Oversight and monitoring
Composition of the coordinating centre and trial steering
committee
{5d}
The trial will be managed through the CTU at the Tata Medical Center.
All PIs of the collaborating institutes will be a part of the trial
management committee. Study coordination, monitoring, data acquisition
and management and statistical analysis will be performed by Tata
Medical Center.
Additionally, we will constitute an outcome assessment committee who
will provide independent and central assessment of the important trial
outcomes.
Composition of the data monitoring committee, its role and
reporting structure
{21a}
An independent data safety and monitoring committee will be constituted
which will provide an independent assessment of the patient safety,
trial progress, making recommendations to the trial management committee
about the continuation of the trial based on the data made available by
the trial investigators. The DSMC will also recommend any revisions in
protocol required as a result of new or emerging information regarding
the adjuvant radiotherapy schedule for this setting. DSMC reports will
be communicated to the institutional review boards of the participating
centers. The DSMC will be composed of four to five members of whom at
least one will be a statistician with significant experience in clinical
trials.
Adverse event reporting and harms
{22}
All adverse events related to radiotherapy as well as any serious
adverse events will be recorded in clinical trial forms which will be
recorded in the centrally managed RedCap database. The investigator at
each site will be responsible for reporting the SAE to the respective
Institutional Review Board as well as the PI at the CTU. Local IRB would
be notified of any SAE within 24 hours on a working day or as per the
institutional norm. The sponsor will be intimated within a period of 10
days from the date of occurrence of the SAE. SAEs must be reported up to
30 days from the end of study intervention.
The following information should be provided for all SAEs:
- Event description including classification according to NCI CTCAE
- Primary and secondary diagnosis of the event (If
death/hospitalisation)
- Severity / Worst Grade
- Attribution to study intervention
- Expectedness (listed in IB/product information)
- Action taken with study intervention
- Impact of SAE (e.g. hospitalisation details)
- The outcome of SAE including end date if recovered
Frequency and plans for auditing trial conduct
{23}
Compliance to protocol will be reviewed after accrual of the first 5,
25, 75 and 200 cases. Any protocol deviation needs to be notified to the
respective IRB, to the chief investigator, coordinating centre and
discussed in the trial management committee meetings. Additionally, PI
at each center should be notified about any changes made to the protocol
in the interest of patient safety as a result of this- this will need
updating in writing in the trial protocol with a change in the version
number of the study protocol. Any major radiation dosimetric protocol
deviation in more than 1 patient of the first 5 patients or more than
10% cases after 10 have been recruited, should be informed and
discussed in the trial management committee. Additional audits and
monitoring as required by trial sponsors would be done as mandated by
institutional and regulatory norms.
Plans for communicating important protocol amendments to
relevant parties (e.g. trial participants, ethical committees)
{25}
Changes and amendments to the protocol would only be made by the Trial
Management Committee. Approval of amendments by the Institutional (IRB)
would be required prior to their implementation. In some instances, an
amendment may require a change to a consent form. In such cases, the
form will be used only after approval from the IRB. All amendments will
be stored in the sponsor site and will be shared with all participating
sites through email as well as during regular trial management committee
meetings.
Dissemination plans {31a}
A Clinical Study Report which summarises and interprets all the
pertinent study data collected will be issued which may form the basis
of a manuscript intended for publication. The Clinical Study Report or
summary thereof will be provided to the local IRB of the institutes
participating in the protocol. Additionally the same will be made
available on the trial registration websites. The Trial Management
Committee will appoint a Writing Committee to draft manuscript(s) based
on the trial data. Manuscript(s) will be submitted to peer-reviewed
journal(s). The Writing Committee will develop a publication plan,
including authorship, target journals and expected dates of publication.