Compassionate Communication and Advance Care Planning to improve End-of-life Care in Treatment of Haematological Disease 'ACT': Study Protocol for a Cluster-randomized trial.

STRENGTHS AND LIMITATIONS OF THIS STUDY

The intervention integrates serious illness conversations into the workflow of treating clinicians.

Physician–nurse teams with patients under their care represent the clusters to minimise bias introduced by randomising at the level of hospital departments.

This study assesses the effects on treating clinicians, patients and their informal caregivers.

The study mitigates the risk of carry-over effects on control clusters’ communication, by providing training, intervention materials and administratively allotted extra time for intervention clusters.

The Advance Consultations Concerning your Life and Treatment intervention is a complex intervention with several components and this study cannot identify the effects of each component but only of the full intervention.

Introduction

Patients with haematological malignancies (HM) are at substantial risk of death, with 5-year survival of 27% for acute leukaemia and 66% for multiple myeloma (MM). 1 Towards the end of life (EOL), these patients experience poor outcomes, as illustrated by low utilisation of palliative care 2 and high treatment activity close to death (eg, chemotherapy and intensive care unit admissions) where clinical benefits are doubtful. 3 Effective communication among patients, their informal caregivers and clinicians regarding prognostic awareness and EOL issues is urgently needed to prevent futile treatments and unnecessary suffering.

EOL care

EOL care is provided during the advanced stages of disease, typically within the last weeks or months before death. 4 5 In this study, EOL care refers to care delivered during the last 30 days of life. 6–9 Indicators of aggressive and low-quality EOL care include overuse of chemotherapy, frequent hospitalisations and underuse of hospice services. 8–13 A longitudinal cohort study of patients with advanced solid cancers and their informal caregivers (n=332 dyads) found aggressive EOL care associated with poorer patient quality of life (QoL) and greater mental health problems in bereaved caregivers. 13 An analysis of EOL care received by 21 033 haematological patients showed 11% received chemotherapy in EOL, 35% were admitted to the intensive care unit in EOL and 44% entered hospice, but 20% shortly before death. 14 Similarly, a Danish cohort study of deceased patients with cancer (n=17 246) reported that patients with HM were more likely to receive chemotherapy in EOL compared with patients with solid tumours. 15 In summary, patients with HM receive low-quality EOL care, 6 8 16–18 leading to increased symptom burden and lower QoL for patients and caregivers. 13 19

Advance care planning and compassionate communication

Advance care planning (ACP) aims to improve EOL care by supporting patients to express preferences and goals and integrating these into the medical care plan. 20 ACP reduces aggressive treatment at EOL, 13 21–23 improving QoL and decreasing the risk of anxiety and depression in patients and informal caregivers. 13 24 25 However, patients with haematological cancers are often excluded from palliative care trials 26 and most studies on early and integrated palliative care within haematology are retrospective observational studies. 9 27–30 Only one randomised trial of 160 adults with acute leukaemia examined the impact of early palliative care intervention on EOL care, 31 reducing the use of chemotherapy in the last 30 days of life, but found no significant effects on other EOL outcomes. 31 Another study, with 160 patients undergoing haematopoietic stem cell transplantation, found early integration of palliative care alleviated anxiety and depression. 32 Despite positive findings, implementation of ACP faces barriers among clinicians, including time constraints, timing uncertainty, lack of communication skills, 33 34 prognostic insecurity 33 and fear of taking away the patients’ hope. 34 Addressing these barriers and improving communication led to the development of the Serious Illness Care Programme (SICP), 35 a communication quality-improvement intervention aiming to improve patient outcomes and goal-concordant care through tools, training and system changes. 36 In a cluster randomised trial of 286 patients with cancer, SICP resulted in more frequent and earlier conversations, greater focus on values, goals, prognosis and illness understanding 37 and reduced symptoms of anxiety and depression. 36 However, the study did not directly evaluate the impact on EOL care or its effect on informal caregivers and included fewer than 10% of patients with HM. Larger randomised trials are needed to investigate the effects of SICP on EOL care in patients with HM.

Feasibility work

We previously conducted a feasibility study within a Danish haematological department, following the UK Medical Research Council framework. 38 The components of the original programme were adapted to Danish sociocultural factors and workflows (unpublished work, under review) and named ‘Advance Consultations Concerning Your Life and Treatment’ (ACT). With an 80% participation rate, the ACT intervention was found feasible in overcoming barriers in clinical practice. Moreover, ACT improved patient–caregiver communication regarding EOL preferences, increased empathy in clinician communication and helped patients prioritise life with serious illness. 39

Aim

This study aims to evaluate the effect of the ACT intervention on the quality of EOL care for patients with HM, as measured by the receipt of chemotherapy at EOL and symptoms of anxiety in patients and informal caregivers.

The intervention consists of the ACT conversation and the following supportive components: (a) clinician training and supervision, (b) preparatory materials for patients and informal caregivers and (c) system changes (see figure 1 ).

Methods and analysis

This study protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials statement. 40

Study design

This nationwide study is conducted across departments of haematology at seven Danish hospitals in a two-arm cluster randomised trial. 40 clusters, each consisting of 1 physician and 2 nurses, are randomised to provide standard care or ACT intervention. A total of 400 patients with HM and their informal caregivers will be included ( figure 2 ). Intervention group clinicians receive ACT training and provide standard care with ACT conversations to participants. Control group clinicians provide standard care according to national guidelines, 41 without ACT conversations. This design allows for complex behavioural interventions that necessitate the education of clinicians, which precludes randomisation at the individual patient level. 38 Based on the recruitment rate in the feasibility study (46 eligible patients identified, 80% acceptance, allocation to 5 doctors over 6 months in one department), recruitment lasts 24 months, and we follow each patient and informal caregiver for 18 months from study entry. The study commenced on 1 August 2022, with expected completion on 1 October 2026.

Participant eligibility

Inclusion criteria for patients and informal caregivers

Eligible patients and informal caregivers are adults (≥18 years old), able to read and speak Danish, complete questionnaires, and provide oral and written informed consent. The informal caregiver is identified by the patient. Patients must have a diagnosis of high-risk myelodysplastic syndrome, acute myeloid leukaemia, lymphoma (diffuse large B-cell lymphoma, T-cell lymphoma, Mantle Cell lymphoma) or MM with limited treatment options, as defined in collaboration with physicians from participating sites specialised in each diagnostic group ( table 1 ). Patients are included either (1) from the date of diagnosis if not eligible for curatively intended treatment, (2) from the date of relapse/refractory disease or (3) from the date of transition to palliative care only ( table 1 ). These criteria standardise the time of invitation across departments.

Exclusion criteria

Patients cannot participate if they have current psychiatric disorders hindering participation, for example, psychotic disorders.

Inclusion criteria for physicians and nurses

Eligible physicians are specialists or haematologists in training and treating patients with eligible haematological diagnoses at each site. Nurses sharing clinical work with participating physicians are eligible. No other inclusion or exclusion criteria apply.

Procedures for inclusion

Clinicians

Eligible physicians in outpatient haematological clinics are invited to participate, as well as nurses working with each recruited physician. Physicians and nurses are matched before randomisation. We aim to recruit two nurses for each physician to accommodate turnover of nurses during the intervention period. Clinicians receive written information by email and after a reflection period of 24–47 hours and are asked to provide written informed consent and complete a baseline questionnaire via REDCap. 42 43

Randomisation

Physician–nurse clusters are randomised 1:1 by a computer-generated sequence to the intervention group or control group, stratified into four groups based on the physician’s subspecialty. The randomisation sequence is provided by an independent statistician and blinded for all project participants including authors of the protocol. Allocation concealment is ensured, as the randomisation is automated and only completed after all baseline questionnaires are received. CBM notifies participants of their assigned group via email. All trial participants will remain in the group they were allocated to (either intervention or control) until study completion unless they choose to withdraw consent.

To investigate selection bias, we invite all non-participating clinicians to complete the baseline survey and collect data on average age and seniority of non-participating clinicians from each site.

Cluster drop-out

If a physician drops out of the study, for example, due to leaving the workplace, the new physician assuming responsibility for the former’s patients is invited to participate in the same allocated group as the previous physician. The new physician cannot be randomised, due to the already included patients. Sensitivity analysis will be used to investigate the consequences of this non-randomised component.

Patients and informal caregivers are recruited based on their treating physician’s randomisation assignment. At each site, one or more nurses are responsible for screening all eligible patients under the care of participating physicians. These ‘project nurses’ screen each cluster’s patients for eligibility weekly and provide written and oral study information to all eligible participants. We obtain information on reasons for declining participation from non-participants and data on diagnosis, age and treatment line from medical records. Participant information and survey responses are collected and stored in REDCap. 42 43

Intervention

The ACT-intervention centres on discussing prognosis, patients’ and informal caregivers’ goals and preferences for future care and treatment. The ACT conversation, lasting 1 hour with 15 min allocated for documentation, is conducted by the nurse–physician team and creates a secure environment for open expression of perspectives and preferences about the illness. Clinicians provide information tailored to patient preferences about their illness and prognosis, followed by a discussion of patient and caregiver goals, values, and priorities. If suitable, clinicians provide recommendations for the next steps in care based on patient goals.

Participants in the intervention group are invited to an ACT conversation by their physician/nurse team, scheduled within 2–4 weeks from the invitation. In case of disease progression or transition to palliative care, an additional conversation is offered. The number of conversations per patient depends on the time of inclusion and disease progression during the project period.

The ACT conversation is supported by the following components ( figure 1 ).

Clinician directed: training, clinical tools and supervision

Training of clinicians: To prepare for the training day, clinicians watch a video demonstration of the ACT conversation. The 7-hour training session accommodates up to five physician–nurse clusters and includes (1) A didactic lesson on the ACT intervention, materials and evidence for the approach, (2) Discussion of possible barriers, (3) Live demonstration in roleplay with debriefing and (4) Skills practice through simulation training with professional actors, facilitated by an experienced psychologist.

Clinical tools consist of a conversation guide for clinicians, and a visual ‘conversation aid’ to assist structuring the conversation and agenda.

Supervision is provided by an experienced psychologist supervisor and a project group member to ensure intervention fidelity and provider confidence. Clinicians receive 1.5-hour group supervision sessions every third month, for a totalling of five supervision sessions.

Patient directed: preparation and follow-up

Preparatory material for patients and informal caregivers, respectively, is provided prior to ACT conversation, encouraging them to reflect on specific issues and take notes prior to and during the conversations. Readiness to discuss prognosis varies, 44 45 therefore, the preparatory material provides an opportunity to express preferences for prognostic information and voice hopes and concerns possibly influencing EOL decisions. 39

A telephone call is completed by the nurse within seven days after the conversation to address any follow-up concerns and questions.

System directed: system changes

Allocated time: To address time constraints, management at each site allocates 60 min intervention slots into the daily clinical programmes of clinicians in the intervention group, which are booked by the project nurse.

A template for documentation in the patient record ensures that the issues discussed and the patient’s preferences are documented.

Control group

Patients treated by physicians and nurses in the control group receive standard care following individual hospitals’ and national haematological medical guidelines, 41 not including ACT conversations.

Power calculation

Power calculations were conducted using the clusterPower package in R. 46 Based on data extraction from medical records of 1128 patients with HM who died between 2016 and 2021 in the Capital region of Denmark (unpublished), we expect that 40% of patients receive chemotherapy within 30 days of death. With 40 physicians randomised as clusters, an intraclass correlation of 0.1, 47–52 alpha of 0.05 and 80% power, we need to include a mean of seven patients for each randomised physician to show an expected reduction of EOL chemotherapy to 20% for patients in the intervention group. As not all patients will reach EOL within the study period, we will recruit 10 patients for each participating physician, totalling 400 patients. Assuming an inclusion rate of 60%, we expect to achieve the required recruitment within 24 months.

Outcome measures

Data are collected from medical records, questionnaires and registers at baseline, during the intervention and up to 18 months after inclusion both in the control and intervention arms ( table 2 ).

Assessment points (see figure 3 ) include:

Study enrolment: For clinicians (CL.T1) and patients and caregiver participants (Part.T1).

Intervention assessment: After every ACT conversation for patient and caregivers (Part.int.T1-3), after 5 completed interventions for clinicians (CL.Int.T1).

Follow-up: At 3, 6, 9, 12 and 18 months for patients and caregivers (Part.T2-6), and after 24 months from study entry for clinicians (CL,T2+CL.int.T2).

Bereaved caregivers if patients die: Time of death (Part.T7) and 1 and 6 months after (Part.T8-9).

Primary outcomes

This study includes two primary outcomes; the receipt of chemotherapy in the last month of life and patients’ and informal caregivers’ symptoms of anxiety (General Anxiety Disorder-7). 53 We selected these outcomes due to the dual importance of very late chemotherapy provision as a likely futile treatment, potentially increasing patients’ and informal caregivers’ suffering including symptoms of anxiety, and as a strong indicator of inadequate discussions about prognosis and treatment preferences. 24 36 54 55 Both outcomes are strong proxies for the quality of EOL care. 56 57

Secondary outcomes

Medical records and national registers

Other measurements assessing the quality of EOL care include days of hospitalisation within the last 30 days of life, the number of medical consultations and referral to hospice in the last 30 days of life (and time from referral to death), as well as overall survival (time from diagnosis to death). All data are collected from medical records by the project nurse at each site. This information will only be shared between the allocated project nurse at the specific site and PhD-student CBM and not between all sites.

The National Register of Causes of Death 58 is used to register whether patients die in hospital, hospice or at home.

Questionnaires

We collect data measuring patients’ and informal caregivers’ depressive symptoms (Patient Health Questionnaire-9 59 ), QoL (EORTC-QLQ-C-15-PAL 60 ), dyadic coping (Ways of Giving Support 61 ), satisfaction with healthcare (FamCare 62 ) and prognostic understanding (single item 63 ) ( table 2 , online supplemental material description’). Satisfaction with intervention sessions is assessed for the intervention group through a self-developed questionnaire based on the feasibility study. Bereaved informal caregivers are asked to complete questionnaires assessing mental health, post-traumatic stress (Impact of Events Scale 64 ), grief (Prolonged grief-13 65 ) and their perception of the patient’s quality of death (Views of Carers-Evaluation of Services (Short form). 66

bmjopen-2024-085163supp001.pdf

Clinicians provide baseline data on their years of experience as senior physicians or nurses, disease group specialty, education level, and prior communication training, and complete questionnaires measuring their self-efficacy (ACP-self-efficacy 67 ) in serious illness conversations, symptoms of burn-out (Copenhagen Burnout Inventory 68 ) and existential communication (existential communication in general practice 69 ). Satisfaction with the intervention is assessed for the intervention group through self-developed questionnaires based on the feasibility study.

Participants who do not respond to surveys will receive email reminders after 7 and 10 days, a personal reminder from the project nurse if attending the clinic, and a phone call after approximately 14 days. If participants continue to not respond to surveys, they will be considered lost to follow-up after 12 months.

Intervention cost

To estimate the opportunity cost of resource use, we plan to aggregate the direct medical costs incurred by patients and public medical expenses, and public nursing care expenses. Drug expenses are estimated based on purchase prices obtained from the national supplier of hospital drugs AMGROS. 70

Data analysis

The proportion of patients in the intervention compared with the control group receiving chemotherapy within 30 days of death,is analysed using generalised mixed-effects models with a logit link function. This model accommodates both fixed effects, that is, allocated treatment and random effects, such as cluster and site, capturing variability within and between clusters. All fixed effects coefficients, including the effect of treatment allocation, are reported in terms of odds ratios and presented with 95% CIs. The null hypothesis of no effect of the intervention is evaluated by means of a likelihood ratio test. Patients who die during the study period are included in the analysis of effects on EOL chemotherapy, whereas all patients and informal caregivers contribute to the assessment of anxiety outcomes.

To estimate the effect on questionnaire-based outcomes, we use mixed effects models assuming the response to be normally distributed. The models include the random effects of cluster and fixed effects of allocated treatment, time (3, 6, 12 and 18 months), time-by-treatment interaction, site, as well as known baseline predictors of the outcome in question. We estimate the overall change from baseline over 3, 6, 12 and 18 months with 95% CI and p value, as well as effect sizes and CIs for effects at each time point using the mixed effects model. Only bereaved caregivers will contribute to the assessments at 1 and 6 months from patients’ deaths.

Effects on overall survival are analysed in Cox proportional hazards models. We estimate the HR and 95% CI of death in the intervention compared with the control group, adjusted for randomisation strata, age and inclusion criterion (inclusion time point). Patients are followed from study inclusion until death or censoring, whichever comes first.

We will analyse data using the intention-to-treat principle. We will use multiple imputation where appropriate. In mixed effects repeated measures models, imputation will not be used, as this approach already accommodates missingness.

We will not conduct interim analyses or use stopping guidelines as there are no expected adverse events.

A statistician blinded to treatment assignment will conduct all analyses.

Audio records

All ACT conversations are audio recorded. A random subset of recordings will be used to investigate fidelity (see implementation and process evaluation).

Implementation and process evaluation

Clinical workflow of recruitment is adapted to fit the local context and resources, for example, the number of allocated project nurses at each site and how screening and inclusion tasks are divided among them. Stakeholders at each site actively participate in codesigning a feasible and sustainable workflow, for example, while a 60 min allocation for each ACT conversation is mandated, strategies to book the conversations are adaptable. Each site can match nurses with physicians to fit the local working context before randomisation. Due to the dynamic clinical practice, one intervention nurse may work with different intervention physicians to provide ACT conversations. Importantly, no intervention nurses will have ACT conversations with physicians or patients in the control group to maintain the integrity of the intervention group assignment.

Sites and stakeholders receive monthly emails with anonymised audit and feedback reports of the progress of inclusion compared with other participating sites. Every 3 months, they receive a newsletter on project progress. Facilitation activities, aiming to aid implementation and sustain practice change (84), include weekly to monthly email or phone check-ins with project nurses providing feedback on recruitment and data collection, and quarterly in-person site visits to address issues such as staff turnover, technical problems and workflow.

Monitoring for fidelity involves logging all intervention components in REDCap, 71 including monitoring the delivery of preparatory materials, documenting dates of conversations and follow-up phone calls, clinician attendance at supervision sessions, and ensuring documentation and audio recording of the conversations. Audits are conducted monthly by CBM.

A trained research assistant assesses intervention fidelity in a random subset of audio recordings and documentation of the ACT conversations in the medical record using a checklist of intervention components (eg, probing for information preference, sharing prognostic information, discussing hopes and worries).

Patient and public involvement

The adaptation of SICP into a Danish haematological setting involved collaboration among five haematologists, five nurses, six patients with HM and four informal caregivers. A feasibility study addressed clinical and procedural uncertainties, examining barriers in clinical practice, recruitment and acceptability by patients and clinicians. 39 72 Clinicians identified the need for a preparatory training video and a phone call to patients and informal caregivers postconversation as essential components. We adapted the intervention to meet these requirements prior to proceeding with this randomised evaluation. 73

Ethics and dissemination

Ethics and data protection

Given the low risk identified in a prior feasibility study of the ACT intervention, a ‘composition of data monitoring committee’ for this behavioural study was not established.

The main risk for patients and caregivers is that they may experience transient distress during discussions in ACT conversations. To mitigate the potential distress, a follow-up phone call is completed within 7 days. The study is registered at ClinicalTrials.gov ( NCT05444348 , version 4, date: 26 February 2024) and approved by the Local Data Protection Agency (record no: P-2022-93). All procedures adhere to Danish regulations, the Helsinki II Declaration and The European general data protection regulations (GDPR).

The Regional Ethics Committee of the Capitol Region of Denmark determined that approval is not necessary as per Danish legislation (record no: 21067634). 74 The protocol will be updated with important modifications, new version nr and date, including at ClinicalTrials.gov. The new protocol version will be communicated orally and in writing to all participating sites and clinicians.

Ph.D. student CBM will have access to the final dataset in REDCap, and the statistician will perform the analysis to pseudonymised data. The data are owned by the Capital Region of Denmark.

Dissemination

The study’s findings will be shared with study funders, healthcare providers, patient organisations and researchers via international conferences and peer-reviewed journals. Access to protocol and statistical code, as well as individual participation data for meta-analysis will be possible on request. Data requestors will need to sign a data access agreement in agreement with the Data Protection Act.

Status of the study

The study has recruited 42 physician–nurse clusters, exceeding the calculated number by 2. To account for potential turnover and drop-out risks, all 42 clusters are included. Currently, we are halfway through the recruitment period of patients and informal caregivers.

Perspective

If our study demonstrates the expected effects in this vulnerable population, it may contribute to improving the EOL experience for patients and their families as well as decrease symptom burden in bereaved informal caregivers. Future research could explore collaboration with specialised palliative care services and care delivery in municipalities.

Supplementary Material

Reviewer comments

Author's manuscript

Acknowledgments

The authors express gratitude to the physicians at each site for their contribution in developing the patient identification criteria, to the statistician Klaus Kaare Andersen for contributing with power calculation and the data analysis plan, and to participants from all seven sites.

Footnotes

Contributors: CBM was the main writer of this manuscript, which was revised critically several times by CJ, SNC, MJ and AvH. All authors contributed equally to the development of the study protocol, and we adhere to the Vancouver recommendations for authorship.

Funding: This study is supported by the Novo Nordisk Foundation (0071520), The Danish Cancer Society (R296-A16986), Helse Foundation (21-B-0301), the Danish Health Authorities(E-23760-01) and The Danish Regions (EMN-2022-00001 1564687).

Disclaimer: This funding sources have no involvement in the design, execution, analyses and interpretation of the data or decision to submit the results.

Competing interests: None declared.

Patient and public involvement: Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

Provenance and peer review: Not commissioned; externally peer reviewed.

Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Ethics statements

Patient consent for publication

Not applicable.

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