Title: CARer-ADministration of as-needed sub-cutaneous medication for breakthrough symptoms in home-based dying patients: a UK study (CARiAD)
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Design: Feasibility study and external randomised pilot trial of carer-administered as-needed sub-cutaneous (SC) medication for common breakthrough symptoms in home-based dying patients, v usual care, with nested qualitative component. An expert consensus group will refine trial processes, education package and resources, and develop the protocol for community administration of palliative care medicines. (2) Trial setting: Community setting without 24/7 paid care Target population: Patient/lay carer dyads Inclusion criteria: Adult patients in the last week of life who prefer to die at home and have able relative/carer over 18 willing to have subcutaneous (SC) injection training. Consent will be sought from both. Technology: Carer-administered as-needed SC medication for breakthrough pain, agitation/restlessness, nausea/vomiting, or noisy breathing supported by a tailored education programme.(3) Costs/outcomes: Pilot randomised trial: Feasibility, acceptability, recruitment, attrition, contamination. Potential main outcomes for definitive trial: Symptom burden (Family MSAS-GDI)(4-8), QOLLTI-F. Also: Time to symptom relief, number of episodes resolved in 30 minutes, safety, Carer Experience Scale, healthcare utilisation. Attribute selection for a future discrete choice experiment. Sample size: A fully justified sample size is not required; sample size is justified by estimating what a future full RCT will need. Assuming an important difference of 0.4(SD=1) on Family MSAS-GDI a sample of ~216 is required to achieve 90% power to detect a difference of this size with a significance level of 0.05 using a two sided test. Equivalently ~550 is required to detect a difference of 0.5(SD=2) on QOLLTI-F. Using the larger of these estimates, we will assume about 9% of the main trial size, to give an 80% CI to exclude a clinically important difference, requires ~25 in each group.(9) Sim and Lewis recommend a sample of about 50-55 to ensure robust estimates of the variance.(10) Using estimates of dropouts we predict we need to approach 200 potential participants to achieve 100 randomised participants, with 50 completers. Qualitative: Interviews at 2-4m post-bereavement (11-13) to explore attitudes and experiences of giving SC medication, experience of trial processes (recruitment, consent, randomisation, training, medication management, outcomes – choice, timing and recording). Purposive sample of 6-10 carers (trained to give SC medication), 6-10 control group, 6-10 declined to participate, and prescribers 10 per group: GPs, DNs, palliative care clinicians. Questions regarding attributes for a discrete choice experiment in a future main trial will be included in these interviews. Analysis – Carers: Interpretative Phenomenological Analysis [IPA] for deeper, experiential inductive analysis.(14) HCP analysis: Process driven deductive approach using Framework Analysis.(15) Pathways: Current (usual): Carers call a HCP who will travel to the home, assess, and give SC medication. Planned: Individually randomised to usual care versus intervention (carers trained to assess need for, and give SC medication, and assess symptom resolution). Analysis: Feasibility metrics, adherence outcomes. Preliminary analysis of intervention outcomes. Point and 95% confidence interval estimates will be calculated and used to estimate standard deviations and effect sizes to further inform the sample size calculation for a definitive study.

Lay abstract: Most people want to be cared for and die at home. As people get weaker in the last weeks or days of life, they usually can’t swallow. In the UK, when this happens, it is standard practice for medicines to be given by a drip under the skin to relieve symptoms. Four symptoms are common in dying people: pain, agitation, nausea and noisy breathing (rattle). These can happen even when a drip is in place, and are called ‘breakthrough’ symptoms. When they do, a family member is advised to call a healthcare professional (HCP), usually a district nurse. The nurse will visit and give the patient an injection under the skin. But, it can take a long time, often much more than an hour, for the nurse to arrive and give the medicine. This wait can be distressing for patient and carer and the symptom can worsen by the time the nurse arrives. Carers tell us that this makes them feel powerless to help their loved ones. In some countries, like Australia, carers are trained to give symptom-relieving medicine to their dying relatives at home. We are working with a team from Brisbane, who have 30 years’ experience of this. We cannot be sure that this approach would be welcomed in the UK, so we need to test it out. When there is uncertainty, the best way to resolve it is to do a randomised controlled trial (RCT). This is a test where, at random, half the patients get ‘usual care’ and the other half the ‘new care’. We hope to conduct a RCT comparing injections given by carers to dying patients looked after at home (the new care) versus HCP-given injections (the usual care). Before doing a large trial, it is good practice to first test the feasibility in a smaller group of patients. Our study is such a feasibility study. Firstly, we will ensure that everyone understands it is legal for carers to give symptom-relieving injections to dying patients as long as they are supported to do so. Our Australian partners have a time-tested education package: we will ensure this is reworked for UK patients, carers and HCPs. We will hold workshops to do this, and decide how best to explain the study to carers and patients. Then we will ask patients and their carers whether they are willing to be randomised to ‘usual care’ or ‘new care’. Carers in the ‘new care’ part will be trained how to recognise symptoms, to give injections and then see if they work to relieve the symptom. Carers in the ‘usual care’ group will be asked to call a HCP if their loved one has breakthrough symptoms. Carers in both parts will be asked to keep a diary of symptoms and treatments. They will be invited to talk about how they found the study and the experience of giving injections. Information from this feasibility study will help us to understand if a large trial, to give a final answer, is possible. We have discussed our study with patients, carers and HCPs. They are greatly in favour of it and have given us their views, particularly with regard to the things we should measure. Two members of the study team are bereaved carers, and one has administered injections to her loved one. They have helped to design the study and will be involved throughout the study time. Study results will be fed back to carers who took part in the study if they wish to receive them, be published in scientific journals and discussed at national / international conferences.

Research activity codes: 7.2 END OF LIFE CARE
Health categories: GENERIC HEALTH RELEVANCE