CONCLUSIONS: In an effort to expedite the publication of articles, AJHP is posting 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.
OBJECTIVE: Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19).
METHODS: We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis.
RESULTS: Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision.
CONCLUSIONS: Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.

Introduction: Revefenacin is a once-daily nebulized long-acting muscarinic antagonist (LAMA). Revefenacin is supplied as single-use nebulized vials, which may be preferable and less costly for hospital and health-system pharmacies to dispense versus multidose tiotropium inhalers. Estimates of LAMA multidose inhaler wasted doses remains unknown. Methods: This was a single-center descriptive cross-sectional study conducted between January 1 2021 and December 31 2021. Adult patients 18 years and older admitted to a 500-bed academic medical center in the southern United States and were ordered multidose tiotropium packages or single-use revefenacin vials during the study period were included. Results: Among 602 inpatients, there were 705 LAMA orders: 541 tiotropium (76.7%) and 164 revefenacin (23.3%). Four hundred ninety-five tiotropium orders (91.5%) wasted between 20% and 90% of multidose packages. Approximately $24,000 tiotropium doses were wasted versus single-use revefenacin vials. Conclusion: Multidose inhalers of tiotropium dispensed to hospitalized patients contributed to wasted doses compared to nebulized single-use revefenacin vials. Opportunities exist to minimize wasted doses of multidose long-acting inhalers dispensed to hospitalized patients.

BACKGROUND: Biosimilars are biologic drugs that have the potential to increase the efficiency of healthcare spending and curb drug-related cost increases. However, their introduction into hospital formularies through initiatives such as non-medical switching must be carefully orchestrated so as not to cause treatment discontinuation or result in increased health resource utilization, such as additional visits or laboratory tests, among others. This retrospective cohort study aims to assess the impact of the introduction of CT-P13 on the healthcare expenditures of patients who were treated with originator infliximab or CT-P13.
METHODS: Gastroenterology, immunoallergology and rheumatology patients treated between September 2017 and December 2020 at a university hospital in Western Switzerland were included and divided into seven cohorts, based on their treatment pathway (i.e., use and discontinuation of CT-P13 and/or originator infliximab). Costs in Swiss francs were obtained from the hospital\'s cost accounting department and length of stay was extracted from inpatient records. Comparisons of costs and length of stay between cohorts were calculated by bootstrapping.
RESULTS: Sixty immunoallergology, 84 rheumatology and 114 gastroenterology patients were included. Inpatient and outpatient costs averaged (sd) CHF 1,611 (1,020) per hospital day and CHF 4,991 (6,931) per infusion, respectively. The mean (sd) length of stay was 20 (28) days. Although immunoallergology and rheumatology patients had higher average costs than gastroenterology patients, differences in costs and length of stay were not formally explained by treatment pathway. Differences in health resource utilization were marginal.
CONCLUSIONS: The introduction of CT-P13 and the disruption of patient treatment management were not associated with differences in average outpatient and inpatient costs and length of stay, in contrast to the results reported in the rest of the literature. Future research should focus on the cost-effectiveness of non-medical switching policies and the potential benefits for patients.

Background: Though The Joint Commission requires health systems perform annual formulary review, guidance for how to perform this review is lacking. Published methods include comprehensive review of all pharmaceutical classes; however, this approach may not be the most efficient or effective option for a health system with a large formulary. Objective: To create a prioritization system for annual formulary review through development of a pharmaceutical class scoring tool. Methods: Drug information pharmacists developed the scoring tool, which used external and internal data to score pharmaceutical classes in 4 categories: safety, efficacy, cost, and utilization. The primary outcome, number of formulary changes resulting from pharmaceutical class review, was compared between the highest-scoring and lowest-scoring class to assess the tool\'s ability to prioritize high-yield class reviews. Results: The tool calculated scores for 91 pharmaceutical classes, altogether containing 962 medications. After review of the highest-scoring class, corticosteroids, 2 formulary changes were made: one dosage form was removed from formulary, and one medication was restricted to outpatient use only. Zero formulary changes resulted from review of the lowest-scoring class, pharmaceutical adjuvants. Conclusions: The tool described in this study prioritized annual formulary review efforts by identifying a pharmaceutical class with meaningful formulary optimization opportunities as the highest-scoring class, while correctly identifying a class with no optimization opportunities as the lowest-scoring class.

The impact of a hospital formulary was evaluated to provide a guide for the establishment of local formularies to optimize patient care and healthcare costs.
A formulary was introduced by formulary pharmacists of the Toda Medical Group for suggesting recommended medicines to physicians based on the medication history. Patients who were hospitalized in the rehabilitation ward of the Niiza Hospital and prescribed medicines according to the formulary introduced between April 2017 and March 2018 were included and followed-up for six months.
Of the 183 patients screened, 154 patients were enrolled as the formulary\'s introduction patients (76 males/78 females, median age 78 years); 92% of these patients received formulary-proposed prescriptions at the specified timepoints; and 19 patients re-consulted at the Niiza Hospital after discharge and continued the same formulary medicines. The proposed acceptance rate by physicians was 100%. Most changes suggested introduced generic formulations. The doses were equivalent for all pharmacological classes with the exception of medicines that interfere with the renin-angiotensin system, which fell from 10.7 to 7.2 mg (P< .0001). Overall daily medication costs fell at discharge compared to admission (38.5 vs. 94.6 yen per patient, respectively, P< .0001). This was valid for all pharmacological classes except for calcium channel blockers.
Hospital formulary-prescribed medications continued after discharge and promoted significant decreases in costs associated with outpatient prescriptions. Introducing a hospital formulary provides a basis for the introduction of local formularies and contributes to the reduction of local healthcare costs.

We conducted research to assess hospital pharmacists\' familiarity with/interpretation of data requirements for the different regulatory approval frameworks and the impact of this on their approach to substitution in the formulary. The online questionnaire included a small molecule (acetylsalicylic acid-follow-ons approved via the generic pathway), two biologic drugs (insulin glargine and etanercept-follow-ons approved via the biosimilar pathway), a non-biologic complex drug (NBCD; glatiramer acetate-follow-ons approved via the hybrid pathway) and a nanomedicine, ferric carboxymaltose (no follow-ons approved as yet). The study was conducted in two phases: an initial qualitative pilot study with 30 participants, followed by a quantitative stage involving 201 pharmacists from five European countries. Most expected negligible safety/efficacy differences between reference and follow-on products. Head-to-head clinical data showing therapeutic equivalence as a prerequisite for reference product/follow-on substitution was perceived to be needed most for biologics (47%), followed by NBCDs (44%)/nanomedicines (39%) and small molecules (23%). Overall, 28% did not know the data requirements for follow-on approval via the hybrid pathway; 16% were familiar with this pathway, compared with 50% and 55% for the generic and biosimilar pathways, respectively. Overall, 19% of respondents thought the European Medicines Agency (EMA) was responsible for defining the substitutability of follow-ons. Education is required to increase hospital pharmacist\'s knowledge of regulatory approval frameworks and their relevance to substitution practices.

BACKGROUND: A multi-criteria decision analysis (MCDA) approach has been suggested for helping purchasers in low- and middle-income countries in an evidence-based assessment of multi-source pharmaceuticals to mitigate potential adverse consequences of price-based decisions on patient access to effective medicines. Six workshops for developing MCDA-instruments for purchasing were conducted in Indonesia, Kazakhstan, Thailand, and Kuwait in 2017-2020. In Indonesia and Thailand, two pilot-initiatives aimed to implement the instruments for hospital drug purchasing decisions.
OBJECTIVE: By analysing and comparing the experiences and progress from the MCDA-workshops and the two case-examples for hospital implementation in Indonesia and Thailand, we aim to gain insights, which will support future implementation.
METHODS: The selection of criteria and their average weight were compared quantitatively across the MCDA-instruments developed in all four countries and settings. Implementation experiences from two case-examples were studied, which included (1) testing the instrument across a variety of drugs in seven hospitals in Thailand and (2) implementation in one specialty hospital in Indonesia. Semi-structured interviews were conducted via web-conferences with four diverse stakeholders in the pilot implementation projects in Thailand and Indonesia. The open responses were evaluated through qualitative content analysis and synthesis using grounded theory coding.
RESULTS: Drivers for implementation were making \'better\' decisions, achieving transparency and a rational selection process, reducing drug shortages, and assuring consistent quality. Challenges were seen on the technical level (definition or of criteria, scoring methods, access to data) or change-related challenges (resistance, perception of increased workload, lack of competencies or capabilities, lack of resources). The comparison of the MCDA instruments revealed high similarity, but also clear need for local adaptations in each specific case.
CONCLUSIONS: A set a of measures targeting challenges related to utility, methodology, data requirements, capacity building and training as well as the broader societal impact can help to overcome challenges in the implementation. Careful planning of implementation and organizational change is recommended for ensuring commitment and fit to local context and culture. Designing a collaborative change program for each application of MCDA-based purchasing will enable healthcare stakeholders to maximally benefit in terms of quality and effectiveness of care and access for patients.

Hospital drug formularies are reduced lists of drugs designed to optimise inpatient care. Adherence to the drugs included in such formularies is not always 100% but is generally very high. Little research has targeted the impact of a change in these formularies on outpatient drug prescriptions. This study therefore sought to evaluate the impact of a change affecting bronchodilator medications in a hospital drug formulary on intra- and out-of-hospital drug prescriptions in a region in north-western Spain. Two new drugs belonging to this same class were brought onto the out-of-hospital market, overlapping with the intervention.
We used a natural before-after quasi-experimental design with control group based on monthly data. The intervention evaluated was the modification of a hospital drug formulary, which involved withdrawing salmeterol/fluticasone in order to retain formoterol/budesonide as the sole inhaled corticosteroid and long-acting beta-agonist (ICS/LABA). Using official data sources, we extracted the following dependent variables: defined daily doses (DDD) per 1000 inhabitants per day, DDD per 100 bed-days, and cost per DDD.
Intra-hospital use showed a 173.2% rise (95% CI 47.3-299.0%) in the medication retained in the formulary, formoterol/budesonide, and a 94.9% drop (95% CI 77.9-111.9%) in the medication withdrawn from the formulary, salmeterol/fluticasone. This intervention led to an immediate reduction of 75.9% (95% CI 82.8-68.9%) in the intra-hospital cost per DDD of ICS/LABA. No significant changes were observed in out-of-hospital use.
Although this intervention was cost-effective in the intra-hospital setting, the out-of-hospital impact of a change in the drug formulary cannot be generalised to all types of medications and situations.

OBJECTIVE: The implementation and maintenance of a process for adding and removing hyperlinks to medication management policies and guidelines approved by a pharmacy and therapeutics (P&T) committee into the electronic health record (EHR) are described.
CONCLUSIONS: Medication management policies and guidelines approved by the P&T committee are published on the University of Utah Health intranet, making it possible to add hyperlinks to this information within the EHR. Adding these hyperlinks allows policy and guideline information to be available to clinicians on the medication ordering, verification, and administration screens without requiring a separate search of the intranet. In a quality-improvement project, all medication management policies and guidelines posted on the intranet were reviewed for relevance to the medication ordering, verification, and administration processes. Hyperlinks to relevant policies and guidelines were implemented into the EHR for specific medications. At the beginning of the review, 100 unique drugs associated with 1 or more hyperlinks were identified. The hyperlinks referenced a total of 33 Web documents: 8 policies and 25 guidelines. There are 74 medication management policies and 78 medication management guidelines approved by the P&T committee at University of Utah Health. After investigator review, 12 of 74 policies (16%) and 41 of 78 guidelines (53%) were deemed relevant during the medication ordering, verification, and administration processes. The review and hyperlink implementation process took a total of 101 hours. A continual review process was developed to enable addition and removal of hyperlinks as appropriate.
CONCLUSIONS: Providing direct access to relevant medication management policies and guidelines approved by the P&T committee during the medication ordering, verification, and administration processes via hyperlinks in the EHR makes formulary information readily accessible by appropriate staff. These hyperlinks may also improve adherence to formulary information, reduce medication expenditure, and improve safety and therapeutic outcomes of medication therapy.

The study covered in- and out-of-hospital care in a region in north-western Spain. The intervention evaluated took the form of a change in the hospital drugs formulary. Before the intervention, the formulary contained four of the five low molecular weight heparins (LMWHs) marketed in Spain. The intervention consisted of withdrawing two LMWHs (bemiparin and dalteparin) from the formulary and restricting the use of another (tinzaparin), leaving only enoxaparin as an unrestricted prescription LMWH. Accordingly, the aim of this study was to evaluate the effect on in- and outpatient drug prescriptions of removing and restricting the use of several LMWHs in a hospital drugs formulary.
We used a natural, before-after, quasi-experimental design with a control group and monthly data from January 2011 to December 2016. Based on data drawn from official Public Health Service sources, the following dependent variables were extracted: defined daily doses (DDD) per 1000 inhabitants per day (DDD/TID), DDD per 100 stays per day, and expenditure per DDD.
The two compounds that were removed from the formulary registered an immediate decrease at both an intra- and out-of-hospital level (66.6% and 55.6% for bemiparin and 73.0% and 92.2% for dalteparin, respectively); similarly, the compound that was restricted also registered an immediate decrease (36.1% and 9.0% at the in- and outpatient levels, respectively); in contrast, the remaining LMWH (enoxaparin) registered an immediate, significant increase at both levels (44.9% and 32.6%, respectively). The intervention led to an immediate reduction of 6.8% and a change in trend in out-of-hospital cost/DDD; it also avoided an expenditure of €477,317.1 in the 21 months following the intervention.
The results indicate that changes made in a hospital drugs formulary towards more efficient medications may lead to better use of pharmacotherapeutic resources in its health catchment area.