Indirect comparisons of adverse events and dropout rates in early Parkinson's disease trials of pramipexole, ropinirole, and rasagiline.

The comparative safety profiles of monotherapeutic treatments for Parkinson's disease (PD) can provide valuable therapeutic information. The objective of this study was to perform an indirect comparison of Adverse Events (AEs) and Dropout Rates (DRs) among clinical trials of pramipexole, ropinirole, and rasagiline. Outcomes analyzed included DRs, total AEs, and AE categories: Cognitive (CG), Gastrointestinal (GI), and Sleep/Fatigue (SF). The odds-ratio (OR) and Credible Interval (CrI) of outcomes between products using placebo as common comparator was calculated using indirect meta-analytical methods. AEs incidences for subjects receiving rasagiline were not significantly different from placebo, whereas DRs were significantly lower than for placebo (OR = 0.55; 95% CrI = 0.34-0.88). Patients receiving pramipexole or ropinirole had higher incidence of all AEs and DRs than patients taking rasagiline, except for the nonsignificant incidence of CG for ropinirole vs. rasagiline (1.76; 0.69-4.70). The incidence of GI (2.11; 1.13-4.06) and SF (2.75; 1.42-5.47) was significantly higher for ropinirole than for pramipexole, whereas the incidence of CG was significantly lower for ropinirole than for pramipexole (0.22; 0.07-0.69). Findings suggest that subjects with early PD treated with rasagiline have fewer AEs and DRs than those treated with pramipexole or ropinirole. GI and SF AEs were highest for subjects treated with ropinirole, while individuals treated with pramipexole exhibited the highest incidence of cognitive AEs.

Treatment of advanced Parkinson's disease in the United States: a cost-utility model.

BACKGROUND: As Parkinson's disease (PD) progresses, patients and their families experience substantial health and economic burdens. Because motor fluctuations (also called 'off-time') are linked to poor quality of life and higher healthcare costs, minimizing off-time is an effective strategy for reducing costs associated with PD. OBJECTIVE: To assess the cost utility of rasagiline or entacapone as adjunctive therapies to levodopa versus levodopa/carbidopa/entacapone (LCE) versus standard levodopa monotherapy in patients with advanced PD and motor fluctuations in the US. METHODS: A 2-year stochastic Markov model was utilized to examine the cost effectiveness of treatments of advanced PD. The model assumed that patients transition health status every 4 months. Transition probabilities, including uncertainties, were estimated from clinical trial data. Medical costs, daily drug costs and utility weights were obtained from published literature. RESULTS: Over 2 years, all therapy options showed greater effectiveness than levodopa alone. Rasagiline+levodopa and LCE were cost saving from a payor perspective, while entacapone+levodopa was cost saving from a societal perspective. Mean benefits over 2 years were 0.12 (90% credibility interval [CI] 0.07, 0.18) additional quality-adjusted life-years (QALYs) for rasagiline+levodopa, entacapone+levodopa and LCE, 5.08 (90% CI 3.87, 6.28) additional months with

Drug therapies for Parkinson's disease: A database analysis of patient compliance and persistence.

BACKGROUND: Evaluating medication adherence in Parkinson's disease (PD) is important to avoid erroneously attributing suboptimal patient outcomes from poor compliance to disease progression or adverse responses to medications. OBJECTIVE: This study of patients with PD who were new to PD drug therapy examined patient compliance and persistence, by drug, to provide a comprehensive investigation of medication-taking behavior in PD. METHODS: A retrospective analysis of patients receiving a new PD drug between March 1 and May 31, 2007, was conducted, using the IMS Health longitudinal prescription database, which contains ∼50% of all retail prescriptions and <150 million patients in the United States. Patients were considered to have received a new PD drug if they initiated PD therapy for the first time, added adjunctive PD therapy, or switched one PD drug for another. Patients were categorized as naive to PD therapy (NT) or having prior PD therapy (PT), which included adjunctive use and switches. The PD medications evaluated were rasagiline, levodopa/carbidopa, levodopa/carbidopa/entacapone, the catechol-O-methyltransferase (COMT) inhibitors (entacapone and tolcapone), pramipexole, ropinirole, and selegiline. The study consisted of a 12-month look-back period (during which patients were required to be active in the database), a 3-month selection period (during which patients received their first prescription), and a 12-month observation period. Compliance was measured using the medication possession ratio (MPR; defined as the number of days' supply of medication divided by the number of available days of therapy, from first dispense date in the selection period to last dispense date in the observation period); noncompliance was defined as an MPR ≤80%. Persistence was measured as the duration (days) of uninterrupted therapy. RESULTS: A total of 29,682 patients with PD (19,673 NT, 10,009 PT) received a new PD drug and were analyzed. Of the 19,510 patients included in the compliance analysis, 10,438 (53.5%) had compliance rates >80% and 9072 (46.5%) were noncompliant. For all patients (NT and PT), compliance rates were significantly higher for patients taking rasagiline than for those taking other PD medications (all P < 0.001). For all patients, the highest mean number of persistent days of treatment (147.5) was reported for rasagiline, followed by levodopa/carbidopa/ entacapone (146.9); persistence for both of these drugs was significantly higher than that for the comparator medications (rasagiline vs levodopa/carbidopa, P = 0.002; rasagiline vs pramipexole, P = 0.003; rasagiline vs COMT inhibitors, ropinirole, and selegiline, all P < 0.001; levodopa/carbidopa/entacapone vs levodopa/carbidopa, P = 0.005; levodopa/carbidopa/entacapone vs pramipexole, P = 0.006; levodopa/carbidopa/entacapone vs COMT inhibitors, ropinirole, and selegiline, all P < 0.001). Almost half of the patients (13,103; 44.1%) remained on their PD medication ≥90 days. CONCLUSIONS: This study found a differential compliance and persistence across PD drug therapies. The compliance rate for rasagiline was significantly higher than that for all of the other PD medications. In addition, rasagiline and levodopa/carbidopa/entacapone were associated with significantly higher persistence rates than were the other PD medications.

Cost sharing, benefit design, and adherence: the case of multiple sclerosis.

PURPOSE: The authors focus on understanding the relationship between costs and cost sharing on medication adherence for individuals who initiated a disease-modifying therapy (DMT) for the treatment of multiple sclerosis (MS). DMTs reduce the risk of relapse and are an essential component of MS treatment. Furthermore, the authors compare monthly payment levels for copayments versus coinsurance and estimate the effects on adherence. METHODS: Using the MarketScan Commercial Claims and Encounters database evidence from July 1 2005 to March 31 2008, the authors employ a multivariate two-stage least-squares model (2SLS) to examine the impact of copayments or coinsurance on the medication possession ratio (MPR). FINDINGS: Descriptive results show that the mean out-of-pocket (OOP) costs of DMT per month were higher for patients with coinsurance than for patients with copayments. For the cohort of patients with copayment there was little difference in monthly copayments across adherence thresholds. Regression analysis shows that an increase in cost sharing reduces adherence overall, but this effect was small and insignificant in the copayment cohort. In contrast, in the coinsurance cohort increased cost sharing was significantly associated with decreased adherence to DMT medication; with a 10% increase in cost sharing leading to an 8.6% decline in adherence. IMPLICATIONS: Employers increasingly rely on coinsurance, despite evidence that reliance on coinsurance results in lower adherence. Our research findings suggest that coinsurance appears to be a greater obstacle to compliance, confirming predictions found in the theoretical literature. ORIGINALITY: This research converted counts of injectable treatments into a continuous adherence measure. Previous literature on cost sharing did not examine MS.

Intraoperative hyperglycemia and postoperative bacteremia in the pediatric cardiac surgery patient.

BACKGROUND: Intraoperative hyperglycemia has been found to be associated with a higher incidence of postoperative infections in the adult cardiac surgery population. The goal of this study was to determine the association of intraoperative hyperglycemia and postoperative bacteremia in the pediatric population. METHODS: A retrospective chart review of all cardiac surgical cases for patients 18 years of age or younger requiring cardiopulmonary bypass support between June 2002 and July 2007 yielded 1,132 total cases representing 992 unique patients. Patient demographic and clinical data of interest were collected. Descriptive statistics and regression analyses were performed to investigate the hypothesized relationship between glucose levels and infection rates. RESULTS: From the 992 patient records examined, 15 patients exhibited a bacteremia within 14 days of surgery (1.5%). The association between the highest glucose during cardiopulmonary bypass and bacteremia reached statistical significance when the glucose level reached 175 mg/dL (chi(2) = 4.59, 1 degree of freedom; p = 0.032). A patient was more than three times as likely to have a postoperative bacteremia when the glucose level reached this amount or exceeded it (odds ratio, 3.3, 95% confidence interval, 1.04 to 10.39). Ten of the 15 (66.7%) postoperative infections occurred in patients with peak bypass glucose levels of at least 175 mg/dL. CONCLUSIONS: Intraoperative hyperglycemia was found to be associated with a higher risk of postoperative bacteremia in the pediatric cardiac surgery population.