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Background: The introduction of biosimilar drugs has significant effects on health care systems, and a variety of approaches are required to support acceptance, adoption, and use of these drugs. Literature exists on the enablers of, and barriers to, biosimilar implementation, but frameworks that support the evaluation of biosimilar implementation strategies are currently lacking. Objective: To develop an evaluation framework for assessing the effects of biosimilar implementation strategies on patients, clinicians, and publicly funded drug programs. Methods: The scope of the evaluation was determined by a pan-Canadian working group through the creation of a logic model of activities and expected outcomes associated with biosimilar implementation. Each component of the logic model was considered under the RE-AIM framework, which led to a set of evaluation questions and indicators. Feedback to inform the final framework was sought from stakeholders through focus group sessions and written responses. Results: An evaluation framework was created that articulates evaluation questions and indicators across 5 priority areas: stakeholder engagement, patient experience, patient outcomes, clinician experience, and system sustainability and affordability. Stakeholder feedback was obtained through 9 focus group sessions with a total of 87 participants. Feedback was used to refine the framework on the basis of stakeholder priorities and feasibility. Conclusions: Through extensive stakeholder consultation, an evaluation framework was developed to measure and monitor the effects of biosimilar implementation on the 5 identified priority areas, as well as to inform future biosimilar implementations. This framework can be used as a starting point for evaluating the implementation of biosimilars across health care systems. RÉSUMÉ Contexte : L’apparition de médicaments biosimilaires a eu et continue d’avoir des effets importants sur les systèmes de soins de santé et diverses approches doivent être mises en place pour qu’ils soient acceptés, adoptés et utilisés. Il existe de la documentation sur les catalyseurs et les obstacles à leur mise en œuvre, mais les cadres entourant l’évaluation des stratégies de mise en œuvre des médicaments biosimilaires font actuellement défaut. Objectif : Développer un cadre d’évaluation pour estimer les retombées des stratégies de mise en œuvre des biosimilaires sur les patients, les cliniciens et les programmes de médicaments financés par les deniers publics. Méthodes : Un groupe de travail pancanadien a déterminé la portée de l’évaluation à l’aide d’un modèle logique des activités et des résultats attendus associés à la mise en œuvre des biosimilaires. Chaque composante du modèle logique a été examinée dans le cadre RE-AIM, ce qui a donné lieu à un ensemble de questions d’évaluation et des indicateurs d’évaluation. Des commentaires pour éclairer le cadre final ont été sollicités auprès des parties prenantes au moyen de groupes de discussion et de réponses écrites. Résultats : Un cadre d’évaluation a été défini. Il articule les questions d’évaluation et des indicateurs d’évaluation dans 5 domaines prioritaires : l’engagement des intervenants, l’expérience des patients, les résultats des patients, l’expérience des cliniciens et la durabilité et l’abordabilité du système. Les commentaires des intervenants ont été obtenus au cours de 9 séances de groupes de discussion avec un total de 87 participants. Les commentaires ont été utilisés pour affiner le cadre sur la base des priorités des parties prenantes et de la faisabilité. Conclusions : Une vaste consultation des parties prenantes a permis de définir un cadre d’évaluation pour mesurer et surveiller les effets de la mise en œuvre des biosimilaires sur les 5 domaines prioritaires identifiés, ainsi que pour éclairer les futures mises en œuvre des biosimilaires. Ce cadre peut être utilisé comme point de départ pour évaluer la mise en œuvre des biosimilaires dans les systèmes de soins de santé.

To compare costs between two different eye drop delivery modalities: multidose bottles and single-use minims.Retrospective cohort study.Monthly dilating eye drop costs and quantities (tropicamide 1%, phenylephrine 2.5%, cyclopentolate 1%) were studied over a 2-year period between April 2013 and March 2015 at 2 tertiary ophthalmic centres (Royal Alexandra Hospital [RAH, Edmonton] and Rockyview General Hospital [RGH, Calgary]). In April 2014, RAH switched its dilating eye drop practice from predominantly multidose bottles to single-use minims, whereas RGH continued using predominantly multidose bottles. Eye drop volume and total and per-patient eye drop costs were quantified at RAH before switching (pre-intervention) and after (post-intervention) using an interrupted time-series analysis with RGH as a control. A counterfactual analysis was also performed. Significance was obtained using independent t-testing.After switching to single-use minims, RAH experienced changes in the following: an increase in single-use minims as a proportion of total eye drop utilization (from 5.6% to 89.1%; p = 0.001), an increase in total eye drop cost by $2117 per month (95% confidence interval [CI], $1354-$2880; p0.001), an increase in per-patient costs by $984 per 1000 patients per month (95% CI, $674-$1293). Contrastingly, RGH did not experience similar changes. Ultimately, the cost of switching to single-use minims was $22 481 (95% CI, $7830-$31 336) over a 12-month period.If safe eye drop practices are enforced via proper protocols, the use of multidose bottles may be a more cost-effective option than single-use minims for routine clinical practice.

Background: Following addition of a biosimilar filgrastim product to the formulary, sites in the authors’ provincial health authority transitioned from using the originator filgrastim to the biosimilar for autologous stem cell mobilization. Objective: To assess the effect on patient outcomes of a universal change to use of the biosimilar filgrastim in stem cell mobilization. Methods: This retrospective pre–post study included patients undergoing autologous stem cell mobilization at 2 cancer hospitals in Alberta, Canada, between July 1, 2018, and November 30, 2019. Clinical outcomes were investigated for patients treated with a granulocyte colony-stimulating factor (biosimilar or originator product) for mobilization before stem cell transplant, approximately 6 months before and after the defined date of product change. Results: In total, 102 patients were treated with the originator product and 101 patients with the biosimilar. Effectiveness was similar between the originator and biosimilar products, with 98% successful harvest of stem cells in all patients treated. Independent t tests showed no statistically significant differences between patients receiving the originator and those receiving the biosimilar in terms of time from mobilization to collection (difference of means –0.9 days, 95% confidence interval [CI] –2.12 to 0.32), time for neutrophil engraftment (difference of means 0 days, 95% CI –0.36 to 0.36), time for platelet engraftment (difference of means 1 day, 95% CI –0.55 to 2.55), average length of stay (difference of means –0.7 day, 95% CI –2.71 to 1.31), and CD34+ value (difference of means –1 × 106/kg body weight, 95% CI –2.11 to 0.11). A 98% rate of conversion to use of the biosimilar filgrastim was achieved, with an estimated annual drug-cost saving of $67 500. Conclusions: In this pre–post study, changing to the biosimilar product from the originator maintained clinical effectiveness outcomes while decreasing overall drug expenditures. A well-planned change to the biosimilar product, executed in conjunction with clinician consultation and monitoring of effectiveness outcomes, can ensure appropriate patient therapy while significantly improving the uptake of biosimilars and decreasing expenditures for biologic drugs. RÉSUMÉ Contexte : À la suite de l’ajout d’un produit filgrastim biosimilaire à la liste des médicaments, les sites relevant de l’autorité sanitaire provinciale des auteurs sont passés de l’utilisation du filgrastim princeps à la version générique pour la mobilisation des cellules souches autologues. Objectif : Évaluer l’effet sur les résultats des patients d’un changement généralisé visant à utiliser le filgrastim générique pour la mobilisation des cellules souches. Méthodes : Cette étude rétrospective pré-post comprenait des patients soumis à une mobilisation des cellules souches autologues dans deux hôpitaux de cancérologie en Alberta (Canada) entre le 1er juillet 2018 et le 30 novembre 2019. L’examen des résultats cliniques des patients traités à l’aide d’un facteur stimulant les colonies de granulocytes (G-CSF) (générique ou princeps) pour une mobilisation avant la greffe de cellules souches a eu lieu environ six mois avant et après la date du changement de produit. Résultats : Au total, 102 patients ont été traités à l’aide du produit princeps et 101 patients à l’aide du générique. Les deux produits présentaient une efficacité similaire, et 98 % de réussite dans la récolte de cellules souches chez tous les patients traités. Des tests t indépendants n’ont montré aucune différence statistique significative entre les patients recevant le princeps et ceux recevant le biosimilaire en termes de temps allant de la mobilisation à la collecte (différence des moyennes –0,9 jour, intervalle de confiance [IC] 95 % –2,12 à 0,32); temps de la prise de la greffe neutrophile (différence des moyennes 0 jour, IC 95 % –0,36 à 0,36); temps de la prise de la greffe des plaquettes (différence des moyennes 1 jour, IC 95 % –0,55 à 2,55); durée moyenne du séjour (différence des moyennes –0,7 jour, IC 95 % –2,71 à 1,31) et valeur CD34+ (différence des moyennes –1 × 106/kg masse corporelle, IC 95 % –2,11 à 0,11). Un taux de conversion de 98 % visant à utiliser le filgrastim générique a été atteint, avec une estimation des économies annuelles sur le coût des médicaments de 67 500 $. Conclusions : Dans cette étude pré-post, le passage du produit princeps au générique a préservé l’efficacité des résultats cliniques, tout en diminuant les dépenses générales liées au médicament. Un changement bien programmé pour passer au produit générique, mené conjointement avec la consultation d’un clinicien et un contrôle des résultats d’efficacité, peut assurer une thérapie du patient appropriée tout en améliorant grandement la prise de produits génériques et en diminuant les dépenses associées aux médicaments biologiques.

Objectives:To measure the impact of an antimicrobial stewardship initiative on the rate of urine culture testing and antimicrobial prescribing for urinary tract infections (UTIs) between control and intervention sites. Secondary objectives included evaluation of potential harms of the intervention and identifying characteristics of the population prescribed antimicrobials for UTI.Design:Cluster randomized controlled trial.Setting:Nursing homes in rural Alberta, Canada.Participants:The study included 42 nursing homes ranging from 8 to 112 beds.Methods/interventions:Intervention sites received on-site staff education, physician academic detailing, and integrated clinical decision-making tools. Control sites provided standard care. Data were collected for 6 months prior to and 12 months after the intervention.Results:Resident age (83.0 vs 83.8 years) and sex distribution (female, 62.5% vs 64.5%) were similar between the groups. Statistically significant decreases in the rate of urine culture testing (−2.1 tests per 1,000 resident days [RD]; 95% confidence interval [CI], −2.5 to −1.7;P< .001) and antimicrobial prescribing for UTIs (−0.7 prescriptions per 1,000 RD; 95% CI, −1.0 to −0.4;P< .001) were observed in the intervention group. There was no difference in hospital admissions (0.00 admissions per 1,000 RD; 95% CI, −0.4 to 0.3;P= .76), and the mortality rate decreased by 0.2 per 1,000 RD in the intervention group (95% CI, −0.5 to −0.1;P= .002). Chart reviews indicated that UTI symptoms were charted in 16% of cases and that urine culture testing occurred in 64.5% of cases.Conclusion:A multimodal antimicrobial stewardship intervention in rural nursing homes significantly decreased the rate of urine culture testing and antimicrobial prescriptions for UTI, with no increase in hospital admissions or mortality.

BACKGROUND Complications after liver transplantation cause additional healthcare costs. The objective of this study was to contrast the length of stay (LOS) costs for recipients with and without surgical site infections (SSIs). METHODS This retrospective observational cohort study was conducted at a transplant center in Canada, between February 2011 and August 2014. The difference in the LOS costs was assessed by the Mann-Whitney U test, while multiple linear regression analysis was used to identify the variables that may have impacted on the costs. RESULTS Two hundred and twenty-nine liver transplant recipients were enrolled. Thirty-six recipients developed SSIs (36/229, 15.7%). The median LOS costs in recipients with and without SSIs were $39,456 Canadian dollars (interquartile range $25,696- 59,722) and $31,084 Canadian dollars (interquartile range $22,712-49 610), respectively (p = .072). There was a trend that the costs were higher for those recipients with versus those without SSIs (p = .088). Transfusion of ≥ 5 units of red cells and dialysis before transplantation impacted on cost. CONCLUSION There was a trend for higher healthcare facility costs for recipients with SSIs. Red cell transfusions and greater dialysis use before transplant were factors associated with the cost. Implementation of cost reduction strategies targeting high-cost recipients is necessary.

Randomized controlled trials (RCTs) usually place less emphasis on the harmful effects than on the efficacy of interventions. The 10 CONSORT (Consolidated Standards of Reporting Trials) recommendations for harms reporting aim to improve harms data reporting of RCTs. The aim of this study was to assess the reporting of harms data in adjuvant trastuzumab studies in early-stage breast cancer. The resources PubMed, Cochrane Library, the American Society of Clinical Oncology, and the San Antonio Breast Cancer Symposium were searched for relevant RCTs that met the eligibility criteria. Each RCT was reviewed to determine whether the reporting of data complied with the 10 CONSORT recommendations for harms reporting, and the frequency of compliance with each CONSORT recommendation criterion was reviewed. Five RCTs met the eligibility criteria. Overall, selected RCTs failed to adhere to CONSORT recommendations in all sections of reporting. These results suggest that there is a need to standardize harms data reporting.

Introduction Antimicrobial stewardship (AS) within acute care facilities is a requirement for Accreditation Canada's Required Organisational Practices. In order to obtain a baseline evaluation of current AS processes, a focus group approach was used to qualitatively assess frontline pharmacy staff and leadership perspectives on AS resources. Methods A semi-structured interview process was applied to focus groups comprised of Pharmacy Services employees throughout Alberta Health Services in Alberta, Canada. A thematic analysis of transcripts was done independently by two investigators, and consensus was reached on identified themes and topics. Codes were recorded for prevalence and total number of mentions. A combination of conventional and deductive approaches was used to identify themes. Results A total of 200 (10%) pharmacy services staff members participated in the focus groups. Eight main themes were identified: antimicrobial resources, influences on antimicrobial utilisation, barriers to antimicrobial stewardship, establishing AS teams, education needs, improving communications, antimicrobial utilisation concerns, and enablers for improvement. Two hundred and six topics were identified to support the themes, with 1924 data points. Prominent topics included ubiquitous awareness of a provincial antimicrobial stewardship reference, prescriber preferences influencing antimicrobial utilisation, and desire to improve interprofessional teamwork, communication and educational opportunities. Conclusions A broad description of the culture of antimicrobial use showed that the themes are interrelated. To successfully change practice, one must take into account the complexity of the relationship between these perceptions.

A pediatric compounded non-sterile products repository (pCNP) to optimize the effectiveness and safety of “off-label” use of compounded pharmacotherapy through complete transmission of electronic prescriptions across the continuum of care is described. The advent of electronic prescribing has the potential to refocus and resolve long-standing issues of prescription therapy for pediatric patients related to formulation, indication, dosing, and outcomes follow-up, among others. This white paper describes the architecture and function of the pCNP repository. Further, it calls on professional societies, health information technology (HIT) and pharmaceutical industries, universities, and government to create a safer pediatric pharmacotherapy system across the continuum of care. This system would include pCNPs within the existing federal and corporate database structures for medical language, and integrates advanced system safety features as requirements for prescribing, compounding, and dispensing non-mass produced prescription therapies for children.

Clopidogrel is a prodrug requiring metabolism by cytochrome P450 3A (CYP3A) isoenzymes, including CYP3A5, in order to be active. It is controversial whether clopidogrel interacts with CYP3A inhibitors. We investigated the influence of CYP3A5 polymorphism on the drug interaction of clopidogrel.In phase 1 of the study, we administered clopidogrel to 16 healthy volunteers who had the CYP3A5 non-expressor genotype (*3 allele) and 16 who had the CYP3A5 expressor genotype (*1 allele) with and without pretreatment with itraconazole, a potent CYP3A inhibitor. A platelet aggregation test was performed at baseline, 4 hours, 24 hours and 6 days after clopidogrel administration. In phase 2, we compared clinical outcomes of 348 patients treated with clopidogrel after successful coronary angioplasty with bare-metal stent implantation according to their CYP3A5 genotype; the primary end point was a composite of atherothrombotic events (cardiovascular death, myocardial infarction and non-hemorrhagic stroke) within 1 and 6 months after stent implantation.In phase 1, the change in platelet aggregation after clopidogrel administration and pretreatment with itraconazole was greater among the subjects with the CYP3A5 expressor genotype than among those with the non-expressor genotype: 24.9% (standard deviation [SD] 13.9%) v. 6.2% (SD 13.5%) at 4 hours (p0.001); 27.7% (SD 16.5%) v. 2.5% (SD 8.3%) at 24 hours (p0.001); and 33.5% (SD 18.6%) v. 17.8% (SD 13.8%) at day 7 (p0.01). In phase 2, atherothrombotic events occurred more frequently within 6 months after stent implantation among the patients with the non-expressor genotype than among those with the expressor genotype (14/193 v. 3/155; p = 0.023). Multivariable analysis showed that the CYP3A5 polymorphism was a predictor of atherothrombotic events in clopidogrel users.People with the CYP3A5 non-expressor genotype are vulnerable to drug interactions between clopidogrel and CYP3A inhibitors. This phenomenon may be associated with worse outcomes in patients with the non-expressor genotype who are given clopidogrel after coronary angioplasty and implantation of bare-metal stents.

Inflammatory conditions reduce clearance, hence increase plasma concentration of drugs such as propranolol that are efficiently cleared by the liver. The therapeutic consequences of this increased plasma drug concentration is mainly unknown. However, for sotalol, another beta-adrenergic antagonist, inflammation causes reduced potency. Sotalol, however, is renally cleared; hence, its clearance is unaffected by inflammation. We examined if the inflammation-induced increased plasma propranolol concentration compensates for the reduced responsiveness. A modified lead I ECG was used to record PR interval and heart rate (HR). ECG was monitored following oral administration of 3, 5, 10, 15, 20, 25, and 30 mg/kg propranolol to both control and adjuvant arthritis (AA) rats. To confirm altered pharmacokinetics, single 25 mg/kg doses of propranolol were administered to both AA and control rats, with an inserted cannula in their right jugular vein for serial blood sampling. As expected, AA caused a significant reduction in the propranolol oral clearance and subsequently substantial increases in plasma total and unbound drug concentration. Interestingly, however, despite the elevated propranolol concentrations, the effect on HR remained unchanged and the prolongation of PR interval was significantly reduced in AA compared with control rats. The reduced sensitivity to propranolol in AA rats is suggestive of altered beta-adrenergic receptors function.