Health plan utilization and costs of specialty drugs within 4 chronic conditions.

BACKGROUND: Drugs are most typically defined as specialty because they are expensive; however, other criteria used to define a drug as specialty include biologic drugs, the need to inject or infuse the drug, the requirement for special handling, or drug availability only via a limited distribution network. Specialty drugs play an increasingly important role in the treatment of chronic conditions such as multiple sclerosis (MS), rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease (IBD), yet little is known regarding the comprehensive medical and pharmacy benefit utilization and cost trends for these conditions. OBJECTIVE: To describe MS, RA, psoriasis, and IBD trends for condition prevalence, treatment with specialty drugs, specialty costs, nonspecialty costs, and total direct costs of care within the medical and pharmacy benefits. METHODS: This was a descriptive analysis of a commercially insured population made up of 1 million members, using integrated medical and pharmacy administrative claims data from 2008 to 2010. Analyses were limited to continuously enrolled commercially insured individuals less than 65 years of age. Condition-specific cohorts for MS, RA, psoriasis, and IBD were defined using standardized criteria. Trends in condition prevalence, specialty drug use for the conditions, and direct total cost of care were analyzed. The direct costs were subcategorized into the following: medical benefit specialty drug costs, medical benefit all other costs, pharmacy benefit specialty drug costs, and pharmacy benefit all other costs. Trends and compound annual growth rates were calculated for the total cost of care and subcategory costs from 2008 through 2010. RESULTS: Condition prevalence ranged from a low of 1,720 per million members for MS to a high of 4,489 per million members for RA. Psoriasis and MS condition prevalence rates were unchanged over the 3 years; however, IBD prevalence increased 7.0%, and RA prevalence increased 9.7%. The rate of specialty drug use was lowest for IBD (13.7%) and highest for MS (71.8%). The lowest total annual cost of care was for psoriasis ($14,815), and the highest total annual cost was for MS ($36,901). The most commonly used specialty drugs for each of the conditions were as follows: glatiramer (MS), etanercept (RA and psoriasis), and infliximab (IBD). The total annual costs were more than double for the specialty drug users for psoriasis compared with all the psoriasis members ($29,565 vs. $14,815). The total costs were only somewhat higher among MS members using specialty drugs ($41,760 vs. $36,901). Among specialty drug users for each of the cohorts, the annual costs of specialty drugs accounted for 50% or more of the total annual costs. The annual spending growth rate for specialty drugs ranged from 4.4% to 18.0%. CONCLUSIONS: Although specialty drug utilization varied widely across the 4 chronic conditions analyzed, when specialty drugs were used they accounted for the majority of the annual total direct cost of care. Because specialty drugs are accounting for a growing portion of chronic disease total cost of care, health insurers will need to become more vigilant regarding specialty drug use and focus on 4 cost saving management opportunities: drug distribution channel, utilization management, contracting activities, and care coordination.

Generic drug discount programs: are prescriptions being submitted for pharmacy benefit adjudication?

UNLABELLED:   BACKGROUND: In 2006, pharmacies began offering select generic prescription drugs at discount prices (e.g., $4 for a 30-day supply) through nonmembership and membership programs. As part of the contract in membership generic drug discount programs, the member agrees to forgo submission of the claim to the insurance company. Claims not submitted for insurance adjudication may result in incomplete pharmacy benefit manager (PBM) and health plan data, which could negatively influence adherence reporting and clinical programs. To address potentially missing claims data, the Centers for Medicare Medicaid Services (CMS) encourages Medicare Part D sponsors to incentivize network pharmacies to submit claims directly to the plan for drugs dispensed outside of a member's Part D benefit, unless a member refuses. The extent of PBM and health plan claims capture loss due to generic drug discount programs is unknown. OBJECTIVE: To identify changes in levothyroxine utilizers' prescription claims capture rate following the advent of generic drug discount membership and nonmembership programs. METHODS: This retrospective concurrent cohort study used claims data from 3.5 million commercially insured members enrolled in health plans located in the central and southern United States with Prime Therapeutics pharmacy benefit coverage. Members were required to be 18 years or older and younger than 60 years as of January 1, 2006, and continuously enrolled from January 1, 2006, through December 31, 2010. Members utilizing generic levothyroxine for at least 120 days during January 1, 2006, through June 30, 2006 (baseline period) from the same pharmacy group with supply on July 1, 2006, were placed into 1 of 3 pharmacy groups: (1) nonmembership (Walmart, Sam's Club, Target, Kroger, City Market, and King Soopers pharmacies), (2) membership (Walgreens, CVS, Albertsons, and Savon pharmacies), or (3) the reference group of all other pharmacies. The index date was defined as July 1, 2006. The levothyroxine claim providing supply on July 1, 2006, was the index claim. Members with a Kmart pharmacy index claim were excluded, since the Kmart membership drug discount program began prior to July 1, 2006. Levothyroxine claims capture nonpersistency, defined as the occurrence of a claim supply end date prior to a 180-day gap, was the primary outcome variable and was assessed from July 1, 2006, through June 30, 2010 (follow-up period). The odds of levothyroxine claims capture nonpersistency by pharmacy group were assessed using a logistic regression analysis adjusted for the following covariates: age, gender, median income in the ZIP code of residence (binomial for ≤ $50,000 vs. greater than $50,000), switch to a brand levothyroxine product during the follow-up period, index levothyroxine claim supply of 90 days or more, and index levothyroxine claim member cost share per 30-day supply in tertiles (≤ $5.00, $5.01-$7.99, ≥ $8.00). RESULTS: Of 2,632,855 eligible members aged 18 years or older, 13,427 met all study eligibility criteria. The baseline pharmacy groups were membership with 3,595 (26.8%), nonmembership with 1,919 (14.3%), and all other pharmacies with 7,913 (58.9%) members. The rates of levothyroxine claims capture persistency throughout the 4-year follow-up period were 85.4% for nonmembership (P = 0.593 vs. all other pharmacies), 77.7% for the membership group (P less than 0.001 vs. all other pharmacies), and 85.9% for all other pharmacies. The Kaplan-Meier comparison of claims capture persistency found nearly identical claims capture loss for the nonmembership compared with all other pharmacies group, and when compared in a multivariate logistic regression model, there was no difference in the odds of levothyroxine claims capture over 4 years follow-up (OR = 1.01, 95% CI = 0.88-1.16, P = 0.900). The membership generic drug discount programs (Walgreens, CVS, Alberstons, and Savon pharmacies) had a statistically significant 61% higher odds (OR = 1.61, 95% CI = 1.45-1.79, P less than 0.001) of levothyroxine claims capture nonpersistency. The onset of the difference between the membership group and the all other pharmacies group was temporally associated with the launch of the membership programs. In comparison to index levothyroxine member cost of ≤ $5.00 per 30-day supply, higher cost shares were associated with higher levothyroxine claims capture nonpersistency ($5.01 to $7.99 OR 1.34, 95% CI 1.19-1.52 and ≥ $8.00 OR 1.60, 95% CI 1.40-1.82). CONCLUSIONS: Among levothyroxine utilizers in 2006 (prior to the advent of drug discount programs), those with claims from a pharmacy that subsequently implemented a nonmembership generic drug discount program did not appear to have a different rate of levothyroxine claims capture than members from the reference group when followed through June 2010. Utilizers with claims from a pharmacy that subsequently implemented a membership program had a significantly lower levothyroxine claims capture rate. Increasing index levothyroxine member cost was associated with higher levothyroxine claims capture loss. Because the analysis could not directly measure claims capture loss associated with members who switched to a new pharmacy group without presenting their insurance information (e.g., membership discount programs), further research is needed to confirm these findings.

Association of prescription abandonment with cost share for high-cost specialty pharmacy medications.

BACKGROUND: In 2008, specialty medications accounted for 15.1% of total pharmacy benefit medication spending, and per member expenditures have increased by 11.1% annually from 2004 to 2008 within a commercially insured population of 8 million members. Insurers face increasing pressure to control specialty medication expenditures and to rely on increasing member cost share through creation of a fourth copayment tier within the incentive-based formulary pharmacy benefit system. Data are needed on the influence that member out-of-pocket (OOP) expense may have on prescription abandonment (defined as the patient never actually taking possession of the medication despite evidence of a written prescription generated by a prescriber). OBJECTIVE: To explore the relationship between prescription abandonment and OOP expense among individuals newly initiating high-cost medication therapy with a tumor necrosis factor (TNF) blocker or multiple sclerosis (MS) biologic agent. METHODS: This observational cross-sectional study queried a midwestern and southern U.S. database of 13,172,480 commercially insured individuals to find members with a pharmacy benefit-adjudicated claim for a TNF blocker or MS specialty medication during the period from July 2006 through June 2008. Prescription abandonment was assessed among continuously enrolled members newly initiating TNF blocker or MS therapy. Prescription abandonment was defined as reversal of the adjudicated claim with no evidence of a subsequent additional adjudicated paid claim in the ensuing 90 days. Separate analyses for MS and TNF blocker therapy were performed to assess the association between member OOP expense and abandonment rate using the Cochran-Armitage test for trend and multivariate logistic regression. Members were placed into 1 of the 7 following OOP expense groups per claim: $0-$100, $101-$150, $151-$200, $201-$250, $251-$350, $351-$500, or more than $500. The association of MS or TNF blocker abandonment rate with OOP expense was tested with logistic regression models using the $0-$100 OOP as the reference group and adjusting for age, gender, formulary status, ZIP code-level income and education, earliest specialty medication claim, and methotrexate use for the TNF blocker analysis. RESULTS: Of 2,791 members presenting a prescription to newly initiate high-cost MS therapy, 1,985 (71.1%) of the claims were for a 1-month supply with most of the remainder for a 3-month supply; 2,303 (82.5%) had an OOP expense of $0-$100, and 5.4% had an OOP expense greater than $500. The abandonment rate increased as OOP increased (test for trend, P < 0.001). Members with an OOP expense of $100 or less had an abandonment rate of 5.7%. Among members in all OOP expense groups greater than $200, the abandonment rate was significantly higher, with more than 1 in 4 members abandoning their MS claims (P < 0.001). In the multivariate logistic regression analysis, the abandonment rate became significantly higher at OOP expenses of $201 to $250 compared with an OOP expense of $100 or less (odds ratio [OR] = 7.3, 95% confidence interval [CI] = 3.3- 16.2). The odds ratios ranged between 6.1 and 7.3 for OOP expense groups greater than $200. Of 7,313 members presenting a prescription to newly initiate TNF blocker therapy, 5,809 (79.4%) of claims were for a 1-month supply with most of the remainder for a 3-month supply; 6,123 (83.7%) had an OOP expense of $0-$100 and 5.7% had an OOP expense greater than $500. The abandonment rate increased as OOP expense increased (test for trend, P < 0.001). In the multivariate logistic regression analysis, the TNF blocker medication abandonment rate was significantly higher for all OOP expense groups greater than $100, with abandonment odds ratios of 2.3 to 4.4 for OOP expense between $101 and $500 compared with OOP expense of $0-$100. The odds of abandonment at OOP expense of greater than $500 were 7-fold higher (OR = 7.0, 95% CI = 5.4-9.1). CONCLUSIONS: This is the first study to perform a focused assessment of an association between specialty medication OOP expense and new therapy prescription abandonment. The study found that per claim OOP expenses greater than $100 for TNF blocker medication and greater than $200 for MS medication were associated with increased prescription abandonment. These findings coupled with previous research identifying a negative relationship between OOP expense above $100 per month and adherence, and the commercial insurance market response to fourth-tier OOP expenses, suggests that insurers should consider the impact that specialty OOP expense may have on adherence and member satisfaction. Further prospective research should be performed to confirm these findings and assess the clinical outcomes associated with prescription abandonment.

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.

Are incentive-based formularies inversely associated with drug utilization in managed care?

OBJECTIVE: To review recent studies comprehensively assessing the impact of incentive-based multitier formularies on pharmaceutical costs and utilization. DATA SOURCES: PubMed (2001-December 2003) was searched using the key terms formularies, cost-sharing, and drug costs. STUDY SELECTION AND DATA EXTRACTION: Studies addressing the impact of implementing multitiered incentive-based formularies as a central component of an outpatient drug benefit were selected. DATA SYNTHESIS: One study using pharmacy claims from 25 employers with data from 402 786 members modeled the range of anticipated plan/employer savings associated with single- to 3-tier shifts and found that, going from a single- to 3-tier benefit results in decreased plan/employer pharmaceutical costs from $650 to $494 (24% decrease) per member per year and decreased pharmaceutical utilization from 12.3 to 9.4 (23.6% decrease) prescriptions per member per year. Another study demonstrated that adding an additional tier decreased pharmaceutical utilization, with a dramatic increase in member contribution offsetting the plan's expected increase in expenditures. This shift in pharmaceutical expenditures appeared to have no effect on overall medical utilization over a 3-year follow-up. Finally, a study converting members from a single- to 3-tier incentive-based formulary, associated with two- to fourfold copayment increases, resulted in a 10% discontinuation rate for angiotensin-converting enzyme inhibitors, statins, and proton-pump inhibitors among members who were primarily hourly employees. For salaried workers, the addition of a tier to their benefit appeared to have minimal impact on pharmaceutical utilization. CONCLUSIONS: Emerging data suggest a potential inverse relationship between pharmaceutical utilization and incentive-based formularies that increase member contribution to drug costs. Future research should focus on identifying price points and percentage increases at which members are likely to begin discontinuing necessary medications.

Pharmacodynamics of pulse dosing versus standard dosing: in vitro metronidazole activity against Bacteroides fragilis and Bacteroides thetaiotaomicron.

Pulse dosing is a novel approach to dosing that produces escalating antibiotic levels early in the dosing interval followed by a prolonged dose-free period. Antibiotic is frontloaded by means of four sequential bolus injections, after which antibiotic levels are allowed to diminish until the next dose. This study compares standard thrice-daily dosing and pulse dosing of metronidazole against Bacteroides spp. in an in vitro model. Two American Type Culture Collection Bacteroides fragilis isolates (metronidazole MIC for each organism = 1 mg/liter) were exposed to metronidazole for 48 or 96 h. Human pharmacokinetics were simulated for an oral 500-mg dose given every 8 h (maximum concentration of drug [C(max)] = 12 mg/liter; half-life = 8 h; area under the curve [AUC] = 294 mg . h/liter) and for pulse dosing. Pulses, each producing an increase in metronidazole concentration of 9 mg/liter, were administered at times 0, 2, 4, and 6 h of each 24-h cycle, with a targeted half-life of 8 h (AUC = 347 mg . h/liter). A metronidazole-resistant B. fragilis strain (metronidazole MIC = 32 mg/liter) was exposed to both dosing regimens and, additionally, to a regimen of 1,500 mg administered once daily (C(max) = 36 mg/liter; AUC = 364 mg . h/liter). Furthermore, regimens against one B. fragilis isolate and one B. thetaiotaomicron isolate corresponding to one-fourth and one-eighth of the thrice-daily and pulse dosing regimens, mimicking peak metronidazole concentrations achieved in abscesses, were simulated in 48-h experiments (metronidazole MIC = 1 mg/liter). Time-kill curves were generated for each experiment and analyzed for bactericidal activity, defined as a bacterial burden reduction >/= 3 log(10) CFU/ml. The results of paired (Wilcoxon matched-pair signed-rank test) and nonpaired (Mann-Whitney test) statistical analyses conducted on time to 3 log(10) kill data and area under the kill curve data from each of the thrice-daily dosing experiments versus each of the pulse dosing experiments were considered not significant for a given isolate-dosing regimen combination. The thrice-daily dosing, pulse dosing, and once-daily dosing regimens all exhibited bactericidal activity. Metronidazole administered in standard or pulse dosing fashion was highly active against both susceptible and resistant strains of Bacteroides spp.

Synergistic activity of colistin and ceftazidime against multiantibiotic-resistant Pseudomonas aeruginosa in an in vitro pharmacodynamic model.

Despite the marketing of a series of new antibiotics for antibiotic-resistant gram-positive bacteria, no new agents for multiple-antibiotic-resistant gram-negative infections will be available for quite some time. Clinicians will need to find more effective ways to utilize available agents. Colistin is an older but novel antibiotic that fell into disfavor with clinicians some time ago yet still retains a very favorable antibacterial spectrum, especially for Pseudomonas and Acinetobacter spp. Time-kill curves for two strains of multiantibiotic-resistant Pseudomonas aeruginosa were generated after exposure to colistin alone or in combination with ceftazidime or ciprofloxacin in an in vitro pharmacodynamic model. MICs of colistin, ceftazidime, ciprofloxacin, piperacillin-tazobactam, imipenem, and tobramycin were 0.125, > or =32, >4, >128/4, 16, and >16 mg/liter, respectively. Colistin showed rapid, apparently concentration-dependent bactericidal activity at concentrations between 3 and 200 mg/liter. We were unable to detect increased colistin activity at concentrations above 18 mg/liter due to extremely rapid killing. The combination of colistin and ceftazidime was synergistic (defined as at least a 2-log(10) drop in CFU per milliliter from the count obtained with the more active agent) at 24 h. Adding ciprofloxacin to colistin did not enhance antibiotic activity. These data suggest that the antibacterial effect of colistin combined with ceftazidime can be maximized at a peak concentration of < or =18 mg/liter.

Comparison of linezolid activities under aerobic and anaerobic conditions against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium.

Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium were exposed to linezolid (MIC of 2 mg/liter) under aerobic or anaerobic conditions in an in vitro pharmacodynamic model. Drug concentration and half-life were adjusted to simulate clinical dosing (600 mg twice daily) of linezolid. Linezolid produced a 2-log(10) killing at 24 h, and rates of killing against each of these facultative organisms as measured by mean survival time appeared similar under aerobic and anaerobic conditions.

Comparative pharmacodynamics of three newer fluoroquinolones versus six strains of staphylococci in an in vitro model under aerobic and anaerobic conditions.

Six strains of staphylococci were exposed to levofloxacin, moxifloxacin, or trovafloxacin in an in vitro pharmacodynamic model under both aerobic and anaerobic conditions. Each agent demonstrated a rapid 3-log(10) kill versus susceptible isolates regardless of condition. Against clinical isolates with reduced susceptibility, regrowth occurred by 24 h and was frequently associated with further increases in MICs.