Economic evaluations of <i>Haemophilus influenzae</i> type b (Hib) vaccine: a systematic review

<p><b>Aims:</b> The World Health Organization (WHO) recommends the use of <i>Haemophilus influenzae</i> type b (Hib) conjugate vaccines, but China and Thailand have not used Hib vaccination in their national immunization programs. This systematic review aimed to update published economic evaluations of Hib vaccinations and to determine factors that potentially affected their cost-effectiveness.</p> <p><b>Methods:</b> Searches were performed from the inception until December 2015 using 13 databases: CAB direct; CEA registry; EconLit; EMBASE; E-library; NHSEED; PAHO; POPLINE; PubMed; Redalyc project; RePEc; SciELO; and WHOLIS. Reference lists of relevant studies and grey literature were also searched. Full economic evaluations of Hib vaccination with results of costs and outcomes were included. The WHO checklist was used to evaluate the quality of the included studies. Data from eligible studies were extracted using a standardized data collection form.</p> <p><b>Results:</b> Out of 830 articles, 27 were included. Almost half of the studies (12/27) were conducted in high-income countries. Twelve studies (12/27) investigated the Hib vaccine as an addition to the existing vaccination program. Most studies (17/27) examined a 3-dose schedule of Hib vaccine. Nineteen studies (19/27) reported the model used, where all were decision tree models. Most of the studies (23/27) demonstrated an economic value of Hib vaccination programs, key influential parameters being incidence rates of Hib disease and vaccine price.</p> <p><b>Conclusions:</b> Hib vaccination programs are mostly found to be cost-effective across geographic regions and country income levels, and Hib vaccination is recommended for inclusion into all national immunization programs. The findings are expected to support policy-makers for making decisions on allocating limited resources of the Hib vaccination program effectively.</p

Policies modeled.

<p>Policies modeled.</p

Prior distributions for epidemiology model used in the base case analysis.

<p>^aAssigns equal probabilities to all values between 0.1 and 5, which includes the entire range of values with non-negligible probabilities from previous studies [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001829#pmed.1001829.ref002" target="_blank">2</a>].</p><p>^bThe serial interval is the sum of the latent period (which has an expected value of 1 d) and the infectious period (which has a gamma-distributed prior with mean 1.5 and standard deviation 0.1).</p><p>CrI, credible interval.</p><p>Prior distributions for epidemiology model used in the base case analysis.</p

Effective reproduction number as a function of vaccination policy, coverage, and vaccine effectiveness.

<p>Color indicates effective reproduction number after vaccination. Columns A, B, and C use a contact matrix derived from all contacts recorded. Columns D, E, and F use a contact matrix derived from physical contacts only. In both cases, baseline immunity assumptions at the start of each influenza season are taken as the mean estimated for each of the six age groups when fitting to data under base case assumptions (21%, 25%, 33%, 33%, 38%, and 37%). <i>R</i> values in column headings indicate the assumed effective reproduction number prior to vaccination.</p

Cost-effectiveness plane, cost-effectiveness acceptability curves, and cost-effectiveness acceptability frontiers.

<p>(A) Cost-effectiveness plane showing samples from the posterior distributions of DALYs averted and incremental costs for the seven vaccination policies compared with no vaccination under base case assumptions. Points to the right of the solid red line (which corresponds to a threshold of I$10,000 per DALY averted) would be considered highly cost-effective compared with no vaccination in Thailand according to the WHO threshold [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001829#pmed.1001829.ref044" target="_blank">44</a>]. (B) CEACs under base case assumptions. (C–K) CEAFs under base case assumptions and for eight sensitivity analyses.</p

DALYs averted by vaccination policies in total and as a result of direct vaccine effects.

<p>The width of bars corresponds to the probability density, the central black line within each bar represents the interquartile range of the DALYs averted, and the white circle represents the median value. Note that all DALYs averted in those 18 y and over or under 2 y are by definition indirect in policies 1–6.</p

Threshold analysis.

<p>Figure shows how the optimal policy (defined as the policy that maximizes the INB) changes with LAIV effectiveness, unit cost of LAIV, and willingness to pay (WTP) per DALY averted (cost-effectiveness threshold). (A) Base case mixing matrix. (B) Contact matrix based on physical contacts only.</p

Schematic illustration of analytic framework.

<p>The directed acyclic graph illustrates the dependencies between model components. Squares represent data sources, and circles represent quantities about which we are uncertain (double circles indicate quantities for which we have external information about their values, which is represented by informative prior distributions). Single and double arrows indicate stochastic and deterministic relationships, respectively, and arrows point towards the dependent variable. ILI, influenza-like illness.</p

Model fits to laboratory-confirmed influenza surveillance data.

<p>Monthly numbers of laboratory-confirmed influenza cases (circles) and model predictions: median (broken line) and 95%, 90%, and 80% (gray shading) prediction intervals for the expected number of cases. Also shown is the estimated value of <i>R</i>₀ and associated 95% CrI.</p

Extent to which the studies included met recommendations for reporting of economic evaluations.⁶

<p>*Number of studies in which the recommendation is applicable.</p><p><b>ICER</b> = Incremental cost effectiveness ratio.</p