Biosimilars 101: considerations for U.S. oncologists in clinical practice.

Biosimilars of biologics used for cancer treatment and supportive care are expected to enter the U.S. market soon. Biosimilars will be highly similar to their reference products, but unlike generic drugs, not identical. Differences between a biosimilar and its reference product may arise because of the complexity of biologics, and differences in the cell lines and processes used during manufacturing. Biosimilars will be approved in the United States through a regulatory pathway based on comparative analytical and clinical studies for their characterization and demonstration of no clinically meaningful differences from their reference products. Unlike generics, initial approval may not include interchangeability, as additional evidence may be required before a biosimilar could be approved as interchangeable with its reference product; interchangeable designation could allow pharmacy-level substitution without prescriber intervention. In some cases, the U.S. Food and Drug Administration (FDA) may extrapolate an indication that has not been formally investigated for the biosimilar but that is approved for the reference product. Robust safety monitoring of all biologics is important to track and accurately attribute adverse events, particularly because their inherent complexity and manufacturing differences make them susceptible to structural changes that can affect safety (e.g., immunogenicity). Accuracy of postapproval safety reports will partly depend on the biosimilar naming approach. Potential cost savings should be evaluated in the context of differences in manufacturers' patient-assistance programs, copayments, and institutional costs. A manufacturer's ability to ensure reliable supply of high-quality biosimilars should also be considered. Broad understanding of these issues is critical for oncologists preparing for their use in clinical practice.

Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection.

INTRODUCTION: Risk factors for Clostridium difficile infection (CDI) include use of broad-spectrum antibiotics, advanced age and lack of an appropriate immune response. Whether antiperistaltics such as opioid analgesics also increase the risk of CDI is uncertain. The purpose of this preliminary study was to determine whether opioid analgesics increase the risk of developing CDI in hospitalized patients receiving broad-spectrum antibiotics. METHODS: Hospitalized patients were assessed for incidence of CDI in relation to usage of opioid analgesics controlling for other known risk factors for CDI. RESULTS: During the study period, a total of 32,775 patients were identified of whom 192 had CDI. In univariate analysis, incidence of CDI increased significantly with moderate or high usage of opioids (P < 0.0001). One hundred of 21,396 (0.47%) patients who did not receive opioids developed CDI. Twenty-two of 6955 patients (0.32%) with mild usage of opioids developed CDI [odds ratio (OR): 0.68; 95% confidence interval (CI): 0.43-1.1; P = 0.10]. Thirty of 33,203 (0.93%) with moderate usage developed CDI (OR: 2.0; 95% CI: 1.3-3.0; P = 0.0009). Forty of 1029 (3.7%) patients with high usage of opioids developed CDI (OR: 8.3; 95% CI: 5.7-12.1; P < 0.0001). Similar results were observed using a multivariate Cox proportional hazard model. CONCLUSIONS: Moderate to high use of opioid analgesics were associated with an increased risk of CDI.

Improving patient care through implementation of an antimicrobial stewardship program.

PURPOSE: The implementation of an antimicrobial stewardship program at a health system is described. SUMMARY: In 2008, the Center for Antimicrobial Stewardship and Epidemiology (CASE) was formed at St. Luke's Episcopal Hospital (SLEH) to improve the quality of care for patients as it related to antimicrobial therapy. The charter of CASE contained specific aims for improving patient care, furthering clinical research, and training the next generation of clinical infectious diseases pharmacists. The CASE team consists of at least two infectious diseases pharmacists and one physician (the medical director) who provide direct oversight for antimicrobial utilization within the hospital. The CASE medical director, an infectious diseases physician, is responsible for overseeing the activities of the center. With the oversight of the CASE advisory board, the medical director develops and implements the antimicrobial stewardship and management policies for SLEH. Another key innovative feature of CASE is its extensive involvement in training new infectious diseases pharmacists and conducting research. CASE uses a model in which a clinical scenario or problem is identified, a research project is undertaken to further elucidate the problem, and policy changes are made to improve patient outcomes. The CASE team is supported by a CASE advisory board, a CASE research collaborative including university faculty, and a dedicated training program for pharmacy fellows, residents, and students. CONCLUSION: Implementation of an antimicrobial stewardship program at a health system helped decrease the inappropriate use of antibiotics, improve patient care and outcomes, further clinical research, and increase training opportunities for future clinical infectious diseases pharmacists.

Effect of bar-code-assisted medication administration on nurses' activities in an intensive care unit: a time-motion study.

PURPOSE: The effect of bar-code-assisted medication administration (BCMA) on nurses' activities in an intensive care unit was evaluated. METHODS: A prospective, observational, time-motion study was conducted by considering two approaches to medication administration in an intensive care unit: paper-based medication administration (PBMA) and BCMA. The time spent on nursing activities was measured using a prevalidated time-motion observation instrument and categorized based on workflow factors such as direct patient care, indirect patient care, administration, and miscellaneous or other. A descriptive analysis was conducted with the amount of time spent on each of the nursing activities. A multivariate analysis of covariance was conducted to assess the difference between the two approaches for the amount of time spent on various categorized nursing activities. Covariates included in the analysis were patient characteristics, medication administration characteristics, and number of nurses involved in medication administration. RESULTS: A total of 101 PBMAs and 151 BCMAs were reviewed. The mean duration of total medication administration time was higher in the BCMA phase compared with the PBMA phase, as was the mean time spent on direct patient care activity. However, nurses spent less time on administration activity during BCMA. Statistical analysis revealed that the medication administration approach (BCMA versus PBMA) had a significant effect on time spent on direct patient care and medication administration activities. CONCLUSION: The implementation of BCMA led to a reduction in the time spent by nurses on medication administration activities and increased the time spent on direct patient care activities.

Descriptive analysis of workflow variables associated with barcode-based approach to medication administration.

Bedside barcode technology is used during medication administration to ensure patient safety. This study evaluated the workflow variables related to a bedside barcode technology-based medication administration process. A time-and-motion technique was used to assess the observational episodes related to medication administration conducted by registered nurses. In an observational episode, nurses spent adequate time in "documenting medications" and "giving medications." Nurses were primarily engaged in tasks at the patient's bedside.

Economic benefit of appropriate timing of vancomycin prophylaxis in patients undergoing cardiovascular surgery.

STUDY OBJECTIVE: To determine if appropriate timing of vancomycin prophylaxis in patients undergoing cardiovascular surgery results in an economic benefit by assessing the differences in total duration of hospitalization and hospital costs based on infusion start time in relation to first surgical incision. DESIGN: Prospective, observational study. SETTING: Tertiary care medical center. PATIENTS: A total of 1666 patients undergoing coronary artery bypass graft (CABG) and/or valve replacement surgery who received prophylactic vancomycin. MEASUREMENTS AND MAIN RESULTS: Appropriateness of vancomycin prophylaxis timing, based on national guidelines defining appropriate timing as start time of infusion ranging from 16-120 minutes before surgery start time, was prospectively monitored. The timing of vancomycin administration was grouped as follows: 0-15 minutes (11 patients), 16-60 minutes (156), 61-120 minutes (772), or more than 120 minutes (727) before incision. Antibiotic timing was appropriate in 928 patients and inappropriate in 738 patients. Length of hospital stay and total hospital costs were compared based on appropriateness of therapy by using multivariate linear regression and validated with a Heckman two-stage model. Median numbers of hospitalization and intensive care unit days were significantly fewer in patients given appropriate prophylaxis at an appropriate time (9 and 2 days, respectively) compared with inappropriate time (10 and 3 days, respectively, p<0.001 for both analyses). Hospital costs were significantly lower in patients who had appropriate timing of antibiotic prophylaxis (median $25,321, interquartile range [IQR] $19,429-35,471) compared with inappropriate timing (median $29,475, IQR $21,507-46,488, p<0.001). Multivariate linear regression and a Heckman two-stage model confirmed that appropriate antibiotic prophylaxis timing was associated with decreased hospitalization duration and hospital costs. CONCLUSION: In patients undergoing CABG or valve replacement surgery, the administration of vancomycin 16-120 minutes before incision significantly reduced patient hospitalization duration and total hospital costs.