1. Tailored GCP & Trial Specific training
FLO-ELA Tailored GCP Training v1.0 10/10/2017

2. What is Good Clinical Practice?
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects

3. GCP Training
The aim of this session is to provide a basic understanding to perform trial-specific tasks and is not a full GCP course
It is based on key slides from the National Institute of Health Research (NIHR) Good Clinical Practice (GCP) slide set
This is not valid training for any other study or trial and is not interchangeable

4. Is this the right level of GCP training for you?
No GCP training needed if:
Aware of the trial and highlighting potential participants to GCP-trained team (e.g. Research nurse)
Tailored GCP training needed if:
Delivering the study intervention / control group care
Making a first approach to patients to describe the trial and give a PIS
(But NOT taking consent)
Entering patients into the randomisation system
No training needed if:
Being aware of the trial and highlighting potential participants to GCP-trained team (e.g. Research nurse)
Tailored GCP:
Delivering the study intervention / control group care
Making a first approach to patients to describe the trial and give a PIS (but NOT taking consent)
Entering patients into the randomisation system
Full GCP:
Assessing eligibility, taking consent (from patient or via consultee agreement / emergency consent)
Trial-related decisions e.g. Judging that an event is a Serious Adverse Event
Full GCP training needed if:
Assessing eligibility, taking consent (from patient or via consultee agreement / emergency consent)
Trial-related decisions e.g. Judging that an event is a Serious Adverse Event

5. Objectives
Understand there is a set of interwoven laws, guidelines and frameworks which govern the set up and conduct of clinical research
Understand basic principles of GCP
Outline roles and responsibilities of different individuals within the research

6. Why do we need GCP?
Each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective task(s)
If you are either giving the study treatment, signing off participants as medically stable or prescribing study treatment, you need to know how GCP applies to those tasks
The ICH Guideline for Good Clinical Practice says:

7. GCP Principles
These form the basis of the guidance and legislation which governs conduct of clinical research carried out in the NHS
Important GCP principles (14 total):
The rights, safety and well-being of the trial subjects shall prevail over the interests of science and society
The necessary procedures to secure the quality of every aspect of the trial shall be complied with
All clinical information shall be recorded, handled and stored in such a way that it can be accurately reported, interpreted and verified, while the confidentiality of records of the trial subjects remains protected

8. What are your overall responsibilities?
Fulfil the duties delegated to you
Ensure the safety and wellbeing of subjects

9. Patient Consent
There is no pressure to participate and if a patient decides not to take part, their existing treatment will not be compromised
That consent can be withdrawn at any time without impacting on their care
Information given to participants/ consultees must be clear and understandable
Participants/ consultees must be given time to consider and to ask questions
Local trial team should be satisfied that suitable consent has been sought before undertaking any task
You will not be expected to consent patients for this trial but it is important to be aware of the consent procedures.

10. Safety Reporting
Data will be gathered in order to monitor the effects of the trial and any interventions on the participants
Regular reviews of data safeguard participant safety by highlighting any trends or unexpected events
Safety reporting is important in order to protect patients during the trial and once a practice or treatment becomes standard care
Notify the research team about any safety events suspected to be related to the trial
Notify the research team about any safety events suspected to be related to the trial - These are not just any expected complications after emergency laparotomy but events that are directly related to the specific interventions associated with the trial.
the research team will then document on a form and report to the central trial team if required

11. Data Capture
A clinical trial is only as good as the quality of the data collected
Inaccurate/incomplete data can prevent trial aims and objectives being met and impact on participant safety

12. Standards for data capture
Make sure your writing is legible
Always write in black
Put a single line through any mistake
Make the amendment clear next to it
Initial and date any alteration
Never occlude the original entry
Never use TIPPEX or POST-IT notes
E.G On anaesthetic/ITU records – ensure it is clear that (1) patient is in the FLO-ELA trial (2) type of COM used [intervention patients only] (3) mark when a fluid bolus is given (4) record enough detail for the total volumes and types of fluids to be calculated

13. If it is not documented, it did not happen!
Useful Tips
Sign/initial and date anything you write or amend
If something doesn’t seem right, check
If you don’t know ask, because someone will ask you
Remember
If it is not documented, it did not happen!

14. Trial Specific Training
Trial Design
Inclusion/ Exclusion Criteria
Patient Consent Pathway
Intervention vs. Usual care
Non Compliance

15. Trial Design
Pragmatic multicentre open randomised trial, supported by data from the ongoing National Emergency Laparotomy Audit (NELA)
Sample size = 7646 patients (3823 per arm)
Emergency surgery only
100 UK Sites
3 Year Recruitment
Internal Feasibility Phase

16. Inclusion Criteria Age ≥50 years
Scheduled to undergo a surgical procedure which fulfils the criteria for entry into the National Emergency Laparotomy Audit (NELA) i.e. an expedited, urgent or emergency abdominal procedure on the gastrointestinal tract within the audit scope
Patient has NHS number

17. Exclusion Criteria Inability or refusal to provide patient consent
Clinician refusal
Previous enrolment in the FLO-ELA trial
Previous inclusion in NELA within the current hospital admission
Scheduled abdominal procedure outside the scope of NELA
Current participation in another clinical trial of a treatment with a similar biological mechanism
During the course of the trial the NELA Project Team may make minor modifications to the definitions of surgical cases included within the audit. In this circumstance the inclusion/exclusion criteria for FLO-ELA will be amended to ensure consistency with NELA.

18. Consent Flowchart

19. Randomisation On day of surgery Via the FLO-ELA randomisation system
As close as possible to the start of anaesthesia, typically when the patient arrives in the theatre suite for surgery
Via the FLO-ELA randomisation system
Enter patient demographics
Confirm eligibility criteria met
FLO-ELA Patient ID generated
Treatment allocation provided

20. Recommended care for all patients
The intervention should begin immediately following induction of anaesthesia and continue at least until the end of surgery. Patients receiving level 2/3 care should have the intervention continued for 6 hours postop. If a patient is already sedated and ventilated before arrival for laparotomy, the intervention start time is counted as the time of their arrival in the theatre/anaesthetic room.
Cardiac output and stroke volume will be measured by one of the three recommended models of cardiac output monitors and algorithm should be followed.
It is important to note that if monitoring has been used for less than 80% of the intervention period this meets the definition of non-compliance and should be reported as such.

21. Intervention Group Please refer to the intervention group SOP
Commence at start of general anaesthesia
FLO-ELA treatment algorithm – see next slide
Stroke volume and stroke volume variation (SVV) will be measured by cardiac output monitor
Clinicians may choose from a range of cardiac output monitors in established use
Continues at least until the end of surgery;
patients receiving level 2/3 critical care after surgery, the intervention will continue for six hours after the end of surgery
The intervention should begin immediately following induction of anaesthesia and continue at least until the end of surgery. Patients receiving level 2/3 care should have the intervention continued for 6 hours postop. If a patient is already sedated and ventilated before arrival for laparotomy, the intervention start time is counted as the time of their arrival in the theatre/anaesthetic room.
Cardiac output and stroke volume will be measured by one of the three recommended models of cardiac output monitors and algorithm should be followed.
It is important to note that if monitoring has been used for less than 80% of the intervention period this meets the definition of non-compliance and should be reported as such.

22. Intervention Algorithm
Handout – laminate
Haemodynamic algorithm.

23. Intervention Flowchart
This is the intervention flowchart.

24. Usual Care Group Please refer to control group SOP
Managed by clinical staff according to usual practice
Broad criteria to emphasise good care
Avoids practice misalignment
No cardiac output monitoring unless required to inform treatment of critically ill patient
Patients should not be randomised if the clinician intends to use cardiac output monitoring regardless of study group allocation; this is considered ‘clinician refusal’
Patients will be managed by the care team according to usual practice. Patients should not be randomised if the clinician intends to use cardiac output monitoring regardless of study group allocation; this is considered ‘clinician refusal’ and is a specific exclusion criteria.
However, clinical staff are free to request cardiac output monitoring if this is required to inform the treatment of a patient who becomes critically ill (e.g. because of severe haemorrhage) during the trial intervention period. In this situation a protocol deviation form will be completed.

25. Non-Compliance
Participant in the intervention group did NOT receive cardiac output monitoring
Participant in the control group DID receive cardiac output monitoring
FLO-ELA algorithm not followed in intervention group
Any suspected protocol deviations should be reported to the local research team for review.
Note that the use of ANY FORM of cardiac output monitoring (including anaesthetic modules providing just PPV/SPV values) count as non-compliance if used in the control group.
Record in the CRF supplementary form – protocol deviations/ Non compliance.