommittee to be considered in reviews of genomic applications. He proposed that the group consider a recently published framework (Tatsioni et al., Challenges in Systematic Reviews of Diagnostic Technologies; Annals of Internal Medicine 2005;142:1048) as a way to organize outcomes for EGAPP. In addition to “patient outcome”, "diagnostic thinking impact", and “societal impact”, the WG noted that additional categories to be considered might be “family impact” and “population impact”. Other key points:


Methods Subcommittee Report & Discussion
Ned Calonge presented the Methods subcommittee work on four key tasks:


Identification of types of evidence to be considered/included in EGAPP evidence-based reviews (EBRs).


Identification of four settings in which genetic tests are used


The WG discussed how analytic frameworks might differ between settings.


Development of an analytic framework for each setting - Domains of analytic questions include efficacy (evidence of utility in controlled settings), effectiveness (evidence of utility in real settings or judgment about ability to operationalize in real settings) and efficiency (cost-effectiveness, judgment about opportunity costs). Model frameworks were discussed.


Development of a taxonomy for conclusions and recommendations - The Working Group reviewed existing approaches for developing conclusions and recommendations, and discussed a preliminary taxonomy for EGAPP reviews that would separate conclusions regarding evidence (i.e., whether the evidence supports net benefit or harm, or is insufficient to reach a conclusion) from the recommendations (i.e., whether the test is or is not recommended). An inconclusive finding would not necessarily be a recommendation not to do the test. The subcommittee will continue to develop the taxonomy.


Topics Subcommittee Report & Discussion


Joan Scott reported that the subcommittee's near term aim was to provide the WG with potential topic choices in sufficient detail that a single topic could be chosen at this meeting. In the long-term, the aim was to provide a comprehensive, updated, organized and prioritized list of potential topics, and a methodology for preliminary prioritization of topics. They started with a list of 28 possible topics. Suggested topics were obtained through preliminary searches (e.g., GeneTests web site, internet, published literature) and from organizations, public health agencies, and health professionals. EGAPP staff prepared two-page summaries for 13 selected topics that included a description of: 1) the disorder tested for, including prevalence and availability of effective intervention; 2) the test(s) to be used; 3) the clinical scenario in which the test would be used; and 4) the number of relevant publications. The group discussed initial criteria for classifying or “binning” topics, including impact (strength of relationship between test and outcome), relevance to health professionals and consumers, availability of the test, severity of the disorder including morbidity and mortality, prevalence/incidence of the disorder (may be number tested), availability of effective intervention for those with positive tests, inappropriate use (or the opportunity for) of testing, if the test is “genetic”, and some expertise available among WG members. A new suggested criterion was potential impact of a systematic evidence review on clinical practice; this may relate to a large patient population or the fact that clinical practice is not well established and the evidence review can bring important information to practice patterns.


There was agreement that a weighting scheme would be useful for broadly classifying the tests, but should not be considered an exact ranking of tests. Going forward, it should be transparent how topics are solicited, added to the list, and prioritized. The current plan for handling topics is that staff will first determine eligibility. Molecular testing for infectious diseases will be excluded from consideration; prenatal and newborn screening tests will be added to the list, but will not be considered further at this time. Staff will produce a very brief (half-page) description for all other suggested topics added to the list. The subcommittee will review the brief descriptions and select topics for which a two-page summary will be prepared; after additional review, the subcommittee will obtain any other information needed to generate a rating of a topic for all criteria. The list of rated topics, with summaries, will be presented to the WG on a regular basis.


Topics of Interest for First Review
Based on discussion using the selected criteria, the four topics that ranked highest were: HER2/neu testing in women with breast cancer; screening for hereditary non-polyposis colorectal cancer (HNPCC) mutations in colorectal cancer patients; BRCA1/2 testing for susceptibility to hereditary breast cancer; and CYP450 testing related to drug therapy for psychiatric diseases. The WG ultimately focused on the HNPCC and CYP450 topics. HNPCC testing is in use and established, but there are still unanswered questions and it is not considered for all new colorectal cancer (CRC) cases (about 145,000 each year). Because HNPCC accounts for only about 3% of all CRC and mutation testing is relatively expensive, it is not feasible to test all newly diagnosed CRC cases; different methods (e.g., clinical and family history, microsatellite instability, immunohistochemical staining) are used to identify CRC patients who are at risk for HNPCC and might be offered mutation testing. This topic raises interesting methodology questions, as the testing results may have a relatively small impact on patient outcome, but a large potential impact on family members.


CYP450 testing is currently being marketed to physicians and has huge potential impact because of the large number of patients taking drugs metabolized by these enzymes. Acknowledging that it would be necessary to narrow the scope of the review, the WG selected depression as a common disorder and a specific category of antidepressant drugs that are very commonly prescribed for depression (selective serotonin reuptake inhibitors or SSRIs). This review is likely to identify a number of gaps in our current knowledge, but could help to shape data collected in the future.


The WG voted to begin work on two evidence-based reviews concurrently.


For the next meeting:



Dr. Berg thanked everyone for their participation and adjourned the meeting.

The next meeting is planned for October 17-18, 2005 in Atlanta, GA


Historical Document
Page last updated: June 1, 2009
Page last reviewed: December 23, 2008
Content Source: OPHG Staff