The ACTION (A
Coronary disease Trial Investigating Outcome with Nifedipine GITS) study was an independent, investigator-initiated, multi-national
trial comparing nifedipine GITS to placebo in 7665 patients with stable angina pectoris. The
trial was sponsored by
the manufacturer of
the medication concerned. 291 centers in 19 countries participated. Results have been published. We defined quality management (QM) as all activities directed at ensuring data integrity and consistency; and ensuring appropriate
trial conduct, including pro-active prevention of deviations from protocol. We describe
the QM framework that was adopted for
the ACTION
trial and
the key tools that were used. In
the protocol, particular attention was paid to explicit definition of tasks and responsibilities of all participants, and to unequivocal operational definitions of terms such as ‘randomized’, ‘follow-up’, etc. that could be applied by investigators, on-site monitors and during data processing at
the coordinating centre. A comprehensive clinical
trial and study management system based on simultaneous display of scanned documents and data base content had a central role. We describe in detail how compliance with good clinical practice was ensured, how
the intention-to-treat principle was implemented, how compliance with study medication and completeness of follow-up was achieved, how double blinding was maintained throughout
the study structure, and how patient safety was protected. The protocol ruled out participation in any o
ther study at
the same time by ACTION participants. Our experience showed that
the reasons for this are not always understood by investigators.
Unequivocal operational definitions of the procedural concepts that characterize randomized clinical trials should not only be the basis of QM, but also of reporting results.