HIDDEN2: Study protocol for the hospital deep vein thrombosis detection study in patients with cancer receiving palliative care.

INTRODUCTION: Medical patients, admitted acutely to hospital, are at risk of venous thromboembolism (VTE). Clinical guidelines advise thromboprophylaxis prophylaxis for those at high risk of VTE. VTE is a common sequela of cancer, but guidelines take little consideration of cancer as an independent risk factor and their utility in palliative care patients is unclear. The hospice inpatient deep vein thrombosis (DVT) detection study (HIDDen) reported a 28% prevalence of asymptomatic iliofemoral DVT in hospice patients of poor performance status (PS) and prognosis, calling into question the utility of thromboprophylaxis in the palliative care setting. However, the majority of cancer inpatients receiving palliative care are admitted to hospital through the acute medical setting, yet their risk factors for VTE may differ from those admitted to hospices. OBJECTIVE: To better understand the prevalence and behaviours of VTE in patients with cancer receiving palliative care who are admitted as an acute medical emergency. DESIGN: Multicentre, observational cohort study. SETTING: Secondary care acute hospitals in South Wales, UK. PATIENTS: We plan to recruit 232 patients≥18 years old with a diagnosis of incurable cancer, and/or receiving palliative or best supportive care who are admitted acutely to hospital. Patients will be followed up for a maximum of 6 months following registration. PRIMARY OUTCOME: Presence of lower extremity DVT. SECONDARY OUTCOMES: Symptom burden attributed to DVT or pulmonary embolism, patient PS, patient demographics and development of new VTE within 90 days of registration. ANALYSIS: The study statistical analysis plan will document analysis, methodology and procedures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee, reference 22/WA/0037 (IRAS 306352)-the main trial results will be analysed as soon as practically possible and the publication shared with investigators and on sponsor website; applications to access trial data will be subject to sponsor review process.

Development of a core outcome set for use in adult primary glioma phase III interventional trials: A mixed methods study.

Background: Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution. Methods: A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified. Results: In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting. Conclusions: A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS.

Development of a Core Outcome Set for the research and assessment of inoperable malignant bowel obstruction.

BACKGROUND: Malignant bowel obstruction is experienced by 15% of people with advanced cancer, preventing them from eating and drinking and causing pain, nausea and vomiting. Surgery is not always appropriate. Management options include tube or stent drainage of intestinal contents and symptom control using medication. Published literature describing palliative interventions uses a broad range of outcome measures, few of which are patient-relevant. This hinders evidence synthesis, and fails to consider the perspectives of people undergoing treatment. AIMS: To develop a Core Outcome Set for the assessment of inoperable malignant bowel obstruction with clinician, patient and caregiver involvement, using COMET methodology (Core Outcome Measures in Effectiveness Trials). METHODS: A systematic review of clinical trials and observational studies, a rapid review of the qualitative literature and in-depth patient and clinician interviews were conducted to identify a comprehensive list of outcomes. Outcomes were compared and consolidated by the study Steering Group and Patient and Public Involvement contributors, and presented to an international clinical Expert Panel for review. Outcomes from the finalised list were rated for importance in a three-round international Delphi process: results of two survey rounds were circulated to respondents, and two separate consensus meetings were conducted with clinicians and with patients and caregivers via virtual conferencing, using live polling to reach agreement on a Core Outcome Set. RESULTS: 130 unique outcomes were identified. Following the independent Expert Panel review, 82 outcomes were taken into round 1 of the Delphi survey; 24 outcomes reached criteria for critical importance across all stakeholder groups and none reached criteria for dropping. All outcomes rated critically important were taken forward for re-rating in round 2 and all other outcomes dropped. In round 2, all outcomes were voted critically important by at least one stakeholder group. Round 2 outcomes were presented again at online consensus meetings, categorised as high ranking (n = 9), middle ranking (n = 7) or low ranking (n = 8). Stakeholders reached agreement on 16 core outcomes across four key domains: Symptom control, Life impact, Treatment outcomes, and Communication and patient preferences. CONCLUSION: Use of this Core Outcome Set can help to address current challenges in making sense of the evidence around treatment for inoperable malignant bowel obstruction to date, and underpin a more robust future approach. Clearer communication and an honest understanding between all stakeholders will help to provide a basis for responsible decision-making in this distressing situation in clinical practice.

Understanding how shared decision-making approaches and patient aids influence patients with advanced cancer when deciding on palliative treatments and care: A realist review.

BACKGROUND: Patients with advanced incurable cancer face difficult decisions about palliative treatment options towards their end of life. However, they are often not provided with the appropriate information and support that is needed to make informed decisions. This review aimed to identify contexts and mechanisms associated with communication tools, patient decision-aids and shared decision-making (SDM) approaches that influence patient outcomes. METHODS: We used a realist review method to search for published studies of patients (adults > 18) with advanced cancer who were expected to make a decision about palliative treatment and/or supportive care in consultation with healthcare practitioners. We appraised and synthesised literature describing the contexts of (when and how) decision aids and SDM approaches are used, and how these contexts interact with mechanisms (resources and reasoning) which impact patient outcomes. Stakeholders including academics, palliative healthcare professionals (HCPs) and people with lived experience of supporting people with advanced incurable cancer contributed to identifying explanatory accounts. These accounts were documented, analysed and consolidated to contribute to the development of a programme theory. RESULTS: From the 33 included papers, we consolidated findings into 20 explanatory accounts to develop a programme theory that explains key contexts and mechanisms that influence patient and SDM. Contexts include underlying patients' and HCPs' attitudes and approaches. These need to be understood in relation to key mechanisms, including presenting information in multiple formats and providing adequate time and opportunities to prepare for and revisit decisions. Contexts influenced mechanisms which then influence the levels of patient decisional satisfaction, conflict and regret. CONCLUSIONS: Our programme theory highlights mechanisms that are important in supporting shared treatment decisions for advanced noncurative cancer. The findings are informative for developing and evaluating interventions to improve understanding and involvement in SDM for patients with advanced incurable cancer. PATIENT AND PUBLIC CONTRIBUTION: We included patient and public involvement (PPI) representatives in four stakeholder meetings. PPI helped to define the scope of the review, identify their unique experiences and perspectives, synthesise their perspectives with our review findings, make decisions about which theories we included in our programme theory and develop recommendations for policy and practice and future research.

Development of a core outcome set and identification of patient-reportable outcomes for primary brain tumour trials: protocol for the COBra study.

INTRODUCTION: Primary brain tumours, specifically gliomas, are a rare disease group. The disease and treatment negatively impacts on patients and those close to them. The high rates of physical and cognitive morbidity differ from other cancers causing reduced health-related quality of life. Glioma trials using outcomes that allow holistic analysis of treatment benefits and risks enable informed care decisions. Currently, outcome assessment in glioma trials is inconsistent, hindering evidence synthesis. A core outcome set (COS) - an agreed minimum set of outcomes to be measured and reported - may address this. International initiatives focus on defining core outcomes assessments across brain tumour types. This protocol describes the development of a COS involving UK stakeholders for use in glioma trials, applicable across glioma types, with provision to identify subsets as required. Due to stakeholder interest in data reported from the patient perspective, outcomes from the COS that can be patient-reported will be identified. METHODS AND ANALYSIS: Stage I: (1) trial registry review to identify outcomes collected in glioma trials and (2) systematic review of qualitative literature exploring glioma patient and key stakeholder research priorities. Stage II: semi-structured interviews with glioma patients and caregivers. Outcome lists will be generated from stages I and II. Stage III: study team will remove duplicate items from the outcome lists and ensure accessible terminology for inclusion in the Delphi survey. Stage IV: a two-round Delphi process whereby the outcomes will be rated by key stakeholders. Stage V: a consensus meeting where participants will finalise the COS. The study team will identify the COS outcomes that can be patient-reported. Further research is needed to match patient-reported outcomes to available measures. ETHICS AND DISSEMINATION: Ethical approval was obtained (REF SMREC 21/59, Cardiff University School of Medicine Research Ethics Committee). Study findings will be disseminated widely through conferences and journal publication. The final COS will be adopted and promoted by patient and carer groups and its use by funders encouraged. PROSPERO REGISTRATION NUMBER: CRD42021236979.

The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review.

BACKGROUND: Malignant bowel obstruction, a complication of certain advanced cancers, causes severe symptoms which profoundly affect quality of life. Clinical management remains complex, and outcome assessment is inconsistent. AIM: To identify outcomes evaluating palliative treatment for inoperable malignant bowel obstruction, as part of a four-phase study developing a core outcome set. DESIGN: The review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); PROSPERO (ID: CRD42019150648). Eligible studies included at least one subgroup with obstruction below the ligament of Treitz undergoing palliative treatment for inoperable malignant bowel obstruction. Study quality was not assessed because the review does not evaluate efficacy. DATA SOURCES: Medline, Embase, the Cochrane Database, CINAHL, PSYCinfo Caresearch, Open Grey and BASE were searched for trials and observational studies in October 2021. RESULTS: A total of 4769 studies were screened, 290 full texts retrieved and 80 (13,898 participants) included in a narrative synthesis; 343 outcomes were extracted verbatim and pooled into 90 unique terms across six domains: physiological, nutrition, life impact, resource use, mortality and survival. Prevalent outcomes included adverse events (78% of studies), survival (54%), symptom control (39%) and mortality (31%). Key individual symptoms assessed were vomiting (41% of studies), nausea (34%) and pain (33%); 19% of studies assessed quality of life. CONCLUSIONS: Assessment focuses on survival, complications and overall symptom control. There is a need for definitions of treatment 'success' that are meaningful to patients, a more consistent approach to symptom assessment, and greater consideration of how to measure wellbeing in this population.

Do palliative care patients and relatives think it would be acceptable to use Bispectral index (BIS) technology to monitor palliative care patients' levels of consciousness? A qualitative exploration with interviews and focus groups for the I-CAN-CARE research programme.

BACKGROUND: Bispectral index (BIS) monitoring uses electroencephalographic data as an indicator of patients' consciousness level. This technology might be a useful adjunct to clinical observation when titrating sedative medications for palliative care patients. However, the use of BIS in palliative care generally, and in the UK in particular, is under-researched. A key area is this technology's acceptability for palliative care service users. Ahead of trialling BIS in practice, and in order to ascertain whether such a trial would be reasonable, we conducted a study to explore UK palliative care patients' and relatives' perceptions of the technology, including whether they thought its use in palliative care practice would be acceptable. METHODS: A qualitative exploration was undertaken. Participants were recruited through a UK hospice. Focus groups and semi-structured interviews were conducted with separate groups of palliative care patients, relatives of current patients, and bereaved relatives. We explored their views on acceptability of using BIS with palliative care patients, and analysed their responses following the five key stages of the Framework method. RESULTS: We recruited 25 participants. There were ten current hospice patients in three focus groups, four relatives of current patients in one focus group and one individual interview, and eleven bereaved relatives in three focus groups and two individual interviews. Our study participants considered BIS acceptable for monitoring palliative care patients' consciousness levels, and that it might be of use in end-of-life care, provided that it was additional to (rather than a replacement of) usual care, and patients and/or family members were involved in decisions about its use. Participants also noted that BIS, while possibly obtrusive, is not invasive, with some seeing it as equivalent to wearable technological devices such as activity watches. CONCLUSIONS: Participants considered BIS technology might be of benefit to palliative care as a non-intrusive means of assisting clinical assessment and decision-making at the end of life, and concluded that it would therefore be acceptable to trial the technology with patients.

Symptom burden and lived experiences of patients, caregivers and healthcare professionals on the management of malignant bowel obstruction: A qualitative systematic review.

BACKGROUND: Malignant bowel obstruction occurs in up to 50% of people with advanced ovarian and 15% of people with gastrointestinal cancers. Evaluation and comparison of interventions to manage symptoms are hampered by inconsistent evaluations of efficacy and lack of agreed core outcomes. The patient perspective is rarely incorporated. AIM: To synthesise the qualitative data regarding patient, caregiver and healthcare professionals' views and experience of malignant bowel obstruction to inform the development of a core outcome set for the evaluation of malignant bowel obstruction. DESIGN: A qualitative systematic review was conducted, with narrative synthesis. The review protocol was registered prospectively (https://www.crd.york.ac.uk/prospero, CRD42020176393). DATA SOURCES: MEDLINE, EMBASE, CINAHL, PsycINFO and Scopus databases were searched for studies published between 2010 and 2021. Reference lists were screened for further relevant publications, and citation tracking was performed. RESULTS: Nine papers were included, reporting on seven studies which described the views and experiences of malignant bowel obstruction through the perspectives of 75 patients, 13 caregivers and 62 healthcare professionals. Themes across the papers included symptom burden, diverse experiences of interventions, impact on patient quality of life, implications and trajectory of malignant bowel obstruction, mixed experience of communication and the importance of realistic goals of care. CONCLUSION: Some of the most devastating sequelae of malignant bowel obstruction, such as pain and psychological distress, are not included routinely in its clinical or research evaluation. These data will contribute to a wider body of work to ensure the patient and caregiver perspective is recognised in the development of a core outcome set.

Development of guidelines to reduce, handle and report missing data in palliative care trials: A multi-stakeholder modified nominal group technique.

BACKGROUND: Missing data can introduce bias and reduce the power, precision and generalisability of study findings. Guidelines on how to address missing data are limited in scope and detail, and poorly implemented. AIM: To develop guidelines on how best to (i) reduce, (ii) handle and (iii) report missing data in palliative care clinical trials. DESIGN: Modified nominal group technique. SETTING/PARTICIPANTS: Patient and public research partners, palliative care clinicians, trialists, methodologists and statisticians attended a 1-day workshop, following which a multi-stakeholder development group drafted the guidelines. RESULTS: Seven main recommendations for reducing missing data, nine for handling missing data and twelve for reporting missing data were developed. The top five recommendations were: (i) train all research staff on missing data, (ii) prepare for missing data at the trial design stage, (iii) address missing data in the statistical analysis plan, (iv) collect the reasons for missing data and (v) report descriptive statistics comparing the baseline characteristics of those with missing and observed data. Reducing missing data, preparing for missing data and understanding the reasons for missing data were greater priorities for stakeholders than how to deal with missing data once they had occurred. CONCLUSION: Comprehensive guidelines on how to address missing data were developed by stakeholders involved in palliative care trials. Implementation of the guidelines will require endorsement of research funders and research journals.

Development and user-testing of a brief decision aid for aspirin as a preventive approach alongside colorectal cancer screening.

BACKGROUND: Several epidemiological and cohort studies suggest that regular low-dose aspirin use independently reduces the long-term incidence and risk of colorectal cancer deaths by approximately 20%. However, there are also risks to aspirin use, mainly gastrointestinal bleeding and haemorrhagic stroke. Making informed decisions depends on the ability to understand and weigh up benefits and risks of available options. A decision aid to support people to consider aspirin therapy alongside participation in the NHS bowel cancer screening programme may have an additional impact on colorectal cancer prevention. This study aims to develop and user-test a brief decision aid about aspirin to enable informed decision-making for colorectal screening-eligible members of the public. METHODS: We undertook a qualitative study to develop an aspirin decision aid leaflet to support bowel screening responders in deciding whether to take aspirin to reduce their risk of colorectal cancer. The iterative development process involved two focus groups with public members aged 60-74 years (n = 14) and interviews with clinicians (n = 10). Interviews (n = 11) were used to evaluate its utility for decision-making. Analysis was conducted using a framework approach. RESULTS: Overall, participants found the decision aid acceptable and useful to facilitate decision-making. They expressed a need for individualised risk information, more detail about the potential risks of aspirin, and preferred risk information presented in pictograms when offered different options. Implementation pathways were discussed, including the possibility of involving different clinicians in the process such as GPs and/or community pharmacists. A range of potentially effective timepoints for sending out the decision aid were identified. CONCLUSION: An acceptable and usable decision aid was developed to support decisions about aspirin use to prevent colorectal cancer.

Using the United Kingdom standards for public involvement to evaluate the impact of public involvement in a multinational clinical study.

BACKGROUND: The publication of the United Kingdom (UK) Standards for Public Involvement (PI) (UK Standards) in research drew a clear line in the sand regarding the importance of utilising the unique experience, skills and expertise that lay people may offer to the development, conduct and dissemination of clinical research. The UK Standards provide a benchmark which researchers should aim to achieve, yet its implementation continues to be a step wise iterative process of change management. A recent evaluation by a regional research group has suggested that our understanding of PI is enhanced through reflection on the UK Standards. We report on the utility of PI in the design, conduct and dissemination of the HIDDen study, a national, multicentre clinical study based across three UK centres. METHODS: A retrospective review of PI within the HIDDen study was conducted using field notes taken by the lead author from interactions throughout their involvement as a lay representative on the study. Key members of the HIDDen study were interviewed and data analysed to explore adherence to the UK Standards. RESULTS: There was universal support for PI across the study management group with genuine inclusivity of lay members of the committee. All six of the UK Standards were met to varying degrees. The greatest opportunities lay in 'working together' and 'support and learning'. There were challenges meeting 'governance' with evidence of participation in decision making but less evidence of opportunities in management, regulation, leadership. CONCLUSION: This study concurs with previous research supporting the utility of the Standards in the conduct and evaluation of PI in clinical research. To our knowledge this is the first multi-national study to be evaluated against the UK Standards.

The past decade has seen a genuine increase in patient and public involvement (PI) in clinical research, far beyond a symbolic presence on a trial management committee or inclusion on a grant application. The United Kingdom (UK) Standards for Public Involvement provide a useful structure to support PI throughout a study as well as defining a benchmark that can be used to improve the involvement of patients and the public in studies.The importance of reflecting on and reporting on PI in specific studies has been recognised since it contributes to a stepwise change process which will eventually lead to PI becoming normal practice for clinical research. A recent review identified a myriad of frameworks by which PI may be evaluated, risking an inconsistent approach to PI evaluation and consequently slowing down its progression.The Hospice Inpatient Deep vein thrombosis Detection study (HIDDen) was a national multicentre study to explore the prevalence and associated variables of blood clots in patients with advanced cancer when they were admitted to the specialist palliative care unit.In this paper we will be considering the HIDDen research in terms of the UK Standards for Public Involvement.

Development of a core outcome set to use in the research and assessment of malignant bowel obstruction: protocol for the RAMBO study.

INTRODUCTION: Studies regarding the management of malignant bowel obstruction (MBO) report conflicting findings. This is partly due to different outcome measures being used to evaluate severity of MBO and the response to treatments. Furthermore, current outcome measures focus mainly on measurable physiological parameters which may not correlate strongly with patient-defined quality of life. The development of core outcome sets allows a consistent approach to evaluating clinical conditions taking into consideration patient, healthcare professional and researcher viewpoints. It follows an internationally recognised standard methodology. We present a protocol for the development of a core outcome set for Research and Assessment of MBO (RAMBO). METHODS: RAMBO is a multicentre study, comprising of four phases: a systematic review to examine current scope of outcome measures associated with MBO (phase I). Interviews with patients, companions and healthcare professionals will explore priorities and preferences for care and outcomes (phase II). An expert panel meeting will collate the findings into a set of outcomes (phase III), refined by consensus through a Delphi survey with key stakeholders (phase IV). The final set of outcomes will be ratified at a consensus meeting. Each step will actively include patient partners. Thematic analysis and descriptive statistics will be used to analyse qualitative and quantitative data, respectively. ETHICS AND DISSEMINATION: Ethical approval was obtained (Wales REC 5, REF: 19/LO/1876). Study participants and relevant stakeholders will be updated with newsletters and a lay summary at the end of the study. Abstracts will be submitted to national and international conferences, result papers will be submitted to peer-reviewed, open access journals. TRIAL AND PROSPERO REGISTRATION NUMBERS: Core Outcome Measures in Effectiveness Trials (1402); Systematic Literature Review (CRD42019150648); Rapid Review (CRD42020176393).

The impacts and effectiveness of support for people bereaved through advanced illness: A systematic review and thematic synthesis.

BACKGROUND: Bereavement support is a key component of palliative care, with different types of support recommended according to need. Previous reviews have typically focused on specialised interventions and have not considered more generic forms of support, drawing on different research methodologies. AIM: To review the quantitative and qualitative evidence on the effectiveness and impact of interventions and services providing support for adults bereaved through advanced illness. DESIGN: A mixed-methods systematic review was conducted, with narrative synthesis of quantitative results and thematic synthesis of qualitative results. The review protocol is published in PROSPERO ( www.crd.york.ac.uk/prospero , CRD42016043530). DATA SOURCES: The databases MEDLINE, Embase, PsycINFO, CINAHL and Social Policy and Practice were searched from 1990 to March 2019. Studies were included which reported evaluation results of bereavement interventions, following screening by two independent researchers. Study quality was assessed using GATE checklists. RESULTS: A total of 31 studies were included, reporting on bereavement support groups, psychological and counselling interventions and a mix of other forms of support. Improvements in study outcomes were commonly reported, but the quality of the quantitative evidence was generally poor or mixed. Three main impacts were identified in the qualitative evidence, which also varied in quality: 'loss and grief resolution', 'sense of mastery and moving ahead' and 'social support'. CONCLUSION: Conclusions on effectiveness are limited by small sample sizes and heterogeneity in study populations, models of care and outcomes. The qualitative evidence suggests several cross-cutting benefits and helps explain the impact mechanisms and contextual factors that are integral to the support.

Coping and wellbeing in bereavement: two core outcomes for evaluating bereavement support in palliative care.

BACKGROUND: Bereavement support is a core part of palliative care. However, the evidence base is limited by a lack of consistency in the outcomes used to evaluate services and models of support, which makes it difficult to compare approaches. Core Outcome Sets (COS) represent the minimum that should be measured in research into specific conditions or services. The aim of this study was to use a stakeholders' perspective to develop a COS for evaluating bereavement support for adults in adult palliative care settings. METHODS: A list of outcomes relevant to bereavement support was created following a systematic review of the quantitative and qualitative literature. At an expert workshop 21 stakeholders discussed their views on the most important outcomes and compared these to and critiqued the lists constructed from the review. These lists and discussions informed a two round international DELPHI survey (n = 240) designed to reach consensus on which outcomes/outcome dimensions should be included in the COS. To prioritise and validate the items emerging from the survey, participants at a subsequent consensus day ranked the relative importance of these items (n = 23). A final feedback exercise with these consensus day participants was conducted to confirm the selection of outcomes and dimensions. RESULTS: 'Ability to cope with grief' and 'Quality of life and mental wellbeing' were selected as two core outcomes. Twenty-one different dimensions to explore when assessing these outcomes were also identified. The coping related dimensions have been categorised as: Negative and overwhelming grief; Communication and connectedness; Understanding, accepting and finding meaning in grief; Finding balance between grief and life going forwards; Accessing appropriate support. Those relating to quality of life and wellbeing have been categorised as; Participation in work and/or regular activities; Relationships and social functioning; Positive mental wellbeing and Negative mental and emotional state. CONCLUSION: This COS outlines a more consistent way forward for bereavement researchers and practitioners, whilst also orientating towards public health and resilience-based approaches to bereavement care. Further work is planned to identify and develop measures which are specific to this core outcome set, and which will facilitate the future comparability of bereavement services and interventions.