The aim of this thesis is to show how clinical trial conduct can be managed
while respecting the underlying scientific principles. Chapter 2 describes the main
results of PICO (PImobendan in COngestive heart failure), a trial which investigated
a positive inotropic agent in patients with heart failure using exercise tolerance as primary outcome. The results of this trial framed our thinking about how to
analyse the balance between positive and untoward effects of treatment, thinking
that is further elaborated in Chapter 3. This chapter also covers issues that relate to
the use of so-called combined endpoints, a feature of many recent large trials focusing
on clinical outcome. Several of the lessons learnt as described in Chapter 3
were implemented while designing the ACTION (A Coronary disease Trial Investigating
Outcome with Nifedipine) trial as described in Chapter 4. In Chapter 5 baseline
data from the same trial are presented. At the time of writing, ACTION was
still ongoing; results will be available in September 2004. In Chapter 6 we describe
the database management system which was implemented to manage the ACTION
study. In Chapter 7, the statistical analysis plan for this trial is reproduced. Finally,
in a general discussion (Chapter 8) we focus on the trial management issues that
arose during the conduct of the PICO and ACTION trials respectively.
Major medical journals will publish trial results only when the “data have
been gathered and are presented in an objective and dispassionate manner”.8 It follows
that scientific integrity cannot be an afterthought when the trial is finished.
Scientific integrity must be ensured by appropriate trial conduct from the beginning.
Otherwise, the results may never see the light of day
