We consider uncertainty in relation to clinical trials for terminal non-small cell lung cancer, which is an aggressive and difficult to treat form of cancer. Using grounded theory to analyse 85 clinical interactions between doctors, patients and family members, we argue that uncertainty is a major source of tension for terminally ill patients, with individuals confronting a choice between transitioning to palliative care or volunteering for an experimental/trial medication that might postpone death. Regardless of their efficacy, patients must also consider how such experimental treatments might impact their quality-of-life. We argue that clinical trials produce uncertainty through (i) discussions about the efficacy of clinical trials; (ii) the physiological consequences of clinical trial medications; and (iii) the impact clinical trials have on patient's prognostic understanding of their terminal cancer. Accordingly, while study participants encounter high prognostic certainty (i.e. they have a fatal cancer), they nonetheless experience considerable uncertainty in relation to their participation in clinical trials.
OBJECTIVES: In non-gynecologic cancers, clinical trial participation has been associated with aggressive care at the end of life. The objective of this investigation was to examine how trial participation affects end of life outcomes in patients with ovarian cancer.
METHODS: In a retrospective review of women diagnosed with ovarian cancer at our institution between January 2010 and December 2015, we collected variables identified by the National Quality Forum as measures of aggressive end of life care including chemotherapy in the last 14 days of life, intensive care unit (ICU) admission in the last 30 days of life, or death in the acute care setting. Trials investigating medications but not surgical interventions were included. The primary outcome of this study was the association between trial participation and the National Quality Forum measures of aggressive end of life care in ovarian cancer decedents. Data were analyzed with univariable and multivariable parametric and non-parametric testing, and time to event outcomes were analyzed using the Kaplan-Meier method and Cox's proportional hazard models.
RESULTS: Among 391 women treated for ovarian cancer, 62 patients (16%) participated in a clinical trial. Patients enrolled in clinical trials were more likely to have chemotherapy administered within 14 days of death; however, no association was found with other metrics of aggressive care at the end of life including the initiation of a new chemotherapy regimen in the last 30 days of life, ICU admissions, and death in an acute care setting. Among patients with recurrent ovarian cancer, median overall survival for trial participants was 57 months compared with only 31 months in non-trial participants (p<0.001).
CONCLUSIONS: In patients with ovarian cancer, clinical trial enrollment is associated with chemotherapy administration within 14 days of death, but not other measures of aggressive care at the end of life. Given the importance of clinical trial participation in improving care for women with ovarian cancer, this study suggests that concerns regarding aggressive care prior to death should not limit clinical trial participation.
Background: There is considerable interest in the use of cannabinoids for symptom control in palliative care, but there is little high-quality evidence to guide clinical practice.
Objectives: Assess the feasibility of using global symptom burden measures to assess response to medicinal cannabis, to determine median tolerated doses of cannabidiol (CBD) and tetrahydrocannabinol (THC), and to document adverse events (AEs).
Design: Prospective two-arm open-label pilot trial of escalating doses of CBD and THC oil.
Setting/Subjects: Participants had advanced cancer and cancer-related symptoms in a palliative and supportive care service in an Australian cancer center.
Measurements: The main outcome measures were the number of participants screened and randomized over the time frame, the number of participants completing days 14 and 28 and providing total symptom distress scores (TSDSs) (measured using the Edmonton Symptom Assessment Scale), and the change from baseline of the TSDS at day 14.
Results: Of the 21 participants enrolled (CBD, n = 16; THC, n = 5), 18 (86%) completed the primary outcome measure at day 14 and 8 completed at day 28. The median maximum tolerated doses were CBD, 300 mg/day (range 100–600 mg); THC, 10 mg/day (range 5–30 mg). Nine of 21 patients (43%) met the definition of response (=6 point reduction in TSDS). Drowsiness was the most common AE.
Conclusions: Trials of medicinal cannabis in advanced cancer patients undergoing palliative care are feasible. The doses of THC and CBD used in this study were generally well tolerated and the outcome measure of total symptom distress is promising as a measure of overall symptom benefit. Trial registration: ACTRN12618001205224.
Importance: High-quality evidence on how to improve palliative care in nursing homes is lacking.
Objective: To investigate the effect of the Palliative Care for Older People (PACE) Steps to Success Program on resident and staff outcomes.
Design, Setting, and Participants: A cluster-randomized clinical trial (2015-2017) in 78 nursing homes in 7 countries comparing PACE Steps to Success Program (intervention) with usual care (control). Randomization was stratified by country and median number of beds in each country in a 1:1 ratio.
Interventions: The PACE Steps to Success Program is a multicomponent intervention to integrate basic nonspecialist palliative care in nursing homes. Using a train-the-trainer approach, an external trainer supports staff in nursing homes to introduce a palliative care approach over the course of 1 year following a 6-steps program. The steps are (1) advance care planning with residents and family, (2) assessment, care planning, and review of needs and problems, (3) coordination of care via monthly multidisciplinary review meetings, (4) delivery of high-quality care focusing on pain and depression, (5) care in the last days of life, and (6) care after death.
Main Outcomes and Measures: The primary resident outcome was comfort in the last week of life measured after death by staff using the End-of-Life in Dementia Scale Comfort Assessment While Dying (EOLD-CAD; range, 14-42). The primary staff outcome was knowledge of palliative care reported by staff using the Palliative Care Survey (PCS; range, 0-1).
Results: Concerning deceased residents, we collected 551 of 610 questionnaires from staff at baseline and 984 of 1178 postintervention in 37 intervention and 36 control homes. Mean (SD) age at time of death ranged between 85.22 (9.13) and 85.91 (8.57) years, and between 60.6% (160/264) and 70.6% (190/269) of residents were women across the different groups. Residents’ comfort in the last week of life did not differ between intervention and control groups (baseline-adjusted mean difference, -0.55; 95% CI, -1.71 to 0.61; P = .35). Concerning staff, we collected 2680 of 3638 questionnaires at baseline and 2437 of 3510 postintervention in 37 intervention and 38 control homes. Mean (SD) age of staff ranged between 42.3 (12.1) and 44.1 (11.7) years, and between 87.2% (1092/1253) and 89% (1224/1375) of staff were women across the different groups. Staff in the intervention group had statistically significantly better knowledge of palliative care than staff in the control group, but the clinical difference was minimal (baseline-adjusted mean difference, 0.04; 95% CI, 0.02-0.05; P < .001). Data analyses began on April 20, 2018.
Conclusions and Relevance: Residents' comfort in the last week of life did not improve after introducing the PACE Steps to Success Program. Improvements in staff knowledge of palliative care were clinically not important.
Trial Registration: ISRCTN Identifier: ISRCTN14741671.
Background/Aims: Numerous changes can occur between the original design plans for clinical trials, the submission of funding proposals, and the implementation of the clinical trial. In the hospice setting, environmental changes can present significant obstacles, which require changes to the original plan designs, recruitment, and staffing. The purpose of the study was to share lessons and problem-solving strategies that can assist in future hospice trials.
Methods: This study uses one hospice clinical trial as an exemplar to demonstrate challenges for clinical trial research in this setting. Using preliminary data collected during the first months of a trial, the research team details the many ways their current protocol reflects changes from the originally proposed plans. Experiences are used as an exemplar to address the following questions: 1) How do research environments change between the initial submission of a funding proposal and the eventual award? 2) How can investigators maintain the integrity of the research and accommodate unexpected changes in the research environment?
Results: The changing environment within the hospice setting required design, sampling, and recruitment changes within the first year. The decision-making process resulted in a stronger design with greater generalization. As a result of necessary protocol changes, the study results are positioned to be translational following the study conclusion.
Conclusion: Researchers would do well to review their protocol and statistics early in a clinical trial. They should be prepared for adjustments to accommodate market and environmental changes outside their control. Ongoing data monitoring, specifically related to recruitment, is advised.
Heart failure (HF) is a progressive condition with high mortality and heavy symptom burden. Despite guideline recommendations, cardiologists refer to palliative care at rates much lower than other specialties and very late in the course of the disease, often in the final 3 days of life. One reason for delayed referral is that prognostication is challenging in patients with HF, making it unclear when and how the limited resources of specialist palliative care will be most beneficial. It might be more prudent to consider palliative care referrals at critical moments in the trajectory of patients with HF. These include: a) the development of poor prognostic signs in the outpatient setting; b) hospitalization or intensive care unit admission, and c) at the time of evaluation for certain procedures, such as left ventricular assist device placement and ablation for refractory ventricular arrhythmias, among others. In this review, we also summarize the results of clinical trials evaluating palliative interventions in these settings.
L’inclusion dans les essais précoces provoque de nombreux questionnements d’un point de vue pratique, mais aussi éthique. L’objectif de ce travail est de montrer que ces enjeux dépassent largement la simple ouverture d’un essai et l’inclusion d’un enfant dont la pathologie correspond aux critères.
BACKGROUND: Research is needed to improve care and diminish suffering for children with life-limiting illnesses and their parents. However, there are doubts about whether it is possible to conduct paediatric end of life research safely and ethically, as it may unduly burden or inadvertently harm participants.
AIM: To compare and evaluate responses from participants to the assessments of burdens and benefits that were conducted at two timepoints during a phenomenological study that investigated parents' experiences of having a child with life-limiting cancer participate in a Phase I clinical trial.
DISCUSSION: Parents reported that participating in the study was beneficial and resulted in minimal burden or distress. The assessment of benefits and burdens at the first timepoint appeared sufficient to understand participants' experiences.
CONCLUSION: This study adds to the evidence that research may be safely and effectively conducted with parents of children who are deceased or have life-limiting illnesses. Further research is needed to evaluate the most effective timing of assessments of the burdens and benefits of their participation in research.
IMPLICATIONS FOR PRACTICE: It is important when conducting research with people with life-limiting illnesses or their family members to assess the burdens and benefits of their participation, to understand their experiences and assist in its conduct.