NTI drug Bioequivalence study Statistical approach [Study Assessment]
As per regulatory,
- Primary pharmacokinetic parameter(s) for the 90% confidence interval of the geometric least square means must fall within 80.00% to 125.00% (both inclusive).
- Reference Scaled Average Bioequivalence:
The 95% upper confidence bound for (μT-μR)2-θ*S2WR must be ≤ 0.
The point estimate of the Test/Reference geometric mean ratio must fall within [0.80, 1.25]
- The within-subject standard deviation of test and reference products will be compared, and the upper limit of the 90% confidence interval for the test-to-reference ratio of the within-subject variability should be ≤ 2.5.
All the above criteria has been met except 90% confidence interval for the test-to-reference ratio of the within-subject variability ≤ 2.5 were not meet the criteria for all PK variables (Cmax, AUCt and inf).
Exercises, Observations and Analysis:
- We have taken subjects who have completed at least 2R or 2T in Reference Scaled Average Bio equivalence calculation (existing study).
- We have done the exercise who have completed all four treatments and did the statistical calculation- still failing on the same criteria marginally(90% confidence interval for the test-to-reference ratio of the within-subject variability should be ≤ 2.5).
- It was observed that if the “SWT” value should be closed to SWR value or lower, then 90% CI for the test-to-reference ratio of the within-subject variability ≤ 2.5 will meet the criteria.
- Which Reference Scaled Average Bioequivalence approach is acceptable in regulatory?
Approach 1: Subject completed at least two test product will consider for SWT calculation and subject who completed at least two reference will consider for SWR calculation.
Approach 2: Subjects who completed four period will be consider for SWR & SWT calculation.
- which are the factors adding variability to SWT?
- Whether same formulation can be taken for the repeat bio-study with some clinical restrictions? If yes then what are the clinical factor to be considered?
Edit: Please follow the Forum’s Policy. Category changed; see also this post #1. [Helmut]