HI Swapnil S Salaskar,
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3.2 SUBJECTS
3.2.1 Number of Subjects
It is recommended that the number of subjects should be justified on
the basis of providing at least 80 % power of meeting the acceptance
criteria. The minimum number of subjects should not be less than 12.
If 12 subjects do not provide 80 % power, more subjects should be
included.
A minimum of 20 subjects is required for modified release oral dosage forms.
The number of subjects required to provide an 80 % power of meeting
and passing the acceptance criteria for the 0,8 to 1,25 acceptable
interval, can be determined from Reference 1.
Alternatively, the sample size can be calculated using appropriate
power equations, which should be presented in the protocol.
The provision for add-ons should be made in the protocol a priori
clearly reflecting the maximum number of subjects to be included.
3.2.2 Drop-outs and withdrawals
Sponsors should enter a sufficient number of subjects in the study to
allow for possible drop-outs or withdrawals. Because replacement of
subjects during the study could complicate the statistical model and
analysis, drop-outs generally should not be replaced. Reasons for
withdrawal (e.g. adverse drug reaction, personal reasons) must be
reported.
Sponsors who wish to replace drop-outs during the study or consider
an add-on design should indicate this intention in the protocol.
It is more appropriate to recruit into the study more subjects than
the sample size calculation requires.
These subjects are designated as extras. The protocol should state
whether samples from extra subjects will be assayed if not required
for statistical analysis.
If the bioequivalence study was performed with the appropriate size
but bioequivalence cannot be demonstrated because of a result of a
larger than expected random variation or a relative difference, an
add-on subject study can be performed using not less than half the
number of subjects in the initial study. Combining is acceptable
only in the case when the same protocol was used and preparations
from the same batches were used.
Add-on designs must be carried out strictly according to the study
protocol and SOPs, and must be given appropriate statistical
treatment, including consideration of consumer risk.
regrds,
shakeel
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shakeel
shakeel_ms2002@yahoo.co.in
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