Designing randomized clinical trials in pediatric neurosurgery.
OBJECTIVE
Randomized clinical trials provide the best evidence for making treatment decisions and their use in pediatric neurosurgery is increasing. In this paper, we review the basic principles of clinical trial design and discuss the unique challenges in trial design in pediatric neurosurgery.


METHODS
To illustrate the basic principles of trial design and highlight the special considerations in pediatric neurosurgery, examples from the Shunt Design Trial and Endoscopic Shunt Insertion Trial were used.


CONCLUSIONS
Each trial should answer one primary study question. Sample size estimates based on error rates and clinically important difference must be calculated. Allocation concealment, randomization, and blinding are critical to prevent selection and ascertainment bias. Standardization of the intervention is important to the result's validity, and study centers/surgeons should be selected on the basis of the trial objective. The effects of dropouts, crossovers, and missing data should be handled with an intention-to-treat analysis. Sample selection, informed consent, and valid outcome measures are specific challenges in the pediatric population.
Kan
Peter
P
Department of Neurosurgery, Primary Children's Medical Center, University of Utah, Salt Lake, UT 84113, USA.
Kestle
John R W
JR
D001927:Brain Diseases / Q000601:surgery; D004311:Double-Blind Method; D006801:Humans; D009493:Neurosurgery; D010372:Pediatrics; D016032:Randomized Controlled Trials as Topic; D012107:Research Design