bluuebunny/crossref_metadata_2025 huggingface dataset:
PP111 Reimbursement And Payment Models: A Survey Of Stakeholders’ Current Experiences And Future Outlook Within The Dutch Policy Setting
Authors: Callenbach Marcelien , Vreman Rick , Mantel-Teeuwisse Aukje , Goettsch Wim
Published: December 2022

Introduction

The constant evolution of high-priced hospital drugs with large uncertainties are increasingly challenging the sustainability of many healthcare reimbursement systems. Consequently, more attention is paid to exploring innovative payment and reimbursement models that may contribute to sustainable healthcare funding mechanisms yet still ensure timely patient access to health intervention. However, more insight is needed into the experiences of stakeholders involved in making payment and reimbursement arrangements as they may play an essential part in successfully implementing innovative reimbursement and payment models in the future.

Methods

Between May and July 2021, a survey was sent out to Dutch stakeholders directly or indirectly involved in payment and reimbursement agreements. The survey questioned the current use of and future preferences for reimbursement and payment models for high priced hospital drugs using Likert scales. Results were analyzed using descriptive statistics.

Results

Our inquiry shows that currently financial-based reimbursement models are applied most often, especially discounts due to their simplicity. In the future, outcome-based reimbursement models are preferred more, particularly pay-for-outcome. The main challenge for implementation is generating evidence in practice.

Upfront payment is currently the most frequently applied payment model, according to the respondents, whereas delayed payment models are preferred to be applied more often. Particularly payment at outcome-achieved models are preferred but they can be administratively difficult to arrange.

The respondents are moderately satisfied with the payment and reimbursing system in the Netherlands, arguing that especially transparency about the final agreement and mutual trust could be improved.

Conclusions

Despite the preference healthcare payers have for using outcome-based reimbursement models and delayed payment models, currently they are rarely applied. The insights from our survey can provide Dutch stakeholders with future direction when implementing innovative reimbursement and payment models. Attention should be paid to which barriers are currently perceived and how policy structures can facilitate implementation. Further research should focus on exploring which combinations of reimbursement and payment models are most likely to be successful in the Netherlands.
PP113 Reimbursement Of Oncology Therapies With Limited Clinical Evidence In The Netherlands
Authors: Smalbrugge David , van Beekhuizen Sophie , Heeg Bart
Published: December 2022

Introduction

The number of novel therapies that achieve registration in oncology based on limited clinical evidence like non-randomized studies (NRS) is increasing. Dutch health authorities determine the therapeutic value of medicines evaluated in randomized controlled trials based on formal criteria for minimal relative efficacy or clinical treatment guidelines. However, there are no criteria to determine the therapeutic benefit of treatments assessed in NRS, which impacts reimbursement and patient access. Additionally, clinicians in the Netherlands see potential clinical benefit in off-label use but are currently unable to prescribe these because of absent clinical evidence.

This review aims to identify and summarize initiatives to improve patient access to oncology therapies with limited or no clinical evidence in the Netherlands.

Methods

Relevant public reimbursement documents for the Netherlands were identified through a pragmatic literature review.

Results

The main initiatives to improve access for therapies with limited clinical evidence are outside regular reimbursement pathways.

The Drug Rediscovery Protocol (DRUP, initiated 2016) and drug access protocol (DAP, initiated 2021) are two initiatives to improve access in solid tumor oncology. DRUP collects real-world data and provides access for targeted therapies in patients with targetable mutations in off-label indications. At least 25 therapies have been included to date.

DAP uses the same data framework to reimburse on-label solid tumor therapies through a managed entry agreement based on response. The first participating therapies are cemiplimab (NRS, failed ZiN reimbursement), entrectinib and larotrectinib (both NRS, tumor-agnostic).

Finally, Dutch clinical experts proposed criteria for therapeutic value of therapies studied NRS in oncology.

Conclusions

Patient access to both off-label and on-label oncology therapies is addressed in DRUP and DAP. New criteria for the therapeutic value of therapies studied in NRS may decrease the relevance of DAP, although these criteria would not address the need for comparative evidence for cost-effectiveness analysis.
PP118 Cyclic Mental Health Technology Assessment with Priority Setting And Involving Stakeholders - A Case Report From The Netherlands
Authors: Böcker Koen , Roebroek Lukas
Published: December 2022

Introduction

For almost ten years a cyclic appropriate care program has been in place in The Netherlands, known as Zinnige Zorg. The program spanned the full International Classification of Diseases (10th Edition). In 2016 a project on mental health was started. A full cycle consisted of four phases: screening (including priority setting), in-depth analysis, implementation and evaluation. During the in-depth analysis phase, the mental health practice as it was provided was compared to the advice in the guidelines. The mental health project is now in the implementation phase. Professionals, mental healthcare institutions, health insurers and patients are now collaborating to reach the goals that have been set at the closure of the analysis phase.

Methods

Project documentation was analysed to describe the way stakeholders were involved in priority setting as well as their subsequent involvement in implementation of appropriate care actions.

Results

The present case report describes two factors that are important in engaging stakeholders:

(i) Priority setting started with interviews with different stakeholders. This led to a selection of 9 themes for investigating appropriate care.

(ii) For these themes stakeholders formulated 45 issues, together with their consequences for mental health patients, without formulating solutions. If necessary they were reformulated as: [group of patients x] experiences [bottleneck y in mental healthcare], this leads to the patients [negative consequence z]. Next, 9 issues were prioritized and 4 selected, with input from the stakeholders.

Finally, two diseases were selected for which the issues were investigated in depth. This focus enables development of specific implementation steps and evaluation of their effects.

Conclusions

Currently, stakeholders are collaborating in a constructive manner in the implementation phase of this cyclic appropriate care program to improve mental health care for patients experiencing psychosis or post-traumatic stress disorder. Important characteristic of the process that might have supported the present collaborative effort in implementation were (i) early involvement of the stakeholders and (ii) an orientation on problems experienced by patients in the priority setting phase.
PP122 Magnetic Resonance-guided High-intensity Focused Ultrasound For Non-surgical Treatment Of Prostate Cancer, Uterine Fibroids, Adenomyosis And Pain In Bone Metastases
Authors: Okesh Makhabbat , Avdeyev Andrey , Benberin Valeriy , Shanazarov Nasrulla , Akhmedullin Ruslan , Bariyeva Gulzada , Akhmetova Makpal , Aimanova Tansolpan
Published: December 2022

Introduction

Magnetic resonance imaging guided high-intensity focused ultrasound (MR-HIFU) is a non-invasive technique with a low risk of complications for the patient and few side effects. Integration with MRI allows monitoring of the temperature regime of thermal doses, which protects important structures from overheating, and at the same time directing a high thermal dose to the target tissue.

MR-HIFU in the treatment of uterine fibroids, prostate cancer and the treatment of pain in bone metastases is compared with both traditional methods of treatment (uterine artery embolization, hysterectomy, prostatectomy, etc.).

Methods

To assess the clinical effectiveness and safety of non-invasive MR-HIFU, a literature search was performed in the MEDLINE database using the following keywords:“MRgFUS” “MR-HIFU”. The following filters were used: (i) article type: meta-analysis, systematic review, guidance; (ii) date of publication: no later than 5 years (from 2016).

Results

According to the search terms, 104 publications were submitted to MEDLINE for keywords. After using filters, 57 publications were identified to familiarize themselves with research abstracts. The analysis included six publications according to PICO criteria.

The use of non-invasive MR-HIFU therapy for the treatment of uterine fibroids, prostate cancer and various forms of metastatic bone lesions does not have convincing evidence of advantages over standard treatment methods (surgical resection, embolization, etc.) and may be used only as an alternative technique or in addition to standard therapy.

Conclusions

Despite some advantages of the MR-HIFU technology, it is experimental and should only be used as an alternative to surgical treatment. Convincing evidence of the efficacy of MR-HIFU treatment in meta-analyses, systematic reviews, and randomized controlled trials has not yet been published.
PP123 Fair Drug Pricing: Review Of Literature And Models
Authors: Wagner Olena , Hurst Samia
Published: December 2022

Introduction

Constantly rising costs of pharmaceuticals and biologics spurred a debate in recent years leading to increasingly persistent public calls to overhaul the existing system of pricing and distributing health technologies. The COVID-19 pandemic exposed the controversies of the current model of access to health commodities in all evidence when the existing discrepancy between the global supply and the global demand in health technology can be viewed as an illustration of a conflict between the neoliberal free market ideal of health innovation genesis and ownership and the original democratic principles of what would now be called sustainable human development.

Methods

Presented here is an integrative literature review of over 265 publications in peer-reviewed journals on Pubmed and Web of Science, academic and “grey” literature, mainly publicism, published in English. We reviewed and analyzed included literature for the purposes of identifying leading ideas with regards to ethical frameworks for evaluating or referencing value for pricing health commodities.

Results

Seven drug pricing models were analyzed in terms of them satisfying the three most common criteria of price adequacy – its fairness (viewed from the point of view of main schools of ethical thought), accountability-for-reasonableness (including transparency of decisions, relevance, existing mechanisms of revisions and governance to ensure compliance), and price functionality. One of the central ideas under controversy is value, its relative character for different contexts due to the high weight of the willingness-to-pay in the value-based health technology assessment (HTA) decisions and the relative value of money, and the attempts to quantify value in a universal way for institutions, patients, and originators.

Conclusions

While the review scored the pricing models on their “public fairness” with volume-based rather than value-based pricing models leading the rating, the main conclusion of the review is that the main meaningful divide is between value creation and value extraction when pricing health innovation.
PP132 Disinvestment Initiatives In Health Care: A Scoping Review Of Systematic Reviews
Authors: Kamaruzaman Hanin , Grieve Eleanor , Wu Olivia
Published: December 2022

Introduction

Disinvestment of ineffective, low value technologies is growing as a priority for international health policy in order to improve quality and maximize value in health care. Different strategies have been implemented at the international and national level using various methods of evidence gathering and technical assessment. However, the success of these initiatives is mixed, with fewer than half of the empirical studies reporting reductions in the use of low value services.

This review explored the role of stakeholders in the disinvestment process by describing the initiatives and analyzing the methods used for reassessment. We also identified the facilitators and barriers related to disinvestment implementation.

Methods

This scoping review was guided by the JBI Manual for Evidence Synthesis and the PRISMA statement for scoping reviews. Strategic literature searches were performed to identify published reviews on disinvestment in health care using the MEDLINE, Web of Science, and Scopus databases. Data were extracted using a predesigned form and then synthesized narratively to identify similarities and differences across the approaches according to prespecified domains.

Results

Sixteen reviews were included. We identified various disinvestment initiatives across 16 countries, with a minimum of 34 initiatives at different levels of implementation and with various agencies responsible for the activities. Two of the most used methods for facilitating disinvestment decisions were program budgeting and marginal analysis (PBMA) and health technology assessment (HTA). Stakeholder involvement was the most important aspect to be addressed since it acts as both a facilitator and a barrier in implementing disinvestment initiatives. Meaningful engagement may be strengthened with continuous stakeholder participation, transparency in methods and processes, and ongoing knowledge transfer.

Conclusions

This scoping review highlights the role of stakeholder involvement in disinvestment, which is a double-edged sword because it both facilitates and hinders disinvestment implementation. The most common methods for assessing candidates for disinvestment are PBMA and HTA, but there is a lack of clarity on which HTA dimension is suitable for a disinvestment process.
PP134 Health Technology Assessment Life Cycle Approach In Asthma Care
Authors: Have Pieter ten , Van Kemenade Geert-Jan
Published: December 2022

Introduction

Within Dutch health care, Zorginstituut Nederland regularly selects topics for reassessment of diagnostic and therapeutic interventions. Until now, about 15 topics have been investigated, such as hip/knee arthrosis, stable angina, low back pain, urinary incontinence, palliative care, retinopathy and asthma.

Methods

For each topic, stakeholders were asked to report what could be improved. Also a working group was created to analyze: what do guidelines recommend, what does actual care look like seen from administrative data, is there a gap between guidelines and delivered care, what can be improved? A report with recommendations was written with a calculation of the impact. Agreements were made on implementation. This report focused on findings relating to asthma.

Results

We identified the multiple issues in the management of asthma: (i) Only 11 percent of patients had their diagnosis confirmed (with spirometry and reversibility or visit to pulmonologist). (ii) 60,000 patients had intensive short acting broncho-adrenegic agents (SABA) without inhaled corticosteroids (ICS) representing overuse of SABA. (iii) 200,000 patients use inhalers that can be empty, without the patient knowing this, as there is no indicator showing the number of actuation/puffs left, which leads to under treatment. (iv) 60.000 patients have aerosol and powder inhalers together, each requiring a different technique, leading to mistakes. (v) 67 percent of asthma adults get a chest x-ray on referral to hospital, which is a high proportion. (vi) 49 percent of patients use inhalers with propellant, which is needlessly high, given their undesirable impact on climate change. This causes 36 million kg co2 equivalent, the same as 36000 extra gasoline cars. (vii) Only 37 percent of patients receive yearly monitoring. We calculated that EUR 14 million annually can be saved as a result of better diagnosis leading to less overdiagnosis and overtreatment and less spacers.

Conclusions

Despite that ‘HTA (Health Technology Assessment) at the doorstep’ has been applied for asthma interventions, we noticed considerable room for improvement. We consider this method important for real HTA life cycle approach.
PP147 Conditional Reimbursement Of Medicinal Products, A Procedure For Orphan Drugs, Conditionals and Exceptionals
Authors: van Heesch Floor , De Vries Marijke
Published: December 2022

Introduction

In 2018 the Dutch Ministry of Health (MoH) introduced a new policy regarding the conditional reimbursement (CR) of drugs in the basic health insurance package. This new policy offers patients with a serious, often rare disease for which no effective treatment is yet available, the possibility of obtaining controlled access to new promising drugs. In the meantime, additional data on (cost-) effectiveness is being collected. The aim was to assess whether this new policy allowed improved inclusion of drugs in the basic health insurance package.

Methods

Marketing authorization holders (MAH) were able to apply for the CR. The drug had to be registered by the European Medicines Agency (EMA) as an orphan drug, conditional or exceptional and address an unmet medical need. The MAH had to submit a dossier which includes a study protocol together with the professionals’ associations, patients’ associations and a research institute. It was possible to engage an ongoing (international) study in the CR application. Based on the proposed study, the National Health Care Institute (ZIN) assessed whether it is possible to determine if the drug should be reimbursed at the end of the CR period. A reduced price was a condition for CR.

Results

Four drugs are currently reimbursed as part of the CR, being: parathyroid hormone, ataluren, larotrectinib and entrectinib. The proposed studies are ongoing and will generate data to support the final reimbursement decision. Progress will be monitored by the researchers and discussed with ZIN.

Conclusions

Four drugs were successfully conditionally reimbursed, concluding the new CR procedure is feasible. Additional data is being collected to aid in the decision on the definitive reimbursement of these drugs. The upcoming period, the focus will be on the quality of the collected data and whether the inclusion of patients is proceeding as planned. The MoH will be informed by ZIN on the study progress annually. The final reimbursement decision is taken at the end of the CR period.
PP148 The Impact Of Health Technology Wales Guidance For Autologous Hematopoietic Stem Cell Transplantation: Two Years Post-Publication
Authors: Elston Lauren , Hughes Sophie , Glarou Eleni , Myles Susan
Published: December 2022

Introduction

Evaluating the impact of health technology assessment (HTA) is vital to measure its contribution to health and social care decision-making and improving citizen outcomes. Health Technology Wales (HTW) is a HTA body committed to evaluating the impact of our work. Here we present HTW’s impact evaluation approach with a case study for autologous hematopoietic stem cell transplantation (AHSCT) for highly active relapsing remitting multiple sclerosis (RRMS).

Methods

Using an outcomes-focused approach based on contribution analysis, HTW has worked with an external evaluation organization to develop a framework to measure the impact of our work. Data on impact was collected from both qualitative and quantitative sources, including social media metrics, surveys, and informal feedback from stakeholders. We engaged with various stakeholders, including clinicians, academics, patient organizations and other HTA bodies.

Results

The technology appraisal and guidance were published in July 2020, recommending AHSCT for routine adoption to treat highly active RRMS. Patient groups welcomed the appraisal findings as an important step forward in recognising the needs of people with RRMS and felt that “people living with MS were listened to throughout the process”. Following publication online, the guidance has had approximately 500 views, and featured on the MS Trust website and in several news articles. The Welsh Health Specialist Services Committee, a commissioning body in Wales, recommended AHSCT for RRMS as a ‘high priority’ for funding in the WHSSC Integrated Commissioning Plan 2021-22.

Conclusions

Since its publication, we have been able to prospectively capture the impact of this guidance through various stakeholders groups and sources. Overall, responses have been positive and the guidance has supported decision makers in Wales. Ongoing evidence capture, including through HTW’s adoption audit processes, will add further understanding to the potential impact of our work.
PP149 A Multidimensional And Multistakeholder Approach: Assessing Ethical, Legal, Organizational, Social or Patient-centered (ELSI+) for Telemedicine In Neurological Diseases
Authors: Toledo-Chávarri Ana , Castaño Alezandra Torres , Rodríguez Janet Delgado , Sacks Analía Abt , Serrano-Aguilar Pedro
Published: December 2022

Introduction

Telemedicine strategies have been broadly introducing in health services during the COVID-19 pandemic, including in care of neurological diseases.

Methods

A rapid realist review was conducted using EUnetHTAs Core Model 3.0 and GRADE evidence to decision frameworks were used as frameworks to describe the ethical, legal, organizational, social and patient aspects (ELSI+) related to the use of teleneurology (TN) A scoping multistakeholder meeting helped defined the scope and research questions of the assessment. Patient representatives, clinicians, scientific society representatives with relevant experience in TN were invited and participated. Industry representatives were also present. Systematic searches for ethical, legal, organizational, social and patients related aspects were conducted. Additional manual searches contributed to contextualize these dimensions in the Spanish context. A narrative synthesis was undertaken.

Results

Main results of the assessment of the ELSI+ aspects of TN were described. TN applications are diverse depending on the condition, objective of care and technology used. The implementation of TN lacks specific legal frameworks which implies legal uncertainty. TN may increase geographical accessibility to neurological care in remote areas and by reducing difficult commuting to specialized care centers. Nevertheless, accessibility is challenged by reduced access to technology, the digital divide, lack of health literacy or technologies not adapted to functional diversity. Therefore, equity is not guaranteed if it is offered as a non-voluntary basis or with no support. TN tends to be accepted by patients and carers if it has enough quality, saves travelling time and costs and does not dehumanize care as it is perceived as more flexible and convenient. Quality of TN needs an interdisciplinary team with skills to coordinate organizational aspects of the implementation which include among others, the planification of the support to patients and carers before, during and after the consultation. Health professionals may also need to learn adapted communicational and technological skills.

Conclusions

The implementation of TN poses many ethical, legal, organizational, social or patient-centered challenges.
PD10 Quality Of Economic Evaluation Of Coronary Stents Based On CHEERS: A Scoping Review
Authors: Ren Yan Feng , Li Fu Ming , Chen Yingyao
Published: December 2022

Introduction

The study aims to systematically review all articles on the economic evaluation (EE) of coronary stenting, to critically assess the reporting quality, and to summarize the results.

Methods

A systematic search was undertaken through seven databases (PubMed, Web of Science, Embase, CNKI, Wanfang data, Vip data and SinoMed.) from inception until March 2021, to identify economic evaluation articles comparing coronary stenting with other therapies, or among different stenting procedures. After screening articles and extracting data independently, we summarized methods, contents, and outcomes of the included articles and appraised their methodological quality using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklists. Then, the literature scores were standardized as a proportion of the total score, and stepwise multiple regression was constructed to verify the factors that might influence the quality of literature.

Results

Of the 3,622 publications identified, 59 articles were included in this review. There were 33 cost-effectiveness studies and 26 were cost-utility studies. The quality of the reports varied between studies, with a standardized mean score of 0.76 (0.40-0.98). According to the Cheers checklist, “Introduction” had the lowest overall score (0.53), with many articles deficient in the description of the study’s perspective; “Discussion” had the highest overall score (0.86), with nearly three-quarters of the articles reporting the full content; “Title and abstract”, “Methods”, “Results”, and “Other” scored 0.71, 0.78, 0.74 and 0.66, respectively. According to the results of the stepwise multiple regression model, “Published year”, “National type”, and “Type of economic analysis” research were significantly associated with the quality of literature.

Conclusion

The quality of current research reports on the economics of coronary stenting is generally satisfactory, but there is potential for improvement and high quality reports can provide evidence to support decision making for policy makers.
PD23 Assessing The Suitability Of Real-World Data For Answering Decision Problems – NICE’s Data Suitability Assessment Tool
Authors: Kincaid Lynne , Ayyar-Gupta Vandana , Rowark Shaun , Kent Seamus , Duffield Stephen , Jonsson Pall
Published: December 2022

Introduction

The National Institute for Health and Care Excellence (NICE) intends to increasingly use real-world evidence in developing guidance. To increase trust in such evidence, NICE has developed a framework for developing and assessing real-world evidence studies, including understanding the value of the selected data source for the decision problem.

Methods

Starting with published high-quality studies about data quality, we developed a conceptual model of the elements needed to understand the quality of a data source. Results from a literature search were then mapped to the model. We used this to design a structured reporting tool, the data Suitability Assessment Tool (dataSAT), and tested it in several cases studies. Additionally, we engaged with internal and external stakeholders to obtain feedback on the tool and revised it accordingly.

Results

DataSAT covers provenance of the data, assessment of data quality, and the data’s relevance to the research question. For data provenance, information is requested about the data source independent of the study’s interests, including the purpose, setting, dates of operation, funding, data specification, and management and quality assurance plans for the data sources. Data quality is covered by quantitively assessing the completeness and accuracy of the following key study elements to inform critical appraisal of the study: population inclusion and exclusion criteria; intervention; comparator; and outcomes and key covariates. The findings on data sources and data quality are then interpreted in terms of relevance to the decision problem. This includes relevance to the population in the United Kingdom, the treatment pathway and care setting, the availability of key study elements, time-related factors such as length of follow up, and the effects of sample size and missing data on the validity of findings.

Conclusions

DataSAT allows summary information on source data, including quality and relevance, to be reported in a structured manner, enabling decision makers to better understand how the data influence the robustness of analyses used in health technology assessment. This helps increase trust in the use of real-world evidence.
PD24 Robust Real-World Evidence Generation In Comparative Effects Studies – NICE’s Methods Guidance
Authors: Duffield Stephen , Kent Seamus , Sharma Manuj , Kincaid Lynne , Ayyar-Gupta Vandana , Rowark Shaun , Jonsson Pall
Published: December 2022

Introduction

Recent reviews have shown that many real-world evidence (RWE) studies suffer from avoidable methodological flaws. Meanwhile, the National Institute for Health and Care Excellence (NICE) is seeing an increase in RWE submissions in Health Technology Appraisals and is keen to support the use of this evidence. However, limited guidance exists for the development and assessment of RWE, risking both missed opportunities for unbiased evidence generation and inconsistent decision making based on that evidence. As part of its RWE framework, NICE has developed methods guidance to provide clear expectations for the conduct and reporting of non-randomized comparative effects studies using real world data.

Methods

A conceptual model and draft framework were developed based on established international best practices in RWE and observational research. This was refined with focused literature searches, for example, on the use of external control arm studies. We then engaged with external stakeholders to incorporate their feedback and develop case studies. A reporting template was developed and tested on multiple use cases.

Results & Conclusions

The guidance stresses the central importance of a target trial approach to study design, e.g., adopting an active comparator, new user design, where possible. Target trial emulation is a useful tool to improve the quality and transparency of RWE studies, helping to overcome selection and confounding biases. Various other study design and analytical approaches are outlined for addressing confounding bias and biases due to missing data, measurement error, or misclassification, which are common challenges in RWE. Alongside traditional approaches to sensitivity analysis, the framework promotes quantitative bias analyses which includes a range of methods to assess and communicate the potential impact of remaining bias to study findings by quantifying the direction, magnitude, and uncertainty of bias. A reporting template, based on common methodological pitfalls, is provided to help evidence developers consider key areas of bias in their work and to inform reviewers of any approaches used to investigate or resolve these.
PD29 Systematic Review With Meta-analysis Of Pharmacokinetic Parameters Of Tyrosine Kinase Inhibitors Used In Chronic Myeloid Leukemia
Authors: Fachi Mariana , de Campos Michel , Junkert Allan , Vilhena Raquel , Böger Beatriz , Cobre Alexandre , Domingos Eric , Leonart Leticia , Tonin Fernanda Stumpf , Pontarolo Roberto
Published: December 2022

Introduction

Therapeutic drug monitoring (TDM) is a cost-effective tool to increase treatments’ efficacy and safety. Analyses of pharmacokinetics proprieties of tyrosine kinase inhibitors (TKI) used for chronic myeloid leukemia (CML) can contribute towards effective TDM, development of tailored treatments and new dosing regimens. We aimed to synthesize the available evidence on pharmacokinetic parameters of imatinib, nilotinib, bosutinib, ponatinib in healthy individuals vs. CML patients.

Methods

Systematic searches were conducted in PubMed, Scopus and Web of Science. We included in vivo studies addressing TKIs’ pharmacokinetics, including maximum observed concentration (Cmax), time of maximum observed concentration (Tmax) and half-life (t1/2). Meta-analyses of event rates (mixed-effect models) were performed for the parameters of interest: area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and from time zero to infinity (AUC 0-∞). Results were presented as event rates with 95 percent confidence intervals. Heterogeneity was assessed using chi-square and I2 statistical tests and considered significant when p<0.05 and high when I2>75 percent (Comprehensive Meta-Analysis v.2 Biostat-Englewood, NJ).

Results

Overall, 50 articles were included for analyses (n=26 imatinib, n=11 nilotinib, n=8 bosutinib, n=5 ponatinib). Most studies were performed in the United States (46.0%), designed as open-label trials (70.0%). Several significant interactions between TKI with enzyme inhibitors (ketoconazole, midazolam, aprepitant, metoprolol, grapefruit juice), proton pump inhibitors (esomeprazole, lanzoprazole, omeprazole), antacids, H2 antagonists (famotidine) and enzyme inducers (St. John’s, rifampicin) were found (p<0.001). Given the significant increase in AUC and Cmax in patients with hepatic/liver impairments currently using TKI, strict therapeutic monitoring is paramount to maintain safety. The between study heterogeneity was rated as moderate to high (I2=75-90%) due the limited number of trials for some drugs, different study design, and populations.

Conclusions

The co-administration of TKI with hepatic enzyme inducers or inhibitors, proton pump inhibitors, antacids, H2 antagonists, as well as in patients with hepatic/liver failures requires caution and additional monitoring. Further well-designed trials are needed to strengthen this evidence for some TKIs, namely bosutinib and ponatinib.
PD36 Outcomes Of Centenaries Hospitalized Due To COVID-19 In A Private Healthcare System
Authors: Camelo Ricardo Mesquita , Cruvinel Horta Maria da Glória , Coelho Ribeiro Geraldo Jose , Beltrão Campos Nelson Otávio , de Oliveira Douglas Ribeiro , Carvalho Lélia Maria de Almeida , de Castro Zocrato Karina , Pitchon dos Reis Daniel , Fernandes Mariana Ribeiro , Terenzi Cunha Patrícia Liz , Dusanek Annemarie , Biscione Fernando Martín , Kelles Silvana
Published: December 2022

Introduction

Life expectancy is increasing worldwide. However, during the COVID-19 pandemic, people 100 years or more (centenaries) were challenged by a potentially fatal disease. We evaluated the outcome of centenaries hospitalized due to COVID-19 in a private healthcare system of Belo Horizonte/Brazil (Unimed-BH).

Methods

Administrative data were collected from the hospital database. Patients were included if they had a severe adult respiratory syndrome due to coronavirus type 2 (SARS-CoV-2) ribonucleic acid identified by quantitative real-time reverse transcriptase polymerase chain reaction (RT-qPCR) or by the International Code of Disease-10th review (ICD-10) hospitalization codes U07.1, B34.2, or B97.2.

Results

From March 1 2020 to October 31 2021, 316.4 ± 12.9 centenaries/month were registered. Eighteen hospitalizations due to COVID-19 were identified. Median age was 101.8 years (inter-quartile range [IQR]:100.7,103.0). Most patients were female (83%). There was a median of 6.0 morbidities per patient (IQR:5.3,7.8), range 2-12 morbidities, among 71 possible morbidities. The most described morbidities were systemic arterial hypertension (94%), dementia (61%), and congestive heart failure (61%). Median length of hospitalization was 6.5 days (IQR:3.3,8.0). No patient was dialyzed. Seven (39%) patients died during hospitalization, of whom 3 (17%) were admitted to the Intensive Care Unit and 2 (11%) were oxygenated by invasive mechanical ventilation. No other patients were admitted to the Intensive Care Unit or invasively mechanically ventilated.

Conclusions

Although the hospitalization rate was low, the mortality rate during hospitalization was high among centenaries. Further research is required to evaluate the actual risks of centenaries to be infected by SARS-CoV-2 and the subsequent outcomes.
PD39 Strategies To Assist People With Disabilities During Health Emergencies, Concerning The COVID-19 – Systematic Review
Authors: Silva Ana Luiza , Ramos Sra Maira , Elias Flávia
Published: December 2022

Introduction

The COVID-19 pandemic has affected thousands of people worldwide. The collapse of health systems led to increased difficulties in accessing health care for people with disabilities. The objective was to define strategies to support the implementation of health care for people with disabilities.

Methods

The protocol for the systematic review was registered on PROSPERO (CRD42021266341). Searches were done in seven databases, using MeSH terms related to COVID-19 and disability, in 2021. We included interventions that addressed health, education and social assistance.

Results

Twenty-nine studies were included. A meta-synthesis identified strategies to assist individuals with disabilities: creation of emergency accommodation and protection programs; flexible work arrangements; cash transfer programs; community participation in planning; establishment of support networks; social assistance even in periods of health emergency; teleconsultation services, telerehabilitation and systems that facilitate the use of digital technologies for telemedicine; inclusive guidelines for computer literacy and learning. The main implementation action was comprehensive health care centered on the needs of people with disabilities, with a focus on training community informants, continuing education of health professionals and caregivers for emergency situations, decentralization of care, identification and elimination of barriers to access.

Conclusions

Even though the focus was on telehealth and social assistance, achieving comprehensive healthcare requires a range of interventions that together will support the reduction of inequity faced by people with disabilities.
PD43 Estimating Societal Costs Associated With Vision Loss And Delayed Cataract Surgery: The Potential Impact Of The COVID-19 Pandemic
Authors: O’Boyle Derek , Naaman Nabeil , Paynton Emily , Dziekan Kristina
Published: December 2022

Introduction

Cataract surgery is the most commonly performed surgical procedure in the UK (approx. 472,000 annually). The suspension of interventions due to the COVID-19 pandemic, has had a devastating impact on patients’ access to care. In the UK a complete cessation of elective cataract surgery during the crisis has been an unfortunate reality and encompassed a 14 week hiatus to services in the National Health Service. Patients on prolonged waiting lists may experience negative outcomes during the wait period, including vision loss, increased risk of falls, and ultimately, poorer health-related quality of life (HRQoL). The objective of this research was to estimate the potential societal costs associated with vision-loss related to prolonged waiting times for cataract surgery, as a consequence of COVID-19 in the UK.

Methods

In this analysis, we present estimates relating to two cohorts: a hypothetical cohort of 1,000 cataract surgeries and quarterly estimates of cataract surgeries in the UK. Quarterly estimates (n=122,969) were chosen to reflect a suspension of cataract surgeries for 14 weeks during the COVID-19 crisis. UK cataract surgery numbers were attained from EUROSTAT. Estimates for decreasing visual acuity for those waiting for surgery were attained from the literature, as were the cost estimates associated with cataract-related sight-loss, which were made up of direct, indirect and intangible costs. Five scenarios (at 20% intervals) were simulated for the cost estimates, assuming from 20 percent to 100 percent clearing of waiting lists.

Results

For cohort 1 (1,000 patients), the societal costs associated patients remaining on waiting list for one year, ranged between GBP 237,765 (EUR 279,533) (20% of patients remain untreated) to GBP 1.18m (EUR 1.39m) (100% remain untreated). For cohort 2 (n=122,969) cost estimates are in the region of GBP 29.23m to GBP 146.18m (EUR 34.36m to EUR 171.73m). Estimates consist of direct (15.6%), indirect (28.7%) and intangible costs (55.6%).

Conclusions

Cataract surgery is a sight saving procedure and its impact on HRQoL is overwhelmingly positive. Prolonged waiting times for cataract patients due to COVID-19 is likely to be associated with significant societal costs.
PD45 Paying For Digital Health: What Evidence Is Needed?
Authors: Burrell Anita , Zah Vlad , Zrubka Zsombor , Asche Carl
Published: December 2022

Introduction

Digital transformation has been promoted by the World Health Organization (WHO), Food and Drug Administration (FDA) and the European Commission (EC) to help improve health outcomes. To ensure sustainability, digital health interventions (DHI) require funding by payers. Evidence-informed decision and policy making requires an assessment of the impact on relevant outcomes vs current healthcare practice. Various national and international organizations are involved in creating or guiding the development of standards for the evidence required for digital technologies.

Methods

We undertook an intensive individual investigation of the websites of leading payer and health technology assessment (HTA) bodies in France, UK, Germany, Belgium, Austria, Finland, Canada, Australia, and the USA to identify new frameworks and any updated information. As the objective focused on evaluation frameworks which were used across DHIs by a particular payer to support pricing and reimbursement decisions, we excluded individual case studies where DHIs had been assessed, regulatory frameworks for approval of DHIs and frameworks which assessed feasibility or applicability of a DHI since these were not directly influencing the decision for funding.

Results

We found six frameworks which directly address digital health interventions for the purposes of pricing and reimbursement: NICE Evidence Standards, FinCCHTA, MSAC, Germany BfArM, Belgium RIZIV and France HAS. The context for the framework and the requirements were compared on parameters including those normally found in HTA and for criteria related to digital technologies. The parameters included varied considerably across the frameworks as did the level of evidence expected to be available for the assessment. In some cases, these related to the level of risk or impact of the intended DHI.

Conclusions

While DHIs are increasingly used in health, HTA is struggling to adapt to assess these technologies. Due to the multidisciplinary nature of digital health (combination of health care and technology), and the speed and rate of change of innovations in this area, an approach based upon the risk assessment posed by the technology seems reasonable. In this way the level of effort can be tailored to those interventions which seek to influence care or predict outcomes rather than those which are tailored to increased awareness of the patient about their condition.
PD50 Value Of Healthcare Journey For Patients With Rare Diseases In The Brazilian Public Healthcare System: Methods And Preliminary Results
Authors: Gargano Ludmila , Salvador Bianca Caroline , Santana-da-Silva Luiz Carlos , Ogata Gabriel , Nita Marcelo Eidi , Félix Têmis Maria ,   JAV-Raras Study Group
Published: December 2022

Introduction

Implementing value-based healthcare (VBHC) services requires the ability to assess and integrate evolution of patient-centered outcomes (PCO), clinical/epidemiological data and resource consumption. Aligned with Porter’s framework of value, the “Value of Healthcare Journey for Patients With Rare Diseases Project” (JAV-RARAS) was implemented to evaluate the value of the healthcare journey of patients with rare diseases (RD) in the Brazilian Public Healthcare System (SUS). The goal of this project is to identify the value (clinical outcomes and costs) associated with the management of RD in the SUS.

Methods

Patients diagnosed with eight pre-defined RD under active clinical follow-up in SUS medical centers were invited. Retrospective data on diagnosis and assistance carried out after diagnosis were collected from medical records. Prospective follow-up of one year will be collected through validated clinical questionnaires on three visits, with an average interval of 6 months. Clinical outcomes include exams and disease-specific features, quality of life, productivity loss, treatment adherence and satisfaction. Total cost of patient’s journey in each medical center will be assessed through Time-Driven Activity-Based Costing method. All data collection is being carried out through the Think Patient Value (TPValue®), a computerized management support system, based on Porter’s paradigm of value.

Results

Thirty-five medical centers currently assisting patients with RD were enrolled, representing all macro-regions in Brazil: Midwest (n=4), North (n=5), Northeast (n=10), South (n=5) and Southeast (n=11). Recruitment started in March, and until November 2021, 28 centers had reported retrospective data of at least one RD. So far, JAV-RARAS recruited patients with osteogenesis imperfecta (number of patients=106), phenylketonuria (n=52), familial amyloidotic polyneuropathy (n=32), classical homocystinuria (n=25), Prader–Willi syndrome (n=30), acromegaly (n=33), hereditary angioedema associated with C1 esterase-inhibitor deficiency (n=42) and mucopolysaccharidosis type-II (n=17).

Conclusions

Future results of JAV-Raras real-world evidence study will bring PCO and costs according to Porter’s Value, bringing insights for decision-makers in SUS. This study was funded by National Council for Scientific and Technological Development –CNPq and Ministry of Health of Brazil –MoH.
PD51 Patient Perspective: A Preliminary Analysis Of The First Year Of The Patient Involvement in CONITEC Meetings
Authors: Portugal Clarice , de Souza Andrea Brigida , Prates Adriana , Almeida Andrija , de Pina Viana Bruna Cabral , Losco Luiza , Canuto Vania
Published: December 2022

Introduction

The Patient Perspective is an initiative to include the testimonials of patients or their representatives at the time of the initial recommendation of health technology assessment (HTA) processes developed by the National Committee for Health Technology Incorporation in the Brazilian Public Health System (CONITEC). It allows these actors to be involved prior to the public consultation. This action is articulated with a framework of strategies to encourage patient and public involvement (PPI) in HTA in Brazilian Public Health System (SUS). This paper aims to analyze the first year of its implementation.

Methods

This is a descriptive study, based on document analysis (minutes of meetings, technical and society reports, videos of CONITEC meetings, tables for internal control, etc.) and systematic observation of the activities related to the initiative. Field notes were taken and their contents were coded, following content analysis criteria.

Results

From December 2020 to November 2021, 1,052 subscribers were registered in 75 public calls, which resulted in the participation of 42 people. The testimonials presented information about the illness experience, its impact on quality of life, use of technologies, and difficulties of accessing and adherence to treatment. The patient perspective has been useful to give visibility to specific dimensions of experiences regarding not only the health conditions but SUS as well. Furthermore, some testimonials produced tensions and repercussions about HTA processes, such as the consideration of aspects or technologies not covered in the clinical studies and thus the HTA, as well as the need of reviewing some results of the technical report.

Conclusions

The patient perspective has had the support of the target audience. Additionally, it has been successful in including various types of participants and different aspects of the experience with the health condition and/or the technologies under evaluation. In general, it has been possible to observe the diversification of modes of PPI and institutional learning towards the improvement of HTA in SUS.