New Framework (GRADE) for Development of Evidence-Based Recommendations by the Advisory Committee on Immunization Practices

The Advisory Committee on Immunization Practices (ACIP) is a federal advisory committee that provides expert advice to the Director of CDC and the Secretary of the U.S. Department of Health and Human Services. This advice comprises recommendations on the use of vaccines and related agents for control of vaccine-preventable diseases in the U.S. civilian population (1,2). To develop its recommendations, ACIP forms work groups that gather, analyze, and prepare scientific information and present it at public meetings. The work groups also present options for recommendations based on the scientific evidence they have assessed. Recommendations that are approved by a majority of ACIP's voting members are then reviewed by the Director of CDC. If approved by the Director, recommendations are published in MMWR. This report briefly summarizes the new framework for developing evidence-based recommendations that ACIP adopted at its October 2010 meeting.

New or substantially revised ACIP recommendations for vaccination will be developed using an evidence-based framework called "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) (3–5). Recommendations will be made in one of two categories. Category A recommendations will include those for which ACIP recommends vaccination for all persons in an age group or a group at increased risk for vaccine-preventable disease. Category B recommendations do not apply to all members of a group; they provide guidance to the clinician in the context of individual clinician-patient interactions to help determine whether or not vaccination is appropriate for a specific patient. In some instances (e.g., when additional information is needed), ACIP might not make a recommendation.

Using the GRADE framework, ACIP will systematically assess the type or quality of evidence about a vaccine's expected health impacts and the balance of health benefits and risks, along with the values and preferences of persons affected, and health economic analyses. The evidence is grouped into four categories, with the order reflecting the level of confidence in the estimated effect of vaccination on health outcomes: 1) randomized controlled trials, or overwhelming evidence from observational studies; 2) randomized controlled trials with important limitations, or exceptionally strong evidence from observational studies; 3) observational studies, or randomized controlled trials with notable limitations; and 4) clinical experience and observations, observational studies with important limitations, or randomized controlled trials with several major limitations (4,5).

Randomized trials often cannot be used to assess the safety and efficacy of vaccination on rare or long-term outcomes, and such trials might be unethical to conduct for vaccines that are already licensed. Observational studies frequently are conducted for such assessments.The GRADE framework allows evaluation of evidence derived from immunogenicity or other intermediate outcomes as well as evaluation of evidence based on extrapolations from findings with similar vaccines in similar populations or other indirect forms of evidence. The balance of benefits and harms is assessed through review of the baseline risk for disease and the expected relative and absolute effects of vaccination on health outcomes. Health economic analyses include computations of cost per quality-adjusted life year gained. Determination of values includes assessing the relative importance of outcomes related to benefits, harms, and health economic analyses. Evidence tables will be used to summarize the type of evidence for a vaccine's health impacts and its expected health benefits and risks.

This standardized and more explicit process for developing ACIP recommendations is expected to enhance transparency, consistency, and communication. Additional information about GRADE is available at http://www.cdc.gov/vaccines/recs/acip/grade/about.htm#resources.

Reported by

ACIP Evidence-Based Recommendations Work Group. Faruque Ahmed, PhD, Immunization Svcs Div, National Center for Immunization and Respiratory Diseases, CDC. Corresponding contributor: Faruque Ahmed, fahmed@cdc.gov, 404-639-8827.

References

1. Advisory Committee on Immunization Practices. Charter of the Advisory Committee on Immunization Practices. Atlanta, GA: US Department of Health and Human Services, Advisory Committee on Immunization Practices; 2012. Available at http://www.cdc.gov/vaccines/recs/acip/downloads/charter.pdf. Accessed May 4, 2012.
2. Smith JC, Snider DE, Pickering LK; Advisory Committee on Immunization Practices. Immunization policy development in the United States: the role of the Advisory Committee on Immunization Practices. Ann Intern Med 2009;150:45–9.
3. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924–6.
4. Ahmed F, Temte JL, Campos-Outcalt D, Schünemann HJ; for the ACIP Evidence Based Recommendations Work Group (EBRWG). Methods for developing evidence-based recommendations by the Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention (CDC). Vaccine 2011;29:9171–6.
5. Ahmed F. US Advisory Committee on Immunization Practices (ACIP) handbook for developing evidence-based recommendations. Version 1.1. Atlanta, GA: CDC; 2012. Available at http://www.cdc.gov/vaccines/recs/acip/grade/about.htm#resources. Accessed May 4, 2012.