The impact of targeted training, a dedicated protocol and on-site training material in reducing observer variability of prostate and transition zone dimensions measured by transrectal ultrasonography, in multicentre multinational clinical trials of men with symptomatic benign prostatic enlargement.
OBJECTIVE
To assess the variability of a standardized protocol of transrectal ultrasonography (TRUS), with targeted training, and compare it to the variability in other multicentre clinical trials, as TRUS-estimated total prostate volume (TPV) and transition zone volume (TZV) are considered important efficacy endpoints in assessing new drug therapies for benign prostatic enlargement (BPE), but standardizing TRUS remains a challenge in such studies.


METHODS
In all, 174 patients with BPE in the placebo arm of a 30-centre clinical trial were analysed at baseline, 13 and 26 weeks with TRUS, to extract TPV and TZV values. All TRUS operators received training in the standardized methods, which was supplemented at the outset by a compact disc-based video.


RESULTS
The mean (sd) changes from baseline in TPV at 13 and 26 weeks were - 2.9 (8.9) and -1.9 (8.5) mL, respectively; the respective mean changes from baseline in TZV were -1.2 (6.4) and + 0.7 (7.8) mL. For TPV, 80% of the measurements had differences of + 5.2 to -13.4 mL at 13 weeks, and + 8.0 to - 10.9 mL at 26 weeks. For TZV, 80% of the differences were + 5.8 to - 7.4 at 13 weeks, and + 9.3 to -6.5 mL at 26 weeks.


CONCLUSIONS
The performance of TRUS compared favourably with similar published multicentre studies, which we suggest relates in part to the careful implementation of the protocol. We showed that diligent implementation of a detailed protocol, supplemented by targeted training of investigators and provision of on-site training material, promoted consistent acquisition and successful derivation of key clinical trial endpoints. Quantifying the variability of such endpoints will enable us to track deployment quality for future clinical trials, and will ensure that trials are sufficiently powered to define small changes in prostate size.
Murphy
Philip S
PS
Pfizer Global Research and Development, Sandwich, Kent, UK. philip.uk.murphy@pfizer.com
Mills
Ian W
IW
Crossland
Anna
A
Patel
Anup
A
D000368:Aged; D002983:Clinical Competence / Q000592:standards*; D016250:Compact Disks; D004311:Double-Blind Method; D004502:Education, Medical, Continuing / Q000379:methods / Q000592:standards*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011470:Prostatic Hyperplasia / Q000601:surgery*; D020728:Transurethral Resection of Prostate / Q000193:education / Q000592:standards*