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.

Clinical outcomes of levalbuterol versus racemic albuterol in pediatric patients with asthma: Propensity score matching approach in a medicaid population.

OBJECTIVE: Racemic albuterol and levalbuterol are used to treat acute episodes of asthma. The main objective of this study was to compare levalbuterol therapy to albuterol therapy on incidence rates of subsequent emergency department (ED) visits and hospitalizations. METHOD: We conducted a retrospective cohort study of asthmatic children who had pharmacy refills for levalbuterol/albuterol in the South Carolina Medicaid database in 2002-2011. Children receiving levalbuterol were matched to those receiving albuterol using propensity score matching technique. For ED visits and separately for hospitalizations, multivariable negative binomial regression was used to estimate the two group-specific incidence rates and the incidence rate ratio (IRR). RESULTS: A total of 8,172 asthmatic patients aged 2-18 years were identified in the South Carolina Medicaid database. During the 12-month follow-up period, the levalbuterol group had fewer asthma-related ED visits and hospitalizations: 939 (11.49%) children had asthma-related ED visits (levalbuterol: 8.76%; albuterol: 14.21%), and 89 (1.09%) children had asthma-related hospitalizations (levalbuterol: 1.07%; albuterol: 1.12%). Comparing the levalbuterol group to the albuterol group, the adjusted IRR estimate was 0.57 (95% confidence interval [CI], 0.49-0.65) for of asthma-related ED visits, and 0.93 (95%CI, 0.99-1.63) for hospitalizations. Children filling levalbuterol also had a lower IRR of all-cause ED visit (0.88; 95%CI, 0.82-0.95), but similar IRR of all-cause hospitalizations (1.08; 95%CI, 0.82-1.42). CONCLUSION: This observational study of children aged 2-18 demonstrated levalbuterol prescription fills were associated with reduced ED visits, but not hospitalizations. Additional research may be necessary to assess this association. Pediatr Pulmonol. 2017;52:516-523. © 2016 Wiley Periodicals, Inc.

US suicide rates by age group, 1970-2002: an examination of recent trends.

US suicide rates have declined in recent years, reversing earlier trends. We examined suicide rates among 4 age groups from 1970 to 2002 and the factors that may have contributed to the decline. We paid particular attention to newer anti-depressants because of recent concerns and controversy about a possible association with suicidal behaviors. These trends warrant more extensive analysis of suicide rates among specific subgroups, including consideration of additional variables that may influence rates differentially. The relative contributions of depression diagnosis and treatment, postsuicide attempt care, and other contextual factors (e.g., overall economic conditions) also deserve attention. If the decline is associated with contextual factors, clarifying these associations will better inform public policy decisions and contribute to more effective interventions for preventing suicide.

Implementation of the American Diabetes Association's Standards of Medical Care post-Medicare Part D: The case of statin utilization in the elderly with diabetes.

BACKGROUND: The American Diabetes Association's (ADA's) Standards of Medical Care in Diabetes for statin use have changed to be driven by risk status rather than low-density lipoprotein cholesterol level. OBJECTIVES: The objectives of this study were to 1) examine how statins were used by risk status in elderly diabetics for whom they are recommended by the ADA's Standards with high levels of evidence, and 2) identify potential predictors of statin non-use using data containing Medicare Part D information in understanding how to further align patient care with the ADA's Standards. METHODS: This study was a pooled cross-sectional study of the Medicare Current Beneficiaries Survey from 2006 to 2010. Sampling weights were applied to generate national estimates. Weighted logistic regression was performed to identify potential predicators of statin non-use. RESULTS: Between 2006 and 2010, 53.96%, 52.14%, 52.28%, 57.74%, and 59.81% of eligible diabetics used statins, respectively. About 70% of the patients with overt cardiovascular disease (CVD) took statins while only about 50% of those with CVD risk factors used statins in 2010. Compared to those with overt CVD, patients with CVD risk factors were less likely to take statins (OR: 0.56; 95% CI: 0.48-0.64). Other non-use predictors included: non-Hispanic Black, non-metropolitan areas, and comorbidities. CONCLUSIONS: Implementation of the ADA's statin recommendations increased over the study period. Statin use differed significantly by patients' risk status. Future ADA's Standards focusing on how to improve utilization of statins for individuals with different risk status, particularly those with CVD risk factors but without overt CVD, are warranted.

Impact of a medication management system on nursing home admission rate in a community-dwelling nursing home-eligible Medicaid population.

BACKGROUND: Community-dwelling frail elderly have an increased need for effective medication management to reside in their homes and delay or avoid admission to nursing homes. OBJECTIVE: The objective of this study was to examine the impact of a medication management system on nursing home admission within the community-dwelling frail elderly. METHODS: This prospective cohort study compared nursing home admission rates in intervention and control clients of a state Medicaid home and community-based waiver program. Groups were matched on age (±5 years), race, gender, and waiver program start date (±120 days). The medication management service consisted of 2 parts: 1) prescription medicines dispensed from the client's local pharmacy in a calendar card, and 2) a coordinating service by a health educator to address medication-related problems as they arose. The primary dependent variable was admission to a nursing home. RESULTS: A total of 273 clients agreed to participate, enrolled, and had at least 1 prescription dispensed. The matched control group was composed of 800 other clients. The client sample was 72 years of age, 73% (785/1073) non-white, 75% (804/1073) female, and enrolled in the waiver program approximately 50 months. The 2 groups were similar on all demographic variables examined. Six clients (2.2%) in the intervention group and 40 clients (5.0%) in the control group were admitted to a nursing home at least once during the study period. Logistic regression was used to test the model predicting at least 1 nursing home admission. Control group clients were 2.94 times more likely to be admitted to a nursing home than clients in the intervention group. CONCLUSIONS: The medication management service implemented within this study was effective in reducing nursing home admissions in a group of frail community-dwelling elderly.

Prophylactic ketoconazole shampoo for tinea capitis in a high-risk pediatric population.

OBJECTIVES: Although topical agents for the treatment of tinea capitis decrease viable fungal elements and reduce shedding, their use as a prophylactic agent has not been investigated. This study evaluated the effectiveness of a prophylactic ketoconazole shampoo (Nizoral 2%) protocol to reduce the number of clinically evident tinea capitis infections in a high-risk African American, urban population. METHODS: We conducted a retrospective analysis of a ketoconazole prophylaxis protocol that was implemented at an urban pediatric clinic for medically fragile children. Patients at high risk for tinea capitis received twice-weekly ketoconazole shampoo. The primary outcome of the study was a reduction in the number of documented tinea capitis infections between the 12-month preprotocol and 12-month postprotocol periods. A secondary outcome included the evaluation of predisposing risk factors for acquiring tinea infections. RESULTS: Ninety-seven patients, with a mean age of 8.06 years, were included. Most patients (78%) were African American. There were a total of 13 tinea capitis infections during the 12-month preprotocol period. During the 12-month postprotocol period, 41 infections were documented: 37 (90.2%) in the prophylaxis group and 4 (9.8%) in the nonprophylaxis group. The average numbers of per-patient infections in the postprotocol period were 0.79 and 0.08 in the prophylaxis and nonprophylaxis groups, respectively. Initiation of prophylaxis did not reduce tinea capitis infections (p=NS). Previous history of infection and a high level of care were significant predictors of infections (p<0.05). CONCLUSIONS: Improved hygiene, adherence to prescribed treatment regimens, and prevention of recurrent environmental exposure to surviving fomites should be stressed in high-risk patients and supersede the need for an antifungal (ketoconazole shampoo) prophylaxis protocol.

Differences in hospital glycemic control and insulin requirements in patients recovering from critical illness and those without prior critical illness.

INTRODUCTION: Hospital patients recovering from critical illness on general floors often receive insulin therapy based on protocols designed for patients admitted directly to general floors. The objective of this study is to compare glycemic control and insulin dosing in patients recovering from critical illness and those without prior critical illness. METHODS: Medical record review of blood glucose measurements and insulin dosing in 25 patients under general ward care while transitioning from the intensive care unit (transition group) and 25 patients admitted directly to the floor (direct floor group). RESULTS: Average blood glucose did not differ significantly between groups (transition group 9.49 mmol/L, direct floor group 9.6 mmol/L; P = 0.83). Significant differences in insulin requirements were observed between groups with average daily doses of 55.9 units in patients transitioning from the intensive care unit (ICU) versus 25.6 units in the direct floor group (P = 0.004). CONCLUSIONS: Patients recovering from critical illness required significantly larger doses of insulin than those patients admitted directly to the floor. Managing insulin therapy in patients transitioning from the ICU may require greater insulin doses.

Cost-benefit analysis of a regional poison center.

BACKGROUND: Funding poison center (PC) operations has become a major challenge nationwide. Increasingly, state and federal budget cuts have resulted in diminished funding to PCs. OBJECTIVES: In an effort to demonstrate the value of current PC phone services, a cost-benefit analysis of a regional center was completed. METHODS: A telephone survey was used to collect data from PC callers during an 8-week period in 2004. Callers with human exposure poisonings determined by the PC to be of minimal or no risk were asked to complete the phone survey. Callers were asked their alternative plan if the PC staff had not been available to assist them. Benefits were measured as healthcare charges potentially avoided. RESULTS: A total of 652 caller surveys were completed. The benefit-to-cost ratio was 7.67 (95% C.I. 6.83, 8.50). CONCLUSION: In addition to non-monetary benefits, the operation of a regional poison center provides significant positive return on investment.

Conversions between monotherapies in epilepsy: expert consensus.

To develop expert consensus for conversion between antiepileptic drug (AED) monotherapies, an 11-member panel used the Delphi Technique over three rounds to: (1) identify relevant issues, (2) vote on the issues, and (3) develop consensus. The panel agreed on the basic principle to taper the existing AED only after a presumably efficacious dose of the planned AED was reached. Application is modified by adverse effects possibly attributable to the existing drug, in which case earlier or more rapid tapering of the existing drug should be considered. Patients with uncontrolled seizures, as well as seizure-free patients for whom driving privileges are a consideration, may benefit from slower tapering by smaller dosage decrements of the existing AED. For 10 of the 12 AEDs considered, the panel made titration recommendations concerning initial and target doses for the planned AED, supplementing limited data in the prescribing information. This expert guidance will aid in the period of transitional polytherapy with AEDs from monotherapy to monotherapy.