TITLE:
On the Use of Local Assessments for Monitoring Centrally Reviewed Endpoints with Missing Data in Clinical Trials
AUTHORS:
Sean S. Brummel, Daniel L. Gillen
KEYWORDS:
Group Sequential; Information; Independent Review; Endpoint; Missing Data
JOURNAL NAME:
Open Journal of Statistics,
Vol.3 No.4A,
August
23,
2013
ABSTRACT: Due to ethical and logistical concerns it
is common for data monitoring committees to periodically monitor accruing
clinical trial data to assess the safety, and possibly efficacy, of a new
experimental treatment. When formalized, monitoring is typically implemented
using group sequential methods. In some cases regulatory agencies have required
that primary trial analyses should be based solely on the judgment of an
independent review committee (IRC). The IRC assessments can produce
difficulties for trial monitoring given the time lag typically associated with
receiving assessments from the IRC. This results in a missing data problem
wherein a surrogate measure of response may provide useful information for
interim decisions and future monitoring strategies. In this paper, we present
statistical tools that are helpful for monitoring a group sequential clinical
trial with missing IRC data. We illustrate the proposed methodology in the case
of binary endpoints under various missingness mechanisms including missing
completely at random assessments and when missingness depends on the IRC’s
measurement.