Specific remarks [Design Issues]
Dear kishpokuri,
The FDA guidance on Brinzolamide gives you very specific details on how to establish BE with the clinical endpoint IOP (intra-ocular pressure.
Quote:
"To establish BE, the limits of each two-sided 95% confidence interval of the treatment difference (test – reference) for mean IOP of both eyes (continuous variable) at all four follow-up points (i.e., at approximately 8:00 a.m. (hour 0; before the morning drop) and 10:00 a.m. (hour 2) at the Day 14 (week 2) and Day 42 (week 6) visits must be within ± 1.5 mm Hg using the PP population for all time points measured and within ± 1.0 mm Hg using the PP population for the majority of time points measured."
Now you have:
Then look for a sample size estimation software which covers equivalence studies using the difference between means (f.i. PASS) with parallel group design.
You may also 'missuse'
Example use with a hypothetical IOP standard deviation and an assumed 'true' difference:
theta0 and standard deviation you must of course qualify from data in the literature.
The target power is ditto at your choice.
Hope this helps
❝ Can anyone suggest the appropriate sample size for a clinical endpoint bioequivalence study of Brinzolamide 1% ophthalmic suspension in chronic open angle glaucoma patients.
The FDA guidance on Brinzolamide gives you very specific details on how to establish BE with the clinical endpoint IOP (intra-ocular pressure.
Quote:
"To establish BE, the limits of each two-sided 95% confidence interval of the treatment difference (test – reference) for mean IOP of both eyes (continuous variable) at all four follow-up points (i.e., at approximately 8:00 a.m. (hour 0; before the morning drop) and 10:00 a.m. (hour 2) at the Day 14 (week 2) and Day 42 (week 6) visits must be within ± 1.5 mm Hg using the PP population for all time points measured and within ± 1.0 mm Hg using the PP population for the majority of time points measured."
Now you have:
- Statistical test = confidence interval inclusion rule, operationally identical with TOST (two one sided t-tests), but here for the difference on the original scale and with 95% CI (alpha=0.025, as usual with clinical endpoints)
- IUT (intersection-union) test of four time points, i.e. at all time points BE must be met. That allowes you to restrict your sample size estimation for one time point.
- Equivalence margin
Then look for a sample size estimation software which covers equivalence studies using the difference between means (f.i. PASS) with parallel group design.
You may also 'missuse'
PowerTOST
, which is intentionally programmed and described for ratios, but works also for differences using the argument logscale=FALSE. Set alpha=0.025, give theta0 as true difference (mm Hg) at which you will be able to accept BE, theta1 and theta2 to the stringenter equivalence margins as -1.0, 1.0 (mm Hg) and set CV to the standard deviation of the IOP (we don't know at moment).Example use with a hypothetical IOP standard deviation and an assumed 'true' difference:
library(PowerTOST)
sampleN.TOST(alpha=0.025, logscale=FALSE, theta0=0.5, theta1=-1.0, theta2=1.0, CV=1.5, targetpower=0.8, design="parallel")
theta0 and standard deviation you must of course qualify from data in the literature.
The target power is ditto at your choice.
Hope this helps
—
Regards,
Detlew
Regards,
Detlew
Complete thread:
- sample size for clinical endpoint BE study of Brinzolamide 1% ophthalmic kishpokuri 2015-11-24 14:18 [Design Issues]
- general remark ElMaestro 2015-11-24 16:50
- Specific remarksd_labes 2015-11-25 11:23
- Specific remarks kishpokuri 2015-11-27 13:46