BACKGROUND: Noncompliance with medications may have major impacts on outcomes measured in research, potentially distorting the validity of controlled clinical trials. Riboflavin is frequently used in trials as a marker of adherence. It can be combined with study medication and is excreted in urine where it fluoresces under UV light. This study compares qualitative visual inspection of fluorescence to quantitative fluorometric analysis of riboflavin concentration in its ability to detect the presence of riboflavin in urine. METHODS: Twenty-four volunteers received 0mg, 25mg, and 50mg doses of riboflavin under single-blind conditions, with 20 also receiving a 100mg dose. Five serial urine samples were collected over the following 36h. Quantitative measurement of riboflavin by fluorometric analysis and qualitative assessment of each sample using visual inspection were performed. RESULTS: The overall false positive rate for qualitative assessment was 53%. For quantitative assessment, a riboflavin concentration of 900ng/mL was established to classify positive samples. More than 80% of samples were positive 2-24h following ingestion of 25mg and 50mg, and less than 80% were positive at 36h. At least 95% of observations for the 100mg dose were above 900ng/mL at all timepoints. CONCLUSIONS: Quantitative fluorometric assessment is superior to qualitative visual inspection alone in determining medication adherence. The combination of 25-50mg of daily riboflavin and a cut-off level of 900ng/mL allows for the acceptable sensitivity of missing detection of non-compliant participants while preserving a high level of power to detect all cases of medication compliance.
BACKGROUND: Noncompliance with medications may have major impacts on outcomes measured in research, potentially distorting the validity of controlled clinical trials. Riboflavin is frequently used in trials as a marker of adherence. It can be combined with study medication and is excreted in urine where it fluoresces under UV light. This study compares qualitative visual inspection of fluorescence to quantitative fluorometric analysis of riboflavin concentration in its ability to detect the presence of riboflavin in urine. METHODS: Twenty-four volunteers received 0mg, 25mg, and 50mg doses of riboflavin under single-blind conditions, with 20 also receiving a 100mg dose. Five serial urine samples were collected over the following 36h. Quantitative measurement of riboflavin by fluorometric analysis and qualitative assessment of each sample using visual inspection were performed. RESULTS: The overall false positive rate for qualitative assessment was 53%. For quantitative assessment, a riboflavin concentration of 900ng/mL was established to classify positive samples. More than 80% of samples were positive 2-24h following ingestion of 25mg and 50mg, and less than 80% were positive at 36h. At least 95% of observations for the 100mg dose were above 900ng/mL at all timepoints. CONCLUSIONS: Quantitative fluorometric assessment is superior to qualitative visual inspection alone in determining medication adherence. The combination of 25-50mg of daily riboflavin and a cut-off level of 900ng/mL allows for the acceptable sensitivity of missing detection of non-compliant participants while preserving a high level of power to detect all cases of medication compliance.
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