The differences and overlaps between 'explanatory' and 'pragmatic' controlled trials: a historical perspective

Paul Glasziou*, Robert Matthews, Isabelle Boutron, Iain Chalmers, Peter Armitage

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)


In designing a controlled trial, a potential tension may exist between (1) providing insights into therapeutic mechanisms and (2) guiding decisions about ‘what works’ in everyday practice. In their 1967 paper in the Journal of Chronic Diseases, Schwartz and Lellouch1 designated these aims as ‘explanatory’ and ‘pragmatic’, illustrating the potential tension with the different trial designs needed to assess the effect of an agent hypothesised to increase responsiveness to radiotherapy (a ‘radiosensitiser’) with immediate initiation of radiotherapy in the ‘pragmatic’ design versus a 30-day delay in initiating radiotherapy for the ‘explanatory’ design. This dilemma is manifest in real clinical situations, such as chemotherapy or radiotherapy prior to cancer surgery (‘neoadjuvant therapy’), ‘pre-habilitation’ to prepare patients for joint surgery and whether to use a placebo when comparing two versus four times daily drug dosing.
Original languageEnglish
Pages (from-to)425-432
Number of pages8
JournalJournal of the Royal Society of Medicine
Issue number12
Early online date22 Nov 2023
Publication statusPublished - Dec 2023
Externally publishedYes


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