Drug Cost Avoidance Resulting from Participation in Clinical Trials: A 10-Year Retrospective Analysis of Cancer Patients with Solid Tumors.

The objective of this single-center retrospective study was to describe the clinical characteristics of adult patients with solid tumors enrolled in cancer clinical trials over a 10-year period (2010-2019) and to assess drug cost avoidance (DCA) associated with sponsors' contributions. The sponsors' contribution to pharmaceutical expenditure was calculated according to the actual price (for each year) of pharmaceutical specialties that the Vall d'Hebron University Hospital (HUVH) would have had to bear in the absence of sponsorship. A total of 2930 clinical trials were conducted with 10,488 participants. There were 140 trials in 2010 and 459 in 2019 (228% increase). Clinical trials of high complexity phase I and basket trials accounted for 34.3% of all trials. There has been a large variation in the pattern of clinical research over the study period, whereas, in 2010, targeted therapy accounted for 79.4% of expenditure and cytotoxic drugs for 20.6%; in 2019, immunotherapy accounted for 68.4%, targeted therapy for 24.4%, and cytotoxic drugs for only 7.1%. A total of four hundred twenty-one different antineoplastic agents were used, the variability of which increased from forty-seven agents in 2010, with only seven of them accounting for 92.8% of the overall pharmaceutical expenditure) to three hundred seventeen different antineoplastic agents in 2019, with thirty-three of them accounting for 90.6% of the overall expenditure. The overall expenditure on antineoplastic drugs in clinical care patients not included in clinical trials was EUR 120,396,096. The total cost of antineoplastic drugs supplied by sponsors in a clinical trial setting was EUR 107,306,084, with a potential DCA of EUR 92,662,609. Overall, clinical trials provide not only the best context for the progress of clinical research and healthcare but also create opportunities for reducing cancer care costs.

Use of Drugs in Clinical Practice and the Associated Cost of Cancer Treatment in Adult Patients with Solid Tumors: A 10-Year Retrospective Cohort Study.

BACKGROUND: Cancer is one of the leading causes of morbidity and mortality in the world. Its growing incidence and prevalence, as well as the advances in diagnostic and treatment tools, motivate an open debate about the economic burden it may place on health systems and have raised concerns about access to this technological innovation. There is a lack of information on the detailed costs of pharmacological treatment of cancer in our health setting. In this context, it is necessary to know the use of drugs in cancer treatment in conditions of real clinical practice. A real-word, evidence-based retrospective cohort study was conducted at Vall d'Hebron University Hospital (VHUH), the largest hospital complex in Catalonia, Spain, in order to determine the use of drugs and the associated cost in real clinical practice for the treatment of solid tumors in adult patients attended at this institution over 10 years (2010-2019). METHODS: This was a single-center retrospective cohort study of adult cancer patients attended in clinical practice at the Medical Oncology Department of VHUH between 1 January 2010 and 31 December 2019. Data of prescription, preparation, and cost of antineoplastic treatments were analyzed by pharmacological class (cytotoxic drugs, immunotherapy, targeted therapy, radiopharmaceuticals, and others), by antineoplastic agent, and by type of tumor. The number of patients and the pharmaceutical expenditure corresponding to all these subgroups were recorded. The cost per patient in each tumor location was also calculated. RESULTS: The study population included 13,209 patients with an overall pharmaceutical antineoplastic expenditure of EUR 120,396,097, increasing from 7.67% in relation to the total HUVH pharmaceutical expenditure in 2010 to 12.82% in 2019. By pharmacological class, the specific weight of the cost of targeted therapy is relevant (75.22% of pharmaceutical antineoplastic expenditure, 21.3% of patients) compared to the group of conventional cytotoxics (17.25% of pharmaceutical antineoplastic expenditure, 76.37% of patients), while immunotherapy has represented the largest relative increase, from 5% in 2014 to 12% in 2019. Eight targeted therapy drugs represented 50% of the costs of the targeted therapy drug class (palbociclib, trastuzumab, pertuzumab, bevacizumab, nivolumab, cetuximab, pembrolizumab, and trastuzumab emtansine). Eleven tumor sites accounted for 90% of the expenditure in 71% of all patients. Breast cancer had the highest expenditure during the study period (EUR 34,332,210) and at each individual year. Melanoma showed the highest increase, with 9.7% of total pharmaceutical antineoplastic expenditure in 2019 (2% of patients), representing a paradigm of the rising costs of cancer treatment due to the incorporation of new high-cost therapies. The average annual cost per patient was highly variable depending on the pathology. There was a growing increase in costs per patient in most tumor locations, particularly in patients with melanoma (from EUR 1922 in 2010 to EUR 37,020 in 2019), prostate cancer (from EUR 2992 in 2010 to EUR 14,118 in 2019), and non-small cell lung cancer (from EUR 3545 in 2010 to EUR 8371 in 2019). The relevance of the difference in monthly cost per patient that has been identified for the different intrinsic subtypes in breast cancer patients during 2019 (HER2+ EUR 2661/month, Luminal EUR 881/month, Triple negative EUR 386/month) makes us consider suggesting differentiated reimbursement rates for certain clinical conditions. Finally, support treatment with antiemetic drugs, erythropoietin stimulating agents, granulocyte-colony stimulating factor (G-CSF), and bone resorption inhibitors has involved a cost of EUR 5,751,910, which represents 4.6% of the overall pharmacological cost of cancer treatment. CONCLUSION: This study provides detailed insights on the oncological pharmaceutical expenditure for the treatment for solid tumors in the VHUH, based on real cost information from our hospital practice and for all antineoplastic therapies and types of solid tumors. This type of information on all the different types of cancer can be useful to better understand the economic burden of the disease and can be decisive for allocating public resources and funds for research, especially in those areas where information is scarce and therefore where further studies are needed. The contribution to knowledge of the cost of oncology therapy is of great value due to its realism and scope.

Comprehensive Multimorbidity Patterns in Older Patients Are Associated with Quality Indicators of Medication-MoPIM Cohort Study.

Multimorbidity is increasing and poses a challenge to the clinical management of patients with multiple conditions and drug prescriptions. The objectives of this work are to evaluate if multimorbidity patterns are associated with quality indicators of medication: potentially inappropriate prescribing (PIP) or adverse drug reactions (ADRs). A multicentre prospective cohort study was conducted including 740 older (≥65 years) patients hospitalised due to chronic pathology exacerbation. Sociodemographic, clinical and medication related variables (polypharmacy, PIP according to STOPP/START criteria, ADRs) were collected. Bivariate analyses were performed comparing previously identified multimorbidity clusters (osteoarticular, psychogeriatric, minor chronic disease, cardiorespiratory) to presence, number or specific types of PIP or ADRs. Significant associations were found in all clusters. The osteoarticular cluster presented the highest prevalence of PIP (94.9%) and ADRs (48.2%), mostly related to anxiolytics and antihypertensives, followed by the minor chronic disease cluster, associated with ADRs caused by antihypertensives and insulin. The psychogeriatric cluster presented PIP and ADRs of neuroleptics and the cardiorespiratory cluster indicators were better overall. In conclusion, the associations that were found reinforce the existence of multimorbidity patterns and support specific medication review actions according to each patient profile. Thus, determining the relationship between multimorbidity profiles and quality indicators of medication could help optimise healthcare processes. Trial registration number: NCT02830425.

Use of chronic medications and risk of severe death due to COVID-19 in hospitalised patients.

OBJECTIVES: To evaluate the potential association between chronic exposure to medication and death related to COVID-19. METHODS: This is a retrospective cross-sectional study that included all patients hospitalised due to COVID-19 from 11 March to 4 June 2020 in our centre. Chronic patient medication was classified by the Anatomical Therapeutic Chemical (ATC) classification; demographic and clinical data were analysed. Multivariate logistic regression models were used to estimate the adjusted odds ratios (aOR) of death for each drug exposure; each aOR represents an independent model adjusted by clinical factors related to COVID-19 mortality. RESULTS: The study included 978 patients with a mean (SD) age of 64.5 (17.7) years who were predominantly male (531, 54.3%). Of all 978 patients, 182 (18.61%) died during the follow-up of the study. The most common Charlson Comorbidity Index (CCI) was 0, 4.2% were smokers, 16.7% were obese, 47.4% had hypertension, and 19.4% were diabetic. Most patients (70.8%) were prescribed at least one treatment, 32.5% used >5 treatments, and 8.6% >10. Our data suggest that COVID-19 hospitalised patients taking trimethoprim and analogues, leukotriene receptor antagonists, calcineurin inhibitors, aldosterone antagonists, selective immunosuppressants, propulsives, insulins and analogues, and benzodiazepine derivatives have a higher risk of death. CONCLUSIONS: This study investigated the association between chronic exposure to drugs and the risk of death in COVID-19 patients. Our results have shed some light on the impact of chronic drug exposure on the risk of severe COVID-19; however, further research is needed to increase the understanding about its relevance.

Factors associated to potentially inappropriate prescribing in older patients according to STOPP/START criteria: MoPIM multicentre cohort study.

OBJECTIVES: The objectives of the present analyses are to estimate the frequency of potentially inappropriate prescribing (PIP) at admission according to STOPP/START criteria version 2 in older patients hospitalised due to chronic disease exacerbation as well as to identify risk factors associated to the most frequent active principles as potentially inappropriate medications (PIMs). METHODS: A multicentre, prospective cohort study including older patients (≥65) hospitalized due to chronic disease exacerbation at the internal medicine or geriatric services of 5 hospitals in Spain between September 2016 and December 2018 was conducted. Demographic and clinical data was collected, and a medication review process using STOPP/START criteria version 2 was performed, considering both PIMs and potential prescribing omissions (PPOs). Primary outcome was defined as the presence of any most frequent principles as PIMs, and secondary outcomes were the frequency of any PIM and PPO. Descriptive and bivariate analyses were conducted on all outcomes and multilevel logistic regression analysis, stratified by participating centre, was performed on the primary outcome. RESULTS: A total of 740 patients were included (mean age 84.1, 53.2% females), 93.8% of them presenting polypharmacy, with a median of 10 chronic prescriptions. Among all, 603 (81.5%) patients presented at least one PIP, 542 (73.2%) any PIM and 263 (35.5%) any PPO. Drugs prescribed without an evidence-based clinical indication were the most frequent PIM (33.8% of patients); vitamin D supplement in older people who are housebound or experiencing falls or with osteopenia was the most frequent PPO (10.3%). The most frequent active principles as PIMs were proton pump inhibitors (PPIs) and benzodiazepines (BZDs), present in 345 (46.6%) patients. This outcome was found significantly associated with age, polypharmacy and essential tremor in an explanatory model with 71% AUC. CONCLUSIONS: PIMs at admission are highly prevalent in these patients, especially those involving PPIs or BZDs, which affected almost half of the patients. Therefore, these drugs may be considered as the starting point for medication review and deprescription. TRIAL REGISTRATION NUMBER: NCT02830425.

A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study).

BACKGROUND: Patient access to orphan medicinal products (OMPs) is limited and varies between countries, reimbursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reimbursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA). METHODS: An MCDA was developed in 3 phases and included 28 stakeholders closely related to the field of rare diseases (6 physicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defined the final list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders' preferences by choosing between pairs of hypothetical financing scenarios. A multinomial logit model was fitted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process. RESULTS: Thirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and economic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efficacy (14.64%), availability of treatment alternatives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%), safety (seriousness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining criteria had a < 3% relative importance: economic burden of disease (2.50%), cost of treatment (1.73%), cost-effectiveness (0.83%) and safety (frequency of adverse events) (0.03%). CONCLUSION: The reimbursement of OMPs in Spain should be determined by its effect on patient's HRQL, the extent of its therapeutic benefit from efficacy and the availability of other therapeutic options. Furthermore, the severity of the rare disease should also influence the decision along with the potential of the treatment to avoid associated costs.

Effects of selective serotonin reuptake inhibitors and other antidepressant drugs on the risk of hip fracture: a case-control study in an elderly Mediterranean population.

OBJECTIVES: To describe the association between exposure to different antidepressant drugs and hip fracture in an elderly Mediterranean population. METHODS: Cases were all patients aged 50-95 years admitted to the emergency room of our hospital with hip fracture not related to a high intensity trauma during 2010. For each case, four controls were identified from primary care electronic medical records matched by age (±3 years), gender, date of consultation at the primary care centre (±1 month) and primary care centre. Pharmacological treatments received within the previous 5 years were retrieved from the prescription records. Crude and adjusted risks associated with exposures were calculated by conditional logistic regression. ORs were adjusted by matching variables and by significant risk factors identified in the bivariate analysis (prescription of ≥4 drugs, osteoporosis, diabetes mellitus and previous fracture). RESULTS: 136 cases and 544 controls were analysed. Adjusted OR (95% CI) for hip fracture associated with exposure to any antidepressants was 2.42 (1.24 to 4.73); for selective serotonin reuptake inhibitors (SSRIs) it was 3.52 (1.67 to 7.41), for non-selective monoamine reuptake inhibitors 1.07 (0.18 to 6.46) and for other antidepressants 0.82 (0.27 to 2.48). Sertraline (OR 3.88 (1.15 to 13.09)) was the only active principle with significant adjusted risk. When only exposures >6 months were considered, significant risks persisted for SSRIs (OR 2.64 (1.10 to 6.37)). CONCLUSIONS: The results of this study are coincident with other studies in which SSRIs, but not other types of antidepressants, are associated with an increased risk of hip fracture in our setting.

Multimorbidity patterns in chronic older patients, potentially inappropriate prescribing and adverse drug reactions: protocol of the multicentre prospective cohort study MoPIM.

INTRODUCTION: Multimorbidity is a major challenge for current healthcare systems and professionals. From the different approaches that have been proposed to analyse this issue, the hypothesis of the existence of association patterns of different chronic conditions is gaining visibility. In addition, multimorbidity can be associated to polypharmacy, which can lead to a higher risk of potentially inappropriate prescribing (PIP) and consequently to adverse drug reactions (ADRs). The general objective of this novel study is to identify the association between PIP, multimorbidity patterns, polypharmacy and the presence of ADRs in older patients admitted for exacerbation of chronic diseases. METHODS AND ANALYSIS: The MoPIM (morbidity, potentially inappropriate medication) study is a multicentre prospective cohort study of an estimated sample of 800 older (≥65 years) patients admitted to five general hospitals in Spain due to an exacerbation of a chronic disease. Patients referred to home hospitalisation, admitted due to an acute process or with a fatal outcome expected at the time of admission are excluded. Sociodemographic data, chronic morbidities and geriatric syndromes, number of chronic prescribed medications, PIP at admission to hospital and on discharge, according to the newest screening tool of older screening tool of older person's potentially inappropriate prescriptions/screening tool to alert doctors to right treatment criteria, and ADRs during hospitalisation are being collected. Multimorbidity patterns will be identified using cluster analyses techniques, and the frequency of polypharmacy, PIP and ADRs will be calculated. Finally, the possible relationship between those indicators will be identified through bivariate and multivariate analyses. ETHICS AND DISSEMINATION: The project has been approved by the clinical research ethics committees of each centre: Comité Ético de investigación Clínica del Parc Taulí, Comitè Ètic d'Investigació Clínica Osona per a la Recerca i Educació Sanitàries (FORES), Comité de Ètica de la Investigación con Medicamentos (CEIm)-Parc de Salut MAR, Comité Ético de Investigación Clínica de Euskadi, Comité de Ética de Investigación del Hospital Universitario de Canarias. The results will be actively and mainly disseminated through publication in peer-reviewed journals and communications in scientific conferences. TRIAL REGISTRATION NUMBER: NCT02830425.

Design of a relative value unit-based tool for the measurement and reimbursement of pharmacy services for clinical trials.

OBJECTIVE: To develop a relative value unit (RVU)-based tool for the measurement and reimbursement of pharmacy services for clinical trials. METHODS: A portfolio of activities was agreed by consensus in four tertiary hospitals. Related activities were pooled into several categories or intermediate products. We recorded the duration of each activity by multiple determinations. We then calculated the average time of all determinations. The reference activity was assigned a value of 1. All other activities were compared to the reference activity to obtain the RVU. To establish which items should be invoiced to third parties for the activities performed, we defined the final products (different types of clinical trials according to their complexity). RESULTS: Ten intermediate products and five final products were differentiated. Six intermediate products could be repeated over the course of a clinical trial and seven were performed whether or not the clinical trial had included patients. Each final product consisted of different categories. The total number of RVUs produced for a clinical trial was the sum of each constant category value plus the repetitive category values multiplied by the number of repetitions. CONCLUSION: The application of RVU methodology in investigational drug services allows a more precise quantification of services performed. After a prospective validation to confirm the applicability of this tool, it may contribute to more appropriate invoicing to third parties for these services.