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control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology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

UID: 114

Author(s): Peter Doshi*, Florence Bourgeois, Kyungwan Hong, Mark Jones, Haeyoung Lee, Larissa Shamseer, O'Mareen Spence, Tom Jefferson * Corresponding Author
Randomised, placebo-controlled clinical trials are considered the gold standard for evaluating new vaccines. To assess its efficacy and safety, the manufacturer of quadrivalent human papillomavirus (qHPV) vaccine conducted multiple clinical trials involving approximately 30,000 volunteers. The trials of the qHPV vaccine are reported as ‘placebo-controlled.’ However, participants in the ‘placebo’ arms received an injection-containing amorphous aluminium hydroxyphosphate sulfate (AAHS), a proprietary adjuvant. AAHS is used in the qHPV vaccine to boost immune response, but the rationale for adding it to the ‘placebo’ is not reported in publications of these trials and is contrary to the advice of the public health bodies and regulators. Standard recommendations for control recipients in trials testing an unlicensed, experimental vaccine include using either an inert substance or an approved efficacious vaccine. 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), the primary objective of this study was to characterize the reporting of the methodology with respect to the rationale for the choice of standalone aluminum-containing adjuvanted controls. Clinical study reports (CSRs) from five randomized controlled trials described as placebo-controlled were obtained from the European Medicines Agency (EMA). Content and rationale for the choice of control used in each trial was extracted across six data sources: trial publications, register records, CSR synopses, CSR main bodies, protocols and informed consent forms. For each source within each trial, the following was recorded: (1) the phrases used to describe the comparator to qHPV vaccine; (2) the rationale for using aluminum-containing adjuvant as a control, if present and (3) all listed contents (ingredients) of formulation received by intervention and control arms. This dataset includes data extraction sheets and RIAT protocol documentation publicly accessible via the Open Science Framework with the CSRs available upon request.
Subject Domain
Access via Open Science Framework (OSF)

Extraction sheets and RIAT Protocol

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Request Clinical Study Reports

Access Restrictions
Unrestricted access
Approval required
Access Instructions
Completed extraction sheets are publicly available on the Open Science Framework. Clinical study reports available upon request. Please contact Peter Doshi.
Associated Publications
Equipment Used
Freedom of Information request to European Medicines Agency
Software Used
Google Sheets
Microsoft Excel
Study Type
Dataset Format(s)
Microsoft Excel, Microsoft Word, Portable Document Format
Grant Support
Arnold Ventures/Laura and John Arnold Foundation
Other Resources
Restoring Invisible and Abandoned Trials (RIAT)

RIAT is an international effort to tackle bias in the way research is reported with the goal of providing more accurate information to patients and other healthcare decision makers