The Effect of Performance Transparency on Adherence to Barcode Scanning During Order Preparation in an Adult Inpatient Satellite Pharmacy.

Purpose: The aim of this study was to investigate the effect of performance transparency and individualized feedback on pharmacy technician compliance with barcode verification technology during inpatient order preparation. Methods: Following the incorporation of barcode scanning technology into the workflow of pharmacy staff, a multiphasic intervention was employed to promote its use. The intervention included verbal feedback and publically posting performance metrics to increase accountability. An interrupted time-series analysis was conducted to ascertain trends and levels in the percent of orders that were dispensed using barcode verification, before and after the study intervention. Analyses were conducted by shift and overall for pharmacy workers in a single satellite pharmacy. Results: A significant increase in percent scanned orders was observed immediately following the intervention in our analysis of all pharmacy workers (+14.4%; P = .045; 95% confidence interval [CI]: 0.35-28.4). In the analysis of each shift, statistically significant increases in percent scanned orders were observed immediately following the intervention for both the evening shift (+5.1%; P = .024; 95% CI: 0.70-9.6) and the night shift (+29.9%; P = .025; 95% CI: 3.9-55.9), but not the day shift (+2.6; P = .707; 95% CI: -11.1 to 16.2). Conclusion: Increasing transparency of individual and team performance metrics in conjunction with targeted feedback is an effective intervention to improve compliance with barcode scanning technology.

Evaluating the Impact of Prescription Fill Rates on Risk Stratification Model Performance.

BACKGROUND: Risk adjustment models are traditionally derived from administrative claims. Prescription fill rates-extracted by comparing electronic health record prescriptions and pharmacy claims fills-represent a novel measure of medication adherence and may improve the performance of risk adjustment models. OBJECTIVE: We evaluated the impact of prescription fill rates on claims-based risk adjustment models in predicting both concurrent and prospective costs and utilization. METHODS: We conducted a retrospective cohort study of 43,097 primary care patients from HealthPartners network between 2011 and 2012. Diagnosis and/or pharmacy claims of 2011 were used to build 3 base models using the Johns Hopkins ACG system, in addition to demographics. Model performances were compared before and after adding 3 types of prescription fill rates: primary 0-7 days, primary 0-30 days, and overall. Overall fill rates utilized all ordered prescriptions from electronic health record while primary fill rates excluded refill orders. RESULTS: The overall, primary 0-7, and 0-30 days fill rates were 72.30%, 59.82%, and 67.33%. The fill rates were similar between sexes but varied across different medication classifications, whereas the youngest had the highest rate. Adding fill rates modestly improved the performance of all models in explaining medical costs (improving concurrent R by 1.15% to 2.07%), followed by total costs (0.58% to 1.43%), and pharmacy costs (0.07% to 0.65%). The impact was greater for concurrent costs compared with prospective costs. Base models without diagnosis information showed the highest improvement using prescription fill rates. CONCLUSIONS: Prescription fill rates can modestly enhance claims-based risk prediction models; however, population-level improvements in predicting utilization are limited.

Prescriber knowledge and attitudes regarding non-administration of prescribed pharmacologic venous thromboembolism prophylaxis.

Pharmacologic venous thromboembolism (VTE) prophylaxis is important patient safety practice in hospitalized patients. However, a substantial number of ordered doses are not administered. Patient and nursing attitudes and behaviors can influence whether a patient receives a dose. The objective of this single center study was to evaluate prescriber knowledge and attitudes regarding missed doses of pharmacologic VTE prophylaxis. An anonymous, 9-question survey was administered to internal medicine and general surgery resident physicians. The survey captured prescriber opinions on issues related to non-administration of VTE prophylaxis. Thirty-two percent of medicine residents compared with 3 % of surgery residents felt pharmacologic VTE prophylaxis was not necessary in an independently ambulating patient (P < 0.001). Medicine residents were more likely to agree that it is appropriate for nurses to make clinical decisions to determine whether a dose of pharmacologic VTE prophylaxis should be administered to a patient (24 vs. 0 %, P < 0.001). Study findings indicate the need for additional resident physician education. Further investigation is needed to assess these beliefs and ensure patients receive necessary VTE prophylaxis.

Evaluating treatments and corresponding costs of prostate cancer patients treated within an inpatient or hospital-based outpatient setting.

AIM: To describe treatments and cost of care for prostate cancer (PCa) in hospital-based outpatient and inpatient settings. METHODS: Hospital encounters associated with PCa (ICD-9 codes 185, 233.4) and PCa-related treatment in a hospital claims database were included. RESULTS: There were 211,440 encounters for PCa between January 2006 and December 2010 (88,151 inpatient and 123,289 outpatient). Average cost per inpatient stay was US$12,286 versus US$4364 per outpatient visit. Most common treatment during an inpatient stay and outpatient visit was surgery (57%) and radiation (76%), respectively. A total of 80% of outpatient visits and 69.9% inpatient stays were associated with a single treatment; remaining encounters were associated with ≥2 treatments. CONCLUSION: Costs are consistent with previous estimates; however, multimodal therapy is an emerging trend that may be related to greater costs in the future which may also be a challenge for hospital decision makers.

Validation of an algorithm to prioritize patients for comprehensive medication management in primary care settings.

BACKGROUND: Comprehensive medication management (CMM) programs optimize the effectiveness and safety of patients' medication regimens, but CMM may be underutilized. Whether healthcare claims data can identify patients appropriate for CMM is not well-studied. AIM: Determine the face validity of a claims-based algorithm to prioritize patients who likely need CMM. METHOD: We used claims data to construct patient-level markers of "regimen complexity" and "high-risk for adverse effects," which were combined to define four categories of claims-based CMM-need (very likely, likely, unlikely, very unlikely) among 180 patient records. Three clinicians independently reviewed each record to assess CMM need. We assessed concordance between the claims-based and clinician-review CMM need by calculating percent agreement as well as kappa statistic. RESULTS: Most records identified as 'very likely' (90%) by claims-based markers were identified by clinician-reviewers as needing CMM. Few records within the 'very unlikely' group (5%) were identified by clinician-reviewers as needing CMM. Interrater agreement between CMM-based algorithm and clinician review was moderate in strength (kappa = 0.6, p < 0.001). CONCLUSION: Claims-based pharmacy measures may offer a valid approach to prioritize patients into CMM-need groups. Further testing of this algorithm is needed prior to implementation in clinic settings.

Impact of a venous thromboembolism prophylaxis "smart order set": Improved compliance, fewer events.

Venous thromboembolism (VTE) affects over 700,000 Americans annually. Prophylaxis reduces the risk of VTE by 60% but many patients still do not receive risk-appropriate VTE prophylaxis. To improve our institution's VTE prophylaxis performance, we developed mandatory computerized clinical decision support-enabled "smart order sets" that required providers to assess VTE risk factors and contraindications to pharmacologic prophylaxis. Using provider responses, the order set recommends evidence-based risk-appropriate VTE prophylaxis. To study the impact of our "smart order set" on prescription of risk-appropriate VTE prophylaxis and clinical outcomes, we conducted a retrospective chart review of consecutive patients admitted to the Medicine service during one month immediately prior to (November 2007) and a single month subsequent to (April 2010) order set launch. Data collection included patient demographics, VTE risk factors, and the use and type of VTE prophylaxis. The pre- and post-implementation cohorts contained 1,000 and 942 patients, respectively. After implementation of the "smart order set", the prescription of risk-appropriate VTE prophylaxis increased from 65.6% to 90.1% (P < 0.0001). Orders for any form of VTE prophylaxis increased from 76.4% to 95.6% (P < 0.0001). Radiographically documented symptomatic VTE within 90 days of hospital discharge declined from 2.5% to 0.7% (P = 0.002). Preventable harm was completely eliminated (1.1% to 0%, P = 0.001) with no difference in major bleeding or all-cause mortality. A VTE prophylaxis computerized clinical decision support-enabled "smart order set" improved prescription of risk-appropriate VTE prophylaxis, reduced symptomatic VTE and eliminated preventable harm from VTE without increasing major bleeding.

Closed-Loop Medication Management with an Electronic Health Record System in U.S. and Finnish Hospitals.

Many medication errors in the hospital setting are due to manual, error-prone processes in the medication management system. Closed-loop Electronic Medication Management Systems (EMMSs) use technology to prevent medication errors by replacing manual steps with automated, electronic ones. As Finnish Helsinki University Hospital (HUS) establishes its first closed-loop EMMS with the new Epic-based Electronic Health Record system (APOTTI), it is helpful to consider the history of a more mature system: that of the United States. The U.S. approach evolved over time under unique policy, economic, and legal circumstances. Closed-loop EMMSs have arrived in many U.S. hospital locations, with myriad market-by-market manifestations typical of the U.S. healthcare system. This review describes and compares U.S. and Finnish hospitals' EMMS approaches and their impact on medication workflows and safety. Specifically, commonalities and nuanced differences in closed-loop EMMSs are explored from the perspectives of the care/nursing unit and hospital pharmacy operations perspectives. As the technologies are now fully implemented and destined for evolution in both countries, perhaps closed-loop EMMSs can be a topic of continued collaboration between the two countries. This review can also be used for benchmarking in other countries developing closed-loop EMMSs.

Validity and reliability of The Johns Hopkins Adapted Cognitive Exam for critically ill patients.

OBJECTIVE: To validate The Johns Hopkins Adapted Cognitive Exam designed to assess and quantify cognition in critically ill patients. DESIGN: Prospective cohort study. SETTING: Neurosciences, surgical, and medical intensive care units at The Johns Hopkins Hospital. PATIENTS: One hundred six adult critically ill patients. INTERVENTIONS: One expert neurologic assessment and four measurements of the Adapted Cognitive Exam (all patients). Four measurements of the Folstein Mini-Mental State Examination in nonintubated patients only. Adapted Cognitive Exam and Mini-Mental State Examination were performed by 76 different raters. MEASUREMENTS AND MAIN RESULTS: One hundred six patients were assessed, 46 intubated and 60 nonintubated, resulting in 424 Adapted Cognitive Exam and 240 Mini-Mental State Examination measurements. Criterion validity was assessed by comparing Adapted Cognitive Exam with a neurointensivist's assessment of cognitive status (ρ = 0.83, p < .001). Ordinal logistic regression established optimal predicted cut points for cognitive status classification (≤ 28 = severely impaired, 29-55 = moderately impaired, ≥ 56 = mildly impaired or normal). Using these cut points, the Adapted Cognitive Exam appropriately classified cognitive status 90% of the time. Construct validity was assessed by comparing Adapted Cognitive Exam with Mini-Mental State Examination in nonintubated patients (ρ = 0.81, p < .001). Face validity was assessed by surveying raters who used both the Adapted Cognitive Exam and Mini-Mental State Examination and indicated the Adapted Cognitive Exam was an accurate reflection of the patient's cognitive status, more sensitive a marker of cognition than the Mini-Mental State Examination, and easy to use. The Adapted Cognitive Exam demonstrated excellent interrater reliability (intraclass correlation coefficient = 0.997; 95% confidence interval 0.997-0.998) and interitem reliability of each of the five subscales of the Adapted Cognitive Exam and Mini-Mental State Examination (Cronbach's α: range for Adapted Cognitive Exam = 0.83-0.88; range for Mini-Mental State Examination = 0.72-0.81). CONCLUSION: The Adapted Cognitive Exam is the first valid and reliable examination for the assessment and quantification of cognition in critically ill patients. It provides a useful, objective tool that can be used by any member of the interdisciplinary critical care team to support clinical assessment and research efforts.

Analysis of the projected utility of dabigatran, rivaroxaban, and apixaban and their future impact on existing Hematology and Cardiology Anticoagulation Clinics at The Johns Hopkins Hospital.

The purpose of this study is to determine the percentage of patients in the Johns Hopkins Anticoagulation Clinics that are potential candidates for the new oral anticoagulants, dabigatran, rivaroxaban, and apixaban. A retrospective chart review was conducted of patients managed in the Johns Hopkins Cardiology and Hematology Anticoagulation Clinics between November 1, 2009 and October 31, 2010. Data elements collected include demographics, primary indication for anticoagulation, renal function, hepatic function, and concomitant medications. These factors were considered against product labeling guidelines and inclusion/exclusion criteria from clinical studies to derive candidacy status for each oral anticoagulant for each patient. Patients who met at least one caution or contraindication criteria were deemed "non-candidates"; potential dosage reductions of the new oral anticoagulants were not considered. Four hundred ninety-one patients participated in the study. Among participants, 63% would be dabigatran candidates, 62% rivaroxaban candidates, and 70% would be candidates for apixaban. Dabigatran use would be cautioned against in 34%, rivaroxaban in 18 %, and apixaban in 30%. Four percent had contraindications to dabigatran, whereas 21% had contraindications to rivaroxaban. More than 60% of patients in the Johns Hopkins Anticoagulation Clinics appear to be potential candidates for each of the new oral anticoagulants, assuming they are eventually approved for the same indications as warfarin. Many patients fell into the "cautioned" category, which demonstrates the complexity associated with selecting candidates for these new agents.

Comparing and validating medication complexity from insurance claims against electronic health records.

BACKGROUND: Patient effort to comply with complex medication instructions is known to be related to nonadherence and subsequent medical complications or health care costs. A widely used Medication Regimen Complexity Index (MRCI) has been used with electronic health records (EHRs) to identify patients who could benefit from pharmacist intervention. A similar claims-derived measure may be better suited for clinical decision support, since claims offer a more complete view of patient care and health utilization. OBJECTIVE: To define and validate a novel insurance claims-based medication complexity score (MCS) patterned after the widely used MRCI, derived from EHRs. METHODS: Insurance claims and EHR data were provided by HealthPartners (N = 54,988) (Bloomington, Minnesota) and The Johns Hopkins Health System (N = 28,589) (Baltimore, Maryland) for years 2013 and 2017, respectively. Yearly measures of medication complexity were developed for each patient and evaluated with one another using rank correlation within different clinical subgroupings. Indicators for the presence of individually complex prescriptions were also developed and assessed using exact agreement. Complexity measures were then correlated with select covariates to further validate the concordance between MCS and MRCI with respect to clinical metrics. These included demographic, comorbidity, and health care utilization markers. Prescribed medications in each system's EHR were coded using the previously validated MRCI weighting rules. Insurance claims for retail pharmacy medications were coded using our novel MCS, which closely followed MRCI scoring rules. RESULTS: EHR-based MRCI and claims-based MCS were significantly correlated with one another for most clinical subgroupings. Likewise, both measures were correlated with several covariates, including count of active medications and chronic conditions. The MCS was, in most cases, more associated with key health covariates than was MRCI, although both were consistently significant. We found that the highest correlation between MCS and MRCI is obtained with patients who have similar counts of pharmacy records between EHRs and claims (HealthPartners: P = 0.796; Johns Hopkins Health System: P = 0.779). CONCLUSIONS: The findings suggest good correspondence between MCS and MRCI and that claims data represent a useful resource for assessing medication complexity. Claims data also have major practical advantages, such as interoperability across health care systems, although they lack the detailed clinical context of EHRs. DISCLOSURES: The Johns Hopkins University holds the copyright to the Adjusted Clinical Groups (ACG) system and receives royalties from the global distribution of the ACG system. This revenue supports a portion of the authors' salary. No additional or external funding supported this work. The authors have no conflict of interest to disclose.

Claims-based pharmacy markers for comprehensive medication management program case identification: Validation against concurrent and prospective healthcare costs and utilization.

BACKGROUND: Three claims-based pharmacy markers (complex, costly and risky medications) were developed to help automatically identify patients for comprehensive medication management. OBJECTIVE: To evaluate the association between newly-developed markers and healthcare outcomes. METHODS: This was a two-year retrospective cohort study using PharMetrics Plus patient-level administrative claims in 2014 and 2015. We included all claims from 1,541,873 individuals with: (1) 24-month medical and pharmacy enrollment in 2014 and 2015, (2) aged between 18 and 63 in 2014, and (3) known gender. Independent/control variables came from 2014 while outcomes came from 2014 (concurrent analysis) and 2015 (prospective analysis). Three pharmacy markers, separately or together, were added to four base models to predict concurrent and prospective healthcare costs (total, medical, and pharmacy) and utilization (having any hospitalization, having any emergency department visit, and having any readmission). We applied linear regression for costs while logistic regression for utilization. Measures of model performances and coefficients were derived from a 5-fold cross-validation repeated 20 times. RESULTS: Individuals with 1+ complex, risky or costly medication markers had higher comorbidity, healthcare costs and utilization than their counterparts. Nine binary risky category markers performed the best among the three types of risky medication markers; the Medication Complexity Score and three-level complex category both outperformed a simpler complex medication indicator. Adding three novel pharmacy markers separately or together into the base models provided the greatest improvement in explaining pharmacy costs, compared with medical (non-medication) costs. These pharmacy markers also added value in explaining healthcare utilization among the simple base models. CONCLUSIONS: Three claims-based pharmacy indicators had positive associations with healthcare outcomes and added value in predicting them. This initial study suggested that these novel markers can be used by pharmacy case management programs to help identify potential high-risk patients most likely to benefit from clinical pharmacist review and other interventions.

Levocarnitine supplementation for management of hypertriglyceridemia in patients receiving parenteral nutrition.

BACKGROUND: Levocarnitine deficiency has been observed in patients receiving parenteral nutrition (PN) and can cause or worsen hypertriglyceridemia. The objective was to characterize use of levocarnitine supplementation in PN and evaluate its effect on triglyceride levels in hospitalized adults. METHODS: This retrospective, single-center study included patients with triglyceride levels ≥175 mg/dl while receiving PN who had a subsequent reduction in lipid injectable emulsion dose. A piecewise linear regression was used to evaluate trends in triglyceride levels before and after the intervention, defined as initiation of levocarnitine in PN for the levocarnitine group, or reduction in lipid injectable emulsion alone for the control group. RESULTS: Two hundred sixty-one patients who received PN had an elevated triglyceride level and lipid injectable emulsion dose reduction, of which 97 (37.2%) received levocarnitine in PN. The median (IQR) levocarnitine dose added to PN was 8.0 (5.7-9.9) mg/kg. Triglyceride levels at 30 days post-intervention did not differ between groups (125 vs 176 mg/dl, P = .345). The addition of levocarnitine to PN was associated with a significantly greater rate of reduction in triglyceride levels pre-intervention to post-intervention compared with a reduction in lipid injectable emulsion alone (-11 vs -3 mg/dl per day; 95% CI, -15 to -2; P = .012). CONCLUSION: In hospitalized adults with hypertriglyceridemia who had a lipid injectable emulsion dose reduction, the addition of levocarnitine in PN was not associated with a difference in triglyceride levels at 30 days; however, a greater rate of improvement in pre-intervention to post-intervention triglyceride levels was observed.

Comparison of Clinical Scoring Tools to Predict Heparin-Induced Thrombocytopenia in Cardiac Surgery.

The 4Ts and HIT-Expert Probability (HEP) scoring tools for heparin-induced thrombocytopenia (HIT) have not been validated in cardiac surgery patients, and the reported sensitivity and specificity of the Post-Cardiopulmonary Bypass (CPB) scoring tool vary widely in the 2 available analyses. It remains unclear which of the available scoring tools most accurately predicts HIT in this population. Forty-nine HIT-positive patients who underwent on-pump cardiac surgery within a 6-year period were loosely matched to 98 HIT-negative patients in a 1:2 case-control design. The 4Ts, HEP, and CPB scores were calculated for each patient. Sensitivity and specificity of each tool were calculated using standard cut-offs. The Youden method was utilized to determine optimal cut-offs within receiver operating characteristic (ROC) curves of each score, after which sensitivities and specificities were recalculated. Using standard cut-offs, the sensitivities for the CPB, HEP, and 4Ts scores were 100%, 93.9%, and 69.4%, respectively. Specificities were 51%, 49%, and 71.4%, respectively. The AUC of the scoring tool ROC curves were 0.961 for the CPB score, 0.773 for the HEP score, and 0.805 for the 4Ts score. Using the Youden method-derived optimal cut-off of  ≥3 points on the CPB score, sensitivity remained 100% with improved specificity to 88.9%. The CPB score is the preferred HIT clinical scoring tool in adult cardiac surgery patients, whereas the 4Ts score performed less effectively. A cut-off of ≥ 3 points on the CPB score could increase specificity while preserving high sensitivity, which should be validated in a prospective evaluation.

The use of lacosamide in refractory status epilepticus.

BACKGROUND: Case reports suggest lacosamide may have a role in status epilepticus (SE). The purpose of this case series is to describe the use of lacosamide in refractory SE (RSE) at our institution. METHODS: Observational study of all patients admitted to the neurosciences intensive care unit with RSE who received at least one dose of lacosamide from October 2009 to September 2010. RESULTS: Nine patients received lacosamide after failure of at least two other agents. Lacosamide was started a median of 2 days (range: 0-14 days) after the onset of SE. The most frequently used dosing regimen was an initial intravenous dose of 200 mg followed by 200 mg every 12 h. Most patients had received 3 (range: 2-5) AEDs prior to lacosamide. Levetiracetam was used prior to lacosamide in all cases. No patients evaluated responded to lacosamide according to our predefined criteria. One patient developed angioedema after receiving two doses; another patient developed angioedema where timing in relation to the lacosamide was unclear. Care was withdrawn in three of the nine patients for reasons unrelated to lacosamide. Lacosamide was continued at discharge on all surviving patients except in one case of angioedema. CONCLUSIONS: This is the largest case series to date describing the use of lacosamide in patients with RSE. Despite the novel mechanism of action, we observed no evidence that lacosamide is effective in RSE; however, our sample size was small. Further study is needed to determine the role of lacosamide in SE, especially early in the treatment course.

Budgeting in the post-COVID era: Be in the room where it happens.

In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Practical utility of mixed methods research in pharmacy practice.

PURPOSE: Our aim was to review key methodological concepts and provide a practical guide to employing mixed methods research to enhance pharmacy practice research. SUMMARY: Mixed methods research provides multiple organized analytic perspectives to thoroughly investigate complex social and scientific problems in a methodologically rigorous manner. This research design incorporates collection and analysis of both qualitative and quantitative data components to create a thorough understanding of a complex question. The 5 most commonly identified reasons for conducting mixed methods research include triangulation, complementarity, development, initiation, and expansion of results. For research questions that benefit from mixed methods research, we review how to structure the study, including timing, sequencing, and prioritization of methods. Illustrative examples from the literature highlight the utility of this methodology for clinical and operational pharmacy research questions. CONCLUSION: Mixed methods designs can enhance pharmacy research inquiry, provide a means to understand complicated issues, and uncover optimal interventions.

Assessment of Availability, Clinical Testing, and US Food and Drug Administration Review of Biosimilar Biologic Products.

Importance: Biosimilar biologic products were authorized in 2010, after the US Congress established an expedited pathway for approval of clinically similar versions of approved biologic products. Unlike for most small-molecule generic drugs, approval requirements for a biosimilar included animal studies and a comparative efficacy clinical trial. Objective: To analyze the evidence required to support a biosimilarity license application, examine the US Food and Drug Administration (FDA) evaluation process, and estimate the costs of the key clinical trial evidence. Design: This study evaluated all biosimilar biologic products approved from January 2010 through October 2019, using the publicly available FDA review documents, disclosures from ClinicalTrials.gov, and the published peer-reviewed literature. The costs of efficacy clinical trials were estimated using licensed proprietary software. Main Outcomes and Measures: The following elements of each approved biosimilar were evaluated: the extent of human clinical testing to establish that the biosimilar had no clinically meaningful differences with the reference product, results of comparative animal studies, and FDA-cited application deficiencies. The cited deficiencies included the following categories: (1) facility inspection, (2) manufacturing or product quality, (3) animal studies, (4) laboratory analytical studies, (5) phase 1 and/or immunogenicity studies, and (6) phase 3 comparative efficacy trials. Results: As of October 2019, the FDA had approved 23 biosimilar biologics for 9 reference products. The 29 clinical trials that established that the efficacy of the biosimilar products was comparable to that of the reference products enrolled a median (interquartile range [IQR]) of 504 (258-612) patients, had a median (IQR) estimated cost of $20.8 ($13.8-$35.3) million, and had a median (IQR) treatment duration of 52 (28-68) weeks. Substantial deficiencies temporarily halted the review of 9 applications, and the most frequent deficits were failed facilities inspections (n = 5) and manufacturing process quality problems (n = 6). The approved biosimilar submissions included 51 animal studies on species that included mice, rats, rabbits, dogs, and cynomolgus monkeys. Negative outcomes in 2 animal studies were attributed to differences between human and test species. The FDA generally met the standard 12-month review deadlines or stopped the review clock when serious deficiencies were identified. Conclusions and Relevance: This study found that most comparative efficacy trials supporting the FDA approval of biosimilars appeared to be as rigorous as and often larger, longer, and more costly than pivotal trials for new molecular entities. Further research is needed into whether less costly comparative efficacy trials could provide adequate evidence of biosimilarity and whether animal studies contribute useful scientific evidence.

Is There Any Research Evidence Beyond Surveys and Opinion Polls on Automatic Substitution of Biological Medicines? A Systematic Review.

BACKGROUND: Biosimilars are expected to decrease growing health care expenditures. Given that uptake of biosimilars has been modest, automatic substitution has been suggested to increase their use, but the practice is not yet allowed or implemented in many jurisdictions. METHODS: A systematic review was performed by searching databases Scopus, Medline (Ovid), CINAHL, and Web of Science. Peer-reviewed, original studies written in English and published during the period January 1, 2006 to April 24, 2021 reporting any interventions, pilots or any other studies including experiences or perceptions of any relevant stakeholders on automatic substitution of biologics were included without limitation by setting or geography. The quality of the included studies were evaluated by pre-determined criteria. RESULTS: Altogether, 27 studies fulfilled the inclusion criteria, of which 23 were surveys, and four semi-structured interviews reporting mainly stakeholders' perceptions on automatic substitution. Most of the studies (56%, 15/27) were from Europe. Studies were conducted among prescribers (n = 12), pharmacists (n = 5), patients (n = 4), payers (n = 1), and mixed stakeholders (n = 5). The primary objective of the majority (81%, 22/27) of the studies was to investigate some other biosimilar topic than automatic substitution. The reported perceptions of substitution were mainly negative. Studies evaluating risks, safety or effectiveness, or reporting real-life experiences of biologic substitution were lacking except one intervention and two prospective risk management studies. The overall quality of the studies was low to moderate, and the results were not generalizable due to convenience sampling not representing the populations of interest, and low response rates. CONCLUSIONS: The current research evidence on the automatic substitution of biologics is scarce and of low to moderate quality, reflecting low stakeholder knowledge and their cautious attitude towards biosimilars. The safe and efficient implementation of automatic substitution requires well-designed practices, pilot studies, and evolving legislation.