How publication guidelines for clinical pharmacology trials may help to accelerate knowledge transfer

Abstract

Keywords clinical pharmacology, clinical trials, drug development, evidence based medicine Reports and publications on late phase clinical trials and other medical research are nowadays highly regulated, in particular confirmatory trials aiming to demonstrate the efficacy and safety of health technologies. This does not only affect the actual submission of drug dossiers to health authorities to achieve marketing authorisation. It already starts with the registration of clinical trials in publicly available registers at the time when the study protocols have been finalised and extends to requirements and guidelines for publications in medical journals [1].The key objective of these regulations is to achieve transparency how the research was actually planned, performed and analysed and which decisions had been made to accommodate unplanned situations. Thereby allowing the internal and external validity of the trial results to be judged, so that the interpretations and conclusions are comprehensible for readers. The targeted audience includes reviewers who are to decide whether an intended publication is fit to be presented to the wider scientific community. Thus, convincing the reader of the quality of one's research means convincing the reviewer first.Accordingly, within the EQUATOR network (Enhancing the QUAlity and Transparency Of health Research), a large number of reporting recommendations have been developed. Starting with the CONSORT statement on confirmatory randomised parallel group clinical trials [2], there are now extensions for trials with particular designs (e.g. equivalence trials or N-of-1 trials), but also more general fields like systematic reviews (PRISMA) or diagnostic/prognostic studies. So it seems that most of the medical research has its own reporting guideline.Interestingly, these guidelines do not cover clinical pharmacology studies. There are some extensions that might appear to be closely related, such as the "reporting withinperson randomised trials," or the "reporting randomised pilot and feasibility trials," but a closer view clarifies that their overlap with clinical pharmacology is rather minor. For example, the "within-person trials" guideline does not cover conventional crossover trials (with sequential treatments), but trials in which two treatments are applied simultaneously to the same person (e.g. to both eyes, to teeth or to different places of the skin). The "pilot and feasibility trial" guideline focuses on the practical development of the trial design and its implementation for a confirmatory trial, rather than on the development of a pharmacological treatment in Phase I-IIa regarding pharmacokinetics, pharmacodynamics and proof of principle with "surrogates" like biomarkers.In a BJCP editorial about 2 years ago [3], it was asked whether clinical pharmacology would benefit from having such guidelines. On one hand, clinical pharmacology trials are very diverse, sometimes not randomised, with quite different objectives, designs, and analysis methods. On the other hand, the ...

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“…The “ClinPK” checklist [ 15 ] was used to assess conformity of the selected studies with the minimum standards for reporting clinical pharmacology studies. Standardized guidelines facilitate transparent and complete reporting of clinical studies, thereby providing guidance to researchers conducting such studies and increasing the usability of their results by clinicians and researchers [ 15 , 53 ]. Clinical pharmacology trials are very diverse, sometimes not randomized, with quite different objectives, designs, and analysis methods [ 53 ].…”

“…Standardized guidelines facilitate transparent and complete reporting of clinical studies, thereby providing guidance to researchers conducting such studies and increasing the usability of their results by clinicians and researchers [ 15 , 53 ]. Clinical pharmacology trials are very diverse, sometimes not randomized, with quite different objectives, designs, and analysis methods [ 53 ]. The different guidelines for reporting clinical studies attempt to account for the diversities in study characteristics.…”