A recent study evaluated the efficacy of a new quadrivalent vaccine in preventing the development of human papilloma virus (HPV) infection–related external genital lesions in boys and men age 16 to 26. A total of 1,320 healthy boys and men who were initially negative for all four vaccine HPV types were given the new vaccine and followed for 3 years. At the end of the follow-up, 24 participants had developed external genital lesions. Which of the following is the most likely reason no conclusion regarding vaccine efficacy can be drawn from these results?
This study is concerned with the efficacy of a new quadrivalent vaccine to prevent the development of human papilloma virus (HPV) infection–related external genital lesions in boys and men age 16 to 26. Vaccine efficacy (VE) is calculated by estimating the risk of disease in a group of vaccinated individuals and in a group of unvaccinated individuals and then determining the percentage reduction among vaccinated individuals relative to unvaccinated individuals.
VE = (risk of disease in unvaccinated − risk of disease in vaccinated) / (risk of disease in unvaccinated)
The greater the percentage reduction of illness in the vaccinated group, the greater the VE.
A total of 1,320 healthy boys and men age 16 to 26 were enrolled in the study and given the new vaccine. The study results showed that 24 of 1,320 vaccinated individuals developed external genital lesions; therefore, the risk of development of external genital lesions among vaccinated individuals is 24/1,320 = 0.0182, or 1.82%. This means that about 100% − 1.82% = 98.18% of vaccinated individuals did not develop external genital lesions.
However, the study does not include an unvaccinated group (ie, control group); therefore, it is not possible to draw conclusions about VE (Choice E). For example, unvaccinated individuals may have developed lesions at the same rate of ~1.82%, suggesting the vaccine had no efficacy.
(Choices A and B) Most genital lesions appear within a few months of HPV infection; therefore, a 3-year follow-up offers sufficient time for the development and diagnosis of external genital lesions. The small number of individuals who developed external genital lesions compared to the total may alter some aspect of the statistical analysis (eg, increase error, lower statistical power). However, the reason no conclusion about VE can be drawn from these results is the absence of a control group of unvaccinated individuals.
(Choice C) Boys and men age 16 to 26 are the study's population of interest; therefore, all conclusions generalize to this population (although they may not generalize to other populations).
Educational objective:
Vaccine efficacy is calculated by estimating the risk of disease in a group of vaccinated individuals and in a group of unvaccinated individuals (ie, control group) and then determining the percentage reduction among vaccinated individuals relative to unvaccinated individuals.