Please note the information displayed is correct at the time of review as content may be subject to change throughout the study duration. [Last update: 13SEP2021, 11:32]

If you have any queries, please contact the Central Trial Team (Study Office): relief-trial@bristol.ac.uk

CONTACT and USEFUL INFORMATION

How can I contact the RELIEF Central Study Office (Team)?

The Central Study Office (Team) is based at the University of Bristol and the general team email address is: relief-trial@bristol.ac.uk

If your email contains confidential data (i.e. patient identifiable information), then please do not use the general email address. Instead use the secure trial email: nbn-tr.relief-trial@nhs.net.

How can I contact the RELIEF Chief Investigator if I need to?

The RELIEF Chief Investigator is Dr Edward Carlton, Consultant in Emergency Medicine, Southmead Hospital, North Bristol NHS Trust. Email: Ed.Carlton@nbt.nhs.uk

Where can I find information about RELIEF, including the research team and other useful information?

Visit the study website: https://relief.blogs.bristol.ac.uk/

 

STUDY DESIGN

Where can I find a “quick read” summary about the study?

The Protocol Synopsis includes: Study summary, Patient flow diagram, Schedule of trial assessment and key participant-related procedures, Inclusion and exclusion criteria, and an overview of trial strategies (interventions).

Full details about the study are provided in the latest version of the Protocol.

A copy of these documents is in your Investigator Site File (ISF) and available via the Study Website: https://relief.blogs.bristol.ac.uk/information-for-sites/

What is the design and setting of the study?

RELIEF is a pragmatic multi-centre feasibility randomised controlled trial (RCT).

RELIEF will take place across at least three sites (Emergency Departments) in the UK to ensure demographic spread. We will select Major Trauma Centres that are more likely to see the more severe end of the injury spectrum, and Major Trauma Units that may see patients with less severe injuries.

Information about participating sites can be found on the website: https://relief.blogs.bristol.ac.uk/relief-sites/

Is RELIEF a CTIMP study?

No. As confirmed by the Medicines and Healthcare products Regulatory Agency (MHRA), the RELIEF feasibility trial is not a Clinical Trial of an Investigational Medicinal Product (CTIMP) as defined by the EU Directive 2001/20/EC.

What are the study timelines and duration of participation?

Contracting for RELIEF started 01 January 2020. The project duration is expected to be 39 months, through to 31 March 2023 (subject to change).

One hundred patients will be recruited and randomised (enrolled) over an 18-month period (subject to change). For all participants, individual study participation will be from the time of (written) informed consent until 30 days (+10 days) after date of initial Emergency Department attendance.

A subset of up to 24 participants and 6 people with carer responsibilities (e.g. Personal Consultees, or equivalent legal representatives in Scotland, or other subsequent carers) will be invited to undertake an interview about their experience of taking part in the study.

What considerations have been made in light of Coronavirus COVID-19?

A range of considerations have been made and incorporated into the study design. These include:

(1) Most hospitals within the UK have imposed visitor restrictions in light of the ongoing COVID-19 pandemic. To facilitate timely and appropriate recruitment of patients with mild to moderate cognitive impairment who may potentially lack capacity to consent for themselves, we have adapted our approach for seeking remote advice from Consultees in England and Wales, or consent from Welfare Guardians/Attorneys/Nearest Relative in Scotland; see Protocol – Sections 8.3/8.4 for details.

(2) To aid infection control at sites, the default method of obtaining written informed consent from potential participants will be via a study-specific online eConsent Form that is signed electronically by the patient during a consultation. eConsent does not need to be followed up with a paper (wet ink) written consent form as an electronic signature constitutes documented informed written consent. A study-specific handheld device (e.g. iPad) will be provided, where feasible; this will require Wifi connection. Using wipeable devices will reduce the transmission of infection from paper records. See Protocol – Section 8 for details.

Furthermore, where paper records are required, we will provide pens for site staff and participants, which they can keep if they wish.

(3) General practicalities. Local site policies and procedures should be followed.

What personal protective equipment (PPE) is required?

There will be no high-risk aerosolising procedures undertaken as a result of the trial intervention, therefore risks to researchers enrolling participants in this trial will be low and only standard personal protective equipment (e.g. surgical masks, gloves and apron) will be required. Local site policies and procedures should be followed.

 

SITE SET UP (INCLUDING PERSONNEL)

Who is responsible for study-related activities?

The Chief Investigator takes overall responsibility for the design and conduct of the study, with support from the Trial Manager who helps coordinates the day-to-day management.

The Principal Investigator (PI) at each recruiting site (hospital) takes overall responsibility for study-related activities at their site. The PI can identify other suitably qualified team members to whom they can delegate duties related to the study; a site delegation log must be maintained and kept in the local Investigator Site File, as well as shared with the Central Trial Team (Study Office) for monitoring purposes.

Who can act as a Principal Investigator (PI) for RELIEF?

A site Principal Investigator (PI) will be an experienced Emergency Medicine clinician (doctor/nurse) who is able to take on the overall responsibility of delivering the study at the site. They will need to have a valid Good Clinical Practice (GCP) certificate and relevant qualifications.

Does the Principal Investigator (PI) / Team Members need to provide a GCP certificate and CV?

Yes. Site team members (i.e. anyone listed on the site delegation log, but especially those who undertake recruitment and consent) are asked to provide the Central Study Office with: (1) a valid Good Clinical Practice (GCP) certificate and (2) a research CV.  At the very least, recruitment cannot begin at the participating site until the Central Study Office have reviewed these documents for the site Principal Investigator (PI).

Are Co-Principal Investigators (Co-PIs) permitted to spread workload?

Yes. The Principal Investigator (PI) can be supported by a local team of clinicians which may include a suitably qualified colleague be designated as Co-PI.

Is RELIEF taking part in the NIHR CRN Associate Principal Investigator (PI) scheme?

Yes. RELIEF has been registered for the NIHR CRN Associate PI Scheme and has been included in the List of Registered Studies on the NIHR Associate PI Scheme website. For further information, visit: https://relief.blogs.bristol.ac.uk/nihr-associate-pi-scheme/.

We ask that all potential Associate PIs also send their research CVs to the Chief Investigator at ed.carlton@nbt.nhs.uk

Who can prescribe study medication as part of the RELIEF protocol?

Treatment (study medication) can be prescribed by a registered medical practitioner or prescribing nurse; see Protocol – Section 10 and 11 for details.

The Sponsor (North Bristol NHS Trust) confirmed that because RELIEF is not a Clinical Trial of an Investigational Medicinal Product (CTIMP), there is no requirement for prescribers of study medication to be listed on the RELIEF Delegation Log. We do, however, need to ensure that any prescriber has appropriate knowledge about the study and that this is monitored at a site level. Please see the supporting Note To File and training materials (under Module 7) in the Training Materials website area for Sites.

Who can recruit participants and assist with other study activities (including follow ups)?

Following the completion of relevant study training, a doctor, research nurse, and/or other suitably qualified member of staff, as delegated by the site Principal Investigator (PI) on the site delegation log, can help with patient recruitment and follow ups and data capture/management.

How will study training be provided to participating sites (staff)?

In the interests of time and flexibility, initial study training is self-directed; all training materials are available via a dedicated section on the study website: https://relief.blogs.bristol.ac.uk/information-for-sites/. Guidance is provided about what training is required according to your role in the study. After staff complete the appropriate training module(s), they will be asked to complete a brief online Training Log form (record) that is available here: https://forms.office.com/r/wwPyu7kQgq

The Central Study Office will also arrange a (remote) meeting to review and discuss your (site’s) understanding of the study and finer details about local practicalities. When satisfied, the Sponsor (North Bristol NHS Trust) will then confirm when recruitment can begin at your participating site (i.e. provide “Greenlight” approval).

NB: There are new training materials and “Information for Prescribers (effective 13SEP2021)”, including the way such training is recorded. Please refer to Training Materials for further information.  

Are any supplies provided to participating sites?

Yes. Full details are provided in Schedule B of the model non-commercial agreement (mNCA); a copy of the mNCA is included in the Local Information Pack.

In summary, the RELIEF Central Study Office will provide participating sites with:

• Study-specific training as part of the site initiation, with subsequent training as required
• Investigator Site File
• Pre-paid envelopes for 30-day (participant) questionnaire return
• Pens to enable participants to complete study documentation while in hospital
• Tablet device to enable eConsent, randomisation and online data collection (loaned for study purpose)
• Envelopes for medication storage and other specified stickers/materials.

Study medication (Lidocaine patches) is not provided by the RELIEF team/research grant. Site teams will need to obtain study medication from normal local site (hospital) pharmacy supplies, ordered and received in accordance with Pharmacy standard operating procedures (SOPs). See Protocol – Section 11 for details.

Who decides when recruitment can begin at participating sites?

Individual NHS Trusts are responsible for assessing and confirming capacity and capability. A signed contract (mNCA) is also required. Following discussion with the Central Study Office (Trial Manager/Chief Investigator), the Sponsor (North Bristol NHS Trust) will then confirm when recruitment can begin at the participating site (i.e. provide “Greenlight” approval).

 

CONTRACTING

What site agreement (contract) is used?

RELIEF uses a model non-commercial agreement (mNCA). As noted in the Organisation Information Document (OID; also included in the Local Information Pack), we expect sites to recruit at least 1-2 patients per month, though more should be encouraged where feasible to support the overall recruitment target of 100 within the available time.

Are there any payments associated with RELIEF?

Yes. Full details are provided in Schedule A of the model non-commercial agreement (mNCA); a copy of the mNCA is included in the Local Information Pack.

In summary, the RELIEF Central Study Office can offer site payment towards:

• Per Participant Research Cost: £135 per participant upon completion of all Case Report Forms and Questionnaire data, up to and including 30 days (+10 days)* post randomisation, and once all data queries have been resolved. [*We note that some participants may not respond to the final 30-day questionnaire which is a feasibility outcome. In such cases, sites will be expected to demonstrate that reasonable efforts to obtain the final 30-day questionnaire have at least been made].
• Archiving of study records: Contribution (to be agreed at end of study) towards archiving of study records as required per protocol.

Are any Excess Treatment Costs (ETCs) associated with RELIEF? Is there a SoECAT that can be shared?

Yes. The SoECAT is included in the Local Information Pack.

Should recruitment data be uploaded by sites to Local Portfolio Management Systems (LPMS)?

Yes. Sites are expected to upload recruitment data to the LPMS. If you are unclear of that process, please speak with your local R&D/R&I department in the first instance.

The Central Study Team (Study Office, University of Bristol) will confirm recruitment on the Central Portfolio Management System (CPMS).

 

PARTICIPANT SELECTION

Who is eligible to take part in RELIEF?

If a patient is 65 years or older, presents to the Emergency Department with traumatic rib fracture(s) confirmed radiologically (by chest X-Ray or CT scan conducted as part of routine care) and requires hospital admission for ongoing care, they may be eligible.

The full list of inclusion/exclusion criteria are available in the Protocol – Section 6.

NB: Imaging to identify the presence of rib fractures will be entirely at the discretion of the treating clinician and not altered for study purposes.

Can patients with suspected/confirmed Coronavirus (COVID-19) take part in RELIEF?

Yes. We have made the active decision not to exclude potential participants with suspected/confirmed COVID-19. As this disease becomes endemic within the community it will be important to test our intervention in all potential participants and the pragmatic/feasibility nature of this trial lends itself to doing this.

Can patients transferred from other (non-recruiting) units take part in RELIEF?

Patients transferred from other (non-recruiting) units (e.g. Major Trauma Units, District General Hospitals, Minor Injuries Units) who have not had a lidocaine patch applied prior to arrival in a recruiting site, may be approached for recruitment.

In the unlikely event that a patient is transferred to a recruiting site from another unit and a lidocaine patch has already been applied as part of standard care, the patient will not be enrolled in the trial but screening data will be collected (see Exclusion criteria, Protocol – Section 6).

Can patients with mild to moderate cognitive impairment take part in RELIEF?

Yes. Patients with mild to moderate cognitive impairment can be approached, but those with end-stage dementia (adjudicated by the treating clinician, e.g. bed-bound and non-verbal) should not be approached.

Patients with mild to moderate cognitive impairment may lack capacity to provide consent for themselves if they are unable to:

• understand the information relevant to the decision
• retain the information
• use or weigh the information
• communicate their decision (by any means).

If a potential participant is identified as lacking capacity to provide consent for themselves at the time a decision or action needs to be taken, then trained research or clinical staff must take reasonable steps to seek an opinion as to whether the patient would wish to participate if they had capacity. You should refer to details provided in the Protocol – Section 8, including reference to patients who may regain capacity during the 30-day study period.

A summary of the various study invitation and consent pathways are shown in:

• Protocol – Figure 2 (patients in England and Wales)
• Protocol – Figure 3 (patients in Scotland), and/or
• Protocol – Appendix 1, which presents an equivalent table.

Can RELIEF participants also take part in other studies?

A co-enrolment agreement will be in place for all known studies* where similar inclusion criteria apply; this will be arranged by the Chief Investigator (RELIEF Central Study Office). This agreement will consider participant burden and where appropriate, will not be applied where randomised interventions are applied in the Emergency Department.

In the event of overlapping randomised interventions, it will be at the discretion of the local Principal Investigator (PI) as to which study a patient should be approached for potential participation. If you have any queries, you can contact the Chief Investigator and/or Central Study Office.

*A co-enrolment agreement is in place with “ORiF: The Operative Rib Fixation Study” (https://orif.octru.ox.ac.uk).

 

CLINICAL PROCEDURES

What clinical procedures can (should) patients have in the Emergency Department?

Study participants will have undergone the standard clinical assessment and treatment of patients with suspected rib fractures in the Emergency Department.  This includes a triage history assessment, routine initial observations of pulse, blood pressure, respiratory rate, and oxygen saturations.

• Details about PAIN CONTROL prior to study screening and imaging are available in the Protocol – Section 7.
• Details about the STUDY INTERVENTIONS (TREATMENT) are available in the Protocol – Section 10. See also the separate FAQ section.

 

RECRUITMENT (INVITATION)

Who can recruit participants and assist with other study activities (including follow ups)?

Following the completion of relevant study training, a doctor, research nurse, and/or other suitably qualified member of staff, as delegated by the site Principal Investigator (PI) on the site delegation log, can help with patient recruitment and follow ups and data capture/management.

Is recruitment time limited?

Yes. To ensure equipoise, given that lidocaine patches are in clinical use by specialist pain services in some centres, patients will be recruited when identified in the Emergency Department and prior to onward referral to the pain team. The length of time patients will have to consider participation will vary due to the nature of Emergency Departments and assessment pathways, however it is estimated to be from 1 to 4 hours. See Protocol – Section 8 for details.

Recruitment will be undertaken by appropriate staff 24 hours a day, 7 days a week. As part of this feasibility trial, it is important to assess participant recruitment by appropriately trained Emergency Department clinicians out of normal research nursing hours.

The Patient Flow Diagram (Protocol – Section 2) presents an overview of the identification and screening of potential participants, and onward study pathway. Further details are also described in Protocol – Section 8.

What information about the study should I give to potential participants?

Which document(s) to provide, and to whom, will depend on whether the patient has capacity to provide informed consent themselves, and if not, whether they are a patient in England and Wales, or Scotland.

Full details are provided in Protocol – Section 8.

A summary of the various study invitation and consent pathways are shown in:

• Protocol – Figure 2 (patients in England and Wales)
• Protocol – Figure 3 (patients in Scotland), and/or
• Protocol – Appendix 1, which presents an equivalent table.

Paper copies of information materials are available where in-person discussion is feasible. Alternatively, the documents can be viewed and downloaded from the study website: https://relief.blogs.bristol.ac.uk/taking-part/, or they can be emailed.

What should I do if a patient doesn’t speak English? Is it possible to provide study documentation in languages other than British?

Patients who are unable to communicate in English language where all reasonable attempts to source translation services are exhausted within the Emergency Department are not able to participate in this study. Study documentation is only available in English; the study questionnaires include instruments validated in English, but if translated to another language, may not be validated.

Do participants receive any reimbursements for taking part in the study?

No. We are unable to offer any payment or expenses for taking part in the study.

Do I (site teams) need to complete a Screening Log?

Hospital staff should complete a RELIEF Screening Log, which will help us to record the flow of potential participants through the recruitment process.

Given the setting of RELIEF (i.e. the Emergency Department, 24 hours a day, 7 days a week), we recognise that completion of screening logs may not be feasible at all times. Thus, a pragmatic approach to screening logs will be taken. Instructions for completing the Log are on the document; guidance is also provided in RELIEF Training Module 3 – Baseline I.

 

INFORMED CONSENT (ADVICE)

Who can receive informed consent (advice)?

Site staff who are trained on the RELIEF protocol and relevant procedures, and listed on the Site Delegation Log, will be able to take informed consent. For example, this may include an attending clinician or an appropriate member of the research team depending on individual circumstances.

Is there any scope to include consent waivers for this study?

No. Consent waivers are not possible for this study.

How should informed consent (advice) for RELIEF be obtained?

The process, and documentation required, to obtain informed consent (advice) will vary depending on whether you are obtaining it from the patient themselves, or from a Consultee/Legal Representative on the patent’s behalf; see Protocol – Section 8 for details. A summary of the various study invitation and consent pathways are shown in:

• Protocol – Figure 2 (patients in England and Wales)
• Protocol – Figure 3 (patients in Scotland), and/or
• Protocol – Appendix 1, which presents an equivalent table.

The default method of obtaining and recording informed consent (advice) will be via an online eConsent Form, which is accessed via a study-specific database system. eConsent does not need to be followed up with a paper (wet ink) written consent form as an electronic signature constitutes documented informed written consent. An approved paper (wet ink) equivalent will be available where eConsent is not feasible.

RELIEF Training Module 3 – Baseline I provides guidance about the study invitation and consent pathways (and process). In addition, there is a ‘Quick Recruitment Guide’ that includes key points when discussing RELIEF with patients.

Is verbal advice/consent from a Consultee/Legal Representative permitted, as hospital visiting is limited?

Yes. To facilitate timely and appropriate recruitment of patients with mild to moderate cognitive impairment who may potentially lack capacity to consent for themselves, we have adapted our approach for seeking remote advice from Consultees in England and Wales, or consent from Welfare Guardians/Attorneys/Nearest Relative in Scotland; see Protocol – Sections 8.3/8.4 for further details.

Who requires a copy of an Informed Consent (Declaration) Form?

Typically, five copies of the completed consent (declaration) form are required. For example, a copy should be:

1. provided to the patient (Consultee/Legal Representative);
2. filed with a copy of the relevant information materials in the participant’s ED records;
3. filed in the Investigator Site File (ISF);
4. provided to the Central Study Office (University of Bristol); and
5. provided to the patient’s General Practitioner.

For full details, see Protocol – Section 8.

What do we do if a participant who entered the study on a basis of consent by themselves, loses capacity during their 30-day study period?

For participants who have capacity at the time of consent in the Emergency Department, but who later lose capacity during their 30-day trial period (e.g. due to developing acute delirium), then suitable clinical/research staff will seek advice/consent from a Consultee/Legal Representative on behalf of the patient. See Protocol – Section 8 for details. A summary of the various study invitation and consent pathways are shown in:

• Protocol – Figure 2 (patients in England and Wales)
• Protocol – Figure 3 (patients in Scotland), and/or
• Protocol – Appendix 1, which presents an equivalent table.

If a Consultee/Legal Representative is not available or is unwilling, or advises that the participant should no longer take part in the study after they have lost capacity, then the participant will be withdrawn but data already collected up to the point of loss of capacity will be retained; see Protocol – Section 17 (Participant Withdrawal).

What do we do if a participant who entered the study on the basis of advice/consent from a Consultee/Legal Representative regains capacity during their 30-day study period?

If a patient (participant) regains capacity to consent during their 30-day trial period, then suitable clinical/research staff will ask them to give their own retrospective consent when and if they are able. Where feasible, the patient will not be informed about their treatment allocation group, nor will any further trial assessments and/or procedures take place until after retrospective consent has been obtained.

See Protocol – Section 8 for details. A summary of the various study invitation and consent pathways are shown in:

• Protocol – Figure 2 (patients in England and Wales)
• Protocol – Figure 3 (patients in Scotland), and/or
• Protocol – Appendix 1, which presents an equivalent table.

If the patient advises that they no longer want to take part in the study the patient will be withdrawn; see Protocol – Section 17 (Participant Withdrawal).

 

RANDOMISATION

What intervention groups will participants be randomised to?

Participants will be randomised on a 1:1 ratio to either the “LIDOCAINE PATCH (INTERVENTION)” or “STANDARD CARE (CONTROL)” group. See Protocol – Section 10 for details.

When can a (potential) participant be randomised?

Randomisation, to inform the treating clinicians which analgesic strategy to follow, can only take place once eligibility screening has been done and (written) informed consent is obtained.

Once a participant has been successfully randomised, they are enrolled in the study and treatment (intervention delivery) can proceed.

Who can randomise a participant and how?

Site staff who are trained on the RELIEF protocol and relevant procedures, and suitably listed on the site delegation log, can randomise a participant.

An online randomisation system will be used to conduct randomisation; the company providing the online system (software) is called “Sealed Envelope^TM”. The website address is: https://www.sealedenvelope.com/access/

You may wish to bookmark this link for future ease of access.

Guidance about how to randomise a participant, and what confirmation is provided, are included in RELIEF Training Module 4 – Baseline II. There is also a range of FAQs on the “Sealed Envelope” website.

Will site staff have their own randomisation system log-ins?

Yes, individual usernames and passwords are required to access the Sealed Envelope randomisation system. The Central Study Office will set-up individual user accounts following satisfactory completion of relevant study training and inclusion on the site delegation log. To create an account, the User’s real name and email address is required.

Once the account is created by the Central Study Office, an automatically generated email is sent to the email address with an invitation (valid for 2 weeks) to log in and set-up the account.

Help, I’ve forgotten my (Sealed Envelope) password!

Click on the Forgot your password? link on the log in page and enter the email address for your account. If you have an account, you will be sent an email with instructions.

If you do not receive the email you either do not have an account or the email has gone to your Spam folder or been blocked by your email provider. Contact your email provider if you are sure you have an account. Contact the Central Study Office if you do not have an account: relief-trial@bristol.ac.uk

I entered the wrong date of birth/gender/other data upon randomisation; what should I do?

Before you submit a randomisation request form, the User is required to review the details entered and confirm they are correct. If there is an error, the User can amend the form before proceeding to submit the request.

If following the completion of a randomisation and error is spotted, please email the RELIEF Central Study Office; if containing patient identifiable information, please ensure you use the secure NHS.net email: nbn-tr.relief-trial@nhs.net

What if I do not have access internet access; can I still randomise a (potential) participant?

There may be rare occasions when you cannot access the online randomisation system (“Sealed Envelope^TM”), either because of an issue with your internet access or down-time at “Sealed Envelope^TM”. On such occasions you should, where feasible, wait until the system is accessible again. We appreciate, however, that treatment should be administered as soon as practical in the Emergency Department. So, if local internet access is the problem, you could ask a system user with an administrative account (such as the Trial Manager) to perform the randomisation on behalf of your site.

NB: typical University (Central Study Office) staff working hours are Monday to Friday, 09:00-17:00 (subject to variation). If the event occurs outside these times and treatment cannot be delayed further, then it may not be feasible to complete the randomisation.

If you cannot complete the randomisation in an acceptable time, you should:

(1) inform the patient that you have not been able to complete their enrolment in the study (due to technical issues) and that they are not a participant of the study. NB: a patient is not fully enrolled in the study and counted as a participant (recruit) until randomisation successfully takes place.

(2) retain a copy of the Consent (Declaration) Form and complete a RELIEF Change of Permissions/Withdrawal Form; see RELIEF Training Module 5 – Participant Follow Ups for further details.

Who is aware of a participant’s treatment allocation?

Those treating the patient (including relevant members of the site research team) and the patient themselves will be aware of treatment allocation. As this is a single blind randomised controlled trial (RCT), only the researchers evaluating clinical outcomes will be blinded to treatment group allocation.

Once the online randomisation process is complete, the on-screen display will indicate which analgesic strategy to follow. An email notification will also be sent if the User has activated email notifications within their account. See Protocol – Section 9 and/or RELIEF Training Module 4 – Baseline II for further details.

 

STUDY INTERVENTION (TREATMENT)

What intervention groups will participants be randomised to?

Participants will be randomised on a 1:1 ratio to one of two intervention groups. That is either:

• “STANDARD CARE (CONTROL)”: Usual Care (standard clinical management); or
• “LIDOCAINE PATCH (INTERVENTION)”: Up to 3 x 700mg lidocaine patch(es) (Ralvo®) applied over the most painful area of rib injury after first diagnosis as soon as practical within the ED. The patches will be applied once daily for 12-hours in accordance with the manufacturer’s (Grünenthal) instructions, followed by a 12-hour patch-free period.  Treatment will continue for up to 72 hours or until the time of discharge, whichever is sooner. The intervention is additive to standard clinical management.

See Protocol – Section 10 for further details, including information about “standard clinical management”.

Where do we obtain study medication (Lidocaine patches) supplies from?

Study medication (Lidocaine patches) will need to be obtained from normal local site (hospital) pharmacy supplies, ordered and received in accordance with Pharmacy standard operating procedures (SOPs). See Protocol – Section 11 for details.

Who can prescribe study medication as part of the RELIEF protocol?

Treatment (study medication) can be prescribed by a registered medical practitioner or prescribing nurse who is listed on the Site Delegation Log. See Protocol – Section 10 and 11 for details.

Are there any ‘cautions’ associated with the study treatment for my patient?

Caution should be applied in the use of lidocaine patches for some patients (as per British National Formulary). Of relevance to the RELIEF study population, these cautions include:

• severe renal impairment
• hepatic impairment, and
• congestive cardiac failure.

Given the pragmatic nature of this study, and to reflect routine prescribing practices, we have excluded patients with end-stage liver failure with jaundice and end-stage heart failure with breathlessness at rest prior to injury. Patients with severe renal failure may still be recruited but routine monitoring for adverse effects will be undertaken.

Adverse effects of medications will be considered in safety monitoring: see Protocol – Sections 11 and 15 / RELIEF Training Module 6 – Safety Reporting for further details.

What should I do if a participant experiences side effects?

Lidocaine patches have been shown to be very safe and some specialist pain doctors already use them. Very rarely, the patch can, for example, irritate the skin. If this happens, you should remove the patch.

You may need to record and/or report an adverse event: see Protocol – Section 15 (Safety), and/or supporting training materials, RELIEF Training Module 6 – Safety Reporting.

Will taking part in RELIEF affect any other medications a participant might be taking?

There are no drug interactions with lidocaine listed within the British National Formulary. However, caution should be taken to monitor for local anaesthetic toxicity when additional local anaesthetics (such as nerve blocks) are used, as per usual clinical practice.

Can a participant access other treatment and/or interventions whilst taking part in RELIEF?

RELIEF is a pragmatic feasibility study. If a participant is randomised to receive Lidocaine patches (Study intervention arm) then this is additive to usual care (standard clinical management); all patients regardless of randomised treatment allocation will receive standardised treatment according to local analgesic guidelines for patients with rib fractures. See Protocol – Section 10 for further details.

Can a participant continue with the trial treatment after the 72 hour treatment (intervention) period if they wish?

It is important that patients are aware that they can ask for stronger pain killers if the patch (where applicable) does not help their pain or if the patch treatment has finished. In some cases, they may be seen by a pain specialist who will discuss their pain relief options with them. We are aware that in some centres (sites) lidocaine patches may be continued outwith the 72 hour trial intervention period and this is not a problem.

A participant does not want to adhere to the intervention (treatment) group they are randomly allocated to; can they still take part in the study?

Yes. Participants can choose to withdraw from complying with the allocated study treatment at any time during their study involvement. In such cases, efforts should be made to continue to obtain future questionnaire/assessment data with the permission of the patient or relevant (legal) representative, as appropriate.

Appropriate site staff should complete the RELIEF Change of Permissions/Withdrawal form as soon a feasible and notifying the Central Study Office; see RELIEF Training Module 5 – Participant Follow Ups for further guidance, and/or Protocol – Section 17 (Participant Withdrawal).

 

DATA COLLECTION

What is the schedule of assessments and outcome data collection for RELIEF?

Protocol – Section 12 provides full details about assessments/outcome measures and participant-related procedures scheduled at various study timepoints. Protocol – Table 3 presents a useful summary.

To summarise, (potential) participants will undergo:

• Screening, Consent and Randomisation
• Assessments and data collection at baseline
• Treatment (intervention) delivery at baseline for up to 72-hours (3-days)
• Assessments and data collection during (and at) the first 72-hours (3-days) post-randomisation
• Follow up at 30-days (+10-days) post-randomisation.

Further guidance, including practical information and data management, is provided in the RELIEF training materials:

• Training Module 4: Baseline stage; recruitment, data collection and treatment delivery
• Training Module 5: Follow Ups

Who can recruit participants and assist with other study activities (including data collection and/or follow ups)?

Following the completion of relevant study training, a doctor, research nurse, and/or other suitably qualified member of staff, as delegated by the site Principal Investigator (PI) on the site delegation log, can help with patient recruitment and follow ups and data capture/management.

Is it possible for participant’s (and/or person with caring responsibilities) to complete study questionnaires via an online survey (rather than paper booklet)?

It is intended that the Baseline Questionnaire and 30 Day (Final) Questionnaire will be available as on online (electronic data collection) questionnaire (survey); supporting information will be provided once the system becomes available. Until then, only paper booklets are available; see below about alternative remote data collection options.

The 72 Hour (3 Day) Questionnaire is only available in a paper questionnaire (booklet) format.

Is it possible to discuss the trial and/or collect data ‘remotely’ (i.e. not in-person)?

It is intended that eConsents, Baseline Questionnaire and 30 Day (Final) Questionnaire can be completed via online data collection tools; supporting information will be provided once the systems become available.

Discussions about the trial with Consultees/Personal Legal Representatives, including receiving appropriate informed advice/consent can be made via telephone (or alternative method if requested by the Consultee and where it is appropriate and feasible, e.g. Sponsor/NHS-approved video/tele-conference platforms). See Protocol – Section 8 for full details.

Completion of the 30 Day (Final) Questionnaire can be done by post, online or over the telephone (or alternative method if requested and where it is appropriate and feasible, e.g. Sponsor/NHS-approved video/tele-conference platforms) with a trained researcher if preferred. See Protocol – Section 12 for details.

Whose responsibility is it to undertake the follow ups post randomisation?

There are two scheduled follow ups after Baseline (point of randomisation): 72 hours (3 days) and 30 days post-randomisation; see Protocol – Section 12 for details.

Hospital (site) research teams (or delegated equivalent) are responsible for conducting and monitoring all participant follow ups (with the support of the Central Trial Team (Study Office) at 30-days, if required and where feasible). The site Principal Investigator (PI) will confirm the staff that will be responsible for undertaking the follow ups and associated documentation, as identified on the RELIEF Site Delegation Log.

I cannot contact a participant at 30 Days (final follow up). What should I do next?

Hospital (site) research teams (or delegated equivalent) are responsible for conducting and monitoring all participant follow ups (with the support of the Central Trial Team (Study Office) at 30-days, if required and where feasible).

If a participant questionnaire response is not received within a reasonable time (e.g. ~2-3 weeks), then researcher should try contacting the participant (and/or carer) to complete the questionnaire, and/or resend another questionnaire pack if appropriate/requested. The researcher will make (up to) three contact attempts on different occasions (allowing at least 7 days between contacts). If no response is received after the third reminder attempt, the questionnaire will be marked as missing.

The feasibility of these follow-up processes will inform the definitive trial.

A participant’s mental capacity status has changed. What should I do next?

It is possible during a participant’s 30 day study involvement that their capacity status may change (e.g. lose and/or regain capacity). Further details about what to do in this situation are provided in the Protocol – Section 8 and 12, and supporting training materials:

• Training Modules 3 & 4: Baseline stage; recruitment, data collection and treatment delivery
• Training Module 5: Follow Ups

What should I do if a participant reports, or I become aware of, an Adverse Event (AE)?

Full details about safety reporting for this study, including a list of definitions and classifications of adverse events, are in the Protocol – Section 15. Additional guidance is provided in RELIEF Training Module 6 – Safety Reporting.

 

INTEGRATED QUALITATIVE STUDY

I see that some patients and people with carer responsibilities will be invited to take part in an interview. What is the purpose of these interviews?

Please read the ‘RELIEF Interviews with Patients and People with Carer Responsibilities: Participant Information Sheet’, which explains what the purpose of the interviews are, as well as what is involved and other relevant details. In brief;

“In the RELIEF study, we want to find out if it is feasible to conduct a study exploring the use of lidocaine patches as a means of pain control for broken ribs. Results from this study will aid the design and development of a larger research study (trial) to explore whether patients who have patches put over their broken ribs may have improved pain. This may influence the treatment of patients in the future.

Qualitative research (interviews) with patients, and people with carer responsibilities, is a vital component of the RELIEF. The purpose of these interviews is to explore their experience of being involved in the trial. For example, we may explore details of the study design, acceptability of proposed outcome measures, and understand recruitment processes.”

Do I need to do anything regarding the interviews with patients and people with carer responsibilities, or who is responsible?

When a patient (or Consultee/Legal Representative) agrees to take part in the (main) RELIEF study, they will be asked to indicate on the study Consent/Declaration Form whether they are interested in taking part in an interview; taking part in an interview is optional and they can still take part in the study if they do not want to take part in an interview. Furthermore, only a few people are needed for the interviews so they may not be contacted, even if they express an interest. At this point you may be asked some questions, so we suggest you provide them with a copy of the ‘RELIEF Interviews with Patients and People with Carer Responsibilities: Participant Information Sheet’, which explains what the purpose of the interviews are, as well as what is involved and other relevant details. It also includes relevant contact details for further information. An electronic version of the information sheet is also available via the study website for review and download directly by the individual: https://relief.blogs.bristol.ac.uk/taking-part/

A qualitative researcher from the University of Bristol (and/or the Chief Investigator) is responsible for contacting interested patients (participants) and people with carer responsibilities and conducting the interviews.

 

SAFETY (ADVERSE EVENTS)

What is a ‘serious’ adverse event, and/or how do I classify an event?

What should I do if a participant reports, or I become aware of, an Adverse Event (AE)?

Full details about safety reporting for this study, including a list of definitions and classifications of adverse events, are in the Protocol – Section 15. Additional guidance is provided in RELIEF Training Module 6 – Safety Reporting.

 

PARTICIPANT CHANGE OF PERMISSIONS / WITHDRAWAL

Can participants change their mind about taking part after they have joined the study?

Yes. Participants can choose to withdraw for any reason at any time during their involvement in the study without affecting their usual care; they do not have to provide a reason for doing so. Participants can withdraw from (a) complying with the allocated trial treatment or (b) the study completely. If a participant wishes to withdraw from receiving the allocated trial treatment, efforts will be made to continue to obtain future questionnaire/assessment data with the permission of the patient or relevant (legal) representative, as appropriate.

In the event a clinician feels it is unsafe for the participant to continue in the study, s/he can withdraw the participant from the study. Furthermore, if a Personal or Nominated Consultee (or legal representative in Scotland) of a participant advises the research team that the participant should be withdrawn from the study, the research team must withdraw them.

Appropriate site staff should complete the RELIEF Change of Permissions/Withdrawal form as soon a feasible and notifying the Central Study Office; for further guidance see RELIEF Training Module 5 – Follow Ups. Also, see Protocol – Section 17.

 

DOCUMENTATION

Will participating sites (hospitals) require an Investigator Site File (ISF)? If so, how will this be arranged?

Yes. The Central Study Office will provide each participating site with an Investigator Site File (ISF) prior to participant recruitment. Delegated site staff will be notified of updates when applicable and updates to study documents will be available via the study website: https://relief.blogs.bristol.ac.uk/information-for-sites/.

Delegated site staff are responsible for maintaining their ISF.

Will a delegation log be made available for each site team?

Yes. Each participating site will be required to maintain a RELIEF Site Delegation Log and retain a copy in their local Investigator Site File. Copies should also be provided to the Central Study Office for monitoring purposes: relief-trial@bristol.ac.uk

Where can I access/obtain copies of the study training materials?

The latest version of RELIEF training materials are available via the study website, see: https://relief.blogs.bristol.ac.uk/information-for-sites/.

Site staff are required to maintain appropriate training records, and retain a copy in their local Investigator Site File.

Where can I obtain copies of the study documentation needed for RELIEF, including ethical and regulatory documents?

RELIEF study documents are available via the study website, see: https://relief.blogs.bristol.ac.uk/information-for-sites/. This is intended to be a single point of access for all study documents and information and will be updated if new documents/document versions are introduced. A document will also be included detailing the latest version of the study documents (i.e. a Version Control document).

Do any study documents require localisation?

Yes. Various study documents require localisation; you should liaise with the RELIEF Central Study Office regarding this. Sites are welcome to localise relevant documents themselves, however the Central Study Office would ask to review any documents you localise before usage to help maintain document control.

Are patient-facing documents available in languages other than English?

No. Patients who are unable to communicate in English language where all reasonable attempts to source translation services are exhausted within the Emergency Department are not able to participate in this study. Study documentation is only available in English; the study questionnaires include instruments validated in English, but if translated to another language, may not be validated.

Are there paper Case Report Forms (CRFs), or should data be added straight to the study database?

Data capture for this study is via a combination of both paper Case Report Forms (CRFs) and direct data capture (entry) to the online study database (when available). For further information, see the latest training materials and documentation that include appropriate instructions.

Where relevant, copies of data capture (e.g. consent forms, paper CRFs, and other documentation) should be retained in the local Investigator Site File (ISF). Any paper documents containing personal identifiable data must be stored in a locked filing cabinet (or locked equivalent) at the site, which only members of the local research team (as listed on the delegation log) have access to.

 

DATA MANAGEMENT

Please note this section is under development. The information displayed is correct at the time of review, but do note that further updates will be made once database development is finalised. If you have any queries, please contact the Central Study Office: relief-trial@bristol.ac.uk  

Do I (site teams) need to enter study data onto a database?

Apart from where highlighted (e.g. eConsent or questionnaires completed by participants online), site staff are not required to enter data to the study database. Instead, sites should securely transfer study data (documents) to the Central Trial Team (Study Office), in a timely manner, for data entry and monitoring. Given the short duration of participation (30-days) it is vital that data are transferred to the Central Trial Team and entered as soon as possible.

Instructions are included on or throughout each document, including useful checklists at the end CRFs.

Data (document) transfer summary:

• Sites should return a copy of all available study-related documents to the RELIEF Central Trial Team as soon as possible following each timepoint (or event) to enable activation of the participant on the study database, data entry and participant monitoring.
• Scanned copies can be emailed securely to: nbn-tr.relief-trial@nhs.net
• Site should retain (original) copy in ISF.

If in doubt, contact the Central Trial Team: relief-trial@bristol.ac.uk

What requirements are there, if any, about how to store data?

Consent forms and clinical letters (and any other documentation) with personal identifiable data must be stored in a locked filing cabinet (or locked equivalent); access should be restricted to those listed on the RELIEF Site Delegation Log.

How are the study data archived (when appropriate)?

Medical case notes containing source data or other study-related information should be identified by a label (or equivalent for electronic notes, where feasible) “Keep until at least dd/mm/yyyy” where the date given is at least five years (or applicable period) after the end of the study.

An archiving plan will be developed for all study materials, but essentially data will be retained for at least 5 years after the end of the study. Sites will be responsible for ensuring that all study records held at their site are archived appropriately when notified to do so by the Sponsor/Central Study Office. Further details will be provided to participating sites when available.

 

MONITORING

What study monitoring procedures do I need to be aware of?

Full information on study monitoring is available in the Protocol – Section 21.

In brief:

• The study will be monitored in accordance with the Sponsor’s (North Bristol NHS Trust) Monitoring SOP, which is consistent with the UK Policy Framework for Health and Social Care Research.
• All study related documents (e.g. local Investigator Site File (ISF)) should be kept up to date and made available for monitoring and audit/inspection upon request.

How do I report a GCP / Protocol non-compliance (deviation)?

Information about Protocol Compliance is available in the Protocol – Section 21.1.

To report a protocol deviation, you must use the RELIEF GCP & Protocol Non-compliance Report Form; instructions about how to complete the form, who to submit it to and when, are included on the form. A blank template can be found in your Investigator Site File (ISF) and from the study website: https://relief.blogs.bristol.ac.uk/information-for-sites/

What is considered a “serious breach” of Good Clinical Practice (GCP) and/or the protocol?

As noted in the Protocol – Section 21.2, a “serious breach” is a breach which is likely to effect to a significant degree:

• The safety or physical or mental integrity of subjects of the study (participants); or
• The scientific value of the study.

The Central Study Office will notify the Sponsor immediately of any breaches, who will determine the seriousness of the breach.

 

ETHICS AND REGULATORY APPROVALS

What ethics and regulatory approvals do I need to be aware of?

Full information on ethics and regulatory approvals is available in the Protocol – Section 22.

In brief:

• The study will be undertaken at several UK sites, subject to appropriate REC approval and HRA approval.
• The study will be conducted in accordance with the Protocol, the conditions and principles of the Declaration of Helsinki and Good Clinical Practice (GCP).
• Any amendments of the protocol will be submitted to the REC for approval.
• On request, the study investigators and their institutions will permit trial-related monitoring and audits by the Sponsor and relevant REC.

Where can I find copies of ethics and regulatory approvals?

Copies of relevant documentation can be found in your Investigator Site File (ISF) and from the study website: https://relief.blogs.bristol.ac.uk/information-for-sites/

A delegate at your site will be notified if new documentation becomes available and they will be responsible for maintaining local (ISF) records.

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