bluuebunny/crossref_metadata_2025 huggingface dataset:
PP102 Selecting The Sequence Of Diagnostic Tests For Leprosy In Brazil
Authors: Barros Bruno , Magliano Carlos Alberto , Santos Marisa
Published: December 2022

Introduction

Hansen’s disease, or leprosy, is a chronic bacterial infection that affects the nerves, skin, eyes, and nose lining. In 2019, there were 202,256 new cases reported globally, and nearly 28,000 new cases are diagnosed each year in Brazil. The best way to prevent the spread of Hansen’s disease is early diagnosis and treatment of infected individuals. Most diagnoses are done clinically, but only the microscopic analysis of slit-skin smears is funded in Brazil. Serologic and polymerase chain reaction (PCR) tests have also been developed to aid in the diagnosis. The goal of this study was to identify the most cost-effective strategy for increasing the diagnosis of Hansen’s disease in Brazil.

Methods

We examined the impact of the following four strategies using a decision tree model: (i) slit-skin smear only; (ii) PCR test only; (iii) serologic testing followed by slit-skin smear for positive samples; and (iv) serologic testing followed by slit-skin smear for positive samples and PCR test for negative serologic tests and negative slit-skin smears. The accuracy of the tests was determined using a systematic review and meta-analysis and validated by experts. The costs were calculated from the Brazilian health system perspective. Univariate and probabilistic analyses were also conducted.

Results

Serologic testing or PCR followed by slit-skin smear was dominated in the economic model (more false-negative samples and more costly). The addition of serologic testing and PCR to the diagnostic sequence made the strategy more expensive than slit-skin smears alone, but it significantly reduced the percentage of false negative results (from 7.3 to 2.9%) at an estimated cost of USD 533.61 per incremental diagnosis. Disease prevalence was the most important variable in the sensitivity analysis.

Conclusions

This is the first cost-effectiveness model undertaken for Hansen’s disease. The results indicate that incorporating serology and PCR testing into the Brazilian health system could be an appealing option for reducing the spread of Hansen’s disease in Brazil.
PP109 Efficacy And Safety Of High-Intensity Focused Ultrasound In Parkinson’s Disease
Authors: Arias-Pacheco Amparo , del Mar Polo-de-Santos María , Luengo-Matos Setefilla , Hijas-Gómez Ana Isabel , Rodríguez-Ortiz-de-Salazar Begoña , Sánchez-Gómez Luis María
Published: December 2022

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world. High-intensity focused ultrasound (HIFU) is a new non-invasive therapeutic option for treating the motor symptoms of PD. HIFU is an imaging-guided procedure for therapeutic brain ablation that has been used for patients with essential tremor and neuropathic pain. It is indicated for patients older than 22 years of age who have PD that is refractory to drug treatment and are ineligible for surgery. The objective of this study was to conduct an early assessment of HIFU subthalamotomy for the treatment of motor symptoms in patients with PD.

Methods

HIFU was identified by the early awareness and alert system, SINTESIS- nuevas tecnologías, of the Agencia de Evaluación de Tecnologías Sanitarias at the Instituto de Salud Carlos III. Relevant literature published to October 2021 was identified by searching PubMed, EMBASE, ClinicalTrials.gov, and the Cochrane Library.

Results

One prospective study and one randomized controlled trial (RCT) were found that assessed the efficacy and safety of HIFU subthalamotomy for treating the motor symptoms of PD. The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) was used to measure changes in symptoms (>30% change from baseline was considered clinically relevant). Both studies reported a reduction of symptoms in the intervention group. The MDS-UPDRS III score changed from 16.6 to 7.5 six months after treatment in the prospective study and from 19.9 to 9.9 four months after treatment in the RCT (a decrease of 11.6 points was observed after 12 months). The main adverse events reported were dyskinesia, speech and gait disturbances, and weakness, all of which resolved without treatment.

Conclusions

The results regarding the efficacy and safety of HIFU for treating the motor symptoms of PD are promising. HIFU is a non-invasive procedure that eliminates the risks associated with surgery. Although rapid diffusion of this technology is expected, further studies and economic evaluation are needed.
PP119 Results And Lessons Learned From The Cyclic Appropriate Care Program From National Health Care Institute Of The Netherlands
Authors: Maagdenberg Hedy , Stam Mariska , Vreugdenhil Tjitske , Böcker Koen , Groeneveld Iris
Published: December 2022

Introduction

Since 2013, the National Health Care Institute in the Netherlands has systematically analyzed the appropriateness of care provided under public health insurance. Here we present the method used, the results up to now, and what we have learned from it.

Methods

The appropriate care program consists of four phases: screening, in-depth analysis, implementation, and evaluation. Stakeholder involvement is a central part of the process. For every ICD-10 area, a screening took place to select care trajectories for in-depth analysis with a potential for wiser choices and more appropriate care. The in-depth analysis indicates which improvements can be made to reach more appropriate care, by assessing guideline adherence. During the implementation phase, which is primarily carried out by clinicians, patients and health insurers, actions are taken to improve care on the identified points. In the evaluation phase, we examine to what extent improvements have been achieved.

Results

Currently, all ICD-10 areas have been screened and 29 selected care trajectories have been subjected to in-depth analyses. The analyses resulted in the identification of more than a hundred areas for potential improvement of the appropriateness of care. For most topics implementation of changes is currently taking place. The four most important impact-enhancing lessons learned by applying the working method are: (i) ICD-10 areas as a starting point for screening are not the most efficient method to reach the biggest impact. (ii) The screening should take a societal perspective. (iii) All public and private parties involved should fulfill their role and take responsibility. (iv) To fulfill our own role better, the working method should be more connected to health technology assessment for reimbursement decisions.

Conclusions

The program has resulted in the identification of many valuable points for improvement which could lead to more appropriate care in the coming years. The impact of the program could be increased through priority setting from a societal perspective and improving the connection to our other health technology assessment processes.
PP120 Fluorescent In Situ Hybridization (FISH) Vs Conventional Cytogenetic (CC) For Detecting High-Risk Genetic Mutations In Multiple Myeloma
Authors: Komoda Denis Satoshi , Visacri Marilia Berlofa , Correa Carlos Roberto , Santos Daniela , Maia Flavia , Ribeiro Mayra
Published: December 2022

Introduction

The Revised International Staging System (R-ISS) International Myeloma Working Group (IMWG) recommends a minimal panel to detect high-risk cytogenetics (del17p, t[4;14], t[14;16]) for patients with multiple myeloma (MM). In the Brazilian Public Health System, the use of FISH is currently authorized for rare diseases only, not including MM. In 2021, the Brazilian National Committee for Health Technology Incorporation, with the purpose of broadening the use of FISH to MM patients, requested a review to be undertaken by the Health Technology Assessment Center of University of Campinas’ Teaching Hospital. This study presents the results of a meta-analysis comparing FISH vs CC to the detection of the above-mentioned aberrations in MM patients.

Methods

On 25 June 2021, a pre-structured search on four databases (Embase, MEDLINE, Cochrane and LILACS) was performed to identify studies comparing FISH and CC results in MM patients for the detection of high-risk cytogenetics (del17p, t[4;14], and t[14;16]) in MM patients’ bone marrow samples. Study selection, risk of bias assessment, data extraction (frequency of positive tests) and quality of evidence assessment were performed by two independent researchers. Conflicts were solved in agreement meetings with a third researcher. Meta-analysis was performed using frequency of positives to obtain Risk Difference (RD), a surrogate measure of the surplus positive tests between FISH and CC.

Results

From a total of 1346 rendered entries, 11 studies were selected. Only observational studies were available. These studies presented an overall high risk of bias (QUADAS-2). A total of 781 patients were assessed (653 evaluated by FISH and 719 by CC). Meta-analysis results showed that, for t(4;14) FISH detected 12 percent more samples (RD:0.12 [95% confidence interval (CI):0.06-0.19]). For t(14;16), FISH detected 0.42 percent more samples (RD:0.00 [95%CI:-0.01-0.02]). And for del17p, FISH detected 1.6 percent more samples (RD:0.12 [95%CI:0.04-0.20]).

Conclusions

FISH appears to be more effective than CC on the detection of t(4;414) and del17p aberrations, and can be a useful tool in hematology practice. The results of t(14;16) presented non-superiority, probably due to the low frequency of this aberration.
PP125 Economic Evaluation Of Molecular Diagnostics – A Review And Future Directions
Authors: Bouttell Janet , Heggie Robert , Oien Karin , Romaniuk Amy , VanSteenhouse Harper , von Delft Stephan
Published: December 2022

Introduction

It has been suggested that health economists need to adapt their methods in order to meet the challenges of evaluating molecular diagnostics. The aim of this review is to categorize and critically examine the challenges and methodological developments identified from the literature and to suggest how such challenges may be addressed.

Methods

We identified challenges and suggested methodological improvements using a systematic rapid review of the literature. We categorized challenges into those common to all economic evaluations, those common to all diagnostic technologies and those relevant to molecular diagnostics. We assessed whether development in the methods of economic evaluation or alternative action was required.

Results

We found forty-one papers which identified twelve challenges. Choice of perspective and time-horizon were challenges common to all economic evaluations. Five challenges were relevant for all diagnostic technologies: complexity of analysis; range of costs; under-developed evidence base; behavioral aspects; and choice of outcome metrics. The final five challenges were specific to molecular diagnostics: heterogeneity of tests and platforms; increasing stratification; capturing personal utility; incidental findings and spill-over effects. The final five challenges may require methodological development. For example, although methods exist to capture the value of a diagnostic test over and above any health gain captured in a quality adjusted life year (‘personal utility’), there is currently no agreed method of incorporating this into a cost-utility analysis. For the other challenges development of evaluation processes is key. In particular, the weak evidence base for diagnostic technologies may require processes to evolve.

Conclusions

Current methods of economic evaluation are generally able to cope with molecular diagnostics although a renewed focus on specific decision-makers’ needs and a willingness to move away from cost-utility analysis may be required. A key issue is the under-developed evidence-base and it may be necessary to rethink translation processes to ensure sufficient, relevant evidence is available to support economic evaluation and adoption of molecular diagnostics.
PP126 Direct Patient Involvement In HTA In Canada And Brazil: The Patients’ Perspectives
Authors: Silva Aline Silveira , Orecklin Paula , Ferrite Silvia
Published: December 2022

Introduction

Since 2019, Canada’s Drug and Health Technology Agency (CADTH) has worked directly with patients through its Patient and Community Advisory Committee (PCAC). In Brazil, Conitec has worked directly with patients since 2021 through testimonials in its committee meetings for all assessed technologies. In this study we explored patients’ perspectives about their participation in these processes.

Methods

Two patients directly involved with both CADTH and Conitec were invited to share their perspectives about the strengths and weaknesses of the patient engagement processes.

Results

For CADTH, the strengths were as follows: PCAC focuses on the whole organization, including the patient engagement strategy and strategic plan, and is on the same level as other professional committees; PCAC members are compensated; the ‘Learning Sessions’ show CADTH staff the ramifications of their work in people’s lives; and there is increased patient engagement on other committees throughout CADTH. The weaknesses identified with the CADTH process were that PCAC is an advisory body with no decision-making authority and that the diversity of people on the PCAC could be increased. In addition, while CADTH informs and consults patients, the PCAC is not involved in individual HTAs.

The strengths of Conitec’s process were that the volunteer is selected by patients; there are opportunities to consolidate direct patient involvement and promote it in other instances; and the technical support is excellent. On the downside, there was a lack of information about this opportunity; the testimonials last only ten minutes and patients are frequently not questioned; only one patient can participate; there is a lack of transparency about testimonial analysis and its role; and being the only representative during a discussion that culminates in a decision can cause anxiety about performance.

Conclusions

Patients felt heard in the engagement processes and stated that the PCAC embeds patient perspectives throughout CADTH, not just in particular HTAs. One patient felt that her participation was essential for the committees to understand patients’ lived experiences.
PP127 Impact Of Brazilian Patient Testimonials On Medical Devices And Public Confidence In The Healthcare Decision-Making
Authors: Toscas Sra Fotini , de Morais Oliveira Vivian Cardoso , Silva Aline Silveira
Published: December 2022

Introduction

Since October 2020, Conitec has made public calls (PCs) to invite patients and family members to express perspectives during committee meetings. This study seeks to reflect about the impact of the newest patient and public involvement (PPI) Conitec strategy and how it can contribute to increase patient direct involvement and public confidence regarding Brazilian health decisions in medical devices.

Methods

We conducted a document analysis after searching for PCs addressed to medical devices in the section “Patient Perspectives” on Conitec´s website until Aug 31, 2021.

Results

From 64 PCs, five were related to medical devices. Rotational thromboelastometry for transfusion controls: Ended upon applicant request. Transcatheter aortic valve implantation (TAVI): One patient gave his testimonial, explaining how it impacted his quality of life and daily activities, besides answering questions from the committee. The testimonial was not included in the recommendation report. After the public consultation, the initial recommendation changed from non-reimbursement to reimbursement. Botton™ probe for gastrotomy: Eleven people volunteered and a family member was selected. She expressed the importance of the device in her son’s quality of life, making ordinary activities more accessible, helping in the physiotherapy sessions, reducing hospitalizations, and supporting her son’s socialization. The initial recommendation was to reimburse it. iStent Inject Trabecular Micro-Bypass System™ (glaucoma treatment): No patients volunteered. The final recommendation report informed that Conitec received 55 comments through public consultation, including experiences and opinions about the technology. After the public consultation, there was a change from the initial to the final recommendation, from non-incorporation to incorporation. Non-invasive ventilation (cystic fibrosis treatment): There were five volunteers and a mother of twins, both with cystic fibrosis, gave her testimonial. She expressed the importance of this device in her kids’ quality of life, allowing them to sleep better, eat and study, control the symptoms, and reduce hospitalizations and antibiotic usage.

Conclusions

Aspects such as documenting this participation, communicating and offering support to the public and patients, analysis and transparency are essential for evaluating and improving this strategy.
PP131 European Market Access Landscape Analysis Of Reimbursement Drivers In Pompe Disease: Results From 26 Payer Interviews
Authors: MacCulloch Alasdair , Raza Syed , Shohet Simon , Schammel Nico , Net Pierre
Published: December 2022

Introduction

Pompe disease (PD) is a rare, progressive neuromuscular disease that severely affects motor and respiratory functions. Late onset PD (LOPD) is the most common phenotype. Current treatment involves enzyme replacement therapy (ERT) with alglucosidase alfa, which was first approved in 2006. In Europe, the treatment landscape is changing as two new ERTs have been filed for regulatory approval: avalglucosidase alfa and cipaglucosidase alfa plus miglustat. We analyzed how health technology assessment (HTA) and reimbursement criteria may be applied to ERTs in key countries for patients with PD.

Methods

Eighteen different factors were identified from the pivotal trials (LOTS, COMET, and PROPEL) for the three recombinant enzymes. These covered the categories of trial design, endpoints, quality of life, and other product characteristics. Twenty-six HTA experts and health economists from Denmark, England, France, Germany, Italy, the Netherlands, Spain, and Sweden with rare disease experience were interviewed during the period from July to September 2021. In structured discussions, each participant was asked to rate (from one to seven) the factors in terms of their importance and impact on the HTA evaluation and reimbursement of treatments for adults with PD.

Results

The following factors were highly rated: a well-defined PD trial population; use of an active trial comparator; efficacy in both treatment naïve and experienced subpopulations; a superiority study design; and payer-relevant endpoints and quality of life improvements. The five lowest rated factors were open-label data, biomarkers, innovation, ease of administration, and mode of action. While the results were mostly consistent across countries, the HTA expert viewpoints varied depending on the country. For example, HTA experts in Italy, the Netherlands, and Sweden rated innovation and biomarkers more highly than German experts.

Conclusions

As new ERTs become licensed, achieving reimbursement and successful HTA of them will require a clear exposition of payer-relevant evidence for the LOPD population in the target country, including comparative randomized controlled trial data, benefits for experienced and treatment naïve subgroups, and payer-relevant endpoints and quality of life gains.
PP143 International Assessment of the Health Care System in Kazakhstan. A performance analysis.
Authors: Vilariño-López María del Carmen , Kosherbayeva Lyazzat , Zhorayev Olzhas , Zhaksylyk Madi
Published: December 2022

Introduction

Measuring the performance of the health systems is an important challenge at international level. The main objective of this work is to analyze the outcomes of the Kazakhstan Health Care System in order to establish the main causes of avoidable mortality in the country. Also, to identify benchmarking possibilities that may support public policy decisions to improve the results.

Methods

To calculate the avoidable mortality indicators due to preventable and treatable causes, the methodology agreed by the OECD and Eurostat based on the International Classification of Diseases, ICD-10 was applied. Starting from the mortality database of the World Health Organization, the standardized indicators of avoidable mortality was calculated for those countries that had available data based on this classification. Based on the outcomes obtained, a “Two-Step” Cluster Analysis was used to identify and characterize the different clusters of countries that present similar results to identify possible affinities and detect benchmarking possibilities.

Results

The main causes of mortality from treatable diseases in Kazakhstan are those related to the circulatory system, followed by different types of cancer and respiratory diseases.

Applying the cluster analysis in the international context, we find important differences between the different clusters, both in the standardized ratios of avoidable mortality and in its causes. Notable differences have also been identified between Kazakhstan and the countries that make up its cluster. Overall, Kazakhstan presents better avoidable mortality results, both from preventable and treatable causes, than the average of the cluster to which it belongs. However, in some causes of death, it presents worse results and high mortality rates, as in the case of those related to the circulatory and respiratory systems or different types of injuries.

Conclusions

The cluster analysis based on the avoidable mortality indicators reveals different conglomerates of countries that show important similarities between them and also some significant differences. Groups of avoidable diseases that characterize each cluster and subcluster, provide key information for the benchmarking and the design of future actions.
PP145 Improving Patient Expert Involvement In The Lifecycle Of Health Technology Assessments To Build Public Confidence In Decision-Making
Authors: Tonkinson Mandy , Livingstone Heidi , Marsden Laura
Published: December 2022

Introduction

Involving patients in the health technology assessment (HTA) lifecycle is a core principle at the National Institute for Health and Care Excellence (NICE). We include both patient organizations and patient experts, which helps build public confidence in healthcare decision-making. We continually work with patient experts to improve their experience and ability to participate by seeking patient expert feedback after every committee meeting.

Methods

We sent patient experts an anonymous experience survey containing a five-point Likert scale and open text boxes to capture qualitative data. The survey covered their overall experience, interaction with the committee Chair, and the support they received from both NICE and the Public Involvement Programme (PIP).

In the 2019 to 2020 period we sent out 59 questionnaires and received 29 responses (47%), all of which were from medicines HTA committee participants. In the 2020 to 2021 period we sent out 120 questionnaires and received 65 responses (54%), of which 64 were from patient experts who attended medicines HTAs and one was from a medical devices HTA committee participant.

Results

Good or excellent experiences were reported by 90 percent of patient experts. The four main success factors noted were: good support before meetings; being welcomed and respected; well organized meetings; and patient expert input being valued. Areas for further improvement included: providing better briefing before meetings; allowing more time to review documents; providing more technical support; and giving more consideration to the opinions of patient experts.

Conclusions

As a result of the feedback received, the PIP now holds monthly group briefing meetings for patient experts. We also publish the anonymized feedback from the patient experts quarterly in a newsletter for committee members and share the data with internal NICE teams. Additionally, NICE aims to: send committee papers out earlier; have the option of holding a technical engagement call before committee meetings; and develop a feedback mechanism to ascertain the impact of patient input.
PP152 The Assessment Of The Price Of A Medicine: The Possible Application Of Cost-Based Pricing Methods
Authors: Van Den Berg Sibren , Canoy Marcel , Timmers Lonneke , Hollak Carla
Published: December 2022

Introduction

Before admission to the insured package, the price of a medicine is usually assessed on the basis of the value of the medicine for the patient: the effect size on health and survival must be in line with the costs. That seems like a fair starting point, but the use of such ‘value-driven’ models sometimes results in unrealistic prices. These prices in turn lead to discussions about limitations within the healthcare budget and may result in delays in the accessibility of medicines. The aim of this study was to review several alternative pricing models and propose possible applications of the models.

Methods

Six pricing models were selected that encompassed cost-based or cost- and value-based aspects. The models were reviewed within the context of the published group of medicines, followed by a discussion on their potential to aid in creating benchmarks for pricing negotiations.

Results

Five cost-based pricing models and one value-based model with a cost-based aspect were found with potential applications. (i) The AIM-model for innovative medicines. (ii) The adjusted AIM-model for repurposed medicines. (iii) The Cancer drug pricing model for innovative oncolytics with information about health benefit. (iv) The discounted cash flow model for orphan medicines with information about health benefit. (v) The value-based rate of return pricing for innovative orphan medicines with information about health benefit. (vi) The P-quad model for drugs with a high budget impact for which there is no generic competition after intellectual property an regulatory exclusivity end.

Conclusions

We argue that it would be more logical for different categories of medicines to base prices on average costs, possibly combined with a bonus for innovation: the cost-based pricing method. The next step is to discuss the possible application of cost-plus methods with stakeholders including patients, industry, payers, and healthcare professionals.
PP153 The Economic And Fiscal Impact Of Public Health Programs For Diabetic Patients In Italy
Authors: Di Brino Eugenio , Basile Michele , Rumi Filippo , Calabrò Giovanna Elisa , Cicchetti Americo
Published: December 2022

Introduction

Technological innovations in the health sector have economic implications that go beyond their effects on health expenditure, expanding into other areas of the state budget (e.g., the social security system). Furthermore, innovation can affect the production of wealth by workers and companies, which in turn affects tax revenues. In addition, the presence of chronic diseases tends to reduce the propensity to consume and changes the allocation of consumption between the different sectors. Allocative decisions in the health system are rarely supported by an analysis that combines the health effects of innovations and their consequences in the economic system.

Methods

The objective of this study was to estimate the value of management programs for patients suffering from type 2 diabetes mellitus that involved different levels of use of innovative technologies and drugs. A tax impact assessment methodology was adopted in the context of chronic conditions to analyze the effect of adopting alternative management models for patients with diabetes on the broader economic system.

Results

Assuming a policy that reduces annual complications by 0.42 percent, there was an increase in tax revenue (cumulative value) of approximately EUR 28,175 and a reduction in productivity losses (cumulative value) of EUR 4,049,890. Projecting the impact on the age trend of the population up to 65 years of age with these estimates, it is possible to have an increase in tax revenue (cumulative value) equal to approximately EUR 7,050,598 and a reduction in productivity losses (cumulative value) equal to EUR 140,235,923.

Conclusions

In light of this work, providing remote patient support (telemedicine) and expanding the provision of innovative oral antidiabetic drugs to family physicians could improve care for patients with type 2 diabetes mellitus. This study provides decision makers with an immediately usable model to broaden the information base for planning and regulatory choices. In addition, it supports the use of economic evaluations that calculate the entire value of a technological innovation or health program.
PD07 Cost-Effectiveness Of Direct Oral Anticoagulants In Chinese Patients With Non-Valvular Atrial Fibrillation
Authors: Peng Kuan , Li Yihua , Li Xue
Published: December 2022

Introduction

The emergence of direct oral anticoagulants (DOACs) has revolutionized the prevention of stroke-related non-valvular atrial fibrillation (NVAF). Although several DOACs are available, studies comparing the cost effectiveness of DOACs with vitamin K antagonists for NVAF are scarce. The objective of this study was to assess the cost effectiveness of DOACs and warfarin from the Hong Kong public institutional perspective to inform formulary listing decisions.

Methods

A previously developed Markov model was adapted to simulate the lifetime disease progression of a hypothetical cohort of 1,000 patients. Net monetary costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed for the following competing alternatives: warfarin, apixaban (5 mg twice daily), dabigatran 110mg or 150mg (twice daily), and rivaroxaban (20mg once daily). Model inputs were sourced from local real-world evidence, landmark trials, and comprehensive literature reviews. Probabilistic sensitivity analyses and deterministic sensitivity analyses were conducted to address study uncertainties. The willingness-to-pay threshold was set at one times the gross domestic product (GDP) per capita (USD 46,091) per QALY gained.

Results

In base case results, all DOACs provided greater improvements in QALYs at a lower cost than warfarin. Using apixaban as the reference for comparisons among the DOACs, dabigatran 110 mg resulted in greater costs and lower QALY gains and was dominated by apixaban, whereas dabigatran 150 mg provided an incremental QALY of 0.005 at an incremental cost of USD 326, leading to an ICER of USD 67,633 per QALY. The lifetime cost associated with rivaroxaban was lower than for apixaban (-USD 151), but with lower QALY gains (-0.147), resulting in an ICER of USD 1,029 per QALY. In probabilistic sensitivity analysis, the probability of warfarin, rivaroxaban 20 mg, dabigatran 110 mg, dabigatran 150 mg, and apixaban 5 mg being cost effective out of 2,000 iterations was 0 percent, 0 percent, 29.4 percent, 33.2 percent, and 37.4 percent, respectively.

Conclusions

The results indicated that apixaban was the most cost-effective treatment in the management of NVAF, compared with other DOACs and warfarin. This conclusion was consistent under all the uncertainty test scenarios.
PD14 A New Equitable Biomedical Research And Development Model: Preliminary Findings From A Pilot Study Applying VALIDATE Value Methods
Authors: Espriu Marina , Bigorra Joan , Gallo Pedro , Sampietro-Colom Laura
Published: December 2022

Introduction

The public health areas without commercial value continue to be underserved, while those of high profit for industry will not be sustainable for much longer. We hypothesize that the lack of equity and efficiency in the biomedical research and development system is mainly due to a pharma-led short-term profit orientation that ignores the values of other relevant stakeholders.

This pilot study reached some consensus on the principles of a co-created biomedical research and development process based on the preferred supplier (PS) model, which proposes a public health procurement system prioritizing business with companies fulfilling the “4 Share” criteria of priorities, risks and rewards, results, and outcomes to ensure that health needs are met.

Methods

A constructive health technology assessment, which included VALues In Doing Assessments of health TEchnologies (VALIDATE) methodology, was used to analyze the values and dissent of a pilot sample of ten global key informants. The methodology comprised qualitative techniques such as an online preliminary survey, in-depth semi-structured interviews, and a Delphi survey to reach a joint construction by reconstructing the stakeholders’ interpretive frames and applying an adaptation of the Richardson model to contested values.

Results

There was consensus on combining efficiency and social justice norms by incentivizing diseases affected by market failure due to small subpopulations (e.g., rare diseases), low availability to pay, restricted use (e.g., antibiotics), and difficulty demonstrating results (e.g., Alzheimer’s disease). Stakeholders mainly agreed on the PS 4 Share principles, highlighting the need for price to be linked to impact modulated by tracked research and development costs and investments, as proposed by the PS model. More market incentives such as push, and especially pull incentives (market access), should be included. The PS model should be cause-solution oriented, promote open-disruptive innovation, and guarantee fast patient access.

Conclusions

The PS model achieved multistakeholder consensus for desirability (values) and plausibility (shifting incentives). Stakeholders pointed out the need to apply health technology assessment to further develop the model and pilot it in the European Union with the NextGenerationEU.
PD15 Horizon Scanning To Nominate Subsidy Evaluation Topics For Medical Technologies: Early Experience From Singapore
Authors: Ju Hong , Ng Zhen Long , Ling Jeffrey , See-Toh Rachel , Ng Kwong
Published: December 2022

Introduction

Horizon scanning (HS) is an early health technology assessment (HTA) method for raising early awareness among policymakers of promising new and emerging health technologies. The Agency for Care Effectiveness (ACE) in Singapore established a HS system in 2019 to complement its HTA process. While the HS system initially focused on cell and gene therapies, this was expanded in 2020 to include medical technologies (MTs). This abstract focuses on the role of HS in nominating MTs for early evaluation to guide subsidy decisions, with the intention of avoiding challenges in altering deeply entrenched practices.

Methods

The ACE methodology for HS aligns with the core principles and methods of international best practice. Generally, MTs addressing national healthcare priorities are tracked. To identify topics for subsidy evaluation, the local registration status of an MT was used as the main selection criterion because of its proximity to the technology’s early diffusion into the healthcare system. MTs with regulatory approval were selected for HTA and subsidy consideration. All nominated technologies were checked against eligibility criteria for HTA and then assessed against a standard checklist for prioritizing HTA topics.

Results

Among the 1,025 MTs tracked by the HS system, 89 were locally registered and nominated for HTA. Following eligibility assessment, 26 topics remained. After the prioritization exercise six topics were shortlisted. To date, two evaluations have been completed to guide subsidy decisions and four topics are undergoing evaluation. Notably, 16 of the 26 eligible topics were excluded due to a lack of sufficient evidence, in terms of both quantity and quality, for evaluation.

Conclusions

HS can be a useful tool for identifying new MTs for evaluation and possible funding prior to further diffusion, but careful selection of the technologies is required to ensure a sufficient evidence base for evaluation. Moving forward, HS can also play a more active role in disinvestment of obsolete or low value health technologies.
PD16 Reassessment And Selection Strategy Of Dipeptidyl Peptidase-4 Inhibitors For Ministry Of Health Malaysia Medicine Formulary
Authors: Idrus Nazatul Syima , Low Ee Vien , Md Yusof Faridah Aryani , Mahamad Dom Siti Hajar , Abd Rahim Sarahfarina
Published: December 2022

Introduction

The number of anti-diabetics listed in the Ministry of Health Medicine Formulary (MoHMF) and the proposal to change prescribing category for usage in primary care facilities has increased each year causing difficulty in monitoring effectiveness, safety and rational use of the treatment and budget management. This study aimed to describe the reassessment and selection strategy of Dipeptidyl Peptidase-4 Inhibitors (DPP4-i), a class of anti-diabetic medicines in the MoHMF.

Methods

A literature review on the comparative effectiveness and safety of all available DPP4-i in MoHMF were conducted. Comparative treatment cost and utilization of DPP4-i were analyzed. Approved MoHMF indications were listed and compared against approved Drug Control Authority (Malaysia) indications. Information on clinical guidelines recommendations and listing or reimbursement status in non-Ministry of Health Malaysia (MoHM) public institutions and other countries were obtained. All findings were presented to MoHM drug expert committee for DPP4-i selection strategy. The final recommendation based on consensus among drug expert committee and Pharmaceutical Services Program were presented to the MoHMF Panel.

Results

The MoHMF Panel acknowledged that the efficacy and safety profile of all DPP4-i were equivalent across therapeutic group as supported by strong evidence, hence, their selection can be made via cost-minimization strategy. The call for contract tender for single tablet was conducted based on therapeutic group (drug class) to encourage price competition and contracts were awarded to two DPP4-i which offered the lowest treatment costs. Saxagliptin and vildagliptin were awarded as contract items while sitagliptin remained as local purchase item. Prescribing category for all DPP4-i in MoHMF were streamlined accordingly. Linagliptin was disinvested due to sufficient availability of alternatives.

Conclusions

Selection strategy and disinvestment has successfully reduced the number of DPP4-i listed in MoHMF thus allowing more efficient clinical and cost monitoring. Cost minimization through tender by therapeutic group was the first to be done and has efficiently provided an avenue for price competition which results in saving to MoHM.
PD17 Automating The Impact Reporting Of NICE Guidance
Authors: Rowark Shaun , Jonsson Pall , Kent Seamus
Published: December 2022

Introduction

The National Institute for Health and Care Excellence (NICE) intends to automate the way it monitors the uptake, impact, and value of its guidance. Traditionally this has been done by developing impact reports, long documents that, while well received, are time consuming to develop and can quickly become outdated.

Methods

We focused on a novel topic that would benefit from new data sources to examine its impact: a rapid guideline for managing the long-term effects of coronavirus disease 2019 (COVID-19). We shortlisted “measurable” recommendations within the guideline that were likely to be captured in data collections. We then reviewed available data sources that included relevant up-to-date data. Finally, we explored what existing methods were available to NICE for automating impact reporting.

Results

For long COVID-19 we accessed OpenSAFELY, a secure, transparent software platform for primary care COVID-19 data that was developed in response to the pandemic. This captured data on the management of long COVID-19 in primary care as well as onward referral to specialist clinics. In addition, we accessed data from the CVD-COVID-UK/COVID-IMPACT Consortium, which links general practice records with primary care dispensing data. This enabled us to analyze the impact of the pandemic on the prescribing and dispensing of cardiovascular disease medications. Working with our digital team we developed an automated impact reporting dashboard using Google’s data studio. This enabled different views of the data, for example by region or socioeconomic status, to be presented in an automated way.

Conclusions

Automating the impact reporting of NICE guidance provides up-to-date information on its value to the health system. While we were able to collect new sources of data and automate some aspects of how these were viewed, full automation requires several enablers. These include an application programming interface between the data sources and NICE, and ensuring that NICE guidance is computer readable so that its measurement is practical in healthcare systems.
PD19 Machine Learning Modelling For Clinical Trial Design Using The National Institute for Health and Care Research Innovation Observatory’s ScanMedicine Database
Authors: Kavalci Ece , Sadek Jawad , Young Michael , Marshall Christopher
Published: December 2022

Introduction

Clinical trials that fail prematurely due to poor design are a waste of resources and deprives us of data for evaluating potentially effective interventions. This study used machine learning modelling to predict clinical trials’ success or failure and to understand feature contributions driving this result. Features to power the modelling were engineered using data collected from the National Institute for Health and Care Research Innovation Observatory’s ScanMedicine database.

Methods

Using ScanMedicine, a large dataset containing 641,079 clinical trial records from 11 global clinical trial registries, was extracted. Sixteen features were generated from the data based on fields relating to trial design and eligibility. Trials were labeled positive if they were completed (or target recruitment was achieved) or negative if terminated/withdrawn (or target recruitment was not achieved). To achieve optimal performance, phase-specific datasets were generated, and we focused on a subsample of Phase 2 trials (n=70,167). Ensemble models using bagging and boosting algorithms, including balanced random forest and extreme gradient boosting classifiers were used for training and evaluating predictive performance. Shapley Additive Explanations was used to explain the output of the best performing model and calculate feature contributions for individual studies.

Results

We achieved a weighted F1-score of 0.88, Receiver Operator Characteristic Area under the Curve score of 0.75, and balanced accuracy of 0.75 on the test set with the xgBoost model. This result shows that the model can successfully distinguish between classes to predict if a trial will succeed or fail and subsequently output the features driving this outcome. The number of primary outcomes, whether the study was randomized, target sample size and number of exclusion criteria were the most important features affecting the model’s prediction.

Conclusions

This study is the first to use predictive modelling on a large sample of clinical trial data obtained from 11 international trial registries. The prediction outcomes achieved by our novel approach, which uses phase-specific trained models, outperforms previous modelling in this space.
PD30 Radioactive Seed Localization And Radio-Guided Occult Lesion Localization For Non-Palpable Breast Cancer Surgery: A Meta-Analysis
Authors: Ferreira Hortência , Rostelato Maria
Published: December 2022

Introduction

Non-palpable breast cancers require intraoperative localization to guide the surgical procedure. The radio-guided occult lesion localization (ROLL) and radioactive seed localization (RSL) techniques use radioactive material (technetium-99m labeled macroaggregated albumin and iodine-125 seeds, respectively) implanted at the lesion site. The success of conservative surgery depends on complete tumor excision with negative surgical margins. The objective of this study was to perform a meta-analysis of the surgical effectiveness of the ROLL and RSL techniques with respect to rates of positive surgical margins, reoperation, and recurrence.

Methods

A systematic search of the PubMed, Embase, LILACS, SciELO, and Web of Science databases was performed on 2 August 2021. A standard form was used to extract data from the studies selected in the screening process. The ROBINS-I tool was used to analyze risk of bias and RevMan 5.4 software was used to perform the meta-analysis.

Results

Four observational studies met the inclusion criteria. The overall evidence quality was moderate. The studies included women aged from 28 to 91 years with non-palpable breast cancer. The results demonstrated similar effectiveness between RSL and ROLL for rates of positive surgical margins (risk ratio [RR] 0.83, 95% confidence interval [CI]: 0.50, 1.39; 763 patients) and reoperation (RR 1.14, 95% CI: 0.75, 1.74; 1,550 patients). Regarding the rate of disease recurrence, RSL was superior to ROLL (RR 0.50, 95% CI: 0.29, 0.87; 939 patients).

Conclusions

The results demonstrate that the ROLL and RSL techniques are equivalent with respect to rates of positive surgical margins and reoperation, although patients undergoing RSL had lower rates of disease recurrence. However, there is a tendency to favor the RSL technique because of the longer interval between implantation and surgery, which is possible due to the longer half-life of iodine-125 (59.4 days). This also means that radioactive seed implantation can occur before neoadjuvant chemotherapy, so the tumor bed remains marked if further interventions are required, obviating the need for another invasive procedure before surgery.
PD37 High-Dose Vitamin D For The Treatment Of COVID-19
Authors: Stürzlinger Heidi , Pentz Richard
Published: December 2022

Introduction

The aim of this EUnetHTA (European Network for Health Technology Assessment) Rolling Collaborative Review on high dose vitamin D for the treatment of COVID-19 was to inform health policy at an early stage in the life cycle of therapies and to monitor ongoing studies in the format of a Living Document.

Methods

The systematic literature search was conducted in Medline, Pubmed, medRxiv, bioRxiv, arXivso, Cochrane COVID-19 Study Register, ClinicalTrials.gov, ISRCTN Registry, EU Clinical Trials Register. The first search was done in January 2021, and the last in November 2021. English and German randomized controlled studies (RCTs) investigating treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals with high dose vitamin D2, D3 or their metabolites were included if examining mortality, length of hospital stay, viral burden, clinical progression, hospitalization rates, intensive care unit (ICU) admission, mechanical ventilation, quality of life or adverse events. Two reviewers independently screened search results and assessed risk of bias and certainty of evidence. One reviewer extracted study data, checked by another.

Results

Of the nine RCTs published to date, two investigate calcifediol, one calcitriol and six vitamin D3. All used different dosing regimens. Disease severity and proportion of vitamin D deficiency varied between studies. Calcifediol treated patients in one study required significantly less ICU admissions than untreated patients. Vitamin D3 in another study led to significantly more SARS-CoV-2 PCR-negative patients before day 21 than placebo. There were no other significant differences between groups. Twenty-five RCTs are ongoing, five of them with over 1,000 patients.

Conclusions

The current evidence is heterogenous regarding form and dosage of vitamin D, baseline disease severity and baseline vitamin D deficiency. There is currently no standardized/recommended level of what constitutes a (beneficial) “high dose”. Most results did not show significant differences between vitamin D treated groups and no vitamin D / placebo groups. Many of the studies are very small and certainty of evidence is predominantly low or very low.