GRADE was used to evaluate 13-valent Pneumococcal Conjugate Vaccine (PCV13) for routine use among immunocompromised children aged 6 through 18 years. 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 children aged 6 through 18 years with immunocompromising conditions?” Due to the limited body of evidence on vaccine efficacy and safety among persons with most immunocompromising conditions and varying formulations of pneumococcal conjugate vaccines (PCV), 7-,9-, and 13-valent PCVs were evaluated using data for HIV-infected adults and children, and children with sickle cell disease. Studies with PCV7 and PCV9 were used as a proxy when no PCV13 studies were available; PCV7 and PCV9 have the same formulation as PCV13 with 7 antigens in common. The benefits considered in GRADE included critical outcomes of prevention of invasive pneumococcal disease (IPD), pneumococcal pneumonia, death, and hospitalizations due to pneumococcal disease; 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 two randomized controlled trials (RCT): PCV9 among HIV-infected children in South Africa.[2] and of PCV7 among HIV-infected adults in Malawi.[3] The effectiveness of PCV13 against IPD was assumed to be the same as that estimated from a pre/post observational study of PCV7 in children <10 years with sickle cell disease (SCD).[4] Evidence used to evaluate efficacy of PCV13 to prevent critical outcomes of pneumonia and death was from the same RCT in South Africa among HIV-infected children.[2] Evidence was not available for critical outcome of hospitalizations.

There are two studies on immunogenicity for children with SCD:

an unpublished pre/post study of immunogenicity of PCV13 in children aged 6 through 18,[5] and a published immunogenicity study of PCV7 and PPSV compared to PPSV alone.[6] There are three published studies for HIV-infected children: one pre/post study and two clinical trials for immunogenicity of PCV.[7-9] Four RCTs of PCV7 have been conducted in HIV-infected adults.[10-13] Safety of PCV13 was evaluated based on a pre/post study in children with SCD[5] and three RCTs of PCV7 in HIV-infected adults.