Cost-effectiveness of granulocyte colony-stimulating factors (G-CSFs) for the prevention of febrile neutropenia (FN) in patients with cancer.

PURPOSE: Clinical practice guidelines recommend the use of all approved granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, as primary febrile neutropenia (FN) prophylaxis in patients receiving high- or intermediate-risk regimens (in those with additional patient risk factors). Previous studies have examined G-CSF cost-effectiveness by cancer type in patients with a high baseline risk of FN. This study evaluated patients with breast cancer (BC), non-small cell lung cancer (NSCLC), or non-Hodgkin's lymphoma (NHL) receiving therapy who were at intermediate risk for FN and compared primary prophylaxis (PP) and secondary prophylaxis (SP) using biosimilar filgrastim or biosimilar pegfilgrastim in Austria, France, and Germany. METHODS: A Markov cycle tree-based model was constructed to evaluate PP versus SP in patients with BC, NSCLC, or NHL receiving therapy over a lifetime horizon. Cost-effectiveness was evaluated over a range of willingness-to-pay (WTP) thresholds for incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analyses evaluated uncertainty. RESULTS: Results demonstrated that using biosimilar filgrastim as PP compared to SP resulted in incremental cost-effectiveness ratios (ICERs) well below the most commonly accepted WTP threshold of €30,000. Across all three countries, PP in NSCLC had the lowest cost per QALY, and in France, PP was both cheaper and more effective than SP. Similar results were found using biosimilar pegfilgrastim, with ICERs generally higher than those for filgrastim. CONCLUSIONS: Biosimilar filgrastim and pegfilgrastim as primary prophylaxis are cost-effective approaches to avoid FN events in patients with BC, NSCLC, or NHL at intermediate risk for FN in Austria, France, and Germany.

European Cancer Organisation Essential Requirements for Quality Cancer Care: Adult glioma.

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCCs) are explanations of the organisation and actions necessary to provide high-quality care to patients with a specific cancer type. They are compiled by a working group of European experts representing disciplines involved in cancer care, and provide oncology teams, patients, policymakers and managers with an overview of the essential requirements in any healthcare system. The focus here is on adult glioma. Gliomas make up approximately 80% of all primary malignant brain tumours. They are highly diverse and patients can face a unique cognitive, physical and psychosocial burden, so personalised treatments and support are essential. However, management of gliomas is currently very heterogeneous across Europe and there are only few formally-designated comprehensive cancer centres with brain tumour programmes. To address this, the ERQCC glioma expert group proposes frameworks and recommendations for high quality care, from diagnosis to treatment and survivorship. Wherever possible, glioma patients should be treated from diagnosis onwards in high volume neurosurgical or neuro-oncology centres. Multidisciplinary team working and collaboration is essential if patients' length and quality of life are to be optimised.

Pilot study of a European oncology regimen reference library and matching algorithm.

OBJECTIVES: As yet, there is no European data standard for naming and describing oncology regimens. To enable real-world cancer treatment data comparisons, the Oncology Data Network created a unified reference database for systemic anti-cancer regimens used in practice across Europe. Data are extracted from clinical systems and mapped to a single standard called the "Core Regimen Reference Library (CRRL)". An automated matching algorithm has been designed based on: drug combinations; administration schedule; and dosing and route of administration. Incomplete matches are flagged for expert review. The aim of this pilot study is to have an expert pharmacist panel test the algorithm's feasibility by comparing computerised and manual matching of regimens that are currently in use in different European countries. METHODS: The combined team pooled a diverse sample of 47 reference regimens used in Europe for solid and haematological cancers. These were then codified to the developed common data standard and the algorithm was used to match them to the CRRL. The expert pharmacist panel from the European Society of Oncology Pharmacy (ESOP) selected 12 regimens from the sample set, ranging from simple to complex, and performed a single-blind test of the algorithm, by systematically matching each original regimen to the CRRL. RESULTS: ESOP validated the algorithm's feasibility based on full concurrence between manual and computer matches thereby validating the algorithm rules and logic with regard to what defines the core characteristics of a regimen and how to compare similarities and differences. CONCLUSIONS: ESOP's validation of the matching algorithm and approach to curating a master library provides confidence in their utility for reliable comparison of real-world regimen usage across Europe.

How to improve efficiency in cancer care: Dimensions, methods, and areas of evaluation.

Efficiency in healthcare is crucial since available resources are scarce, and the cost of inefficient allocation is measured in prior outcomes. This is particularly relevant for cancer. The aim of this paper is to gain a comprehensive overview of the areas and dimensions to improve efficiency, and establish the indicators, different methods, perspectives, and areas of evaluation, to provide recommendations for how to improve efficiency and measure gains in cancer care. METHODS: We conducted a two-phase design. First, a comprehensive scoping literature review was conducted, searching four databases. Studies published between 2000 and 2021 were included if they described experiences and cases of efficiency in cancer care or methods to evaluate efficiency. The results of the literature review were then discussed during two rounds of online consultation with a panel of 15 external experts invited to provide insight and comments to deliberate policy recommendations. RESULTS: 46 papers met the inclusion criteria. Based on the papers retrieved we identified six areas for achieving efficiency gains throughout the entire care pathway and, for each area of efficiency, we categorized the methods and outcomes used to measure efficiency gain. CONCLUSION: This is the first attempt to systemize a scattered body of literature on how to improve efficiency in cancer care and identify key areas of improvement. POLICY SUMMARY: There are many opportunities to improve efficiency in cancer care. We defined seven policy recommendations on how to improve efficiency in cancer care throughout the care pathway and how to improve the measurement of efficiency gains.

Identifying options for oncology therapy regimen codification to improve standardization-combined results of an expert panel and a review.

WHAT IS KNOWN AND OBJECTIVE: Chemotherapy drugs are often administered in combinations with predefined interdependent doses and cycle intervals. As yet, there is no global standardization system to describe these complex regimens in a universally comprehensive manner. The aim of this review is to identify which efforts for standardization have been undertaken and which recommendations for databases and nomenclature of chemotherapy regimens are available. METHODS: A literature review was performed to identify all peer-reviewed full-text articles about oncology therapy regimen codification. In addition, the results of this search were evaluated and consensus recommendations from a European expert panel were subsequently added. RESULTS: This review gives an overview of attempts to standardize chemotherapy nomenclature described in the literature, as well as of previously published identified gaps in regimen codification. In addition, we summarized the suggestions for improvement of chemotherapy codification found in the available literature, combining them with the expertise from a European expert panel of oncology pharmacists. WHAT IS NEW AND CONCLUSIONS: We believe that one of the most important error-prevention measures is standardization. However, there is a paucity of data how it may be achieved. Currently available data suggest that standardization has a positive impact on usability for data networks, prescription software, safety and the measurement of the quality of cancer care delivery. Standardization is also a strong pre-requisite for all discussions including oncology pharmacists and oncologists when evaluating chemotherapy regimen in countries in Europe but also all over the world. The recommendations compiled in this review can help to support overdue standardization efforts in this important therapeutic area.

Stakeholder opinions on value in healthcare.

OBJECTIVES: To determine how the value of new medicines is defined from the perspective of different stakeholders in nine European countries. METHODS: We carried out an explorative survey by conducting in-depth qualitative interviews with a range of experts with health technology assessment, clinical provision, health economics, payer, academic and industry experience. Experts were asked to distribute 100 points over a predefined list of attributes related to value. In total, 30 interviews were conducted with seven academics, five clinicians, nine economists, five payers and four providers. Each of these categories was represented in responses from France, Germany, the Netherlands and the UK. RESULTS: Comments on the interview guide were all positive. There was substantial variation in definitions of value provided by respondents. Most respondents indicated that delivering benefits to the patient is a prerequisite for a healthcare product to be of value, but only half included costs or resource use in their definition. Quantitative responses showed that effectiveness and efficacy were considered the most important attributes of value, followed by safety and side effects. Lower scores were given to other attributes, such as dignity and individualism, and invasiveness of the treatment. Resources and costs associated with complications and readmissions were considered important by academics and economists, but not clinicians. CONCLUSIONS: The interview findings indicate that the value of a drug is subjective in being perceived differently by different stakeholders, and for different treatment types. Future research will require evaluation of the views of a larger number of stakeholders in more and different countries to confirm these findings.

Defining and Measuring the Affordability of New Medicines: A Systematic Review.

BACKGROUND: In many healthcare systems, affordability concerns can lead to restrictions on the use of expensive efficacious therapies. However, there does not appear to be any consensus as to the terminology used to describe affordability, or the thresholds used to determine whether new drugs are affordable. OBJECTIVES: The aim of this systematic review was to investigate how affordability is defined and measured in healthcare. METHODS: MEDLINE, EMBASE and EconLit databases (2005-July 2016) were searched using terms covering affordability and budget impact, combined with definitions, thresholds and restrictions, to identify articles describing a definition of affordability with respect to new medicines. Additional definitions were identified through citation searching, and through manual searches of European health technology assessment body websites. RESULTS: In total, 27 definitions were included in the review. Of these, five definitions described affordability in terms of the value of a product; seven considered affordability within the context of healthcare system budgets; and 15 addressed whether products are affordable in a given country based on economic factors. However, there was little in the literature to indicate that the price of medicines is considered alongside both their value to individual patients and their budget impact at a population level. CONCLUSIONS: Current methods of assessing affordability in healthcare may be limited by their focus on budget impact. A more effective approach may involve a broader perspective than is currently described in the literature, to consider the long-term benefits of a therapy and cost savings elsewhere in the healthcare system, as well as cooperation between healthcare payers and the pharmaceutical industry to develop financing models that support sustainability as well as innovation.

The Value of Medicines: A Crucial but Vague Concept.

Health Technology Assessment is increasingly used to evaluate the value of healthcare products and to prioritize resources; however, defining exactly what value is and how it should be measured remains a challenge. In this article, we report the results of a literature review, focusing on nine European countries, with the aim of investigating how value is defined from the perspective of different stakeholders, how definitions of value are used, and how value is incorporated into decision making. Only three articles were identified that presented definitions of value, and there was no single shared definition of value in healthcare, which appears to be a highly subjective concept. The majority of the countries investigated combine clinical assessment with economic evaluation to make reimbursement recommendations; the quality-adjusted life-year is the most commonly used measure of value but does not capture broader aspects of value that may be important to patients and healthcare systems. We describe the use of value-based pricing and multi-criteria decision analysis, two approaches to the incorporation of broader aspects of value into decision making. Overall, we have identified considerable variation in how a product's value is defined by different stakeholders. Although a universal understanding of value in healthcare is important, it is clear that current definitions are insufficient, potentially leading to inconsistent reimbursement decisions. Ultimately, the establishment of clearer policies for defining and measuring value in healthcare is needed, and is likely to lead to improvements in the consistency of decision making.

Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel.

Although there has been a significant increase in the availability and use of oral chemotherapeutic agents, the guidelines around their safe handling are still evolving. Although oral chemotherapy is associated with ease of administration, it has the same exposure risks to health care practitioners, patients, and their caregivers as intravenous formulations, and because it is administered in the home, to the families of patients. However, the general misconception appears to be that exposure risk is low and therefore oral chemotherapeutic agents present little risk and are safer to handle. In a series of three roundtable meetings, a team of international pharmacists from North America and Europe reviewed existing guidelines and identified gaps in recommendations that we believe are important for safe handling. The present article is a compilation of these gaps, especially applicable to manufacturers and distributors, storage and handling, and patient education regarding safe handling. These recommendations, on the basis of our experience and of best practices, provide an international perspective and can be adapted by institutions and practices for development of standardized procedures specific to their needs for the safe handling of oral chemotherapeutic agents.

Clinical and economic aspects of KRAS mutational status as predictor for epidermal growth factor receptor inhibitor therapy in metastatic colorectal cancer patients.

Treatment of metastasized colorectal cancer (mCRC) patients with anti-epidermal growth factor receptor (EGFR)-directed monoclonal antibodies is driven by the results of the KRAS mutational status (wild type [WT]/mutated [MUT]). To find out as to what extent the treatment selection based on the KRAS status had impact on overall costs, a retrospective analysis was performed. Of 73 mCRC patients 31.5% were MUT carriers. Costs of EGFR inhibitor treatment for WT patients were significantly higher compared to those for patients with MUT (p = 0.005). Higher treatment costs in WT carriers reflect a significantly higher number of treatment cycles (p = 0.012) in this cohort of patients. Savings of drug costs minus the costs for the determination of KRAS status accounted for EUR 779.42 (SD ±336.28) per patient per cycle. The routine use of KRAS screening is a cost-effective strategy. Costs of unnecessary monoclonal EGFR inhibitor treatment can be saved in MUT patients.

[Pharmacy standards for clinical trials]. / Pharmazeutische Standards für klinische Studien.

The procurement, transport, storage, manufacturing or compounding, the application, disposal, documentation, and the quality assurance of investigational medicinal products (IMPs) have to be done according to the pharmaceutical sciences. Medicines related to clinical trials in the European Union are regulated in volume 10 of the EudraLex. The rules for commercially manufactured medicines for human use are not valid for medicines which are individually compounded for a certain patient in the pharmacy. They are also not valid for medicines dedicated for experiments in research and development. The present article describes standards concerning the participation of the pharmacy in clinical trials, the pathway of the drug including the role of the study personnel, and its qualification and training. The issue of stability and compatibility of IMPs is an important topic which may influence the outcome of clinical trials. To avoid quality shifts Standard Operating Procedures (SOPs) have to be established.

[Extravasation of cytotoxic agents]. / Paravasation von Zytostatika.

A variety of antineoplastic agents is associated with toxicity to healthy tissue and therefore represents a hazard for patients in case of extravasation. The most common risk factors include patient associated and iatrogenic risk factors. Due to the possible complications after extravasation, the knowledge of these risk factors is the basis for prevention, which is of utmost importance. A classification of antineoplastic agents according to the type of tissue damage includes the categories vesicant, irritant, and non-vesicant. Dependent on the extravasated agent, a series of emergency measures should be considered, preferably adhering to a standard operation procedure. There is good evidence for the successful use of antidotes to some antineoplastic agents. These antidotes are dimethylsulfoxide or hyaluronidase, often combined with topical measures such as cooling or application of heat. The application of sodium bicarbonate, sodium thiosulfate, and heparin is not recommended, whereas the usefulness of corticosteroids is still a matter of controversial discussions. Ambiguity in the management of extravasation is often a consequence of limited clinical evidence. Due to our deficient knowledge about some of the administered cytotoxics, there is ongoing need for action even after decades of therapy with antineoplastic agents.