Defining and analysing symptom palliation in cancer clinical trials: a deceptively difficult exercise

The assessment of symptom palliation is an essential component of many trea tment comparisons in clinical trials, yet an extensive literature search re vealed no consensus as to its precise definition, which could embrace relie f of symptoms, time to their onset, duration, degree, as well as symptom co ntrol and prevention. in an attempt to assess the importance of these aspec ts and to compare different methods of analysis, we used one symptom (cough ) from a patient self-assessment questionnaire (the Rotterdam Symptom Check list) in a large (>300 patient) multicentre randomized clinical trial (cond ucted by the Medical Research Council lung Cancer Working Party) of palliat ive chemotherapy in small-cell lung cancer. The regimens compared were a tw o-drug regimen (2D) and a four-drug regimen (4D). No differences were seen between the regimens in time of onset of palliative or its duration. The de gree of palliation was strongly related to the initial severity: 90% of the patients with moderate or severe cough at baseline reported improvement, c ompared with only 53% of those with mild cough. Analyses using different la ndmark time points gave conflicting results: the 4D regimen was superior at 1 month and at 3 months, whereas at 2 months the 2D regimen appeared super ior. When improvement at any time up to 3 months was considered, the 4D reg imen showed a significant benefit (4D 79%, 2D 60%,, P= 0.02). These finding s emphasize the need for caution in interpreting results, and the importanc e of working towards a standard definition of symptom palliation. The curre nt lack of specified criteria makes analysis and interpretation of trial re sults difficult, and comparison across trials impossible. A standard defini tion of palliation for use in the analysis of clinical trials data is propo sed, which takes into account aspects of onset, duration and degree of pall iation, and symptom improvement, control and prevention.