Publications

BACKGROUND: Clinical validation studies of the Healthcare Effectiveness Data and Information Set (HEDIS®) measures of inappropriate prescribing in the elderly are limited.

OBJECTIVES: The objective of this study was to examine associations of new exposure to high-risk medication in the elderly (HRME) and drug-disease interaction (Rx-DIS) with mortality, hospital admission, and emergency care.

METHODS: A retrospective database study was conducted examining new use of HRME and Rx-DIS in fiscal year 2006 (Oct 2005-Sep 2006; FY06), with index date being the date of first HRME/Rx-DIS exposure, or first day of FY07 if no HRME/Rx-DIS exposure. Outcomes were assessed 1 year after the index date. The participants were veterans who were ≥65 years old in FY06 and received Veterans Health Administration (VA) care in FY05-06. A history of falls/hip fracture, chronic renal failure, and/or dementia per diagnosis codes defined the Rx-DIS subsample. The variables included a number of new unique HRME drug exposures and new unique Rx-DIS drug exposure (0, 1, >1) in FY06, and outcomes (i.e., 1-year mortality, hospital admission, and emergency care) up to 1 year after exposure. Descriptive statistics summarized variables for the overall HRME cohort and the Rx-DIS subset. Multivariable statistical analyses using generalized estimating equations (GEE) models with a logit link accounted for nesting of patients within facilities. For these latter analyses, we controlled for demographic characteristics, chronic disease states, and indicators of disease burden the previous year (e.g., number of prescriptions, emergency/hospital care).

RESULTS: Among the 1,807,404 veterans who met inclusion criteria, 5.2 % had new HRME exposure. Of the 256,388 in the Rx-DIS cohort, 3.6 % had new Rx-DIS exposure. Multivariable analyses found that HRME was significantly associated with mortality [1: adjusted odds ratio (AOR) = 1.62, 95 % CI 1.56-1.68; >1: AOR = 1.80, 95 % CI 1.45-2.23], hospital admission (1: AOR = 2.31, 95 % CI 2.22-2.40; >1: AOR = 3.44, 95 % CI 3.06-3.87), and emergency care (1: AOR = 2.59, 95 % CI 2.49-2.70; >1: AOR = 4.18, 95 % CI 3.71-4.71). Rx-DIS exposure was significantly associated with mortality (1: AOR = 1.60, 95 % CI 1.51-1.71; >1: AOR = 2.00, 95 % CI 1.38-2.91), hospital admission for one exposure (1: AOR = 1.12, 95 % CI 1.03-1.27; >1: AOR = 1.18, 95 % CI 0.71-1.95), and emergency care for two or more exposures (1: AOR = 1.06, 95 % CI 0.97-1.15; >1: AOR = 2.0, 95 % CI 1.35-3.10).

CONCLUSIONS: Analyses support the link between HRME/Rx-DIS exposure and clinically significant outcomes in older veterans. Now is the time to begin incorporating input from both patients who receive these medications and providers who prescribe to develop approaches to reduce exposure to these agents.

OBJECTIVE: The objective of the study was to assess the adherence to hormonal contraception (pill, patch, ring, or injectable) among women veterans and examine the relationships between race/ethnicity and the months of contraceptive supply dispensed with contraceptive adherence.

STUDY DESIGN: We conducted a retrospective analysis of the Department of Veterans Affairs (VA) national databases to examine the adherence to hormonal contraception over 12 months among women aged 18-45 years who had hormonal contraceptive coverage during the first week of fiscal year 2008. We examined several adherence indicators including gaps between refills and months of contraceptive coverage. Descriptive statistics and multivariable models were used to examine the associations between race/ethnicity and contraceptive supply dispensed with adherence.

RESULTS: Our cohort included 6946 women: 47% were white, 6% were Hispanic, 22% were black, and 25% were other race or had missing race information. Most women (83%) received a 3 month supply of contraception at each fill. More than 64% of women had at least 1 gap in coverage of 7 days or longer. Only 22% of women received a full 12 months of contraception without any gaps (perfect adherence). Compared with whites, Hispanics were significantly more likely to experience gaps (64% vs 70%; P = .02), and Hispanics and blacks received fewer months of contraceptive coverage (9.3 vs 8.9 and 9.0, P < .001). Compared with women receiving 3 month supplies, those receiving 1 month supplies had a higher likelihood of a gap (63% vs 72%, P < .001), fewer months of coverage (9.3 vs 6.9, P < .001), and a lower likelihood of perfect adherence (22% vs 11%, P < .001).

CONCLUSION: Adherence to hormonal contraception among women veterans is poor. Efforts to improve contraceptive adherence and lower risk of unintended pregnancy are needed; dispensing more months of supply for hormonal contraception may be a promising strategy.

BACKGROUND: Medicare Part D and the U.S. Department of Veterans Affairs (VA) use different approaches to manage prescription drug benefits, with implications for spending. Medicare relies on private plans with distinct formularies, whereas the VA administers its own benefit using a national formulary.

OBJECTIVE: To compare overall and regional rates of brand-name drug use among older adults with diabetes in Medicare and the VA.

DESIGN: Retrospective cohort.

SETTING: Medicare and the VA, 2008.

PATIENTS: 1,061,095 Medicare Part D beneficiaries and 510,485 veterans aged 65 years or older with diabetes.

MEASUREMENTS: Percentage of patients taking oral hypoglycemics, statins, and angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) who filled brand-name drug prescriptions and percentage of patients taking long-acting insulins who filled analogue prescriptions. Sociodemographic- and health status-adjusted hospital referral region (HRR) brand-name drug use was compared, and changes in spending were calculated if use of brand-name drugs in 1 system mirrored the other.

RESULTS: Brand-name drug use in Medicare was 2 to 3 times that in the VA: 35.3% versus 12.7% for oral hypoglycemics, 50.7% versus 18.2% for statins, 42.5% versus 20.8% for ACE inhibitors or ARBs, and 75.1% versus 27.0% for insulin analogues. Adjusted HRR-level brand-name statin use ranged (from the 5th to 95th percentiles) from 41.0% to 58.3% in Medicare and 6.2% to 38.2% in the VA. For each drug group, the 95th-percentile HRR in the VA had lower brand-name drug use than the 5th-percentile HRR in Medicare. Medicare spending in this population would have been $1.4 billion less if brand-name drug use matched that of the VA.

LIMITATION: This analysis cannot fully describe the factors underlying differences in brand-name drug use.

CONCLUSION: Medicare beneficiaries with diabetes use 2 to 3 times more brand-name drugs than a comparable group within the VA, at substantial excess cost.

PURPOSE: A Web-based application for coordinating medication-use evaluation (MUE) initiatives within the Veterans Affairs (VA) health care system is described.

SUMMARY: The MUE Tracker (MUET) software program was created to improve VA's ability to conduct national medication-related interventions throughout its network of 147 medical centers. MUET initiatives are centrally coordinated by the VA Center for Medication Safety (VAMedSAFE), which monitors the agency's integrated databases for indications of suboptimal prescribing or drug therapy monitoring and adverse treatment outcomes. When a pharmacovigilance signal is detected, VAMedSAFE identifies "trigger groups" of at-risk veterans and uploads patient lists to the secure MUET application, where locally designated personnel (typically pharmacists) can access and use the data to target risk-reduction efforts. Local data on patient-specific interventions are stored in a centralized database and regularly updated to enable tracking and reporting for surveillance and quality-improvement purposes; aggregated data can be further analyzed for provider education and benchmarking. In a three-year pilot project, the MUET program was found effective in promoting improved prescribing of erythropoiesis-stimulating agents (ESAs) and enhanced laboratory monitoring of ESA-treated patients in all specified trigger groups. The MUET initiative has since been expanded to target other high-risk drugs, and efforts are underway to refine the tool for broader utility.

CONCLUSION: The MUET application has enabled the increased standardization of medication safety initiatives across the VA system and may serve as a useful model for the development of pharmacovigilance tools by other large integrated health care systems.

BACKGROUND: Pharmacists successfully manage patients with anemia and chronic kidney disease (CKD), but the cost effectiveness of these programs is unknown.

OBJECTIVE: To compare the cost effectiveness of pharmacist-managed erythropoiesis-stimulating agent (ESA) clinics with that of usual care in patients with non-dialysis-dependent (NDD)-CKD.

METHODS: A Markov model was used to estimate the incremental cost effectiveness of pharmacist-managed ESA clinics compared with usual care in outpatient veterans receiving ESAs for NDD-CKD in 2009. The analysis was conducted from a US Veterans Health Administration perspective with a 5-year time horizon, and the year of valuation for cost results was 2012. The effect of parameter uncertainty was explored in one-way and probabilistic sensitivity analyses.

RESULTS: In the deterministic base case analysis, costs and effectiveness per patient over 5 years were US$13,412 and 2.096 quality-adjusted life-years (QALYs) in the pharmacist-managed ESA clinics and US$16,173 and 2.093 QALYs in usual care; ESA clinics dominated usual care. In one-way sensitivity analyses, ESA clinics no longer dominated if their patients' probability of being in the target hemoglobin range fell to 52 % (base case 71 %) or if the mean cost/patient/month of epoetin or darbepoetin in ESA clinics increased to approximately US$382 (base case US$226) or US$477 (base case US$268), respectively. When all parameters were varied simultaneously in a probabilistic sensitivity analysis, ESA clinics were favored ≥80 % of the time at willingness-to-pay thresholds of US$0-$100,000 per QALY gained.

CONCLUSIONS: Pharmacist-managed ESA clinics were less costly and more effective than usual care in patients receiving ESAs for anemia and NDD-CKD. Results were robust to variation and support the use of pharmacist-managed ESA clinics.

BACKGROUND: Cholinesterase inhibitors and memantine are prescribed to slow the progression dementia. Although the efficacy of these drugs has been demonstrated, their effectiveness, from the perspective of patients and caregivers, has been questioned. Little is known about whether the demand for cholinesterase inhibitors and memantine are sensitive to out-of-pocket cost. Using the 2006 implementation of Medicare Part D as a natural experiment, this study examines the impact of changes in drug coverage on use of cholinesterase inhibitors and memantine by comparing use before and after Medicare Part D implementation among older adults who did and did not experience a change in coverage.

METHODS: Retrospective analyses of claims data from 35,102 community-dwelling Medicare beneficiaries in Pennsylvania aged 65 or older. Beneficiaries were continuously enrolled in a Medicare Advantage plan from 2004 to 2007. Outcome variables were any use of donepezil (Aricept(®)), galantamine (Razadyne(®)), rivastigmine (Exelon(®)), tacrine (Cognex(®)), or memantine (Namenda(®)) each year and the number of 30-day prescriptions filled for these drugs. Independent variables included type of drug benefit pre-Part D (No coverage, $150 cap, $350 cap, and No cap as the reference group), time period, and their interaction. Sensitivity analyses were conducted to test if there are differences in use by drug class or if beneficiaries with a diagnosis of dementia pre-Part D experienced an increase in use post-Part D.

RESULTS: The No coverage group had a 38% increase in the odds ratio of any use of antidementia medications (P = 0.0008) post-Part D relative to the No cap group. All four coverage groups had significant increases in number of 30-day prescriptions (P < 0.001) over the study period. In adjusted models that included the sub-sample with any use pre-Part D, the No coverage group had a 36% increase in prescriptions (P = 0.002) and the $350 cap group had a 15% increase (P = 0.003) after adjusting for trends in the No cap group. Results from the sensitivity analysis for the sub-sample with a diagnosis of dementia pre-Part D show that each group had significant increases in 30-day prescriptions compared to the No cap control group (P < 0.05).

CONCLUSIONS: Use of cholinesterase inhibitors and memantine in our sample increased and a greater increase in use was observed among Medicare beneficiaries who experienced improvements in drug coverage under Medicare Part D.

OBJECTIVE: The authors examined physician adoption of second-generation antipsychotic medications and identified physician-level factors associated with early adoption.

METHODS: The authors estimated Cox proportional-hazards models of time to adoption of nine second-generation antipsychotics by 30,369 physicians who prescribed antipsychotics between 1996 and 2008, when the drugs were first introduced, and analyzed the total number of agents prescribed during that time. The models were adjusted for physicians' specialty, demographic characteristics, education and training, practice setting, and prescribing volume. Data were from IMS Xponent, which captures over 70% of all prescriptions filled in the United States, and the American Medical Association Physician Masterfile.

RESULTS: On average, physicians waited two or more years before prescribing new second-generation antipsychotics, but there was substantial heterogeneity across products in time to adoption. General practitioners were much slower than psychiatrists to adopt second-generation antipsychotics (hazard ratios (HRs) range .10-.35), and solo practitioners were slower than group practitioners to adopt most products (HR range .77-.89). Physicians with the highest antipsychotic-prescribing volume adopted second-generation antipsychotics much faster than physicians with the lowest volume (HR range .15-.39). Psychiatrists tended to prescribe a broader set of antipsychotics (median=6) than general practitioners and neurologists (median=2) and pediatricians (median=1).

CONCLUSIONS: As policy makers search for ways to control rapid health spending growth, understanding the factors that influence physician adoption of new medications will be crucial in the efforts to maximize the value of care received by individuals with mental disorders as well as to improve medication safety.

OBJECTIVE: Effectiveness trials have confirmed the superiority of clozapine in schizophrenia treatment, but little is known about whether the drug's superiority holds across racial-ethnic groups. This study examined the effectiveness by race-ethnicity of clozapine relative to other antipsychotics among adult patients in maintenance antipsychotic treatment.

METHODS: Black, Latino, and white Florida Medicaid beneficiaries with schizophrenia receiving maintenance treatment with clozapine or other antipsychotics between July 1, 2000, and June 30, 2005, were identified. Cox proportional hazard regression models were used to estimate associations between clozapine and race-ethnicity and their interaction; time to discontinuation for any cause was the primary measure of effectiveness.

RESULTS: The 20,122 members of the study cohort accounted for 20,122 antipsychotic treatment episodes; 3.7% were treated with clozapine and 96.3% with other antipsychotics. Blacks accounted for 23% of episodes and Latinos for 36%. Unadjusted analyses suggested that Latinos continued on clozapine longer than whites and that Latinos and blacks discontinued other antipsychotics sooner than whites. Adjusted analyses of 749 propensity score-matched sets of clozapine users and other antipsychotic users indicated that risk of discontinuation was lower for clozapine users (risk ratio [RR]=.45, 95% confidence interval [CI]=.39-.52), an effect that was not moderated by race-ethnicity. Times to discontinuation were longer for clozapine users. Overall risk of antipsychotic discontinuation was higher for blacks (RR=1.56, CI=1.27-1.91) and Latinos (RR=1.23, CI=1.02-1.48).

CONCLUSIONS: The study confirmed clozapine's superior effectiveness and did not find evidence that race-ethnicity modified this effect. The findings highlight the need for efforts to increase clozapine use, particularly among minority groups.

BACKGROUND: Medicare Part D and the U.S. Department of Veterans Affairs (VA) use different approaches to manage prescription drug benefits, with implications for spending. Medicare relies on private plans with distinct formularies, whereas the VA administers its own benefit using a national formulary.

OBJECTIVE: To compare overall and regional rates of brand-name drug use among older adults with diabetes in Medicare and the VA.

DESIGN: Retrospective cohort.

SETTING: Medicare and the VA, 2008.

PATIENTS: 1,061,095 Medicare Part D beneficiaries and 510,485 veterans aged 65 years or older with diabetes.

MEASUREMENTS: Percentage of patients taking oral hypoglycemics, statins, and angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) who filled brand-name drug prescriptions and percentage of patients taking long-acting insulins who filled analogue prescriptions. Sociodemographic- and health status-adjusted hospital referral region (HRR) brand-name drug use was compared, and changes in spending were calculated if use of brand-name drugs in 1 system mirrored the other.

RESULTS: Brand-name drug use in Medicare was 2 to 3 times that in the VA: 35.3% versus 12.7% for oral hypoglycemics, 50.7% versus 18.2% for statins, 42.5% versus 20.8% for ACE inhibitors or ARBs, and 75.1% versus 27.0% for insulin analogues. Adjusted HRR-level brand-name statin use ranged (from the 5th to 95th percentiles) from 41.0% to 58.3% in Medicare and 6.2% to 38.2% in the VA. For each drug group, the 95th-percentile HRR in the VA had lower brand-name drug use than the 5th-percentile HRR in Medicare. Medicare spending in this population would have been $1.4 billion less if brand-name drug use matched that of the VA.

LIMITATION: This analysis cannot fully describe the factors underlying differences in brand-name drug use.

CONCLUSION: Medicare beneficiaries with diabetes use 2 to 3 times more brand-name drugs than a comparable group within the VA, at substantial excess cost.