Submission of outlines and protocols to the EORTC Protocol Review Committee

Protocols are submitted for the EORTC approval in two steps:

1. A study outline, approved by one (or several) EORTC Group(s) is submitted to the PRC for review and approval of the principal characteristics of the project (scientific background, medical relevance, general design and important logistic issues)
2. The full protocol, based on a PRC approved outline, and developed according to the EORTC standard methodology, is submitted to the PRC for final approval (EORTC label), and allocation of Headquarters support.

EORTC clinical trials should aim at answering an original and scientifically relevant medical question. The answer provided by the trial should contribute to a treatment development strategy ultimately expected to influence clinical practice.
The principal elements of the proposed study should be summarized by answering the standard EORTC “outline questionnaire”, which can be used as a check-list of the principal points to be discussed and decided with the potential investigators, with the EORTC Headquarters (HQ) and with other eventual partners (other groups, pharmaceutical industry…).
The “study outline” should include a clear and concise answer to all questions and must satisfy the following conditions:

• It must be approved by (at least) one EORTC Group(s) that can demonstrate a sufficient interest and potential recruitment to conduct the study in a reasonable time frame.
• One single Study Coordinator must be appointed by the EORTC Group(s).
• The HQ must have been involved in the study design, and must have approved the outline. In case of major disagreement between the HQ team and the Group, the outline proposed by the Group can be submitted to the PRC, but the HQ will inform the PRC of its position.
• The HQ should have the appropriate resources to support the development, conduct and analyses of the trial. If this is not the case, after discussion with the group, the HQ team can delay the outline or protocol submissions until these resources become available.

Outline submission

Approval or rejection of a clinical trial project is essentially based on the information provided in the study outline.
The “outline questionnaire” has to be completed interactively on the EORTC web site, in one or several sessions, by one or more individuals. It remains accessible for modifications (with password protection) until flagged as “final”.
The PRC secretariat will allocate an EORTC study number to each project and ask a “green light” to the HQ team and a support letter (or e-mail) from the Group Chairman before submitting the final version to the PRC.
In the case of projects dealing with investigational agents, the investigator brochure (and international publication(s) if applicable) must be sent, preferably in an electronic format, to the PRC secretariat.
The first PRC decision will be notified to the EORTC Study Coordinator(s), the EORTC Group Chairman and the EORTC HQ team within one month of receipt of the outline and can be:

• Acceptance of the outline.
• Substantially modify the outline, and submit a new version.
• Reject the project.
• Decide that the outline should be further discussed during a plenary meeting of the PRC with the Study Coordinator.

Full protocol submission

Full protocols are developed in a modular way with the logistic support of the HQ Protocol Help Desk and of the HQ team. Appropriate instructions, guidelines and templates will be addressed to the Study Coordinator after outline approval and feasibility green light.
Development of the full protocol (final version, with all appendices) must be completed within six months of outline approval; EORTC Groups have the possibility to shorten this deadline.
When completed, the Study Coordinator should send a submission letter (or e-mail) to the PRC secretariat, which includes:

• An answer to all questions, comments and suggestions included in the outline decision letter.
• The description of eventual differences between the accepted outline and the full protocol.

All Study Coordinators need to complete a conflict of interest form, according to the EORTC Conflict of Interest and Confidentiality Policy. The form is sent to the Study Coordinator at the time of outline approval and must be signed by the Study Coordinator and returned to the PRC secretariat before submission of the full protocol.
The final decision will be notified to the EORTC Study Coordinator(s), the EORTC Group Chairman and the EORTC HQ team within one month of full protocol submission. The review of the full protocol may:

• Approve the full protocol (with or without suggestion for minor modifications to be incorporated in the full protocol).
• Require major modifications to the protocol, to be resubmitted with an accompanying letter (or e-mail) addressing all (major and minor) PRC comments individually.

In all cases, the final PRC approved version of the protocol must be available within 12 months of outline approval.

Intergroup studies

Intergroup studies should follow the EORTC Intergroup Policy.
If the trial is coordinated by an EORTC Group or the EORTC HQ, the EORTC approval will be obtained through the usual submission procedure (see above).
If EORTC is neither the Coordinating Group, nor the Coordinating Data Center, the EORTC Group(s) should appoint an “EORTC Coordinator” who will:

• Complete an outline questionnaire (even if the full protocol is already available).
• Send to the PRC secretariat a copy of all available documentation of prior peer reviews of the project (preferable as electronic documents).
• If the study is already active in another group, explain in the comment section of the outline questionnaire the reasons why the EORTC will join the trial at a late stage.
• If the full protocol is already finalized, it should be sent to the PRC secretariat at the time of outline submission (preferably as an electronic document).
• If the “EORTC Group Appendix” (see hereunder) is already finalized and approved by the EORTC Intergroup Office, the PRC Secretariat should be informed.

Development of the full protocol is normally the responsibility of the Coordinating Group. The EORTC HQ will develop an “EORTC Group Appendix”. The further review process will be decided by the PRC on the basis of the information provided at the time of outline submission.

Amendments

After PRC approval, any modifications to the protocol must be discussed with the EORTC HQ, submitted or notified to the PRC, and eventually submitted or notified to all Institution Review Boards (depending on the type of amendment).
Amendments should be sent to the HQ team that will appropriately:

• submit or notify changes to the PRC
• implement changes in the protocol, and issue a new version
• circulate the amendment and the new version of the protocol to all investigators, indicating if IRB submission or notification is required

Phase II / III studies

Continuation of a feasibility phase II study as a full phase III study will be considered as a protocol amendment if:

• the feasibility study is randomized
• the intention to perform the phase III trial is included in the phase II trial
• the decision rule foreseen in the phase II trial is satisfied, or phase III extension is recommended by the Independent Data Monitoring Committee

Practical information

Outlines are submitted to the PRC secretariat via Internet (outline questionnaire). Practical instructions are available from this web site. For each new submission, an outline number and a password are automatically generated and communicated at the end of the submission process. An EORTC study number will be allocated and added to the outline questionnaire by the PRC secretariat, at the latest when the outline is final.
Full protocols are assembled at the EORTC HQ by the Protocol Help Desk. Official submission only requires a submission letter (or e-mail) from the Study Coordinator.
All documents and all correspondence should be addressed to:
EORTC PRC secretariat
Avenue Mounier 83, bte 11 B 1200 - Brussels (Belgium)
E-mail: prc.sec@eortc.be
Electronic format should be used for all documents (if no electronic version is available, the review process may be delayed).