BACKGROUND: Several authors have hypothesized that adverse drug events (ADEs) upon switching from reference biologics to biosimilar products are related to the nocebo effect. However, a thorough and current review of the existing literature has not been conducted. OBJECTIVE: To evaluate if patient and/or physician knowledge of a switch from a reference biologic product to a biosimilar product was associated with an increase in ADEs likely to be susceptible to the nocebo effect.METHODS: Studies reporting efficacy and safety outcomes of a switch from a reference product to a biosimilar product were reviewed. Biologics with FDA-approved biosimilars in the United States were considered for review, including adalimumab, bevacizumab, etanercept, and infliximab. Studies were identified by searching controlled vocabulary (e.g., MeSH terms) and keywords within MEDLINE (via PubMed) and Embase. Descriptive statistics were used to quantify subjective and objective complications in doubleblinded and single-blinded or open-label studies.RESULTS: Thirty-one trials including 3,271 patients were reviewed in the full analysis. Median discontinuation rates for any reason were 14.3% (range = 0.0-33.3) in open-label studies compared with 6.95% (range = 5.2-11.0) in double-blinded studies. Discontinuation rates for ADEs were 5.6% (range = 0.0-24.2) in open-label studies versus 3.1% (range = 2.0-5.2) in double-blinded studies, suggesting the nocebo effect does affect biosimilar adoption. Subgroup analyses of antidrug antibody (ADA) development and infusion reactions were similar between infliximab open-label and doubleblinded studies. Discontinuation rates for any reason, for ADEs, and for lack of efficacy were generally higher in infliximab open-label trials compared with double-blinded trials. Etanercept biosimilar discontinuation rates for any reason were similar between study designs; however, incidences of injection site reactions and discontinuation rates for ADEs were higher in double-blinded compared with open-label study designs.CONCLUSIONS: Current evidence is insufficient to confirm a biosimilar nocebo effect, although higher discontinuation rates in infliximab biosimilar open-label studies support this theory. Further studies are needed to evaluate the existence of a biosimilar nocebo effect.
Purpose To evaluate the validity and reliability of select recommended triggers, defined as flags found on review of the medical record that prompt further investigation to determine the presence or absence of an adverse drug event (ADE), selected from a list initially constructed based on severity, frequency, and detectability of triggers within a pediatric population. Methods This was a single-center, retrospective cohort analysis of pediatric patients admitted to University of North Carolina (UNC) Children’s Hospital who received trigger-associated medications between January 2015 and December 2016. Patient-care areas of the emergency department, operating rooms, and post-anesthesia care units were excluded. Trigger-detection encounters were evaluated by two reviewers using pre-established, consensus ADE criteria as determined by a panel of pediatric and medication safety specialists at UNC Medical Center. Events were categorized according to medication-related trigger and analyzed using descriptive statistics. Results A total of 3,836 positive triggers were included in this study. For the aggregate 12-part trigger tool package, 1,055 positive ADEs were identified, leading to a positive predictive value (PPV) of 27.5%. A 50% increase from baseline serum creatinine, resulting from co-administration of 2 or more nephrotoxic medications accounted for a total of 3,698/3,836 (96.4%). Incomplete documentation was the leading cause for event exclusion, 8/27 (30%). The triggers with the highest PPV included protamine 4/4 (100%), flumazenil 1/1 (100%), and vancomycin-related events 51/67 (76.1%), respectively. Phenytoin level >30 µg/mL or free level >2.5 µg/mL resulted in the lowest PPV, 1/12 (8.3%). Conclusion This study lays the foundation for further studies to develop a robust pediatric trigger tool that may involve developing multi-element triggers, determining sensitivity and specificity of triggers, or mobilizing the trigger tool to an automated system. Trigger tools can be individualized to meet each institutions’ needs and unique patient population.
Purpose Review lessons learned during the development and implementation of a pharmacy-focused Morbidity, Mortality, and Improvement conference at an academic medical center. Summary Since the early 1900s, Morbidity and Mortality conferences have provided a forum for clinicians to discuss medical errors and adverse outcomes. Many institutions have now added “improvement” to the conference title to emphasize the goal of approaching these conferences in a systems-oriented manner. To date, a gap remains in the literature evaluating the impact of a pharmacy-focused Morbidity, Mortality, and Improvement (MM&I) conference. The primary goal in establishing this pharmacy-focused conference was to foster and strengthen the culture of medication safety within our department. In establishing our program, we identified an opportunity to leverage pharmacy residents similar to a medical resident–facilitated conference. After gaining leadership buy-in, a core planning team was formed to identify events and create conference materials. Primary metrics to gauge the success of implementation included event reporting trends and medication-safety strategic initiative tracking. The first year of MM&I conferences provided forward momentum for our department’s safety culture. Safety event reporting by pharmacy staff increased by 150% over the fiscal year, and more frontline staff expressed a personal interest in becoming involved in safety projects and initiatives outside of their normal shift responsibilities. Conclusion We have learned several important lessons that may be helpful to others, the primary of which is that improving a culture of safety takes time.
In 2017, due to a fluid shortage secondary to Hurricane Maria's devastation of Puerto Rico, hospitals and health-systems began to substitute rolapitant for fosaprepitant as part of chemotherapy-induced nausea and vomiting prevention and treatment strategies. However, despite advantageous pharmacologic and formulation (e.g. long half-life, quicker time to onset, and lack of first-pass hepatic metabolism) profiles, there seems to be significant risk of infusion-related hypersensitivity reactions associated with the administration of intravenous rolapitant. In January 2018, the U.S. FDA issued a Health Care Provider Letter stating that anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions have been reported in the postmarketing setting. Importantly, these reactions were observed at a higher rate than initially reported in the phase 1 bioequivalence study that led to FDA approval of intravenous rolapitant (2.8%), with many resulting in hospitalizations. At our institution, rolapitant-induced infusion-related reactions also occurred in more patients than expected (8.7%). Described herein are six cases of infusion-related hypersensitivity reactions with intravenous rolapitant at the North Carolina Cancer Hospital. Due to the quick onset of the infusion-related hypersensitivity reactions with intravenous rolapitant, interpatient differences in pharmacokinetics or pharmacodynamics are unlikely to be the cause. An objective assessment utilizing the Naranjo Causality Scale rates these infusion-related hypersensitivity reactions as definite adverse drug reactions.
Objectives: Beers Criteria and the Screening Tool of Older Persons' Prescriptions (STOPP) Criteria/Screening Tool to Alert to Right Treatment Criteria are used to assess potentially inappropriate prescribing and medications, which could pose a harm to those of older age. The purpose of this study was to assess and compare the use of Beers and STOPP Criteria in older kidney transplant recipients.Methods: This was a dual-center, retrospective chart review from May 1, 2014, to March 1, 2018, including kidney transplant recipients 65 years and older. Those who underwent a dual transplant or had incomplete medical records were excluded. Outcomes included number of potentially inappropriate medications (PIMs) comparing Beers and STOPP Criteria on transplant admission, number of PIMs on admission compared with discharge, and readmissions within 3 months related to these medications.Results: A total of 121 recipients were evaluated. On admission, 60 medications were listed on the STOPP Criteria compared with 106 medications on the Beers Criteria. When comparing PIMs on admission to discharge, there was a 38% decrease in the number of medications on discharge using the STOPP Criteria, whereas there was a 9% increase using the Beers Criteria.Conclusions: Older recipients were more likely to be on a medication listed in the Beers Criteria on admission and have a new medication listed in the Beers Criteria upon discharge compared with the STOPP Criteria.
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