Analyzing oncology clinical trial data using the Q-TWiST method: clinical importance and sources for health state...

The Quality-adjusted Time Without Symptoms of disease and Toxicity (Q-TWiST) analysis method is frequently applied to evaluating outcomes in cancer clinical trials, but there is little information on what constitutes a clinically important difference (CID). We reviewed the Q-TWiST, health-related quality of life (HRQL) and utility measurement literature to develop recommendations for CID for the Q-TWiST. We also provide recommendations for measuring health utilities and for the design of Q-TWiST studies.

The English language literature was searched between 1986 and 2003 for Q-TWiST studies in oncology. We estimated the percent differences between treatments based on median follow-up duration for overall, progression-free and quality-adjusted survival. We also reviewed the relevant HRQL and utility literature on clinical importance.

The overall differences between treatments for most (56%) of the observed, published values for Q-TWiST analyses ranged between 12% and 19%. Three-fourths of the Q-TWiST studies had gains in survival of 12%-17%, while differences in progression-free survival ranged from 12% to 26%. Studies that have evaluated the clinical importance of changes in HRQL scores suggest that changes of 5%-10% are clinically meaningful, and other research suggests that 0.5 standard deviation is a reasonable threshold for changes in HRQL for chronic diseases. Similarly, one guideline from the health state utility literature is that a 5%-10% difference in standard gamble utility scores is clinically important. Various sources are available for health utilities for Q-TWiST studies and the most valid are derived from patients or the general public, although most studies rely on sensitivity analyses with no collection of utilities.

We recommend that the CID for Q-TWiST is 10% of overall survival in a study, and differences of 15% are clearly clinically important. If less is known about a specific treatment and/or disease area, the CID should be greater than 5% but not more than 10% in planning sample size and statistical power. These CID estimates should be interpreted with caution, pending confirmation in future studies by direct patient assessment of the clinically relevant health states for Q-TWiST.