Randomised controlled trials of palliative care – a survey of the views of advanced cancer patients and their relatives

doi:10.1016/j.ejca.2008.05.003

European Journal of Cancer

Volume 44, Issue 13, September 2008, Pages 1820-1828

https://doi.org/10.1016/j.ejca.2008.05.003 Get rights and content

Abstract

Purpose

To determine if patients with advanced cancer are interested in participation in palliative care research, particularly RCTs, and the importance of demographic factors in decision making. It sought relatives’ views towards supporting trial entry, and assessed if demographic factors can predict participation.

Methods

A questionnaire was developed through multiprofessional focus groups, patient and relative interviews and pilot studies. Consecutive patients known by the palliative care service to have advanced disease were approached. Relatives of consenting patients completed a parallel survey. K-means cluster analysis was used to differentiate between those willing and unwilling to participate. Multivariate logistic regression identified demographic factors predicting willingness.

Results

One hundred and one patients and 100 relatives were included. 92% of patients would participate in studies involving simple interventions, whereas only 26% would consider studies of complex interventions. A similar pattern was observed for relative support. Over 75% of participants expressed altruistic views. Concepts of ‘randomisation’, ‘placebo-control’ and ‘blinding’ deterred about one-half. Many were prepared to complete short questionnaires, accept extra medications, investigations, hospital visits or admissions within a trial context but the possibility of side-effects was a major deterrent. Patient age was the only significant predictor of willingness to participate, with older patients less likely to participate.

Conclusion

Despite the likely absence of individual benefit, many patients appear willing to participate in palliative care research. Trial design and the possibility of side-effects proved very influential in their decision making. Clinical trials in palliative care are more likely to be successful if developed in accordance with the views of patients and their relatives.

Introduction

Evidence-based practice forms an essential part of modern medicine and yet many treatments and interventions used in palliative care have never been evaluated. There are wide variations in clinician practice not only internationally, but within countries and even institutions due to a lack of high-level evidence.1, 2 An example is the uncertainty that surrounds opioid dose equivalence and conversion ratios.³

Research in palliative care focuses on symptom control and supportive care for patients and their families. It is widely acknowledged that research in the palliative population is difficult and therefore is often not attempted. Many well-designed randomised controlled trials (RCTs) have failed. The literature is littered with poor studies or studies that have not accrued sufficient numbers of patients.1, 4 Specific challenges include difficulties in recruiting patients of poor performance status, small sample sizes, high attrition rates (up to 60%),⁵ rapidly changing clinical situations, limited survival times and the reluctance of health professionals to refer patients for research studies.

It has been argued that research in patients with far-advanced disease is inappropriate as it disrespects a patient’s emotional and physical state.⁶ Sound evidence is essential to guide decision making,⁷ however, and research must be performed in relevant patient groups for it to be clinically applicable.

Research in palliative care requires realistic studies that are practical and achievable. It is necessary to design trials that are acceptable to patients, their families and healthcare professionals. Perceived concerns of patients receiving palliative care have generally been defined by the views of family and healthcare professionals, and often relate to patients with chronic illnesses and not those close to death.⁸ Previous studies considering the views of palliative care patients and their relatives have small sample sizes 9, 10 and are often qualitative in nature.8, 11

The aim of this study was to determine if patients with advanced cancer are interested in participation in research that does not involve anti-cancer therapy, particularly in the context of a RCT, and if so, what factors are important in their decisions. What level of inconvenience is tolerable and is willingness to participate influenced by demographic or other factors? As patients with advanced disease are often highly dependant on their relatives or partners, it was important to determine their views to gauge whether they would support trial entry.

Section snippets

Setting

The study was performed at the Mater Misericordiae Hospital in Brisbane, a university teaching hospital for public patients with a tertiary referral service for oncology. The palliative care service is integrated within the oncology service and provides support and symptom control for patients on the in-patient ward, day oncology unit and in the outpatient department. Patients are seen according to need at any stage of their disease course. Those requiring terminal care are generally

Questionnaire development

A questionnaire was designed through a literature search, focus groups with healthcare professionals (HCPs), patient and relative interviews and pilot studies. This resulted in parallel surveys to assess the views of patients and relatives towards patient participation in palliative care trials, in particular RCTs, which do not involve specific anti-cancer treatment but focus on symptom control.

The final self-administered questionnaires had three sections to assess factors that may affect both

Patients

Eligible patients were over 18 years of age with a diagnosis of cancer who met the following definition: ‘patients with an active, progressive, far-advanced disease for whom prognosis is limited and the focus of care is quality of life’.¹² Patients had to be aware of the advanced state of their disease, have a good understanding of English and cognitive function that allowed fully informed consent. Patients who were receiving chemotherapy had to be aware of its palliative intent. Patients

Statistical methods

The sample size required for this study was determined assuming multiple regression as the analysis tool. As there were no available estimates of the multiple correlation coefficient (R) for this topic it was anticipated that a small to medium effect size (f²) would be observed. Consequently, assuming f² = 0.09, the multiple correlation coefficient was calculated as 0.2873.¹³ Using this parameter, as well as an acceptable type I error rate of 0.05 and 11 predictor variables, 197 participants

Results

Of the 125 patients screened over a 10 week period (September to November 2006), 20 were excluded. One hundred and five were approached, 101 completed and returned the questionnaire, two refused and two consented but failed to complete the questionnaire (Fig. 1). One hundred and five relatives were nominated, all consented and 100 completed questionnaires were returned. The median number of participating relatives per patient was one (range 0–5); 37 patients had no participating relatives.

Discussion

There has been controversy amongst healthcare professionals about the appropriateness of involving patients with advanced disease in research, especially when the patients themselves may not directly benefit. In this survey, over three quarters of patients and relatives expressed altruistic views in that they were interested in participating in, or supporting a study that would be unlikely to help the patient but might help others in the future. This is consistent with findings from other

Conclusion

This survey has confirmed findings from other studies. Patients with advanced cancer are interested in participating in RCTs that focus on symptom control and not cancer treatment, and their relatives are frequently willing to support participation. It refutes the suggestion that this patient group should not be involved in research as many have altruistic views towards research participation.

This survey has highlighted methodological factors that need to be considered in trial design in order

Conflict of interest

None declared

Acknowledgements

The authors thank Palliative Care Research Fund, Mater Health Services for its support, and Macmillan Cancer Support for funding for C.W. and they also thank Mr. Andrew Monington for data entry.

References (32)

M. Henderson et al.
The willingness of palliative care patients to participate in research
J Pain Symptom Manage
(2005)
L. Fallowfield et al.
Attitudes of patients to randomised clinical trials of cancer therapy
Eur J Cancer
(1998)
J. Ling et al.
What influences participation in clinical trials in palliative care in a cancer centre?
Eur J Cancer
(2000)
J. Hardy
Placebo-controlled trials in palliative care: the argument for
Palliat Med
(1997)
P. Good et al.
What are the essential medications in palliative care? – a survey of Australian palliative care doctors
Aust Fam Physician
(2006)
H. Berdine et al.
Equianalgesic dosing of opioids
J Pain Palliat Care Pharm
(2006)
G. Rinck et al.
Methodologic issues in effectiveness research on palliative cancer care: a systematic review
J Clin Oncol
(1997)
M. Jordhoy et al.
Challenges in palliative care research; recruitment, attrition and compliance: experience from a randomized controlled trial
Palliat Med
(1999)
L. deRaeve
Ethical issues in palliative care research
Palliat Med
(1994)
S. Aoun et al.
Challenging the framework for evidence in palliative care research
Palliat Med
(2005)

W. Terry et al.

Hospice patients’ views on research in palliative care

Int Med J

(2006)

C. Ross et al.

Attitudes of patients and staff to research in a specialist palliative care unit

Palliat Med

(2003)

M. Dobratz

Issues and dilemmas in conducting research with vulnerable home hospice participants

J Nurs Schol

(2003)

Schedule of pharmaceutical benefits for approved pharmacists and medical practitioners. In: Australian Government...

J. Cohen

Statistical power analysis for the behavioural sciences

(1988)

J. Fleiss

Statistical methods for rates and proportions

(1981)

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Randomised controlled trials of palliative care – a survey of the views of advanced cancer patients and their relatives

Abstract

Purpose

Methods

Results

Conclusion

Introduction

Section snippets

Setting

Questionnaire development

Patients

Statistical methods

Results

Discussion

Conclusion

Conflict of interest

Acknowledgements

J Pain Symptom Manage

Eur J Cancer

Eur J Cancer

Placebo-controlled trials in palliative care: the argument for

Palliat Med

What are the essential medications in palliative care? – a survey of Australian palliative care doctors

Aust Fam Physician

Equianalgesic dosing of opioids

J Pain Palliat Care Pharm

Methodologic issues in effectiveness research on palliative cancer care: a systematic review

J Clin Oncol

Challenges in palliative care research; recruitment, attrition and compliance: experience from a randomized controlled trial

Palliat Med

Ethical issues in palliative care research

Palliat Med

Challenging the framework for evidence in palliative care research

Palliat Med

Hospice patients’ views on research in palliative care

Int Med J

Attitudes of patients and staff to research in a specialist palliative care unit

Palliat Med

Issues and dilemmas in conducting research with vulnerable home hospice participants

J Nurs Schol

Statistical power analysis for the behavioural sciences

Statistical methods for rates and proportions