Back to the Top
From: pablo.-at-.unidavi.edu.br
Date: Thu, 5 Jun 2003 13:04:09 -0300
Subject: sample size in BE
The following message was posted to: PharmPK
Dears, I have an basic doubt. How Do I determine the sample size for
bioequivalence studies? Thanks, Pablo A. Pereira
Back to the Top
Hi Pablo,
all following references are given for AVERAGE bioequivalence.
Tables give EXACT sample sizes for given variability, alpha- and
beta-error, estimated deviation of the point estimate from unity (or
zero) at an desired level of statistical power. Don't interpolate
within table values, since power curves are VERY nonlinear, use the
approximations instead.
Approximations are easy to implement in any spreadsheet application (or
if you are a little patient, give results with only the aid of a table
of the t-distribution and a pocket calculator within a couple of
minutes). Estimated same sizes return table values or are sligthly
higher (i.e., conservative, so you are on the safe side anyway). They
are very useful if you want to estimate "exotic" input (e.g., point
estimate -7%, acceptance range 0.75-1.33, 85% power).
ADDITIVE MODEL (RAW DATA), 2x2 CROSSOVER
==
TABLES
K.F. PHILLIPS;
Pharmacometrics. Power of the Two One-Sides Tests
J. Pharmacokin. Biopharm 18/2, 137-144 (1990)
APPROXIMATION
LIU, J.-P. and S.-C. CHOW;
Sample Size Determination for the Two One-Sided Tests Procedure in
Bioequivalence
J. Pharmacokin. Biopharm 20/1, 101-104 (1992)
MULTIPLICATIVE MODEL (LOG-TRANSFORMED DATA), 2x2 CROSSOVER
==
TABLES
DILETTI, E., HAUSCHKE, D. and V.W. STEINIJANS;
Sample size determination for bioequivalence assessment by means of
confidence intervals
Int. J. Clin. Pharm. Ther. Toxicol. 29/1, 1-8 (1991)
DILETTI, E., HAUSCHLE, D. and V.W. STEINIJANS;
Sample size determination: Extended tables for the multiplicative model
and bioequivalence ranges of 0.9 to 1.11 and 0.7 to 1.43
Int. J. Clin. Pharm. Ther. Toxicol. 30/Suppl.1, S59-62 (1992)
APPROXIMATION
HAUSCHKE, D., STEINIJANS, V.W., DILETTI, E. and M. BURKE;
Sample Size Determination for Bioequivalence Assessment Using a
Multiplicative Model
J. Pharmacokin. Biopharm. 20/5, 557-561 (1992)
Tables and Appoximation-formulas for all the cases above plus the
parallel design are given at
S.-C. CHOW and H. WANG;
On Sample Size Calculation in Bioequivalence Trials
J. Pharmacokin. Pharmacodyn. 28/2, 155-169 (2001)
unfortunately the original reference contains a lot of typographical
errors, so please also consult with
D. HAUSCHKE;
A Note on Sample Size Calculation in Bioequivalence Trials
J. Pharmacokin. Pharmacodyn. 29/1, 89-94 (2002)
P. BLOOD;
Sample Size Calculation in Bioequivalence Trials
J. Pharmacokin. Pharmacodyn. 29/1, 95-97 (2002)
and author's response and errata
J. Pharmacokin. Pharmacodyn. 29/1, 99-102 (2002)
Tables for 4 different replicate designs (Balaam's, 2-sequence dual,
4-period 2-sequence, 4-period 4 sequence), both in raw scale and
log-transformed are given at
CHEN, K.-W., CHOW, S.-C., and G. LI;
A Note on Sample Size Determination for Bioequivalence Studies with
Higher-Order Crossover Designs
J. Pharmacokin. Biopharm. 25/6, 753-765 (1997)
many useful references are also given in
S.C. CHOW and J.-P. LIU;
Design and Analysis of Bioavailability and Bioequivalence Studies
Second Edition, Revised and Expanded
Marcel Dekker, New York, Basel 2000
Since you are located in Brazil, don't forget ANVISA ;-)
http://www.anvisa.gov.br/hotside/genericos/legis/resolucoes/
478_02_re_e.htm
Resolution No 478 of March 19, 2002 states under 1.f)
"The minimum number of subjects is generally 24..."
Regards
Helmut Schütz
Head Biostatistics
Biokinet GmbH Tel +43(0)1 4856969-62
Nattergasse 4 Fax +43(0)1 4856969-90
A-1170 Vienna/Austria mailto:helmut.schuetz.at.chello.at
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)