1. EVIDENCE BASED SURGERY
WHAT IS THE PURPOSE OF THE STUDY?
o Most studies : one of two general categories
o Descriptive (or exploratory) : Hypothesis-generating identifying possible associations.
o Analytic : Test a pre-specified hypothesis
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WHAT IS THE STUDY DESIGN?
o Appropriate study design selection depends on the study question or aim and the availability of resources to conduct
the research.
Randomized Controlled Trials
o Provide the highest level of evidence supporting causality—one intervention leads to betteroutcomes when
compared with another—or non inferiority.
o If randomization is performed properly, variables that might bias results or act as confounding agents should be
distributed equally between groups, resulting in the main advantages ofan RCT.
o However, conducting an RCT is challenging because of issues associated with
o Subject accrual and retention,
o Complex nature of surgical interventions
o Significant research costs
o Problems relating to the unique environments in which RCTs are usually performed.
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o To increase the quality and transparency of RCTs, many journals now require online study registration with the
International Standard Randomized Controlled Trial Number (ISRCTN) registry so that the research questions,study
population, and analytic plan are detailed before the study begins,as well as requiring minimum reporting standards
based on the Consolidated Standards of Reporting Trials (CONSORT) guidelines.
o The CONSORT guidelines require that details about
o Various methodologic issues pertinent to the conduct of RCTs (e.g., randomization, blinding, intent to treat)
be included in the final manuscript.
o In an RCT,
o subjects are randomly assigned
to an intervention group, where they receive an experimental intervention (a given trial may
randomize to one or more interventions) OR
to a control group, where they receive a controlled measurable alternative (placebo or a standard
form of existing therapy).
o Subjects are then followed to measure the occurrence of the outcome(s) of interest.
o Successfulrandomization eliminates systematic differences in potential confounding variables between the
study groups.
Blinding:
Blinding of study subjects is intended to mitigate the influence of a placebo effect.
o Subjects (single-blind)
o Investigators (double-blind) : reduces bias from differential delivery of care and outcomes assessment
between study groups.
o Analyst ( Triple blind)
o
2. o An important analytic issue with RCTs is INTENT-TO-TREAT (ITT).
o When an analysis is conducted following the ITT principle, outcome comparisons between control and
treatment groups are based on the initial randomization and disregard any crossover, that is
subjects who were randomized to control but received the study intervention
or those assigned to an intervention but received the control.
o If analytic approaches otherthan ITT are used,the benefits of randomization will be lost.
o Without performing the analysis based on the initial randomization, the absence of systematic differences in
patient characteristics (confounders) cannot be guaranteed.
o For example,
o An investigatorwho is an advocate of an intervention might prefer that only those patients in an
RCT who actually underwent that procedure be included in the analysis (known as a per-protocol
analysis),excluding those randomized to the treatment but who crossed over to the control group.
o However, ITT analysis is essentialbecause it allows surgeons and patients to discuss whether
choosing that intervention is best for that particular patient.
o At the point of a care decision (should the patient agree to undergo a procedure or not), neither the
patient nor the surgeon knows whether the patient will be able to complete the intervention or
strategy or will require a more conventionalapproach, perhaps because of the patient’s inability to
tolerate the procedure.
o ITT creates an evidence-based approach to inform patients about how the intervention compares at
the moment the decision is being made, because ITT incorporates all the factors affecting that
decision.
o Noninferiority RCTs are a special case in which the hypothesis is that competing interventions have
equivalent outcomes (i.e., no difference in outcome between therapies).
o It is mathematically impossible to design a study with sufficient power to prove no difference in
outcomes.
o Investigators specify a priori the minimum difference in outcome that would be clinically
important.
o The analysis is then designed to determine whether differences in outcomes are greater than this
minimally important difference.
o Although noninferiority designs have clear value insurgical research, they are uncommon.
One example of a noninferiority RCT was a study conducted by the Clinical Outcomes
Surgical Therapy Study Group evaluating whether minimally invasive colon resection
provided equivalent oncologic outcomes compared with conventional resection.
Prior to the study,the investigators determined that a 23% higher risk of tumor
recurrence in the laparoscopic group would be clinically important.
The results of the trial showed no statistically significant difference betweenrecurrence
rates for laparoscopic and open colon resection and also found that laparoscopic
resection had a risk of recurrenceno higher than 17%, representing the upper bound of
the confidence interval.
Because the 95% confidence interval did not include what was determined to be a
clinically meaningful difference (23%), the investigators safely concluded equivalence
for these two interventions.
o RCTs are not ideal for all research questions.
o For example, an RCT would be suboptimal for assessing rare safety events orfor addressing questions about
the effectiveness of an intervention across broad populations of patients and practice environments.
