Bioequivalence and Bioavailability Forum

Hi John, Lara, Detlew and Helmut

Please do not underestimate the article by looking at journal name. You all are requested to see the formulas mentioned to arrive at sample size estimations, since it is pure Mathematics. Please be noted that Mathematics is same throughout the globe.

You all believe following is the formula for sample size estiamtion? Please be noted that the same formula used world wide for sample size estimation.

SAMPLE SIZE ESTIMATION (The formula obtained from the book “design and analysis of BA and BE Studies, SHEIN-Chung CHOW, JEN-PEI LIU”), Refer Page no: 153.

ne = [t(α, 2n-2) + t(β, 2n-2)]2 * [CV/(V-δ)]2

Where

n- is sample size as per pilot study.
CV- is Coefficient of Variation (intra-subject variability) of that PK parameter which has maximum variability.
V- is Log of Bioequivalence limit (0.8 or 1.25) i.e. 20% difference.
(In general 10% difference is considered. In case of highly variable drugs go for 5% difference of Generic Vs Innovator)
δ- is Absolute value of expected/ observed difference.
α- is level of significance, generally 5%.
β- is probability of Type II error.
Note: The minimum number of subjects that would be acceptable is 12. Care should be taken to avoid any bitter any experience.

The formula correlating intra-subject variability of reference and within subject standard deviation of reference obtained from the EU directives of Doc. Ref.: CPMP/EWP/QWP/1401/98 Rev. 1/ Corr ** (Refer page no: 17 of 27).

CV(%)=100*Sqrt((e^(S[2]/WR])-1)

We noted that the incomplete sentence in the article and suggested to delete the same before publishing, but unfortunately it was not deleted by the Editor. Please refer to detailed communication with the Editor.

Dear Editor

We have given comments to delete the below mentioned incomplete sentence (page no: 5045) from the manuscript, but unfortunately that was not done.

We appreciate, if you could able to delete this.

Thanking you.

Best Regards,

Someswar Korla

From: Recentscientific Recentscientific [mailto:[email protected]]
Sent: Wednesday, July 29, 2015 11:20 AM
To: Someswar.Korla
Subject: Article has been published

Dear author,

The Editor-in-Chief is pleased to inform you that, submitted your research article has been published in the International Journal of Recent Scientific Research through

recentscientific.com/sample-size-estimation-highly-variable-drugs-using-reference-scaled-average-bioequivalence-criteria

You can now download your published paper.

Hope to get more papers from you and your colleagues.

With Regards,
Editorial Office
International Journal of Recent Scientific Research
www.recentscientific.com
Email: [email protected]

Research Article are Invited for Publication
www.recentscientific.com

For any query in this regard feel free to contact me at any time
with regards
--------------------
Editorial Office
International Journal of Recent Scientific Research
www.recentscientific.com
email: [email protected]

Moreover, we have validated obtained sample size estimations against the published article “Sample Sizes for Designing Bioequivalence Studies for Highly Variable Drugs, J Pharm Pharmaceut Sci (www.cspsCanada.org) 15(1) 73 - 84, 2011”. The same article did not specify the sample size estimations beyond 60% ISCV and above. Our intention to provide sample size estimations with 60% ISCV and above as pharmaceutical scientists are frequently using scaled average bioequivalence studies.

If anything not understand please send your comments to me, I will make you understand.

If you all are “gems” please provide sample size estimation formula for scaled average bioequivalence studies from your end and educate the pharmaceutical world.

Best Regards,
Someswara Rao