High Cost Of Therapy Research Articles

Malpractice litigation in multidisciplinary cancer care: Navigating medico-legal challenges and shared decision making in India

Healthcare professionals participating in multidisciplinary team (MDT) cancer meetings may not have a comprehensive understanding of their medicolegal responsibilities in current times. This article aims to delineate the principal medicolegal issues pertinent to multidisciplinary cancer care and offer recommendations for future implementation. Key concerns highlighted in this literature encompass patient consent and privacy during MDT meetings, professional liability, the formal expression of dissenting views and the duty of care. The analysis of existing literature prioritizes several recommendations for addressing these issues. Given the limited precedent available for formulating recommendations, this article identifies foundational evidence that can inform the practicing clinicians of these concerns in future MDT practices.Navigating decision-making processes in cancer care poses significant challenges for patients. This article seeks to elucidate the significance of shared decision making (SDM) within the Indian clinical context while pin pointing disparities compared to Western practices. Through a systematic search conducted in Medline and Google Scholar from 2000 to 2019, approximately 400 articles were screened, resulting in the selection of 43 relevant articles (5 from India and 38 from Western sources). The literature underscores a scarcity of information on shared decision making in India as compared to Western contexts, potentially leading to adverse physical, psychological and financial consequences reported by patients. According to one study, While Western data demonstrate extensive involvement of both patients and physicians in consensus-building for treatment decisions, such engagement in India is predominantly observed in tertiary care settings, academic institutions or cases with high therapy costs. Cultural beliefs and biases further influence patient engagement, while communication breakdowns correlate strongly with medicolegal malpractice litigations. Future research endeavours are warranted to explore strategies for integrating shared decision making into routine oncology practice in India. Physicians must actively involve patients or their immediate family members in decision-making processes to ensure a patient-centric approach, thereby mitigating the risks of un-informed decision-making or mistrust in the treating physician's expertise. Efforts such as physician and patient education, tool development, policy formulation, widespread implementation and periodic assessments hold promise for advancing the practice of shared decision making.

Redefining chimeric antigen receptor T-cell (CAR-T) regulation: China's responses to address secondary cancer risks of CAR-T therapy.

Since the United States Food and Drug Administration (FDA) approved the first chimeric antigen receptor T-cell (CAR-T) therapy in 2017, it has marked a major breakthrough in cancer treatment, leading to a surge in global research and applications in this field. In recent years, China has made rapid progress, quickly catching up through heavy investment in CAR-T construction, preparation processes, and treatment strategies. China's CAR-T therapy market is driven by substantial pharmaceutical investment targeting its vast population, yet high therapy costs remain uncovered by basic medical insurance. In November 2023, FDA issued a warning about the risk of secondary cancers in patients undergoing CAR-T therapy, sparking global concern. In fact, the China National Medical Products Administration (NMPA) preemptively implemented a series of measures to address the safety concerns of CAR-T therapy, emphasizing the risk of secondary cancers and advising lifelong monitoring as part of the approval process for CAR-T products. Nevertheless, additional regulatory measures are needed to address emerging risks, particularly the threat of secondary cancers. The authors believe that raising the standards for Investigational New Drug (IND) approval and establishing a dynamic reporting and feedback system based on real-world data will strengthen regulatory oversight and support the sustainable growth of the CAR-T industry in China.

Healthcare Resource Utilization and Associated Costs in Patients With Chronic Graft-Versus-Host Disease Post-Allogeneic Hematopoietic Stem Cell Transplantation in England

Limited evidence suggests chronic graft-versus-host disease (cGvHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases healthcare resource utilization (HCRU) and costs. However, this burden has not been well characterized in England. This study assesses secondary care HCRU and costs for patients following allo HSCT in England with cGvHD and patients who did not develop graft-versus-host disease (GvHD). Further stratification was performed among patients who did or did not subsequently receive high-cost therapies for the treatment of cGvHD. This descriptive, retrospective cohort study used Hospital Episode Statistics (HES) data from April 2017 to March 2022. HES data captures information on reimbursed diagnoses and procedures from all National Health Service (NHS) secondary care admissions and attendances in England. High-cost drugs as defined by NHS England are recorded in HES, these drugs and other procedures including plasma exchange, were used to identify patients with cGvHD who were in receipt of high-cost therapies. HCRU and costs were described for patients with cGvHD following allo-HSCT (n = 721) and were matched with patients with no evidence of GvHD following allo-HSCT (n = 718). HCRU and costs were also described for the subset of patients with cGvHD (n = 198) following receipt of high-cost therapies and patients with cGvHD prior to or without such therapies (n = 523). A higher proportion of patients with cGvHD had at least one inpatient or intensive care unit (ICU) admission or emergency care attendance than patients without GvHD (inpatient: 74.6% versus 66.6%; emergency care: 39.3% versus 30.5%; ICU: 7.4% versus 4.7%; respectively); whilst the proportion of patients with an outpatient attendance were similar for both groups (outpatient: 80.3% versus 84.1%; respectively). The cost across all secondary care settings was higher for patients with cGvHD than patients without GvHD, with a mean cost of inpatient admissions of £17,339 ppy for those with cGvHD versus £8548 ppy in patients without GvHD. A higher proportion of patients who received high-cost therapies for the treatment of cGvHD had at least one secondary care admission or attendance, than patients who did not (inpatient: 85.4% versus 66.4%; ICU: 7.1% versus 5.4%; outpatient: 87.9% versus 76.7%; emergency care: 44.4% versus 36.5%; respectively). Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean number (14.6 versus 8.2 ppy, respectively) for all-cause inpatient admissions after treatment than patients who did not. In all secondary care settings, the total cost ppy was higher for patients who received high-cost therapies for the treatment of cGvHD, than for those who did not. Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean cost (£21,137 versus £15,956 ppy, respectively) for all-cause inpatient admissions than patients who did not. This study demonstrates that cGvHD and the use of associated high-cost therapies impacts healthcare activity and costs across various secondary care settings in England more than patients without GvHD and patients with cGvHD who received no high-cost therapies.

Plant-Based Therapies for Atopic Dermatitis Management: A Review

Dermatological issues pose a frequent challenge for small clinical practitioners, presenting a spectrum of conditions encompassing otitis, pyoderma, anal sac problems, flea allergy, and atopic dermatitis (AD). Atopic Dermatitis (AD) is a chronic and recurring skin condition characterized by distributed skin lesions. In recent decades, researchers have shown a keen interest in AD due to its increased prevalence in developed countries. While various treatment strategies, including biological and immune modulators, are available for AD, each has certain limitations. Researchers have exhibited a significant interest in managing AD with herbal medicines. The use of herbal drugs for AD could potentially eliminate local and systemic adverse effects associated with long-term corticosteroid use, as well as reduce the high cost of therapy with biological drugs. This review discusses traditional East Asian herbal medicines as well as scientific data related to newer herbal extracts or compositions for the treatment of AD. The paper also delves into in vivo animal models and in vitro cell cultures that have been investigated with herbal medicines to establish a potential role in the treatment of AD. In conclusion, herbal medicines could serve as a better and safer complementary and alternative treatment option for AD.

Bevacizumab-Based Therapies in Malignant Tumors-Real-World Data on Effectiveness, Safety, and Cost.

For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. The study consisted of 657 treatment episodes in 625 patients (F/B = 1.62/1, with a median age of 57.6 years) which were treated for malignant tumors (majority colorectal, non-small cell lung, ovarian, and breast cancer). First-line treatment was administered in 229 patients, and the rest received Bevacizumab as second or subsequent lines of treatment. The overall response rate to Bevacizumab-based therapies was around 60-65% across all indication except for subsequent treatment lines in colorectal and ovarian cancers, where lower values were recorded (27.1%, and 31.5% respectively). Median PFS for the entire cohort was 8.2 months (95% CI 6.8-9.6), and the median OS was 13.2 months (95% CI 11.5-14.9). Usual bevacizumab-related toxicities were observed, including bleeding, hypertension, wound-healing complications, gastrointestinal perforation, other types of fistulas, septic complications, and thromboembolic events. Although the clinical benefits are undeniable, the addition of Bevacizumab to standard chemotherapy increased the overall treatment cost by 213%. Bevacizumab remains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Off-label usage is encountered in clinical practice, and this aspect should be monitored given the potential adverse effects of the therapy.

Mental health stigma and internship nursing students’ attitudes toward seeking professional psychological help: a cross-sectional study

BackgroundSelf-stigma and negative attitudes toward mental illness have been identified as significant barriers that hinder individuals from seeking psychological assistance, leading to adverse consequences in their lives.AimThis study aimed to assess mental health stigma and internship nursing students’ attitudes toward seeking professional help.MethodsA cross-sectional design was conducted in the current study including a purposive sample of 228 participants of internship nursing students using a Socio-demographic data sheet, Self-Stigma of Seeking Help scale (SSOSH), and Attitude toward seeking professional psychological help scale (ATSPPH). The data acquisition period spanned from August to November 2022.ResultsThis study revealed significant insights into the attitudes of internship nursing students toward seeking professional psychological help. Gender emerged as a notable factor, with males exhibiting higher levels of self-stigma compared to females (mean = 2.872). Attitudes towards seeking professional help varied significantly based on age, gender, residence, and marital status. Specifically, participants aged 23 years, females, rural residents, and married individuals demonstrated the highest Mean scores reflecting attitudes that lean more positively towards seeking help. Furthermore, a significant negative correlation (r = -0.372, p < 0.01) was observed between self-stigma and attitudes toward seeking professional help.ConclusionThis study concluded that more than three-fifths of internship nursing students hadn’t stigma towards seeking professional psychological help while the vast majority had a positive attitude towards seeking professional psychological help. However, the majority of students reported that financial barriers, specifically the high cost of therapy, prevent them from seeking psychological help. This highlights the need for more affordable mental health services for this population.

Psychometric assessment of patients with treatment-resistant schizophrenia

IntroductionTreatment-resistant schizophrenia (TRS) is one of the most pressing issues in the field of treatment and research of psychotic disorders. The pronounced decline in social and professional functioning in this group of patients as well as high costs of therapy determine high interest in TRS. This is a part of an ongoing study on the clinical and biological features of TRS.ObjectivesThe aim of this study is to identify the leading symptoms in patients with TRS.MethodsUsing the Personal and Social Performance Scale (PSP), Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for schizophrenia (CDSS), 30 male patients (age 28.99 ± 8.08 years) diagnosed with paranoid schizophrenia (F20.0) were examined. All patients had persistent productive symptoms and met the criteria for TRS. The average daily doses of antipsychotics in chlorpromazine equivalent were 1382.07 ± 897.15 mg/day. The average age of onset of the disease was 19.52 ± 5.97 years, the average disease was 9.47 ± 7.61 years.ResultsThe average scores were: on the PSP scale: 46.05 ± 9.17, on the CDSS scale 8.10 ± 4.53, on the PANSS positive symptoms subscale - 21.52 ± 4.24, on the PANSS negative symptoms subscale - 24.67 ± 4.42, on the general psychopathology subscale PANSS – 45.62 ± 6.11 . Positive symptoms were represented mainly by delusions (P1, 4.14 ± 0.85 points) and hallucinations (P3, 4.10 ± 1.76 points). Blunted affect (N1, 4.29 ± 0.56 points) and emotional withdrawal (N2, 3.67 ± 0.73 points) predominated among negative symptoms, while the least prominent negative symptom was poor rapport (N3, 3.24 ± 0.94). The most pronounced general psychopathology symptoms were depression (G6, 4.00 ± 1.10 ) and lack of judgment and insight (G12, 4.05 ± 0.92). The total score on the PANSS was 91.81 ± 12.40.ConclusionsThe CDSS score indicates a high incidence of depressive symptoms in patients with TRS. A low PSP score reflects poor social functioning. The most common symptoms according to the PANSS are delusions, hallucinations, blunted affect, emotional withdrawal, depression and lack of judgment and insight.Disclosure of InterestNone Declared

Challenges and opportunities for access to Advanced Therapy Medicinal Products in Brazil

Background aimsThe marketing authorization of Advanced Therapy Medicinal Products (ATMPs) in Brazil is recent. The features of these therapies impose specialized regulatory action and are consequently challenging for developers. The goal of this study was to identify the industry's experience in clinical development, marketing authorization and access to ATMPs through the Unified Health System (SUS, acronym in Portuguese), from a regulatory perspective. MethodsA survey containing structured questions was conducted among research participants who work at companies that commercialize ATMPs. A descriptive analysis was performed. ResultsWe invited 15 foreign pharmaceutical companies, of which 10 agreed to participate. Overall, participants assessed that Brazil has a well-established regulatory system, especially the sanitary registration by the National Health Surveillance Agency (Anvisa), which ensures the quality, safety, and efficacy of the products. The Agency's good interaction with the regulated sector, the harmonization of sanitary and ethical assessment systems with other countries, and the analysis time in the biosafety assessment of Genetically Modified Organisms (GMOs) stand out as positive in industry's evaluation. On the other hand, it is important to advance the pricing regulation for these products since Brazilian regulations do not establish specific criteria for ATMP. One of the biggest challenges is the difficulty for the SUS in reimbursing these very high-cost therapies, especially using current Health Technology Assessment (HTA) methods. ConclusionsConsidering the increasing number of approvals of cell and gene therapies in Brazil in the coming years, a close dialogue between the industry and the public sector is recommended to advance regulatory improvements (pricing and HTA). Additionally, the construction of policies to promote the national Health Economic-Industrial Complex, based on a mission-oriented vision that encourages innovative models of financing, especially those that consider risk-sharing and co-financing technologies, will help provide the population with universal, equitable and sustainable access to ATMP in the SUS.

Cost and value of cancer medicines in a single-payer public health system in Ontario, Canada: a cross-sectional study

The financial impact of cancer medicines on health systems is not well known. We describe temporal trends in expenditure on cancer medicines within the single-payer health system of Ontario, Canada, and the extent of clinical benefit these treatments offer. In this cross-sectional study, we identified cancer medicines and expenditures from formularies and costing databases (the New Drug Funding Program, Ontario Drug Benefit Program, and The High-Cost Therapy Funding Program) during 10 consecutive years (April 1, 2012, to March 31, 2022) in Ontario, Canada. For intravenous medicines, we applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) to identify expenditures associated with substantial clinical benefit. We also identified treatments associated with improved overall survival or quality of life. 69 intravenous and 98 oral or injectable medicines were funded during 2012-22. Annual expenditure on cancer medicines increased by approximately 15% per year during 2012-22; the increase was more rapid in the most recent 4 years. Total expenditure on cancer medicines in the 2021-22 financial year was CA$1·7 billion. Immune checkpoint inhibitors were the single biggest expense by class ($284 million), representing 17% of the entire cancer medicine annual budget. Drugs with the highest individual costs were lenalidomide ($178 million) and pembrolizumab ($163 million), each accounting for around 10% of the entire budget. 29 (76%) of 38 indications eligible for ESMO-MCBS scoring met the threshold for substantial clinical benefit. Eight (21%) indications had no randomised trial evidence of improved overall survival, and only four (11%) were associated with improved QOL. $346 million (67% of the expenditure on intravenous cancer medicines) was spent on drugs that improved median overall survival by more than 6 months, $82 million (16%) was spent on medicines with overall survival gains of 3-6 months, and $32 million (6%) was spent on medicines with overall survival gains of less than 3 months. $53 million (10%) was spent on medicines with no established improvement in overall survival. Costs of cancer medicines to the Canadian health system are increasing rapidly. Most funded indications met thresholds for substantial clinical benefit and two-thirds of the expenditure were for medicines that improve survival by more than 6 months. Whether this cost trajectory can be maintained in a sustainable, equitable, high-quality health system is unclear. Efforts are needed to ensure the price of medicines with substantial benefit is affordable and funding of treatments with very modest benefit might need to be re-assessed, particularly when alternative supportive and palliative therapies are available. None.

Cost-effectiveness analysis of continuing bevacizumab plus chemotherapy versus chemotherapy alone after first progression of metastatic colorectal cancer.

Continuation of bevacizumab plus second-line chemotherapy has significantly improved overall and progression-free survival in patients with metastatic colorectal cancer (mCRC). However, the cost-effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost-effectiveness of these treatment options from the Chinese health care system perspective. A cost-effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.gov identifier NCT00700102) by modeling a partitioned survival model. Main evaluation indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) with a willingness to pay (WTP) threshold of $38,201 per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the robustness and stability of the model. Subgroup and scenario analyses were also performed to make our study more relevant. Bevacizumab plus chemotherapy increased 0.12 QALYs and an incremental cost of $22,761.62 compared with chemotherapy, resulting in an ICER of $188,904.09 per QALY. The model was most sensitive to the utility of progression-free survival and the cost of bevacizumab. Compared with chemotherapy, bevacizumab plus chemotherapy had a 0% cost-effectiveness probability, and no cost-effectiveness in subgroups at the WTP threshold of $38,201 per QALY. The scenario analysis found that bevacizumab biosimilar gained an ICER of $126,397.38 per QALY when assuming the cost of drugs was calculated at the most affordable price. At the WTP threshold of $38,201 per QALY, continuation of bevacizumab plus chemotherapy is unlikely considered cost-effective for patients after first progression of mCRC.

Biogenic synthesis of iron oxide nanoparticles using Hibiscus sabdariffa extract: Potential for antibiotic development and antibacterial activity against multidrug-resistant bacteria

Expand emergence of antibiotic resistance in different strains of bacteria has become an essential global problem in the health area. This case leads to several medical difficulties such as increased death rates, high therapy costs and long-infected patients remaining in hospitals. This study is designed to evaluate the efficacy of incorporating antibiotics with nanomaterials to combat MDR bacteria. biogenic FeO NPs were synthesised using Hibiscus sabdariffa calyces extract through an eco-friendly and easy method. FeO NPs were subjected to characterisation using some physical techniques, including UV–Visible, FTIR, XRD, SEM and AFM. Characterisation results indicated that the FeO NPs exhibited a crystalline structure, mainly spherical, absorption peak between 290 and 300 nm, and had an average size of 61 nm. The bactericidal activity of the FeO NPs was estimated against three MDR pathogenic bacteria. The results revealed the efficacy of the FeO NPs in inhibiting the growth of the MDR K. pneumoniae, E. coli, and P. aeruginosa. The MIC of the FeO NPs against these bacteria was determined to be 6.25, 12.5, and 25 μg/ml for K. pneumoniae, E. coli, and P. aeruginosa, respectively. Moreover, when combined with antibiotics, the incorporation of FeO NPs significantly enhanced the effectiveness of multiple antibiotics against MDR bacteria. These findings suggest that FeO NPs have promising applications as antibacterial compounds and as additives to enhance antibiotic efficacy.

Insights into the Purification of C1-esterase Inhibitor from Human Plasma

Hereditary angioedema (HAE) is a rare but often life-threatening genetic disorder caused by either lack of or dysfunctional C1-esterase inhibitor (C1-I3NH). C1-INH is a high-cost therapy for HAE. Because plasma-derived C1-INH has a higher half-life than other therapeutics, it may be considered a suitable treatment option for HAE. However, the high cost of plasma-derived C1-INH may make the therapy unaffordable to some patients. Herein, we review the C1-INH purification processes used to date to identify the reasons for the high costs of this therapy and assess the scope of improvements in the purification processes to develop a cost-effective product. A literature search was conducted in PubMed and Google Scholar in January 2023 to identify the relevant articles. The following keywords were used: “C1 esterase inhibitor,” “hereditary angioedema,” and “C1 esterase inhibitor purification from human plasma.” All English-language articles published from 1960 to February 2021 were included. Several plasma products can be purified using the Cohn fractionation process; this decreases the cost of individual products. However, many C1-INH purification strategies developed to date fail to purify other products from the unused plasma fraction (ie, the fraction remaining after C1-INH purification) because of changes in the physical characteristics of the plasma, such as pH and ionic strength; as a result, it is unavailable for the Cohn fractionation process, leading to the high cost of C1-INH. Using cutting-edge purification technologies and more efficient virus removal steps can decrease manufacturing costs, thereby increasing the affordability and safety of the product.

OP43 Translating Cell And Gene Therapy HTA Into Practice – Building The Plane As We Fly It

IntroductionAssessing, funding, and implementing cell and gene therapies are usually based on limited evidence. This requires health technology assessment (HTA) agencies to develop new methodologies; payers to accept risk-based funding; industry to consider the right evidence and price; hospitals to consider if they have the necessary requirements; patients to consider their risk appetite for gene therapies; and health departments to consider all the above. Ensuring timely patient access to these therapies is challenging in Australia’s federated health system. To ensure stakeholders are aligned, all must come to the table and share their respective insights, experiences, and expertise to support planning, decision-making, funding, and commissioning of these therapies. It is time to develop a new consultative and decision-making paradigm to expedite HTAs, funding, commissioning, and timely patient access for cell and gene therapies.MethodsAustralian federal, state, and territory government representatives agreed to develop a framework that clarifies processes around information sharing, HTA, funding, commissioning, and monitoring of highly specialized therapies and services (including cell and gene therapies). A draft national framework was developed that addresses assessment, funding, and implementation of high cost, highly specialized therapies and services (e.g., bone marrow transplants). However, it is unclear whether non-government stakeholders have been consulted.ResultsThe framework for assessing, funding, and implementing high cost, highly specialized therapies and services across Australia’s public hospital system is pending endorsement by each of the jurisdictional governments. High-level in nature, the framework’s primary audiences are industry and public hospitals. While not all processes are in place, the framework is forward-looking. A detailed implementation plan is warranted to better inform the roles and requirements of each stakeholder.ConclusionsThe framework allows stakeholders to better understand government processes regarding assessment, funding, and implementation of high-cost therapies and services, thereby fostering a collaborative environment that supports timely patient access. Articulating process details in a follow-up implementation plan is essential to gain the trust of, and input from, industry, clinicians, and patient representatives.

Use of Health Technology Assessment for the Continued Funding of Health Technologies: The Case of Immunoglobulins for the Management of Multifocal Motor Neuropathy.

Funding decisions for many health technologies occur without undergoing health technology assessment (HTA), in particular, without assessment of cost effectiveness (CE). Immunoglobulins in Australia are an interesting case study because they have been used for a long time for various rare disorders and their price is publicly available. Undertaking an HTA enables us to assess CE for an intervention for which there is limited clinical and economic evidence. This study presents a post-market review to assess the CE of immunoglobulins for the treatment of multifocal motor neuropathy (MMN) compared with best supportive care. A Markov model was used to estimate costs and quality-adjusted life-years (QALYs). Input sources included randomised controlled trials, single-arm studies, the Australian clinical criteria for MMN, clinical guidelines, previous Medical Services Advisory Committee (MSAC) reports and inputs from clinical experts. Sensitivity analyses were conducted to assess the uncertainty and robustness of the CE results. The cost per patient of treating MMN with immunoglobulin was AU$275,853 versus AU$26,191when no treatment was provided, with accrued QALYs of 6.83 versus 6.04, respectively. The latter translated into a high incremental cost-effectiveness ratio (ICER) of AU$317,552/QALY. The ICER was most sensitive to the utility weights and the price of immunoglobulins. MSAC advised to continue funding of immunoglobulins on the grounds of efficacy, despite the high and uncertain ICER. Beyond the ICER framework, other factors were acknowledged, including the high clinical need in a patient population for which there are no other active treatments available. This case study highlights the challenges of conducting HTA for already funded interventions, and the efficiency trade-offs required to fund effective high-cost therapies in rare conditions.

Access and use of WHO essential medicines in Italy.

Many countries use the WHO Essential Medicines List (EML) as a guide for health policy choices to promote the efficient use of healthcare resources or adopt the concept of essential medicines (EMs) to develop their own national list of essential medicines. The aim of this study is to analyse the availability and use of medicines included in the 22nd WHO EML in Italy. Using the ATC code (5th level), a comparison was made between the medicines included in the WHO EML and those retrieved from the Italian Medicines Agency (AIFA) database. The availability (regulatory and reimbursement status) of EMs, as well as the market share in expenditure (million euros) and consumption [measured in WHO-defined daily doses (DDDs)], compared to all reimbursed medicines in 2021, were analysed. In 2021, approximately 85.2% (n = 414) of medicines included in the WHO EML were commonly marketed in Italy. Of these, 396 EMs were fully reimbursed by the Italian National Healthcare Service (INHS), corresponding to 81.5% (396/486) of the WHO EML, while the remaining 18.5% (90/486) were neither authorised (n = 72) nor reimbursed (n = 18). The study found a low coverage for anti-parasitic, insecticides, and repellent products (ATC P) in addition to medicines for the genitourinary system and sex hormones (ATC G). Even though medicines on the WHO EML, including therapeutic alternatives, accounted for ~48.5% of the expenditure for medicines reimbursed by INHS, the list covered 74% of all national drug consumed. Novel high-cost therapies indicated in high-prevalence diseases and rare conditions, mostly antineoplastic and immune-modulating agents (ATC L) not included in the WHO EML, were also guaranteed. In Italy, high coverage of EMs was found. It was largely reimbursed by the INHS, even when compared to other European countries. Essential medicines represented a high percentage of the overall expenditure and consumption in Italy. The WHO EML could be an important tool to guide the health policy choices of high-income countries, although a more frequent update and easier access to information on rejected medicines are needed.

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.

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). 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. 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. 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.

Multiple Myeloma: Current Clinical Landscape and Compounding Costs.

The treatment landscape of multiple myeloma (MM) has evolved resulting in MM becoming a chronic condition. The costs of MM therapies are substantial and compound as patients remain on long-term maintenance therapies and progress through multiple lines of high-cost therapies. MM predominantly impacts the elderly population insured by Medicare; here, we analyze how these costs impact patients and the Medicare trust fund. With the recent passing of the Inflation Reduction Act (IRA), we postulate how costs may be impacted and debate future policy initiatives that may result in sustainability. The IRA will impact drug pricing and likely reduce the costs of some treatments used in MM; there is still a lot of room for policy reform to reduce financial toxicity to patients and prevent depletion of the Medicare trust fund.

(117) Postpartum Vulvovaginal Dryness: Disparities in Adequate Treatment for Postpartum Patients’ Sexual Health

Abstract Introduction Vaginal estrogen therapy (VET) use and efficacy is well established for genitourinary symptoms commonly seen in menopause. Despite the similar symptom profile and dramatic hormonal shifts in postpartum (PP) patients, they are not routinely offered the same therapies. The pathophysiology of these symptoms PP is multifactorial and frequently dismissed as “normal,” even with the subsequent negative effect on their quality of life. Concerns regarding potential harm on lactation and infant development further decreases utilization. However, these apprehensions may be outdated due to evolution of VET, warranting review of available literature. Objective To review the efficacy, concerns, and barriers of utilization of VET for vulvovaginal symptoms in PP patients. Methods A systematic review in the PubMed database spanning from January 1990 – June 2022 was performed to assess the relevant medical literature on the utilization of VET for vulvovaginal symptoms in PP patients. MeSH terms used to narrow the search include: [“dyspareunia” OR “vulvovaginal atrophy” OR “genitourinary”] AND [“hypoestrogenic state” OR “estrogenic endocrine disrupting compounds” OR “estrogen responsive tissues”] AND [“postpartum” OR “menopausal” OR “infant”] AND [“estrogen preparations” OR “vaginal estrogen”]. Results The published literature (n=33) was analyzed by relevant key terms. FDA has approved a number of estrogen-based formulations for vulvovaginal atrophy and dysparenuia in menopausal patients, including: 7.5ug/day (vaginal ring), ultra low dose 10ug (vaginal tablet), 0.01% estradiol creams, premarin (conjugated estrogen) cream, and vaginal DHEA. Data for PP patients is limited with varying results. Nonetheless, drastic improvement in tissue thickening, lubrication, and baseline elasticity within a few weeks of minimal applied dosage of VET has been shown. Addressing primary worries, while higher doses (&amp;gt;50mcg) of estrogen in the early PP period may negatively affect lactation, initiating VET after supply is well established (at 6-8 weeks) or using lower dose estrogen (≤50mcg) has no changes in lactation. In fact, the ultra-low-dose combined oral contraceptive pill (20mcg of ethinyl estradiol with progestins) is approved PP for contraception after 30 days with no adverse impact on breastfeeding. VET concentrations are smaller, and locally applied, implying even less risk of systemic effects. Tolerability is further enhanced with a personalized approach, prescribing the smallest effective dose for the shortest duration of time. Additionally, data suggests that if lactation is affected, there is no significant alteration to the infant’s growth, no to minimal increase of estradiol or estriol in breastfed infants, nor significant evidence of long-term prolongation of physiologic estrogenization. PP patients face numerous barriers, further limiting access to effective treatment, such as: varied clinical presentations, relatively high cost of therapies, minimal time and access to providers resulting in poor communication and hesitation, and limited research focused on therapeutic options for health concerns. Conclusions This review outlines the proven therapeutic uses, indications, and safety of VET, along with the scarcity of current literature for the PP population. The concurrent sexual dysfunction and discomfort can be devastating, supporting the need for focused research on the efficacy of VET connected to the specific needs and concerns of PP patients. Disclosure No

(195) Postpartum Vulvovaginal Dryness: Disparities in Adequate Treatment for Postpartum Patients’ Sexual Health

Abstract Introduction Vaginal estrogen therapy (VET) use and efficacy is well established for genitourinary symptoms commonly seen in menopause. Despite the similar symptom profile and dramatic hormonal shifts in postpartum (PP) patients, they are not routinely offered the same therapies. The pathophysiology of these symptoms PP is multifactorial and frequently dismissed as “normal,” even with the subsequent negative effect on their quality of life. Concerns regarding potential harm on lactation and infant development further decreases utilization. However, these apprehensions may be outdated due to evolution of VET, warranting review of available literature. Objective To review the efficacy, concerns, and barriers of utilization of VET for vulvovaginal symptoms in PP patients. Methods A systematic review in the PubMed database spanning from January 1990 – June 2022 was performed to assess the relevant medical literature on the utilization of VET for vulvovaginal symptoms in PP patients. MeSH terms used to narrow the search include: [“dyspareunia” OR “vulvovaginal atrophy” OR “genitourinary”] AND [“hypoestrogenic state” OR “estrogenic endocrine disrupting compounds” OR “estrogen responsive tissues”] AND [“postpartum” OR “menopausal” OR “infant”] AND [“estrogen preparations” OR “vaginal estrogen”]. Results The published literature (n=33) was analyzed by relevant key terms. FDA has approved a number of estrogen-based formulations for vulvovaginal atrophy and dysparenuia in menopausal patients, including: 7.5ug/day (vaginal ring), ultra low dose 10ug (vaginal tablet), 0.01% estradiol creams, premarin (conjugated estrogen) cream, and vaginal DHEA. Data for PP patients is limited with varying results. Nonetheless, drastic improvement in tissue thickening, lubrication, and baseline elasticity within a few weeks of minimal applied dosage of VET has been shown. Addressing primary worries, while higher doses (&amp;gt;50mcg) of estrogen in the early PP period may negatively affect lactation, initiating VET after supply is well established (at 6-8 weeks) or using lower dose estrogen (≤50mcg) has no changes in lactation. In fact, the ultra-low-dose combined oral contraceptive pill (20mcg of ethinyl estradiol with progestins) is approved PP for contraception after 30 days with no adverse impact on breastfeeding. VET concentrations are smaller, and locally applied, implying even less risk of systemic effects. Tolerability is further enhanced with a personalized approach, prescribing the smallest effective dose for the shortest duration of time. Additionally, data suggests that if lactation is affected, there is no significant alteration to the infant’s growth, no to minimal increase of estradiol or estriol in breastfed infants, nor significant evidence of long-term prolongation of physiologic estrogenization. PP patients face numerous barriers, further limiting access to effective treatment, such as: varied clinical presentations, relatively high cost of therapies, minimal time and access to providers resulting in poor communication and hesitation, and limited research focused on therapeutic options for health concerns. Conclusions This review outlines the proven therapeutic uses, indications, and safety of VET, along with the scarcity of current literature for the PP population. The concurrent sexual dysfunction and discomfort can be devastating, supporting the need for focused research on the efficacy of VET connected to the specific needs and concerns of PP patients. Disclosure No

Early and sustained improvements of lung clearance index from two to sixteen weeks of elexacaftor/tezacaftor/ivacaftor therapy in patients with cystic fibrosis-a real world study.

Since the introduction of CFTR modulator therapies, longitudinal real-life data of lung clearance index (LCI) during treatment is scarce. In this single-centre, post-approval setting, we report data of 51 patients with different stages of lung disease, age 2-52years with repeated measurements of forced expiratory volume as a percentage of the predicted value (ppFEV₁) and LCI after 2, 4, and 16weeks of CFTR modulator treatment and at baseline. In 25 patients during elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) treatment, significant improvements of LCI (median -1.4) and ppFEV₁ (median +8.3%) were observed after only 2weeks, and were maintained after 4 and 16weeks of treatment (LCI: -2.0, -2.2; ppFEV₁: +7.2%, +11.8%). We observed a significant correlation between LCI improvement at week 16 and lower baseline LCI. In 26 younger and healthier patients receiving lumacaftor/ivacaftor (LUM/IVA) treatment, no significant changes of LCI and ppFEV₁ occured. With ELX/TEZ/IVA, our data shows rapid, significant improvements of LCI and ppFEV₁ already after 2weeks. Early LCI measurements can help to assess the patient's response to this high-cost therapy.