Fidaxomicin for Clostridium difficile-associated diarrhoea: epidemiological method for estimation of warranted price.

BACKGROUND: Fidaxomicin is a macrocyclic antibiotic approved in 2011 by the US Food and Drug Administration for treatment of Clostridium difficile-associated diarrhoea (CDAD). OBJECTIVE: Herein, we present an epidemiological method to estimate, on a case mix basis, and from the perspective of the US health system, the warranted (justifiable) price per day for fidaxomicin, as a percent of the wholesale acquisition cost (WAC) per day for fidaxomicin ($US280). METHODS: Data from two randomized controlled studies (Optimer-003 [n = 596] and Optimer-004 [n = 509]) were used to discern the number-needed-to-treat (NNT = 7.1) for sustained clinical response. Sustained clinical response was defined as clinical response at the end of treatment, and survival without proven or suspected CDAD recurrence through 25 days beyond the end of treatment. National data for primary and secondary cases (the case mix) of CDAD (mean hospital length of stay [LOS], and mean cost) were derived from the 2009 US Healthcare Cost and Utilization Project. The method for attribution of hospital LOS for secondary cases of CDAD was derived from a study published by O'Brien et al. in 2007. Comparative regimens of vancomycin were: (i) injectable used orally, 125 mg four times daily (qid; WAC of $US6/day), with use of vancomycin hydrochloride (HCl) capsules, 125 mg qid (WAC of $US106/day) post-hospital discharge; (ii) vancomycin HCl capsules, 125 mg qid; and (iii) vancomycin HCl capsules, 250 mg qid (WAC of $US196/day). Findings are expressed in 2011 US dollars. The study perspective is that of the US health system. RESULTS: The warranted price per day for fidaxomicin represented 95% of the WAC per day for fidaxomicin compared with use of injectable vancomycin (orally) 125 mg qid (with subsequent use of vancomycin HCl capsules, 125 mg qid post-hospital discharge); 109% of the WAC per day for fidaxomicin compared with use of vancomycin HCl capsules, 125 mg qid; and 141% of the WAC per day for fidaxomicin when compared with use of vancomycin HCl capsules, 250 mg qid. CONCLUSION: From the perspective of the US health system, fidaxomicin represents value for money in the treatment of CDAD. The methodology employed in this research has application beyond antimicrobial pharmacotherapy.

Concomitant use of triptan, and SSRI or SNRI after the US Food and Drug Administration alert on serotonin syndrome.

OBJECTIVE: The present study was designed to discern the prevalence of concomitant use of a 5-hydroxytryptamine receptor agonist (triptan), and a selective serotonin reuptake inhibitor (SSRI) or a selective serotonin/norepinephrine reuptake inhibitor (SNRI) after the US Food and Drug Administration issued an alert regarding serotonin syndrome in 2006 and to contrast findings with data published prior to the federal warning. BACKGROUND: In July 2006, the US Food and Drug Administration warned patients and health-care professionals to be aware that use of a triptan in combination with an SSRI or SNRI may result in a potentially life-threatening problem known as serotonin syndrome. In 2010, the American Headache Society published a position paper noting that there existed conflicting and insufficient information to discern the risk of serotonin syndrome with the use of triptan, and SSRI or SNRI, and that said Class IV data were not to be used as the basis for limiting the prescribing of triptan with SSRI or SNRI (Level U). Clinicians were cautioned as to the seriousness of serotonin toxicity and that monitoring was warranted. METHODS: We used weighted data from the US National Ambulatory Medical Care Survey for years 2007 and 2008 to derive national estimates of the number of office-based physician-patient encounters (visits), documenting the concomitant use of triptan, and SSRI or SNRI. Results are compared with previously published findings for the years 2003 and 2004. RESULTS: During the time-frame 2007-2008, an annualized mean of 5,256,958 patients were prescribed a triptan (vs 3,874,367 in 2003-2004, a 35.7% increase), and 68,603,600 patients were prescribed an SSRI or SNRI (vs 50,402,149 in 2003-2004, a 36.1% increase). An annualized mean of 1,319,763 patients were simultaneously prescribed or continued use of triptan, along with SSRI or SNRI (vs 694,276 in 2003-2004, a 90.1% increase). CONCLUSION: Our study documents that 1.8% (1,319,763/73,860,558) of patients in 2007-2008 were prescribed triptan, and SSRI or SNRI (vs 1.3% in 2003-04, an increase of 38.5%). While this is a small fraction overall, the actual number of patients on a nationwide basis is substantial. What remains missing from the literature is documentation as to the number of cases of serotonin syndrome and resulting consequences (clinical and economic) because of the concomitant use of triptan, and SSRI or SNRI in the time-frame 2007-2008. Absent in these data, it remains difficult to assess the risk benefit associated with the use of triptan, and SSRI or SNRI.

Diagnosis of depression and use of antidepressant pharmacotherapy among adults in the United States: does a disparity persist by ethnicity/race?

BACKGROUND AND OBJECTIVE: Both the rate of diagnosis of depression in the US and the rate of prescribing an antidepressant for its treatment have increased substantially over the past two decades. Previous research has also indicated that the rates of diagnosis and treatment of depression with an antidepressant vary widely by ethnicity/race. The objective of this study was to discern ethnic/race-specific (non-Hispanic Black; Hispanic; non-Hispanic White) population-adjusted rates of US office-based physician-patient encounters (office-based visits) documenting a diagnosis of depression, and the extent of the use of antidepressant pharmacotherapy for its treatment. METHODS: Data from the US National Ambulatory Medical Care Survey (NAMCS) for the years 1992-1997 and 2003-2008 were utilized for this analysis. The years 1998-2002 were excluded due to the magnitude of missing data for the variable ethnicity. The US NAMCS is a national probability sample designed and conducted by the US National Center for Health Statistics of the US Centers for Disease Control and Prevention. Depression was defined via International Classification of Diseases, 9th Revision, Clinical Modification codes 296.2-296.36; 300.4; 311. Antidepressants were defined as US National Drug Code category 0630 prior to 2005, and category 249 in Lexicon Plus® thereafter. Data were partitioned into six 2-year time intervals for trend analysis of population-adjusted rates (per 100) among patients aged 20-79 years. Rates per 2-year time interval are based on US Census Bureau national resident population estimates for the ethnicity/race categories examined. Comparisons within and across time-frames were assessed by chi-squared (χ2) analysis. The a priori level of significance for all statistical tests was set at p < 0.05. Analyses were performed using SAS Release 9.1.3. RESULTS: Over the 12-year time-frame examined, the rate of office-based visits documenting a diagnosis of depression increased 28.4% for non-Hispanic Whites (from 10.9 to 14.0 per 100; p < 0.001), 54.8% for non-Hispanic Blacks (from 4.2 to 6.5 per 100; p < 0.001), and 37.5% for Hispanics (from 4.8 to 6.6 per 100; p < 0.001). The rate of office-based visits with a recorded diagnosis of depression in concert with the prescribing of an antidepressant increased 66.2% for non-Hispanic Whites (from 6.5 to 10.8 per 100; p < 0.001), 69.2% for non-Hispanic Blacks (from 2.6 to 4.4 per 100; p < 0.001), and 36.7% for Hispanics (from 3.0 to 4.1 per 100; p < 0.001). CONCLUSION: By 2003-2004, the population-adjusted rates for non-Hispanic Blacks and Hispanics were similar, and remained so through 2007-2008. However, over the 12-year time-frame examined, the rates for both minority groups were, in each 2-year interval, far less than that observed in non-Hispanic Whites. Disparities remain by ethnicity/race in the diagnosis and treatment of depression in the US.