Clinical research brings new treatments to patients. New treatments can be new medicines, new cell therapies and other forms of advanced therapies, new surgical procedures or other new approaches to managing a patient. Randomised controlled prospective clinical trials are generally agreed to be the gold-standard for clinical research. A randomised controlled trial compares two or more treatments or approaches in a controlled setting.
A prospective clinical trial is required if the trial protocol includes an intervention that is outside of the patient’s routine medical care, such as an unlicensed medicine. All prospective clinical trials must follow a protocol that has prior ethics committee and competent authority approval and must be conducted in compliance with the EU Clinical Trials Directive (2001/20/EC) and the EU Good Clinical Practice directive (2005/28/EC). From late 2011, all EBMT-sponsored prospective clinical trials will be approved by the Clinical Trials Office.
EBMT-sponsored prospective clinical trials are run by the EBMT Clinical Trials Offices in Leiden, often in conjunction with a CRO. The CTOs support multinational, multicentre trials. The services that the CTOs provide vary between trials and include study design and operational feasibility, protocol and patient information leaflet writing, ethics committee and competent authority submissions, insurance, site selection and set up, monitoring and/or auditing, pharmacovigilance, data management, and day-to-day project management and documentation. The services that the CTO will provide for an individual study will be agreed with the Chief Investigator.
If you would like to know more about the EBMT Clinical Trials Offices, or are interested in sponsoring a trial, please contact Marianne Mol, Clinical Studies Operations Manager: firstname.lastname@example.org. If you would like more details about the procedures for submitting a proposal for a Clinical Trial, see the How to Submit a Proposal section below.
How to submit a clinical trial proposal
1. The Investigator proposes his or her trial idea to the appropriate Working Party (WP) Chair. All EBMT-sponsored and EBMT-labelled prospective clinical trials must be submitted via a WP chair.
Two of the Working Parties, the Inborn Errors WP and the Infectious Diseases WP, have specific procedures for proposing new studies. For all other WPs, contact the Chair or the Secretary.
2. Preparation and review of the proposal within the WP and with a WP statistician. For guidance, download the Protocol Proposal Template and the Protocol Assessment Form for details on how your proposal will be reviewed.
The WP statistician will write the statistical section. The Clinical Trials Operations Manager and the study statistician can be approached during this period for advice.
3. The WP Chair submits the proposal to the Clinical Trials Office with budget estimates. A Word version and a signed PDF of the proposal, along with a budget estimate spreadsheet must be submitted to email@example.com.
Confirmation of receipt will be provided and the WP Statistician must be able to provide clarifications and missing material if required.
4. The Clinical Trials Office will review the proposal in terms of Science, Statistics, Finance & Legal, and Operational feasibility, and may seek external advice. If requests are made for further information, you will have 1 week to respond.
5. The Clinical Trials Office will rank the proposed trial and present it to the Board. You will not receive your overall ranking, but will be provided with feedback from the Committee after the Board meeting.
6. The Board will select 1-2 trials for EBMT sponsorship per year and the Clinical Trials Office will inform the WP Chair. There will be a second review of the selected trials when the full protocol and contracts are available.
Prospective Clinical Trial FAQs
What do I do if my WP doesn't have am EBMT statistician?
If there is no WP statistician, then at least 1 month before the submission deadline the WP chair must contact: for Paris-based WPs, Myriam Labopin (firstname.lastname@example.org); for Leiden-based WPs, Ronald Brand (R.Brand@lumc.nl), to allocate an EBMT statistician to the trial. Please see the Statistical Support document above for further details.
How do I decide what the level of risk is for my trial?
Please use the guidance in the table below and discuss your selection with the CTO if needed. Categorizations based on Brosteanu O et al. Clinical Trials 2009 Dec; 6: 585-96
|Trial Categories based upon the potential risk associated with the Investigational Medicinal Product (IMP)||Examples of types of clinical trials|
|Type A: no higher than that of standard medical care||
Trials involving medicinal products licensed in any EU Member State if they relate to the licensed range of indications dosage and form or they involve off-label use (such as in paediatrics and in oncology etc) if this off-label use is established practice and supported by sufficient published evidence and/or guidelines
|Type B: somewhat higher than that of standard medical care||
Trials involving medicinal products licensed in any EU Member State if such products are used for a new indication (different patient population/disease group) or substantial dosage modifications are made for the licensed indication or if they are used in combinations for which interactions are suspected
Trials involving medicinal products not licensed in any EU Member State if the active substance is part of a medicinal product licensed in the EU
|Type C: markedly higher than that of standard medical care||Trials involving a medicinal product not licensed in any EU Member State (A grading other than TYPE C may be justified if there is extensive class data or pre-clinical and clinical evidence)|
How should I estimate the budget needed for my trial?
- Contact the CTO (email@example.com). You will be given a spreadsheet that can help to estimate the budget required
- Please complete it and then discuss it with the CTO
a. The cost of the trial is highly dependent on the number of countries, centres and patients, so please choose these carefully
b. Please remember that delays to a trial increase the costs of many tasks, such as insurance, monitoring and project management
When do I need to submit my proposal to the EBMT?
The timeline for review in 2018 is below:
|WP Chair to contact Statistical Coordinator if there is no WP Statistician|
|Submission Deadline for proposal and budget|
|Requests for more information if applicable|
|Submit additional information (1 week)|
|TC to confirm scores/ranking|
|Exec committee TC|
|Board Meeting: Trials selected|
How will the EBMT choose the trials for EBMT sponsorship?
All proposals will be scored by the members of the Clinical Trials Office using the Protocol Proposal Assessment Form. You may be asked for more information to help with this review.
The Clinical Trials Office will present the trials to the Board, with a recommendation for sponsorship. After the Board meeting, you will receive feedback from the CTO coordinator.
What will happen after my trial is selected?
You will need to complete a full protocol for the trial (download the template above, or you may use your own template). The Clinical Trials Office will complete a second review of the proposal when the full protocol and contract(s) are available. See the Protocol Proposal Assessment form above.
If your trial is confirmed as an EBMT sponsored trial, you will be allocated an EBMT Clinical Trial Coordinator (CTC) in London or Leiden. The CTC will provide you with more information, but in general, you will be given:
- Proposed timelines for the trial, including expected set-up and reporting times
- A list of tasks to be managed by the EBMT CTO and those to be managed by the Chief Investigator/National Groups, eg ethics and regulatory submissions, randomisation, monitoring, pharmacovigilance, data management (roles and responsibilities)
- Support for insurance and contract negotiation
- Support for publication planning
What can I do if my trial is not selected for sponsorship?
Following the Board meeting, you will be given detailed feedback about the trial. You may discuss this feedback with the CTO, however, if you want to re-submit, you must wait until the following cycle of reviews. You can of course proceed with your trial if you can find an alternative sponsor and you can request to have the trial scientifically endorsed by the EBMT (“EBMT-labelled trial”). Rules for EBMT-labelled trials are available from the CTO.
Golden rules for setting up a clinical trial
- Ensure everyone is on board before you finalise the protocol - this must have been reviewed by the Working Party, the WP statistician and any relevant national coordinating groups. This avoids subsequent avoidable amendments to the protocol.
- Work with the CTO early to develop a budget for the trial so that you can raise funds to support it. Include a payment for centres. This is almost always needed now due to charges by institutions. All EBMT-sponsored clinical trials must have adequate funding. It is best if the CTO negotiates directly with any pharmaceutical companies.
- Be clear in the questions that will be answered by the trial. This ensures that the CRFs can be well designed so that the correct data are collected.
- Allow the CTO to advise which centres should participate in a trial, based on transplant data and past experiences.
- Ensure that all inclusion and exclusion criteria are warranted to ensure adequate patient recruitment, and have contingency plans for poor recruitment (back up centres/countries, advertising).
- Support the CTO’s Risk Management Plans (safety, monitoring, quality management) - these ensure that we fulfil our legal obligations and that our trials protect the rights, safety and well-being of subjects, and that the data generated are reliable and robust.
- Support the Clinical Trial Coordinators (CTCs) by providing all essential documents and requested information in a timely manner.