Health Technology Assessment Evidence Research Articles

Real-World Evidence to Reinforce Clinical Trial Evidence in Health Technology Assessment: A Critical Review of Real-World Evidence Requirements from Seven Countries and Recommendations to Improve Acceptance.

Real-world evidence (RWE) can reinforce clinical trial evidence in health technology assessment (HTA). Review HTA bodies' (HTAbs) requirements for RWE, real uses, and acceptance across seven countries (Brazil, Canada, France, Germany, Italy, Spain, and the United Kingdom) and outline recommendations that may improve acceptance of RWE in efficacy/effectiveness assessments and appraisals processes. RWE requirements were summarized based on HTAbs' guidelines. Acceptance by HTAbs was evaluated based on industry experience and case studies. As of June 2022, RWE methodological guidelines were in place in three of the seven countries. HTAbs typically requested analyses based on local data sources, but the preferred study design and data sources differed. HTAbs had individual submission, assessment, and appraisal processes; some allowed early meetings for the protocol and/or results validation, though few involved external experts or medical societies to provide input to assessment and appraisal. The extent of submission, assessment, and appraisal requirements did not necessarily reflect the degree of acceptance. All the countries reviewed face common challenges regarding the use of RWE. Our proposals address the need to facilitate collaboration and communication with industry and regulatory agencies and the need for specific guidelines describing RWE design and criteria of acceptance throughout the assessment and appraisal processes.

Acceptability of Using Real-World Data to Estimate Relative Treatment Effects in Health Technology Assessments: Barriers and Future Steps

ObjectivesEvidence about the comparative effects of new treatments is typically collected in randomized controlled trials (RCTs). In some instances, RCTs are not possible, or their value is limited by an inability to capture treatment effects over the longer term or in all relevant population subgroups. In these cases, nonrandomized studies (NRS) using real-world data (RWD) are increasingly used to complement trial evidence on treatment effects for health technology assessment (HTA). However, there have been concerns over a lack of acceptability of this evidence by HTA agencies. This article aims to identify the barriers to the acceptance of NRS and steps that may facilitate increases in the acceptability of NRS in the future. MethodsOpinions of the authorship team based on their experience in real-world evidence research in academic, HTA, and industry settings, supported by a critical assessment of existing studies. ResultsBarriers were identified that are applicable to key stakeholder groups, including HTA agencies (eg, the lack of comprehensive methodological guidelines for using RWD), evidence generators (eg, avoidable deviations from best practices), and external stakeholders (eg, data controllers providing timely access to high-quality RWD). Future steps that may facilitate future acceptability of NRS include improvements in the quality, integration, and accessibility of RWD, wider use of demonstration projects to highlight the value and applicability of nonrandomized designs, living, and more detailed HTA guidelines, and improvements in HTA infrastructure relating to RWD. ConclusionNRS can represent a crucial source of evidence on treatment effects for use in HTA when RCT evidence is limited.

Advancing the use of real world evidence in health technology assessment: insights from a multi-stakeholder workshop.

Introduction: Real-world evidence (RWE) in health technology assessment (HTA) holds significant potential for informing healthcare decision-making. A multistakeholder workshop was organised by the European Health Data and Evidence Network (EHDEN) and the GetReal Institute to explore the status, challenges, and opportunities in incorporating RWE into HTA, with a focus on learning from regulatory initiatives such as the European Medicines Agency (EMA) Data Analysis and Real World Interrogation Network (DARWIN EU®). Methods: The workshop gathered key stakeholders from regulatory agencies, HTA organizations, academia, and industry for three panel discussions on RWE and HTA integration. Insights and recommendations were collected through panel discussions and audience polls. The workshop outcomes were reviewed by authors to identify key themes, challenges, and recommendations. Results: The workshop discussions revealed several important findings relating to the use of RWE in HTA. Compared with regulatory processes, its adoption in HTA to date has been slow. Barriers include limited trust in RWE, data quality concerns, and uncertainty about best practices. Facilitators include multidisciplinary training, educational initiatives, and stakeholder collaboration, which could be facilitated by initiatives like EHDEN and the GetReal Institute. Demonstrating the impact of "driver projects" could promote RWE adoption in HTA. Conclusion: To enhance the integration of RWE in HTA, it is crucial to address known barriers through comprehensive training, stakeholder collaboration, and impactful exemplar research projects. By upskilling users and beneficiaries of RWE and those that generate it, promoting collaboration, and conducting "driver projects," can strengthen the HTA evidence base for more informed healthcare decisions.

Establishing a Health Technology Assessment Evidence Ecosystem in India’s Pradhan Mantri Jan Arogya Yojana

ABSTRACT The introduction of the Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (AB PM-JAY) scheme in India was a significant step toward universal health coverage. The PM-JAY scheme has made notable progress since its inception, including increasing the number of people covered and expanding the range of services provided under the health benefit package (HBP). The creation of the Health Financing and Technology Assessment (HeFTA) unit within the National Health Authority (NHA) further enhanced evidence-based decision-making processes. We outline the journey of HeFTA and highlight significant cost savings to the PM-JAY as a result of health technology assessment (HTA). Our paper also discusses the application of HTA evidence for decisions related to inclusions or exclusions in HBP, framing standard treatment guidelines as well as other policies. We recommend that future financing reforms for strategic purchasing should strengthen strategic purchasing arrangements and adopt value-based pricing (VBP). Integrating HTA and VBP is a progressive approach toward health care financing reforms for large government-funded schemes like the PM-JAY.

OP153 Access To Real-World Data For Use In Health Technology Assessment – Still Work To Be Done

IntroductionReal-world data (RWD) is an important source of evidence for health technology assessment (HTA). It is widely used to fill clinical trial data gaps and to inform risk-sharing agreements. HTA is mandatory in many jurisdictions as it is used for price negotiation between a manufacturer and a payer. HTA practitioners have so far had limited involvement in the debate surrounding access to RWD as regulators have primarily focused on scientific research and market authorization. This study examined the challenges of obtaining RWD for HTA decision-making that is beneficial at the population level when data sources are restricted to maintain the data integrity and rights of the public.MethodsTypes of RWD and processes for obtaining data were assessed for two jurisdictions (Australia and Denmark). Types of data considered were national registries, ongoing or completed cohorts, surveys at various universities, archived historical data, and medical claims data. The assessment was performed by analyzing a series of cases.ResultsThere were similarities and differences between the two jurisdictions. In both jurisdictions the process for obtaining data included an ethics application as well as data handling fees. Patients and clinicians had little to no say in what their data are used for. It can take up to six months to obtain data. Person identification numbers enable linking of different datasets. Population wide data are accessible in Denmark only through secure servers, whereas full data sets, such as prescription data, can be released for research in Australia. Public hospital data, such as electronic health records, are not easily obtained in Denmark. In Australia, public hospitals are run by individual states and, therefore, additional effort is required to access nationwide data.ConclusionsAccess to RWD for HTA is challenging in both Australia and Denmark. Improvements in the process of applying for data and linking different data sources for HTA purposes are still needed.

HTA208 Paradigm Shift or Incremental Change? Real-World Evidence for Health Technology Assessment: A Critical Appraisal

HTA208 Paradigm Shift or Incremental Change? Real-World Evidence for Health Technology Assessment: A Critical Appraisal

PP70 Mapping Of Health Technology Assessment In China: A Comparative Study Between 2016 And 2021

IntroductionThis study aimed to compare changes in the level of health technology assessment (HTA) development from 2016 to 2021, and to inform policies and decisions to promote further development of HTA in China.MethodsWe conducted a cross-sectional and anonymous web-based survey to relevant stakeholders in China in 2016 and 2021 respectively. The mapping of the HTA instrument was used to reflect the HTA development from eight domains. To reduce the influence of confounders and to compare the mapping outcomes between 2016 and 2021 groups, we performed 1:1 propensity score matching methodology in this study. Univariate analysis was performed to compare the differences in these two groups. We also compared the overall results with that of a mapping study that included ten countries.ResultsA total of 212 and 255 respondents completed the survey in 2016 and 2021 respectively. After propensity score matching methodology, 183 cases from the 2016 group and 2021 group were matched. Overall, the mean score of 2021 in most of the domains was higher than in 2016 in China (p < 0.05), matching the level of HTA institutionalization and dissemination strategy, except for the assessment domain. Although China scored significantly lower among the three developed countries, the overall HTA development score for China was comparable among the ten countries.ConclusionsOur study suggested the level of HTA development in China has made great progress from 2016 to 2021. Prior to HTA activities, the researcher or policy makers should first formulate an explicit assessment goal and scope, and during the assessment process, more attention should be paid to the clinical effectiveness and cost-effectiveness indicator to ensure a higher quality of HTA evidence.

OP106 Standing On The Shoulders Of Giants: Adapting Published Health Technology Assessments On Medical Technologies To Singapore’s Context

IntroductionGiven time and resource constraints, health technology assessments (HTAs) should avoid duplicating prior HTAs. This abstract describes the experience of the Agency for Care Effectiveness (ACE) with adapting and building on published HTAs of medical technologies to support efficient decision-making.MethodsUpon defining the scope of an evaluation topic, searches were performed on reference agency websites and HTA networks, such as the International Network of Agencies for Health Technology Assessment, to identify relevant published HTAs. Identified reports were included for evidence synthesis if the inclusion criteria were met. If multiple relevant HTAs were identified, the most recent or comprehensive HTA identified was used as the foundational evidence base and supplemented by additional primary or secondary literature as needed. When deemed necessary, de novo economic models were developed. Where available, reimbursement decisions or recommendations from published HTAs and their applicability to Singapore’s context were also considered. Following ACE’s evaluations, the Ministry of Health Medical Technology Advisory Committee (MTAC) made subsidy recommendations.ResultsTo date, ACE has completed 54 HTA evaluations of medical technologies, 47 (87%) of which incorporated published HTA evidence. Although some MTAC recommendations were aligned with published HTAs, discrepancies were observed that were mainly attributed to evolution of the technology or evidence since publication of HTAs; different local clinical needs or management algorithms; and different local costs of the intervention and comparator. Key challenges in adapting published HTAs included differences in the target population and intervention or comparator in published HTAs, mixed recommendations from published HTAs, and non-English language reports, which may underscore the need to adapt published HTAs to Singapore’s context. To overcome some of these challenges, close consultation with stakeholders is critical to understand local clinical need and care pathways and to gather key information such as costs.ConclusionsPublished HTAs, when used as an evidence base and supplemented by evidence updates and local contextualization, allow for efficient and robust HTA to support decision-making.

Unmet need: definitions, literature evidence and implications for HTA

The present paper illustrates the definition of unmet need provided by the peer-reviewed literature and the Health Technology Assessment (HTA) authorities across Europe in the assessment and appraisal process and within the early access schemes for medicines. The analysis relied on a descriptive review of the peer-reviewed literature and HTA documents on the definition of need (disease severity) and the way it is satisfied (existence and validity of alternatives). HTA agencies were found using (i) a narrow definition of need, focused on the clinical impact and the impact on health-related quality of life of the disease and (ii) a broad definition of comparators, including treatments used off-label in the clinical practice. Most of the contributions of the literature advocated for a broader definition of need, including additional dimensions (for example, the socio-economic impact of the disease) and the effects of existing treatments beyond their risk-benefit profile (for example, acceptability to patients). On the one hand, these contributions should be considered by HTA agencies, considering its multi-disciplinary and multi-stakeholder nature. On the other one, the explicit inclusion of the unmet need domains, at present disregarded, should depend on the decisions taken on the ground of the assessment.

Toward Best Practices for Economic Evaluations of Tumor-Agnostic Therapies: A Review of Current Barriers and Solutions

ObjectivesCancer therapies targeting tumor-agnostic biomarkers are challenging traditional health technology assessment (HTA) frameworks. The high prevalence of nonrandomized single-arm trials, heterogeneity, and small benefiting populations are driving outcomes uncertainty, challenging healthcare decision making. We conducted a structured literature review to identify barriers and prioritize solutions to generating economic evidence for tumor-agnostic therapies. MethodsWe searched MEDLINE and Embase for English-language studies conducting economic evaluations of tumor-agnostic treatments or exploring related challenges and solutions. We included studies published by December 2022 and supplemented our review with Canadian Agency for Drugs and Technologies in Health and National Institute for Health and Care Excellence technical reports for approved tumor-agnostic therapies. Three reviewers abstracted and summarized key methodological and empirical study characteristics. Challenges and solutions were identified through authors’ statements and categorized using directed content analysis. ResultsTwenty-six studies met our inclusion criteria. Studies spanned economic evaluations (n = 5), reimbursement reviews (n = 4), qualitative research (n = 1), methods validations (n = 3), and commentaries or literature reviews (n = 13). Challenges encountered related to (1) the treatment setting and clinical trial designs, (2) a lack of data or low-quality data on clinical and cost parameters, and (3) an inability to produce evidence that meets HTA guidelines. Although attempted solutions centered on analytic approaches for managing missing data, proposed solutions highlighted the need for real-world evidence combined with life-cycle HTA to reduce future evidentiary uncertainty. ConclusionsTherapeutic innovation outpaces HTA evidence generation and the methods that support it. Existing HTA frameworks must be adapted for tumor-agnostic treatments to support future economic evaluations enabling timely patient access.

Recommendations to overcome barriers to the use of artificial intelligence-driven evidence in health technology assessment.

Artificial intelligence (AI) has attracted much attention because of its enormous potential in healthcare, but uptake has been slow. There are substantial barriers that challenge health technology assessment (HTA) professionals to use AI-generated evidence for decision-making from large real-world databases (e.g., based on claims data). As part of the European Commission-funded HTx H2020 (Next Generation Health Technology Assessment) project, we aimed to put forward recommendations to support healthcare decision-makers in integrating AI into the HTA processes. The barriers, addressed by the paper, are particularly focusing on Central and Eastern European (CEE) countries, where the implementation of HTA and access to health databases lag behind Western European countries. We constructed a survey to rank the barriers to using AI for HTA purposes, completed by respondents from CEE jurisdictions with expertise in HTA. Using the results, two members of the HTx consortium from CEE developed recommendations on the most critical barriers. Then these recommendations were discussed in a workshop by a wider group of experts, including HTA and reimbursement decision-makers from both CEE countries and Western European countries, and summarized in a consensus report. Recommendations have been developed to address the top 15 barriers in areas of (1) human factor-related barriers, focusing on educating HTA doers and users, establishing collaborations and best practice sharing; (2) regulatory and policy-related barriers, proposing increasing awareness and political commitment and improving the management of sensitive information for AI use; (3) data-related barriers, suggesting enhancing standardization and collaboration with data networks, managing missing and unstructured data, using analytical and statistical approaches to address bias, using quality assessment tools and quality standards, improving reporting, and developing better conditions for the use of data; and (4) technological barriers, suggesting sustainable development of AI infrastructure. In the field of HTA, the great potential of AI to support evidence generation and evaluation has not yet been sufficiently explored and realized. Raising awareness of the intended and unintended consequences of AI-based methods and encouraging political commitment from policymakers is necessary to upgrade the regulatory and infrastructural environment and knowledge base required to integrate AI into HTA-based decision-making processes better.

Frameworks for Synthesizing Qualitative Evidence in Health Technology Assessment: A Scoping Review Protocol

Health Technology Assessment (HTA) agencies and researchers recognize that evidence-based methodologies should be based on more than just quantitative evidence. Qualitative data enable evaluation based on feasibility, appropriateness, meaningfulness, patient values and preferences, acceptability, and equity. Despite some guidelines explaining how to conduct evidence synthesis of qualitative data, a specific framework or guideline for the HTA recommendation process is only recent and requires clarification . This scoping review aims to describe the frameworks, tools, and processes used to synthesize qualitative evidence and rate the quality of HTA. This scoping review follows the JBI methodology. The databases accessed were Medline (Pubmed), LILACS, CINAHL, Embase, Web of Science, Scopus, PsycINFO, Cochrane Library, JBI Database, and ScienceDirect. Grey literature was searched on PROQUEST, Open Grey, CADTH’s Grey Matters, Google Scholar, and HTA Agencies’ websites. The inclusion criterion was the synthesis of qualitative evidence frameworks as a concept, which refers to methods to synthesize evidence and rate the quality of evidence. HTA is applied worldwide, and there is no specific population . Data are presented in a tabular format and include fundamental concepts, frameworks, methods, subjects, and objectives.

Dynamic HTA for digital health solutions: opportunities and challenges for patient-centered evaluation.

Germany's 2019 Digital Healthcare Act (Digitale-Versorgung-Gesetz, or DVG) created a number of opportunities for the digital transformation of the healthcare delivery system. Key among these was the creation of a reimbursement pathway for patient-centered digital health applications (digitale Gesundheitsanwendungen, or DiGA). Worldwide, this is the first structured pathway for "prescribable" health applications at scale. As of October 10, 2023, 49 DiGA were listed in the official directory maintained by Germany's Federal Institute for Drugs and Medical Devices (BfArM); these are prescribable by physicians and psychotherapists and reimbursed by the German statutory health insurance system for all its 73 million beneficiaries. Looking ahead, a major challenge facing DiGA manufacturers will be the generation of the evidence required for ongoing price negotiations and reimbursement. Current health technology assessment (HTA) methods will need to be adapted for DiGA. We describe the core issues that distinguish HTA in this setting: (i) explicit allowance for more flexible research designs, (ii) the nature of initial evidence generation, which can be delivered (in its final form) up to one year after becoming reimbursable, and (iii) the dynamic nature of both product development and product evaluation. We present the digital health applications in the German DiGA scheme as a case study and highlight the role of RWE in the successful evaluation of DiGA on an ongoing basis. When a DiGA is likely to be updated and assessed regularly, full-scale RCTs are infeasible; we therefore make the case for using real-world data and real-world evidence (RWE) for dynamic HTAs. Continous evaluation using RWD is a regulatory innovation that can help improve the quality of DiGAs on the market.

OP84 Cost Consequence Analysis: A Potential Framework To Incorporate Patient Preferences Into Health Technology Assessment And Reimbursement Decisions

IntroductionPatient preferences (PPs) are an important source of evidence in health technology assessment (HTA). However, a methodological framework to achieve their integration in decision-making is lacking. We aim to investigate the potential role of evaluative frameworks to integrate PP evidence into HTA and decision-making.MethodsWe undertook a scoping review to identify potential methodological frameworks to consider PP evidence in HTA and evidence of the acceptability of these frameworks for decision-makers. We searched PubMed, Cochrane, and the grey literature to identify relevant studies, reports, or guidance documents. We restricted our search to the use of PP rather than patient experience data and excluded articles solely relating to deliberative approaches.ResultsFrameworks identified as having the potential to integrate PP evidence included cost-utility analysis, cost-consequence analysis (CCA), the efficiency-frontier approach, and multi-criteria decision analysis. All have been used in various HTA contexts, but not necessarily for inclusion of PP evidence. Distinct benefits and challenges of integrating PP data were identified for each framework. These included the theoretical basis of the frameworks, their ability to consider non-health as well as health outcomes, and their ability to separate outcomes based on PPs from outcomes based on population preferences. There is limited evidence and no consensus on the application of these frameworks to consider PPs in HTA or on their acceptability for decision-makers. However, CCA has the advantage that it is both based on economic decision theory and it leaves patient preferences disaggregated from population preferences in an HTA.ConclusionsThe frameworks identified in this review offer potential approaches to systematically and transparently integrate PPs into HTA and decision-making. Based on the review findings, we propose a research agenda to explore the potential of CCA in particular. We anticipate that our findings will augment the recommendations of the Innovative Medicines Initiative PREFER project, which are expected to report in 2022.

OP18 Applicability of Appraisal Tools of Real-World Evidence in Health Technology Assessment: A Literature Review and Content Analysis

OP18 Applicability of Appraisal Tools of Real-World Evidence in Health Technology Assessment: A Literature Review and Content Analysis

RWD147 Demonstrating the Application of Real-World Evidence for Health Technology Assessment Using a Federated Data Network

The European Health Data and Evidence Network (EHDEN.eu) is a large-scale federated network in development of real-world data from across Europe, standardised to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We demonstrate how EHDEN can facilitate the generation of real-world evidence (RWE) to support health technology assessment (HTA) in the context of cancer and COVID-19 use cases.

OP28 Health Technology Assessment: A Situation Analysis Of Zimbabwe

IntroductionWith ever increasing burden of disease and limited resources, health technology assessment (HTA) is required for efficient resources allocation and priority setting in healthcare. The objective of this study was to establish the baseline HTA evidence generation and use in Zimbabwe.MethodsIn 2019, we convened a stakeholder workshop on HTA at the University of Zimbabwe. Presentations on HTA processes, current healthcare reimbursement model, priority setting in the Ministry of Health and selection of medicines into the treatment guidelines, were done by the experts. We adapted the Health Intervention and Technology Assessment Program questionnaire for situational analysis of HTA introduction at national level and administered it among the workshop participants. We report the baseline information on HTA situation, the need, demand and supply of HTA in Zimbabwe obtained from the presentations and responses from workshop participants.ResultsA total of 33 participants attended the workshop. Participants indicated that there is no formal HTA agency or process in Zimbabwe. The selection of medicines into treatment guideline is determined by disease burden, safety, efficacy and cost data, and it is done by a group of experts. The Association of Healthcare Funders of Zimbabwe (AFHOZ) reported that private healthcare funders use resource-based relative value scale system to determine tariffs and reimbursement levels. The regulator requires safety, efficacy and product quality data for the registration of medicines. Transparency in decision-making, registration of heath technology and formulation of essential medicines and treatment guidelines were reported as the major needs of HTA. The major users of HTA outputs were reported as medicines regulator, AFHOZ and Ministry of Health. Key suppliers of HTA evidence are academic and clinical research institutions and healthcare workers. Lack of training in health economics was cited as the major challenge to supply of HTA evidence.ConclusionsThere is a need to institute a formal, systematic and transparent processes of determining value of health technologies.

Real-world data and evidence in health technology assessment: When are they complementary, substitutes, or the only sources of data compared to clinical trials?

Within the life-cycle assessment of health technologies, real-world data (RWD) have until now been of secondary importance to clinical trial data. The availability of massive, better quality RWD, particularly with the emergence of connected devices, the improvement of methods for characterizing populations, make it possible to have a better insight into the effects of treatment, sometimes on a national scale the importance of RWD is likely to progress in the eyes of health technology assessors, going from being traditionally complementary to possibly replacing clinical trial data. This is the fundamental question that the round table, involving experts from the academic and/or hospital, institutional, and industrial worlds, set out to answer. This work served first to establish the current role of RWD in health technology assessment, by distinguishing the main purposes of RWD, the timing of the evaluation in relation to the life cycle of the technology, and then according to the party commissioning or receiving the outcomes of RWD-based studies. Secondly, the round table proposed six general recommendations for more intensive and decisive use of RWD in the assessment and decision-making process.

The role of real world data and real world evidence in health technology assessment

Real world data (RWD) and real world evidence (RWE) is one of the most rapidly developing areas in the modern health care systems, which is caused by the development of technologies for both collecting and analyzing data, the emergence of new data sources and the formation of needs both by regulatory bodies, health technology assessment (HTA) agencies, and by the clinical and scientific communities. However, at the moment, there is no universal approach to RWD/E generation and application in the context of HTA. Over the past few years, the rate of including RWD/E in the HTA dossier has noticeably increased, but the nature of the existing guidelines and recommendations is rather fragmentary, which might create obstacles in the way of RWD/E study development and submission. The publication is aimed to describe and summarize the main and most rapidly developing spheres of RWD/E applications and analyze the possibilities of using RWD/E in various HTA areas in the world and in the Russian Federation considering the main trends in the further HTA development.

Real-world evidence in health technology assessment of high-risk medical devices: Fit for purpose?

Health technology assessment (HTA) of medical devices (MDs) increasingly rely on real‐world evidence (RWE). The aim of this study was to evaluate the type and the quality of the evidence used to assess the (cost‐)effectiveness of high risk MDs (Class III) by HTA agencies in Europe (four European HTA agencies and EUnetHTA), with particular focus on RWE. Data were extracted from HTA reports on the type of evidence demonstrating (cost‐)effectiveness, and the quality of observational studies of comparative effectiveness using the Good Research for Comparative Effectiveness principles. 25 HTA reports were included that incorporated 28 observational studies of comparative effectiveness. Half of the studies (46%) took important confounding and/or effect modifying variables into account in the design and/or analyses. The most common way of including confounders and/or effect modifiers was through multivariable regression analysis. Other methods, such as propensity score matching, were rarely employed. Furthermore, meaningful analyses to test key assumptions were largely omitted. Resulting recommendations from HTA agencies on MDs is therefore (partially) based on evidence which is riddled with uncertainty. Considering the increasing importance of RWE it is important that the quality of observational studies of comparative effectiveness are systematically assessed when used in decision‐making.