These are described in detail in the Methods section
ReviewConsensus-based standards for best supportive care in clinical trials in advanced cancer
Introduction
For more than 20 years, patients with advanced cancer have been enrolled in clinical trials comparing experimental antineoplastic therapy with a supportive care control.1 The control group is often called palliative care or best supportive care, and trials in which some patients receive only supportive care are called best supportive care trials. This trial design is popular; a search of the National Institutes of Health website, ClinicalTrials.gov in May, 2010, showed more than 40 open or pending phase 2 or phase 3 studies with best supportive care as a part of the study design.2 However, such care is incompletely defined, with substantial variation in breadth, frequency, and documentation of care provided.3, 4, 5 In a systematic review of best supportive care trials reported since 1966, most studies complied poorly with well-recognised requirements of trial design and reporting, including the Helsinki requirements and the CONSORT standards for the reporting of clinical trials.5 Few studies cited best available evidence as the basis for delivery of best supportive care. Most studies failed to report delivery of best supportive care in a way that would allow consistency across sites or study replication. A clear need was identified for best supportive care in clinical trials for patients with advanced cancer to be described and formalised.
When best supportive care is poorly defined and documented, patients in the same group in a particular trial might be receiving very different care. Outcomes including survival and quality of life could be affected, resulting in a risk to internal validity (figure 1).6 Furthermore, trial interventions are inconsistently translated into routine clinical practice, and the external validity of trial results might be at risk (figure 1).6 Until the comparator group is uniformly defined, some best supportive care trials will not provide clinically meaningful information, despite the best intentions of clinical triallists providing supportive care. This inconsistency is profoundly atypical of the rigour expected in clinical trial design.
Evidence increasingly shows that palliative care can improve quality of life7, 8, 9 and potentially affect survival.10 This survival benefit is of the same order of magnitude as that reported for many antineoplastic therapies when compared with ill-defined best supportive care.11, 12, 13, 14 For example, Temel and colleagues10 showed an improvement in overall survival and quality of life in patients with lung cancer who received early palliative care and standard oncological care compared with those who received standard oncological care alone. The results and implications of this study are awaiting further validation; however, the findings clearly support the optimisation of best supportive care control groups in advanced cancer trials to meet a contemporary standard. Survival and quality-of-life benefits of any experimental antineoplastic regimen can then be compared with the evolving best standard of care.
The Institute of Medicine reviewed the National Cancer Institute's clinical trials programme with a recommendation, among others, to improve the design and implementation of clinical trials.15 In view of evidence showing the effect of supportive care, and in response to the Institute of Medicine report, we sought to improve the internal and external validity of best supportive care trials for patients with advanced cancer. We developed consensus recommendations for best supportive care consistent with the Helsinki declaration's requirement that control groups receive “the best current proven intervention”.16
Section snippets
Methods
We recruited a panel of international experts to develop consensus statements by the Delphi method.17, 18, 19, 20, 21, 22, 23 Experts were defined as individuals with relevant knowledge, interest, and skills drawn from diverse professional backgrounds (characteristics of the panellists are described in the appendix).17, 19, 24 40 participants were contacted to ensure at least 20 responses for each survey, as recommended for this process.19 Responses were kept anonymous.
The first round in the
Results
40 experts were initially identified and approached through personal contact; 36 experts from six countries agreed to participate from the disciplines of oncology, clinical trial design or cancer cooperative group research, palliative or supportive care, nursing, health services research, medical ethics, social work, and the pharmaceutical industry (appendix). The four who were contacted but who chose not to participate did not provide a reason for non-participation (three were oncologists and
Multidisciplinary care
The highest degree of consensus in multidisciplinary care was for the recommendation of access to palliative care specialists for patients in trials of advanced cancer. This statement is consistent with the guidelines of major societies, including the American Society of Clinical Oncology and the Institute of Medicine, which emphasise collaboration with palliative care services in the management of patients with advanced cancer.28 Our panel encouraged standard and codified access to these
Conclusions
Patients with advanced cancer are generally near the end of life, yet they are keen to participate in studies and contribute to advancing science. When patients are enrolled in studies with groups given supportive care, ethical and moral imperatives dictate that the care they receive can be reproduced and is based on the best available evidence.
A diverse panel of experts, including key informants in design of cancer clinical trials, arrived at a clear consensus about the features of best
Search strategy and selection criteria
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