Recent clinical trials comparing initial treatment with dopamine agonists to initial levodopa therapy in early Parkinson's disease (PD) have shown that each treatment policy generates distinct effect profiles [1–3]. Initial use of dopamine agonists compared with initial use of levodopa results in reduced risk of developing dyskinesias and wearing off over the first 4 to 5 years of treatment. Initial use of levodopa compared with dopamine agonists, however, results in a sustained five- to seven-point improvement on the Unified Parkinson's Disease Rating Scale (UPDRS) [1,2] and significantly less somnolence and edema. Treatment guidelines have stated that both are options as initial therapy and the available evidence does not favor one treatment option over another.
Several types of outcomes are used in patient outcomes research, including cost-effectiveness studies. The concept of health-related quality of life (HRQOL) was developed to evaluate quantitatively person's well-being [4, 5]. Utility scores reflect person's preferences for health states. Utilities are used as weights when calculating quality-adjusted life-years (QALYs) that capture both duration of life in a particular health state and utility of that state [6–8]. Health states could be defined by their HRQOL. Utilities are assessed using preference-based methods, such as time trade-off for EQ-5D . Visual analog scale is often used for simplicity but it does not provide utility values. HRQOL and utility evaluations are different from the assessment of health status that is typically performed via health status questionnaires .
Prior studies have shown that HRQOL is correlated with important aspects of PD. Cross-sectional studies in PD have shown that HRQOL is influenced by age, disease severity, depression, sleep-related events, and motor fluctuations [11–14]. Longitudinal studies [15,16] have shown that quality of life in PD patients decreases as the disease progresses. Although HRQOL assessments have been included in multiple PD clinical trials, little is known about differential effects of treatments on HRQOL of PD population over time.
The 4-year trial  comparing initial pramipexole and initial levodopa showed that between the treatment arms there was no difference in the mean changes in the HRQOL scores from the 48-month visit to the baseline visit. In this study, we estimate longitudinal models to characterize HRQOL profiles taking into account the HRQOL values for all visits and accumulate gains and losses over time, by treatment arm . This approach takes into account the transient interim values of HRQOL during the trial rather than ignoring dynamic patterns in HRQOL between randomization and the end of the trial. This may be of particular relevance given that the beneficial quality of life effects associated with delaying dopaminergic complications by using initial dopamine agonists instead of levodopa may be delayed and accrue over years of therapy .
Using this method, we address the following questions: 1) in early PD patients, which treatment alternative generates more benefit in terms of HRQOL, and 2) how does the difference in HRQOL gains between treatments change as time goes on. In addition, we explore whether patients who experience adverse events (dyskinesias, edema, and somnolence) have worse quality of life than patients who do not experience adverse events.