Levothyroxine Sample size and study design [Power / Sample Size]
Dear Prasad,
OGD product specific guidance is for 2x2x4, following NTID rules (laid out in Warfarin guidance). Yes, this is a recent change, most levo generic drugs on market right now were approved with a CO study. Current OND guidance (for NDA) is 2x2x2 crossover.
Variability would be much smaller without baseline correction. For either test, baseline correction must be applied, which is subtracting the average of 3 predose measurements from all further PK samples.
Regarding the studies you found with a sample size of 50-72, that may be required if they were powering the study for the NTID test. OR, the large sample size may be used to pass a drug with a small (e.g. GMR of 1.05) bias. AFAIK the FDA doesn't get too upset over conservative sample sizes unless they are outrageous.
Hope that helps,
BF
OGD product specific guidance is for 2x2x4, following NTID rules (laid out in Warfarin guidance). Yes, this is a recent change, most levo generic drugs on market right now were approved with a CO study. Current OND guidance (for NDA) is 2x2x2 crossover.
Variability would be much smaller without baseline correction. For either test, baseline correction must be applied, which is subtracting the average of 3 predose measurements from all further PK samples.
Regarding the studies you found with a sample size of 50-72, that may be required if they were powering the study for the NTID test. OR, the large sample size may be used to pass a drug with a small (e.g. GMR of 1.05) bias. AFAIK the FDA doesn't get too upset over conservative sample sizes unless they are outrageous.
Hope that helps,
BF
Complete thread:
- Levothyroxine Sample size and study design lakshmiprasad 2018-04-11 15:09 [Power / Sample Size]
- Levothyroxine Sample size and study design jag009 2018-04-12 22:47
- Levothyroxine Sample size and study designbebac_fan 2018-04-12 22:49
- Levothyroxine Sample size and study design balakotu 2018-04-13 07:15
- Levothyroxine Sample size and study design lakshmiprasad 2018-04-14 12:55