TITLE:
Bias-Variation Dilemma Challenges Clinical Trials: Inherent Limitations of Randomized Controlled Trials and Meta-Analyses Comparing Hernia Therapies
AUTHORS:
U. Klinge, Andreas Koch, D. Weyhe, Enrico Nicolo, R. Bendavid, Anette Fiebeler
KEYWORDS:
Randomized Controlled Trial, Hernia Surgery, Registry, Meta-Analysis, Clinical Study
JOURNAL NAME:
International Journal of Clinical Medicine,
Vol.5 No.13,
July
16,
2014
ABSTRACT: Purpose:Evaluation of hernia therapies according to the current
rules of Evidence Based Medicine is widely reduced to results of RCTs or meta-analyses.
RCTs have been accepted as a most important tool to confirm a superior effect of
an intervention. Unfortunately, in hernia surgery, comparisons of RCTs and correspondingly
their use in meta-analyses, are not, surprisingly often, able to confirm any significant
impact of a specific procedure due to intrinsic restrictions in a multi-causal setting
with its web of influences. Methods:Based on our own experiences of clinical studies in surgery,
the present article outlines several situations, with their respective reasons,
which argue the severe limitations of RCTs and meta-analysis to define an optimum
treatment. Results:Meta-analyses accumulate the variations of each trial,
which then may cover any clear causal relationship. RCTs usually are dealing with
subgroups of standard patients thus excluding the majority of our patients. Low
statistical power of current cohort sizes restricts the analysis of subgroups or
of effects with low incidences. Simple comparisons of means frequently are hampered
by nonlinear relationships to outcome. The relevance of a specific variable is difficult
to separate from other influences. The limited surveillance period of studies ignores
a delayed change in outcome. Randomization cannot guarantee a standardized patient’s
condition. All the arguments have to be considered as a crucial and fundamental
consequence of the bias-variance dilemma or principle of uncertainty in medicine,
and underline the many limitations of RCTs to evaluate any specific impact of hernia
therapies on e.g. infection, pain or recurrence. Conclusions: Many surgical issues
cannot be and should not be investigated by RCTs, in particular, if a marked patients’
heterogeneity has to be considered or the low incidences of the outcome readout
cannot be addressed with sufficient statistical power without getting lost in the
variation mire. Registries with their non-restricted data-acquisition should be
regarded as reliable alternatives for postoperative outcome quality surveillance
studies.