Clinical trials

In planning a clinical trial it is fundamental to consider the number of patients required to demonstrate the anticipated change in treatment outcome. When survival is the primary endpoint of the study, this may be expressed as the anticipated improvement in median survival time or reduction in hazards ratio for the test group over the control. In trials comparing treatments in terms of QoL, it is difficult to quantify the 'gain' (or 'loss') that may be anticipated with the test therapy. In addition, there will be many aspects of QoL that are measured and it may be difficult to predict which of these should be the primary endpoint variable that is required for sample size calculations. In practice, QoL data are rarely used as the primary determinant of trial size.

There are important challenges in reporting QoL outcomes in clinical trials. These include the description of compliance, summarizing longitudinal data in a complete yet clinically meaningful way, balancing the multiple endpoints under consideration, and perhaps, most importantly, relating the findings with regards to QoL to other treatment outcomes such as patient survival and treatment-related toxicity.

Attempts have been made to integrate QoL and survival data into quality-adjusted life years (QALY). The duration of survival is adjusted according to periods of different levels of QoL before summing to give the overall survival time for analysis. Thus, a month during which the QoL is high will contribute more to the QALY than will a month with a lower score. The final QALY can then be used for a comparison between treatments, embracing both survival effects and changes in QoL. However, this integration process has not been readily accepted—its application is clearly limited by the arbitrary choice of weights or values put onto different levels of QoL.

It should be recognized that including the measurement of QoL into cancer clinical trials adds a considerable burden. This burden is felt immediately by the trial team as it may affect the basic trial design, the content of the protocol, and patient follow-up schedules. It may impact on patient numbers. Implementing the trial will burden the patients themselves and the clinical team. It will increase the volume of data to be collected and may adversely affect the overall data quality. It will certainly increase the complexity of analysis and reporting. All this adds to overall trial costs.

It is important to give due consideration to these factors when considering whether or not assessment of QoL is an essential part of a trial. In general however the difficulties are justified in cancer studies.

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