FUTURE I trial (ph3,4v).
| Methods | Phase III randomised, placebo‐controlled, double‐blind trial | |
| Participants | Participants: 5455 women (2723 women in the vaccine arm and 2732 in the placebo arm) from 62 study centres in 16 countries Age range: 16 to 24 years Inclusion criteria: healthy women who were not pregnant and had no history of genital warts or abnormal results on cervical cytologic testing, had a lifetime number of no more than four sex partners and agreed to use contraception during the vaccination period |
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| Interventions | Vaccine: quadrivalent HPV 6/11/16/18 vaccine Placebo: visually indistinguishable aluminium‐containing placebo |
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| Outcomes | Efficacy (CIN of any grade, AIS, cervical cancer, VIN, VaIN, GW, vulvar‐vaginal cancer, Pap abnormalities), immunogenicity and safety | |
| Notes | Main reports: Garland 2007; Last report average follow‐up time: 4.9 years (Munoz 2010) |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | A computer‐based randomised allocation schedule provided by the statistician was used for sequence allocation |
| Allocation concealment (selection bias) | Low risk | An interactive voice response system was used to randomise participants within each study centre |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | The participants, investigator and sponsor were blinded to the allocated trial arm |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Central laboratory was unaware of treatment‐group assignment and HPV status. A panel of 4 pathologists was unaware of diagnosis made at the central laboratory, clinical findings, treatment group, and HPV status |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Outcomes are assessed in the PP cohort (received 3 doses without protocol violations, being HPV DNA negative for the relevant HPV vaccine type from enrolment to 1 month after dose 3), in the unrestricted susceptible group (all women who were negative on HPV DNA and serology negative for the relevant HPV vaccine type at enrolment) and in the ITT cohort (all participants who had undergone randomisation, regardless of baseline HPV status or presence of HPV‐associated an\anogenital disease). Reasons for exclusion were presented |
| Selective reporting (reporting bias) | Low risk | All outcomes (efficacy, safety and immunogenicity) reported |