Statistical methods for primary and secondary outcomes {20a}
pain
REGRESSION
The primary outcome is physical functioning 4 weeks after the start of the treatment, which will be expressed as a score on a 0–100 scale. First, we will calculate within-group changes from baseline to 4 weeks after the start of the treatment, which will be expressed as mean changes with corresponding 95% confidence intervals. Linear regression analysis or analysis of covariance (ANCOVA) following the intention-to-treat principle will be performed to compare the intervention arm with the control arm in terms of physical functioning, controlling for baseline physical functioning, age, Karnofsky performance score, and medication use. Differences between treatments and 95% confidence intervals will be calculated.The proportion of patients in the intervention and control arm reporting a pain response will be compared by Fisher’s exact test or Within-group changes in HRQOL from baseline to 4 and 8 weeks and 3 and 6 months will be expressed as mean change with corresponding 95% confidence intervals. We will assess between-group differences in HRQOL as a continuous outcome using linear regression analysis. The proportion of patients with a clinically relevant improvement or deterioration, i.e., an increase or decrease, respectively, of at least 10 points will be compared between the intervention and control arm at every time point by Fisher’s exact test or A cost-effectiveness analysis will be performed to assess whether same-day SBRT and surgery is cost-effective compared with the standard of care, from a societal perspective. If same-day SBRT and surgery is more costly and more effective than the standard of care, an incremental cost-effectiveness ratio (ICER) will be calculated by dividing the extra QALYs by the extra effects. This will give an estimation of the extra costs that are needed to gain one QALY. If this is below the cost-effectiveness threshold, same-day SBRT and surgery is deemed cost-effective. If either same-day SBRT and surgery or the standard of care is less costly and more effective than the standard of care, no ICER is necessary to determine cost-effectiveness. Uncertainty surrounding the costs, effects and ICER will be addressed by means of bootstrapping. Overall mean and median costs will be compared across the randomization groups and, where relevant, differences will be calculated inclusive of 95% confidence intervals. Also, a budget impact analysis (BIA) will be performed using the ZonMw tool to address the question whether same-day SBRT and surgery contributes to an affordable and more efficient and sustainable healthcare system. Data that will be used reflect the size and characteristics of the population, the current and new treatment mix, the efficacy of same-day SBRT and surgery and the standard of care, the resource use, and costs for the treatments and symptoms (