As one of the eligibility criteria is the clinician's uncertainty of the appropriateness of TXA, does the person taking consent have to be a doctor? And if so, does the doctor have to be on the delegation log and be GCP trained? Or is it enough that the local PI is GCP trained and has overall responsibility?

As the eligibility criteria require the assessment of the appropriateness of TXA, it necessarily has to be a doctor carrying out this task. As this assessment requires knowledge of the trial Protocol, the content of the Investigator’s Brochure etc, this doctor must be part of the trial team (on the Delegation Log and trained on the trial procedures and GCP).
The person taking the consent can be a doctor or nurse (depending on local Trust regulations), as long as he/she is part of the HALT-IT team (i.e. on the delegation log, GCP trained and also trained in the trial procedures).
The person taking Consent can be a Doctor or Nurse (if allowed by your Trust) but again this person must be on the delegation log, GCP trained and also trained in the trial procedures).
It is never appropriate for the PI to take responsibility for procedures carried out by another person who is not formally delegated that task and not appropriately trained.

If we recruit a patient with waiver of consent, who regains capacity, but when approached refuses to give consent, is this counted as a withdrawal or a protocol deviation/violation?

If a patient who is randomised into the trial under the waiver of consent, regains capacity and refuses consent, this would count as consent withdrawal. It would not be protocol violation, if the patient was correctly randomised into the trial as per the waiver of consent process in the protocol (section 2.6.c) - and as per the eligibility criteria, of course!
The patient's wish must be respected so if the patient refuses to give consent then that would be the end of the trial for that particular patient. It would not be appropriate to seek consent by a representative.
It is really important that you establish what the patient is withdrawing from. If the patient or patient representative withdraws consent for the intervention, then stop the trial treatment administration if it is still ongoing. We advise that you ask for data collection to be continued as this will be from the medical records and won't impact on the patient in any way. This is important as Adverse Events, if not reported, could impact other patients in the trial. However, the patient/representative's wishes must be respected. In any case, data already collected up to the point of withdrawal will be used as approved in the Protocol so will need to be submitted to us.

What is the most appropriate way to classify a bleed as serious so we have consistency within our clinical and research team, and to help us to assess our potential recruitment target?

The diagnosis of significant bleeding is clinical but may include patients with hypotension, tachycardia, or those likely to need transfusion, urgent endoscopy or surgery. The fundamental eligibility criterion is the responsible clinician’s ‘uncertainty’ as to whether or not to use TXA in a particular patient with GI bleeding.
The decision is a clinical one and would take into account the history (including the age of the patient and co-morbidities) and the symptoms and signs on presentation. Patients with a initial Rockall score of 3 out of 7 or more would certainly be eligible for inclusion. Although many patients will have tachycardia and hypotension, some because of physiological compensation could have normal physiology. We should also bear in mind that a ‘normal’ blood pressure - might indicate the presence of a significant bleed in an older patient who was previously hypertensive.

Do you have a working definition of what a GI bleed is?

A GI bleed is any bleeding from the GI tract from the mouth to the anus.

Drug administration: Can all ED nurses administer the trial drug if trained or is it only the research nurses who are GCP trained?

The prescription needs to be written by the enrolling physician but a trained ED nurse (or anyone authorised to administer intravenous drugs at your hospital) can administer the trial treatment. There is no need for GCP training.

Professional Legal representative (PrR) and follow-up consent

It would appear from our consent monitoring that the waiver of consent procedure is being used well. However, using a PrR consent procedure seems to be problematic. It is only being considered as a last resort when all else fails. This should not be the case. Remember that written consent should be considered as soon as possible after the emergency is over. At this stage, neither the patient nor their personal representative may have the capacity to consent. PrR consent should be considered at this stage. Continue to re-assess the patient / relative for their capacity to consent and obtain informed consent where possible.

Site initiation and training

We do most of our Initiation visit using teleconference, video-conference or other web-based methods for training. In advance of the Initiation, you will receive all the trial materials which will include a DVD that covers all the procedures in the trial. So Initiation meeting is usually to address any remaining questions. This usually takes about 1 hour and 15 minutes.
We will arrange a date with you as soon as the materials have been dispatched to you or earlier if needed. For the UK sites we will arrange a date with you as soon as you have obtained Trust approval. However, the training can only take place when all trial materials are at site.

Out of hours recruitment: Can you advise who has recruited patients out of hours and at weekends in other sites as our research nurse will not be present at these times

This is important to consider when you are setting up your trial team. Patients will be admitted any time of the day. You will need to consider getting buy-in from the medical staff also who will be seeing these patients out of hours (e.g. Gastro and your A&E Regs). The team cannot be only the research nurses otherwise we will miss the majority of patients. Also, have you discussed with your CLRN their willingness to fund Research Nurses to extend cover? This might be worth doing as there is recognition now that this is needed for emergency care research.

Patient transfer to another hospital

When a patient is transferred to another hospital for further acute treatment, an outcome form needs to be completed at the randomising hospital at the point of transfer (e.g. day 14 after randomization if this is the day that the patient is being transferred).
We will send you transfer packs with trial information, to accompany the patient in cases such as this.
Thereafter, there are two ways to follow up the patient:
If you have an honorary contract or if there is an agreement between your hospital and the transfer hospital that allows you to have access to the patients medical notes at the transfer hospital then you can complete another Outcome Form at death, discharge or 28 days post randomization and combine the information from you original Outcome Form and the medical notes from the transfer hospital to create a final Outcome Form. This is then entered in the HALT-IT database.
If the patient is being transferred to another HALT-IT collaborating hospital. The team there may be able to complete a second Outcome Form and send a copy (they'll keep the original). Again, you will need to combine your original Outcome Form and that from the transfer hospital to generate a final Outcome Form.

How to distinguish between "diagnostic radiological procedure" and "therapeutic radiological procedure" on the Outcome Form (section 4c and 4d)

Diagnostic radiological procedure: any radiological procedure that it is done primarily to establish the cause / source of the GI bleeding and no therapeutic intervention was carried out.
Therapeutic radiological procedure: any radiological procedure that it is performed where therapeutic intervention for the GI bleeding was carried out as part of the procedure.
If there is uncertainty as to whether a procedure was done for diagnostic or therapeutic reasons, please discuss with the PI or the doctor who carried out the procedure before completing the outcome form.

Do the databases use encryption to protect data when stored? If so, what encryption standard are used to achieve this (i.e. AES256?)

Stored passwords and PINS are salted and hashed.
The database server is not exposed externally or internally.
Only HTTPS access allowed from outside LSHTM.