Adoption of the HPV vaccine: a case study of three emerging countries

A multi-country collective case study was designed, and a review of relevant HTA literature was conducted to identify good HTA practices, concepts to be used and previous HTA surveys.

A questionnaire was developed according to Drummond et al.’s key principles for HTA [16], and key trends and issues in HTA methodology, application and process from several studies/international experiences [17,18]. The instrument – consisting of 38 questions – grouped according to the three dimensions: first, the HTA process – introduction, institutions, unbiased and transparent, stakeholders; second, methods and criteria for conducting HTA – structure and methods, evidence, methods for assessing cost and benefits, social perspective, uncertainty; third, link between HTA and decision-making – implementation, decision-making, timely and communicated. The questionnaire was revised and pilot-tested with HTA experts from different countries and organizations (e.g., for format, structure, formulation of questions and answer options). It included both dichotomous and multiple choice questions, as well as a number of open-ended questions to allow for clarification and explanation of responses (full questionnaire available upon request).

Key informants were purposively selected from HTA organizations that were members of Health Technology Assessment Network of the Americas (RedETSA; Colombia and Brazil, among 14 countries 27 institutions that comprise it) and of the European Network for Health Technology Assessment (EUnetH TA; Poland). The contacts were mainly identified through personal contact and internet searches. By email, they were asked whether they had evaluated the HPV vaccine and invited to complete the survey (among EUnetHTA members, seven countries were invited to participate and Poland was the only country that accepted to participate). E-mails were sent from July to October 2014, and respondents were followed up by e-mail and telephone until survey completion (December 2014). The data gathered from survey responses (n = 3) were examined following a content analysis approach. Results were contrasted with the information available on the vaccine health technology assessment/appraisal reports that were carried out by these countries [19–21]. In addition, to ensure the quality of information, those results were contrasted with a previous mapping survey from the ADVANCE_HTA project [22], highlight that this study had a clarification and validation step provided by country experts. The ADVANCE_HTA project had the necessary authorizations; furthermore, at the local level, the project was authorized by the research committee of the Andalusian School of Public Health.

Overall, the HPV vaccine was evaluated as an established technology, and recommended by the respective appraisal committees for inclusion in the national immunization programs (NIP) in all three countries. Findings are presented according to the following three domains: HTA process from topic selection to appraisal, methods and criteria for conducting HTA and the link between HTA and decision-making.

This case study provides a description and comparison of the HTA of the HPV vaccine – including relevant stakeholders, criteria considered and final decisions – across three emerging settings in the use of HTA. This study shows that there are common elements of good practice in the processes and methods used, as reported by some authors [11,18], with all countries arriving at the same appraisal recommendations. However, the influence of socio-politico-economic factors appears to be determinant on the final decisions and restrictions to access made, as the case of Poland (in the other two countries no signs of being pressure). This case study intends to draw useful lessons for other emerging countries interested in the adoption of the HPV vaccine supported by evidence-informed processes, such as those offered by institutionalized HTA.

The value of our contribution lies in offering an overview of the HTA processes that the HPV vaccine underwent, from the institution charged of the selection as a topic for assessment to its implementation as part of the NIP in the countries adopting it. Although earlier case studies of decision-making related to the HPV vaccine have been published [23–25], our paper provides first-hand information on HTA processes themselves, rather than an examination of external influences on the policy debate arising from the launch of the vaccine.

We are aware that our research may have some limitations. The first is related to the comparability of results. Although all settings compared are emergent in the use of HTA, they are part of different geographic regions with specific socio-political environments. Nonetheless, there is evidence indicating that countries may reach the same conclusions due to similar political pressures [24]. The second one is related to the difficulty of collecting data in this field. The authors could not ensure that the survey was always filled out by the most informed person on the subject. In addition, full HTA products could only be retrieved from Brazil and Colombia, because part of this information was confidential in Poland. Another factor that affects the reliability of the results is that the HPV vaccine was evaluated in Colombia by CRES and an HTA unit that does not currently exist. Thus, the country survey was completed by a professional from Institute for Health Technology Assessment (IETS), who was unaware of certain information asked. Despite these issues, the authors have paid special attention to the analysis and triangulation of data, confirming data with country experts and available HTA reports.

In general, most countries evaluated the HPV vaccine within well-structured HTA processes, with an acceptable degree of transparency supported by publicity of rules/criteria and outcomes of the process. An area that was not as well developed across all settings was the provision of rationales supporting the recommendations and decisions made. Although some countries provided a discussion around these items, it is not possible to ascertain the weight that each scientific/social value carried compared with others. There is also scope for improving the level of participation of stakeholders at the appraisal phase of HTA, and for creating channels for the appeal against the decisions made. In particular, there was no broad and genuine participation of relevant actors in the case of Colombia, and stakeholders were only present at the final stages of the assessment and appraisal in Poland and Brazil, respectively [16,26]. As others have highlighted [27], a multitiered and wider involvement of stakeholders throughout HTA promotes local relevance, accountability and transparency, thereby creating legitimacy and reducing contestability.

As recommended by some authors [28–30], the assessment of the vaccine evidence took account of long-term effectiveness, postmarketing safety and cost–effectiveness in all settings. Given the fact that vaccines are administered to healthy populations and long-term benefits of the HPV vaccine are still uncertain, the societal acceptance of risks is generally lower than for drugs. In line with this, it is important to highlight that a re-assessment of safety and effectiveness was needed in Colombia a few years after the initial evaluation. Moreover, the duration of vaccine protection – an end point not yet well known – was taken into consideration across all countries.

According to our analysis of the different HTA bodies, only one of them took account of quality-of-life dimensions by using quality adjusted life years (QALYs) as an outcome, ‘the best measure currently available for valuing health states’ [29]. A rigorous assessment should allow determining how the costs of vaccination to gain a quality adjusted life year compared with those of other health interventions, such as cervical cancer screening or sexual and reproductive health promotion programs [31].

In terms of models used, all were static in nature. Although it has been argued that dynamic models are more suitable for responding complex policy questions (e.g., coverage levels), static models are equipped to answer simpler questions and give more conservative results, such as whether to introduce a vaccine or not, and are easier to develop and interpret, thus these appraisal could be an acceptable choice [29]. In line with the latter, the CERVIVAC decision-tree software – developed by the ProVac Initiative for Latin America – was used by CONITEC to build their model. In addition, direct health costs from the payer’s perspective were used across all evaluations, when indirect costs are typically high in infectious diseases.

Although all three countries concluded that the HPV vaccine was cost effective and recommended it for NIP inclusion, Polish decision-makers decided against it. All countries considered value for money and budget impact, given the high government investment required [24], but none included the social perspective in estimating costs. The role that other criteria, such as burden of disease, uncertainties (e.g., effectiveness and safety), industrial policy and ethical issues, played in the final decisions is less clear. In some countries, industrial policies can be indirect implicit criteria in order to set the medicines or vaccines prices, producing as effect higher prices of the national companies or companies with higher number of employees in the country.

Similarly to the case of Poland, about 21% of EU and Economic Area and 60% of LAC countries had not yet adopted the HPV vaccine due to financial restrictions and uncertain evidence (data 2014) [30,32–33]. Both Brazil and Colombia decided to administer the third vaccine dose at 60 months instead of the manufacturer’s recommendation at 6 months. Equity principles (increasing coverage) were declared in Brazil, although other reasons may have influenced the implementation program, such as feasibility and deferment of expenditures [30].

According with our experience, there are some common future trends in the use of HTA as a criteria for setting price and reimbursement of vaccines and medicines:

The findings of this study suggest that decisions should be based on a wide range of criteria, such as burden of disease, available evidence, value for money, affordability, the value of other alternative interventions and health system sustainability, but it is difficult to know the weight assigned to each. Therefore, it is important for policymakers in emerging settings to support the establishment and development of HTA systems, which provide a framework that at least the main determinants of decision were transparent, thanks to a clear HTA process supporting decisions [34]. There is a challenge of avoiding duplication of work and obtaining a more effective use of national HTA. There is a need to find more standardized approaches in order to provide tools that help HTA actors to reuse the work of others. Future studies are also recommended to elucidate the specific roles that social values and uncertainties play in vaccine decision-making across different societies [35].

J Espín Balbino and A Lemgruber conceived the study. J Espín Balbino, A Lemgruber and A Caro Martínez designed the study. A Caro Martínez and F Lessa collected data. A Caro Martínez drafted the first version of the manuscript. All authors contributed with ideas for discussion, reviewed the manuscript, and approved the final version.

The authors gratefully acknowledge all key informants and survey respondents who have voluntarily collaborated in the development of this study. The authors also thank the organizations who participated in this study and Work Package 6 partners.

This work was part of ADVANCE-HTA, a broader, multipartner and multidisciplinary research project [15], funded by the European Commission’s Research Framework Program (Nº 305983). It comprises several complementary streams of research that aim to advance and strengthen the methodological tools and practices relating to the application and implementation of HTA. This paper comes from the Work Package 6, Strengthening and Implementing HTA in Emerging Settings. The design, interpretation and presentation of results are independent from the funding organization. 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.

No writing assistance was utilized in the production of this manuscript.