Preferences for pharmacogenomic testing in polypharmacy patients: a discrete choice experiment.

Aim: To elicit preferences for pharmacogenomic (PGx) testing in polypharmacy patients. Materials & methods: A face-to-face discrete choice experiment survey was designed and administered to adult polypharmacy patients recruited at a local retail pharmacy in Albuquerque (NM, USA). Results: A total of 128 eligible polypharmacy patients completed the discrete choice experiment survey and significantly preferred a PGx test with lower cost, better confidentiality and higher certainty of identifying best medication/dose and side effects and one that can be used to advocate for their treatment needs (all p < 0.01). Conclusion: This is the first study eliciting preferences for PGx testing among polypharmacy patients. The study found most polypharmacy patients were willing to take a PGx test and their preferences were mostly influenced by test cost.

Patients who concurrently take five or more medications are at a higher risk of experiencing side effects related to drug­drug/drug­gene interactions. 'One size doesn't fit all' ­ individuals may respond differently to the same dose of a medication. Pharmacogenomic (PGx) testing identifies individual genetic information that may help explain better or worse outcomes or potential problems with drug therapies and eventually may help optimize patient treatment. The authors conducted a face-to-face survey to assess preferences for PGx testing in polypharmacy patients and found that most polypharmacy patients were willing to take a PGx test and their preferences were mostly influenced by test cost and performance, as well as the confidentiality of test results.

A case-based learning exercise to increase students' understanding of the pharmacist's role in public health interventions for individual patients.

INTRODUCTION: The purpose of this study was to evaluate whether a public health (PH) micro-level case-based learning exercise increased pharmacy students' self-perceived understanding and confidence in their role as PH pharmacists. METHODS: Three PH micro-level case-based learning exercises in community pharmacy settings were developed and integrated into the third professional year PH course. Students enrolled in the PH course from January 2012 - May 2015 completed a pre- and post-activity survey consisting of 22 statements with Likert scale responses. Survey questions were grouped into domains: perceptions of pharmacist roles (ROLES) in PH, confidence in ability to identify and address PH problems (CONF), pharmacist impact on improving PH outcomes for patients with human immunodeficiency virus (IMPACT-HIV), diabetes (IMPACT-DM), or alcoholism (IMPACT-AL), perceiving pharmacists as role models in PH (MODEL), and whether PH is beyond the scope of pharmacy practice (SCOPE). Within each domain, paired t-tests were performed on summated scores (pre- vs. post-, alpha = 0.05). RESULTS: Both surveys were completed by 271 of 336 students (80.7%). Baseline scores were lowest in the CONF and MODEL domains. The activity resulted in significant changes in 21 out of 24 survey questions. Significantly higher scores were found for domains of ROLES (+1.22), CONF (+1.60), IMPACT-HIV (+0.65), IMPACT-DM (+0.42), IMPACT-AL (+0.70), and MODEL (+1.50). Cronbach's alpha ranged from 0.73 to 0.93 for each domain. CONCLUSION: A PH case-based learning session increased students' scores on a pre- and post-activity survey regarding PH challenges at the micro-level. The activity improved students' perceptions and confidence in providing PH interventions.

Regulatory and Clinical Experiences with Biosimilar Filgrastim in the U.S., the European Union, Japan, and Canada.

Biosimilar filgrastims are primarily indicated for chemotherapy-induced neutropenia prevention. They are less expensive formulations of branded filgrastim, and biosimilar filgrastim was the first biosimilar oncology drug administered in European Union (EU) countries, Japan, and the U.S. Fourteen biosimilar filgrastims have been marketed in EU countries, Japan, the U.S., and Canada since 2008, 2012, 2015, and 2016, respectively. We reviewed experiences and policies for biosimilar filgrastim markets in EU countries and Japan, where uptake has been rapid, and in the U.S. and Canada, where experience is rapidly emerging. U.S. regulations for designating biosimilar interchangeability are under development, and such regulations have not been developed in most other countries. Pharmaceutical substitution is allowed for new filgrastim starts in some EU countries and in Canada, but not Japan and the U.S. In EU countries, biosimilar adoption is facilitated with favorable hospital tender offers. U.S. adoption is reportedly 24%, while the second filgrastim biosimilar is priced 30% lower than branded filgrastim and 20% lower than the first biosimilar filgrastim approved by the U.S. Food and Drug Administration. Utilization is about 60% in EU countries, where biosimilar filgrastim is marketed at a 30%-40% discount. In Japan, biosimilar filgrastim utilization is 45%, primarily because of 35% discounts negotiated by Central Insurance and hospital-only markets. Overall, biosimilar filgrastim adoption barriers are small in many EU countries and Japan and are diminishing in Canada in the U.S. Policies facilitating improved U.S. adoption of biosimilar filgrastim, based on positive experiences in EU countries and Japan, including favorable insurance coverage; larger price discount relative to reference filgrastim pricing; closing of the "rebate trap" with transparent pricing information; formal educational efforts of patients, physicians, caregivers, and providers; and allowance of pharmaceutical substitution of biosimilar versus reference filgrastim, should be considered. IMPLICATIONS FOR PRACTICE: We reviewed experiences and policies for biosimilar filgrastims in Europe, Japan, Canada, and the U.S. Postmarketing harmonization of regulatory policies for biosimilar filgrastims has not occurred. Acceptance of biosimilar filgrastims for branded filgrastim, increasing in the U.S. and in Canada, is commonplace in Japan and Europe. In the U.S., some factors, accepted in Europe or Japan, could improve uptake, including acceptance of biosimilars as safe and effective; larger cost savings, decreasing "rebate traps" where pharmaceutical benefit managers support branded filgrastim, decreased use of patent litigation/challenges, and allowing pharmacists to routinely substitute biosimilar for branded filgrastim.

Relationships Between Social/Emotional Support and Quality of Life, Depression and Disability in Patients With Chronic Obstructive Pulmonary Disease: An Analysis Based on Propensity Score Matching.

BACKGROUND: Patients with chronic obstructive pulmonary diseases (COPD) suffer from impaired Health-Related Quality of Life (HRQoL). Having an adequate social/emotional support may improve the quality of life of COPD patients. OBJECTIVE: To study the relationships between social/emotional support and HRQoL, depression and disability among patients with COPD. METHODS: We applied a propensity score model using data from a large U.S. population-based health survey to match COPD patients who reported rarely/never receiving social/emotional support with those who received that support. Social/emotional support and all dependent variables were dichotomized into yes/no responses. For HRQoL domains, number of days of poor physical or mental health and activity limitations, "yes" indicated ≥14 unhealthy days in the last 30 days. McNemar's test was used to compare the matched groups. RESULTS: Social/emotional support was rarely/never received by 37% of responders. Standardized differences between matched groups, after propensity score matching, were less than 10% indicating successful matching. COPD patients who rarely/never receive social/emotional support were more likely to report: depression (n = 321 pairs, odds ratio (OR) = 2.2, 95% confidence interval (CI): 1.56-3.14, p < .001), ≥14 poor mental HRQoL days (n = 310 pairs, OR = 3.12, 95% CI: 2.1-4.73, p < .001) and ≥14 poor physical HRQoL days (n = 307 pairs, OR = 1.5, 95% CI: 1.06-2.13, p = .02). There were no significant differences in general health, disability, or activity limitations. CONCLUSION: Among COPD patients, lower levels of social/emotional support are associated with depression and deterioration of mental and physical HRQoL. The importance of social/emotional support should be emphasized by policy makers, healthcare providers, and family members, to improve functioning among COPD patients.

Randomized Controlled Trial to Evaluate an Internet-Based Self-Management Program in Systemic Sclerosis.

OBJECTIVE: In a pilot study, our group showed that an internet-based self-management program improves self-efficacy in systemic sclerosis (SSc). The objective of the current study was to compare an internet-based self-management program to a patient-focused educational book developed to assess measures of self-efficacy and other patient-reported outcomes in patients with SSc. METHODS: We conducted a 16-week randomized, controlled trial. RESULTS: Of the 267 participants who completed baseline questionnaires and were randomized to the intervention (internet: www.selfmanagescleroderma.com) or control (book) group, 123 participants (93%) in the internet group and 124 participants (94%) in the control group completed the 16-week randomized controlled trial (RCT). The mean ± SD age of all participants was 53.7 ± 11.7 years, 91% were women, and 79.4% had some college or a higher degree. The mean ± SD disease duration after diagnosis of SSc was 8.97 ± 8.50 years. There were no statistical differences between the 2 groups for the primary outcome measure (Patient-Reported Outcomes Measurement Information System Self-Efficacy for Managing Symptoms: mean change of 0.35 in the internet group versus 0.94 in the control group; P = 0.47) and secondary outcome measures, except the EuroQol 5-domain instrument visual analog scale score (P = 0.05). Internet group participants agreed that the self-management modules were of importance to them, the information was presented clearly, and the website was easy to use and at an appropriate reading level. CONCLUSION: Our RCT showed that the internet-based self-management website was not statistically superior to an educational patient-focused book in improving self-efficacy and other measures. The participants were enthusiastic about the content and presentation of the self-management website.

The impact of a theory-based web-intervention on the intention to use prescription drugs for non-medical purposes among college students: a randomized controlled trial.

The non-medical use of prescription drugs (NMUPD) among college students is escalating at an alarming rate. A limited number of studies have utilized a theoretical framework to influence this behavior. To utilize the reasoned-action approach theory to design and evaluate a web-based intervention to influence students' attitudes, perceived norms (PNs), perceived behavioral control (PBC) and intentions toward NMUPD. Using a two-group post-test only controlled trial, students were randomized to view either a general health website or a web-based intervention focused on NMUPD. The intervention was presented in multiple sections to address each component of the reasoned-action approach. Subsequently, respondents completed a web-survey. Independent t-tests were used to compare responses between the two groups. Of 391 respondents, 112 (28.9%) students indicated previous NMUPD. The intervention group had significantly (P = 0.04) more negative attitudes toward NMUPD. No significant differences were found in PNs (P = 0.11), PBC (P = 0.68) or intentions to NMUPD (P = 0.97). The intervention was successful in changing attitudes toward NMUPD. Targeting the intervention toward college students regardless of previous experiences of NMUPD might have led to insufficiency of the intervention to influence intentions. Additional research is needed to improve the intervention dissemination and utilization.

Dietary Intake Among Opioid- and Alcohol-Using Pregnant Women.

BACKGROUND: Substance abuse in nonpregnant adults has been associated with increased intake in calories and decreased intake of nutrient-dense foods; however, studies examining dietary intake in opioid-using and alcohol-using pregnant women are lacking. OBJECTIVE: The objective of this study was to evaluate dietary intake in opioid-using pregnant women with or without concurrent light-to-moderate alcohol use as compared to abstaining controls. METHODS: This prospective birth cohort included 102 pregnant women classified into four study groups: controls (n = 27), medication-assisted treatment (MAT; n = 26), alcohol (ALC; n = 22), and concurrent use of both substances (MAT + ALC; n = 27). Percentage differences in macro- and micronutrient intake were estimated from the food frequency questionnaire and compared among the study groups. Proportions of participants with intakes below the estimated average requirements (EAR) based on diet and diet with supplements were estimated. RESULTS: Three exposed groups had lower prevalence of multivitamin use in periconceptional period (11.5-31.8%) than controls (44.4%). Unadjusted mean energy intake was significantly higher in the MAT + ALC group compared to controls, while micronutrient intake per 1000 kcal was the highest in the control group for almost all of the micronutrients analyzed. After adjustment for energy intake and sociodemographic characteristics, MAT group had lower estimated dietary intake of iron (-15.0%, p = 0.04) and folate (-16.8%, p = 0.04) compared to controls. A high proportion of participants in all study groups had dietary intake below the EAR for vitamin E, iron, and folate. CONCLUSION: Results highlight the need for targeted dietary interventions for opioid-using pregnant women.

Influenza vaccination for patients with chronic obstructive pulmonary disease: Implications for pharmacists.

BACKGROUND: Influenza virus is responsible for substantial morbidity and mortality. Specific populations are at higher risk for exacerbations from influenza virus, such as patients with chronic obstructive pulmonary disease (COPD). Influenza vaccination coverage among COPD patients is low. Pharmacists can improve influenza vaccination among COPD patients by recognizing factors that influence vaccination and addressing these factors. OBJECTIVES: To (1) determine the recent influenza vaccination coverage among patients with COPD, (2) identify factors that were associated with immunization, and (3) interpret the results based upon Andersen's healthcare utilization model. METHODS: The 2012 Behavioral Risk Factor Surveillance System (BRFSS) was accessed for the study. Among respondents age ≥ 25 years with COPD, presence of influenza vaccination was captured along with demographic, provider, insurance, and clinical variables. Weighted multiple logistic regression was used to identify significant factors associated with receiving influenza vaccination. The findings were interpreted according to predisposing, enabling, and need factors relevant to Anderson's model. RESULTS: Influenza vaccination rate was 53% among COPD patients. Older age was a significant predisposing factor that increased vaccination (adjusted odds ratio [AOR] = 2.4; 95% CI:2.02-2.88). Predisposing factors that decreased vaccination were being Black or Hispanic (AOR = 0.72, 95% CI:0.59-0.86, and AOR = 0.78, 95% CI:0.61-0.98 respectively), and being a non smoker (former and never smokers had higher vaccination rates [AOR = 1.53, 95% CI = 1.3-1.72, and AOR = 1.36, 95% CI = 1.19-1.55 respectively]). Significant enabling factors included having health insurance (AOR = 1.68, 95% CI = 1.37-2.06), a primary physician (AOR = 1.63, 95% CI = 1.30-2.02), and the ability to see a physician regardless of cost (AOR = 1.33, 95% CI = 1.17-1.52). Significant need factors included the presence of comorbidities such as asthma (AOR = 1.18, 95% CI = 1.1-1.3), or diabetes (AOR = 1.36, 95% CI = 1.20-1.53), activity limitation (AOR = 1.16, 95% CI = 1.04-1.29), and having the last medical checkup within less than one year (AOR = 1.49, 95% CI = 1.31-1.70). CONCLUSION: Influenza vaccination coverage among COPD patients is far below the Healthy People 2020 national goal. Several predisposing, enabling, and need factors influenced vaccination rate among COPD patients. Pharmacists can improve vaccination rate among COPD patients by recognizing these influencing factors and by acting as advocates, counselors, and administrators of influenza vaccine. Ultimately, with the collaborative efforts of other healthcare providers and public health initiatives, pharmacists can help achieve Healthy People 2020 objectives related to influenza vaccination.

Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR).

A 43-year-old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk-exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab-associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) (2004-2014), a FDA Advisory Committee Meeting Report, and peer-reviewed publications. In the United States, the manufacturer maintains an FDA-mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health (TOUCH)) of natalizumab-treated patients. We statistically compared reporting completeness for natalizumab-associated melanoma cases in FAERs for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab-associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21-74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab-treated MS patients who developed biopsy-confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38-48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1-77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8-possible items, P < 0.0007). Clinicians should monitor existing nevi and maintain suspicion for melanoma developing in natalizumab-treated patients. The TOUCH Safety Surveillance Program, currently focused on progressive multifocal leukoencephalopathy, should be expanded to include information on other serious complications including malignancies, particularly if they are immunologic in nature.

Hepatotoxicity with Vismodegib: An MD Anderson Cancer Center and Research on Adverse Drug Events and Reports Project.

BACKGROUND: On 30 January 2012, the US FDA approved vismodegib (Erivedge®, Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma. OBJECTIVE: Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers. METHODS: FAERS was searched for reports dated 1 January 2009 through 31 December 2015 using terms including hedgehog pathway and vismodegib and hepatic-related terms such as liver, jaundice, and hepatitis, among others. Disproportionality analyses with estimates of proportional reporting ratio and empirical Bayesian geometric mean were conducted. A comprehensive literature review was conducted, and the clinical databases at the University of Texas MD Anderson Cancer Center and Robert H. Lurie Comprehensive Cancer Center of Northwestern University were searched. RESULTS: Two cases of severe liver dysfunction were published (Common Terminology Criteria for Adverse Events [CTCAE] class III), and 94 reports of adverse events (AEs) were detected in FAERS, 35 of which were serious AEs. Safety notifications related to hepatotoxicity have not been issued by the manufacturer or the FDA, although vismodegib is listed in LiverTox and the European Medicines Agency website. CONCLUSION: We identified a detectable safety signal for hepatotoxicity for vismodegib within 4 years of FDA approval. Vismodegib should be used in patients with severe liver disease only after careful consideration, and concomitant hepatotoxic medications should be avoided. Rapid dissemination of such safety concerns is expected to result in fewer serious hepatotoxic AEs and more optimal outcomes for patients with cancer receiving vismodegib.

Generic oncology drugs: are they all safe?

Although the availability of generic oncology drugs allows access to contemporary care and reduces costs, there is international variability in the safety of this class of drugs. In this Series paper, we review clinical, policy, safety, and regulatory considerations for generic oncology drugs focusing on the USA, Canada, the European Union (EU), Japan, China, and India. Safety information about generic formulations is reviewed from one agent in each class, for heavy metal drugs (cisplatin), targeted agents (imatinib), and cytotoxic agents (docetaxel). We also review regulatory reports from Japan and the USA, countries with the largest pharmaceutical expenditures. Empirical studies did not identify safety concerns in the USA, Canada, the EU, and Japan, where regulations and enforcement are strong. Although manufacturing problems for generic pharmaceuticals exist in India, where 40% of all generic pharmaceuticals used in the USA are manufactured, increased inspections and communication by the US Food and Drug Administration are occurring, facilitating oversight and enforcement. No safety outbreaks among generic oncology drugs were reported in developed countries. For developing countries, oversight is less intensive, and concerns around drug safety still exist. Regulatory agencies should collaboratively develop procedures to monitor the production, shipment, storage, and post-marketing safety of generic oncology drugs. Regulatory agencies for each country should also aim towards identical definitions of bioequivalence, the cornerstone of regulatory approval.

Assessing the Quality of Economic Evaluations of FDA Novel Drug Approvals: A Systematic Review.

OBJECTIVE: To systematically review and assess the quality of the novel drugs' economic evaluation literature in print during the drugs' early commercial availability following US regulatory approval. DATA SOURCES: MEDLINE and the United Kingdom National Health Service Economic Evaluation Database were searched from 1946 through December 2011 for economic evaluations of the 50 novel drugs approved by the FDA in 2008 and 2009. STUDY SELECTION AND DATA EXTRACTION: The inclusion criteria were English-language, peer-reviewed, original economic evaluations (cost-utility, cost-effectiveness, cost-minimization, and cost-benefit analyses). We extracted and analyzed data from 36 articles considering 19 of the 50 drugs. Two reviewers assessed each publication's quality using the Quality of Health Economic Studies (QHES) instrument and summarized study quality on a 100-point scale. DATA SYNTHESIS: Study quality had a mean of 70.0 ± 16.2 QHES points. The only study characteristics associated with QHES score (with P < 0.05) were having used modeling or advanced statistics, 75.1 versus 61.9 without; using quality-adjusted life years as an outcome, 75.9 versus 64.7 without; and cost-utility versus cost-minimization analysis, 75.9 versus 58.7. Studies most often satisfied quality aspects about stating study design choices and least often satisfied aspects about justifying design choices. CONCLUSION: The reviewed literature considered a minority of the 2008-2009 novel drugs and had mixed study quality. Cost-effectiveness stakeholders might benefit from efforts to improve the quality and quantity of literature examining novel drugs. Editors and reviewers may support quality improvement by stringently imposing economic evaluation guidelines about justifying study design choices.

Detection of cases of progressive multifocal leukoencephalopathy associated with new biologicals and targeted cancer therapies from the FDA's adverse event reporting system.

OBJECTIVE: To identify and summarize FDA's Adverse Event Reporting System (FAERS) cases of progressive multifocal leukoencephalopathy (PML) associated with biological and targeted cancer therapies (BTCT) that were approved between 2009 and 2015. METHODS: FAERS was searched using each BTCT name as primary or secondary suspect drug and the adverse reaction of PML. Among BTCTs with >2 case reports of PML, proportional reporting ratios (PRR) and 95% confidence intervals (CI) were calculated. RESULTS: Among 49 new BTCTs, 82 cases of PML were found for 16 drugs. Significant PRR signals were found among 7 (14.6%) BTCTs including: brentuximab (24.5, CI:14.8-40.6), ofatumumab (16.3, CI:9.6-27.4), alemtuzumab (9.9, CI:6.0-16.4), obinutuzumab (7.4, CI:2.4-22.8), ibrutinib (5.6 CI:3.0-10.5), belimumab (4.5 CI:2.3-9.0), and idelalisib (4.1, CI:1.3-12.6). Among the 82 cases with significant signals, confirmation of the diagnosis of PML using objective criteria was found in 56% of the cases. A limitation of FAERS data is that missing data are common. CONCLUSIONS: When using BTCTs, clinicians and patients consider the risk of PML versus the therapeutic benefit, particularly when used in combination with other drugs which may cause PML, such as rituximab. It is important to recognize that PML may occur in some conditions, such as chronic lymphocytic leukemia, regardless of drug therapy.

Fluoroquinolone-related neuropsychiatric and mitochondrial toxicity: a collaborative investigation by scientists and members of a social network.

BACKGROUND: The 3 fluoroquinolone (FQ) antibiotics - ciprofoxacin, levofoxacin, and moxifoxacin - are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia. New serious FQ-associated safety concerns have been identified through novel collaborations between FQ-treated persons who have developed long-term neuropsychiatric (NP) toxicity, pharmacovigilance experts, and basic scientists. OBJECTIVE: To conduct basic science and clinical investigations of a newly identified adverse drug reaction, termed FQ-associated disability. METHODS: 5 groups of C57BL/6 mice receiving the antibiotic ciprofoxacin in 10-mg increments (10 mg/kg-50 mg/kg) and 1 group of control mice were evaluated. The Southern Network on Adverse Reactions (SONAR) and a social network of FQ-treated persons with long-term NP toxicity (the Floxed Network) conducted a web-based survey. The clinical toxicity manifestations reported by 94 respondents to the web-based survey of persons who had received 1 or more doses of an FQ prescribed for any indication (generally at FDA-approved dosages) and who subsequently experienced possible adverse drug reactions were compared with adverse event information included on the product label for levofoxacin and with FQ-associated adverse events reported to the FDA's MedWatch program. RESULTS: Mice treated with ciprofoxacin had lower grip strengths, reduced balance, and depressive behavior compared with the controls. For the survey, 93 of 94 respondents reported FQ-associated events including anxiety, depression, insomnia, panic attacks, clouded thinking, depersonalization, suicidal thoughts, psychosis, nightmares, and impaired memory beginning within days of FQ initiation or days to months of FQ discontinuation. The FDA Adverse Event Reporting System (FAERS) included 210,705 adverse events and 2,991 fatalities for FQs. Levofoxacin and ciprofoxacin toxicities were neurologic (30% and 26%, respectively), tendon damage (8% and 6%), and psychiatric (10% and 2%). In 2013, an FDA safety review reported that FQs affect mammalian topoisomerase II, especially in mitochondria. In 2013 and 2014, SONAR fled citizen petitions requesting black box revisions identifying neuropsychiatric toxicities and mitochrondrial toxicity as serious levofoxacin-associated adverse drug reactions. In 2015, FDA advisors recommended that FQ product labels be revised to include information about this newly identified disability syndrome termed "FQ-associated disability" (FQAD). LIMITATIONS: Basic science studies evaluated NP toxicity for only 1 FQ, ciprofoxacin. CONCLUSION: Pharmacovigilance investigators, a social network, and basic scientists can collaborate on pharmacovigilance investigations. Revised product labels describing a new serious adverse drug reaction, levofoxacin-associated long-term disability, as recommended by an FDA advisory committee, are advised.

Fluoroquinolone-associated tendon-rupture: a summary of reports in the Food and Drug Administration's adverse event reporting system.

OBJECTIVE: To review and summarize reports of tendon rupture associated with each fluoroquinolone (FQ) currently marketed in the United States (US), as reported to the FDA's Adverse Event Reporting System (FAERS). METHODS: FAERS data were reviewed for reports of tendon rupture associated with each FQ from their respective approval date through September 2012. Disproportional reporting signal detection was estimated using empirical Bayes geometric mean (EBGM) with 95% confidence intervals (CI). RESULTS: There were 2495 FAERs reports of tendon rupture associated with currently approved FQs. Most FAERS reports were associated with levofloxacin (n = 1555) followed by ciprofloxacin (n = 606) and moxifloxacin (n = 230). Signal detection results for FQs were as follows: levofloxacin (EBGM = 55.2, 95% CI = 52.3 - 58.0), ciprofloxacin (EBGM = 20.0, 95% CI = 18.2 - 21.6), moxifloxacin (EBGM = 13.3, 95% CI = 11.7 - 15.1), norfloxacin (EBGM = 9.6, 95% CI = 6.5 - 13.5), ofloxacin (EBGM = 8.2, 95%CI = 6.3 - 10.2) and gemifloxacin (EBGM = 1.9, 95% CI = 0.7 - 4.5). The mean age of affected individuals was 59.6 ± 5.1 years. Corticosteroids were administered concomitantly with FQs in 21.2% of cases. CONCLUSION: As noted in boxed warnings, FQ use is associated with increased tendon rupture risk. Risk factors for FQ associated tendon rupture include use in the elderly, and in patients with concomitant corticosteroids. Further monitoring may be needed due to antibiotic overuse and marketing of newer FQs.

Severe COPD Exacerbation Risk and Long-Acting Bronchodilator Treatments: Comparison of Three Observational Data Analysis Methods.

OBJECTIVE: Results from three observational methods for assessing effectiveness of long-acting bronchodilator therapies for reducing severe exacerbations of chronic obstructive pulmonary disease (COPD) were compared: intent-to-treat (ITT), as protocol (AP), and an as-treated analysis that utilized a marginal structural model (MSM) incorporating time-varying covariates related to treatment adherence and moderate exacerbations. STUDY DESIGN AND SETTING: Severe exacerbation risk was assessed over a 2-year period using claims data for patients aged ≥40 years who initiated long-acting muscarinic antagonist (LAMA), inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), or triple therapy (LAMA + ICS/LABA). RESULTS: A total of 5475 COPD patients met inclusion criteria. Six months post-initiation, 53.5 % of patients discontinued using any therapy. The ITT analysis found an increased severe exacerbation risk for triple therapy treatment (hazard ratio [HR] 1.24; 95 % confidence interval [CI] 1.00-1.53). No increased risk was found in the AP (HR 1.00; 95 % CI 0.73-1.36), or MSM analyses (HR 1.11; 95 % CI 0.68-1.81). The MSM highlighted important associations among post-index events. CONCLUSION: Neglecting to adjust for treatment discontinuation may produce biased risk estimates. The MSM approach is a promising tool to compare chronic disease management by illuminating relationships between treatment decisions, adherence, patient choices, and outcomes.

Assessing disparities in the receipt of inhaled corticosteroid prescriptions for asthma by Hispanic and non-Hispanic white patients.

RATIONALE: Inhaled corticosteroids (ICS) are widely used in the management of asthma. Prior research suggests that access to ICS among patients with asthma may vary by ethnicity. OBJECTIVES: Study objectives were to determine if there is a difference in the proportion of Hispanic and non-Hispanic white patients with asthma in the receipt of an ICS prescription and to determine independent predictors for the receipt of an ICS prescription for asthma. METHODS: The 2009 U.S. Medical Expenditure Panel Survey data were used to compare the receipt of ICS prescription among patients with asthma with the following inclusion criteria: Hispanic and non-Hispanic white ethnicity, age over 4 years, and diagnostic codes for asthma. Multiple logistic regression was used to determine the influence of race/ethnicity and other significant factors on the receipt of an ICS prescription. MEASUREMENTS AND MAIN RESULTS: There were 1,469 patients with asthma, corresponding to a weighted sample of 14,401,069 U.S. patients with asthma who met the inclusion criteria, represented by 16.1% Hispanic, 59.5% female, and mean age of 39.9 years. Among non-Hispanic white patients with asthma, 39.7% (35% children and 41% adults) had a receipt of an ICS prescription compared with 22.2% of Hispanic patients (23.9% children and 21.2% adults); P < 0.001. In the multiple regression model, Hispanic patients aged 18 years or older had 43% lower odds (odds ratio, 0.6; 95% confidence interval, 0.3-0.9) of having a receipt of an ICS prescription compared with non-Hispanic white patients, independent of other factors. There was no significant difference in receipt of an ICS prescription between Hispanic and non-Hispanic white children with asthma (aged 4-17 yr). CONCLUSIONS: The disparity in the receipt of ICS prescription between Hispanic and non-Hispanic white adult patients with asthma could result in suboptimal asthma management, a higher rate of exacerbations, and higher health care costs in this growing minority population. The differences and potential disparities in the receipt of an ICS prescription between Hispanic and non-Hispanic white patients with asthma warrant further investigation to better understand the reasons for such disparities, along with their impact on the U.S. health care burden and interventions that can be undertaken to reduce these disparities.

Improving the effectiveness of pharmacist-assisted tobacco cessation: a study of participant- and pharmacy-specific differences in quit rates.

BACKGROUND: The New Mexico Pharmaceutical Care Foundation provided a pharmacist-assisted tobacco cessation program from 2004 to 2010. In evaluating the program, discrepant 6-month quit rates were observed between pharmacies. OBJECTIVE: To identify participant- and pharmacy-specific factors associated with improved quit rates. METHODS: To supplement data regarding participant characteristics and quit rates, semistructured interviews of 7 participating pharmacists were conducted. Multivariate logistic regression quantified associations between successful abstinence at 6 months and participant characteristics and pharmacy-specific factors. RESULTS: Quit rates by pharmacy ranged from 1.1% to 59.4% (mean = 19.1%). There were 1235 participants enrolled at 7 pharmacies, and because of missing participant data, 883 were included in the quantitative analysis. Three pharmacy-specific characteristics distinguished 6-month success rates: number and duration of follow-ups and format of counseling sessions. Participants followed up at least 3 times were more likely to quit at 6 months than those contacted once or twice (odds ratio [OR] =4.9; 95% CI = 1.6-15.0). Compared with follow-ups of <15 minutes, longer durations of follow-ups were associated with higher success rates: 15 to 30 minutes, OR = 7.2, 95% CI = 3.7-14.3); >30 minutes, OR = 10.0, 95% CI = 3.5-28.9. Participants who attended group sessions were more likely to quit at 6 months than those who attended individual sessions: OR = 8.2; 95% CI = 2.8-23.9. Most pharmacists (88%) noted that participants' high or low commitment to quit was associated with success or failure, respectively. Several pharmacists (43%) noted difficulties with follow-up associated with participants' relapse. Time constraints were an obstacle noted by 70% of pharmacists. CONCLUSIONS: Pharmacy-specific factors, including counseling format and program intensity, affected success.

Regulatory and clinical considerations for biosimilar oncology drugs.

Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents-molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs-provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.