The efficacy of the 9-valent human papillomavirus vaccine (9vHPV) to prevent infection and disease was established in a Phase III clinical study in women 16-26 years of age. Here we present the unique design of a long-term follow-up (LTFU) study to assess effectiveness of the 9vHPV vaccine for upto 14 years post start of vaccination.
A long-term follow-up (LTFU) study was initiated as an extension of the Phase III clinical study to assess effectiveness of the 9vHPV vaccine for at least 14 years after the start of vaccination. It includes participants from Denmark, Norway and Sweden and uses national health registries from these countries to assess incidence of cervical pre-cancers and cancers due to the 7 oncogenic types in the vaccine (HPV 16/18/31/33/45/52/58). Incidences will be compared to the estimated incidence rate in an unvaccinated cohort of similar age and risk level. This LTFU study is unique in design as it is an extension of a Phase III clinical study and also has elements of an epidemiological study (i.e., endpoints based on standard clinical practice; surveillance using searches from health registries). A control chart method to determine whether vaccine effectiveness may be waning is utilized.
Experience from this innovative study design using Control chart methods may be applicable to other medicinal products when long-term outcomes need to be assessed.
These methods can be used to monitor disease incidence in real-time and promptly detect a decrease in vaccine effectiveness.