Sponsorship, antidepressant dose, and outcome in major depressive disorder: meta-analysis of randomized controlled trials.

OBJECTIVE: Differences in dosing may influence results of pharmaceutical industry-sponsored medication trials. This study aims to determine the relationship between sponsorship and antidepressant dosing and efficacy in randomized controlled trials for major depressive disorder. DATA SOURCES: Trials were identified through English-language searches of MEDLINE and PsycINFO (January 1996-June 2010) using specific drug names and classes and depressive disorder or major depression and double blind or double-blind method. Other limitations included human subjects and treatment study designs using the clinical queries option. Other sources were also searched following a strict set of inclusion and exclusion criteria. STUDY SELECTION: Randomized controlled trials were included if they examined antidepressant treatment for major depressive disorder, reported mean final medication dosages, acknowledged an association with industry, and included study arms of medications produced by the associated manufacturer and a competitor ("sponsor" and "nonsponsor" arms) (58 trials involving 15,026 patients from 101 citations identified). DATA EXTRACTION: Data on dosing, efficacy, baseline severity, and adverse events were extracted by 2 of the authors. RESULTS: Meta-analyses were used to examine dosing and efficacy data. Using consensus guidelines for medication dosing, we determined that sponsor medication was dosed relatively higher than nonsponsor medication, in 37% (22/60) of comparisons as opposed to 5% (3/60) in which the nonsponsor medication was dosed higher (χ²2 = 25.9, P < .001). Trials in which sponsor drugs were dosed higher than nonsponsor drugs demonstrated higher remission rates for the sponsor drug (OR = 1.28, 95% CI = 1.11-1.47, P < .001). These results were confirmed using regulatory dosing guidelines. There was no significant correlation between dosing or outcome with baseline severity or adverse events. CONCLUSIONS: Sponsor drugs are dosed higher than nonsponsor drugs in antidepressant randomized controlled trials, and higher dosing is associated with better sponsor drug outcomes in some cases.

Validity and responsiveness to change of clinically derived MDS scales in Alzheimer disease outcomes research.

This analysis assessed 3 subscales derived from the nursing home Minimum Data Set (MDS), the Cognitive Performance Scale (CPS), Depression Rating Scale (DRS), and Aggressive Behavior Scale (ABS), as outcome measures in clinical trials of long-term care residents with Alzheimer disease (AD). A total of 26 patients with moderate-to-severe AD and agitation/aggression enrolled in a trial of memantine were assessed using the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory Nursing Home Version (NPI-NH), and the Cohen-Mansfield Agitation Inventory (CMAI) administered by trained researchers. MDS data were collected as part of their standard clinical care. The MDS subscales correlated significantly with their corresponding research scales: CPS and MMSE (r = -0.57, P = .003); DRS and NPI-NH total (r = 0.42, P = .038); DRS and NPI-NH depression (r = 0.41, P = .04), and ABS and CMAI (r = 0.54, P = .004). DRS and ABS scores did not change significantly from baseline to 3 months though the NPI-NH and CMAI did, indicating limited sensitivity to change. This suggests that the MDS subscales measure comparable aspects of cognitive function and depressive and agitated/aggressive behavior as the MMSE, NPI-NH, and CMAI. However, this analysis also suggests that sensitivity to change of the DRS and ABS may be limited compared to the NPI-NH and CMAI. As these findings are preliminary, further research is needed to determine the utility of MDS scales in outcomes research.

Changing costs and the impact on RSV prophylaxis.

OBJECTIVE: Acquisition costs of palivizumab have increased in Canada since 2007. This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada for premature infants born between 32 and 35 weeks' gestational age using updated 2010 healthcare costs compared to those used in a 2007 decision analytic model. METHODS: New costs (CAN$) were acquired from the same Health Canada and Ontario Ministry of Health sources that were utilized in the previously published 2007 model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as of August 2010. RESULTS: Incremental cost-effectiveness ratios (ICERs) rose by $742, going from $30,618/QALY to $31,360/QALY. ICER changes increased from a range of $801,297 to $820,701 for infants with zero risk factors to a decrease from $808 to $192 for infants with four or more risk factors. CONCLUSIONS: Palivizumab ICERs remained fairly stable from 2007 to 2010. The original recommendation stating that palivizumab is cost effective in infants born between 32 and 35 weeks' GA with two or more risk factors, or who are at moderate-to-high risk based on a risk assessment model, does not change. Analyses founded on evolving country-specific variables are needed in order to accurately reassess the cost effectiveness of interventions as costs change worldwide. LIMITATIONS: There are a limited number of publications reporting mortality in premature Canadian infants with RSV as a primary outcome. In addition, conclusions drawn from this analysis are country-specific and limited to premature infants dwelling in Canada.

The cost effectiveness of palivizumab: a systematic review of the evidence.

OBJECTIVE: Palivizumab is a prophylactic therapy shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations but has a high acquisition cost. The objective was to systematically examine the cost effectiveness of palivizumab in defined infant groups and identify important cost and outcome determinants. METHODS: Literature searches of MedLine, the Cost-Effectiveness Analysis registry and the UK NHS Economic Evaluation Database (NHS EED) were conducted to identify economic evaluations of palivizumab compared to no prophylactic treatment for RSV prevention in any infant population. Study quality was evaluated using Quality of Health Economic Studies (QHES) criteria and results converted to 2009 CAN$ for comparison. RESULTS: A total of 23 articles meeting inclusion criteria were identified, including 11 cost-utility analyses (CUAs) and 12 cost-effectiveness analyses (CEAs). Quality of individual analyses was fairly high (range 60-100, median 86). Results ranged from cost dominance for prophylaxis to $3,365,769/QALY depending on population, outcome measures, and input parameters. Base-case and sensitivity-analysis mortality rates varied between studies and influenced results. CONCLUSIONS: RSV prophylaxis with palivizumab is cost effective in specific groups of high-risk infants, especially those with multiple environmental risk factors. Cost-effectiveness estimates vary between populations and settings and are more positive in those at highest risk for RSV hospitalization. LIMITATIONS: Direct comparison of the published reports was limited by restriction to English language articles and the varied methodologies, input measures, and populations across the studies reviewed. Although reported currencies were converted to a common unit for comparison, this does not completely account for monetary and inflation differences.