Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Seeing is believing – the problem of blinding in psychological research

    Research output: Contribution to journalLetter

  2. Should antidepressants be used for major depressive disorder?

    Research output: Contribution to journalReviewpeer-review

  3. Statins for primary prevention: what is the regulator's role?

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Assessing assumptions for statistical analyses in randomised clinical trials

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Updated 2018 NICE guideline on pharmacological treatments for people with ADHD: a critical look

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Statins for primary prevention: what is the regulator's role?

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Increased incidence of cervical cancer in Sweden: an unlikely link with human papillomavirus (HPV) vaccination

    Research output: Contribution to journalComment/debateResearchpeer-review

  3. Challenges of independent assessment of potential harms of HPV vaccines

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Peter Doshi
  • Florence Bourgeois
  • Kyungwan Hong
  • Mark Jones
  • Haeyoung Lee
  • Larissa Shamseer
  • O'Mareen Spence
  • Tom Jefferson
View graph of relations

PURPOSE: Trustworthy 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.

METHODS: We 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.

RESULTS: Across 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'.

CONCLUSIONS: The 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.

Original languageEnglish
JournalBMJ Evidence-Based Medicine
Volume25
Issue number6
Pages (from-to)213-219
Number of pages7
ISSN1356-5524
DOIs
Publication statusPublished - Dec 2020

    Research areas

  • paediatric infectious disease & immunisation

ID: 59639315