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Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2023 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2023 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, diabetes medications, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2023 were based on a combination of quantitative analyses and expert opinion. Results In 2022, overall pharmaceutical expenditures in the US grew 9.4% compared to 2021, for a total of $633.5 billion. Utilization (a 5.9% increase), price (a 1.7% increase) and new drugs (a 1.8% increase) drove this increase. Adalimumab was the top-selling drug in 2022, followed by semaglutide and apixaban. Drug expenditures were $37.2 billion (a 5.9% decrease) and $116.9 billion (a 10.4% increase) in nonfederal hospitals and clinics, respectively. In clinics, new products and increased utilization growth drove growth, with a small impact from price changes. In nonfederal hospitals, a drop in utilization led to a decrease in expenditures, with price changes and new drugs contributing to growth in spending. Several new drugs that will influence spending have been or are expected to be approved in 2023. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. Conclusion For 2023, we expect overall prescription drug spending to rise by 6.0% to 8.0%, whereas in clinics and hospitals we anticipate increases of 8.0% to 10.0% and 1.0% to 3.0%, respectively, compared to 2022. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2021 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2021 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, generics, coronavirus disease 2019 (COVID-19) pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2021 were based on a combination of quantitative analyses and expert opinion. Results In 2020, overall pharmaceutical expenditures in the United States grew 4.9% compared to 2019, for a total of $535.3 billion. Utilization (a 2.9% increase) and new drugs (a 1.8% increase) drove this increase, with price changes having minimal influence (a 0.3% increase). Adalimumab was the top drug in 2020, followed by apixaban and insulin glargine. Drug expenditures were $35.3 billion (a 4.6% decrease) and $98.4 billion (an 8.1% increase) in nonfederal hospitals and clinics, respectively. In clinics, growth was driven by new products and increased utilization, whereas in hospitals the decrease in expenditures was driven by reduced utilization. Several new drugs that will influence spending are expected to be approved in 2021. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. Conclusion For 2021, we expect overall prescription drug spending to rise by 4% to 6%, whereas in clinics and hospitals we anticipate increases of 7% to 9% and 3% to 5%, respectively, compared to 2020. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

The 2006 FDA's Unapproved Drug Initiative (UDI) aimed to improve safety and public health by decreasing the availability of drug products that never obtained FDA approval (unapproved drug products) in the market and incentivizing manufacturers to emphasize that these products must obtain FDA approval. The objective of this study was to measure changes in the prices, sales, and quantities sold of drug products approved under the FDA-UDI.Drug products that obtained voluntary approval under FDA-UDI from 2006 to 2015 were identified and trends in prices, sales, and units sold were analyzed using the IQVIA National Sales Perspective database.Eleven drug products were included in the final analysis. Relative to baseline levels 2 years before approval, a steep increase in price and sales was observed 2 years postapproval for all except 2 of the drug categories-with median percent change of 245% (range: -37% to 9618%) for price and 238% (range: -4% to 6707%) for sales. Substantial variance was observed in the changes in units sold.A marked increase was seen in postapproval prices and sales for the vast majority of drug products approved in the FDA-UDI with mixed results in changes in units sold. In addition to increased information on safety, the policy's impact on postapproval drug prices and associated effects on units sold should be considered in assessing the policy, especially when substantial price increases and decreases in units sold may negatively impact health.

Background Concomitant use of central nervous system (CNS) medications frequently occurs in older adults with persistent opioid use. The risks of adverse outcomes associated with combinations of opioids, sedative-hypnotics, or skeletal muscle relaxants have not been sufficiently described in this population. Objective To compare the overall and incremental risk of 1) fall-related injury and 2) all-cause hospitalization associated with sedative hypnotics and skeletal muscle relaxants among older persistent opioid users. Methods A case-time-control study was conducted using administrative claims of adults ages ≥66 years with a history of persistent (≥90 days) opioid use. Cases included those with first 1) emergency department, hospital, or outpatient visit for a fall-related injury, or 2) all-cause hospitalization. Exposure to CNS medications prior to the case event versus earlier periods, and the risk associated with CNS drug class combinations and sequence of use, was estimated using conditional logistic regression, adjusted for time trends and time-varying covariates. Results Among 140,101 older persistent opioid users, 20,723 experienced fall-related injury and 39,444 were hospitalized during follow-up. Skeletal muscle relaxant use was associated with an increased risk of fall-related injury (Odds ratio [OR] 1.28) and all-cause hospitalization (OR 1.11). Statistically significant associations were observed for the joint effects of interactions involving skeletal muscle relaxants on fall-related injury (with opioid: OR 1.25; with sedative hypnotic: OR 1.24), and interactions involving opioids on all-cause hospitalization (with sedative hypnotic: OR 1.10; with skeletal muscle relaxant: OR 1.17). The addition of a skeletal muscle relaxant to an opioid regimen was associated with a 25% increased risk of fall-related injury. Additions of other CNS medications did not have apparent incremental effects on the risk of all-cause hospitalization. Conclusion The excess risks of fall-related injury and hospitalization associated with various combinations of CNS medications among older persistent opioid users should be considered in therapeutic decision-making. Further research is needed to confirm these findings.

Background Although pediatric cancer survivors in the United States are at an increased risk of developing chronic conditions, to the authors' knowledge there is limited information regarding the types and combinations of conditions they experience in the years immediately after the completion of cancer therapy. Methods An observational cohort study of early pediatric cancer survivors (children who were ≥2 years from the end of therapy and aged ≤18 years) was conducted using the Truven Health MarketScan (r) Commercial Claims and Encounters database (2009-2014). Latent class analysis was used to identify comorbidity groups among the subset with ≥2 conditions. Group-level health care use was compared with survivors without chronic conditions using multivariate regression. Results A total of 3687 early survivors were identified, of whom approximately 41.2% had no chronic conditions, 22.5% had 1 chronic condition, and 36.3% had ≥2 chronic conditions. Among those with ≥2 chronic conditions, 5 groups emerged: 1) general pediatric morbidity (35.4%); 2) central nervous system (CNS) (22.4%); 3) mental health conditions (22.2%); 4) endocrine (26.2%); and 5) CNS with endocrine (3.8%). The CNS group experienced the highest expenditures, at $17,964 more per year (95% CI, $1446-$34,482) compared with survivors without chronic conditions. The CNS group also had the highest odds of an emergency department visit (adjusted odds ratio, 1.71; 95% CI, 1.15-2.56). The endocrine group had the highest odds of hospitalization (odds ratio, 2.29; 95% CI, 1.24-4.22). Conclusions Multimorbidity is common among pediatric cancer survivors. The current study identified 5 distinct comorbidity subgroups, all of which experienced high, yet differential, rates of health care use. The results of the current study highlight the complex health care needs of early survivors and provide evidence for the design of targeted survivorship services and interventions.

This observational cohort study compares the odds of cardiac events among new users of azithromycin relative to new users of amoxicillin using real-world data., Key Points Question Using a large health care database, what is the risk of cardiac events in azithromycin users compared with amoxicillin users? Findings In a cohort study of 2 141 285 episodes of azithromycin use that were matched to episodes of amoxicillin use with high-dimensional propensity scores, no difference in the rate of cardiac events occurred at 5, 10, and 30 days after therapy initiation. However, concurrent use of QT-prolonging drugs with azithromycin was associated with 40% greater odds of cardiac events compared with amoxicillin. Meaning Azithromycin and amoxicillin appear to pose similar odds of cardiac events except for concurrent use of QT-prolonging drugs with azithromycin; therefore, clinicians should use amoxicillin or another antibiotic among such patients., Importance Conflicting evidence exists on the association between azithromycin use and cardiac events. Objective To compare the odds of cardiac events among new users of azithromycin relative to new users of amoxicillin using real-world data. Design, Setting, and Participants This retrospective cohort study used data from Truven Health Analytics MarketScan database from January 1, 2009, to June 30, 2015. Patients receiving either amoxicillin or azithromycin and enrolled in a health care plan 365 days before (baseline period) the dispensing date (index date) were included in the study. Patients were matched 1:1 on high-dimensional propensity scores. Data were analyzed from October 1, 2018, to December 31, 2019. Exposures New use of azithromycin compared with new use of amoxicillin. Main Outcomes and Measures The primary outcome consisted of cardiac events, including syncope, palpitations, ventricular arrhythmias, cardiac arrest, or death as a primary diagnosis for hospitalization at 5, 10, and 30 days from the index date. Logistic regression models were used to estimate odds ratios (ORs) with 95% CIs. Results After matching, the final cohort included 2 141 285 episodes of each index therapy (N = 4 282 570) (mean [SD] age of patients, 35.7 [22.3] years; 52.6% female). Within 5 days after therapy initiation, 1474 cardiac events (0.03%) occurred (708 in the amoxicillin cohort and 766 in the azithromycin cohort). The 2 most frequent events were syncope (1032 [70.0%]) and palpitations (331 [22.5%]). The odds of cardiac events with azithromycin compared with amoxicillin were not significantly higher at 5 days (OR, 1.08; 95% CI, 0.98-1.20), 10 days (OR, 1.05; 95% CI, 0.97-1.15), and 30 days (OR, 0.98; 95% CI, 0.92-1.04). Among patients receiving any concurrent QT-prolonging drug, the odds of cardiac events with azithromycin were 1.40 (95% CI, 1.04-1.87) greater compared with amoxicillin. Among patients 65 years or older and those with a history of cardiovascular disease and other risk factors, no increased risk of cardiac events with azithromycin was noted. Conclusions and Relevance This study found no association of cardiac events with azithromycin compared with amoxicillin except among patients using other QT-prolonging drugs concurrently. Although azithromycin is a safe therapy, clinicians should carefully consider its use among patients concurrently using other QT-prolonging drugs.

Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2020 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2020 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for specialty drugs, biosimilars, and diabetes medications. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2020 were based on a combination of quantitative analyses and expert opinion. Results In 2019, overall US pharmaceutical expenditures grew 5.4% compared to 2018, for a total of $507.9 billion. This increase was driven to similar degrees by prices, utilization, and new drugs. Adalimumab was the top drug in US expenditures in 2019, followed by apixaban and insulin glargine. Drug expenditures were $36.9 billion (a 1.5% increase from 2018) and $90.3 billion (an 11.8% increase from 2018) in nonfederal hospitals and clinics, respectively. In clinics, growth was driven by new products and increased utilization, whereas in hospitals growth was driven by new products and price increases. Several new drugs that will likely influence spending are expected to be approved in 2020. Specialty and cancer drugs will continue to drive expenditures. Conclusion For 2020 we expect overall prescription drug spending to rise by 4.0% to 6.0%, whereas in clinics and hospitals we anticipate increases of 9.0% to 11.0% and 2.0% to 4.0%, respectively, compared to 2019. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

Purpose: Recent cancer drug approvals are lauded as being more effective with relatively fewer adverse effects, but these treatments come with a great cost to the US health care system. There is little information on recent trends in actual antineoplastic expenditures representative of the whole US health care system or by sector. Therefore, the objective of this study was to describe antineoplastic expenditures in the United States by year and sector. Methods: This was a retrospective, cross-sectional study of IQVIA (formerly QuintilesIMS) National Sales Perspective data for the period of January 1, 2011, to December 31, 2016. Actual expenditures were totaled by health care sector and calendar year, then adjusted for medical-cost inflation to 2016 dollars. Growth was calculated as the percentage increase from the previous year. Results: Total expenditures of antineoplastic agents across all channels grew from $26.8 billion in 2011 to $42.1 billion in 2016. Antineoplastic spending increased 12.2% in 2016 (compared with the previous year), followed by 15.6% in 2015, 13.4% in 2014, 6.3% in 2013, and 0.4% in 2012. Throughout the study period, 96.5% of total antineoplastic expenditures occurred within clinics, mail-order pharmacies, nonfederal hospitals, and retail pharmacies. Conclusion: Antineoplastic expenditures are expected to increase because of continuing development and approval of costly targeted cancer therapies. Cost containment and utilization management strategies must be balanced so as not to restrict access or disrupt innovation. Future policies should focus on ensuring safe and appropriate use of antineoplastics while balancing long-term drug costs.

PURPOSE Studies examining the association between use of oseltamivir and neuropsychiatric events (including suicide) among children have had mixed findings and have been limited by small sample size, reliance on older data, and potential confounding. We undertook an analysis that addresses these limitations. METHODS Using a national administrative claims database and a case-crossover design that minimized confounding, we analyzed data from 5 contemporary influenza seasons (2009–2013) for individuals aged 1 to 18 years and ascertained oseltamivir exposure from pharmacy dispensing. RESULTS We identified 21,407 suicide-related events during this study period, 251 of which were in oseltamivir-exposed children. In case-crossover analysis, we did not find any significant association with suicide either for oseltamivir exposure (odds ratio = 0.64; 95% CI, 0.39–1.00; P = .05) or for influenza diagnosis alone (odds ratio = 0.63; 95% CI, 0.34–1.08; P = .10). CONCLUSION Our findings suggest that oseltamivir does not increase risk of suicide in the pediatric population.

With increasing health care costs that have outpaced those of other industries, payers of health care are moving from a fee-for-service payment model to one in which reimbursement is tied to outcomes. Chronic obstructive pulmonary disease (COPD) is a disease where this payment model has been implemented by some payers, and COPD exacerbations are a quality metric that is used. Under an outcomes-based payment model, it is important for health systems to be able to identify patients at risk for poor outcomes so that they can target interventions to improve outcomes.To develop and evaluate predictive models that could be used to identify patients at high risk for COPD exacerbations.This study was retrospective and observational and included COPD patients treated with a bronchodilator-based combination therapy. We used health insurance claims data to obtain demographics, enrollment information, comorbidities, medication use, and health care resource utilization for each patient over a 6-month baseline period. Exacerbations were examined over a 6-month outcome period and included inpatient (primary discharge diagnosis for COPD), outpatient, and emergency department (outpatient/emergency department visits with a COPD diagnosis plus an acute prescription for an antibiotic or corticosteroid within 5 days) exacerbations. The cohort was split into training (75%) and validation (25%) sets. Within the training cohort, stepwise logistic regression models were created to evaluate risk of exacerbations based on factors measured during the baseline period. Models were evaluated using sensitivity, specificity, and positive and negative predictive values. The base model included all confounding or effect modifier covariates. Several other models were explored using different sets of observations and variables to determine the best predictive model.There were 478,772 patients included in the analytic sample, of which 40.5% had exacerbations during the outcome period. Patients with exacerbations had slightly more comorbidities, medication use, and health care resource utilization compared with patients without exacerbations. In the base model, sensitivity was 41.6% and specificity was 85.5%. Positive and negative predictive values were 66.2% and 68.2%, respectively. Other models that were evaluated resulted in similar test characteristics as the base model.In this study, we were not able to predict COPD exacerbations with a high level of accuracy using health insurance claims data from COPD patients treated with bronchodilator-based combination therapy. Future studies should be done to explore predictive models for exacerbations.No outside funding supported this study. Samp is now employed by, and owns stock in, AbbVie. The other authors have nothing to disclose. Study concept and design were contributed by Joo and Pickard, along with the other authors. Samp and Lee performed the data analysis, with assistance from the other authors. Samp wrote the manuscript, which was revised by Schumock and Calip, along with the other authors.

Evidence from comparative effectiveness research (CER) and patient-centered outcomes research (PCOR) studies are increasingly available in the literature. However, there remain opportunities to better integrate that evidence into decision-making. An invitation-only conference held in January 2017, titled “Comparative Effectiveness and Patient-Centered Outcomes Research: Enhancing Uptake and Use by Patients, Clinicians and Payers” , sought to identify and discuss both gaps in the uptake and use of CER/PCOR, and approaches to enhance the uptake and use of CER/PCOR evidence by patients, clinicians and payers. In this article, we summarize the conference proceedings, and highlight the themes and recommendations that resulted from the sessions. This paper also introduces other articles in this issue of CER from that conference.

Purpose Historical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2017 in nonfederal hospitals, clinics, and overall (all sectors). Methods Drug expenditure data through calendar year 2016 were obtained from the QuintilesIMS National Sales Perspectives database and analyzed. Other factors that may influence drug spending in hospitals and clinics in 2017, including new drug approvals and patent expirations, were also reviewed. Expenditure projections for 2017 for nonfederal hospitals, clinics, and overall (all sectors) were made based on a combination of quantitative analyses and expert opinion. Results Total U.S. prescription sales in the 2016 calendar year were $448.2 billion, a 5.8% increase compared with 2015. More than half of the increase resulted from price hikes of existing drugs. Adalimumab was the top drug overall in 2016 expenditures ($13.6 billion); in clinics and nonfederal hospitals, infliximab was the top drug. Prescription expenditures in clinics and nonfederal hospitals totaled $63.7 billion (an 11.9% increase from 2015) and $34.5 billion (a 3.3% increase from 2015), respectively. In nonfederal hospitals and clinics, growth in spending was driven primarily by price increases of existing drugs and increased volume, respectively. Conclusion We project a 6.0–8.0% increase in total drug expenditures across all settings, an 11.0–13.0% increase in clinics, and a 3.0–5.0% increase in hospital drug spending in 2017. Health-system pharmacy leaders should carefully examine their own local drug utilization patterns to determine their own organization’s anticipated spending in 2017.

Background: The recent approval of several fixed-dose combination long-acting β2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) products has increased the use of dual bronchodilators in the treatment of chronic obstructive pulmonary disease (COPD). Understanding the comparative safety of this combination is important for informing treatment decisions. Objective: To compare the risk of cardiovascular and cerebrovascular (CCV) events associated with LABA/LAMA compared with a combination of LABA and inhaled corticosteroid (ICS). Methods: This was a retrospective, observational cohort study using health insurance claims data to identify COPD patients initiating LABA/LAMA or LABA/ICS. CCV outcomes included hospitalizations with a primary diagnosis for acute coronary syndrome, heart failure, cardiac dysrhythmia, stroke, or transient ischemic attack. Patients were followed until they experienced an event, discontinued treatment, initiated medication from the opposite cohort, or lost enrollment. Patients were matched 1:4 on propensity scores, and time to event was compared using Cox proportional hazards models. Results: After matching, there were 3842 patients in the LABA/LAMA cohort and 15 225 in the LABA/ICS cohort. Cardiovascular events in the LABA/LAMA cohort were lower than in the LABA/ICS: hazard ratio (HR) = 0.794; 95% CI = 0.623-0.997. No significant difference in the risk of cerebrovascular events (HR = 1.166; 95% CI = 0.653-1.959) was observed. Conclusions: Despite concerns about the CCV effects of LAMA and LABA monotherapy, the LABA/LAMA combination had similar or lower risk of these events in comparison to LABA/ICS. Further studies are recommended to confirm these findings.

Objectives TNF-α inhibitors (TNFIs) have a black box warning for increased risk of serious infection that was based on evidence from studies of adults. Evidence of the association is lacking for children. We aimed to examine the risk of infection posed by TNFIs compared with DMARDs in children with JIA. Methods We conducted a cohort study using the 2009-13 Truven MarketScan Commercial Claims and Encounters database. Children

Introduction Several dual bronchodilator fixed-dose inhaler medications were recently approved for the treatment of chronic obstructive pulmonary disease (COPD). These products combine a long-acting β2-agonist (LABA) and long-acting muscarinic antagonist (LAMA). In clinical trials, the separate mechanisms of the bronchodilators resulted in improved lung function. COPD treatment guidelines currently recommend combination LABA/LAMA as alternative therapy to combination LABA/inhaled corticosteroid (ICS). Evidence is limited on the comparative effectiveness of LABA/LAMA and LABA/ICS in COPD. The objective of this study was to compare real-world COPD exacerbation rates among patients treated with LABA/LAMA with those treated with LABA/ICS. Methods This was a retrospective observational study of COPD patients in the United States treated with LABA/LAMA or LABA/ICS combination. Insurance claims from January 1, 2004, through December 31, 2014, were used as the data source. Patients were required to have greater than one prescription filled for the combination medications, and they were followed from 30 days after drug initiation. Individuals were censored if they discontinued a study medication, initiated medication from the opposite cohort (LAMA or ICS), lost enrollment eligibility, or at the study period end. Exacerbation rates were compared using Poisson regression. Results There were 5384 patients in the LABA/LAMA cohort and 473,388 patients in the LABA/ICS cohort. The LABA/LAMA cohort was older, had more comorbidities, and more severe COPD. Unadjusted annual exacerbation rates were 2.87 events per person-year (standard deviation [SD] 5.14) in the LABA/LAMA cohort and 1.68 (SD 9.82) in the LABA/ICS cohort. The adjusted incidence rate ratio was 0.98 (95% confidence interval 0.95–1.01) for LABA/LAMA compared with LABA/ICS. Conclusions The LABA/LAMA combination had similar effectiveness to LABA/ICS as measured by exacerbation rates in COPD patients. As a result, characteristics other than effectiveness, such as symptom control, cost, patient preferences, and adverse events, may be important in selecting between the two regimens.

Adherence and persistence with diabetes medication play an important role in glycemic control and may differ by medication class. However, there is a lack of research comparing diabetes medications in patients with renal impairment, despite the challenges and higher burden associated with managing this population.To compare adherence and persistence among patients with type 2 diabetes mellitus (T2DM) and nondialysis chronic kidney disease (CKD) treated with dipeptidyl peptidase-4 (DPP-4) inhibitors versus pioglitazone.This retrospective cohort study used Truven MarketScan administrative claims databases from 2009 to 2015. One-year adherence for patients with T2DM and nondialysis CKD who initiated therapy with either a DPP-4 inhibitor or pioglitazone was measured by proportion of days covered (PDC) following an initial dispensing, and PDC ≥ 0.80 was coded as adherent. Persistence was calculated as the days between the index date and last day with the index medication on hand, based on the end of the last days supply or the end of follow-up (i.e., 365 days), whichever occurred first. Multivariate logistic regression and Cox proportional hazards models were used to estimate confounder-adjusted differences between the groups for adherence and persistence.The final cohort included 9,019 patients (DPP-4 inhibitors: 7,002; pioglitazone: 2,017). In the adjusted analysis, DPP-4 inhibitor users demonstrated a 1.41 (95% CI = 1.25-1.59) higher odds of being adherent compared with pioglitazone users. Overall adjusted HR for persistence was 0.74 (95% CI = 0.69-0.79), which favored DPP-4 inhibitors compared with pioglitazone. Relative to 2010, persistence with pioglitazone decreased in 2011-2012 and then increased in 2013-2014. In the subgroup analysis, DPP-4 inhibitors first had lower (2010: OR = 0.78, 95% CI = 0.70-0.87; 2011-2012: OR = 0.60, 95% CI = 0.54-0.66) and then similar (2013-2014: OR = 1.03, 95% CI = 0.88-1.19) hazards of nonpersistence compared with pioglitazone.Among patients with T2DM and nondialysis CKD, the use of DPP-4 inhibitors was associated with better adherence compared with pioglitazone. However, following the approval of generic pioglitazone and associated lower cost sharing after 2012, the magnitude of difference in adherence between the medication classes reduced. Similarly, safety warnings in 2011 and approval of generic products in 2012 may have affected pioglitazone persistence, leading to first higher and then similar hazards for nonpersistence with pioglitazone as compared with DPP-4 inhibitors. These shifts in the results for pioglitazone warrant further investigation and close monitoring of the population initiating this medication.No funding was received for this study. The authors have no conflicts of interest to disclose. An abstract for this study was presented as a podium presentation at the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) 2019 Annual Meeting; May 18-22, 2019; New Orleans, LA.

STUDY OBJECTIVE To measure the prevalence of cardiac risk factors among patients prescribed azithromycin before and after the United States Food and Drug Administration (FDA) issued a warning on May 17, 2012, on the risk of potentially fatal heart rhythms associated with the drug. DESIGN Retrospective cohort study using administrative claims data. DATA SOURCE Truven Health Analytics MarketScan database. PATIENTS A total of 12,971,078 unique patients with 23,749,652 azithromycin prescriptions dispensed between January 2009 and June 2015 were included. Patients had to be continuously enrolled in a health plan for at least 365 days (baseline) before the date of azithromycin dispensing (index date). Cohorts were assigned based on the index dates of the azithromycin prescriptions, either before (January 1, 2009-May 1, 2012) or after (June 1, 2012-June 30, 2015) the FDA warning was issued. MEASUREMENTS AND MAIN RESULTS A cardiac risk factor included either a cardiac condition (heart failure or dysrhythmias) or concurrent use of drugs that prolong the QT interval. The unit of analysis was each prescription of azithromycin. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the prevalence of cardiac risk factors. Mean age of the patients was 40.1 ± 21.3 years old, with 60.8% females. Prior to the FDA warning, 11,596,022 (48.8%) azithromycin prescriptions were identified, and 12,153,630 (51.2%) were identified after the warning. The prevalence of a preexisting cardiac condition was 7.3% versus 7.9% (p

PurposeHistorical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2019 in nonfederal hospitals, clinics, and overall (all sectors).MethodsDrug expenditure data through calendar year 2018 were obtained from the IQVIA National Sales Perspectives database and analyzed. New drug approvals, patent expirations, and other factors that may influence drug spending in hospitals and clinics in 2019 were also reviewed. Expenditure projections for 2019 for nonfederal hospitals, clinics, and overall (all sectors) were made through a combination of quantitative analyses and expert opinion.ResultsU.S. prescription sales in calendar year 2018 totaled $476.2 billion, a 5.5% increase from 2017 spending. The top 3 drugs by expenditures were adalimumab ($19.1 billion), insulin glargine ($9.3 billion), and etanercept ($8.0 billion). Prescription expenditures in nonfederal hospitals totaled $35.8 billion, a 4.8% increase from 2017. Expenditures in clinics in 2018 increased by 13.0% to $80.5 billion. The increase in spending in nonfederal hospitals was largely driven by new products and increased utilization of existing products. The list of the top 25 drugs by expenditures in nonfederal hospitals and clinics was dominated by specialty drugs.ConclusionWe predict continued moderate growth of 4–6% in overall drug expenditures (across the entire U.S. market). We expect the clinic sector to continue to experience high (11–13%) growth in drug spending in 2019. Finally, for nonfederal hospitals we anticipate growth in the range of 3–5%. These estimates are at the national level. Health-system pharmacy leaders should carefully examine local drug utilization patterns to determine their own organization’s anticipated spending in 2019.

Purpose To determine the risk of fractures associated with sodium-glucose co-transporter 2 inhibitors (SGLT2i) compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Methods We conducted a retrospective cohort study using data from the Truven Health MarketScan (2009-2015) databases. Our cohort included patients newly initiating treatment with SGLT2i or DPP-4i between 1 April 2013 and 31 March 2015 that were matched 1:1 using high dimensional propensity scores. Patients were followed up in an as-treated approach starting from initiation of treatment until the earliest of any fracture, treatment discontinuation, disenrollment, or end of data (31 December 2015). Risk of fractures was determined at any time during the follow-up, early in therapy (1-14 days of the follow-up), and later in therapy (15 days and beyond). Cox proportional hazards models were used to determine hazard ratios and robust 95% confidence intervals (95% CI). Results After matching, our cohort included 30 549 patients in each treatment group. Over a median follow-up of 219 days, there were 745 fractures overall. The most common site for fractures was the foot (32.7%). The effect estimates for fracture risk occurring at any time during follow-up, early in therapy, and later in therapy were HR 1.11 [95% CI 0.96-1.28], HR 1.82 [95% CI 0.99-3.32], and HR 1.07 [95% CI 0.92-1.24], respectively. Conclusion There is a possible increase in risk for fractures early in therapy with SGLT2i. Beyond this initial period, SGLT2is had no apparent effect on the incidence of fractures.

Study objective New hepatitis C virus (HCV) antivirals have been shown to be highly effective with minimal adverse effects, but they are costly. Little is known, however, about the impact of the new HCV antivirals on expenditures in the overall U.S. health care system or by health care sector. Thus the objective of this study was to describe HCV antiviral expenditures by agent, year, and health care sector. Design Retrospective cross-sectional study. Data source QuintilesIMS National Sales Perspectives database. Measurements and main results QuintilesIMS National Sales Perspectives data for the period of January 1, 2009, to December 31, 2015, were used to describe HCV antiviral expenditures. HCV antiviral expenditures grew each year from $78 million in 2009 to $18 billion in 2015, except during 2013 when spending on HCV drugs dropped by $684 million (41%) compared with 2012. Although most expenditures in 2009 and 2010 were for interferons, this shifted to telaprevir in 2011-2013 and sofosbuvir-containing regimens in 2014-2015. Mail service and community pharmacies were associated with most of the expenditures throughout the study period. Conclusion New HCV antivirals are driving the increased expenditures for this class. Decreased expenditures in 2013 may have been secondary to delaying HCV treatment until new therapies received approval from the U.S. Food and Drug Administration (termed "warehousing"). With continued drug development and approval of HCV therapies, expenditures are expected to continue to increase, barring actions by payers that may impede this trend. Medication policies guiding HCV treatment should focus on safety and efficacy while balancing the long-term costs of HCV.

Purpose Historical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2016 in nonfederal hospitals, clinics, and overall (all sectors). Methods Drug expenditure data through calendar year 2015 were obtained from the IMS Health National Sales Perspectives database and analyzed. Other factors that may influence drug spending in hospitals and clinics in 2016, including new drug approvals and patent expirations, were also reviewed. Expenditure projections for 2016 were based on a combination of quantitative analyses and expert opinion. Results Total U.S. prescription sales in the 2015 calendar year were $419.4 billion, which was 11.7% higher than sales in 2014. Prescription expenditures in clinics and nonfederal hospitals totaled $56.7 billion (a 15.9% increase) and $33.6 billion (a 10.7% increase), respectively, in 2015. In nonfederal hospitals, growth in spending was driven primarily by increased prices for existing drugs. The hepatitis C combination drug ledipasvir–sofosbuvir was the top drug overall in terms of 2015 expenditures ($14.3 billion); in both clinics and nonfederal hospitals, infliximab was the top drug. Individual drugs with the greatest increases in expenditures in 2015 were specialty agents and older generics; these agents are likely to continue to influence total spending in 2016. Conclusion We project an 11–13% increase in total drug expenditures overall in 2016, with a 15–17% increase in clinic spending and a 10–12% increase in hospital spending. Health-system pharmacy leaders should carefully examine local drug utilization patterns in projecting their own organization’s drug spending in 2016.

This Chapter provides an introduction and overview of the U.S. FDA REMS program and applicable regulatory aspects. Topics covered include the 2015 Draft Guidance, organization structure and functions, a discussion on pharmacovigilance and adverse event reports, and a discussion of the applicability of REMS in oncology.

This Chapter provides an introduction and overview of the U.S. FDA REMS program and applicable regulatory aspects. Topics covered include the 2015 Draft Guidance, organization structure and functions, a discussion on pharmacovigilance and adverse event reports, and a discussion of the applicability of REMS in oncology.

Early survivors of pediatric cancer are at increased risk of experiencing chronic conditions; however, little is known about the morbidity burden in this population. In this observational cohort study of commercially insured pediatric cancer survivors in the United States (2009-2014), we find that 22.5% of survivors had one chronic condition, and 36.3% had multiple. Compared with survivors without chronic conditions, the presence of multiple conditions significantly increased the odds of an emergency department visit by 70% (odds ratios [OR], 1.7; 95% confidence interval [CI], 1.4-2.1) and of a hospitalization almost four-fold (OR, 3.8; 95% CI], 2.5-5.5). Findings are important for informing pediatric survivorship care plans in the years following completion of therapy.

Aims To determine the risk of mycotic infections associated with the use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in a real-world setting. Methods We conducted a prescription sequence symmetry analysis using data from Truven Health MarketScan (2009-2015). We selected continuously enrolled patients newly initiating both an SGLT2i and an antifungal between 1 April 2013 and 31 December 2015 within time periods of 30, 60, 90, 180 or 365 days of each other. Adjusted sequence ratios (ASR) were calculated for each time period as the ratio of patients initiating SGLT2i first over those initiating an antifungal first adjusted for time trends in prescribing. Analyses were stratified by sex and type of SGLT2i. Results There were 23 276 patients who newly initiated both SGLT2i and an antifungal in our study period. These patients were further classified into those initiating the two drugs within 365 (n = 17 504), 180 (n = 11 873), 90 (n = 7697), 60 (n = 5856) or 30 (n = 3650) days of each other. Increased risks of mycotic infections were present across all time periods, with the strongest effect observed in the 90-day interval [ASR 1.53 (confidence interval, CI 1.43-1.60)]. Findings differed by sex [90-day ASR females: 1.65 (CI 1.56-1.74); males 1.25 (CI 1.14-1.36)] and by SGLT2i [90-day ASR canagliflozin 1.57 (CI 1.49-1.66); non-canagliflozin 1.42 (CI 1.31-1.55)]. Conclusion Initiation of SGLT2i was associated with an increased risk for mycotic infections. Findings from this commercially insured population in the real world are consistent with evidence available from clinical trials.

Objective Use of second-generation antipsychotics (SGAs) for treatment of depression has increased, and patients with depression and comorbid diabetes or cardiovascular disease are more likely to use SGAs than those without these conditions. We compared SGA and non-SGA depression pharmacotherapies on the risk of diabetes hospitalization or treatment intensification in adults with depression and preexisting diabetes. Methods This was a retrospective cohort study of US commercially insured adults (2009-2015 Truven MarketScan Commercial Claims and Encounters Database) aged 18-64 years old with type 2 diabetes mellitus and unipolar depression previously treated with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor. New users of SGAs versus non-SGAs, as well as specific treatments (aripiprazole, quetiapine, bupropion, mirtazapine, and tricyclic antidepressants [TCAs]) were matched on class/medication-specific high-dimensional propensity score. Cox proportional hazard models were used to compare the risk of diabetes-related hospitalization or treatment intensification. Results We identified 6,625 SGA (aripiprazole = 3,461; quetiapine = 1,977; other = 1,187) and 23,921 non-SGA patients for inclusion (bupropion = 15,511; mirtazapine = 1,837; TCAs = 5,989; other = 584) with a mean age of 51 years. In the matched cohort, the rate of diabetes-related hospitalization or drug intensification was 47.9 per 100 person-years in the SGA group and 43.5 per 100 person-years in the non-SGA group (adjusted hazard ratio [aHR] = 1.03; 95% CI, 0.96-1.11). When comparing treatment subgroups, the risk of events was lower for bupropion versus TCAs (aHR = 0.85; 95% CI, 0.76-0.98), quetiapine versus mirtazapine (aHR = 0.82; 95% CI, 0.67-0.99), and quetiapine versus TCAs (aHR = 0.84; 95% CI, 0.72-0.98). For other comparisons, differences were small and not statistically significant. Conclusions While drug-specific effects on risk of diabetes hospitalization or treatment intensification most likely guide clinical decision making, we observed only modest differences in risk. The overall impact of SGAs on diabetes control depends not only on direct effects on glucose metabolism but also on effectiveness of depression symptom relief. Future studies evaluating other diabetes outcomes (glycosylated hemoglobin, diabetes complications) are needed.

Aim To determine the risk of amputations associated with sodium-glucose co-transporter-2 inhibitors (SGLT2i) relative to dipeptidyl peptidase-4 inhibitors (DPP4i). Materials and methods We conducted an active comparator, new user cohort study using data from the Truven Health MarketScan (2009-2015) databases. Patients aged ≥18 years newly initiating SGLT2i or DPP4i between April 1, 2013 and March 31, 2015 were included. Patients were matched 1:1 on high dimensional propensity scores and followed until the earliest of any amputation, treatment discontinuation, disenrollment or end of study period (December 31, 2015). Cox proportional hazards models were used to estimate hazard ratios (HR) and robust 95% confidence intervals (CI) for amputation risk. Results There were 30 216 comparable patients in each arm after matching. Over a median follow-up of 0.6 years, there were 60 amputations (SGLT2i: 36; DPP4i: 24), most at the level of partial foot (75%) and associated with diabetes-related vascular disease (66.7%). The incidence of amputations was higher among SGLT2i patients (1.62 vs. 1.15 per 1000 person-years) with a HR of 1.38 (CI: 0.83-2.31). In subgroup analyses, risk differed by type of SGLT2i: canagliflozin, HR 1.15 (CI: 0.63-2.09); dapagliflozin or empagliflozin, HR 2.25 (CI: 0.78-6.47). Conclusion All SGLT2i had an elevated, though not statistically significant, risk for amputations.

Purpose Current benchmark statistics on staffing, workload, and productivity in hospital pharmacy departments of state psychiatric hospitals are described and assessed by hospital size. Methods An electronic survey of state psychiatric hospitals was conducted. Hospitals were categorized based on number of occupied beds. Descriptive statistics using Student’s t tests, Pearson’s chi-square tests, and Pearson’s correlation coefficients were used to characterize the data and compare productivity by hospital size. Results Responses were received from 41 of 116 hospitals, yielding a response rate of 35.3%. Respondent hospitals did not differ from nonrespondents based on demographic data. Average inpatient census, patient days per year, expenditures, and workload were found to correlate positively with hospital size ( r = 0.381–0.991, p p = 0.017 and 0.05, respectively), mean full-time equivalents (FTEs) per 1,000 doses dispensed or administered per month and per 100 occupied beds ( p = 0.042 and 0.026, respectively), and mean pharmacist and technician FTEs per 100 occupied beds ( p = 0.012 and 0.019, respectively). Conclusion A survey of pharmacies in state psychiatric hospitals provided metrics data on staffing, workload, and productivity that may be used as benchmarks in efforts to improve workforce efficiency, pharmaceutical care services, and financial performance.

Background Prior studies evaluating the relationship between tumor necrosis factor-alpha inhibitors (TNFI) and infection were conducted in adults and had conflicting findings. We sought to examine the risk of serious infection associated with TNFIs compared with nonbiologic immunomodulators in children and young adults with inflammatory bowel disease (IBD) and to compare the risk among individual TNFIs. Methods We conducted a cohort study using the Truven MarketScan Commercial Claims and Encounters database of patients age

The term comparative effectiveness research (CER) took center stage with passage of the American Recovery and Reinvestment Act (2009). The companion US$1.1 billion in funding prompted the launch of initiatives to train the scientific workforce capable of conducting and using CER. Passage of the Patient Protection and Affordable Care Act (2010) focused these initiatives on patients, coining the term ‘patient-centered outcomes research’ (PCOR). Educational and training initiatives were soon launched. This report describes the initiative of the Pharmaceutical Research and Manufacturers Association of America (PhRMA) Foundation. Through provision of grant funding to six academic Centers of Excellence, to spearheading and sponsoring three national conferences, the PhRMA Foundation has made significant contributions to creation of the scientific workforce that conducts and uses CER/PCOR.

Purpose An analysis of trends in U.S. pharmaceutical spending is presented, including projections for drug expenditures in nonfederal hospital and clinic settings in 2015. Methods Prescription drug expenditure data through September 2014 were obtained from the IMS Health National Sales Perspectives database and were analyzed descriptively. Other factors that may influence prescription spending in hospitals and clinics in 2015, including new drug approvals and patent expirations, were analyzed. Expenditure projections were based on a combination of quantitative and qualitative analyses and expert opinion. Results Total prescription sales for the 12 months ending September 30, 2014, were $360.7 billion, 12.2% higher than during the previous 12 months. With $6.6 billion in expenditures in the first 9 months of 2014, sofosbuvir topped the overall list of drugs based on sales, followed by aripiprazole and insulin glargine. Pharmaceutical spending by clinics and nonfederal hospitals rose by 13.3% and 4.0%, respectively. For the first 9 months of 2014, the top drugs based on expenditures were infliximab, pegfilgrastim, and epoetin alfa in clinics and infliximab, rituximab, and pegfilgrastim in hospitals. Specialty drugs continued to constitute an increasing portion of drug expenditures and will contribute to higher expenditures in 2015. Conclusion Growth in U.S. prescription drug expenditures is expected to continue to increase in 2015. The projected increases in total drug expenditures are 7–9% across all settings, 12–14% in clinics, and 5–7% in hospitals. Health-system pharmacy leaders should carefully examine their own local drug utilization patterns to determine their own organization’s anticipated spending in 2015.

Aims To compare adherence and persistence to oral antidiabetic drugs (OAD) between patients who are new users of second generation antipsychotics (SGA) versus new users of other depression therapies in adults with type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD). Methods Adults 18–64 years with previously-treated T2DM and MDD (past OAD and SSRI/SNRI use) who are new users of SGA or non-SGA therapies (bupropion, lithium, mirtazapine, thyroid hormone, tricyclic antidepressant) were identified in the 2009–2015 MarketScan® Commercial Claims and Encounters database. Multivariate regression models were used to determine the odds of a ≥10% decline in OAD adherence over 180- and 365-days, and time to OAD discontinuation, adjusting for differences between groups. Results A total of 8664 (21.5% SGA), 8311 (22.1% SGA), and 17,524 (21.3% SGA) patients met inclusion criteria for the 180-day adherence, 365-day adherence, and persistence cohorts, respectively. Over 180-days, 16.6% of SGA and 13.3% of non-SGA initiators had a ≥10% decline in OAD adherence (adjusted odds ratio [OR] = 1.41, 95% CI 1.21–1.63). Over 365-days, 22.3% of SGA and 18.9% of non-SGA initiators had a ≥ 10% decline (OR = 1.34, 95% CI 1.17–1.53). Time to OAD discontinuation was similar between groups (adjusted hazard ratio = 1.03, 95% CI 0.94–1.12). Conclusion Use of SGA was associated with a 1.3–1.4 times higher odds of a ≥10% decline in OAD adherence. Adherence to OAD is critical for optimal diabetes control and reductions in this magnitude may impact A1C. Close monitoring of OAD adherence after SGA initiation is warranted.

Strategies to improve public health may benefit from targeting specific lifestyles associated with poor health behaviors and outcomes. The aim of this study was to characterize and examine the relationship between health and lifestyle-related attitudes (HLAs) and self-rated health and life-satisfaction. Secondary analyses were conducted on data from a 2012 community wellness survey in Kirklees, UK. Using a validated HLA tool, respondents (n = 9130) were categorized into five segments: health conscious realists (33%), balanced compensators (14%), live-for-todays (18%), hedonistic immortals (10%), and unconfident fatalists (25%). Multivariate regression was used to examine whether HLAs could explain self-rated health using the EQ-5D visual analog scale (EQ-VAS) and life-satisfaction. Health conscious realists served as the reference group. Self-rated health differed by HLA, with adjusted mean EQ-VAS scores being significantly higher (better) among balanced compensators (1.15, 95% CI 0.27, 2.03) and lower scores among unconfident fatalists (− 9.02, 95% CI − 9.85, − 8.21) and live-for-todays (− 1.96, 95% CI − 2.80, − 1.14). Balanced compensators were less likely to report low life-satisfaction (OR 0.75, 95% CI 0.62, 0.90), while unconfident fatalists were most likely to have low life-satisfaction (OR 3.51, 95% CI 2.92, 4.23). Segmentation by HLA explained differences in self-rated health and life-satisfaction, with unconfident fatalists being a distinct segment with significantly worse health perceptions and life-satisfaction. Health promotion efforts may benefit from considering the HLA segment that predominates a patient group, especially unconfident fatalists.

Based on limited evidence, the U.S. Food and Drug Administration (FDA) issued a black box warning for the use of tumor necrosis factor-alpha inhibitors (TNFIs) and risk of non-Hodgkin lymphoma (NHL). Our objective was to determine the risk of NHL associated with TNFI use by duration and type of anti-TNF agent. We performed a nested case-control study within a retrospective cohort of adults with rheumatologic conditions from a U.S. commercial health insurance database between 2009 and 2015. Use of TNFIs (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol) and conventional-synthetic disease-modifying antirheumatic drugs (csDMARDs) was identified, and conditional logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL. From a retrospective cohort of 55,446 adult patients, 101 NHL cases and 984 controls matched on age, gender and rheumatologic indication were included. Compared to controls, NHL cases had greater TNFI use (33% vs. 20%) but were similar in csDMARD use (70% vs. 71%). TNFI ever-use was associated with nearly two-fold increased risk of NHL (OR = 1.93; 95% CI: 1.16-3.20) with suggestion of increasing risk with duration (P-trend = 0.05). TNF fusion protein (etanercept) was associated with increased NHL risk (OR = 2.73; 95% CI: 1.40-5.33), whereas risk with anti-TNF monoclonal antibodies was not statistically significant (OR = 1.77; 95% CI: 0.87-3.58). In sensitivity analyses evaluating confounding by rheumatologic disease severity, channeling bias was not likely to account for our results. Our findings support the FDA black box warning for NHL. Continued surveillance and awareness of this rare but serious adverse outcome are warranted with new TNFIs and biosimilar products forthcoming.

The recent approval of several fixed-dose combination long-acting βTo compare the risk of cardiovascular and cerebrovascular (CCV) events associated with LABA/LAMA compared with a combination of LABA and inhaled corticosteroid (ICS).This was a retrospective, observational cohort study using health insurance claims data to identify COPD patients initiating LABA/LAMA or LABA/ICS. CCV outcomes included hospitalizations with a primary diagnosis for acute coronary syndrome, heart failure, cardiac dysrhythmia, stroke, or transient ischemic attack. Patients were followed until they experienced an event, discontinued treatment, initiated medication from the opposite cohort, or lost enrollment. Patients were matched 1:4 on propensity scores, and time to event was compared using Cox proportional hazards models.After matching, there were 3842 patients in the LABA/LAMA cohort and 15 225 in the LABA/ICS cohort. Cardiovascular events in the LABA/LAMA cohort were lower than in the LABA/ICS: hazard ratio (HR) = 0.794; 95% CI = 0.623-0.997. No significant difference in the risk of cerebrovascular events (HR = 1.166; 95% CI = 0.653-1.959) was observed.Despite concerns about the CCV effects of LAMA and LABA monotherapy, the LABA/LAMA combination had similar or lower risk of these events in comparison to LABA/ICS. Further studies are recommended to confirm these findings.

Purpose Overall and specific class trends in systemic antifungal expenditures in various U.S. healthcare settings from 2005 through 2015 were evaluated. Methods Systemic antifungal expenditures from January 1, 2005, through December 31, 2015, were obtained from the QuintilesIMS National Sales Perspective database, which provides a statistically valid projection of medication purchases from multiple markets throughout the United States. Summary data for total antifungal expenditures over the entire period are reported, as are growth and the percentage change in expenditures from one year to the next. Expenditures were also assessed specifically by year, class, and healthcare setting. Expenditure trends over the study period were assessed using simple linear trend regression models. Results Overall expenditures for the 11-year period were $9.37 billion. The greatest proportion of expenditures occurred in nonfederal hospitals (47.2%) and for triazoles (57.6%). From 2005 through 2015, total expenditures decreased from $1.1 billion to $894 million (−18.8%, p = 0.09); however, expenditures in clinics and retail pharmacies increased (202%, p p = 0.04, respectively), a trend most pronounced after 2012. Expenditures for flucytosine also increased (968.1%, p p Conclusion From 2005 through 2015, an increase in systemic antifungal expenditures was observed in community settings, despite an overall decrease in total antifungal expenditures in the United States. Large increases in flucytosine expenditures were observed, particularly in the community.

Purpose An analysis of trends in U.S. pharmaceutical spending is presented, including projections for drug expenditures in nonfederal hospital and clinic settings in 2014. Methods Trends in pharmaceutical expenditures and developments likely to influence future spending, including new drug approvals and patent expirations, were analyzed using data from the IMS Health National Sales Perspectives database. Projections were based on a combination of quantitative and qualitative analyses and expert opinion. Results Total prescription sales for the 12 months ending September 2013 were approximately $326 billion, 0.7% lower than sales during the previous 12 months; pharmaceutical spending by clinics and nonfederal hospitals grew by 4.5% and 1.8%, respectively. Vaccines were among the products driving large sales increases in clinic settings, with alteplase and pegfilgrastim topping the list of fast-growing drugs by hospital expenditures. Few new drug approvals anticipated in 2014 are expected to result in major expenditures by hospitals and clinics. Expansion of access to health care and other changes related to the Patient Protection and Affordable Care Act, as well as continued improvement in the U.S. economy, may drive growth in pharmaceutical spending over the next 12–24 months. Conclusion Growth in U.S. prescription drug expenditures is expected to rebound in 2014, with a projected 3–5% increase in total drug expenditures across all settings this year, including a 5–7% increase in clinic spending and a 1–3% increase in hospital spending. Health-system pharmacy leaders should carefully examine local drug-utilization patterns to determine their respective organization’s anticipated spending in 2014.

Purpose: Propensity scores (PS) are frequently used in observational studies. PS are usually estimated over the entire study period without consideration of the effect of changing patterns of the included variables over time. This study sought to compare PS estimated using the entire study period (conventional PS) and PS estimated for specific periods (calendar time-specific PS (CTS-PS)), and to determine whether there are differences in estimated treatment effects using these approaches. Methods: We conducted a claims data analysis. Asthmatic patients who received an asthma controller during 1997-2008 were included. Exposed patients were those who received an inhaled long-acting beta-2 agonist. Conventional PS used the entire period to estimate a PS for individuals. CTS-PS approach divided the study period into 1-year periods and estimated PS separately for each period. Each individual had two PS. Both PS approaches were used to estimate adjusted hazard ratio (HR) for asthma exacerbations using Cox proportional hazard models. Results: A total of 288,518 patients with an average age of 11.9±5.8years were included. The difference between conventional PS and CTS-PS in each period ranged from -0.213 to 0.098. The adjusted HR of conventional PS-matched cohort was 1.20 (95%CI: 1.18-1.22), whereas the estimate for the CTS-PS-matched cohort was 1.24 (95%CI: 1.23-1.37). Conclusion: Focusing on a specific year, there was a difference between conventional PS estimated versus CTS-PS for that year. However, there was minimal effect of CTS-PS on the observed treatment effects compared with conventional PS approach.

Study objective To evaluate the risk of arrhythmias associated with inhaled anticholinergic (IAC) use in young patients with asthma. Design Population-based nested case-control study. Database IMS LifeLink Health Plan Claims Database. Patients Patients 5-24 years of age who were diagnosed with asthma and were new users of asthma controller medications were identified between July 1997 and April 2010. Cases were newly diagnosed with arrhythmia and were matched with up to 10 controls based on age, gender, geographic region, and quarter and year of first controller medication dispensing. Measurements and main results Exposure to IACs was determined in the 180 days prior to the event date, defined as date of arrhythmia claim. Active use was defined as sufficient days' supply of a prescription to extend through the event date. Among 283,429 patients with asthma, 7656 cases were matched to 76,304 controls. Most of those included were female (58.8%) and 12 years or older (73.3%). Active exposure of IACs was observed in 0.69% of cases and 0.18% of controls. Active use was associated with a 1.56-fold increase in arrhythmia risk compared with nonactive users or nonusers (adjusted odds ratio [ORadj ] 1.56, 95% confidence interval [CI] 1.08-2.25]). Risk was highest among active users of ipratropium (ORadj 1.59, 95% CI 1.08-2.33). Active high-dose users of IACs (more than 0.114 mg of ipratropium equivalents) had a 69% increase in risk (ORadj 1.69, 95% CI 1.10-2.59), whereas the added risk for active users receiving low-dose IACs (0.114 mg of ipratropium equivalents or less) was not statistically significant (ORadj 1.22, 95% CI 0.53-2.65). Conclusion Use of ipratropium bromide was associated with an increased risk of arrhythmias in 12-24-year-old patients with asthma.

Purpose The results of a survey evaluating pharmacy staffing and vacancies in small and rural hospitals in Illinois are reported. Methods Questionnaires were mailed in November 2011 to pharmacy directors at 86 small and rural hospitals in Illinois. The survey included several items regarding human resources and staffing, and it used work-force items and methods similar to surveys conducted in 1991 and 2001. Descriptive analyses were used to assess differences in staffing and vacancies across different hospital sizes (number of staffed beds), and inferential statistics were used to compare selected hospital characteristics. Results A total of 40 responses were received, yielding a response rate of 46.5%. Most rural hospitals reported having no vacancies in their pharmacy work force (62.5%, n = 25). Vacancy rates in 2011 were very low for pharmacists (1.8%), pharmacy technicians (2.5%), and pharmacy staff overall (2.1%). For several specific occupational titles, vacancy rates were zero. Nonetheless, adverse consequences (sites could report more than one effect) of vacancies included longer hours worked by part-time staff (27.5%, n = 11), reduced time to provide clinical pharmacy services (20.0%, n = 8), job dissatisfaction of remaining staff (17.9%, n = 7), and reduced time to provide drug distribution services (10.0%, n = 4). Conclusion The shortage of pharmacists in small and rural hospitals in Illinois largely subsided from 2001 to 2011, with many hospitals reporting no vacancies at all. The total number of actual full-time equivalent pharmacy staff has sizably increased since 2001.

Objective To characterize the use of tumor necrosis factor-α inhibitors (TNFIs) in children with juvenile idiopathic arthritis (JIA) and young adults with rheumatoid arthritis (RA). Methods Patients with incident JIA or RA were identified by using the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. The incident diagnosis was defined as no prior claims with a JIA/RA code and no JIA/RA medications recorded during the previous 6 months. TNFI use patterns were examined, including switching among TNFIs, adherence, persistence, and time from diagnosis to TNFI use. Earlier TNFI treatment without prior use of traditional disease-modifying antirheumatic drugs (DMARDs) and use of specific TNFIs were analyzed by age group. Results Of 6929 children and young adults with new diagnoses of JIA/RA, 18.6% were treated with TNFIs. In these TNFI users, 39.1% received earlier TNFI therapy without prior use of DMARDs. The use of TNFIs was higher in patients diagnosed between 2012 and 2013 than that in patients diagnosed between 2009 and 2011 (hazard ratio 1.13, 95% confidence interval 1.00–1.28). Etanercept was the most commonly used, especially by children aged < 12 (75.5%) and adolescents aged 12 to 17 (62.5%) years. Adherence measured as mean proportion of days covered ranged from 70.4% to 93.2% for individual TNFI agents. Only about 60% of patients continuously took TNFIs for 12 months. When switching occurred, switching from etanercept to adalimumab was the most common pattern. Conclusion Earlier TNFI therapy was observed in 39.1% of children and young adults taking TNFIs. In addition, the time to the first TNFI prescription became shorter over the study period. Future research should evaluate the long-term effectiveness and safety of this more aggressive TNFI therapy.

Background Early initiation of tumor necrosis factor-alpha inhibitor (TNFI) therapy for children and young adults with inflammatory bowel disease (IBD) is not well described. Methods We conducted a retrospective cohort study of children and young adults (≤24 yr) newly diagnosed with IBD using health insurance claims from 2009 to 2013. The conventional "step-up" approach was defined as TNFI initiation >30 days after first IBD medication prescription, whereas the "top-down" approach was defined as new TNFI prescription within 30 days of first IBD medication prescription. Switching rates, time to initiation, discontinuation, and adherence to TNFIs were compared between the 2 strategies. Results A total of 11,962 IBD patients were identified. Among 3300 TNFI users, 1298 (39.3%) were treated with the top-down approach, whereas 2002 (60.7%) were treated with the step-up approach. Top-down approach use increased from 31.4% to 49.8% during the 5-year period, and under this approach, most patients were treated with TNFIs alone. Time to TNFI initiation was shorter for patients diagnosed in more recent years. Patients treated with the top-down strategy had lower rates of corticosteroid use (32.5% versus 94.2%) compared with step-up treatment but presented a higher rate of TNFI discontinuation. The 2 strategies both exhibited high adherence (mean proportion of days covered: 83.7%-95.4%). Conclusions Early TNFI initiation increased over time for children and young adults with IBD and was related to lower rates of corticosteroid use compared with the conventional approach. However, the higher rate of TNFI discontinuation under the top-down approach requires further examination.

Comparative effectiveness research includes cohort studies and registries of interventions. When investigators design such studies, how important is it to follow patients from the day they initiated treatment with the study interventions? Our article considers this question and related issues to start a dialogue on the value of the incident user design in comparative effectiveness research. By incident user design, we mean a study that sets the cohort's inception date according to patients' new use of an intervention. In contrast, most epidemiologic studies enroll patients who were currently or recently using an intervention when follow-up began. We take the incident user design as a reasonable default strategy because it reduces biases that can impact non-randomized studies, especially when investigators use healthcare databases. We review case studies where investigators have explored the consequences of designing a cohort study by restricting to incident users, but most of the discussion has been informed by expert opinion, not by systematic evidence.