Palliative Care Clinical Studies Collaborative (PaCCSC) - Collected Works
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Item Palliative care clinical trials: how nurses are contributing to ethical, integrated and evidence based care of palliative care patients participating in clinical trials(Max Allen Healthcare, 2011) Hosie, Annmarie; Fazekas, Belinda Susan; Shelby-James, Tania Maree; Mills, Elaine; Byfieldt, Naomi; Margitanovic, Vera; Hunt, Jane; Phillips, JaneThe aim of this paper is to describe the emerging role of the palliative care clinical trials nurse in an era of evidence based practice and increasing clinical trial activity in palliative care settings across Australia. An overview of the current clinical trials work is provided with a focus on three aspects of clinical trials nursing practice which have significant implications for patients: (1) the consent process; (2) integration of clinical trials into multidisciplinary care, and (3) promotion of evidence based practice in palliative care settings. Clinical trials roles provide palliative care nurses with an opportunity to contribute to clinical research, help expand palliative care’s evidence base as well as develop their own research capabilities.Item Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study(Elsevier, 2011-04-04) Currow, David Christopher; McDonald, Christine; Oaten, Sheila; Kenny, Bernadette; Allcroft, Peter; Frith, Peter Anthony; Briffa, Michael; Johnson, Miriam J; Abernethy, Amy PickarContext Randomised controlled trials (RCTs) can answer questions of efficacy, but rarely generate a complete safety profile. Long term pharmacovigilance studies complement RCTs. Objectives Level I evidence supports short term efficacy of opioids in reducing refractory dyspnoea. This study aims to determine: the minimum effective daily dose of sustained release morphine to reduce refractory breathlessness; and whether net clinical benefits are sustained safely. Methods In a phase II dose increment study, 10mg sustained release morphine was administered daily, and increased by 10mg daily each week to a maximum of 30mg daily. The participant was withdrawn if there were unacceptable side-effects or no response to maximum dose. If participants had a 10% improvement in dyspnoea over their own baseline, they joined a long-term phase IV effectiveness/safety study at that dose. Complying with STROBE guidelines for reporting observational studies, response and side-effects are described, with demographic and clinical characteristics of responders. Results Eighty five participants (65 males, mean age 74, 59% with chronic obstructive pulmonary disease (COPD) provided >30 patient-years of data. Fifty three participants derived ≥10% benefit (35.4% improvement over baseline) giving a response rate of 62% (number needed to treat of 1.6); for 70%, this dose was 10mg/24hours. Benefit was maintained at three months for 28 (33%) people. Breathlessness was reduced significantly (p<0.001) but constipation increased (p<0.001) despite aperients. There were no severe adverse events including no respiratory depression nor hospitalisations. Conclusion Ten mg of sustained release oral morphine daily is safe in this population, and effective for most people.Item The evidence base for oxygen for chronic refractory breathlessness: issues, gaps, and a future work plan(Elsevier, 2012-09-26) Johnson, Miriam J; Abernethy, Amy Pickar; Currow, David ChristopherBreathlessness or “shortness of breath”, medically termed dyspnoea, remains a devastating problem for many people and those who care for them. As a treatment intervention, administration of opioids to relieve breathlessness is an area where progress has been made with the development of an evidence base. As evidence in support of opioids has accumulated, so has our collective understanding about trial methodology, research collaboration and infrastructure that is crucial to generate reliable research results for palliative care clinical settings. Analysis of achievements to date and what it takes to accomplish these studies provides important insights into knowledge gaps needing further research as well as practical insight into design of pharmacological and non-pharmacological intervention trials in breathlessness and palliative care. This paper presents current understanding of opioids for treating breathlessness, what is still unknown as priorities for future research and highlights methodological issues for consideration in planned studies.Item Planning phase III multi-site clinical trials in palliative care: the role of consecutive cohort audits to identify potential participant populations(Springer-Verlag, 2010) Currow, David Christopher; Shelby-James, Tania Maree; Agar, Meera Ruth; Plummer, John Lewis; Rowett, Debra Sharon; Glare, Paul; Spruyt, Odette; Hardy, JanetGoals of Work: Multiple sites enable more successful completion of adequately powered phase III studies in palliative care. Audits of the frequency and distribution of the symptoms of interest can better inform research planning by determining realistic recruitment goals for each site. The proposed studies are to improve the evidence-base for registration and subsidy applications for frequently encountered symptoms where current pharmacological interventions are being used ‘off-licence’. Methods: Six services participated in a standardized, retrospective, consecutive cohort audit of five symptoms of their inpatient populations to inform the design of double blind randomised controlled phase III studies to which each site would recruit simultaneously. The audit covered all deaths in a three month period for people who were referred to a specialist palliative care service who had at least one inpatient admission between referral and death regardless of when the person was referred to the service. The audits were based around inclusion and exclusion criteria for the proposed studies. Main Results: Of the 468 people whose medical records were reviewed, potential study participant rates varied by symptom having accounted for general and specific inclusion and exclusion criteria: pain 17.7%; delirium 5.8%; anorexia 5.1%; bowel obstruction 2.8% and cholestatic itch 0%. For those people with a symptom of interest, it was noted at the beginning of the inpatient admission more than half the time. Of all inpatients, fewer then one third would be eligible to participate in at least one study. Conclusions: These data provide a baseline estimate of potential people to approach about clinical trials in supportive care but do not account for clinician ‘gate-keeping’, lack of interest in participating nor withdrawal from the study once initiated. The data are retrospective and therefore limited by clinical documentation. The audit directly informed an increase in the number of participating sites.Item Promoting the consumer voice in palliative care: exploring the possibility of using consumer impact statements(John Wiley and Sons Ltd, 2013-08-19) McConigley, Ruth; Shelby-James, Tania Maree; Currow, David ChristopherBackground: It can be difficult to engage consumers in health decision making. This is particularly so in the area of palliative care, where consumers are very unwell and are unlikely to become involved in long term programs that promote consumer input. This paper explores the possibility of using ‘Consumer Impact Statements’ to facilitate the inclusion of the viewpoint of people at the end of life in the process of policy and decision making, particularly in the area of subsidy of pharmaceuticals used in palliative care. Search Strategy: A broad search was conducted to find information about the use of impact statements in any health field. The health literature and grey literature were searched to explore the use of Consumer Impact Statements to date. Results: No papers were found describing the use of Consumer Impact Statements in the palliative care setting. Health impact assessment is used in the areas of environmental health and community health. Impact statements are less commonly used in other areas of health, especially policy development, and no formal description of a Consumer Impact Statement was found. Discussion: There is considerable scope for developing the use of Consumer Impact Statements to promote the consumer viewpoint in health decision making, because it will allow people who are otherwise unlikely to contribute to the public debate to have their views heard by decision makers. Conclusion: The use of Consumer Impact Statements is particularly suited to palliative care, given that consumers are often otherwise unable to contribute to the public debate.Item Off-label prescribing in palliative care – a cross-sectional national survey of Palliative Medicine doctors(SAGE Publications, 2012-11-05) To, Timothy H M; Agar, Meera Ruth; Shelby-James, Tania Maree; Abernethy, Amy Pickar; Doogue, Matthew; Rowett, Debra Sharon; Ko, Danielle N; Currow, David ChristopherBackground: Regulatory bodies including the European Medicines Agency register medications (formulation, route of administration) for specific clinical indications. Once registered, prescription is at clinicians’ discretion. Off-label use is beyond the registered use. While off-label prescribing may, at times, be appropriate, efficacy and toxicity data are often lacking. Aim: The aim of this study was to document off-label use policies (including disclosure and consent) in Australian palliative care units and current practices by palliative care clinicians. Design: A national, cross-sectional survey was conducted online following an invitation letter. The survey asked clinicians their most frequent off-label medication/indication dyads and unit policies. Dyads were classified into unregistered, off-label and on-label, and for the latter, whether medications were nationally subsidised. Setting/participants: All Australian palliative medicine Fellows and advanced trainees. Results: Overall, 105 clinicians responded (53% response rate). The majority did not have policies on off-label medications, and documented consent rarely. In all, 236 medication/indication dyads for 36 medications were noted: 45 dyads (19%) were for two unregistered medications, 118 dyads (50%) were for 26 off-label medications and 73 dyads (31%) were for 12 on-label medications. Conclusions: Off-label prescribing with its clinical, legal and ethical implications is common yet poorly recognised by clinicians. A distinction needs to be made between where quality evidence exists but registration has not been updated by the pharmaceutical sponsor and the evidence has not been generated. Further research is required to quantify any iatrogenic harm from off-label prescribing in palliative care.Item The role of ondansetron in the management of cholestatic or uremic pruritis - a systematic review(2012-11) To, Timothy H M; Clark, Katherine; Lam, Lawrence; Shelby-James, Tania Maree; Currow, David ChristopherPruritus associated with hepatic or renal failure can be a troublesome symptom, refractory to treatment, associated with significant physical and emotional distress, and reduction in quality of life for patients already burdened with chronic disease. Serotonin has been implicated as a possible pathological mediator, and therefore 5HT3 antagonists have been suggested as a possible therapeutic intervention. Objectives This review of the literature systematically explores the role of ondansetron in the management of cholestatic or uraemic pruritus. Methods Electronic databases were systematically searched for randomized controlled trials (RCTs) examining the role of ondansetron in cholestatic or uraemic pruritus between 1966 and 2008. Results Five RCTs were included in this systematic review: three for cholestatic pruritus, and two for uraemic pruritus. All trials examined ondansetron versus placebo, however with differing treatment protocols. Overall, three studies showed no benefit to ondansetron over placebo, however two studies in cholestatic pruritus showed small reductions in pruritus with questionable clinical significance. Conclusion Ondansetron was demonstrated to have negligible effect on cholestatic or uraemic pruritus on the basis of a limited number of studies.Item How should we conduct and interpret phase III clinical trials in palliative care?(Elsevier, 2010-01) Abernethy, Amy Pickar; Clark, Katherine; Currow, David ChristopherThe article by Wildiers et al.1 raises some challenges in terms of ethical approaches to phase III end-of-life studies and their interpretation. Although the authors should be commended for undertaking a large, multisite, randomized, controlled trial in palliative care, there are fundamental questions that do need to be addressed before the first steps can be taken to adopt the study's findings into practice.Item Measuring impacts of value to patients is crucial when evaluating palliative care(Elsevier, 2009-06) McCaffrey, Nicola; Currow, David Christopher; Eckermann, Simon DouglasThe inclusion of preparation for death and managing affairs in the end-of-life instrument designed by Borreani et al.1 to elicit preferences about dying is commendable. Of note, few quality-of-life (QOL) measurement tools contain or adequately assess this patient-valued domain. Given the importance that patients place on these issues, it is possible that evaluations of palliative health care interventions, including comparative effectiveness and cost-effectiveness analyses, could easily misinterpret the net benefit of such interventions without inclusion of this domain as an outcome measure. Better assessment methods that incorporate preparation for death and managing affairs are needed.Item Promoting patient centred palliative care through case conferencing(Royal Australian College of General Practitioners, 2007-11) Shelby-James, Tania Maree; Currow, David Christopher; Phillips, Paddy Andrew; Williams, Helena; Abernethy, Amy PickarBACKGROUND What are the characteristics of case conferences between general practitioners and specialised palliative care services (SPCS)? METHODS Study participants were adults (N=461) with pain in the preceding 3 months who were referred to a SPCS and their GPs (N=230). Patients were randomised to case conferences or routine care by SPCS. RESULTS One hundred and sixty-seven conferences were held; 46 patients withdrew and 142 died before the conference could be conducted. Medicare payment was requested for 72 (43%) conferences. Median time from randomisation to case conference was 52 days (SD: 55), and from case conference to death/end of study was 79 days (SD: 166). Twenty-five percent of conferences had over three health professionals participant; patients and/or their caregivers participated in 91%. Average conference duration was 39 minutes (SD: 13). Mean conference length did not increase when more health professionals were present (3 vs. >3, 39 [SD: 14] vs. 42 [SD 11] minutes, p=0.274), nor when patients/caregivers were present (present vs. absent, 39 [SD: 13] vs. 44 [SD: 14] minutes, p=0.159). DISCUSSION Case conferencing involving SPCS, the GP, other health professionals and the patient can be an efficient part of routine care.Item Evolution of palliative care in Australia 1973-2013(Cancer Council Australia, 2013-03) Currow, David Christopher; Phillips, JaneIn parallel with the rapid development of oncology in Australia, palliative and supportive care has evolved rapidly. The sponsorship for such development was largely generated by oncology services in response to unmet needs that were encountered daily. Development of state, territory and national strategies has mirrored the professional development in service delivery, education (of existing practitioners and tomorrow’s clinicians) and research. More recently, national programs are delivering better outcomes for palliative care patients and their families, world-leading clinical research, improved access to essential medications in the community and the ability to access quality evidence to inform practice and policy. These initiatives provide a valuable foundation for continuing to improve access to high quality clinical care wherever people live.Item Quality use of medicines for palliative care(Cancer Council Australia, 2007-03) Hardy, JanetMany of the drugs commonly used in palliative care are not listed on the Pharmaceutical Benefits Scheme in Australia and are therefore not freely available to patients outside the acute hospital system. In an attempt to address the inequity faced by patients being cared for in the community or hospices, the Palliative Care Medicines Working Group was established by the Australian Government. This has resulted in a separate palliative section within the Schedule of Pharmaceutical Benefits Scheme which allows for authority prescribing of a number of medications that may be required by a palliative care patient. This paper discusses the medications currently on this listing, the processes by which they were selected and the ongoing efforts to broaden access to required medications.Item Anti-cholinergic load, health care utilization, and survival in people with advanced cancer: a pilot study(Mary Ann Liebert, Inc., 2010-07-02) Agar, Meera Ruth; To, Timothy H M; Plummer, John Lewis; Abernethy, Amy Pickar; Currow, David ChristopherIntroduction: Anti-cholinergic medications have been associated with increased risks of cognitive impairment, premature mortality and increased risk of hospitalisation. Anti-cholinergic load associated with medication increases as death approaches in those with advanced cancer, yet little is known about associated adverse outcomes in this setting. Methods: A substudy of 112 participants in a randomised control trial who had cancer and an Australia modified Karnofsky Performance Scale (AKPS) score (AKPS) of 60 or above, explored survival and health service utilisation; with anti-cholinergic load calculated using the Clinician Rated Anti-cholinergic Scale (modified version) longitudinally to death. A standardised starting point for prospectively calculating survival was an AKPS of 60 or above. Results: Baseline entry to the sub-study was a mean 62 ± 81 days (median 37, range 1–588) days before death (survival), with mean of 4.8 (median 3, SD 4.18, range 1 – 24) study assessments in this time period. Participants spent 22% of time as an inpatient. There was no significant association between anti-cholinergic score and time spent as an inpatient (adjusted for survival time) (p = 0.94); or survival time. Discussion: No association between anti-cholinergic load and survival or time spent as an inpatient was seen. Future studies need to include cognitively impaired populations where the risks of symptomatic deterioration may be more substantial.Item Current approaches to diagnosing and managing constipation in advanced cancer and palliative care(Mary Ann Liebert, Inc., 2010-04-12) Clark, Katherine; Urban, Kat; Currow, David ChristopherConstipation is common in advanced cancer. Despite this, clinicians' understanding of the underlying changes affecting the colon and the rest of the gastrointestinal tract are limited. Two case histories are used to illustrate the problems encountered when the current approaches to diagnosing and managing altered bowel habits are unsuccessful. An alternative paradigm in which to consider the problems of constipation encountered by some people with advanced cancer is proposed.Item A strategy to advance the evidence base in palliative medicine: formation of a palliative care research cooperative group(Mary Ann Liebert, Inc., 2010-11-24) Abernethy, Amy Pickar; Aziz, Noreen M; Basch, Ethan; Bull, Janet; Cleeland, Charles S; Currow, David Christopher; Fairclough, Diane; Hanson, Laura; Hauser, Joshua; Ko, Danielle N; Lloyd, Linda; Morrison, R Sean; Otis-Green, Shirley; Pantilat, Steve; Portenoy, Russell K; Ritchie, Christine; Rocker, Graeme; Wheeler, Jane L; Zafar, S Yousuf; Kutner, Jean SBackground: Palliative medicine has made rapid progress in establishing its scientific and clinical legitimacy, yet the evidence base to support clinical practice remains deficient in both the quantity and quality of published studies. Historically, the conduct of research in palliative care populations has been impeded by multiple barriers including health care system fragmentation, small number and size of potential sites for recruitment, vulnerability of the population, perceptions of inappropriateness, ethical concerns, and gate-keeping. Methods: A group of experienced investigators with backgrounds in palliative care research convened to consider developing a research cooperative group as a mechanism for generating high-quality evidence on prioritized, clinically relevant topics in palliative care. Results: The resulting Palliative Care Research Cooperative (PCRC) agreed on a set of core principles: active, interdisciplinary membership; commitment to shared research purposes; heterogeneity of participating sites; development of research capacity in participating sites; standardization of methodologies, such as consenting and data collection/management; agile response to research requests from government, industry, and investigators; focus on translation; education and training of future palliative care researchers; actionable results that can inform clinical practice and policy. Consensus was achieved on a first collaborative study, a randomized clinical trial of statin discontinuation versus continuation in patients with a prognosis of less than 6 months who are taking statins for primary or secondary prevention. This article describes the formation of the PCRC, highlighting processes and decisions taken to optimize the cooperative group's success.Item Adverse events in hospice and palliative care: a pilot study to determine feasibility of collection and baseline rates(Mary Ann Liebert, Inc., 2011-01-19) Currow, David Christopher; Agar, Meera Ruth; To, Timothy H M; Rowett, Debra Sharon; Greene, Aine; Abernethy, Amy PickarBackground: Continuous quality improvement is fundamental in all health care, including hospice and palliative care. Identifying and systematically reducing symptomatic adverse events is limited in hospice and palliative care because these events are mostly attributed to disease progression. Objectives: The aim of this study was to assess the feasibility of symptomatic adverse events in hospice and palliative care and assessing their incidence. Methods: A retrospective, consecutive cohort of notes from a specialist palliative care inpatient service was surveyed by a clinical nurse consultant for symptomatic adverse events: falls, confusion, decreased consciousness, hypo- and hyperglycaemia, urinary retention, and hypotension. Demographic and clinical factors were explored for people at higher risk. Results: Data were available on the most recent admissions of 65 people, generating >900 inpatient days. Fifty people (78%) had events precipitating admission, of whom 31 (62%) had at least one further event during admission. Eleven of 15 people who were admitted without an event experienced at least one during their admissions. Only 4 did not have an adverse event. During their stay, there were 0.13 (standard deviation [SD] = 0.19) events per patient per day. No drug-drug or drug-host events were noted. No clinical or demographic factors predicted groups at higher risk. Conclusions: This pilot highlights the feasibility of collecting, and ubiquity of, symptomatic adverse events, and forms a baseline against which future interventions to decrease the frequency or intensity can be measured. Given the frailty of hospice and palliative patients, any adverse event is likely to accelerate irreversibly their systemic decline.Item The role of benzodiazepines in breathlessness: a single site, open label pilot of sustained release morphine together with clonazepam(Mary Ann Liebert, Inc., 2013-04-18) Allcroft, Peter; Margitanovic, Vera; Greene, Aine; Agar, Meera Ruth; Clark, Katherine; Abernethy, Amy Pickar; Currow, David ChristopherBackground: Breathlessness at rest or on minimal exertion despite optimal treatment of underlying cause(s) is distressing and prevalent. Opioids can reduce the intensity of chronic refractory breathlessness and an anxiolytic may be of benefit. This pilot aimed to determine the safety and feasibility of conducting a phase III study on the intensity of breathlessness by adding regular benzodiazepine to low-dose opioid. Methods: This is a single site, open label phase II study of the addition of regular clonazepam 0.5 mg nocte orally to KapanolR 10 mg (sustained release morphine sulphate) orally mane together with docusate/sennosides in people with modified Medical Research Council Scale ≥2. Breathlessness intensity on day four was the efficacy outcome. Participants could extend for another 10 days if they achieved >15% reduction over their own baseline breathlessness intensity. Results: Eleven people had trial medication (eight males, median age 78 years (68 to 89); all had COPD; median Karnofsky 70 (50 to 80); six were on long-term home oxygen. Ten people completed day four. One person withdrew because of unsteadiness on day four. Five participants reached the 15% reduction, but only three went on to the extension study, all completing without toxicity. Conclusion: This study was safe, feasible and there appears to be a group who derive benefits comparable to titrated opioids. Given the widespread use of benzodiazepines for the symptomatic treatment of chronic refractory breathlessness and its poor evidence base, there is justification for a definitive phase III study.Item A pilot study to assess the feasibility of measuring the prevalence of slow colon transit or evacuation disorder in palliative care(Mary Ann Liebert, Inc., 2013-04-27) Clark, Katherine; Currow, David ChristopherContext: Constipation is prevalent in palliative care. Whilst numerous factors contribute to this problem, opioid analgesia remains the most quoted aetiology. However, in gastroenterology, constipation is classified as a problem of prolonged transit times of colonic contents, impaired function of the structures of defecation or both. Little work in palliative care has used these assessments. Aims: The report aims to describe the feasibility of assessing the colon transit times and pelvic floor structures of constipated palliative care patients and to report the results of a pilot study of 10 people who underwent these investigations. Methods: Colon transit times were measured with a combination of orally administered radio-opaque markers and a single plain radiograph of the abdomen at day 5. Anal manometry plus rectal balloon expulsion was used to assess the pelvic floor. The results of the investigations were used to allocate people to one of four constipation subcategories: 1). slow colonic transit; 2) evacuation disorders; 3) mixed disorder or 4) normal transit. Results: Two people had slow transit only, 2 people had evacuation disorders only and 5 had both. Only person had neither problem. The investigations were well tolerated and took a small amount of people's time. Conclusion: These pilot data strongly support the feasibility of undertaking comprehensive assessments of the colon and pelvic floor in palliative care patients with the results, although preliminary, highlighting the complexity of the problem of constipation. The results of this work underpin the need to progress to a much larger study.Item Informed consent in palliative care clinical trials: challenging but possible(Mary Ann Liebert, Inc., 2013-04-30) Agar, Meera Ruth; Ko, Danielle N; Sheehan, Caitlin; Chapman, Michael; Currow, David ChristopherObtaining informed consent is a key protection that should be afforded universally to people using health services and the basis around which any participation in clinical trials is built. Randomized controlled effectiveness studies are necessary to answer key questions in hospice and palliative care, in order to help systematically improve the quality of care. In order to be properly generalizable, such trials need to have broad inclusion criteria to reflect the population most likely to be affected by the condition. The inclusion of patients who are seriously ill, and therefore potentially vulnerable, requires careful exploration of ethical and legal principles that underpin informed consent. Specific challenges in obtaining informed consent for randomised clinical trials (RCTs) in clinically unstable populations such as hospice and palliative care include higher rates of people with impaired cognitive capacity as well as interventional studies in clinical situations which may present as a sudden change in condition. None of these challenges is unique to hospice and palliative care research, but the combination and frequency with which they are encountered require systematic and considered solutions. This article outlines five different ethically valid consent approaches and discusses their applicability to hospice and palliative care research trials. These include: consent by the patient (at the time of enrolment, in advance of the study, or delayed until after the study has commenced); a proxy (or legally authorised representative); or a consent waiver. Increased use of the less traditional modes of informed consent may lead to greater participation rates in hospice and palliative care trials, thereby improving the evidence base more rapidly in part by better reflecting the population served and hence improving generalizability.Item Letter to the Editor re "Four essential drugs needed for quality care of the dying: a Delphi-study based international expert consensus opinion"(Mary Ann Liebert, Inc., 2013-06-21) Clark, Katherine; Sheehan, Caitlin; Currow, David ChristopherHigh-quality patient care can be defined as an approach that minimizes harm whilst aligning with people's expectations. Dying people and their relatives have articulated that they expect health care providers to manage physical and psychological symptoms well, with expectations even higher when such care is delivered by specialist services. Despite excellent intentions, palliative care clinicians and researchers have done little to improve systematically the evidence base for prescribing when people are actually dying. Few data exist to inform clinicians' understanding of how people's actual experiences align with their articulated wishes. Symptoms are managed based on relatives' and staff's assumptions of the experience of the dying person, with a “good death” often being seen as quiet and calm. Achieving this often requires sedation, for which the dying person will very rarely have given consent. This requires consideration, especially when evidence suggests people facing death will forgo symptom control to remain as alert and interactive for as long as possible. We ignore patients' wishes at our peril if we are to be truly patient centered.