Plan designs that encourage the use of generic drugs over brand-name drugs: an analysis of a free generic benefit.

OBJECTIVE: To evaluate the effect on adherence and medical care expenditures of a pharmacy benefit change that included free generic drugs and higher copayments for brand-name drugs. STUDY DESIGN: Quasi-experimental pre-post study of patients with ischemic heart disease (1286 control and 555 intervention) and patients with diabetes mellitus (4089 control and 1846 intervention). METHODS: Medical and pharmacy claims data were analyzed for continuously enrolled members from January 1, 2005, through December 31, 2008. A generalized linear model was used to predict costs as adherence changed. RESULTS: The rate of switching from brand-name drugs to generic drugs in the intervention group was not statistically different from that in the control group. The net change in adherence was higher only for the intervention group patients taking statins who switched to generic drugs, a 6.2% increase compared with an 8.5% decrease in the control group. The estimate of medical cost savings attributable to this benefit change was significant for only the metformin class of diabetes drugs. Improved adherence independent of this benefit change was estimated to reduce all-cause medical costs for patients taking sulfonylureas, metformin, and thiazolidinediones. CONCLUSIONS: Altering copayments for pharmaceuticals may affect the rate of conversion to generic drugs but is unlikely in and of itself to result in complete conversion. However, increasing adherence can result in net savings for specific diabetic drug classes, as savings from all-cause medical costs offset the increase in pharmacy costs.

An evaluation of the relationship between the implementation of a newly designed prescription drug label at Target pharmacies and health outcomes.

BACKGROUND: Medication errors represent a major public health concern, and inadequate prescription drug labels have been identified as a root cause of errors. A new prescription medication labeling system was implemented by Target pharmacies in May 2005 and aimed to improve health outcomes. OBJECTIVES: To evaluate whether the new Target label influenced patient health services utilization. SUBJECTS: Derived from 2 large health plans. RESEARCH DESIGN AND MEASURES: Using administrative claims, we identified patients with 1 of 9 chronic diseases who filled prescriptions at Target pharmacies and a matched sample who filled prescriptions at other community pharmacies. We stratified our cohort into new and prevalent medication users and evaluated the impact of the Target label on outpatient, emergency department and inpatient health services use. We used linear regression and segmented linear regression to evaluate the new-user and prevalent-user analyses, respectively. RESULTS: Our sample included 23,745 Target pharmacy users and 162,369 matched non-Target pharmacy users. In the new-user analysis, we found no significant change in rates of both outpatient (event rate ratio: 0.53; 95% CI: 0.15-1.86) and inpatient and emergency department (Event rate ratio: 0.88; 95% CI: 0.62-1.24) health services utilization in Target users after implementation when compared with non-Target users. Similarly, in the prevalent user analysis, we found no change in the level or slope of outpatient or emergency/inpatient services in Target users after implementation of the new label when compared with non-Target users. CONCLUSIONS: We found no statistically significant change in health services use attributable to the implementation of the new prescription drug label at Target pharmacies. These findings highlight the challenge of influencing health outcomes with interventions to improve health literacy.

Can improved prescription medication labeling influence adherence to chronic medications? An evaluation of the Target pharmacy label.

BACKGROUND: Prescription medication labels contain valuable health information, and better labels may enhance patient adherence to chronic medications. A new prescription medication labeling system was implemented by Target pharmacies in May 2005 and aimed to improve readability and understanding. OBJECTIVE: We evaluated whether the new Target label influenced patient medication adherence. DESIGN AND PATIENTS: Using claims from two large health plans, we identified patients with one of nine chronic diseases who filled prescriptions at Target pharmacies and a matched sample who filled prescriptions at other community pharmacies. MEASUREMENTS: We stratified our cohort into new and prevalent medication users and evaluated the impact of the Target label on medication adherence. We used linear regression and segmented linear regression to evaluate the new-user and prevalent-user analyses, respectively. RESULTS: Our sample included 23,745 Target users and 162,368 matched non-Target pharmacy users. We found no significant change in adherence between new users of medications at Target or other community pharmacies (p = 0.644) after implementing the new label. In prevalent users, we found a 0.0069 percent reduction in level of adherence (95% CI -0.0138-0.0; p < 0.001) and a 0.0007 percent increase in the slope in Target users (the monthly rate of change of adherence) after implementation of the new label (95% CI 0.0001-0.0013; p = 0.001). CONCLUSIONS: We found no changes in adherence of chronic medication in new users, and small and likely clinically unimportant changes in prevalent users after implementation of the new label. While adherence may not be improved with better labeling, evaluation of the effect of labeling on safety and adverse effects is needed.

Rosiglitazone and pioglitazone utilization from January 2007 through May 2008 associated with five risk-warning events.

BACKGROUND: Rosiglitazone was approved by the U.S. Food and Drug Administration (FDA) for type 2 diabetes in 1999. The unique mechanism of action and low risk of hypoglycemia contributed to rapid market uptake of rosiglitazone, but safety concerns became more prominent in 2007. There were 5 major events on 4 calendar days in 2007 regarding safety concerns related to rosiglitazone in certain patients: (1) the May 21, 2007, online release of the rosiglitazone meta-analysis performed by Nissen and Wolski and the FDA safety warning on the same day; (2) the July 30, 2007, conclusion of an FDA advisory committee meeting that rosiglitazone increased cardiac ischemic risk; (3) the August 14, 2007, update of thiazolidinedione (TZD) labels with a black-box warning for heart failure; and (4) the November 14, 2007, update to the warnings and precautions section of the rosiglitazone label for coadministration of nitrate or insulin. OBJECTIVES: To (1) describe TZD (rosiglitazone and pioglitazone) utilization trends from January 1, 2007, continuing through May 2008 amid public announcements of safety concerns and (2) determine the percentage of TZD users who had medical claims indicating increased cardiovascular (CV) risk before and after release (May 21, 2007) of the FDA safety warning and online release of the meta-analysis performed by Nissen and Wolski. METHODS: A retrospective analysis of pharmacy claims was performed from 9 commercial plans with a combined 9 million eligible members, including a 1.4 million-member cohort from 1 of the plans for which medical claims data were available. We evaluated trends in TZD use for each month for the 17-month period from January 1, 2007, through May 31, 2008, including the percentage of TZD users at increased CV risk. In the trend analysis, for each calendar month of 2007, we calculated mean pharmacy claim counts per day per million members for each of the 2 TZD drugs and for a comparison drug, sitagliptin, a new oral hypoglycemic agent in a different class (dipeptidyl-peptidase-IV inhibitors). For the CV risk analysis, we used the database of integrated medical and pharmacy claims for the 1.4 million-member cohort to identify patients with a current days supply of a TZD on May 20, 2007, December 7, 2007, or May 20, 2008. The medical claims for all identified patients were queried back 2 years from May 20, 2007, December 7, 2007, or May 20, 2008, respectively. Rosiglitazone users at increased CV rsk were defined as those with a medical claim with a primary diagnosis for congestive heart failure (CHF; International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 428.xx or 398.91), those with a current supply of nitrate or insulin therapy, or those with ischemic heart disease, including myocardial infarction (MI; ICD-9-CM codes 410.xx through 414.xx, or surgical procedure codes [36.0x through 36.3x for removal of obstruction and insertion of stents, bypass surgery, and revascularization] in the primary diagnosis field). Pioglitazone users at increased risk were identified from medical claims with a CHF diagnosis code. RESULTS: The average number of claims per day per million members in January 2007 was 97.3 for rosiglitazone and 107.2 for pioglitazone. The average number of claims for rosiglitazone per day per million members began to decrease in May 2007, falling to 41.0 in December 2007, for a total decrease of 58.6% from the February 2007 peak (99.1), and fell further to 31.8 in May 2008. Pioglitazone use increased 8.0% from January to June 2007 (107.2 to 115.8) and remained relatively flat through December 2007 (114.6) and through May 2008 (108.9). Sitagliptin claims increased 5-fold, at a consistent rate, from an average of 8.6 claims per day per million members in January 2007 to 43.4 in December 2007, and continued to increase to 48.7, in May 2008. Of the 5,117 rosiglitazone users on May 20, 2007, 1,296 (25.3%) were identified at increased CV risk versus 590 (22.5%) of 2,621 users on December 7, 2007 (P = 0.006), and 336 (21.8%) of 1,541 users in May 2008 (P = 0.005). Of 6,056 pioglitazone users on May 20, 2007, 170 (2.8%) had a CHF diagnosis versus 160 (2.5%) of 6,275 users on December 7, 2007 (P = 0.376), and 122 of 5,998 users in May 2008 (P = 0.006). CONCLUSIONS: Although rosiglitazone utilization per million members declined by more than half in 2007, when CV safety concerns started to emerge, about 1 in 5 rosiglitazone users had elevated CV risk at year-end 2007 and in May 2008. About 3% of pioglitazone users in May 2007 had a diagnosis of CHF in claims history, which declined to 2% in May 2008. Insurers should consider the impact of persistent utilization of TZDs among members with CV risk factors when making formulary decisions.

Clinical and economic outcomes of medication therapy management services: the Minnesota experience.

OBJECTIVES: To (1) provide medication therapy management (MTM) services to patients, (2) measure the clinical effects associated with the provision of MTM services, (3) measure the percent of patients achieving Healthcare Effectiveness Data and Information Set (HEDIS) goals for hypertension and hyperlipidemia in the MTM services intervention group in relationship to a comparison group who did not receive MTM services, and (4) compare patients' total health expenditures for the year before and after receiving MTM services. DESIGN: Prospective study. SETTING: Six ambulatory clinics in Minnesota from August 1, 2001, to July 31, 2002. PATIENTS: 285 intervention group patients with at least 1 of 12 medical conditions using prestudy health claims; 126 comparison group patients with hypertension and 126 patients with hyperlipidemia were selected among 9 clinics without MTM services for HEDIS analysis. INTERVENTION: MTM services provided by pharmacists to BlueCross BlueShield health plan beneficiaries in collaboration with primary care providers. MAIN OUTCOME MEASURES: Drug therapy problems resolved; percentage of patients' goals of therapy achieved and meeting HEDIS measures for hypertension and hypercholesterolemia. Total health expenditures per person were measured for a 1-year period before and after enrolling patients in MTM services. RESULTS: 637 drug therapy problems were resolved among 285 intervention patients, and the percentage of patients' goals of therapy achieved increased from 76% to 90%. HEDIS measures improved in the intervention group compared with the comparison group for hypertension (71% versus 59%) and cholesterol management (52% versus 30%). Total health expenditures decreased from $11,965 to $8,197 per person (n = 186, P < 0.0001). The reduction in total annual health expenditures exceeded the cost of providing MTM services by more than 12 to 1. CONCLUSION: Patients receiving face-to-face MTM services provided by pharmacists in collaboration with prescribers experienced improved clinical outcomes and lower total health expenditures. Clinical outcomes of MTM services have chronic care improvement and value-based purchasing implications, and economic outcomes support inclusion of MTM services in health plan design.

Utilization, cost trends, and member cost-share for self-injectable multiple sclerosis drugs--pharmacy and medical benefit spending from 2004 through 2007.

BACKGROUND: In 1993, interferon beta-1b became the first of 4 self-injectable multiple sclerosis (MS) drugs to be approved by the U.S. Food and Drug Administration. Initially covered as a medical expense, self-injectable MS drugs are increasingly considered specialty pharmaceuticals and are often covered under the pharmacy benefit. Self-injectable MS drugs are expensive, costing approximately $2,000 per month per patient in 2007. OBJECTIVES: To (1) determine the trends for price and utilization of self-injectable MS drugs, (2) meld medical and pharmacy claims data to capture total health care spending on self-injectable MS drugs, and (3) calculate the out-of-pocket cost-share for members with pharmacy benefits. METHODS: A pharmacy benefits manager with integrated medical claims for approximately 1.8 million commercial members, about 20% of its total of 9 million commercial members, analyzed self-injectable MS pharmacy claims for a 45-month period beginning in January 2004 and ending in September 2007 and integrated medical and pharmacy claims for a 42-month period beginning in January 2004 and ending in June 2007. The 9 million members are beneficiaries of 10 Blue Cross Blue Shield (BCBS) health plans distributed throughout the United States, and the subset of 1.8 million members are enrolled in 1 BCBS health plan in the Northern Plains states. Self-injectable MS drugs were identified using Generic Product Identifier (GPI) codes for the National Drug Code (NDC) numbers on pharmacy claims. Mail order pharmacy claims with up to a 90-day supply were counted as 3 claims, and community pharmacy claims dispensed with up to a 34-day supply were counted as 1 claim. Self-injectable MS drugs were identified from medical claims using Healthcare Common Procedure Coding System (HCPCS) codes: J1595 for glatiramer, J1830 for subcutaneous interferon beta-1b, Q3026 for subcutaneous interferon beta-1a, and Q3025 and J1825 for intramuscular interferon beta-1a. RESULTS: For the approximately 9 million members with data from pharmacy claims only, these 4 self-injectable MS drugs accounted for approximately 1.8% of total pharmacy benefit spending in 2004, 1.9% in 2005, 2.3% in 2006, and 2.4% in 2007. The mean average wholesale price (AWP) per member per month (PMPM) increased by 56.8%, from $1.11 PMPM in the first quarter of 2004 to $1.74 PMPM in the third quarter of 2007. Utilization was flat at about 82-83 claims per 100,000 members per month during the 45-month measurement period. The average annual price increase per unit ranged from 8.9% for interferon beta-1a to 13.3% per year for interferon beta-1b. Members paid a median out-of-pocket cost per pharmacy claim of $15 in 2004, $20 in 2005 and 2006, and $25 in the first 9 months of 2007. For the 1.8 million members with both pharmacy and medical benefit claims, the medical benefit accounted for 2.5% of total spending on MS self-injectables in 2004, 2.0% in 2005 and 2006, and 1.2% in 2007. CONCLUSION: The percentage of all pharmacy expenditures that was attributable to self-injectable MS drugs increased from 1.8% in 2004 to 2.5% in 2007. Nearly all of the increase in spending on self-injectable MS drugs over the nearly 4-year period was attributable to drug price increases because PMPM utilization was essentially unchanged. The median member cost-share was approximately 1% of the total cost of self-injectable MS drugs.

Relationship of the magnitude of member cost-share and medication persistence with newly initiated renin angiotensin system blockers.

BACKGROUND: Effective treatment for chronic diseases often requires medication refill persistence. Health plans have frequently increased the amount of member cost-sharing by implementing tier-copayment pharmacy benefit designs and raising copayments. However, increased member costshare may present a barrier to the management of chronic conditions. Little is known about the relationship between the magnitude of member cost-sharing and antihypertensive persistence among members newly initiating therapy. OBJECTIVE: To investigate and quantify the relationship between amount of prescription cost-sharing and medication refill persistence among members newly initiating therapy with a single-agent angiotensin system blocker--either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). METHODS: This was an observational cohort study of pharmacy and medical claims data for 29 employers with approximately 310,000 beneficiaries that did not have a change in pharmacy benefits including the amount of member cost-share in 2004. The claims data were supplemented with census data for household income and race at the Zip Code level. Selected patients were new users of single-agent ACEIs or ARBs (i.e., excluding ACEI or ARB in combination with hydrochlorothiazide or amlopdipine) between January 1 and June 30, 2004, without a pharmacy claim for an ACEI or an ARB in the 6 months prior to the index claim for either drug type. Medication refill persistence was measured in 3 ways: (1) total number of days without ACEIs or ARBs during 6 months follow-up, (2) proportion of days covered (PDC) with less than 80% defined as nonpersistent during 6 months follow-up, and (3) number of days to the first gap of more than 30 days in medication coverage from the index date to end of 2004 (mean [SD] follow-up=9.2 [1.8] months). Three statistical models were fit: Tobit model, examining the association between cost-sharing and total number of medication gap days; logistic regression, testing the association between cost-sharing and odds of being nonpersistent; and Cox proportional hazards model, assessing the association between cost-sharing and time to a 30-day gap. RESULTS: Among the eligible population, a study cohort of 1,351 members newly initiating a single-agent ACEI or ARB was identified. These members were 41.8% female and had a mean age of 55.9 (SD=13.1) years. On average, their member cost-share was $12.42 (SD=$8.50) per 30-day supply. Each $1 increment in per 30-day cost-share was associated with a 1.9% increase in total gap (beta=0.019, 95% confidence interval [CI], 0.007-0.030, P=0.001), a 2.8% increase in the odds of being nonpersistent (odds ratio [OR]=1.028, 95% CI,1.011-1.045, P=0.001), and a 1.0% increase in the risk of having a gap of more than 30 days (hazard ratio [HR]=1.010, 95% CI, 1.001-1.019, P=0.034). Following transformation of the cost-sharing coefficient in each model, a $10 increment in cost-share had a consistent negative influence; 18.9% greater total gap days (beta=0.189, 95% CI, 0.073-0.304), 31.9% greater odds of being nonpersistent (OR=1.319, 95% CI, 1.120-1.553), and 10.2% larger hazard of having a gap of more than 30 days (HR=1.102, 95% CI, 1.007-1.205). CONCLUSION: For members newly initiating single-agent angiotensin system blocking medication, the amount of prescription cost-sharing was associated with a negative impact on refill persistence.

Telithromycin: the perils of hasty adoption and persistence of off-label prescribing.

BACKGROUND: Telithromycin (Ketek) was approved in April 2004 for the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB), bacterial sinusitis, and community-acquired pneumonia. The approval of telithromycin was controversial due to trial irregularities, noninferiority study designs, and use of foreign safety data. Safety concerns involving hepatotoxicity, myasthenia gravis exacerbation, and visual disturbances were increasingly documented in the literature after approval. On February 12, 2007, the U.S. Food and Drug Administration (FDA) removed the bacterial sinusitis and ABECB indications and strengthened safety warnings for telithromycin. OBJECTIVE: To (1) assess the prevalence and distribution of on-label telithromycin utilization before and after the revisions of the product label and (2) assess the association of pivotal events in the life cycle of telithromycin with its use as reflected in pharmacy and medical claims. METHODS: Using retrospective administrative medical and pharmacy claims from a large midwestern commercial insurer with an eligible membership of 1.8 million members, individuals with a telithromycin claim during January 1, 2007, through April 13, 2007, were identified. Their medical claims within 30 days prior to or on the initial telithromycin claim were analyzed for the presence of an on-label diagnosis code. Monthly telithromycin and clarithromycin claim totals per million members from January 2004 through March 2007 were calculated. Claim totals were plotted to identify utilization trends in relation to the FDA health advisory for telithromycin on January 20, 2006, and the telithromycin label changes on February 12, 2007. RESULTS: The medical diagnosis analysis consisted of 507 members with 1 or more medical claims with dates of service within 30 days of at least 1 pharmacy claim for telithromycin. Using the original approved telithromycin indications, 52.3% (256 of 507) of telithromycin use was on-label. The most common on-label diagnoses were sinusitis (33.9%) and bronchitis (14.4%). A diagnosis of pneumonia was present for 3.9% of telithromycin utilizers. After the February 12, 2007, label change limiting telithromycin to community-acquired pneumonia, on-label use was 6.7% (12 of 179) of utilizers. Telithromycin claims were first detected in August 2004 and overtook the clarithromycin rate of 729 claims per million members in January 2005, reaching a peak rate of 940 claims per million members in January 2006. Telithromycin monthly claims remained higher than clarithromycin until April 2006, 3 months after the liver toxicity health advisory. In comparison with January 2006, the January 2007 telithromycin claims were 186 claims per million members, a decrease of 80%. CONCLUSION: Despite revised FDA indications and safety warnings, fewer than 1 in 15 active telithromycin users have a medical claim consistent with the only currently approved indication (pneumonia). Pharmacy claims for telithromycin dropped substantially following reports of severe hepatotoxicity and strengthened safety warnings. The high prevalence of telithromycin off-label use despite hepatotoxicity and other safety risks is cause for continued concern.

Effects of collaborative drug therapy management on patients' perceptions of care and health-related quality of life.

BACKGROUND: It has been demonstrated that collaborative drug therapy management may result in enhanced medication adherence and improved clinical outcomes. It is not yet known whether CDTM is associated with patients' perceptions of care or self-reports of health-related quality of life. OBJECTIVES: Examine the impact of collaborative drug therapy management (CDTM) on patients' perceptions of care and health-related quality of life in 15 ambulatory clinics (6 intervention, 9 comparison) in the Fairview system of Minneapolis-St Paul, Minn. METHODS: The intervention was medication therapy management provided by pharmacists in collaboration with physicians (CDTM) for a 12-month period. Subjects were selected by age, gender, and presence of one of 12 medical conditions in the intervention (n=285) and comparison (n=285) group of patients. Comparison patients received usual care while intervention patients received at least 2 CDTM encounters. The CAHPS (formerly called the Consumer Assessment of Health Plans) 2.0 survey was administered to both the intervention and comparison groups poststudy to analyze patients' perceptions of care. The Short Form-12 (SF-12v2) was administered to intervention group patients pre-CDTM and 6 months post-CDTM to measure health-related quality of life in the intervention group. RESULTS: Differences in CAHPS scores were not statistically significant (P>.05), although there was a trend toward higher ratings of patients' personal doctor/nurse and doctors' communication in the CDTM intervention group relative to the comparison group. Physical role, social functioning, and physical component summary scales of the SF-12v2 improved significantly (P=.001, P=.014, and P=.024, respectively; P< or =.025 level). CONCLUSIONS: A trend toward improvements in patient perceptions of effectiveness of care using CAHPS suggests a need for further study. Health-related quality of life improvements in this study meet or exceed previous results incorporating pharmacists into primary care. Intensity and integration of CDTM services may be an explanation; however, prepost study design limits inferences.

The DERP: is it an effective methodology?

The Drug Effectiveness Review Project (DERP) is a process with challenges as well as rewards. This Perspective explores the issues that hamper the DERP's effectiveness and discusses the changes it has generated in the drug review process for pharmacy and therapeutics (P&T) committees. The need for more timely and substantial evidence is a key barrier to all drug review processes; here I offer some alternative methods for comparing new drugs that have few comparators. A perfect process is a long way off. However, continuing to explore the methodologies in place today can lead us to more effective processes and metrics.