Methods of normalizing measured drug concentrations and testing for non-compliance with a drug treatment regimen

A method of generating a normalized opioid value for a daily dose of an opioid, the method comprising:

• (a) assigning a plurality of subjects to a population;
• (b) administering to the plurality of subjects a same daily dose of an opioid for a time sufficient for the opioid to reach a steady state concentration in the subjects;
• (c) thereafter measuring a fluid opioid concentration and one or more parameter for said plurality of subjects, wherein said fluid opioid concentration is measured by at least one of GC-MS or LC-MS-MS;
• (d) determining a normalized opioid value for the daily dose of the opioid as a function of the fluid opioid concentration and one or more parameter associated with said plurality of subjects.

A method of normalizing clinical data comprising:

• (a) administering to a plurality of subjects a daily dose of an opioid for a time sufficient to achieve steady state;
• (b) measuring a steady state opioid levels in fluid of the subjects by at least one of GC-MS or LC-MS-MS;
• (c) measuring one or more parameters associated with said subjects;
• (d) normalizing the measured steady state opioid levels as a function of the one or more parameters;
• and
• (e) calculating a normalized reference opioid level and associated confidence intervals corresponding to the daily dose of the opioid.

A method of generating a normalized drug testing standard curve for a population, the method comprising:

• assigning each of a plurality of subjects to one of a plurality of population subgroups;
• administering to each population subgroup one of a plurality of daily doses of a drug for a time sufficient to achieve steady state;
• measuring a steady state drug level in fluid of each subject;
• measuring one or more parameters in each subject;
• normalizing the steady state drug level for each subject as a function of the one or more parameters;
• and
• calculating a mean or median drug level and associated confidence intervals corresponding to each of the plurality of daily doses of the drug.