CDC Recommendation for Hepatitis B Vaccination among Adults with Diabetes: Grading of Scientific Evidence in Support of Key Recommendations

Background

Evidence of benefits, harms, values and preferences, and cost effectiveness were reviewed in accordance with GRADE methods to determine the recommendation category (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 U.S. Centers for Disease Control and Prevention (CDC). Vaccine 29(49):9171-6, 2011). Pooled data from 6 placebo-controlled randomized trials (5798 subjects) indicated a relative risk for hepatitis B infection events of 0.37 (95% CI 0.29, 0.48) among vaccinated subjects, although evidence type was downgraded for indirectness as trials did not focus on subjects with diabetes. Pooled data from 5 observational studies (285 subjects with diabetes) indicated 91.6% of subjects with diabetes achieved seroprotection, although evidence type was downgraded for imprecision due to small numbers. No serious vaccine-related adverse events were reported in any study. The Institute of Medicine found evidence supporting a causal relationship between hepatitis B vaccination and anaphylaxis in yeast-sensitive individuals; the risk of anaphylaxis following hepatitis B vaccine is estimated at 1.1 per million doses. [IOM (Institute of Medicine). 2011. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press; Bohlke K, Davis RL, Marcy SM, Braun MM, DeStefano F, Black SB, Mullooly JP, Thompson RS; Vaccine Safety Datalink Team. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003;112:815-20]

GRADE Tables: Hepatitis B Vaccination Among Persons with Diabetes

Table 1. Benefits and Harms of Hepatitis B Vaccination Among Persons with Diabetes^a

Table 1 Footnotes

^aSome studies include persons with and without diabetes

^bFollow-up ranged from 12-29 months; figures do not account for person-time of follow-up for all studies; relative risk and 95% CI calculated from RevMan software version 5.1

^cCalculated from GRADEprofiler software version 3.6 assuming fixed effects

^dNumber needed to treat (number needed to vaccinate) calculated from modeling analysis of adults with diabetes ages ≥20 years (lifetime perspective)

^eNo serious events reported. Study sizes not sufficient to detect rare serious adverse events

Table 2. Type of Evidence for Hepatitis B Vaccination Benefits and Harms among Persons with Diabetes^a

Table 2 Footnotes

^aSome studies include persons with and without diabetes

^bSubjects with diabetes not focus of RCT studies; one RCT used 3 mcg dose on 0,1,2 month schedule; one study used 5 mcg dose on 0,1,2 month schedule with subcutaneous administration

^cTotal number of events <300, 95% CI 0.88, 0.94

^dStudy sizes not sufficient to detect rare adverse events: rate of anaphylaxis estimated 1.1 per million doses (95% CI 0.1, 3.9 per million doses); (Bohlke K. et al. Pediatrics 2003;112:815-20). Widespread vaccine use for 30 years has not revealed other serious adverse events (IOM (Institute of Medicine). 2011. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press)

Table 3. Summary of Evidence for Benefits and Harms of Hepatitis B Vaccination among Adults with Diabetes^a

Table 3 Footnotes

^aSome studies include persons with and without diabetes

^bStudy sizes not sufficient to detect rare adverse events

Table 4. Considerations for Formulating Recommendations: Hepatitis B Vaccine for Adults with Diabetes

^aPreventable outcomes consist of acute hepatitis, fulminant hepatitis, chronic hepatitis, cirrhosis, hepatocellular carcinoma, liver transplantation, death

Summary: Benefits are greater than potential harms; overall evidence is type 2. High values were placed on prevention of the morbidity and mortality of hepatitis B virus infection among adults with diabetes.