Highlights
- •An increased focus on sample size calculations and adequately powered studies will allow for more robust and valid findings in clinical trials.
- •Blinding in orthopaedic trials is challenging, but there has been effort to increase blinding to reduce the risk of exaggerated effect sizes.
- •Expertise-based trials represent a novel design in surgical based trials, with the potential to reduce bias and increase validity and feasibility.
- •Patient reported outcomes and minimal important differences represent important trial outcomes that have seen increased uptake.
Abstract
Introduction
The adoption of evidence-based orthopaedics has shifted the focus from expert base
opinions and anecdotal evidence to a focus on integrating the best available clinical
research. This shift has led to an increased focus on randomized controlled trials
(RCTs) within the field. Although RCTs are considered the highest level of evidence,
methodologic errors can introduce bias and limit the validity of the results. Early
trials were hampered by lack of blinding, inadequate sample sizes and other design
flaws. The objective of this review was to examine the current literature to determine
if the design and execution of RCTs has improved.
Design Errors
The awareness of the importance of sample size increased over time with substantially
more trials reporting sample size calculations. However, many contemporary RCTs are
still underpowered and fail to reach their calculated sample size. Given the challenges
of surgically based RCTs, the majority of historical trials lacked blinding, increasing
the risk of bias. There is evidence that there has been a concerted effort to increase
the blinding in RCTs, particularly in outcome assessors. A more recent development
in the design of surgical trials is the introduction of expertise-based trial designs
in which patients are randomized to a surgeon with expertise in a particular intervention.
These trials minimize the bias that can arise from differential expertise bias and
have the potential to improve the validity and feasibility of RCTs. Finally, there
has been an increased focus on the reporting of patient reported outcomes (PROs) in
orthopaedic RCTs. Alongside this movement has been the development of minimal important
differences (MIDs) to define the changes that are relevant and meaningful to patients.
Both PROs and MIDs should be taken into consideration when calculating the sample
size and study power in clinical trials.
Conclusions
Although marked improvements have been made in the design and implementation of trials,
there is still considerable room for improvement. Adequately blinded and powered studies
evaluating clinically important outcomes and differences should be key considerations
in trial design moving forward.
Keywords
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Article info
Publication history
Published online: December 08, 2021
Accepted:
December 4,
2021
Publication stage
In Press Journal Pre-ProofFootnotes
This paper is part of a supplement supported by AOTrauma Europe.
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
