CFMATTERS research will be conducted to the highest ethical standards, in accordance with Good Clinical Practise, all regulatory requirements and appropriate confidentially legislation. Central to this is the protection of the rights and welfare of our research participants. No patient related activity will take place at any site prior to written receipt of approval from the appropriate local Ethics Committee. The Initial ethics submission, the Patient Information Leaflet and the informed consent form will be developed by the Quality Manager in the Clinical Trials Unit of the CRF-C who is very familiar with this process and who will work in conjunction with the principle coordinator. The quality Manager will develop a specific SOP for taking informed consent and for version control.
The informed consent process will be based on current SOPs in the CRF-C and will ensure that the background, potential risks and benefits of participation, and alternatives to participation and fairly presented to the subject in a fashion that can be readily understood. The informed consent document will emphasise that participation in the trial is completely voluntary and that non-participation will result in absolutely no negative repercussion for the potential subject. 3 key questions will be developed to aid formal assessment by the researcher into the subject’s level of understanding of the trial protocol. This study will be performed in Adult CF centres, however, a number of these do cater for the clinical needs of CF children aged between 16 and 18 years of age (i.e. minors). Minors will be required to offer their free assent to participating in the study in conjunction with the consent of either their parents or legal guardians as specified in local legislation. Minors will also be re-asked for their consent as soon as they reach the legal majority, in compliance with Article 29 working group WP147 00483/08/EN Document 5.The subject will be encouraged to ask questions about the study, to discuss it with family, friends or other health care providers or advocates and to spend as long as they wish thinking about it before deciding to participate. It will be emphasised that regardless of the protocol the attending physician is in no way prevented from any action or intervention which is felt to be necessary for the subject, also that regardless of providing initial consent the subject will be able to revoke that consent at any time, and can elect in as much as is possible to not have their data used in any study report. Issues related to the protection of the participant’s research information will be provided, including who will have access and right to review this information. The extent to which the study will provide indemnity from any act of negligence or error in the protocol that results in injury to the subject will be provided. Any conflict of interest or commercial interest of the investigator(s)in the project will be declared. Contact details for the relevant investigator and the local approving ethics committee will be provided. The process of obtaining informed consent and the associated documentation will be reviewed and approved by both the Steering Committee and the independent Ethics, Data and Safety Review Group (EDSRG).
On completion of contract negotiations the permanent staff within the CRF at UCC in conjunction with the Project Manager will immediately commence work on the Ethic Submission, so that a draft application can be reviewed by Steering Committee and EDSRG members at the start of study and may rapidly be submitted for ethics approval allowing for start of recruitment at Month 4 Regarding the dissemination of findings, the consortium will:
- address any issues with reference to the contents of the Guide to Intellectual Property Rules for FP7 projects;
- comply with any applicable contents of the Open access pilot in FP7 project (see www.openaire.eu);
- have noted the policy direction indicated by the COMMISSION RECOMMENDATION of 17.7.2012 on access to and preservation of scientific information (17.7.2012 C(2012) 4890).
Ethical Advisory Board
The Ethics, Data and Safety Review Group will monitor all issues with respect to observation of ethical principles in human and animal studies. This board will consist of
- Dr. Edward McKone a CF Clinician and established European Clinical Trial expert,
- Ms. Ulrike Pypops a European Lawyer with Cystic Fibrosis who has extensive clinical trial ethical experience and
- Professor Scott Bell an International CF Clinician from outside the jurisdiction of the trial (Australia) with significant experience with both clinical trials and translational research.
A member of the Scientific Advisory Board will also be nominated to join this group. The EDSRG will also organize ethics courses on a regular basis at annual meetings.
To ensure the ethical and appropriate conduct of the study all study procedures will be described in detail in a manual of operations. Researcher will be trained in the study protocol and manual of operations at the Initiation meeting in accordance with the trial training plan (WP01). To ensure the ongoing appropriate conduct the trial will be monitored by a trained and experienced monitor based in the CRF-C using a combination of onsite inspection, source data validation and central monitoring as per the trial Monitoring Plan (WP01). All of these reports will be forwarded to the Project Coordinator, who will oversee the development and implementation of a corrective action plan in conjunction with the monitor if necessary. He will also forward any documentation to the EU Commission to ensure transparency with regard to the ethical conduct of the project. Also a report by the EDSRG will be submitted to the European Commission with the Periodic Reports.
Identification of countries
All research activities will be undertaken in 5 EU member states (Ireland, UK, France, Germany, Belgium) and 1 North American centre (UW, Seattle):
Monitoring of Patient Safety: The trial will monitor (and report during study) any study death, ITU admission, requirement for non-invasive ventilation, all direct trial related AE, as well as the occurrence of all drug reactions, new onset or worsening of diarrhea while on antibiotics and clinically diagnosed C Difficile infection. At any time the physician is able to adjust the trial directed antibiotics if he/she feels it appropriate to do so. The EDSRG will review the occurrence of any potential attributable adverse event related the trial, forward its conclusions onto the Steering Committee and Regulatory Ethics Committee and require any necessary remediable steps to be undertaken. While there are no formal a priori stopping rules applied to the study, in conjunction with independent statistical advice as needed the EDSRG will monitor for any evidence that Tailored therapy arm may be less efficacious than standard therapy (See WP01, WP04).
Further ethical consideration relates to cross border data transfer between the EU and the USA. CFMATTERS will work in accordance with the US-EU Safe Harbor Framework in 2000.