Overcoming recruitment challenges in palliative care clinical trials

Purpose: Palliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research - especially participant recruitment - is difficult. Major barriers include (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study. Patients and Methods: The PCT was a 2 x 2 x 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of "social marketing," an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications. Results: From an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%). Conclusion: Challenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing-based protocol shows the benefits of such an approach. Copyright © 2013 by American Society of Clinical Oncology

Two colliding epidemics - obesity is independently associated with chronic pain interfering with activities of daily living in adults 18 years and over; a cross-sectional, population-based study.

BACKGROUND: Chronic pain interfering with activities of daily living is highly prevalent in the community. More than 600 million people worldwide are obese. The aim of this paper is to assess if such chronic pain is associated independently with obesity across the adult population, having controlled for other key factors. METHODS: The South Australian Health Omnibus is an annual, population-based, cross-sectional study. Data on 2616 participants were analysed for episodes of daily pain for three of the preceding six months. Obesity was derived from self-reported height and weight. Multivariable logistic regression analysed the associations between chronic pain interfering with activities of daily living, body mass index (BMI) and key socio-demographic factors. RESULTS: Chronic pain interfering with activities of daily living peaks in people ≥75 years of age while obesity peaks in the 45-54 age group. Pain and obesity together peak in the 55-74 year age group. In the adjusted multinominal logistic regression model, compared to those with no pain, there was a strong association between obesity and pain that interfered moderately or extremely with day-to-day activities (OR 2.25; 95 % CI 1.57-3.23; p < 0.001) having controlled for respondents' age, gender, rurality, country of birth and highest educational attainment. People over 65 years of age and those with lower educational levels were more likely to experience such chronic pain related to obesity. CONCLUSION: This study demonstrates a strong association between chronic pain and obesity/morbid obesity in the South Australian population. Prospective, longitudinal data are needed to understand the dynamic interaction between these two prevalent conditions

Prospectively Collected Characteristics of Adult Patients, Their Consultations and Outcomes as They Report Breathlessness When Presenting to General Practice in Australia

Introduction:Breathlessness is a subjective sensation, so understanding its impacts requires patients' reports, including prospective patient-defined breathlessness as a reason for presenting to general practitioners (GP).The aim of this study was to define the prevalence of breathlessness as a reason for GP consultations while defining the clinico-demographic factors of these patients and the characteristics and outcomes of those consultations.Methods:Using nine years of the Family Medicine Research Centre database of 100 consecutive encounters from 1,000 practices annually, the patient-defined reason for encounter 'breathlessness' was explored using prospectively collected data in people ≥18 years with clinical data coded using the International Classification for Primary Care V2. Dichotomous variables were analysed using chi square and 95% confidence intervals calculated using Kish's formula for a single stage clustered design.Results:Of all the 755,729 consultations collected over a nine year period from 1 April, 2000, 7255 included breathlessness as a reason for encounter (0.96%; 95% CI 0.93 to 0.99) most frequently attributed to chronic obstructive pulmonary disease. Only 48.3% of GPs saw someone reporting breathlessness. The proportion of consultations with breathlessness increased with age. Breathlessness trebled the likelihood that the consultation occurred in the community rather than the consulting room (p<0.0001) and increased 2.5 fold the likelihood of urgent referral to hospital (p<0.0001). Of those with breathlessness, 12% had undiagnosed breathlessness at the end of the consultation (873/7255) with higher likelihood of being younger females.Discussion:Breathlessness is a prevalent symptom in general practitioner. Such prevalence enables future research focused on understanding the temporal pattern of breathlessness and the longitudinal care offered to, and outcomes for these patients, including those who leave the consultation without a diagnosis. © 2013 Currow et al

Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality.

BACKGROUND: The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. MATERIALS AND METHODS: We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993-2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. RESULTS: Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths-with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths-with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. CONCLUSION: Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina

Best supportive care in clinical trials: Review of the inconsistency in control arm design

© 2015 Cancer Research UK. All rights reserved. Best supportive care (BSC) as a control arm in clinical trials is poorly defined. We conducted a review to evaluate clinical trials' concordance with published, consensus-based framework for BSC delivery in trials.Methods:A consensus-based Delphi panel previously identified four key domains of BSC delivery in trials: multidisciplinary care; supportive care documentation; symptom assessment; and symptom management. We reviewed trials including BSC control arms from 2002 to 2014 to assess concordance to BSC standards and to selected items from the CONSORT 2010 guidelines.Results:Of 408 articles retrieved, we retained 18 after applying exclusion criteria. Overall, trials conformed to the CONSORT guidelines better than the BSC standards (28% vs 16%). One-third of articles offered a detailed description of BSC, 61% reported regular symptom assessment, and 44% reported using validated symptom assessment measures. One-third reported symptom assessment at identical intervals in both arms. None documented evidence-based symptom management. No studies reported educating patients about symptom management or goals of therapy. No studies reported offering access to palliative care specialists.Conclusions:Reporting of BSC in trials is incomplete, resulting in uncertain internal and external validity. Such studies risk systematically over-estimating the net clinical effect of the comparator arms

Caregiver characteristics and bereavement needs: Findings from a population study

© 2016, © The Author(s) 2016. Background: Globally, most care for people with life-limiting illnesses is provided by informal caregivers. Identifying characteristics of caregivers that may have unmet needs and negative outcomes can help provide better support to facilitate adjustment. Aim: We compared characteristics, expressed unmet needs and outcomes for spousal caregivers, with other caregivers at the end of life, by gender and age. Design: The South Australian Health Omnibus is an annual, random, face-to-face, cross-sectional survey wherein respondents are asked about end-of-life care. Setting/participants: Participants were aged over 15 years, resided in households in South Australia and had someone close to them die from a terminal illness in the last 5 years. Results: Of the 1540 respondents who provided hands-on care for someone close at the end of life, 155 were widows/widowers. Bereaved spousal caregivers were more likely to be older, female, better educated, have lower incomes, less full-time work, English as second language, sought help with grief and provided more day-to-day care for longer periods. Spousal caregivers were less likely to be willing to take on caregiving again, less able to ‘move on’ with life and needed greater emotional support and information about illness and services. The only difference between widows and widowers was older age of spouse in women. Younger spousal caregivers perceived greater unmet emotional needs and were significantly less likely to be able to ‘move on’. Conclusion: Spousal caregivers are different from other caregivers, with more intense needs that are not fully met. These have implications for bereavement, health and social services

Handheld computers for data entry: high tech has its problems too

BACKGROUND: The use of handheld computers in medicine has increased in the last decade, they are now used in a variety of clinical settings. There is an underlying assumption that electronic data capture is more accurate that paper-based data methods have been rarely tested. This report documents a study to compare the accuracy of hand held computer data capture versus more traditional paper-based methods. METHODS: Clinical nurses involved in a randomised controlled trial collected patient information on a hand held computer in parallel with a paper-based data form. Both sets of data were entered into an access database and the hand held computer data compared to the paper-based data for discrepancies. RESULTS: Error rates from the handheld computers were 67.5 error per 1000 fields, compared to the accepted error rate of 10 per 10,000 field for paper-based double data entry. Error rates were highest in field containing a default value. CONCLUSION: While popular with staff, unacceptable high error rates occurred with hand held computers. Training and ongoing monitoring are needed if hand held computers are to be used for clinical data collection

Study protocol: A phase III randomised, double-blind, parallel arm, stratified, block randomised, placebo-controlled trial investigating the clinical effect and cost-effectiveness of sertraline for the palliative relief of breathlessness in people with chronic breathlessness

© Published by the BMJ Publishing Group Limited. Introduction: Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses. Methods and analysis: A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0-100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained. Ethics and dissemination: Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. Trial registration number ACTRN12610000464066

Sertraline in symptomatic chronic breathlessness: a double blind, randomised trial

Copyright ©ERS 2019. Does sertraline provide symptomatic relief for chronic breathlessness in people with advanced disease whose underlying cause(s) are optimally treated?223 participants with chronic breathlessness (modified Medical Research Council breathlessness scale ≥2) who had optimal treatment of underlying cause(s) were randomised 1:1 to sertraline 25-100 mg (titrated upwards over 9 days) or placebo for 4 weeks. The primary outcome was the proportion who had an improvement in intensity of current breathlessness >15% from baseline on a 100-mm visual analogue scale.The proportion of people responding to sertraline was similar to placebo for current breathlessness on days 26-28 (OR 1.00, 95% CI 0.71-1.40) and for other measures of breathlessness. Quality of life in the sertraline arm had a higher likelihood of improving than in the placebo arm over the 4 weeks (OR 0.21, 95% CI 0.01-0.41; p=0.044). No differences in performance status, anxiety and depression, or survival were observed. Adverse event rates were similar between arms.Sertraline does not appear to provide any benefit over placebo in the symptomatic relief of chronic breathlessness in this patient population