Clinical trials in cancer: the role of surrogate patients in defining what constitutes an ethically acceptable clinical experiment

Abstract

Summary Doctors who treat lung cancer in Ontario were previously asked how they would wish to be managed if they developed non-small cell lung cancer and whether they would consent to participate in six clinical trials for which they might be eligible. The proportion of these expert surrogate patients who would consent to each clinical trial ranged from 11 to 64%. The results of this study were transmitted to the same group of doctors who were asked to comment on the ethical acceptability of each trial in the light of this information. The majority of physicians said that those trials to which less than 50% of expert surrogates consented should not have been opened to patients. Sixty-nine per cent of doctors thought that new trials should be evaluated in this way. We also present the results of a survey of 400 lay people in Ontario who were asked to imagine that they had lung cancer and whether they would consent to participate in two of these same clinical trials. Fifty per cent of lay people consented to a randomised trial of lobectomy versus segmentectomy in early, operable disease (LCSC-821) compared to 64% of expert surrogates, and 48% of lay people consented to a randomised trial of five different forms of chemotherapy in metastatic disease (SWOG-8241) compared to 19% of doctors. It was concluded that the lay people were unable to discern differences in the acceptability of clinical trials which were clear to experts in the field. Subsequently, respondents were told about the decisions which doctors would make in the same circumstances and asked if this information would modify their previous decisions. There is no net change in the proportion of patients consenting to the surgery trial but the proportion of people consenting to the chemotherapy trial decreased by 40%. The majority of lay people said that they would wish to have access to this type of information before consenting to participate in a clinical trial.

A survey of the views of palliative care healthcare professionals towards referring cancer patients to participate in randomized controlled trials in palliative care

“…Gatekeeping from research is not exclusive to palliative care, and the reluctance of clinicians to enter eligible patients into trials has been described as a more limiting factor than patient reluctance to participate in the oncology setting [11,23,37], in general practice research [27] and in other settings [2,21]. This will inevitably result in selection bias [19], thus making RCTs more difficult to complete and interpret.…”

Participating in a cancer clinical trial? The balancing of options in the loneliness of autonomy: A grounded theory interview study

“…It is in principle undisputed that lack of equipoise would render a trial unethical. However, not even specialists in the field are always in agreement concerning whether clinical equipoise exists, and the matter of acceptability of studies without equipoise and increasing differences in effects/adverse effects between treatment arms have been discussed [28]. The experience or judgment of equipoise is, seemingly, a very personal matter depending on numerous factors.…”

Randomized controlled trials in health technology assessment: Overkill or overdue?

“…Freedman's proposition is that a clinician can ethically randomize patients in his or her care among various treatment options even when he or she would have a personal preference, provided that a collective equipoise exists. This proposition forms the widely accepted ethical basis for the conduct of clinical trials and does provide an ethical way around the fact that surrogate patient studies have shown that many clinicians are willing to accrue patients into randomized trials that they would not volunteer to participate in if they were patients themselves [31]. Logically, there will be some loosely defined limit to the lack of individual equipoise, before randomizing patients will cause ethical concerns for the individual treating physician.…”