Results & Conclusions

Results & Conclusions

Table 2 shows the number of LC-MS-MS lab tests administered on days 3 and 4 by respective dose. In general, more tests were administered on day 3 than day 4, with 152,104 and 117 total lab tests administered (for 80, 160 and 240 mg, respectively).

The concordance correlation coefficient1 for the raw LC-MS-MS values between days 3 and 4 was 0.689 (95% confidence intervals = 0.515, 0.864), whereas the concordance correlation coefficient for the LC-MS-MS values using the algorithm (i.e., normalized values) was higher at 0.882 (95% confidence intervals = 0.808, 0.956).

Figures 1 and 2 illustrate the distributions of raw and normalized LC-MS-MS values, respectively, by the daily doses under study. Upon visual inspection, it is clear that none of the doses under either method represent normal distributions. Moreover, there is no consistency in the general form among the distributions. The estimators of shape parameters are not reported, such as skewness and kurtosis coefficients, because they generally exhibit large sampling variability in small samples and are biased (toward normality) in non-normal distributions.2 These concerns led to the choice of a median analysis using Bonett-Price confidence intervals.

Table 3 presents the median estimates and Bonett-Price 95% confidence intervals for raw and normalized LC-MS-MS values by dose, both with and without Bonferroni adjustment. As shown, the confidence intervals for the raw LC-MS-MS levels do not overlap among any of the three doses (80, 160 and 240 mg), but in applying the more conservative Bonferroni adjustment, discrimination between the 160 and 240 mg doses disappears. Conversely, the confidence intervals for the normalized LC-MS-MS levels do not overlap among any dose level.

In summary, the normalized LC-MS-MS method using the algorithm shows excellent discrimination among 80, 160 and 240 mg doses of OxyContin® even when conservative adjustments are applied to account for multiple comparisons.

Table 2. Number of LC-MS-MS tests administered on days 3 and 4
by daily dosage.

Ameritox Table 2

 

Table 3. Median estimates and Bonett-Price 95% confidence intervals for raw and adjusted LC-MS-MS values by dose (with and without Bonferroni adjustment).

Ameritox Table 3