Understanding lower leg volume measurements used in clinical studies focused on venous leg edema.

The aim of this review was to discuss the different techniques of leg edema measurement that have been used in clinical trials to help determine the most appropriate method of assessment and quantification for use in future research. Venoactive drugs such as micronized purified flavonoid fraction (MPFF) are established agents for the treatment of venous leg edema, but results from randomized- controlled trials vary depending on the method of edema assessment. The medical literature was searched for published articles using the terms venous lower limb edema and method of edema assessment. Clinical trials performed with MPFF used leg circumference and optometry for leg edema assessment. Indirect methods of lower limb volume assessment can be made by measurement of leg circumference with a tape or Leg-O-Meter. These are reliable and standardized instruments and simple and rapid to perform. Leg circumference measurements can also be used to indirectly estimate leg volume using the Frustum method. Direct methods such as Water Displacement Volumetry (WDV) are generally regarded as the gold standard for measurement of lower limb volume with low inter- and intra-individual variability. Nevertheless, to minimize variation in results measurement conditions must be standardized. The reproducibility of optometry can be considered good when positioning of the limb is appropriate. Other techniques also exist such as ultrasound imaging, bioelectrical impedance, tomodensitometry, Dual X-ray absorptiometry, computed tomography and magnetic resonance imaging. The different methods may be used to measure different compartments of the leg with or without the foot volume. For all techniques, strict standardization of measurement conditions is mandatory.

CONCLUSIONS

Patient heterogeneity and method of edema assessment impact clinical trial results. In particular, there are a number of error sources with several methods of assessment that can lead to variability in trial results. Consequently, pilot studies are required to validate new methods of edema assessment using innovative technologies.