1. Implementing GRADE in Guideline Development: Real-World Experiences NIAID Guidelines for the Diagnosis and Management of Food Allergy Dr. Matthew Fenton Asthma Allergy & Inflammation Branch DAIT, NIAID, NIH September 15, 2009

2. Food Allergy Guidelines: Background July 2007 workshop assessed the need for clinical guidelines that could be used by health care providers across various medical specialties. More than 30 professional organizations, federal agencies, and advocacy groups unanimously agreed that NIAID should develop the guidelines. Guidelines should be developed using both evidence-based data and expert opinion. Wide dissemination of the guidelines by participating organizations would be needed.

3. Food Allergy Guidelines: Process Overview Literature Review and Evidence Grading (RAND Corp.)  Comprehensive literature search  Prepares evidence tables  Assesses quality of body of evidence using GRADE Expert Panel (Chair: Dr. Joshua Boyce)  Drafts the guidelines based on RAND’s literature review and expert clinical opinion  Identifies both knowledge gaps and areas of agreement* Drafting, Review and Final Guidelines  Guidelines draft prepared by the Expert Panel to be edited based on Coordinating Committee # review and public comment *across medical specialties # Committee comprised of professional organizations, Federal agencies, and advocacy groups

4. Guidelines Timeline  July 2007: Meeting highlighting the need for Guidelines  September 2008: First meeting of the Coordinating Committee & award of RAND contract for evidence based review  July 2009: First draft of RAND report given to Expert Panel  October 2009: Expert Panel meets to review first draft of the guidelines  Dec 2009: Final draft of Expert Panel guidelines to be completed and forwarded to the Coordinating Committee  Jan-Feb 2010: 60 day public comment period  May 2010: Final guidelines document ready for release

5. Food Allergy Guidelines: Implementing GRADE  Training the Expert Panel Members  Dissemination of papers from the GRADE Working Group  GRADE presentation at March 18, 2009 Expert Panel Kick Off Meeting  Ongoing discussion to refine recommendations for grading/strength  RAND provides additional training

6. Food Allergy Guidelines: Implementing GRADE (Cont’d) ■ Preliminary Scoring plan:  5 distinct writing groups to prepare guidelines “chapters”  Each small group will propose the strength of a recommendation based on RAND evidence and expert opinion using GRADE  Vote by entire EP upon integration will determine final grading strengths ■ Tentative plan to assess agreement by Panel members  Each section of the guidelines will contain a “agreement” score to compliment the evidence grade and recommendation strength Uniform (100% agree), Substantial majority (80%), majority (50- 80%), No agreement (<50%) Agreement will be assessed upon integration of the 5 guideline chapters using the GRADE grid

7. Food Allergy Guidelines & GRADE: Potential Difficulties  Nature of food allergy and state of the science  Few DBPC clinical trials (ethical issues)  No existing treatments for food allergy  Relatively few population-based studies  Reported trials use different endpoints  Potential population & environmental differences

8. Food Allergy Guidelines & GRADE: Potential Difficulties  Difficult to rate some evidence highly, leading to a lack of strong recommendations  Example: Oral food challenge as a study endpoint Oral food challenges, the gold standard for food allergy diagnosis, can be very risky for those with severe food allergies Many clinical trials use oral preparations to desensitize patients, but, to minimize risk, do not use oral food challenge as the endpoint to test the success of the intervention Such studies are not considered the highest quality, due to lack of the gold standard endpoint Does GRADE work where the body of evidence is considered weak, but expert opinion is strong?