Clinical benefit in oncology trials: Is this a patient-centred or tumour-centred end-point?

BackgroundClinical benefit (CB) was first successfully used as an end-point in 1997 in the pivotal study of gemcitabine in advanced pancreas cancer. In the trial by Burris et al. CB was a composite measure of pain, performance status and weight. Here we describe how CB has been used in oncology trials since that time.MethodsWe performed an electronic search (www.jco.org) for reports of all clinical trials (phase I, II and III) published in the Journal of Clinical Oncology 1997–2008 citing ‘clinical benefit’. Eligible trials were those reporting clinical benefit as an end-point. Details related to study methodology, sponsorship and end-points were abstracted. Use of CB was classified as patient centred if it referred to improvement in the clinical parameters used by Burris et al. or in other disease-related symptoms. CB was classified as tumour centred if it related to objective tumour criteria for partial/complete response and/or stable disease. Descriptive statistics were used to summarise findings and the chi-square test was used to compare proportions.ResultsSeventy-one trials reporting CB as an end-point were identified: 37 in breast, 8 in pancreas and 26 in other cancers. The definition of CB was patient centred in 20 trials (28%) and tumour centred in 51 trials (72%). Only 20% (14/71) of trials (including all 8 pancreas studies) used the original Burris definition. Among the 71 trials reporting clinical benefit, in only 31 (44%) cases was the end-point defined as a primary or secondary study objective. Trials with a patient-centred definition of CB were considerably more likely to do so than trials with a tumour-centred definition (19/20, 95% versus 12/51, 24%, p < 0.0001). Study variables associated with the use of a tumour-centred definition include: disease site (breast 35/37, 95%; all others 16/34, 47%, p < 0.001) and intervention (hormone or targeted agent 38/40, 95%; chemotherapy 13/31, 42%, p < 0.001). There has been a steady increase in the number of trials using CB as an end-point; in the second half of the study period the number of trials increased from 17 to 54, along with the proportion of trials with a tumour-centred definition (10/17, 59% to 41/54, 76%, p = 0.09).ConclusionsDespite its initial definition, clinical benefit is often used to describe objective tumour findings. Clinical trials should use end-points in a consistent manner to enable clear communication between investigators, clinicians and patients about the benefit of novel therapies.