Budget impact analysis of pneumococcal conjugate vaccines in Colombia. Response to letter to the editor

KEYWORDS:

• Budget impact analysis
• Colombia
• pneumococcal conjugate vaccination
• pneumococcal non-typeable haemophilus influenzae protein D conjugate vaccine
• 13-valent pneumococcal conjugate vaccine

This letter is to respond to the questions and challenges raised by Reyes and colleagues in their response to our original study ‘Budget impact analysis of pneumococcal conjugate vaccines in Colombia.’ Reyes and colleagues are concerned that the assumptions used in our analysis may have unintended negative impacts for the decision-making process in Colombia, and it is important to clarify any potential misinterpretation of our assessment.

We based our vaccine effects scenarios for the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix, GSK) and a 13-valent PCV (PCV-13, Prevnar 13, Pfizer) not in qualitative and narrative review as Reyes and colleagues mentioned in their response but on the systematic literature reviews and conclusions provided by supranational organizations. First [1], a systematic review of the literature on the impact or effectiveness of PCVs on deaths, or hospitalizations due to invasive pneumococcal disease (IPD), pneumonia, meningitis, and sepsis conducted in Latin America concluded that there was a significant impact of both PHiD-CV and PCV-13 in the outcomes evaluated, with no evidence of superiority of one vaccine over the other on pneumonia, IPD or meningitis hospitalization reduction in children under 5 years old. Additionally, a systematic review was conducted by experts from the International Vaccine Access Center of Johns Hopkins Bloomberg Scholl of Public Health, the U.S. Centers for Disease Control among others (convened by the World Health Organization; WHO) [2] on PCV products (including unpublished data) to inform the policy review process developed by the Strategic Advisory Group of Experts on Immunization (SAGE) PCV Working Group of the WHO. That document provided specific information about the two currently available, licensed PCV products along with advice about the considerations a country should weigh in making a product choice. The SAGE PCV Working Group reviewed the data on the optimal use of PCV with respect to dosing schedules and products [3] and concluded that both vaccines have substantial impact against pneumonia, vaccine-type invasive disease and carriage. They also mentioned that there was no evidence of different net impact on overall disease burden between the two products and finally added that PCV-13 may have additional benefit in settings, where disease attributable to serotype 19A or 6 C (ST6C) is significant. Finally, the World Health Organization has developed their position paper on the use of PCVs in February 2019 [4] based on the results of systematic review of primary evidence from the literature on the immunogenicity and effectiveness against clinical disease (IPD and pneumonia) and NP carriage of the two available PCV products at that time, stating that both PHiD-CV and PCV-13 were safe and effective and have direct and indirect effects against pneumococcal disease caused by vaccine serotypes. Similarly, they report that the available evidence indicates that both products are effective in reducing overall vaccine-type IPD in both vaccinated and unvaccinated individuals. Although PCV-13 contains 3 additional serotypes, there is currently insufficient evidence to determine whether they change the impact on overall IPD burden (vaccine type and non-vaccine-type disease combined). All this new evidence prompted us to analyze further the present PCV scenario of Colombia, developing a budget impact analysis to assess the decision of maintaining or switching PCVs in Colombia and its sustainability. As a consequence of using new evidence in our economic scenarios, our results diverge from previous analysis completed before all these studies were published [5–8].

After PHiD-CV has been included in the national immunization program (NIP) of Colombia for many years, the theoretical difference in serotype coverage between PCVs or the latest serotype distribution (generated by the SIREVA II laboratory network [9]), are not the best methods to estimated disease burden or vaccine impact. The surveillance of pneumococcal serotypes is a non-population-based laboratory-surveillance system, which specifically monitors IPD (and invasive disease due to P. Neumoniae, Haemophilus influenzae and Neisseria meningitidis) in Latin American countries, providing unique data on the identification, distribution, and anti-microbial susceptibility of pneumococcal strains [9,10]. Although of great value in monitoring IPD, not all the aspects of pneumococcal disease are subject to a systematic routine surveillance with a standardized case definition [9]. The system describes adequately that the proportion of 19A-IPD cases in the residual IPD but is unable to assess the residual burden or the vaccine impact. It is critical to identify the attributable residual pneumococcal burden due to 19A and not only the proportion of residual IPD cases. The serotype content of PCVs may not automatically translate into disease protection against included serotypes and the absence of a certain serotype will not automatically translate into the absence of an effect, as cross-protection has been demonstrated [1–3,10–15]. In this respect, we agree with Reyes and colleagues that the PCV efficacy & effectiveness are parameters that might be influenced by the serotype content of the vaccines, but this effect has to be demonstrated in real life and not only based on the theoretical estimation of serotype coverage.

Finally, we have used a pre/post vaccine introduction to NIP in our analysis because it is the most robust procedure to analyze the economic consequence of vaccine effects. Baseline epidemiologic data is obtained from surveillance system, Ministry of Health data and expert opinion, while the vaccine effects are simulated based on the results of randomized clinical trials or case control studies identified on the systematic literature reviews of independent international organizations previously mentioned [1–3,11]. Evaluating intermediate scenarios with a static markov model to assess the potential health and economic effects of both PCVs (to assess PCV switching) requires challenging assumptions to estimate the PCV effects to be used for the intermediate scenarios [8]. The study mentioned by Reyes and colleagues [8] is very informative for Colombia, but its limitations and weaknesses have to be considered when interpreting their results. In addition, the ICERs reported [8] showed unconfirmed differences for decision making when the 95% confidence intervals are considered. Therefore, with all these evidence already published, we thought it might be valuable for the present scenario of Colombia to present a different economic analysis focusing in the budget impact of the PCV immunization program of Colombia and its sustainability on time, based on systematic literature reviews previously described of international organizations [1–3,11].

Declaration of interests

Jorge A. Gomez, Diana Caceres and Edisson Rodriguez are employees of GSK group of companies. Jorge A. Gomez and Diana Caceres holds shares in GSK group of companies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Editor disclosures

The editor who approved this letter for publication has no relevant financial relationships or otherwise to disclose.

Acknowledgments

The authors thank Business & Decision Life Sciences platform (on behalf of GSK) for editorial assistance, manuscript coordination and writing support. Pierre-Paul Prevot coordinated the manuscript development and editorial support.

Additional information

Funding

GlaxoSmithKline Biologicals SA (HO-19-20065) funded all costs associated with the development of this publication.