A Manual for Participants in Clinical Trials of Investigational Agents ...

Any source eligible to submit a phase 2 trial (see Section 5.2) as well as other NCIsponsored
investigators (e.g., SPORE investigators) may submit phase 3 trials, but the
NCI disease-specific Steering Committee that oversees the particular disease area
and/or CTEP must evaluate and approve the phase 3 trial concept. Because sample
sizes required for such studies are usually quite large, a multicenter approach is usually
the only feasible way to conduct such a trial. It is expected, therefore, that the clinical
trials Cooperative Groups will be the major clinical site for such trials (or another entity
that is conducting the trial in collaboration with a Cooperative Group). Proposals for
phase 3 studies should document very specific accrual potential. Furthermore, if the
proposal includes a collaboration with NCI-sponsored institutions not formally affiliated
with a Cooperative Group/clinical site, the protocol should include a description of
procedures by which the collaborating institutions will manage the conduct of the
protocol. It is expected that in most cases this will also include a collaboration with one
of the clinical trials Cooperative Groups (see Section 7.2.14).
6.3 Eligibility Requirements
Phase 3 clinical trials must include a review of the available evidence to show whether or
not clinically important gender or race/ethnicity differences in the response to the
intervention are expected. The trial’s design must reflect the current state of knowledge
about expected differences. Phase 3 clinical trials are, in addition, required to provide
valid analysis to measure differences of clinical or public health importance in
intervention effects based on gender or racial/ethnic subgroups where evidence
supports differences.
Investigators should consider the following circumstance when planning a phase 3
clinical trial:
• Prior data strongly indicate that the intervention will show significant clinical or public
health differences among gender, racial, and/or ethnic subgroups. In this case, the
proposed phase 3 trial’s primary question(s) to be addressed and design must
specifically accommodate these differences. For example, if men and women are
thought to respond differently to an intervention, the phase 3 trials must be designed
to answer two separate primary questions, one for men and the other for women,
with adequate sample size for both.
• Prior data strongly support no significant clinical or public health differences among
subgroups from the intervention. In this case, gender, race, and/or ethnicity will not
be required as subject selection criteria. However, the inclusion of gender, racial,
and/or ethnic subgroups is still strongly encouraged.
• Prior data neither strongly support nor negate the existence of significant clinical or
public health differences among groups. In such cases, the phase 3 trial must
include sufficient and appropriate gender, racial, and/or ethnic subgroups, so that
valid analysis of the intervention effects on subgroups can be performed. However,
the trial will not be required to provide high statistical power for each subgroup.
Cooperative Group Phase 3 studies:
Effective October 1, 1995, all phase 3 protocols must include accrual targets for males,
females, and minorities (protocol specific accrual targets for phase 1 and 2 studies are
NOT required). The accrual targets should reflect the expected accrual over the life of
the study. The NCI suggests the accrual targets be based on data from similar trials
Section 6 - Investigator’s Manual 2009 26