WP01 - Set up framework for research study


Workpackage lead and partners:

WP leader:
Dr. Keith Barrington, CHU

WP partners:

Workpackage objectives: 

  • Development of an effective management framework (coordination, managerial and administrative tasks to facilitate the clinical trial) which will ensure the correct progress of the project towards its planned objectives.
  • Development and facilitation of the foundation for study participation at each individual centre (safety, legal and ethical issues)

Workpackage description:

The study will involve a clinical trial conducted in eight tertiary level neonatal intensive care centres from four different European countries (participants) and two Canadian centres requiring a detailed framework which will be set up during the first 6 months. This will involve general communication activities in order to communicate information between members of the consortium, such as budget, resources, expected end date, expected deliverables, risk adjustments and ensuring that all participants are informed of the strategic aims and project development.

WP 01 will set up an independent advisory board in this period and ensure that the relevant advisory groups such as ethics advisory board (EAB) (WP 05), clinical development management unit (WP 11) and the data and safety monitoring board (DSMB) (WP 05) are set up in accordance with the project milestones.

Task 1. Central tasks

Task 1a Finalising the clinical trial protocol and SOP for pharmacovigilance
The clinical trial protocol will be finalised and the necessary quality standards will be observed. This will include finalising and distribution of Standard Operating Procedures (SOPs) in such areas as case documentation, data collection, validation, evaluation, archiving and reporting of adverse events. This will require input from WPs 04, 05, 06, 07, 08, 09 and WPs 12, 13. The responsibility for pharmacovigilance will lay with the sponsor (P10), with medical input from P1, P4. For this, Standard Operating Procedures (SOPs) will be written and distributed. This will require input from WP05 and WP11.

Task 1b Trial initiation and pre-trial monitoring report
WP 01 in collaboration with WPs 04, 05, and 12 will review trial procedures and ensure that all sites are suitable for the trial. A trial initiation and pre-trial monitoring report will be produced. This will require input from WP 05 and WP12.

Task 1c Trial Master File
WP 01 will also oversee and facilitate the development, finalisation and distribution of essential study documents which will be kept in the Trial Master File (TMF).

The TMF will be prepared by the sponsor, with input from WPs 01, 05, 10, and 12. It will include: investigators brochure (WP 11), signed protocol (WP 01), patient information sheets (WP 05), consent forms (WP 05), financial agreements if appropriate, insurance statement (WP 11), agreements between all parties involved, approval of ethics advisory board (EAB) (WP 05), regulatory authority approval, CVs of all investigators and co-investigators, normal values and ranges for laboratory results (WP 09), certification of competence of involved laboratories (WP 09), sample of label on the Investigational Medicinal Product (IPM) container, shipping records for IMP and trial related materials (WP 10 and WP11), certificate of analysis of IMP (WP 11), master randomisation list (WP 05), trial initiation and pre-trial monitoring report (WP 01), monitoring visit reports, signed and dated case report forms (CRF), procedures for the notification of serious adverse events (SAE) and sudden unexpected adverse reactions SUDAR (WP 05 and WP11), notification of safety information (WP 11), interim reports (WP 04 and WP 11), drug (IMP) accountability at the sites (WP 11), signature sheet, record of retained body fluids, a copy of GCP and the declaration of Helsinki, sample of the eCRF, and any revisions of the above. The Trial Master File will be updated on a regular basis by leads from WP 04, WP 05, WP 10 and W P11. The overall responsibility of the Trial Master File will lay with the sponsor.

Task2: Local centres

Task 2a Ethical approval, patient information sheets and consent forms
The scientific leads in all participating centres will be responsible for the development of parent information leaflets (PIL) and consent forms and for obtaining approval from their local Ethics Committees. Approval from the healthcare providers in each of the participating hospitals involved in the trial will be obtained by local investigators after local ethics committees have given their approval for the clinical trial. Approval from local Research and Development centres will also be obtained in all clinical sites by local investigators. All of this will be facilitated by WP 01.

Task 2b Clinical Trial Authorisation
Each local investigator will apply to the Competent Authorities (for example Medicines and Healthcare products Regulatory Agency, MHRA in the UK) for Clinical Trial Authorisations (CTA) in their own country. This will be facilitated by WP 01 and the sponsor.

Task 2c Labelling and randomisation of investigational medicinal products
The active drugs will be provided by BREPCO and will be labelled according to the requirements for investigational medicinal products (IMPs) used in clinical trials (Directive 2001/20/EC and the Medicines for Human Use (Clinical Trials) Regulations 2004). The randomisation will be done by WP12. The coordination of these activities will be ensured by WP 01.

Task 2d Final selection of centres for the study
Further hospitals may be invited to enrol patients into the study. Participating centres and local investigators will need to provide evidence of relevant qualifications in the area and demonstrate adequate resources. The consortium will provide assistance with ethics applications, patient information sheets and setting up the local infrastructure. These hospitals will receive ?1,000 compensation per baby completing the interventional phase of the study. A final list of recruiting centres and local investigators will be provided before the trial commences.

Task 2e Training manual and workshop
A training manual designed by WP 02 (Education and training) and WPs 06, 07, and 08 (Echo, NIRS, EEG analysis) will be distributed to the centres before the start of the trial. Before a centre begins recruiting patients, a member of the Project Coordination Committee will visit the site for training and questions regarding Good Clinical Practice (GCP), protocol, enrolment, monitoring, randomization, safety, and possible adverse events. One workshop will be held at each participating centre for acute care neonatologists, nurses and technicians prior to the start of patient recruitment by local investigators. This will be facilitated and supported by WP 01 and WP 02.

Task 2f Good Clinical Practice (GCP)
Training in GCP is essential for all investigators and clinical trial staff. It is the responsibility of each local scientific team leader to ensure that all clinical trial staff involved in the trial has completed a training course in GCP. Once all of the above tasks are completed, the sponsor will be able to give the go ahead and the study will commence.