Racial and Ethnic Disparities in Initiation of Direct Oral Anticoagulants Among Medicare Beneficiaries.

Importance: The influence of race and ethnicity on initiation of direct oral anticoagulants (DOACs) is relatively understudied in Medicare data. Objective: To investigate disparities in the initiation of DOACs compared with warfarin by race, ethnicity, and social vulnerability. Design, Setting, and Participants: This retrospective cohort study used a 50% sample of Medicare fee-for-service data from January 1, 2010, to December 31, 2019 (mean patient enrollment duration, 7.7 years). Analysis took place between January 2023 and February 2024. A cohort of older adults (aged ≥65 years) with atrial fibrillation who newly initiated warfarin or DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) was identified. Exposure: Patients were classified as non-Hispanic White, non-Hispanic Black, and Hispanic. Main Outcomes and Measures: The likelihood of starting use of DOACs compared with warfarin was modeled, adjusting for race, ethnicity, age, sex, county-level social vulnerability, and other clinical factors. Results: Among 950 698 anticoagulation initiations, consisting of 680 974 DOAC users and 269 724 warfarin users (mean [SD] age, 78.5 [7.6] years; 52.6% female), 5.2% were Black, 4.3% were Hispanic, and 86.7% were White. During the 10-year study period, DOAC use increased for all demographic groups. After adjustment, compared with White patients, Black patients were 23% less likely (adjusted odds ratio [AOR, 0.77; 95% CI, 0.75-0.79) and Hispanic patients were 13% less likely (AOR, 0.87; 95% CI, 0.85-0.89) to initiate DOAC use. Disparities in DOAC initiation were greatest among Black patients in the earlier years but attenuated during the study period. For instance, in 2010, the OR of Black patients initiating DOACs was 0.54 (95% CI, 0.50-0.57), attenuating linearly over time to 0.69 by 2013 (95% CI, 0.65-0.74) and 0.83 (95% CI, 0.78-0.89) by 2017. By 2019, these differences became nonsignificant (OR, 1.08; 95% CI, 0.99-1.18). Conclusions and Relevance: In this cohort study of Medicare patients with atrial fibrillation, Black and Hispanic patients were less likely to initiate DOACs for atrial fibrillation, although these differences diminished over time. Identifying the factors behind these early disparities is crucial for ensuring equitable access to novel therapies as they emerge for Black and Hispanic populations.

Prescribing trends of SGLT2 inhibitors among HFrEF and HFpEF patients with and without T2DM, 2013-2021.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended for treatment of heart failure (HF), regardless of type 2 diabetes (T2DM) status. However, limited data exist on SGLT2i prescribing in HF patients without T2DM or across HF subtypes. METHODS: This was a serial, cross-sectional study of US MarketScan commercial and Medicare claims (2013-2021). Prevalence of SGLT2i was calculated by calendar year among HFrEF and HFpEF patients and stratified by T2DM status. RESULTS: Among 218,066 HFrEF patients [mean (SD): 54.9 (8.92) years; 66.4% male], the prevalence of SGLT2i use increased from 0.3 to 18.6%, while among 150,437 HFpEF patients [56.5 (7.77) years; 47.6% male], it rose from 0.5 to 9.9%. These increases were driven by the subgroup with comorbid T2DM. SGLT2i prevalence use ratios among patients with T2DM compared to those without decreased from > 100 in 2018 to 3.8 in 2021 among HFrEF patients, and from 83.1 in 2018 to 17.5 in 2021, coinciding with the publication of landmark trials and corresponding changes in clinical guidelines. CONCLUSIONS: SGLT2i use rose rapidly following changes in guidelines but remained low among those without T2DM. By the end of the study, approximately 1 in 3 HFrEF and 1 in 5 HFpEF patients with T2DM were using an SGLT2i, compared to only 1 in 11 HFrEF and 1 in 85 HFpEF patients without T2DM. Future work identifying barriers with the uptake of GDMT, including SGLT2i, among HF patients is needed.

The impact of drug shortages on drug prices: evidence from China.

Introduction: Drug shortages pose a serious global public health challenge, affecting China and other countries. Evidence from USA shows that short-supplied drugs demonstrated a very high price growth during and after a shortage. However, the effect of shortages on drug prices in China remains unknown. This paper aims to understand the impact of drug shortages on prices and explore implications for shortage prevention policy. Methods: We collected the purchase prices and delivery rates of 120 drugs from April 2019 to December 2021 across whole China. We examined price progression of affected drugs using linear mixed-effects models and performed subgroup analyses based on the number of manufacturers and the severity of shortage. Results: Non-shortage cohort had an annual price growth of 11.62% (95% confidence interval [CI] 8.34 to 14.98). Shortage cohort demonstrated an annual price growth of 8.08% (95%CI 0.12 to 16.77) in the period preceding a shortage, 27.57% (95%CI 6.17 to 52.87) during a shortage, and 9.38% (95%CI -12.64 to 36.39) in the post-shortage period. Drug shortages' impact on prices varied across subgroups. Compared with that of drug markets supplied by a single manufacturer, the price growth rate of markets supplied by more than one manufacture declined more after the shortage resolution. Conclusion: Shortages resulted in significant price increases of study markets, especially the low-priced markets, while the shortage resolution slowed the growth. The primary shortage driver has shifted from the low price to others drivers, such as unavailability of active pharmaceutical ingredients. For currently sole-supplied drugs, the expedited review of applications from other manufacturers should be considered.

Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction.

BACKGROUND: No study has compared the cardiovascular outcomes for sodium-glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)-which also have cardiovascular benefits-in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction. METHODS: Medicare fee-for-service data (2013-2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting. RESULTS: Among HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses. CONCLUSIONS: Bias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.

Validity of International Classification of Diseases (ICD)-10 Diagnosis Codes for Identification of Acute Heart Failure Hospitalization and Heart Failure with Reduced Versus Preserved Ejection Fraction in a National Medicare Sample.

BACKGROUND: Heart failure (HF) is a leading cause of hospitalization in older adults. Medicare data have been used to assess HF outcomes. However, the validity of ICD-10 diagnosis codes (used since 2015) to identify acute HF hospitalization or distinguish reduced (heart failure with reduced ejection fraction) versus preserved ejection fraction (HFpEF) is unknown in Medicare data. METHODS: Using Medicare data (2015-2017), we randomly sampled 200 HF hospitalizations with ICD-10 diagnosis codes for HF in the first/second claim position in a 1:1:2 ratio for systolic HF (I50.2), diastolic HF (I50.3), and other HF (I50.X). The primary gold standards included recorded HF diagnosis by a treating physician for HF hospitalization, ejection fraction (EF)≤50 for heart failure with reduced ejection fraction, and EF>50 for HFpEF. If the quantitative EF was not present, then qualitative descriptions of EF were used for heart failure with reduced ejection fraction/HFpEF gold standards. Multiple secondary gold standards were also tested. Gold standard data were extracted from medical records using standardized forms and adjudicated by cardiology fellows/staff. We calculated positive predictive values with 95% CIs. RESULTS: The 200-chart validation sample included 50 systolic, 50 diastolic, 47 combined dysfunction, and 53 unspecified HF patients. The positive predictive values of acute HF hospitalization was 98% [95% CI, 95-100] for first-position ICD-10 HF diagnosis and 66% [95% CI, 58-74] for first/second-position diagnosis. Quantitative EF was available for ≥80% of patients with systolic, diastolic, or combined dysfunction ICD-10 codes. The positive predictive value of systolic HF codes was 90% [95% CI, 82-98] for EFs≤50% and 72% [95% CI, 60-85] for EFs≤40%. The positive predictive value was 92% [95% CI, 85-100] for HFpEF for EFs>50%. The ICD-10 codes for combined or unspecified HF poorly predicted heart failure with reduced ejection fraction or HFpEF. CONCLUSIONS: ICD-10 principal diagnosis identified acute HF hospitalization with a high positive predictive value. Systolic and diastolic ICD-10 diagnoses reliably identified heart failure with reduced ejection fraction and HFpEF when EF 50% was used as the cutoff.

Healthcare costs associated with comorbid cardiovascular and renal conditions among persons with diabetes, 2008-2019.

BACKGROUND: There is paucity of data examining healthcare costs among persons with comorbid diabetes and cardiorenal conditions. OBJECTIVE: To elucidate the longitudinal trends and quantify the incremental healthcare costs associated with the following cardiorenal conditions: atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and kidney disease, among persons with diabetes. METHODS: Medical Expenditure Panel Survey data (2008-2019) were used to identify adults with diabetes and comorbid cardiorenal conditions. Overall, medical and pharmaceutical costs were ascertained (in 2019 US dollars). Analyses were adjusted for 14 variables using a two-part regression model. RESULTS: Among 32,519 adults with diabetes, the mean (standard error [SE]) annual healthcare costs were $13,829 ($213), with medical and prescription components contributing $9301 ($172) and $4528 ($98), respectively. Overall healthcare costs rose by 26.8% from $12,791 (2008-2009) to $16,215 (2018-2019) over the study period, driven by 42.5% and 20.3% increase in pharmaceutical and medical spending, respectively. Similar trends were observed for subgroup of persons with cardiorenal conditions. Compared to their counterparts without cardiorenal conditions and prior to adjustment, persons with ASCVD, HF and kidney disease incurred healthcare costs that were approximately 2.2, 3.3, and 2.7 times greater. After adjustment, comorbid ASCVD, HF and kidney disease were associated with annual excess spending of $8651 (95% CI $7729-$9573), $9373 (95% CI $9010-$9736), and $9995 (95% CI $8781-$11,209), respectively. CONCLUSIONS: Study results are generalizable to non-institutionalized US persons. Healthcare costs associated with the management of diabetes are high-especially among those with comorbid cardiorenal conditions, and have risen in recent years.

Risks for Anaphylaxis With Intravenous Iron Formulations : A Retrospective Cohort Study.

BACKGROUND: The risks for anaphylaxis among intravenous (IV) iron products currently in use have not been assessed. OBJECTIVE: To compare risks for anaphylaxis among 5 IV iron products that are used frequently. DESIGN: Retrospective cohort study using a target trial emulation framework. SETTING: Medicare fee-for-service data with Part D coverage between July 2013 and December 2018. PARTICIPANTS: Older adults receiving their first administration of IV iron. MEASUREMENTS: The primary outcome was the occurrence of anaphylaxis within 1 day of IV iron administration, ascertained using a validated case definition. Analysis was adjusted for 40 baseline covariates using inverse probability of treatment weighting. The adjusted incidence rates (IRs) for anaphylaxis per 10 000 first administrations and odds ratios (ORs) were computed. RESULTS: The adjusted IRs for anaphylaxis per 10 000 first administrations were 9.8 cases (95% CI, 6.2 to 15.3 cases) for iron dextran, 4.0 cases (CI, 2.5 to 6.6 cases) for ferumoxytol, 1.5 cases (CI, 0.3 to 6.6 cases) for ferric gluconate, 1.2 cases (CI, 0.6 to 2.5 cases) for iron sucrose, and 0.8 cases (CI, 0.3 to 2.6 cases) for ferric carboxymaltose. Using iron sucrose as the referent category, the adjusted ORs for anaphylaxis were 8.3 (CI, 3.5 to 19.8) for iron dextran and 3.4 (CI, 1.4 to 8.3) for ferumoxytol. When cohort entry was restricted to the period after withdrawal of high-molecular-weight iron dextran from the U.S. market in 2014, the risk for anaphylaxis associated with low-molecular-weight iron dextran (OR, 8.4 [CI, 2.8 to 24.7]) did not change appreciably. Anaphylactic reactions requiring hospitalizations were observed only among patients using iron dextran or ferumoxytol. LIMITATION: Generalizability to non-Medicare populations. CONCLUSION: The rates of anaphylaxis were very low with all IV iron products but were 3- to 8-fold greater for iron dextran and ferumoxytol than for iron sucrose. PRIMARY FUNDING SOURCE: None.

Risk of clinically relevant hyperglycemia with metoprolol compared to carvedilol in older adults with heart failure and diabetes.

BACKGROUND: Although prior literature suggests that metoprolol may worsen glucose control compared to carvedilol, whether this has clinical relevance among older adults with diabetes and heart failure (HF) remains an open question. METHODS: This was a US retrospective cohort study utilizing data sourced from a 50% national sample of Medicare fee-for-service claims of patients with part D prescription drug coverage (2007-2017). Among patients with diabetes and HF, we identified initiators of metoprolol or carvedilol, which were 1:1 propensity score matched on >90 variables. The primary outcome was initiation of a new oral or injectable antidiabetic medication (proxy for uncontrolled diabetes); secondary outcomes included initiation of insulin and severe hyperglycemic event (composite of emergency room visits or hospitalizations related to hyperglycemia). RESULTS: Among 24 239 propensity score-matched pairs (mean [SD] age 77.7 [8.0] years; male [39.1%]), there were 8150 (incidence rate per 100 person-years [IR] = 33.5) episodes of antidiabetic medication initiation among metoprolol users (exposure arm) compared to 8576 (IR = 33.4) among carvedilol users (comparator arm) compared to corresponding to an adjusted hazard ratio (aHR) of 0.97 (95% confidence interval [CI]: 0.94, 1.01). Similarly, metoprolol was not associated with a significant increase in the risk of secondary outcomes including insulin initiation: aHR of 0.98 (95% CI: 0.93, 1.04) and severe hyperglycemic events: aHR of 0.98 (95% CI: 0.93, 1.02). CONCLUSIONS: In this large study of older adults with HF and diabetes, initiation of metoprolol compared to carvedilol was not associated with an increase in the risk of clinically relevant hyperglycemia.

Estimating The Cost Of Delayed Generic Drug Entry To Medicaid.

Delays in market entry of generic drugs are common. This study sought to identify the prevalence of delayed entry, the reasons for the delays, and the delays' effects on Medicaid spending in a recent cohort of brand-name medications. We estimated excess Medicaid spending in 2010-16 in the delayed quarter-years after accounting for market average predictions of brand-name market share, ratios of generic to brand-name prices, and Medicaid rebates (60 percent for brand-name and 15 percent for generic drugs). Among sixty-nine brand-name drugs that were predicted to lose market exclusivity, generic entry occurred either before or within a quarter-year of the expected date for thirty-eight products (55 percent), was delayed by more than one quarter for twenty products (29 percent), and did not occur for eleven products (16 percent). For the thirty-one products (45 percent) for which generic entry was delayed by more than one quarter or did not occur, Medicaid spent an estimated excess of $761 million over seven years ($109 million annually). Patent litigation was the most common cause of generic entry delays. Policies that expedite the resolution of patent challenges are needed to ensure the timely entry of generic drugs.

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Severe Urinary Tract Infections: A Population-Based Cohort Study.

Background: Prior studies evaluating risk for severe urinary tract infections (UTIs) with sodium-glucose cotransporter-2 (SGLT-2) inhibitors have reported conflicting findings. Objective: To assess whether patients initiating use of SGLT-2 inhibitors were at increased risk for severe UTI events compared with those initiating use of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor (GLP-1) agonists. Design: Population-based cohort study. Setting: 2 large, U.S.-based databases of commercial claims (March 2013 to September 2015). Participants: Within each database, 2 cohorts were created and matched 1:1 on propensity score. Patients were aged 18 years or older, had type 2 diabetes mellitus, and were initiating use of SGLT-2 inhibitors versus DPP-4 inhibitors (cohort 1) or GLP-1 agonists (cohort 2). Measurements: The primary outcome was a severe UTI event, defined as a hospitalization for primary UTI, sepsis with UTI, or pyelonephritis; the secondary outcome was outpatient UTI treated with antibiotics. Hazard ratios (HRs) were estimated in each propensity score-matched cohort, with adjustment for more than 90 baseline characteristics. Results: After 1:1 matching on propensity score, 123 752 patients were identified in cohort 1 and 111 978 in cohort 2 in the 2 databases. In cohort 1, persons newly receiving SGLT-2 inhibitors had 61 severe UTI events (incidence rate [IR] per 1000 person-years, 1.76), compared with 57 events in the DPP-4 inhibitor group (IR, 1.77) (HR, 0.98 [95% CI, 0.68 to 1.41]). In cohort 2, those receiving SGLT-2 inhibitors had 73 events (IR, 2.15), compared with 87 events in the GLP-1 agonist group (IR, 2.96) (HR, 0.72 [CI, 0.53 to 0.99]). Findings were robust across sensitivity analyses; within several subgroups of age, sex, and frailty; and for canagliflozin and dapagliflozin individually. In addition, SGLT-2 inhibitors were not associated with increased risk for outpatient UTIs (cohort 1: HR, 0.96 [CI, 0.89 to 1.04]; cohort 2: HR, 0.91 [CI, 0.84 to 0.99]). Limitation: Generalizability of the study findings may be limited to patients with commercial insurance. Conclusion: In a large cohort of patients seen in routine clinical practice, risk for severe and nonsevere UTI events among those initiating SGLT-2 inhibitor therapy was similar to that among patients initiating treatment with other second-line antidiabetic medications. Primary Funding Source: Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics.

Prevalence of Maternal-Risk Factors Related to Neonatal Abstinence Syndrome in a Commercial Claims Database: 2011-2015.

BACKGROUND: Despite the rising incidence of neonatal abstinence syndrome (NAS), data evaluating trends in maternal risk factors associated with NAS have not been available for recent years, a period characterized by declining opioid prescriptions. The objective of this study was to examine the prevalence of opioid- and non-opioid-related factors associated with NAS, and by mutually exclusive subgroups of deliveries without prescription-opioid use, with prescription-opioid use, and with opioid-use disorder (OUD). METHODS: A cohort of pregnancies resulting in live births in a commercial claims data base in 2011-2015 was identified. Examples of maternal risk factors of interest included antepartum prescription-drug use (e.g., opioids, selective serotonin reuptake inhibitors [SSRIs], antipsychotics) and nonprescription-related factors (e.g., smoking, OUD). RESULTS: A total of 659 cases of NAS among 621,940 deliveries was identified. Among NAS deliveries, prescription opioids were the most commonly used drug-class (39.0%). Adjusted relative risk (RR) for NAS was 5.43 (95% confidence interval [CI] 4.25-6.95), followed by SSRIs (20.9%; RR 3.16, CI 2.43-4.11); OUD was noted in 36.3% of the deliveries (RR 40.74, CI 22.64-73.32). In the subgroup of deliveries without a prescription opioid (33% of overall NAS deliveries), the absolute incidence of NAS was low (0.3 cases/1000 deliveries), and SSRIs were the most commonly used medication class (32.7%; RR 10.21, CI 7.28-14.31). In the subgroup of deliveries with an opioid prescription, the absolute incidence of NAS was 7.7/1000 (29% of all overall NAS deliveries), and 22.7% of these deliveries were exposed to one other psychotropic agent in addition to the opioid, most commonly an SSRI (18.0%). In the subgroup of deliveries with a diagnosis of OUD, the NAS incidence was high (214.3/1000 [36% of all NAS cases]). CONCLUSION: A third of NAS deliveries did not have evidence of prescription opioids. Other psychotropic medications, especially SSRIs, were strong predictors of NAS in this stratum but had no relevance among deliveries with OUD, suggesting varying etiologies and the need for tailored preventive approaches to reduce NAS effectively.

Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors.

The extent to which sodium-glucose co-transporter-2 (SGLT2) inhibitors increase the risk of genital infections in routine clinical care, compared with other antidiabetic medications, is not clear, or whether the increased risk is consistent across gender or age subgroups, within individual SGLT2 agents, or if it is more pronounced at a particular time after treatment initiation. We conducted a retrospective cohort study using two US commercial claims databases (2013-2017). In the primary analysis, 1:1 propensity score-matched cohorts of female and male subjects with type 2 diabetes mellitus initiating SGLT2 versus dipeptidyl peptidase-4 inhibitors were created. The outcome was a composite of genital candidal infections, vaginitis or vulvovaginitis in women, and genital candidal infections, balanitis, balanoposthitis, phimosis or paraphimosis in men. Among propensity score-matched cohorts of 129 994 women and 156 074 men, the adjusted hazard ratio (HR) and excess risk per 1000 person-years for SGLT2 versus DPP-4 inhibitors was 2.81 (95% confidence interval [CI], 2.64, 2.99) and 87.4 (95% CI, 79.1, 96.2) respectively for women, and was 2.68 (95% CI, 2.31, 3.11) and 11.9 (95% CI, 9.3-15.0) for men. Findings were similar in the SGLT2 inhibitor versus GLP-1 agonist comparison, more pronounced in the subgroup of patients aged ≥60 (HR, 4.45 [95% CI, 3.83-5.17] in women and 3.30 [95% CI, 2.56-4.25] in men), and no meaningful difference across individual SGLT2 inhibitors was identified. This increase in risk was evident in the first month of treatment initiation and remained elevated throughout the course of therapy. SGLT2 inhibitors were associated with an approximately 3-fold increase in risk of genital infections.

Predictors of Drug Shortages and Association with Generic Drug Prices: A Retrospective Cohort Study.

BACKGROUND: Prescription drug shortages can disrupt essential patient care and drive up drug prices. OBJECTIVE: To evaluate some predictors of shortages within a large cohort of generic drugs in the United States and to determine the association between drug shortages and changes in generic drug prices. METHODS: This was a retrospective cohort study. Outpatient prescription claims from commercial health plans between 2008 and 2014 were analyzed. Seven years of data were divided into fourteen 6-month periods; the first period was designated as the baseline period. The first model estimated the probability of experiencing a drug shortage using drug-specific competition levels, market sizes, formulations (e.g., capsules), and drug prices as predictors. The second model estimated the percentage change in drug prices from baseline on the basis of drug shortage duration. RESULTS: From 1.3 billion prescription claims, a cohort of 1114 generic drugs was identified. Low-priced generic drugs were at a higher risk for drug shortages compared with medium- and high-priced generic drugs, with odds ratios of 0.60 (95% confidence interval [CI] 0.44-0.82) and 0.72 (95% CI 0.52-0.99), respectively. Compared with periods of no shortage, drug shortages lasting less than 6 months, 6 to 12 months, 12 to 18 months, and at least 18 months had corresponding price increases of 6.0% (95% CI 4.7-7.4), 10.9% (95% CI 8.5-13.4), 14.2% (95% CI 10.6-17.9), and 14.0% (95% CI 9.1-19.2), respectively. CONCLUSIONS: Study findings may not be generalizable to drugs that became generic after 2008 or those commonly used in an inpatient setting. The lowest priced drugs are at a substantially elevated risk of experiencing a drug shortage. Periods of drug shortages were associated with modest increases in drug prices.

High Generic Drug Prices and Market Competition: A Retrospective Cohort Study.

BACKGROUND: Prices for some generic drugs have increased in recent years, adversely affecting patients who rely on them. OBJECTIVE: To determine the association between market competition levels and the change in generic drug prices in the United States. DESIGN: Retrospective cohort study. SETTING: Prescription claims from commercial health plans between 2008 and 2013. MEASUREMENTS: The 5.5 years of data were divided into 11 study periods of 6 months each. The Herfindahl-Hirschman Index (HHI)-calculated by summing the squares of individual manufacturers' market shares, with higher values indicating a less competitive market-and average drug prices were estimated for the generic drugs in each period. The HHI value estimated in the baseline period (first half of 2008) was modeled as a fixed covariate. Models estimated price changes over time by level of competition, adjusting for drug shortages, market size, and dosage forms. RESULTS: From 1.08 billion prescription claims, a cohort of 1120 generic drugs was identified. After adjustment, drugs with quadropoly (HHI value of 2500, indicating relatively high levels of competition), duopoly (HHI value of 5000), near-monopoly (HHI value of 8000), and monopoly (HHI value of 10 000) levels of baseline competition were associated with price changes of -31.7% (95% CI, -34.4% to -28.9%), -11.8% (CI, -18.6% to -4.4%), 20.1% (CI, 5.5% to 36.6%), and 47.4% (CI, 25.4% to 73.2%), respectively, over the study period. LIMITATION: Study findings may not be generalizable to drugs that became generic after 2008. CONCLUSION: Market competition levels were associated with a change in generic drug prices. Such measurements may be helpful in identifying older prescription drugs at higher risk for price change in the future. PRIMARY FUNDING SOURCE: None.

Trends of Neonatal Abstinence Syndrome Epidemic and Maternal Risk Factors in Florida.

OBJECTIVE: This study aimed to examine secular trends of (i) maternal prescription opioid use in late pregnancy, (ii) neonatal abstinence syndrome (NAS) stratified by late maternal prescription opioid use, and (iii) maternal risk factors among NAS deliveries. METHODS: Women with a live birth who were enrolled 90 days before and 30 days after delivery in Florida Medicaid Analytic Extract billing records linked to birth certificates from 2000 to 2010 were identified for the study. Changes in the annual prevalence of prescription opioid use during pregnancy were tested with use of the Cochran-Armitage trend test. Temporal trends of NAS deliveries were estimated with the use of Poisson regression and stratified by prescription opioid exposure in the last 90 days of pregnancy in the study period. To identify contributors to the increase in NAS cases, variations in prevalence of opioid dispensing, tobacco use, antidepressant use, and substance use disorder among NAS and non-NAS deliveries were examined. RESULTS: There were 41,968 (9.4%) deliveries exposed to at least one opioid prescription in late pregnancy, and this rate remained stable from 2000 to 2010. Among prescription opioid-exposed deliveries, frequency of NAS increased from 1.6 to 25.2 per 1000 live births during the study period (p<0.05). Although the prevalence of maternal use of prescription opioid, tobacco, and antidepressants remained stable among NAS deliveries from 2000 to 2010, the prevalence of substance use disorder diagnoses increased substantially from 38.9% in 2000 to 67.9% in 2006 (p<0.05). CONCLUSIONS: The prevalence of NAS increased dramatically whereas the prevalence of major risk factors, including maternal prescription opioid use, remained stable in Florida between 2000 and 2010. The increase in substance use disorder may be responsible for the sharp increase in NAS deliveries.