The feasibility of a single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease.

BACKGROUND: The Breathlessness Intervention Service is a novel service for patients with intractable breathlessness regardless of aetiology. It is being evaluated using the Medical Research Council's framework for the evaluation of complex interventions. This paper describes the feasibility results of Phase II: a single-blinded fast-track pragmatic randomised controlled trial. METHODS: A single-blinded fast-track pragmatic randomised controlled trial was conducted for patients with chronic obstructive pulmonary disease referred to the service. Patients were randomised to either receive the intervention immediately for an eight-week period, or receive the intervention after an eight-week period on a waiting list during which time they received standard care. Outcomes examined included: response rates to the trial; response rates to the individual questionnaires and items; comments relating to the trial functioning made during interviews with patients, carers, referrers and service providers; and, researcher fieldwork notes. RESULTS: 16 of the 20 eligible patients agreed to participate in a recruitment visit (16/20); 14 respondents went on to complete a recruitment visit/baseline interview. The majority of those who completed a recruitment visit/baseline interview completed the RCT protocol (13/14); 12 of their carers were recruited and completed the protocol. An unblinding rate of 6/25 respondents (patients and carers) was identified. Missing data were minimal and only one patient was lost to follow up. The fast-track trial methodology proved feasible and acceptable. Two of the baseline/outcome measures proved unsuitable: the WHO performance scale and the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW). CONCLUSION: This study adds to the evidence that fast-track randomised controlled trials are feasible and acceptable in evaluations of palliative care interventions for patients with non-malignant conditions. Reasonable response rates and low attrition rates were achieved. Further, with adequate preparation of the research and randomisation teams, clinicians, and responders, and effective liaison with the clinicians, single-blinding proved possible. Methods were identified to reduce unblinding through careful attention to the type of data collected at unblinded measurement points; the content of interviews should be carefully considered when designing blinded-trial protocols. TRIAL REGISTRATION: Clinical Trials.gov NCT00711438.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Study protocol: Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease.

BACKGROUND: Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals. The Breathlessness Intervention Service (BIS) seeks to improve the care of breathless patients with advanced disease (regardless of cause) through the use of evidence-based practice and working with other healthcare providers. BIS delivers a complex intervention (of non-pharmacological and pharmacological treatments) via a multi-professional team. BIS is being continuously developed and its impact evaluated using the MRC's framework for complex interventions (PreClinical, Phase I and Phase II completed). This paper presents the protocol for Phase III. METHODS/DESIGN: Phase III comprises a pragmatic, fast-track, single-blind randomised controlled trial of BIS versus standard care. Due to differing disease trajectories, the service uses two broad service models: one for patients with malignant disease (intervention delivered over two weeks) and one for patients with non-malignant disease (intervention delivered over four weeks). The Phase III trial therefore consists of two sub-protocols: one for patients with malignant conditions (four week protocol) and one for patients with non-malignant conditions (eight week protocol). Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol. Qualitative interviews are conducted with referring and non-referring health care professionals (malignant disease protocol only). The primary outcome measure is 'patient distress due to breathlessness' measured on a numerical rating scale (0-10). The trial includes economic evaluation. Analysis will be on an intention to treat basis. DISCUSSION: This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast track methodology and single-blinding. The results will provide evidence of the clinical and cost-effectiveness of the service, informing its longer term development and implementation of the model in other centres nationally and internationally. It adds to methodological developments in palliative care research where complex interventions are common but evidence sparse. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00678405ISRCTN: ISRCTN04119516.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Is a specialist breathlessness service more effective and cost-effective for patients with advanced cancer and their carers than standard care? Findings of a mixed-method randomised controlled trial.

BACKGROUND: Breathlessness is common in advanced cancer. The Breathlessness Intervention Service (BIS) is a multi-disciplinary complex intervention theoretically underpinned by a palliative care approach, utilising evidence-based non-pharmacological and pharmacological interventions to support patients with advanced disease. We sought to establish whether BIS was more effective, and cost-effective, for patients with advanced cancer and their carers than standard care. METHODS: A single-centre Phase III fast-track single-blind mixed-method randomised controlled trial (RCT) of BIS versus standard care was conducted. Participants were randomised to one of two groups (randomly permuted blocks). A total of 67 patients referred to BIS were randomised (intervention arm n = 35; control arm n = 32 received BIS after a two-week wait); 54 completed to the key outcome measurement. The primary outcome measure was a 0 to 10 numerical rating scale for patient distress due to breathlessness at two-weeks. Secondary outcomes were evaluated using the Chronic Respiratory Questionnaire, Hospital Anxiety and Depression Scale, Client Services Receipt Inventory, EQ-5D and topic-guided interviews. RESULTS: BIS reduced patient distress due to breathlessness (primary outcome: -1.29; 95% CI -2.57 to -0.005; P = 0.049) significantly more than the control group; 94% of respondents reported a positive impact (51/53). BIS reduced fear and worry, and increased confidence in managing breathlessness. Patients and carers consistently identified specific and repeatable aspects of the BIS model and interventions that helped. How interventions were delivered was important. BIS legitimised breathlessness and increased knowledge whilst making patients and carers feel 'not alone'. BIS had a 66% likelihood of better outcomes in terms of reduced distress due to breathlessness at lower health/social care costs than standard care (81% with informal care costs included). CONCLUSIONS: BIS appears to be more effective and cost-effective in advanced cancer than standard care. TRIAL REGISTRATION: RCT registration at ClinicalTrials.gov NCT00678405 (May 2008) and Current Controlled Trials ISRCTN04119516 (December 2008).The study was supported by the following funders: NIHR Research for Patient Benefit (for Phase III RCT funding); Macmillan Cancer Support (MF’s post-doctoral fellowship); The Gatsby Foundation for the initial funding of BIS; and AT Prevost was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The study sponsor was CUHNFT.This is the final published version. It first appeared at http://www.biomedcentral.com/1741-7015/12/194

Does the carer support needs assessment tool cover the established support needs of carers of patients with chronic obstructive pulmonary disease? A systematic literature search and narrative review

Background: Informal carers play a key supportive role for patients with chronic obstructive pulmonary disease. However, caring can have a considerable impact on health and wellbeing. Carers may have unidentified support needs that could be a target for intervention. Literature on the support needs of informal carers has not been fully synthesised, and our knowledge of the comprehensiveness of the Carer Support Needs Assessment Tool for these individuals is limited. Aim: To explore whether the Carer Support Needs Assessment Tool covers the support needs of carers of patients with chronic obstructive pulmonary disease identified in published literature. Design: English language studies were identified against predetermined inclusion/exclusion criteria through database searching. Further studies were identified through searching reference lists and citations of included papers. Papers were critically appraised and data extracted and synthesised by two reviewers. Identified needs were mapped to Carer Support Needs Assessment Tool questions. Data sources: MEDLINE, CINAHL, EMBASE, CDSR, ASSIA, PsycINFO and Scopus databases (Jan 1997–Dec 2017). Results: Twenty-four studies were included. Results suggest that carers have support needs in a range of domains including physical, social, psychological and spiritual. Many of these needs are unmet. Particular areas of concern relate to prolonged social isolation, accessing services, emotional support and information needs. Findings also suggest amendment of the Carer Support Needs Assessment Tool may be required relating to difficulties within relationship management. Conclusion: Evidence suggests that carers of patients with chronic obstructive pulmonary disease would benefit from identification and response to their support needs by healthcare professionals but to enable this, the Carer Support Needs Assessment Tool requires an additional question. Future planned work will explore this with carers of patients with chronic obstructive pulmonary disease

The TEAM Approach to Improving Oncology Outcomes by Incorporating Palliative Care in Practice

Palliative care (PC) concurrent with usual oncology care is now the standard of care that is recommended for any patient with advanced cancer to begin within 8 weeks of diagnosis on the basis of evidence-driven national clinical practice guidelines; however, there are not enough interdisciplinary palliative care teams to provide such care. How and what can an oncology office incorporate into usual care, borrowing the tools used in PC randomized clinical trials (RCTs), to improve care for patients and their caregivers? We reviewed the multiple RCTs for common practical elements and identified methods and techniques that oncologists can use to deliver some parts of concurrent interdisciplinary PC. We recommend the standardized assessment of patient-reported outcomes, including the evaluation of symptoms with such tools as the Edmonton or Memorial Symptom Assessment Scales, spirituality with the FICA Spiritual History Tool or similar questions, and psychosocial distress with the Distress Thermometer. All patients should be assessed for how they prefer to receive information, their current understanding of their situation, and if they have considered some advance care planning. Approximately 1 hour of additional time with the patient is required each month. If the oncologist does not have established ties with spiritual care and social work, he or she should establish these relationships for counseling as required. Caregivers should be asked about coping and support needs. Oncologists can adapt PC techniques to achieve results that are similar to those in the RCTs of PC plus usual care compared with usual care alone. This is comparable to using data from RCTs of trastuzamab or placebo, adopting what was used in the RCTs without modification or dilution

Strategies designed to help healthcare professionals to recruit participants to research studies.

BACKGROUND: Identifying and approaching eligible participants for recruitment to research studies usually relies on healthcare professionals. This process is sometimes hampered by deliberate or inadvertent gatekeeping that can introduce bias into patient selection. OBJECTIVES: Our primary objective was to identify and assess the effect of strategies designed to help healthcare professionals to recruit participants to research studies. SEARCH METHODS: We performed searches on 5 January 2015 in the following electronic databases: Cochrane Methodology Register, CENTRAL, MEDLINE, EMBASE, CINAHL, British Nursing Index, PsycINFO, ASSIA and Web of Science (SSCI, SCI-EXPANDED) from 1985 onwards. We checked the reference lists of all included studies and relevant review articles and did citation tracking through Web of Science for all included studies. SELECTION CRITERIA: We selected all studies that evaluated a strategy to identify and recruit participants for research via healthcare professionals and provided pre-post comparison data on recruitment rates. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results for potential eligibility, read full papers, applied the selection criteria and extracted data. We calculated risk ratios for each study to indicate the effect of each strategy. MAIN RESULTS: Eleven studies met our eligibility criteria and all were at medium or high risk of bias. Only five studies gave the total number of participants (totalling 7372 participants). Three studies used a randomised design, with the others using pre-post comparisons. Several different strategies were investigated. Four studies examined the impact of additional visits or information for the study site, with no increases in recruitment demonstrated. Increased recruitment rates were reported in two studies that used a dedicated clinical recruiter, and five studies that introduced an automated alert system for identifying eligible participants. The studies were embedded into trials evaluating care in oncology mainly but also in emergency departments, diabetes and lower back pain. AUTHORS' CONCLUSIONS: There is no strong evidence for any single strategy to help healthcare professionals to recruit participants in research studies. Additional visits or information did not appear to increase recruitment by healthcare professionals. The most promising strategies appear to be those with a dedicated resource (e.g. a clinical recruiter or automated alert system) for identifying suitable participants that reduced the demand on healthcare professionals, but these were assessed in studies at high risk of bias.We would like to acknowledge the support of the Methodology theme of theCancer ExperiencesCollaborative (CECo), who have supported this review.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/14651858.MR000036.pub2/abstract

Implementation of a complex intervention to improve care for patients whose situations are clinically uncertain in hospital settings: A multi-method study using normalisation process theory

Purpose: To examine the use of Normalisation Process Theory (NPT) to establish if, and in what ways, the AMBER care bundle can be successfully normalised into acute hospital practice, and to identify necessary modifications to optimise its implementation. Method: Multi-method process evaluation embedded within a mixed-method feasibility cluster randomised controlled trial in two district general hospitals in England. Data were collected using (i) focus groups with health professionals (HPs), (ii) semi-structured interviews with patients and/or carers, (iii) non-participant observations of multi-disciplinary team meetings and (iv) patient clinical note review. Thematic analysis and descriptive statistics, with interpretation guided by NPT components (coherence; cognitive participation; collective action; reflexive monitoring). Data triangulated across sources. Results: Two focus groups (26 HPs), nine non-participant observations, 12 interviews (two patients, 10 relatives), 29 clinical note reviews were conducted. While coherence was evident, with HPs recognising the value of the AMBER care bundle, cognitive participation and collective action presented challenges. Specifically: (1) HPs were unable and unwilling to operationalise the concept of ‘risk of dying’ intervention eligibility criteria (2) integration relied on a ‘champion’ to drive participation and ensure sustainability; and (3) differing skills and confidence led to variable engagement with difficult conversations with patients and families about, for example, nearness to end of life. Opportunities for reflexive monitoring were not routinely embedded within the intervention. Reflections on the use of the AMBER care bundle from HPs and patients and families, including recommended modifications became evident through this NPT-driven analysis. Conclusion: To be successfully normalised, new clinical practices, such as the AMBER care bundle, must be studied within the wider context in which they operate. NPT can be used to the aid identification of practical strategies to assist in normalisation of complex interventions where the focus of care is on clinical uncertainty in acute hospital settings

Predicting response to holistic breathlessness services: a pooled analysis of trial data

Background: Holistic breathlessness services have been developed for people with advanced disease and chronic breathlessness, leading to improved psychological aspects of breathlessness and health. The extent to which patient characteristics influence outcomes is unclear. Aim: To identify patient characteristics predicting outcomes of mastery and distress around breathlessness following holistic breathlessness services. Design: Secondary analysis of pooled individual patient data from three clinical trials. Our primary analysis assessed predictors of clinically important improvements in Chronic Respiratory Questionnaire mastery scores (+0.5 point), and our secondary analysis predictors of improvements in Numerical Rating Scale distress due to breathlessness (-1 point). Variables significantly related to improvement in univariate models were considered in separate backwards stepwise logistic regression models. Participants: The dataset comprised 259 participants (118 female; mean (standard deviation) age 69.2(10.6) years) with primary diagnoses of chronic obstructive pulmonary disease (49.8%), cancer (34.7%) and interstitial lung disease (10.4%).Results: Controlling for age, sex, and trial, baseline mastery remained the only significant independent predictor of improvement in mastery (odds ratio 0.57, 95% confidence intervals 0.43 to 0.74; p <0001), and baseline distress remained the only significant predictor of improvement in distress (odds ratio 1.64; 95% confidence intervals 1.35 to 2.03; p<001). Baseline lung function, breathlessness severity, health status, mild anxiety and depression, and diagnosis did not predict outcomes. Conclusions: Outcomes of mastery and distress following holistic breathlessness services are influenced by baseline scores for these variables, and not by diagnosis, lung function, or health status. Stratifying patients by levels of mastery and/or distress appears appropriate for clinical trials and services

Holistic services for people with advanced disease and chronic or refractory breathlessness: a mixed-methods evidence synthesis

Background : Breathlessness is a common and distressing symptom of many advanced diseases, affecting around 2 million people in the UK. Breathlessness increases with disease progression and often becomes chronic or refractory. Breathlessness-triggered services that integrate holistic assessment and specialist palliative care input as part of a multiprofessional approach have been developed for this group, offering tailored interventions to support self-management and reduce distress. Objectives : The aim was to synthesise evidence on holistic breathlessness services for people with advanced disease and chronic or refractory breathlessness. The objectives were to describe the structure, organisation and delivery of services, determine clinical effectiveness, cost-effectiveness and acceptability, identify predictors of treatment response, and elicit stakeholders’ evidence-based priorities for clinical practice, policy and research. Design : The mixed-methods evidence synthesis comprised three components: (1) a systematic review to determine the clinical effectiveness, cost-effectiveness and acceptability of holistic breathlessness services; (2) a secondary analysis of pooled individual data from three trials to determine predictors of clinical response; and (3) a transparent expert consultation (TEC), comprising a stakeholder workshop and an online consensus survey, to identify stakeholders’ priorities. Results : Thirty-seven papers reporting on 18 holistic breathlessness services were included in the systematic review. Most studies enrolled people with thoracic cancer, were delivered over 4–6 weeks, and included breathing training, relaxation techniques and psychological support. Meta-analysis demonstrated significant reductions in the Numeric Rating Scale (NRS) distress due to breathlessness, significant reductions in the Hospital Anxiety and Depressions Scale (HADS) depression scores, and non-significant reductions in the Chronic Respiratory Disease Questionnaire (CRQ) mastery and HADS anxiety, favouring the intervention. Recipients valued education, self-management interventions, and expertise of the staff in breathlessness and person-centred care. Evidence for cost-effectiveness was limited and inconclusive. The responder analysis (n = 259) revealed baseline CRQ mastery and NRS distress to be strong predictors of the response to breathlessness services assessed by these same measures, and no significant influence from baseline breathlessness intensity, patient diagnosis, lung function, health status, anxiety or depression. The TEC elicited 34 priorities from stakeholders. Seven priorities received high agreement and consensus, reflecting stakeholders’ (n = 74) views that services should be person-centred and multiprofessional, share their breathlessness management skills with others, and recognise the roles and support needs of informal carers.  Limitations : The evidence synthesis draws predominantly from UK services and may not be generalisable to other settings. Some meta-analyses were restricted by reporting biases and statistical heterogeneity.  Conclusions : Despite heterogeneity in composition and delivery, holistic breathlessness services are highly valued by recipients and can lead to significant improvements in the distress caused by breathlessness and depression. Outcomes of improved mastery and reduced distress caused by breathlessness are not influenced by patient diagnosis, lung function or health status. Stakeholders highlighted the need for improved access to person-centred, multi professional breathlessness services and support for informal carers.  Future work : Our research suggests that key therapeutic components of holistic breathlessness services be considered in clinical practice and models of delivery and educational strategies to address stakeholders’ priorities tested