Ecological validity of cost-effectiveness models of universal HPV vaccination: a protocol for a systematic review.

Background: Sexually transmitted infection with high-risk, oncogenic strains of human papillomavirus (HPV) still induces a relevant burden of diseases on both men and women. Although vaccines appear to be highly efficacious in preventing the infection of the most common high-risk strains (HPV 6, 11, 16, 18), important questions regarding the appropriate target population for prophylactic vaccination are still debated. Models in the extant literature seem to converge on the cost-effectiveness of high coverage (>80%) of a single cohort of 12-year-old girls. This vaccination strategy should provide an adequate level of indirect protection (herd immunity) to the unvaccinated boys. This argument presupposes the ecological validity of the cost-effectiveness models; the implicit condition that the characteristics of the individuals and the sexual behaviours observed in the models is generalisable to the natural behaviours of the population. The primary aim of this review is to test the ecological validity of the cost-effectiveness models of universal HPV vaccination available in the literature. The ecological validity of each model will be defined by the number of representative characteristics and behaviours taken into consideration.

Methods: Nine bibliographic databases will be searched: MEDLINE (via PubMed); Scopus; Science Direct; EMBASE via OVID SP, Web of Science, DARE, NHIR EED and HTA (via NHIR CRD); and CINHAL Plus. An additional search for grey literature will be conducted on Google Scholar and Open Grey. A search strategy will be developed for each of the databases. Data will be extracted following a pre-determined spreadsheet and then clustered and prioritised: the main outcomes will report the inputs to the demographic and epidemiological model, while additional outcomes will refer to basic inputs to the cost-effectiveness valuation. Each study included in the review will be scored by the number of representative characteristics and behaviours taken into consideration (yes or no) on both dimensions. Individual study's scores will be plotted in a 2 by 2 matrix: studies included in the upper right quadrant will be defined as ecologically valid, since which both individuals' characteristics and their sexual behaviours are representative.

Discussion: The proposed systematic review will be the first to assess the ecological validity of cost-effectiveness studies. In the context of sexually transmitted diseases, when this condition is violated, an error in predicting the protective impact of herd immunity would occur. Hence, a vaccination policy informed on ecologically invalid models would potentially expose boys to a residual risk of contracting HPV-induced malignancies.

Systematic Review Registration: PROSPERO CRD42016034145.