Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) for Pneumococcal Vaccines for Immunocompromised Adults
MMWR recomm. rep; 61 (40), 2012
Publication year: 2012
GRADE was used to evaluate 13-valent Pneumococcal Conjugate Vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) for routine use among immunocompromised adults.
Evidence of benefits, harms, values and preferences, and cost-effectiveness were reviewed in accordance with GRADE methods.[1] The primary policy question was “Should PCV13 be administered routinely to adults with immunocompromising conditions?” For consistency, evidence for both PPSV23 (recommended for use since 1983) and PCV13 were evaluated by applying the GRADE framework. Due to the limited body of evidence on vaccine efficacy and safety among persons with most immunocompromising conditions, both vaccines were evaluated using data for HIV-infected adults. Additionally, studies with 7-valent pneumococcal conjugate vaccine (PCV7) were used as a proxy when no PCV13 studies were available; PCV7 has the same formulation as PCV13 but contains 6 fewer antigens. The benefits considered critical outcomes in GRADE included prevention of death, invasive pneumococcal disease (IPD), pneumococcal pneumonia, hospitalizations due to pneumococcal disease, and vaccine-induced immunogenicity was considered an important outcome. The harms considered were serious adverse events and systemic adverse events. Evidence type for each critical or important outcome was derived through a review of study design, risk of bias, inconsistency, indirectness, and imprecision.
Evidence used to evaluate efficacy of PCV13 to prevent IPD was from a randomized controlled trial (RCT) of PCV7 among HIV-infected adults in Malawi.[2] Evidence was not available for critical outcomes of pneumonia, hospitalizations, or deaths. Immunogenicity of PCV13 compared to PPSV23 was evaluated based on 2 phase III RCTs among healthy adults[3] and 4 RCTs of PCV7 in HIV-infected adults.[4-7] Safety of PCV13 was evaluated based on 6 RCTs in immunocompetent adults.[3]
The evidence used to evaluate efficacy of PPSV23 compared to placebo against IPD, pneumonia, and deaths was drawn from one RCT among HIV-infected adults in Uganda[8] as well as 9 observational studies in the United States and Europe.[9-17] Evidence was not available for the critical outcome of hospitalization due to pneumococcal disease. Immunogenicity was evaluated in 2 RCTs and 2 observational studies among HIV-infected people.[4, 7, 18-20] Safety was assessed by review of post-licensure surveillance data.