Trial reportBMJ evidence-based medicine2020
Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology.
Trial report in BMJ evidence-based medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Safety, Immunogenicity, and Efficacy of Gardasil (V501 (Human Papilloma Virus [Types 6, 11, 16, 18] Recombinant Vaccine) in Mid-Adult Women - The FUTURE III (Females United to Unilaterally Reduce Endo/Ectocervical Cancer) Study
An Investigational Vaccine in Reducing the Incidence of Anogenital Warts in Young Men
Immunogenicity and Safety of Gardasil (V501) Quadrivalent HPV (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) Vaccine in Consistency Lots for 16- to 23-Year-Old Women With and Additional Immunogenicity Bridge to the Monovalent HPV 16 Vaccine Pilot Manufacturing Lot Study-The F.U.T.U.R.E. Study (Females United to Unilaterally Reduce Endo/Ectocervical Disease)
A Study to Evaluate the Efficacy of Quadrivalent HPV Vaccine in Reducing the Incidence of HPV 6-, 11-, 16-, and 18-Related CIN, AIS, and Cervical Cancer, and HPV 6-, 11-, 16-, and 18-Related External Genital Warts, Vulvar Intraepithelial Neoplasia Vaginal Intraepithelial Neoplasia, Vulvar Cancer, and Vaginal Cancer in 16- to 23-Year-Old Women
A Randomized, Worldwide, Placebo-Controlled, Double-Blind Study to Investigate the Safety, Immunogenicity, and Efficacy on the Incidence of HPV 16/18-Related CIN 2/3 or Worse of the Quadrivalent HPV (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) Vaccine in 16- to 23-Year Old Women - The FUTURE II Study (Females United to Unilaterally Reduce Endo/Ectocervical Disease)
Who cites it
4 citing papers in PubMed.
- A reactogenic "placebo" and the ethics of informed consent in Gardasil HPV vaccine clinical trials: A case study from Denmark.The International journal of risk & safety in medicine · 2024Article
- Article
- Was amorphous aluminium hydroxyphosphate sulfate adequately evaluated before authorisation in Europe?BMJ evidence-based medicine · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
purposeTrustworthy reporting of quadrivalent human papillomavirus (HPV) vaccine trials is the foundation for assessing the vaccine's risks and benefits. However, several pivotal trial publications incompletely reported important methodological details and inaccurately described the formulation that the control arms received. Under the Restoring Invisible and Abandoned Trials initiative (RIAT), we aim to restore the public record regarding the content and rationale of the controls used in the trials.
methodsWe assembled a cohort (five randomised controlled trials) described as placebo-controlled using clinical study reports (CSRs) obtained from the European Medicines Agency. We extracted the content and rationale for the choice of control used in each trial across six data sources: trial publications, register records, CSR synopses, CSR main bodies, protocols and informed consent forms.
resultsAcross data sources, the control was inconsistently reported as 'placebo'-containing aluminium adjuvant (sometimes with dose information). Amorphous aluminium hydroxyphosphate sulfate (AAHS) was not mentioned in any trial registry entry, but was mentioned in all publications and CSRs. In three of five trials, consent forms described the control as an 'inactive' substance. No rationale for the selection of the control was reported in any trial publication, register, consent form, CSR synopsis or protocol. Three trials reported the rationale for choice of control in CSRs: to preserve blinding and assess the safety of HPV virus-like particles as the 'safety profile of (AAHS) is well characterised'.
conclusionsThe stated rationale of using AAHS control-to characterise the safety of the HPV virus-like particles-lacks clinical relevance. A non-placebo control may have obscured an accurate assessment of safety and the participant consent process of some trials raises ethical concerns. TRIAL REGISTRATION NUMBERS: NCT00092482, NCT00092521, NCT00092534, NCT00090220, NCT00090285.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.