## Regulatory acceptance pre-mature discontinuation of study [Study Per­for­mance]

» which assumptions (CV, T/R-ratio) and target power lead to the sample size?

T/R ratio- 95%
Power ≥ 80%
CV%- 25%

One statement they mentioned in protocol “Additional subjects may be randomized in case of excessive drop outs, to get at least 36 subjects with complete pharmacokinetic assessment if required”

» Apart from the cost, using different batches in a study is not acceptable. See below why there are no problems expected with 31 subjects. Send me a check for \$ 500,000 (peanuts) for delivering the soothing news.

For Eg. If we compare New RLD dissolution data Vs OLD RLD dissolution data. And if we found dissolution data of both RLDs is comparable. Still can’t we use new lot of RLD?

» » 1. Can we stop the study with 37 subjects and perform stat. analysis with 31 subjects?
» Yes.

Good.

» » 2. Does FDA accept this type of study if we perform analysis with 31 subjects and file pre-plan deviation.
» Why not? Your sample size was based on an assumed recruitment rate and an anticipated dropout-rate.
»

[…]
» Planned power: 91.45% (n = 36)
» Actual power : 87.14% (n = 31)
» Relative loss:  4.71%
»
» Would such a relative loss in power really hurt?

NO

Development of Abbreviated New Drug Applications During the COVID-19 Pandemic mentions April 2021. Updated on September 8, 2021.
“It may be acceptable to utilize a different batch of unexpired reference product to complete a BE study, so long as the prospective applicant provides adequate scientific justifications for the use of different batches of reference product in the BE studies. A prospective applicant that intends to use a different batch of reference product for such purposes may submit additional inquiries with specific proposals or alternative proposals to demonstrate BE for the development program via the controlled correspondence pathway or, if applicable, via the pre-ANDA meeting request pathway”