Over the past decades, the randomized controlled trial has entered an era o
f continuous improvement and has gradually become accepted as the most effe
ctive way of determining the relative efficacy and toxicity of new therapie
s because it controls for placebo and time effects. However, even sensitive
and properly designed and executed trials do not always confirm hypotheses
to be tested, and conclusions are not always confirmed by subsequent trial
s. Although the former may be due to wrong hypotheses, the latter is likely
to be due to the presence of certain imperfections within the design and e
xecution of the trial itself.
In this opinion paper, while focusing on such imperfections, the author sea
rched for methods for further improvement of controlled trials, particularl
y clinical trials. The examples used in this paper are obtained from litera
ture search as well as recent studies performed by the Netherlands Working
Group on Cardiovascular Research (WCN).
Methods for improvement could include: 1. making every effort to avoid asym
metries in the treatment groups; 2. emphasis on statistical power rather th
an just null-hypothesis testing; 3. adjusting for asymmetries not only of p
atient characteristics but also of outcome variables; 4. accounting routine
ly for type III errors; 5. routinely weighing benefits of a new drug agains
t risks.