Publications

BACKGROUND: Recent publications report that gatifloxacin might be associated with a greater incidence of Clostridium difficile-associated diarrhea (C. difficile, CDAD) than are other fluoroquinolones. We performed a drug use evaluation to examine this issue after adding gatifloxacin to the formulary and changing from levofloxacin to gatifloxacin as the preferred oral fluoroquinolone in 10 Department of Veterans Affairs (VA) medical centers in the northeastern United States.

OBJECTIVES: To estimate (1) the overall incidence of CDAD before and after the change from levofloxacin to gatifloxacin as the preferred oral fluoroquinolone and (2) the incidence rates for ciprofloxacin, levofloxacin, and gatifloxacin separately.

METHODS: Using the VA's Pharmacy Benefits Management database, the total number of days of antibiotic therapy was determined for all inpatients and outpatients of the 10 medical centers who filled at least 1 antibiotic prescription between July 1, 2003, and June 30, 2004. This time frame was chosen because it included 6 months before and 6 months after the change in the preferred oral fluoroquinolone from levofloxacin to gatifloxacin for the VA health system on January 1, 2004. For the same study period and medical centers, the electronic medical records of all inpatients and outpatients with an entry for a positive C. difficile toxin were reviewed. Positive toxins that occurred within 6 weeks of a previous positive result in the same patient were excluded. Exact Poisson tests were used to compare the incidence rates of CDAD (number of CDAD cases per 1,000 days of antibiotic treatment) for antibiotics overall, the fluoroquinolones as a group, non-fluoroquinolone antibiotics, and the individual fluoroquinolones, com-paring the 6-month time periods before (pre-change) versus after (post-change) the addition of gatifloxacin as the preferred oral fluoroquinolone.

RESULTS: Of 505 cases of CDAD in the 12-month study period, 413 (81.7%) were associated with antibiotic use in the previous 6 weeks. Among anti-biotic users, incidence rates of CDAD were 166 per 72,114 days of antibiotic therapy in the pre-change period (2.3 cases per 1,000 days of antibiotics) versus 247 per 72,354 days in the post-change period (3.4 cases per 1,000 days of antibiotics, P < 0.001). Fluoroquinolones accounted for 54.8% of the CDAD cases in the pre-change period and 67.2% in the post-change period, representing a 22.6% relative increase in the percentage of CDAD cases that were associated with fluoroquinolone use. The CDAD incidence rates per 1,000 days of fluoroquinolone therapy were 3.7 in the pre-change period versus 7.0 in the post-change period (P < 0.001). Among fluoroqui-nolone users, gatifloxacin accounted for none of the cases of CDAD in the pre-change period when it was nonformulary and 65.1% of the cases in the post-change period, for an incidence rate of 7.6 (108 per 14,239 days). The CDAD incidence rates per 1,000 antibiotic days for patients treated with ciprofloxacin were 4.6 (24 per 5,260 days) in the pre-change period and 7.4 (40 per 5,429 days) in the post-change period, a nonsignificant trend (P = 0.079). The incidence rate of CDAD for levofloxacin increased significantly from 3.9 (75 per 19,417 days) in the pre-change period to 10.7 (44 per 4,108 days) in the post-change period (P < 0.001). The incidence rates of CDAD in the post-change period did not differ significantly for ciprofloxacin, levofloxacin, and gatifloxacin (P = 0.119).

CONCLUSIONS: There was an increase in the incidence of CDAD among all antibiotic users and fluoroquinolone users, but not among users of non-fluoroquinolone antibiotics, in the period following the formulary change from levofloxacin to gatifloxacin as the preferred fluoroquinolone. However, rates of CDAD among the 3 fluoroquinolone antibiotics in the post-change period were not significantly different, and levofloxacin was the only fluoroquinolone that was associated with a significant increase in the rate of CDAD between the pre-change and post-change periods. These findings suggest that the increase in the CDAD incidence rate was probably not attributable to the addition of gatifloxacin to the formulary.

The Department of Veterans Affairs (VA) provides an ideal opportunity to conduct mental health services research among vulnerable populations, given its extensive data sources, disproportionate number of vulnerable patients (older, often with comorbidities), and quality improvement mission. Although VA facilities are often affiliated with universities, successful VA-academic research partnerships are sometimes elusive. The Continuous Improvement for Veterans in Care: Mood Disorders (CIVIC-MD) study was a partnership with a VA facility that had not been engaged in mood disorders research. This column describes how the partnership formed, key elements of its success, and challenges and opportunities to inform future research partnerships.

BACKGROUND: Despite the dissemination of practice guidelines for bipolar disorder, outcomes remain suboptimal, largely due to poor treatment adherence. The episodic nature of bipolar disorder disrupts appropriate patient-provider dynamics, interfering with appropriate care. Maintaining a beneficial therapeutic alliance with providers is one important strategy for improving adherence. We examine the association between adherence and therapeutic environment perceptions among veterans with bipolar disorder.

METHODS: Participants were recruited from the Continuous Improvement for Veterans in Care–Mood Disorders (CIVIC-MD) study (N=435). Individual items and a summary score from the Health Care Climate Questionnaire (HCCQ) for bipolar disorder solicited patient evaluations of their therapeutic environment. Multivariable logistic analyses examined the association between therapeutic alliance and two measures of adherence (missed medication days and intrapersonal barriers), adjusting for relevant patient characteristics.

RESULTS: Adherence difficulty was reported on both measures, with substantial differences between perceived barriers and actual medication behavior. Significantly fewer minority veterans endorsed good adherence than white patients (59% versus 77%), although no ethnic differences were noted in therapeutic environment perceptions. Multivariable results indicated that positive therapeutic alliance was associated with better adherence (HCCQ effect sizes 13-20%). Notably, patients reporting providers encouraged "staying in regular contact" were more likely to be adherent, as were patients whose "providers regularly review their progress".

LIMITATIONS: Generalizability from observational study; adherence defined by cross-sectional patient self-report.

CONCLUSIONS: The observed association between medication adherence and therapeutic alliance with bipolar treatment supports intervention efforts to strengthen the patient-provider relationship, a bond likely to yield positive clinical outcomes.

PURPOSE: The growing presence of female veterans within the Department of Veterans Affairs (VA) health care system highlights the need to assess the quality of and access to gender-specific care for menopause. We assessed the use of hormone therapy (HT) among female veterans before and after the release of the Women's Health Initiative clinical trial results and evaluated whether the structure of women's health care services within the VA system affects the use of HT.

METHODS: We identified all female veterans using HT in 2001 by using the VA pharmacy benefits management database and administrative data. Subjects identified as using HT in 2001 were evaluated to determine estrogen use status in 2003 and 2004. We calculated the change in HT use over time and performed multivariate analyses to identify patient and utilization determinants of HT discontinuation.

RESULTS: In 2001, 36,222 female veterans used HT. By 2004, 23,924 (66%) had discontinued HT. Subjects who had used a VA women's clinic or were younger (40-54 years of age) were significantly less likely to discontinue HT. However, Hispanic ethnicity, African American race, and clinical diagnoses such as heart disease and mastectomy were significantly associated with discontinuation.

CONCLUSION: Discontinuation rates in the VA system parallel those in the private sector. However, patients with any use of VA women's clinics were less likely to discontinue HT, indicating a practice setting variation that may indicate either more specific care or differential implementation of the new HT guidelines. Further research is warranted to assess whether a disparity occurs according to practice setting (or provider factors) with rapid shifts in guidelines.

BACKGROUND: Studies that have assessed antibiotic appropriateness in acute respiratory tract infections (RTIs) with a likely bacterial etiology have focused only on antibiotic choice and ignored other important aspects of prescribing, such as dosing, drug-drug interactions, and duration of treatment.

OBJECTIVE: The aim of this study was to determine the prevalence and predictors of inappropriate antibiotic prescribing practices in outpatients with acute bacterial RTIs (community-acquired pneumonia [CAP], sinusitis, or acute exacerbations of chronic bronchitis [AECB]).

METHODS: This retrospective, cross-sectional study enrolled outpatients with CAP, sinusitis, or AECB who were evaluated in a Veterans Affairs emergency department over a 1-year period. Using electronic medical records, trained research assistants completed data-collection forms that included patient characteristics (eg, marital status, history of alcohol abuse), diagnosis, comorbidities, concurrent medications, and antibiotics prescribed. To assess antimicrobial appropriateness, a trained clinical pharmacist reviewed the data-collection forms and applied a Medication Appropriateness Index (MAI), which rated the appropriateness of a medication using 10 criteria: indication, effectiveness, dosage, directions, practicality (defined as capability of being used or being put into practice), drug-drug interactions, drug-disease interactions, unnecessary duplication, duration, and expensiveness (defined as the cost of the drug compared with other agents of similar efficacy and tolerability). Previous studies have found good inter- and intrarater reliabilities between a clinical pharmacist's and an internal medicine physician's MAI ratings (kappa=0.83 and 0.92, respectively).

RESULTS: One hundred fifty-three patients were included (mean age, 58 years; 92% male; and 65% white). Overall, 99 of 153 patients (65%) had inappropriate antibiotic prescribing as assessed using the MAI. Expensiveness (60 patients [39%]), impracticality (32 [21%]), and incorrect dosage (15 [10%]) were the most frequently rated problem. Penicillins, quinolones, and macrolides were the most common antibiotic classes prescribed inappropriately. A history of alcohol abuse was associated with a lower likelihood of inappropriate prescribing compared with no history of alcohol abuse (adjusted odds ratio [AOR], 0.32; 95% CI, 0.10-0.98), while patients who were married were more likely to receive inappropriately prescribed antibiotics than those who were not married (AOR, 2.64; 95% CI, 1.25-5.59).

CONCLUSIONS: Inappropriate antibiotic prescribing based on the MAI criteria was common (65%) in this selected patient population with acute bacterial RTIs, and often involved problems with expensiveness (39%), impracticality (21%), and incorrect dosage (10%). Future interventions to improve antibiotic prescribing should consider aspects beyond choice of agent.

OBJECTIVE: To estimate potential savings associated with the Consumer Reports Best Buy Drugs program, a national educational program that provides consumers with price and effectiveness information on prescription drugs.

DATA SOURCES: National data on 2006 prescription sales and retail prices paid for angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, calcium channel blockers, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-coA) reductase inhibitors (statins).

STUDY DESIGN: We converted national data on aggregate unit sales of drugs in the four classes to defined daily doses (DDD) and estimated a range of potential savings from generic and therapeutic substitution.

PRINCIPAL FINDINGS: We estimated that $2.76 billion, or 7.83 percent of sales, could be saved if use of the drugs recommended by the educational program was increased. The recommended drugs' prices were 15-65 percent lower per DDD than their therapeutic alternatives. The majority (57.4 percent) of potential savings would be achieved through therapeutic substitution.

CONCLUSIONS: Substantial savings can be achieved through greater use of comparatively effective and lower cost drugs recommended by a national consumer education program. However, barriers to dissemination of consumer-oriented drug information must be addressed before savings can be realized.

BACKGROUND: Previous research has shown that a manufacturer's promotional strategy for a brand name drug is typically affected by generic entry. However, little is known about how newer strategies to extend patent life, including product reformulation introduction or obtaining approval to market for additional clinical indications, influence promotion.

OBJECTIVE: To examine the relationships among promotional expenditures, generic entry, reformulation entry and new indication approval.

METHODS: We used quarterly data on national product-level promotional spending (including expenditures for physician detailing and direct-to-consumer advertising [DTCA], and the retail value of free samples distributed in physician offices) for selective serotonin reuptake inhibitors (SSRIs) over the period 1997-2004. We estimated econometric models of detailing, DTCA and total quarterly promotional expenditures as a function of the timing of generic entry, entry of new product formulations and US FDA approval for new clinical indications for existing medications in the SSRI class. Expenditures by pharmaceutical manufacturers for promotion of antidepressant medications was the main outcome measure.

RESULTS: Over the period 1997-2004, there was considerable variation in the composition of promotional expenditures across the SSRIs. Promotional expenditures for the original brand molecule decreased dramatically when a reformulation of the molecule was introduced. Promotional spending (both total and detailing alone) for a specific molecule was generally lower after generic entry than before, although the effect of generic entry on promotional spending appears to be closely linked with the choice of product reformulation strategy pursued by the manufacturer. Detailing expenditures for Paxil were increased after the manufacturer received FDA approval to market the drug for generalized anxiety disorder (GAD), while the likelihood of DTCA outlays for the drug was not changed. In contrast, FDA approval to market Paxil and Zoloft for social anxiety disorder (SAD) did not affect the manufacturers' detailing expenditures but did result in a greater likelihood of DTCA outlays.

CONCLUSION: The introduction of new product formulations appears to be a common strategy for attempting to extend market exclusivity for medications facing impending generic entry. Manufacturers who introduced a reformulation before generic entry shifted most promotion dollars from the original brand to the reformulation long before generic entry, and in some cases manufacturers appeared to target a particular promotion type for a given indication. Given the significant impact that pharmaceutical promotion has on demand for prescription drugs in the US, these findings have important implications for prescription drug spending and public health.

OBJECTIVE: Previous studies reported that some minority childhood cancer patients are likely to develop worse outcomes than white children. This study examines whether there are racial and ethnic disparities in health expenditures among children with cancer.

RESEARCH DESIGN AND METHODS: A retrospective study was conducted among children (younger than 20) with cancer diagnoses in the Medical Expenditure Panel Survey (MEPS; 1996 to 2004). Total health expenditures and the following subcategories were examined across racial and ethnic groups: (1) office-based visits; (2) outpatient visits; (3) inpatient and emergency room visits; (4) home health care; (5) prescription drugs; and (6) dental, vision, and other health care expenditures. Consumer price indexes were used to convert all expenditures to 2004 dollars. A classical linear model was analyzed using the natural logarithm of health expenditures as the dependent variable, with the purpose of determining whether there were racial and ethnic differences in health expenditures after adjusting for confounding factors.

RESULTS: Study sample included 394 non-Hispanic whites (weighted to 4 958 685), 53 non-Hispanic blacks (weighted to 352 534), and 94 Hispanic whites (weighted to 424 319). Hispanic blacks and other minority populations were excluded from the analysis due to insufficient sample size. The annual total health expenditure for treating each child with cancer was $3467.40, $2156.15, and $5545.34, respectively, among non-Hispanic whites, non-Hispanic blacks, and Hispanic whites. The differences in the various subcategories of health expenditures across racial and ethnic groups were generally not significant according to both descriptive and analytical analyses with very few exceptions.

CONCLUSIONS: This study did not identify significant racial and ethnic disparities in health care costs. However, one important study limitation is the small sample size of the minority populations in the study sample.

BACKGROUND: Despite the importance of equal access to prescription drugs by racial and ethnic groups, studies on access to prescription drugs have been incomprehensive.

OBJECTIVE: To describe the Medical Expenditure Panel Survey (MEPS) as a valuable data source to study racial and ethnic disparities in prescription drug use.

METHODS: Use of the MEPS database to study disparities in prescription drug use is detailed. This includes strengths and limitations of the database, as well as key methodological, sampling, and statistical issues to consider when using it.

RESULTS: Using MEPS allows researchers to control for sociodemographic and health status information when studying racial and ethnic disparities in prescription drug use. MEPS has taken measures to improve reliability of the information on the utilization of prescription drugs. An additional benefit of MEPS is that it has oversampled Hispanics, Blacks, and Asians; as such, it affords the statistical power to examine these minority groups. One limitation of MEPS is the inability of researchers to study some drug categories, because of limitations in statistical power. Moreover, the names of the prescription medications are not standardized in MEPS, and some information is not publicly available in MEPS databases. When conducting studies requiring information not publicly available, researchers may commute to the MEPS Data Center or may request the Data Center to run statistical programs for them.

CONCLUSIONS: Using MEPS to study racial and ethnic disparities in prescription drug use has significant benefits. Nonetheless, researchers need to keep in mind the limitations of using MEPS.