Addendum 4

Trial Chair Responsibilities of International SIOPEL Trials  Ver. 5.1 – 31.01.2008

The following relates to the conduct of SIOPEL international trials. 

Definitions:

  • International Trial Chair (ITC) – the lead clinician responsible for the conduct of the trial.
  • International Vice-Chair (IVC) – the deputy of the lead clinician responsible for the conduct of the trial.
  • Chief Investigator (CI) - clinician responsible for the opening and running the trial in a given region or country.
  • Principal Investigator (PI) – clinician responsible for the opening and running the trial in a center.
  • Investigator - Any clinician or non-clinical researcher responsible for carrying out trial-related procedures according to the study protocol.
  • Internal Trial Consultation Service – electronic consultation service for patients registered in the trial in case of requests by local centers or by the ITC
  • SAE – Serious Adverse Event.
  • SUSAR - Suspected Unexpected Serious Adverse Reactions.

General Responsibilities of the International Trial Chair

  • To be qualified by education, experience, and available time, to be the lead clinician responsible for the conduct of the trial.
  • To have a sound understanding of the principles of GCP and the requirements for running a trial governed by the relevant national and/or international trial legislation.
  • To supervise and head the submission to the SIOPEL Council, as well as subsequently to required  funding and regulatory bodies, of the concept proposal for this trial developed by the working trial committee and to present oneself as the clinician applying for approval as the ITC. Approval by the Council to develop a full protocol will be granted based on scientific review of the proposal, on acceptance of the trial into the current SIOPEL portfolio and on the suitability of the clinician as ITC for the study.
  • To formally resign from the position of the International Trial Chair, if the requirements of the role can no longer be fulfilled for whatever reason, such that a replacement can be identified.

Development of trial documentation

  • To lead the development of the protocol for the SIOPEL in conjunction with CCLG and the SIOPEL statistician, ensuring appropriate and timely input from all specialist disciplines followed by review and approval of the protocol content.
  • To be involved with the Remote Data Entry (RDE) web based development, in conjunction with the trial coordinator, statistician and other discipline groups as required, to produce a data collection tool that accurately reflects the data collection requirements of the trial. The ITC and IVC will take the responsibility for requesting modifications from CINECA staff the RDE system and web database in such a way that it fulfils best their needs and requirements regarding given trial.
  • To assess the need for protocol amendment(s) and to ensure the relevant ethics and regulatory approvals are obtained.

Responsibility for cooperation with national chief investigators in obtaining necessary approvals and sponsorship

  • Ensure in cooperation with the UK Chief Investigator or other required bodies that competent authority approval is granted as a Clinical Trials Authorisation (CTA) where Investigational Medicinal Products (IMPs) are to be given; provide input into the application if this is completed at the CCLG Data Centre. Verify that the available non-clinical and clinical information on the Investigational Medicinal Product is adequate to support the proposed clinical trial. Ensure that an investigators’ brochure, or a SmPC ideally containing paediatric data where available, is provided. If necessary, co-sign the application to approve its content and authorise its submission to the competent authority.
  • Assist the UK Chief Investigator in obtaining regulatory approval for a protocol or amendment.

Safety monitoring and reporting responsibilities

  • Ensure SAE reporting and monitoring system in place for a given trial.
  • Ensure clear reporting mechanisms are in place for other Principal Investigators (PIs) to notify the International Trial Chair of SUSARs (via the cooperation with the Trial Data Centre).
  • Review all SAEs to establish whether or not these are SUSARs requiring expedited reporting to the regulatory authorities.
  • Notify all other PIs of SUSARs reported on the trial by dissemination from the Data Centre.
  • Promptly inform all investigators of any urgent actions taken because of safety concerns.
  • Notify the CCLG Data Centre of annual or other extended leave and cover arrangements for SAE reporting.
  • Take responsibility for set up of a IDMC if required by the protocol. Ensure that it meets the criteria required by the protocol and ensure its recommendations are carried out during trial conduct.  Provide feedback from the IDMC to all other PIs, as appropriate.

Trial conduct and reporting responsibilities

  • Ensure, when appropriate, that the trial is initiated by means of an Investigator Meeting and/or adequate web-based teaching such that all PIs and relevant specialist disciplines are trained in the procedures and requirements of the trial protocol.
  • Take responsibility for ensuring that PIs understand their requirements for locally monitoring and reporting protocol compliance and deviations. Monitor these for implications with regard to the need to produce a protocol amendment and for detailing in annual reports as applicable.
  • Ensure availability during the course of the trial for clarification of queries from other investigators, referring where appropriate to other PIs or discipline representatives.
  • Ensure, in conjunction with the trial statistician, that appropriate monitoring of stopping rules/analysis of data is carried out.
  • Together with relevant discipline leads on trial, ensure that appropriate submission of pathology material, biological or pharmacokinetic samples, or scans are submitted and reviewed according to the specific requirements of the protocol.
  • To organize internal Trial consultation service.
  • Feed back on trial progress at bi-annual SIOPEL meetings.
  • In conjunction with the Data Centre/CINECA and the Biostatistical Office, produce annual trial progress reports.
  • Consider specific requests for data release and, in conjunction with the trial statistician, grant approval if appropriate.
  • Ensure together with the UK Chief Investigator that a final study report is submitted to the main UK REC and regulatory authority within 12 months of the end of the trial. This report should give full details of the progress and outcome of all study participants, it should state whether the study achieved its objectives, and it should include arrangements for publication or dissemination of the research including feedback to participants.

Other responsibilities

Trial registration – publication purposes

  • Before trial participants are enrolled into the study, the ITC must ensure in cooperation with the Data Centre that the protocol is registered on a database that meets the requirements of journal editors according to the WHO criteria. In practice this trial registration will be managed by the CCLG Data Centre. For RCTs the database of choice will be the International metaRegister of Controlled Trials for the issue of an ISRCTN number. For all other trials the protocol will be registered via the National Cancer Institute’s (NCI) Physician Data Query (PDQ) cancer database for issue of an NCT number and posting on the International ClinicalTrials.gov register.

Informed consent

  • The ITC is responsible for ensuring that appropriate and up-to-date information is provided to the PIs, and that approved informed consent procedures are adhered to throughout the trial.

Contracts

  • Ensure that any written legal contracts are in place prior to the start of the study. These may include agreement with RDE provider, etc.

Publication

  • The ITC  is expected to ensure that the trial is analysed and written up for publication in a timely manner, ensuring that any sub-group analyses are scheduled for publication at an agreed time without jeopardising the main study publication.
  • The ITC is also expected to publicise the results or outcome of the trial by inclusion in the background information and Patient Information Sheets for any subsequent trial.

International Trial Chair - Summary of Responsibilities

The following represents a summary of the various responsibilities of the International Trial Chair, by process and stage of trial development.  Responsibilities marked with an asterisk (*) will be carried out with support from UK Chief Investigator and staff in the CCLG, either the trial coordinator assigned to the specific trial, or the Executive Director or Senior Trials Manager, or the SIOPEL Biostatistical Office.

GENERAL RESPONSIBILITIES

  • Suitably trained, experienced and qualified to undertake the research
  • Conduct the study according to the principles of GCP and all relevant regulations, and the documented requirements of an Investigator for CCLG trials

RESPONSIBILITIES PRE-TRIAL OPENING

  • Commitment to the role of ITC
  • Awareness of regulatory requirements for trial start up, including trial and other related contracts
  • Development of trial documentation (protocol, CRF, PIS and Consent Forms) (*)
  • Ensure, if appropriate, DMC set up
  • Obtain appropriate approvals (*): Ethics / Clinical Trial Authorisation (regulatory)
  • Centre initiation – Investigator Meeting or web-based training, staff training etc (*)
  • Trial Registration for publication purposes (*)

RESPONSIBILITIES FOR DURATION OF TRIAL

  • Safety monitoring (*): to ensure that PIs conduct the study in accordance with protocol, good clinical practice rules (GCP), ethics and regulatory approvals and relevant standard operating procedures (SOPs), and to make all reasonable efforts to ensure that data collected are accurate, complete and reported in timely manner.
  • SAE reporting as required.
  • SUSAR review/notification
  • Monitoring trial progress for safety
  • Production of trial reports as required (*):
  • Clarification of any clinical queries
  • Ensuring monitoring of stopping rules, conduct of interim analyses etc (*)
  • Through monitoring of trial conduct, ensuring informed consent obtained as required by protocol (*)
  • Review and approval of applications for data release (*)
  • Processing of any protocol amendments (*)
  • Active assistance (when required) in GCP Inspections either linked to CCLG Data Centre or participating sites (*)
  • Notifying the Data Centre and Biostatistical Office of periods of absence through annual or other leave, and ensuring appropriate ITC cover arrangements are in place

RESPONSIBILITIES POST TRIAL CLOSURE

  • Notifications of closure to appropriate bodies and to CCLG centres/Principal Investigators and all other participating sites (*)
  • Production and dissemination of trial results and Interim Treatment Guidelines, if appropriate (*)

 

 

DECLARATION