Contains Nonbinding Recommendations
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involvement can be quite limited provided that (1) appropriate care is taken to ensure that
the sponsor does not see outcome data separately by study arm and (2) the sponsor does
not unduly influence the closed deliberations of the committee.
On the other hand, involvement by sponsor representatives and certain investigators in
the portion of the DMC meeting where unblinded data are reviewed presents substantial
disadvantages, as discussed in Sections 6.1 and 6.3. Even so, such involvement is not
entirely without rationale. When a DMC is facing difficult decisions based on interim
safety or efficacy data, the sponsor representatives, study statisticians, and study
investigators may contribute valuable perspectives that may not be available from more
independent sources. For example, such individuals might point out that unanticipated
difficulties in collecting certain data may affect their reliability. In addition, such
individuals might have detailed knowledge of other relevant information about the drug
(or disease) gained from the trial in question or from other studies that could enhance the
DMC’s ability to monitor the current trial. To the extent such perspectives can be
obtained through a combination of having independent DMC members who are very
familiar with the drug, the disease, and trial and having sponsor involvement in open
session only, some risks (see Section 6.3) will be minimized. When a trial’s procedures
are such that sponsor representatives or investigators do see unblinded data with the
DMC, the DMC may wish to develop its recommendations in an executive session (see
Section 4.3.1.2).
6.3. Risks of Sponsor Exposure to Interim Comparative Data
Sponsor exposure to unblinded interim data, through the DMC or otherwise, can present
substantial risk to the integrity of the trial. One concern is that unblinding of the sponsor
increases the risk of further unblinding, e.g., of participants, potential participants, or
investigators, thereby potentially compromising objective safety monitoring, equipoise,
recruitment, administration of the intervention, or other aspects of the trial. In some
cases, this risk may be limited and manageable. However, even when unblinding is
limited to a small group or a single individual within the sponsoring organization who
maintains confidentiality of the results, it is possible that an individual with knowledge of
interim data may reveal, or be perceived to reveal, information inadvertently, e.g., by
facial expression or body language.
An additional problem arising from a sponsor’s access to interim data is the diminution of
the sponsor’s ability to manage the trial without introducing bias. Many trials,
particularly those with DMCs, take place over several years. During that time, it is not
uncommon for scientific advancements, e.g., development of new tests, approval of new
products, announcement of results of other trials, to significantly affect a given trial.
Such developments may suggest a need for modifications of the experimental protocol,
e.g., allowing certain concomitant treatments, changing endpoints. Non-scientific
developments, such as new financial considerations, production problems, enrollment
problems, and missing data, may also suggest the need for protocol changes. If the
sponsor has had access to interim data, it may be impossible to avoid allowing that
knowledge to influence decisions regarding modifications of the trial; it may also be