bluuebunny/crossref_metadata_2025 huggingface dataset:
OP38 Managed (Early) Access In England: The ‘Ins And Outs’
Authors: Bee Charlotte , Hawksworth Claire , Wakefield Leanne , Groves Brad
Published: December 2022

Introduction

Managed access approaches have been used by The National Institute for Health and Care Excellence (NICE) in partnership with NHS England since 2015. The Cancer Drugs Fund is an exemplar of this approach which enables earlier patient access to promising new treatments while further real-world data is collected to address evidential uncertainties. Increasingly, this approach is being applied to rare diseases and other conditions to address unmet clinical need with extensive involvement from patient organizations and clinicians.

Methods

All Managed Access Agreements (MAAs) in development or published in England were reviewed to present data on the number of technologies (i) entering, (ii) in active monitoring, and (iii) exiting managed access, for both cancer and other disease areas.

Results

After six years since the first MAA (at December 2021), over 73,000 patients have benefited from earlier access to promising new treatments for cancer, genetic and rare diseases, including cystic fibrosis, spinal muscular atrophy and sickle cell disease via managed access. Fifty-eight technologies were commissioned via managed access: thirty technologies in active data collection, eleven technologies being re-evaluated, and seventeen technologies have exited managed access. Patient and clinical engagement have been essential to the successful real-world data collections delivered and underway.

Conclusions

Managed access is an approach for providing earlier patient access to promising new technologies that would not otherwise be recommended for use in England. The approach to managed access in England is maturing at the same time the volume of topics entering and exiting managed access in England is expected to grow throughout 2022 with the introduction of the Innovative Medicines Fund.
OP39 The Real-Option Rate Of Return Approach To Inform The Pricing Of Medicines
Authors: van der Schans Simon , Schöttler Marcel , Postma Maarten , Boersma Cornelis
Published: December 2022

Introduction

Prices of medicines have increasingly come under payer and societal scrutiny in many countries around the world. As the price-setting process is quite untransparent, the concept of cost-based pricing has been brought forward as an alternative method to inform reimbursement decision-making. A Real-Option rate of Return (ROroR) approach, was recently proposed as a method for a multi-stakeholder driven collaborative investment model. This study showed that there are public-private medicine development opportunities that could lead to lower research and development (R&D) costs for products with a challenging business model. The aim of the current study is to assess the practical use of the ROroR approach and highlight its sensitivity regarding input parameters.

Methods

The ROroR approach incorporates medicine-specific parameters: R&D costs, the number of patients treated per year, the time horizon for recouping the investments set by the stakeholders, the production costs and a predefined profit margin. Three hypothetical case-studies were selected for the ROroR analysis comprising of an orphan, oncology, and a more regular medicine. Parameter input data was derived from the available literature. Cost-based prices were calculated based on applying the ROroR equation under a constant profit margin. Ultimately, the corresponding prices of the case-studies were analyzed for their sensitivity using ten changes of the original value.

Results

The ROroR approach was most sensitive to the length of the time horizon and the number of patients treated per year. The largest sensitivity was found for the oncological drug, with an asymmetric price change ranging from -25 percent to +271 percent if varying the time horizon or number of patients. The profit margin, and total R&D costs have the least effect on the price: +/-4 percent and +/-45 percent, respectively.

Conclusions

This study shows that cost-based pricing is highly beneficial in uncovering pricing-underlying business or economic mechanisms and suggesting a transparent price. Further research is needed on implementing public-private development models and cost-based price determination using the core parameters.
OP43 Conceptual And Methodological Factors Driving The Integration Of Real-World Evidence In Drugs And Technologies Reimbursement Appraisals
Authors: Plamondon Geneviève , Auclair Yannick , Tremblay Marie-Ève , Beha Sara , Ganache Isabelle
Published: December 2022

Introduction

Real-world evidence (RWE) can be of value to support comparative effectiveness of drugs and technologies by providing additional information about their use for a variety of patients in real contexts of care. However, the integration of RWE in appraisals can be challenging, and INESSS felt the need to reinforce and explicit the underlying methodological and theoretical foundations.

Methods

A comprehensive literature review was carried out, followed by collaborative development work by members of the methodological and assessment teams.

Results

The literature review led to a common understanding of RWE underlying principles and fed the subsequent phases of the project. Three factors were identified as driving the integration of RWE in reimbursement appraisals at INESSS. Specifically, (i) the design and conduct of the real-world studies are done in accordance with best practices, (ii) the results are presented transparently and include all relevant information to assess the quality of the study and the data, and (iii) the RWE submitted is appropriate and relevant for decision-making. This third component is further ascertained by considering the decisional context (what are the circumstances motivating the submission of RWE and how does it correlate or not with existing evidence?), the data (is the dataset fit for decision needs?) and the study methods (are study design and analytical methods robust enough?). Globally, INESSS considers the integration of RWE in appraisals and its weighting, in relation with the (more traditional) available evidence, to be a case-by-case exercise.

Conclusions

The characterization of the main factors driving the integration of RWE in reimbursement appraisals at INESSS serves as a basis for communicating the requirements for evaluation submissions by sponsors. It further reinforces INESSS capabilities in assessing innovations, which can imply an appraisal of value at various moments along the lifecycle and with a diversity of evidence types. Considering the rapidly evolving literature and international experience, this work is expected to evolve too, and will be updated as needed.
OP48 Interactions Between Regulatory, Health Technology Assessment And Companies: Multi-Stakeholder Survey On The Current Experiences And Future Landscape Evolvement
Authors: Wang Tina
Published: December 2022

Introduction

The interactions between regulators, health technology assessment (HTA), and companies play a significant role in the process of getting medicine to patients. These have evolved at a product level as well as at a policy and cross-jurisdictional level; however, it is important these activities are adding value for stakeholders involved. A survey conducted in March 2021 assessed the current interactions from multi-stakeholders, and their perceptions on the added value these interactions bring to better decision-making.

Methods

Three separate questionnaires containing nine questions were developed to assess the perceptions from pharmaceutical companies, regulators, and HTA agencies. The three questionnaires contained analogous questions where appropriate. The company questionnaire was sent to senior management at 19 international pharmaceutical companies, the agency survey was sent to 32 agencies (17 regulatory agencies and 15 HTA agencies) in Australia, Canada, Europe, and Asia.

Results

Seven regulators, seven HTA agencies, and nine companies responded to the survey. All regulators and HTAs indicated they have interactions with their peer agencies, as well as between regulators and HTA. The top areas of interactions for regulators were formal work-sharing between regulators during review (86% response) and regulatory strengthening (86%), whilst for HTAs, interactions between HTA on methodology/framework (83%) and HTA capacity building (67%). Regulatory-HTA interactions were seen to have fewer practical benefits, which may suggest areas for improvement. Both companies and agencies believed an effective engagement model should support evidence generation; agencies also viewed an aligned process and improved decision-making as important. Respondents believed that an ideal ecosystem for interactions should facilitate separate remits for stakeholders, converged requirements, aligned process and increased transparency and trust.

Conclusions

This survey provided a snapshot of the current landscape interactions between stakeholders during the life cycle of new medicines, identified the areas where value is added and improvement are needed. Suggested building blocks to improve future interactions included early scientific advice, alignment of evidence requirements, and a collaborative approach among all stakeholders.
OP52 Health Technology Assessment Of Pain-Free Blood Draw Devices In Pediatrics
Authors: Cristiano Ilaria , Faggiano Francesco , Esposito Maria Teresa , Porzio Ottavia , Ritrovato Matteo
Published: December 2022

Introduction

Blood collection in a pediatric population is a time-consuming activity and an unpleasant experience. Moreover, many laboratory tests require only small amounts of blood while larger quantity of blood is usually drawn, generating excess waste that must be properly disposed of. To solve patient concerns and workflow inefficiencies biomedical companies developed Pain-Free Blood Draw (PFBD) devices. The aim of this health technology assessment (HTA) study is to compare the performances of PFBD devices with the standard venipuncture to evaluate the potential benefits of introducing PFBD devices into clinical practice.

Methods

PFBD devices use microneedles that breach the stratum corneum, significantly reducing the pain perception due to the superficial skin penetration. Decision-oriented HTA method, was applied to conduct the HTA process. It is an analytical instrument that integrates the EunetHTA CoreModel with the analytic hierarchy process, to choose the best technology solution by identifying the main evaluation criteria and defining the weightsof system and performance values. Eight professionals have been involved to define the evaluation criteria and to measure the two technologies’ performance. As the method requires, a literature review was conducted to define the evaluation scheme represented by a multilevel decision tree composed of evaluation areas (domains) and key performance indicators (KPI).

Results

Five evaluation domains were included in the analysis (clinical effectiveness, safety, costs, organizational aspects, and technical characteristics), described by 35 KPIs. Preliminary clinical effectiveness results showed diagnostic concordance between blood samples obtained with PFBD and venipuncture. Even if the additional costs of PFBD, these devices seem to improve the safety by reducing the biological risks for operators. Moreover, considering pediatric patients, organizational aspects would benefit by the use of PFBD in terms of ease of use, compliance of patients, and time reduction for blood collection.

Conclusions

Results showed that PFBD not only have great repercussions in terms of clinical benefits, especially for pediatric patients, but also a significant impact in terms of organizational aspects.
OP56 A Life Cycle Approach To Horizon Scanning Outputs - From Signals To Guidelines
Authors: Gonzalez Moral Sonia Garcia , Khan Sarah Khalid , Lanyi Katherine , Ogunbayo Dapo , Craig Dawn
Published: December 2022

Introduction

The National Institute for Health and Care Research Innovation Observatory (IO) is a horizon scanning centre based at Newcastle University, United Kingdom. The IO provides horizon scanning intelligence on new and innovative medicinal products to the National Institute for Health and Care Excellence (NICE) as technology briefing notifications (TBNs). We present an analysis of how TBNs produced between April 2017 and October 2021 feed into the NICE HTA process and used to inform their Technology Appraisal (TA) programme.

Methods

TBNs were mapped to relevant published NICE TA guidance and time from horizon scanning identification to NICE recommendation was studied. For mapping technologies undergoing appraisal, provisional guidance-in-development (GID) identification numbers (IDs) were used. For technologies that had not reached the NICE scoping stage yet, the NICE Topic Selection decision and ID was used.

Results

Six hundred and ninety-three TBNs were submitted to NICE between April 2017 and October 2021; 653 were prioritised for TA. Of those, eleven percent mapped to a published NICE TA guidance; forty-three percent to a GID, twenty-two percent were undergoing consultation, and three percent were not traced. Further twenty-one percent mapped to a suspended or terminated TA. Reasons for this included HTA timeliness, regulatory issues or companies unwilling to submit evidence to NICE. Time from technology identification to TA guidance publication ranged from twenty-two to 115 months. The average time from TBN submission to NICE recommendation was thirty months.

Conclusions

Timely notification is key in achieving TA recommendation aligned with market authorization but not the only influencing factor. After issuing a TBN, the NICE appraisal process might be terminated, suspended or withdrawn due to unforeseen factors. Horizon scanning plays a key role triggering the NICE TA process; understanding factors that influence the successful TA completion would streamline processes and find efficiencies.
OP62 Patients’ Opinion On Health Technology Assessment Reports: An Analysis Of Brazilian Health Technology Assessment In 2021
Authors: Komoda Denis Satoshi , Correa Carlos Roberto , Visacri Marilia Berlofa , Santos Daniela , Maia Flavia
Published: December 2022

Introduction

The Brazilian health technology assessment (HTA) process includes calls for public consultations, in which society can give its opinion on reports emitted by the National Committee for Health Technology Incorporation (CONITEC). Open and closed queries for public consultation are performed by official formularies and can be accessed online at CONITEC webpage. Queries are divided into two categories of reports: clinical protocols and guidelines, and incorporation/exclusion demands. Incorporation/exclusion queries are subdivided in two additional categories: opinion and experience, or technical. In this study we analyze the weight of patients’ participation in opinion and experience queries and their opinion (pro or con) on inclusion/exclusion of health technologies.

Methods

Formularies concerning concluded public consultations on health technology incorporation/exclusion reports were extracted from CONITEC website from 1 January to 26 November 2021. Entries on the opinion and experience formularies included amongst others, a close-ended question about the opinion of participants on health technology incorporation/exclusion reports (“favorable”/“against”/“neither”). In this study, we analyzed patients’ opinion contained within concluded public consultations on incorporation/exclusion of health technologies.

Results

A total of 63 health technology incorporation/exclusion queries were performed in the analyzed period, of which there were only four exclusions. A total of 32,209 contributions were registered. “Patients”, “Health professionals”, “Family or caregivers”, “Interest on the theme”, accounted for 99.4 percent (13.5, 16.7, 32.3, 36.7%, respectively). Patient participation accounted for 4,367 (13.5%) entries. The total number of opinions in favor of the presented documents by the “Patients” was 4,268 (97.7%), 59 (1.4%) disagreed and 40 (0.9%) had no opinion.

Conclusions

Public consultation of official HTA reports is a very useful tool to legitimize decisions through social participation. Although patient participation is not numerically the most important category to contribute on public consultation queries, patients are, if not the most influential stakeholder, the main recipient of decisions concerning health technologies incorporations. Further analyses shall investigate experience narratives included in public consultation queries.
OP63 Patient and Public Perspectives On The Scottish Medicines Consortium Detailed Advice Document
Authors: Pierre Miranda , Dickson Jennifer , Lockhart Lindsay , McCormack Jackie
Published: December 2022

Introduction

The Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines, the primary output of which is a document referred to as the Detailed Advice Document (DAD). This comprises an overview of all data considered on the clinical and cost-effectiveness of the medicine, as well as the input from patient groups (PGs), patients, and carers. In 2020, SMC commenced a stakeholder evaluation of the DAD including a workshop with PGs and public partners (members of the public who volunteer with SMC) to explore the potential for using the DAD more widely.

Methods

PGs and public partners, all having significant experience of engaging with SMC, participated in the workshop. Feedback was gathered using virtual post-it notes, collated and analysed for key themes. We also gathered oral feedback from participants. Sample DADs were distributed for two medicines recently appraised, one of which included a Patient and Clinician Engagement (PACE) meeting. These were chosen because they reflect different aspects of public and patient involvement at SMC, including how this is presented in the DAD.

Results

Overall, the workshop participants (n=7) recognised the DAD was a useful document for the clinicians who are its primary audience. Its language was perceived to be challenging, including complex information that is not accessible to a wide audience and may only be fully understood by those with a good understanding and knowledge of HTA. This was a key barrier to using the DAD more widely, in particular the health economics information. Suggestions for broadening the audience of the DAD included summaries of key points and an introductory section clarifying the purpose of the DAD and its intended audience, along with signposting to the plain language summary produced by SMC. These will be implemented where possible.

Conclusions

Improving how SMC communicates decisions to patients and the public, by working in partnership with these stakeholders, will help strengthen public involvement throughout the HTA process.
OP68 Real-World Experience With The National Institute For Health And Care Excellence’s Willingness To Accept Less Costly, Less Effective Healthcare Technologies
Authors: Caverly Suzanne , Falla Edel , Gaultney Jennifer , Boyers Dwayne , Jacobsen Elisabet
Published: December 2022

Introduction

Research suggests a different willingness to pay for more effective interventions than willingness to accept (WTA) for less effective interventions which has prompted debate as to whether the threshold in the southwest (SW) quadrant should be kinked to reflect this disparity. Acceptance of less costly, less effective interventions with incremental cost-effectiveness ratios (ICERs) in the SW-quadrant presents an opportunity for resource-constrained healthcare systems by releasing resources for other purposes, which is of particular importance during a pandemic. The National Institute for Health and Care Excellence (NICE)’s methods guide suggests the threshold for decision-making for SW-quadrant interventions be the same as for more expensive, more effective interventions. To assess NICE’s WTA less effective treatments, the objective was to review the outcomes and decision drivers for interventions presenting SW-quadrant ICERs.

Methods

A review of NICE health technology appraisals (HTAs) containing SW-quadrant ICERs identified from 2015-2021 was conducted. Appraisal details were extracted and analyzed to identify trends in the WTA and decision drivers.

Results

The HTA review identified twenty-one submissions containing SW-quadrant ICERs in the base-case/scenario analysis. Eighty-one percent received a positive recommendation, with ICERs ranging from GBP 30,000-GBP 4.2m (EUR 35,264-EUR 5m) compared to a range of GBP 789-GBP 50,905 (EUR 927-EUR 59,837) for negative recommendations. The HTAs covered a wide range of therapeutic areas including psoriasis, multiple sclerosis and multiple oncology indications. Decision drivers identified that may have had a positive influence on final outcomes included a high net monetary benefit, a small QALY difference, clinical unmet need, poor tolerability of existing treatments, and oral administration route.

Conclusions

The analysis suggests that there is a high rate of acceptance of interventions with ICERs in the SW-quadrant, however, the threshold for acceptance is unclear. The high frequency of HTAs with SW-quadrant ICERs identified in this review indicates the need for further guidance on such interventions in the NICE reference case.
OP70 Gaps In The Evaluation Of Clinical Decision Support Software (CDSS): Interviews With Australian Policymakers
Authors: Laka Mah , Carter Drew , Merlin Tracy
Published: December 2022

Introduction

Clinical Decision Support Software (CDSS) can improve the quality and safety of care by providing patient-specific diagnostic and treatment recommendations. However, robust evaluation is required to ensure that the recommendations provided are clinically valid, up-to-date, and relevant to a specific clinical context. Most evaluation studies assess CDSS performance from the perspective of end-user requirements. But only occasionally is CDSS subject to stringent pre- and post-market evaluation, making it difficult to determine the safety and quality in practice. This study aimed to assess CDSS evaluation in Australia to identify gaps in evaluation approaches.

Methods

We conducted 11 semi-structured interviews with different policymakers from committees involved in digital health activities in Australia. Data were thematically analyzed using both theory-based (deductive) and data-driven (inductive) approaches.

Results

Our findings indicated that evaluating CDSS as a purely technical intervention has overly narrowed the assessment of benefits and risks by inadequately capturing the sociotechnical environment. Existing evaluation methods, adopting a static view of the implemented system, cannot discern the impact of the dynamic clinical environment and rapidly evolving technology on CDSS performance. The timeframe of evaluation studies are also incongruent with fast software upgrade cycles, with clinical practices and software potentially changing by the time evaluation is complete. The regulation of software as a medical device depends on the intended use. CDSS are exempt from regulation because they only ‘produce advice’; however, this ignores the fact that they can transition to specifying a diagnosis and treatment after a software update. There is no framework for continuous post-market monitoring, and this is especially important when a CDSS algorithm can change and impact on patient management.

Conclusions

The sociotechnical environment is a significant factor influencing the impact of CDSS on clinical practice, therefore evaluation approaches must acknowledge the dynamic nature of clinical and organizational contexts. Pragmatic and data-driven methodologies are required for CDSS evaluation that acknowledge the evolving landscape of clinical practice and its relationship to technology.
OP72 Software Tools For Systematic Literature Review In Medicine: A Review And Feature Analysis
Authors: Kallmes Kevin , Cowie Kathryn , Hardy Nicole , Holub Karl
Published: December 2022

Introduction

Systematic reviews (SRs) are central to evaluating therapies but have high costs in time and money. Many software tools exist to assist with SRs, but most tools do not support the full process, and transparency and replicability of SR depends on performing and presenting evidence according to established best practices. In order to provide a basis for comparing between software tools that support SR, we performed a feature-by-feature comparison of SR tools.

Methods

We searched for SR tools by reviewing any such tool listed the Systematic Review Toolbox, previous reviews of SR tools, and qualitative Google searching. We included all SR tools that were currently functional, and required no coding and excluded reference managers, desktop applications, and statistical software. The list of features to assess was populated by combining all features assessed in four previous reviews of SR tools; we also added five features (manual addition, screening automation, dual extraction, living review, and public outputs) that were independently noted as best practices or enhancements of transparency/replicability. Then, two reviewers assigned binary ‘present/absent’ assessments to all SR tools with respect to all features, and a third reviewer adjudicated all disagreements.

Results

Of 53 SR tools found, 29 were excluded, leaving 24 for assessment. Thirty features were assessed across six classes, and the inter-observer agreement was 86 percent. DistillerSR (Evidence Partners; n = 26/30, 87%), Nested Knowledge (Nested Knowledge; n = 25/30, 83%), and EPPI-Reviewer Web (EPPI-Centre; n = 24/30, 80%) support the most features followed by Giotto Compliance (Giotto Compliance; n = 23/30, 77%), LitStream (ICF; n = 22/30, 73%), and SRDB.PRO (VTS Software; n = 21/30, 70%). Seven tools support fewer than half of all features assessed: RobotAnalyst, SyRF, Data Abstraction Assistant, SWIFT-Review, SR-Accelerator, RobotReviewer, and COVID-NMA. Notably, only 10 tools (42%) support direct search, 7 (29%) offer dual extraction, and 13 (54%) offer living/updatable reviews.

Conclusions

DistillerSR, EPPI-Reviewer Web, and Nested Knowledge each offer a high density of SR-focused web-based tools. By transparent comparison and discussion regarding SR tool functionality, the medical community can choose among existing software offerings and note the areas of growth needed, most notably in the support of living reviews.
OP73 Tools That Can Aid Adaptive HTA To Ensure Rapid, Efficient, And Pragmatic Priority Setting: A Scoping Review
Authors: Heupink Lieke Fleur , Peacocke Elizabeth , Sæterdal Ingvil , Chola Lumbwe , Frønsdal Katrine
Published: December 2022

Introduction

Producing new health technology assessments (HTA) can be a time-consuming process. With finite resources in HTA agencies, limited capacities in countries without formalized HTA processes, and growing interest for lifecycles approaches valuing health technologies; innovative and efficient HTA processes are needed. “Adaptive HTA”, referring to the pragmatic use of HTA methods and existing (HTA) evidence, might offer solutions. We will present the results from a scoping review that mapped existing tools, methods, practices to transfer existing HTAs; and reflect on these findings given our own experiences of adaptation processes in LMICs.

Methods

We undertook a scoping review and systematically searched five electronic databases. Inclusion of articles followed strict in- and exclusion criteria. Data extraction focused on information regarding tools, methods, and practices that could aid the transferability of HTA analysis. Here, HTAs referred to full-HTAs and other HTA products, as partial HTAs, economic evaluations, or systematic reviews. Lastly, we mapped the possible overarching factors that can affect transferability.

Results

The search (November 2020) identified 2030 hits, of which 19 were included. Most HTA transfers followed five steps that closely resemble a de novo HTA process. The identified transferability tools, often checklists, were merely aids or a “catalyst” for the transfer and provided limited guidance for the whole transfer process. Contrastingly, we identified three frameworks that can support the whole process: European Network for HTA (EUnetHTA) Adaptation Toolkit, TRANSFER framework for systematic reviews, and paper series on systematic reviews for economic evaluations. Lastly, our findings pointed to various challenges and knowledge gaps; especially for transfers in low and middle income countries evidence is limited.

Conclusions

The re-use of existing evidence in HTA reports is not new; and readily part of de novo and adaptive processes. The innovative nature of adaptive HTA comes from its ability to unpack the process of adaptation and transferability. Simultaneously, this scoping review highlighted gaps in existing adaptive methods, and could aid future adaptive HTA process for experienced and new HTA-doers.
OP79 Incorporating Environmental Impacts Into Health Technology Assessment: An Examination Of Potential Approaches And Challenges
Authors: Kenny Juliet , Shah Koonal , Toolan Michael , Crabb Nick , Greaves Felix , Jónsson Páll , Richardson Judith , Walpole Sarah
Published: December 2022

Introduction

In light of government and healthcare system commitments to reducing the carbon footprint of healthcare, health technology assessment (HTA) agencies are increasingly motivated to investigate how to consider environmental sustainability in their assessments and guidance. This constitutes a major departure from the existing remits and objectives of most agencies, which typically focus on improving population health outcomes. This presentation seeks to identify options for incorporating environmental impact data into HTA and to examine the main challenges, focusing on the National Institute for Health and Care Excellence (NICE) as a case study.

Methods

We present four broad approaches that could be pursued, informed by policy analysis undertaken by NICE. The strengths, weaknesses and implications of each approach are assessed.

Results

The first option is to act as an ‘information conduit’, aggregating and distributing in a standardized format environmental impact information that is provided voluntarily by health technology manufacturers. The second is to present complementary analyses of environmental impact data, separately but alongside results from established health economic analyses (‘parallel evaluation’ model). The third is to incorporate environmental impact data into health economic analyses, for example by monetizing environmental outcomes, so that quantitative estimates of treatment value are directly affected by environmental benefits and costs (‘integrated evaluation’ model). The fourth is to create new decision-making frameworks for evaluating healthcare interventions that are not expected to improve health-related outcomes, but claim to have relative environmental benefits.

Conclusions

We conclude that these approaches are not mutually exclusive, and all involve some degree of benefit and risk. We explain why the parallel evaluation model may be the most appropriate approach for NICE as a first response to the increased demand for guidance on the environmental impact of health technologies. We also outline activities being undertaken by NICE and other agencies such as the Canadian Agency for Drugs and Technologies in Health to develop new methodologies for incorporating environmental impact data into their HTAs.
OP86 Chatbot-Based Symptom-Checkers: A Systematic Review
Authors: Jeindl Reinhard , Goetz Gregor
Published: December 2022

Introduction

Symptom-checkers are digital health applications (DHA) with diagnostic algorithms. These symptom-checkers claim to improve the diagnostic process and patient guidance. After asking the user to describe the symptoms using a chatbot interface, the symptom-checkers offer a list of potential diagnoses, and/or give recommendations for appropriate action (self-care, doctor’s visit, or emergency care). Because of the growing number and increasing use of these diagnostic DHA, there is a need to evaluate the evidence.

Methods

We updated a British evidence synthesis on symptom-checkers from the National Institute for Health Research (NIHR, 2019). For the systematic update search, we selected four databases. The following endpoints were selected: effectiveness, safety, diagnostic accuracy, triage accuracy, organizational and patient-relevant endpoints. For accuracy studies included from the update search, we assessed the risk of bias (RoB) using the quality assessment tool of diagnostic accuracy studies (QUADAS-2).

Results

The NIHR-report included 27 studies. We added 14 additional studies via update search. One randomized-controlled-trial (RCT) reported a prolonged illness duration when using symptom-checkers (statistically non-significant). No harms when using symptom-checkers were identified (six observational studies). The diagnostic accuracy ranged from 14-84.3 percent (ten observational studies), the triage accuracy ranged from 33-100 percent (eleven observational studies). For organizational endpoints, the results were inconsistent (one RCT, six observational studies). The patient perspective indicates a high usability for symptom-checkers, but the limited description of symptoms and the missing verbal interaction with health personnel were mentioned as hindering factors (nine survey-studies). The QUADAS-2 assessment for RoB was low in one, and high in seven studies.

Conclusions

The studies were often conducted using fictitious case-vignettes, limiting the validity of the evidence. Therefore, the results for the diagnostic and triage accuracy are insufficient to demonstrate a benefit in real-world settings. Additionally, there is a concern for misdiagnosis and overdiagnosis. We recommend a continuous monitoring of these diagnostic DHA, using high-quality studies.
OP91 The Current State Of Disease-Specific Registries For The Monitoring Of Expensive Pharmaceuticals In The Netherlands
Authors: Goettsch Wim , Timmers Lonneke , Lobbezoo Dorien , Hagen Marielle
Published: December 2022

Introduction

On a regular basis, new and innovative medicines come to the market; with uncertainties surrounding their exact effect in patients. To address these uncertainties, disease-specific registries are commonly being used. The Dutch National Health Care Institute (Zorginstituut Netherland [ZIN]) started, in collaboration with stakeholders, a national program on the management and coordination of disease-specific registries. The main goal is to improve the quality and consistency of these registries and thereby increase the value of the data in monitoring innovative, expensive medicines. As a starting point for this program, we performed a study on the current state of these registries in the Netherlands.

Methods

Using an initial list of 114 registries, we sent out questionnaires to 58 disease-specific registries that collected information on medicine use. Thirty registries responded and their registries were used for the analysis.

Results

Of 30 registries that responded, 15 registries collect information on orphan medicinal products. Most registries are in the field of internal medicine (n = 8), oncology (n = 6), and rheumatology (n = 5). The size of the registries ranged between 250 patients (orphan diseases) and more than 10,000 patients (oncology). Only 13 registries collect information on patient reported outcomes. Data collection is mostly performed manually and standard coding systems such as Systemized Nomenclature of Medicine (SNOMED), Logical Observation Identifiers, Names, and Codes (LOINC), and The International Classification of Diseases 10th Revision (ICD-10) are not routinely used. Finally, our results show that most registries are (partly) dependent on the funding of pharmaceutical companies.

Conclusions

Our assessment shows variation in the type, goal of, governance, and funding of the disease-specific registries investigated. We believe that these results show the importance of further national coordination of the disease-specific registries to increase the usability of their data to address the uncertainties surrounding these innovative, expensive medicines.
OP93 Informing Efficient Diagnostic Monitoring Pathways Using Prospective Cohort Data: A Case Study In Neovascular Age-Related Macular Degeneration
Authors: Scotland Graham , Hernández Rodolfo , Kennedy Charlotte , Banister Katie , Goulao Beatriz , Cook Jonathan , Sivaprasad Sobha , Hogg Ruth , Azuara-Blanco Augusto , Heimann Heinrich , Dimitrova Maria , Gale Richard , Porteous Mia , Ramsay Craig , Chakravarthy Usha
Published: December 2022

Introduction

Several diagnostic tests are often adopted into diagnostic pathways for specific indications without strong evidence to support their use. In this context, real-world prospective cohort studies in combination with decision modelling can generate evidence to support decision-making. The Early Detection of neovascular Age-Related Macular Degeneration (EDNA) study was a prospective cohort designed to assess the diagnostic accuracy and cost-effectiveness of several diagnostic monitoring tests used in routine practice for the detection of neovascular age-related macular degeneration (nAMD) in the second eye of patients being treated for unilateral disease.

Methods

Five-hundred and fifty-two participants with newly diagnosed unilateral nAMD were monitored for up to 3 years in 24 UK eye clinics. The diagnostic monitoring performance of five index tests was compared: self-reported change in visual function, Amsler test, clinic measured change in visual acuity, fundus assessment by clinical examination or colour photography, and spectral-domain optical coherence tomography (SD-OCT). The reference standard was fundus fluorescein angiography (FFA). A patient-level state transition model was used to simulate the onset of nAMD in the second eye, and assess the impact of different tests on the timing of detection and treatment, and associated costs and quality adjusted life years (QALYs) over a 25-year time-horizon.

Results

One hundred and forty-five (26.3%) patients developed active nAMD in the study eye, of whom 120 had an FFA at detection. SD-OCT had the highest sensitivity (91.7 percent (95% CI: 85.2-95.6) and provided high specificity (87.8% (95% CI: 83.8-90.9)). It generated more QALYs and lower health and personal social care costs compared to all other monitoring tests. The combination of SD-OCT with fundus-examination provided a marginal increase in sensitivity over OCT alone, but the associated incremental cost-effectiveness ratios was >GBP 100,000 per QALY.

Conclusions

The efficiency of diagnostic pathways for nAMD may be improved by using SD-OCT alone to monitor the second eye of people being treated for unilateral disease. Prospective cohort studies embedded into routine practice offer value for informing decisions surrounding the use of technologies already in routine use.
PP02 Is Glycated Hemoglobin A Valid Surrogate Endpoint To Evaluate The Effectiveness Of Drugs In Diabetes Mellitus Studies?
Authors: Rivera Paola Andrea , Fiestas Fabián
Published: December 2022

Introduction

In the field of drug development and effectiveness evaluation, the use of surrogate endpoints is acceptable if they reliably predict a positive effect on clinical outcomes such as mortality or morbidity. Hemoglobin A1c (HbA1c) is a widely used surrogate endpoint in phase 3 and 4 clinical trials evaluating drugs in patients with diabetes mellitus (DM). The objective of this study was to investigate whether HbA1c is a valid surrogate endpoint for evaluating the effectiveness of antihyperglycemic drugs in DM trials.

Methods

We conducted a systematic review of randomized placebo-controlled trials evaluating the effect of a treatment on levels of HbA1c and clinical outcomes in patients with DM. The association between the effects of treatment on HbA1c levels and clinical outcomes was then investigated using regression analysis at the trial level. The correlation coefficients (R) were interpreted using the cut-off points suggested by the German Institute for Quality and Efficiency in Health Care (IQWiG). HbA1c was considered a valid surrogate endpoint if it demonstrated a strong association with clinical outcomes (i.e., the lower limit of the 95% confidence interval [CI] of R≥ 0.85).

Results

Nineteen phase 3 or 4 randomized controlled trials (RCTs) were identified. All studies included adults with type 2 DM. None of the associations evaluated was strong enough to validate HbA1c as a surrogate endpoint for any clinical outcome: mortality (R 0.34, 95% CI: -0.14, 0.69); myocardial infarction (R 0.20, 95% CI: -0.30, 0.61); heart failure (R 0.08, 95% CI: -0.40, 0.53); kidney injury (R -0.04, 95% CI: -0.52, 0.47); and stroke (R 0.81, 95% CI: 0.54, 0.93).

Conclusions

The evidence from multiple placebo-controlled RCTs of antihyperglycemic drugs in patients with type 2 DM suggests that a reduction in levels of HbA1c does not meet the IQWiG criteria for a valid surrogate endpoint. Consequently, the risk-benefit ratio of antihyperglycemic drugs in terms of patient relevant clinical outcomes, regardless of their hypoglycemic effect, should be the focus of therapeutic, regulatory, and reimbursement decisions.
PP11 Impact Of Qualitative Research In The Spanish Network Of Health Technology Assessment
Authors: Toledo-Chávarri Ana , Triñanes Yolanda , Ramos-García Vanesa , Perestelo-Pérez Lilisbeth , Reviriego Eva
Published: December 2022

Introduction

Qualitative research is being increasingly integrated in heath technology assessments (HTA) within the Spanish Network of Agencies for Assessing National Health System Technologies and Performance (RedETS). Qualitative research methodological guidelines are given in RedETS HTA guidelines and the Patient Involvement Strategy. A specific methodological guideline to systematically review qualitative studies was published in 2007 and is pending its update. The impact of their implementation is unknown. The aim of this work is to analyze the techniques, impact and reporting of qualitative research (primary and secondary) in HTAs.

Methods

A manual search of the HTAs published in the last 5 years in RedETS was conducted to locate assessments that include qualitative research. To ensure a complete identification, RedETS agencies and units were consulted to provide information about the assessments that have used qualitative techniques in their development over the past 5 years. A content analysis of the selected assessments was conducted to analyze the techniques, impact and reporting of qualitative research in HTA.

Results

In the past five years, focus groups, semi-structured interviews, evidence synthesis of observational studies including qualitative studies have been used and integrated in HTA in RedETS. Most of them have been linked to patient involvement facilitation or the inclusion of patient perspectives in HTA. Qualitative research has been used to analyze patient’s experiences and values, to elicit and select important outcome measures for patients, to research for barriers-facilitators for technology implementation and to inform evidence to decision frameworks.

Conclusions

Qualitative primary and secondary research is being used in HTA in Spain. It is mainly linked to patient involvement strategies both to elicit patient perspectives directly or to collect patient-based evidence. The impact of qualitative research in HTA is broad and diverse, extending from the scope of the assessments to the drafting of the recommendations.
PP12 Challenges In Assessing The Efficacy Of Non-Pharmacological Measures In The Context Of The COVID-19 Pandemic
Authors: Aguilera-Cobos Lorena , Isabel-Gómez Rebeca , Blasco-Amaro Juan Antonio
Published: December 2022

Introduction

The outbreak of the COVID-19 global pandemic in 2020 has been a major challenge for the world’s population and governments. The lack of vaccines, the saturation of health systems, and its rapid spread forced governments to take non-pharmacological interventions (NPI) that had a high impact on the population. Assessing the efficacy of these measures is a challenge for health technology assessment bodies.

Methods

The main NPIs for which assessment was required were: mobility restrictions, social distancing, cancellation of events or reduction of seating capacity, closure or reduction of seating capacity in non-essential businesses, closure or limitation of seating capacity in educational establishments, and promotion of teleworking in potential jobs. The implementation of these measures at a global level provides a large population for the study of the impact of these measures. However, the challenges for their evaluation are numerous:

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The joint implementation of these measures makes it difficult to evaluate them in an isolated manner.

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The heterogeneity between countries and regions of the pandemic situation at the time when these measures are initiated and terminated.

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The different accuracy in the application of the measures.

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Heterogeneity in the quality and accessibility of public health services for citizens.

Results

Outcome variables to assess the effectiveness of these measures should include parameters related to:

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Incidence variables: the number of new or accumulated cases in a given time range, the variation in the number of cases in a given time range and the proportion of positive tests.

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Transmission variables: the basic reproductive number (R0) and the effective reproductive number (Rt).

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Severity and mortality variables: the number or variation of hospitalizations, the number or variation of intensive care unit (ICU) hospitalizations and the number or variation of deaths.

Conclusions

The large number of available data, the heterogeneity of the measures, the differences between populations, the numerous outcome variables and the possible inclusion of mathematical modelling studies, are a methodological challenge for the HTA bodies.
PP13 Development Of Recommendations And Proposal For A Value-Based Managed Entry Agreement For Italian Setting
Authors: Cicchetti Americo , Xoxi Entela , Rumi Filippo
Published: December 2022

Introduction

The continuous and pressing challenge that the drug regulatory authorities in Italy and in Europe are facing is that of guaranteeing patients’ quick access to new drugs, ensuring the economic sustainability of the system at the same time. In recent years, flexible and diversified approaches have been developed known as Managed Entry Agreements (MEA).

Methods

We performed an analysis of the Italian legislative and regulatory aspects in reference to a new Value-based Managed Entry Agreement (VBMEA) pathway. Thus, we tried to investigate the rationale for a new pathway analyzing three main dimensions related to the new medical product (MP): value; time to entry access; and, data quality and registry design. Moreover, we shared the discussion of the proposal with an international experts’ panel.

Results

The proposal for a new pathway of VBMEA from a procedural point of view shows the novelty related to the possibility to organize joint CTS (Technical Scientific Committee) and CPR (Price and Reimbursement Committee) assessment. A 24-month contract with an ex-factory price (PP) equal to X EUR per dose and a transfer price to the National Public Health System (NPHS), following application of a confidential discount for public structures (-X%), of X EUR per dose. After 24-months, an analysis of VBMEA is carried out. The price of the MP is therefore established based on AIFA registries and VBMEA results. The cost value incurred by the NPHS, intended as the difference between the price in market (entry) access phase and the price negotiated (PVB) in the light of the VBMEA results, shall be returned by the pharmaceutical company in the form of a payback.

Conclusions

Currently, MEAs represent one of the main topics of discussion between the European National Payers Authorities. There is very little information on product performance that results from MEAs. This research project could provide advice to policy makers to decrease negotiation time by ensuring earlier access to innovation for patients.