Análise das solicitações de medicamentos não padronizados de um hospital universitário terciário / Analysis of requests for non-standard medicines from a tertiary university hospital

Introdução: O uso extensivo de medicamentos não padronizados causa aumento de custos em saúde, além de potencial redução de segurança e uso racional de medicamentos. A Comissão de Farmácia e Terapêutica orienta a prescrição de medicamentos, por meio da avaliação e seleção de medicamentos a serem incluídos no formulário de medicamentos padronizados, com base nas melhores evidências científicas disponíveis e no perfil dos pacientes locais, promovendo o uso racional de medicamentos. O objetivo deste trabalho foi analisar as solicitações de fornecimento de medicamentos não padronizados na instituição. Métodos: Trata-se de um estudo observacional e descritivo onde foram analisadas as solicitações de medicamentos não padronizados realizadas entre fevereiro de 2016 e dezembro de 2021, identificando os medicamentos envolvidos e seus respectivos custos. Resultados: Foram realizadas 203 solicitações no período, sendo 174 incluídas no estudo. Os medicamentos que tiveram mais solicitações foram o rituximabe (41), a imunoglobulina humana (31), o sucralfato (23), a nitazoxanida (12) e o eltrombopague (7). As solicitações com maior custo foram as de imunoglobulina humana (US$ 799,702.38), rituximabe (US$ 717,320.26), eltrombopague (US$ 281,062.50), ruxolitinibe (US$ 167,867.46) e bortezomibe (US$ 149,033.52). As principais clínicas que solicitaram medicamentos não padronizado foram a neurologia (47), a hematologia (30), as moléstias infecciosas e parasitárias (17), e a anestesiologia (12). As solicitações de maior custo foram realizadas pela neurologia (US$ 145,519.08), hematologia (US$ 120,980.25), transplante de medula óssea (US$ 51,635.11) e dermatologia (US$ 44,813.40). Conclusão: O estudo demonstrou que há um fluxo estruturado de solicitação de medicamentos não padronizados na instituição, sendo uma importante ferramenta de gerenciamento dessas solicitações, evitando a aquisição desnecessária de itens que não compõem o elenco terapêutico do hospital.

Introduction: Widespread use of non-formulary drugs (NFD) increases cost and may reduce safety and rational use of medicines. The Pharmacy and Therapeutics Committee provides guidance on drug prescription by evaluating and selecting medications to be included in a hospital's formulary based on best scientific evidence available and local patients' profile, promoting rational use of medicines. The objective of this study was to assess non-formulary drugs prescriptions at a tertiary hospital. Methods: This was a retrospective study. NFD prescribed and its associated costs were assessed through NFD request forms received from February 2016 to December 2021. Results: A total of 203 NFD request forms were received, from which 174 were included in this study. The most frequently prescribed NFD included rituximab (n = 41), immunoglobulin (31), sucralfate (23), nitazoxanide (12), and eltrombopag (7), with the highest costs being with immunoglobulin (US$ 799,702.38), rituximab (US$ 717,320.26), eltrombopag (US$ 281,062.50), ruxolitinib (US$ 167,867.46), and bortezomib (US$ 149,033.52). The most frequent requesting specialties were neurology (n = 47), hematology (30), infectious disease (17) and anesthesiology (12), and highest costs requests were from neurology (US$ 145,519.08), hematology (US$ 120,980.25), bone marrow transplant unit (US$ 51,635.11), and dermatology (US$ 44,813.40). Conclusion: This study showed that a structured request flow for NFD prescription is a critical procedure in order to better manage drug prescription within the hospital, promoting rational use of medicines and preventing unnecessary spending with drugs for which the clinical indication may be covered by a drug already in the hospital's formulary.

Pharmacist perspectives and considerations for implementation of therapeutic oncology biosimilars in practice.

PURPOSE: An overview of therapeutic oncology biosimilars, the U.S. biosimilars regulatory pathway, and the clinical development of selected biosimilar products is provided, including discussion of considerations in adopting biosimilars into oncology practice. SUMMARY: Biosimilars are biologic agents that are highly similar to and have no clinically meaningful differences from an approved reference product in terms of safety, purity, and potency. There is a large market for cancer biologics, and approval of biosimilars has the potential to increase access to care and reduce costs. An abbreviated regulatory pathway for the development and approval of biosimilars defines a stepwise approach to demonstrating biosimilarity and conducting clinical comparative trials to confirm equivalent pharmacokinetics, efficacy, safety, and immunogenicity to the reference product. Three therapeutic biologics (bevacizumab, trastuzumab, and rituximab) have been used extensively in the treatment of a variety of cancers and are targets for biosimilar product development. Preclinical and clinical experience with 2 recently approved biosimilars to bevacizumab and trastuzumab is reviewed. Challenges faced by pharmacy and therapeutics committees when considering oncology biosimilars for formulary inclusion are discussed. CONCLUSION: Increased adoption of biosimilars could potentially lower treatment costs and improve access to biologics for patients with cancer. Key considerations in formulary review of biosimilars include the quality and quantity of data from comparative clinical trials, economic factors, manufacturer reliability, and challenges associated with incorporating biosimilars into practice.

Application of pharmacoeconomics to formulary management in a health system setting.

PURPOSE: A novel value-based approach to evaluate costly specialty drugs for formulary addition was developed. SUMMARY: In February 2016, Stanford Health Care launched the specialty drug subcommittee (SDSC), a subcommittee of the pharmacy and therapeutics committee, responsible for the formulary review of specialty pharmaceuticals. A process was developed for value-based review that includes not only consideration of clinical trial data and institutional acquisition costs but also internal patient outcomes and a cost-effectiveness model using internal financial data. A Markov model was developed to assess the value of trabectedin, which was approved for formulary addition in April 2016, relative to the addition of dacarbazine. The economic model and internal patient outcome analysis were presented to the prescribing oncologist and the SDSC for review. Internal data revealed that fewer patients than had been estimated received trabectedin, with outcomes significantly worse than those observed in the clinical trial leading to Food and Drug Administration approval. In the cost-effectiveness model, trabectedin had higher costs and poorer outcomes compared with dacarbazine. Based on the economic model, low utilization, and real-world outcomes, trabectedin was removed from formulary and a restrictive treatment pathway for nonformulary use, developed by the primary prescriber, was implemented. This process has since been applied to 11 more specialty drugs. CONCLUSION: Internal cost-effectiveness models in combination with real-world patient outcomes data can be effective formulary management tools. Engagement and collaboration with the requesting provider are key to developing thoughtful treatment pathways.

Prognosis of lung cancer patients in Japan according to data from the Japanese Joint Committee of Lung Cancer Registry.

An organ-based lung cancer registry is currently maintained by the Japan Joint Committee of Lung Cancer Registry; this registry contributes to the development of lung cancer treatments and provides TNM classification data. In Japan, the overall 5-year survival rate has improved over time to 52% in 2004; the corresponding rates for each pathologic stage have also improved. Previously, separate registries were maintained for surgical and non-biased cases, whereas a prospective registry for non-surgical cases was added in 2012, and a follow-up examination of those data will be conducted in 2016. In addition, a registry of surgical cases from 2010 will be constructed in 2016. The information provided by these registries should better reveal the status of lung cancer patients in Japan.

Approaches to phase 1 clinical trial design focused on safety, efficiency, and selected patient populations: a report from the clinical trial design task force of the national cancer institute investigational drug steering committee.

The goals and objectives of phase 1 clinical trials are changing to include further evaluation of endpoints such as molecular targeted effects, in addition to dose-toxicity profile of the investigational agent. Because of these changes in focus, the National Cancer Institute and Investigational Drug Steering Committee's Task Force on Clinical Trial Design met to evaluate the most efficient ways to design and implement early clinical trials with novel therapeutics. Clinical approaches discussed included the conventional 3 + 3 cohort expansion phase 1 design, multi-institutional phase 1 studies, accelerated titration designs, continual reassessment methods, the study of specific target patient populations, and phase 0 studies. Each of these approaches uniquely contributes to some aspect of the phase 1 study, with all focused on dose and schedule determination, patient safety, and limited patient exposure to ineffective doses of investigational agent. The benefit of labor-intensive generation of preliminary biomarker evidence of target inhibition, as well as the value of molecular profiling of the study population, is considered. New drug development is expensive and the failure rate remains high. By identifying patient populations expected to respond to the study agent and tailoring the treatment with a novel drug, investigators will be one step closer to personalizing cancer treatment. The "fail early and fast" approach is acceptable if the appropriate patient population is evaluated in the phase 1 trial. The approaches outlined in this overview address the merits, advantages, disadvantages, and obstacles encountered during first in human studies.

Guidelines for the development and incorporation of biomarker studies in early clinical trials of novel agents.

The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) charged the Biomarker Task Force to develop recommendations to improve the decisions about incorporation of biomarker studies in early investigational drug trials. The Task Force members reviewed biomarker trials, the peer-reviewed literature, NCI and U.S. Food and Drug Administration (FDA) guidance documents, and conducted a survey of investigators to determine practices and challenges to executing biomarker studies in clinical trials of new drugs in early development. This document provides standard definitions and categories of biomarkers, and lists recommendations to sponsors and investigators for biomarker incorporation into such trials. Our recommendations for sponsors focus on the identification and prioritization of biomarkers and assays, the coordination of activities for the development and use of assays, and for operational activities. We also provide recommendations for investigators developing clinical trials with biomarker studies for scientific rationale, assay criteria, trial design, and analysis. The incorporation of biomarker studies into early drug trials is complex. Thus the decision to proceed with studies of biomarkers should be based on balancing the strength of science, assay robustness, feasibility, and resources with the burden of proper sample collection on the patient and potential impact of the results on drug development. The Task Force provides these guidelines in the hopes that improvements in biomarker studies will enhance the efficiency of investigational drug development.

The design of phase II clinical trials testing cancer therapeutics: consensus recommendations from the clinical trial design task force of the national cancer institute investigational drug steering committee.

The optimal design of phase II studies continues to be the subject of vigorous debate, especially studies of newer molecularly targeted agents. The observations that many new therapeutics "fail" in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials, further emphasize the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force (CTD-TF) of the National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations about aspects of phase II trial design that are the subject of frequent debate, such as endpoints (response versus progression-free survival), randomization (single-arm designs versus randomization), inclusion of biomarkers, biomarker-based patient enrichment strategies, and statistical design (e.g., two-stage designs versus multiple-group adaptive designs). Although these recommendations in general encourage the use of progression-free survival as the primary endpoint, randomization, inclusion of biomarkers, and incorporation of newer designs, we acknowledge that objective response as an endpoint and single-arm designs remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on characteristic specific to the situation.

[Analysis of the selection process for new drugs in a tertiary hospital 2004-2007]. / Análisis del proceso de selección de nuevos medicamentos en un hospital terciario. Años 2004-07.

OBJECTIVE: The purpose of this study is to describe the structure of the CFyT, the Pharmacy and Therapeutics Committee, and a tertiary hospital's selection process for new drugs. MATERIAL AND METHODS: All annals of the P&TC and the New Drug Incorporation Guides (GINF) to incorporate new drugs received at Hospital Virgen del Rocío between 2004 and 2007 were reviewed. We carried out a descriptive study which collected variables having to do with the drug (drug type, type of register, route of administration and legal category), the petitioner (responsible division, professional category and request type) and the result of the evaluation (final decision, elapsed time between the request and the decision). RESULTS: Of the 72 requested drugs, 45 (62.5%) were approved: six as equivalent treatments, 36 (80%) with specific recommendations, and three (4.2%) with no restrictions. Twelve drugs (81.1%) were not included due to insufficient evidence of their effectiveness compared with the current treatment. The most frequently-requested drug type was the antineoplastics, most commonly requested by Oncology and Haematology divisions. We highlight the fact that many of the petitioners included clinical trials (97.2%) and data referring to costs (84.7%). CONCLUSIONS: There is a high level of compliance with the GINF guide in our centre, which guarantees that the P&TC's final decision is based on scientific evidence.

Pain management pharmacy service in a community hospital.

PURPOSE: The implementation of a pain management pharmacy service in a community hospital is described. SUMMARY: The medical staff at Saint John's Health Center (SJHC) in Santa Monica, California, decided that one of the steps toward the goal of appropriate and adequate analgesia was the addition of a full-time pain management pharmacist (PMP) in 1999 along with a new pain physician. In preparation for the PMP position, the PMP attended conferences and continuing- education seminars on the treatment of acute and chronic pain. The PMP also conducted daily patient rounds with the pain physician. The daily responsibilities of the PMP include printing a daily list of patients using patient-controlled analgesia (PCA), making rounds for all patients receiving PCA, and completing an initial review and evaluation of the patient within 24 hours of starting PCA. In addition, the PMP is responsible for providing recommendations to the attending physician if the patient's pain control is inadequate or if intolerable adverse effects are noted and documenting these recommendations in the physician's progress notes, providing education to the patient regarding PCA use, and recommending a consultation with the pain physician in complicated cases. In the eight-year period that the PMP service has been established, the number of PCA patients has progressively increased more than 50%, from approximately 1200 PCA patients per year in 1999 to 1710 in 2007. CONCLUSION: The pharmacy department at a community hospital successfully implemented a pain management program. The PMP provided pain management services to patients and a valuable resource to other health care staff.

Access to drugs for cancer: Does where you live matter?

BACKGROUND: Provincial governments are responsible for administering publicly-funded anti-cancer drug benefit programs in Canada. This study examines inter-provincial variations in not only the content of such programs, but also the policies/processes used when considering a new drug for coverage. METHODS: Pharmaceutical manufacturers and provincial/regional cancer boards were surveyed to identify the drugs covered by public drug benefit plans. Kappa coefficients were calculated to determine inter-provincial coverage variations. The comprehensiveness of availability of anti-cancer drugs across the country was also assessed. A semi-structured survey of all 10 provincial/regional cancer board pharmacy and therapeutics (P&T) committees was employed to examine decision-making policies/procedures. It included questions on committee composition and processes and on factors influencing decisions regarding the introduction of new drugs. Completed surveys were analyzed using qualitative and quantitative techniques. RESULTS: All cancer boards and 75% of manufacturers contacted provided information on drugs covered in each province. Where lists were obtained from both sources, there was full agreement on content. Kappa values calculated ranged from -0.403 to 0.594, indicating poor to moderate agreement on anti-cancer drug coverage between provinces. Only 7 of the 115 drugs were available in all 10 provinces. Regarding decision-making processes, while ratings for both the relative importance and use of factors involved in decision-making (clinical effectiveness, patient preference, etc.) were similar across provinces, those for the relative importance and use of different information types (clinical trials, expert opinion, etc.) varied. CONCLUSION: Access to anti-cancer drugs clearly varies across the country. In part, this may be due to differences in the views of P&T committees on the usefulness of information they use in their deliberations.

Access to new cardiovascular therapies in Canadian hospitals: a national survey of the formulary process.

BACKGROUND: Access to new therapies in hospitals depends upon both clinical trial evidence and local Pharmacy and Therapeutics (P&T) committee approval. The process of formulary evaluation by P&T committees is not well-understood. OBJECTIVES: To describe the formulary decision-making process in Canadian hospitals for cardiovascular medications recently made available on the Canadian market. METHODS: Postal survey of hospital pharmacy directors in all Canadian hospitals with more than 50 beds. Target drugs included abciximab, enoxaparin, dalteparin, clopidogrel, eptifibatide and tirofiban. RESULTS: Of 428 surveys mailed, responses were received from 164 P&T committees representing 350 hospitals for an effective response rate of 82%. While physicians make up the largest proportion of committee membership, pharmacists play an influential role. Information most commonly cited as influencing formulary decisions included published clinical trials (97%), regional guidelines (90%), pharmacoeconomic data (84%), decisions at peer hospitals (73%) and local opinion leaders (60%). However, this information was often not required on formulary applications. Approval timelines varied widely for target medications but there were no regional, hospital or P&T committee characteristics that were independent predictors of early formulary application or approval. CONCLUSIONS: There is wide variability in the time taken for Canadian institutions to adopt new cardiovascular therapies, which is not explained by regional, hospital or P&T committee characteristics. Standardization of the formulary application and evaluation processes, including sharing of information amongst institutions, would lead to broader understanding of the applicable issues, more objectivity and improved efficiency.

Drug and Therapeutics (D & T) committees in Dutch hospitals: a nation-wide survey of structure, activities, and drug selection procedures.

AIMS: To determine structure, activities and drug selection processes used by Dutch hospital drug and therapeutics (D & T) committees. METHODS: A pretested structured survey questionnaire based on the Australian process and impact indicators, previous research, and consultation of professionals was developed. Subsequently, D & T committees that met predefined selection criteria were asked to participate. RESULTS: The overall response rate was 70% (38/54). D & T committees varied considerably in size and representation of clinical expertise. Although responsibilities were theoretically alike, actual responsibilities were frequently passed on to other authorities, such as pharmacy staff. Few committees used detailed guidelines or decision supportive matrices to establish transparency in drug selection. With respect to drug selection, the value scores on the information resources used, the factors involved, and the selection criteria used varied. Hospital pharmacists were likely to be most involved and to have the greatest impact. A consensus was most difficult to achieve for drugs used in cardiology, oncology, and psychiatry. Interference of industrial marketing strategies on drug selection was recognized and identified. CONCLUSIONS: Our results indicate that Dutch hospital D & T committees differ with respect to their clinical expertise and their activities, a situation comparable with that observed in other countries. Furthermore, the lack of transparency in drug selection was considerable. These findings clarify the differences previously found between Dutch hospital drug formularies.

Japan Clinical Oncology Group (JCOG).

The Japan Clinical Oncology Group (JCOG) is a cooperative oncology group with the aims of conducting, developing, coordinating and stimulating clinical research in Japan on the treatment of cancer and related problems. The purpose of JCOG is to establish and improve the standard of cancer treatment, mainly in solid cancer, through the testing of new therapeutic regimens or combined modalities, using drugs that are newly-approved or already commercially available. Research sponsored by JCOG is accomplished mainly through the execution of large, prospective, randomized, multicenter, clinical trials. In this way, JCOG facilitates the passage of new clinical trial discoveries into state-of-the-art treatment.

Multidisciplinary task force for controlling drug expenses.

The establishment of a multidisciplinary task force to control increasing drug costs is described. From 1986 to 1992, dollars spent on drugs at a 964-bed teaching hospital increased from $9.8 million to $26.8 million, despite a tightly controlled formulary, prudent purchasing practices, prescribing restrictions, an antimicrobial order form program, a target-drug program, and an active pharmacy-run cost intervention program. These increases occurred as a result of changes in the mix of drugs prescribed, increases in outpatient volume, inflation, and price increases resulting from the Omnibus Budget Reconciliation Act of 1990. A multidisciplinary task force composed of seven teams--AIDS and related issues, ambulatory care, medicine, obstetrics and gynecology, pediatrics, surgery, and systems and procedures--was formed to identify ways to reduce drug expenses and enhance revenue. Each team made recommendations designed to reduce the rate of growth of pharmaceutical expenses. To implement these recommendations, the task force used a variety of verbal and written strategies to educate and communicate with physicians, pharmacists, nurses, pharmaceutical company representatives, and patients. A system was developed so that goal achievement could be monitored. The program, which was implemented on September 16, 1991, and continued through September 30, 1992, reduced the growth in drug expense by $2.33 million. As a result of the program, control of the drug expenses became an institutional priority, not merely a pharmacy department priority. By establishing a multidisciplinary team approach involving physicians, administrators, nurses, and pharmacists, a substantial reduction in the growth of drug expenses can be achieved.

Formulary issues at a pediatric hospital: experience at Children's National Medical Center.

At Children's National Medical Center in Washington, DC, patients treated range from premature babies to 21-year-olds. Therefore, a broad base of drug therapy is practiced. University affiliated, the facility serves as the pediatric department for George Washington University School of Medicine. This hospital is seen as an innovator in specialized areas, such as neonatology, pediatric trauma, oncology, and organ and bone marrow transplantation. P & T Committee participation and communication are excellent, allowing members to focus sharply on therapeutic issues. One of their successful strategies has been the institution of a rather extensive subcommittee structure, which has facilitated intense but timely formulary review and strengthened drug policy. In this exclusive Hospital Formulary interview, Dr. George Cohen and Mr. Stephen Allen, Chairman and Secretary of the P & T Committee, respectively, share their experiences, providing insight for other P & T Committee members in hospitals serving both children and adults nationwide.

Achieving an effective committee through reorganization: the Ohio State University Hospital's experience.

The P & T Committee at Ohio State University (OSU) Hospitals, Columbus, is unique in that it accomplishes the bulk of its tasks through subcommittees. Four subcommittees are currently in place: a formulary subcommittee, a policy and surveillance subcommittee, an antibiotic subcommittee, and a therapeutic drug monitoring subcommittee. An advantage to this method of organization is that it allows for much more medical staff involvement in P & T Committee activities. Other unique aspects of this P & T Committee are that it is responsible for maintaining both an inpatient and outpatient formulary, and it provides decision-making services for a specialty cancer hospital. Expansion of their drug usage evaluation program, further development of their therapeutic monitoring program, and improved communication with the medical staff are future goals of this P & T Committee.

P & T Committee problem-solving in a Canadian specialty hospital.

Princess Margaret Hospital in Toronto is a specialty hospital that deals primarily with cancer patients from Ontario Province. In an exclusive Hospital Formulary interview, Dr. Ron Feld, chairman of Princess Margaret's P & T Committee, discusses some of the special challenges and problems that their P & T Committee, working in a specialized referral setting, has faced. He also briefly describes the similarities and differences between Canadian and American P & T practices. Included in his discussion are the formulary addition request process, cost containment strategies, adverse reaction reporting, and the role of the P & T Committee in patient and physician education.