What to do once your study has been approved
You may find that a lot of the work listed on this page has already been going on in parallel to getting R&D approval. As the PI for the study you are responsible for making sure all the things listed below have been completed before patients are recruited to the study. However, you can delegate these tasks to the relevant research nurse or other member of staff working on the study.
If you are a Research Nurse, Fellow or other member of staff working with the PI on a study you should support the PI to ensure the work listed below is completed and kept up-to-date.
Prepare the Local Paperwork for Study Startup
The trial documentation such as patient Information sheets (PIS’s) and consent forms (CF’s), GP letter templates, Case Report Forms (CRFs) or other trial related paperwork that needs to have local contact details added and be put on local headed paperwork should have been created ready to be added to the Site Specific assessment ( SSI) application.
For a multi-site study ensure that CRFs are designed to capture required data at all sites in a standardised manner. Where additional data is to be collected ensure that supplemental CRFs designed to capture that data are also provided (ICHGCP 5.23.2).
If the study is commercial, then the likelihood of the sponsor company providing a site study file is probable, but, if your study is academic then it will be your responsibility to create a site file from scratch using either an National Institute of Health Research (NIHR) template or one that can be provided by the R&D office (see link for R&D SOPs and templates). These site file contents list are not ‘set in stone’ and can be adapted to meet the requirements of the study. You should also refer to the R&D and, where applicable, research support departments SOPs.
- Click here to view the NIHR Quality Tool Template
- Click here to view the Example Investiagtor Site File Index – CTIMP
- Click here to view the Example Investigator Site File Index- non CTIMP study
Delegation of Duties
Prior to study start up, responsibilities need to be assigned to members of your Research Team authorising them to perform certain tasks according to their training and qualifications. The delegation of roles and responsibilities needs to be documented and signed by the individual taking on a task or particular set of tasks, and authorised by the PI. Refer to the R&D templates for an example template of a Delegation of Duties Log.
If you are the CI the responsibilities of coordinating investigator(s) and other participating investigators need to be documented prior to the start of your study (ICH GCP 5.23.3). This can be done by ensuring local investigators have provided evidence of their CVs and GCP and copies of the Delegation of Duties Log for their local Research Team.
Confirm Training of Staff
Those involved in the conduct and delivery of the research must be appropriately qualified or trained to do so. Where additional training is required this should be arranged prior to study start up. Training records should be maintained and updated as required throughout the duration of the study.
All CV’s and GCP certificates for staff that will be involved in the study need should be collected for the site file prior to study start up.
If you are the CI you must ensure that all investigators and trial staff should be trained on the current protocol and study specific procedures. Instructions on following the protocol and complying with uniform standards for assessments of clinical and laboratory findings, and completion of CRFs must be provided to all investigators (ICH GCP 5.23.4).
Confirm Management of Investigational Products
A named individual must be identified and included on the delegation of duties log to take accountability for investigational products at the study site. This tends to be a nominated trials pharmacist.
The following should be checked with the trials pharmacist to ensure compliance with ICH GCP 5.13.1:
- Storage conditions as per the Investigator Brochure and/or Summary of Product Characteristics (as applicable) can be met
- Where required there are adequate facilities available for reconstitution of fluids and conduct of procedures
- Where product infusion is needed that devices to enable this are available.
The PI is expected to ensure that:
- the responsibility for investigational products accountability at the study sites is taken by the PI/Organisation,
- where appropriate the PI/Organisation assigns some or all of their duties for investigational products accountability at the study sites to an appropriate pharmacist or another appropriate individual who is under the supervision of the PI /Organisation,
- records are kept of the delivery of products to the study site, the inventory at the site, the use by each subject, and the return to the sponsor or alternative disposal of unused products. This information should be kept in the pharmacy file which ultimately is part of the main site file and should be archived along with the main site file.
- robust mechanisms are in place to ensure that study products are not made available to the subject before all necessary approvals and documentation are in place (including where applicable, qualified person certification),
- records are maintained (by the PI) to adequately document that the subjects were provided the doses specified by the study protocol and reconcile all investigational products received from the sponsor,
- investigational products are stored as specified by the sponsor and in accordance with applicable regulatory requirements,
- investigational products are used only in accordance with the approved study protocol, and reference safety information available ( as documented within Investigator Brochure, SmPC where applicable).
- the appropriate person explains the correct use of the investigational products to each subject and checks, at appropriate intervals, that each subject is following the instructions properly and, where appropriate, compliance with study protocol requirements is documented.
Identification, Recruitment and Enrolment of Subjects
The research nurse on behalf of the PI is expected to ensure that:
- If patients can be identified on paper as possibly suitable by fulfilling the inclusion /exclusion criteria prior to being approached, this will help speed up the process of making contact in clinic or help rule out those definitely not suitable so the PI in clinic can maximize those he talks to about the study.
- the number of suitable subjects within the agreed recruitment period is recruited and that those subjects meet the criteria specified in the study protocol,
- records of screening, subject identification, enrolment (see ICH GCP 8.3.20 – 8.3.22) and, where applicable, randomisation are held in the study file in the confidence of the investigator, unless consent is explicitly given by the trial subject that any of the information can be shared.
If applicable, the process for randomization should be performed in accordance with the study protocol. Randomisation procedures should be clearly documented including whether paper based or whether a web-based application will be utilised.
Authorised members of the Research Team responsible for randomisation must be identified on the delegation of duties log. In some instances the sponsor may have an agreement with a trials unit to perform randomisation, which may have their own randomisation procedures that would need to be adhered to.
Maintaining the Blind and Considerations for Un-blinding
If your study involves blinding the following considerations must be taken into account:
- An authorised member of the team is identified who will ensure the blind is maintained and will have access to the codes, ideally this person should be independent to data collection and validation,
- access to the randomisation code for double-blind studies is restricted and withheld from members of the operational research team except where access is required in an emergency,
- the code is only broken in accordance with the study protocol,
- if the study is prematurely un-blinded the PI promptly documents the event, provides an explanation to the Sponsor (e.g. accidental or due to serious adverse event) and considers the need for any appropriate applicable onward reporting procedures (e.g. Urgent Safety Measures and / or SAE/SUSAR reports).
Obtaining informed consent
Informed consent is a process of obtaining permission from a potential participant before carrying out any intervention or study specific procedures on them. The potential participant must be provided with all the information relating to the study including the nature of the procedures involved, benefits, risks and potential implications of that particular research project. They should be allowed time to fully consider their involvement based on the information provided in accordance with the study protocol.
All staff authorised to take consent have a duty towards protecting the rights, safety and well being of a potential trial participant and must adhere to the instructions provided in the study protocol and study specific procedures where applicable.
The PI is expected to ensure compliance with the appropriate regulatory requirements and adherence to GCP and to the ethical principles that have their origin in the Declaration of Helsinki when obtaining and documenting informed consent.
Medical care of study subjects
It is expected that medical care of study subjects is be provided to those participating in the study by a qualified physician (who is an investigator or sub-investigator). However, the responsibility of medical intervention is with the Trust.
You should ensure that:
- the rights, safety and wellbeing of the subject take precedent and are protected in all circumstances
- adequate medical care is provided to a subject for any adverse events and any related follow-up of events in accordance with the requirements and timelines specified in legislation and appropriate guidance,
- where relevant the subject’s general practitioner (GP) is informed by the investigator about the subject’s participation in the study provided the subject agrees to the GP being informed,
- the PI makes a reasonable effort to ascertain the reasons for a subject withdrawing prematurely from a study.