Objective: To evaluate the effect of the number and positioning during follow-up of ultrasound examinations on the rate of change in carotid intima-media thickness (CIMT) using METEOR (Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin) as an example.
Methods: METEOR was a randomized, placebo-controlled trial showing that rosuvastatin reduced progression of 2-year change in CIMT among low-risk patients with subclinical atherosclerosis. In the full METEOR protocol, ultrasound examinations were performed twice before randomization, once each at 6, 12, and 18 months after randomization, and then twice at the end of study at 24 months. For the present study, 17 study designs were retrospectively constructed with varying number and position of ultrasound examinations during the study. Differences in the rate of change in maximum CIMT between these study designs were compared.
Results: Variations in frequency of ultrasound visits gave results in the same direction and magnitude for the change in maximum CIMT for both groups (i.e. nonsignificant change for rosuvastatin and significant progression for placebo, and a significant difference between treatments). However, standard errors were larger when the number of exams reduced. This finding was consistent over different lengths of follow-up, sample sizes, and with CIMT measurements made on different locations.
Conclusion: Protocols with different number and timing of ultrasound examinations minimally affect the direction and magnitude of treatment effects on the rate of change in CIMT. However, reductions in exam frequency increase standard errors of rates of change, suggesting larger sample sizes would be required to have the same level of statistical power.
Trial registration: ClinicalTrials.gov NCT00225589.