Related Experiment Video
Updated: Sep 30, 2025
A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition
Published on: September 20, 2019
Methodological aspects of a randomized within-patient concurrent controlled design for clinical trials in spine
A Mechteld Lehr1, Wilco Ch Jacobs2, Rebecca K Stellato3
1Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Introduction:
Randomized controlled trials are considered the highest level of evidence, but their feasibility in the surgical field is severely hampered by methodological and practical issues. Concurrent comparison between the experimental and control conditions within the same patient can be an effective strategy to mitigate some of these challenges and improve generalizability, mainly by the elimination of between-patient variability and reduction of the required sample size. This article aims (1) to describe the methodological aspects of a randomized within-patient controlled trial and (2) to quantify the added value of this design, based on a recently completed randomized within-patient controlled trial on bone grafts in instrumented lumbar posterolateral spinal fusion.
Methods:
Boundary conditions for the application of the randomized within-patient controlled trial design were identified. Between-patient variability was quantified by the intraclass correlation coefficient and concordance in the primary fusion outcome. Sample size, study duration and costs were compared with a classic randomized controlled trial design.
Results:
Boundary conditions include the concurrent application of the experimental and control conditions to identical but physically separated sites. Moreover, the outcome of interest should be local, uncorrelated and independently assessable. The spinal fusion outcomes within a patient were found to be more similar than between different patients (intraclass correlation coefficient 32% and concordance 64%), demonstrating a clear effect of patient-related factors. The randomized within-patient controlled trial design allowed a reduction of the sample size to one-third of a parallel-group randomized controlled trial, thereby halving the trial duration and costs.
Conclusion:
When suitable, the randomized within-patient controlled trial is an efficient design that provides a solution to some of the considerable challenges of a classic randomized controlled trial in (spine) surgery. This design holds specific promise for efficacy studies of non-active bone grafts in instrumented posterolateral fusion surgery.
Related Concept Videos
01:11Blinding
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
01:16Crossover Experiments
Crossover designs are performed even with smaller sample sizes since the samples can act as their controls. These are better than simple randomized trials since patients are exposed to all the treatments.
01:13Randomized Experiments
Simple randomization
Simple...
02:07Blind Procedures
01:15Study Design in Statistics
Does aspirin reduce the risk of heart attacks? Is one brand of fertilizer more effective at growing roses than another? Is fatigue as dangerous to a driver as the influence of alcohol? Questions like these are answered using randomized experiments with proper...