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Activity Number:
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119
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Type:
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Contributed
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Date/Time:
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Monday, August 9, 2004 : 10:30 AM to 12:20 PM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #301644 |
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Title:
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Choosing the Analysis Population in Noninferiority Studies: Per Protocol or Intent-to-treat
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Author(s):
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M. Matilde Sanchez*+ and Xun Chen
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Companies:
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Merck & Co., Inc. and Merck & Co., Inc.
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Address:
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RY34-A316, PO Box 2000, Rahway, NJ, 07065,
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Keywords:
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dropout due to lack of efficacy ; hybrid ITT/PP analysis ; nontrivial missing ; LVCF method ; MLE method ; noncompliance
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Abstract:
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For superiority trials, the intent-to-treat population (ITT) is considered the primary analysis population because it tends to avoid the over-optimistic estimates of efficacy that results from a per-protocol population (PP). However, the roles of the ITT and PP population in noninferiority studies are not clearly defined. A simulation study is conducted to systematically investigate the impact of different types of missingness and protocol violation on the conservatism or anti-conservatism of ITT and PP analyses in noninferiority trials. The requirement that noninferiority be shown for both population does not necessarily guarantee the validity of a noninferiority conclusion and a sufficiently powered PP analysis is not necessarily powered for ITT analysis. It is important to assess the potential types and rates of protocol deviation and missingness and to obtain some prior knowledge regarding the treatment trajectory of the test treatment versus the active control at the design stage such that proper analysis plan and careful power estimation can be carried out.
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