title: Features, process and methods of early health technology assessment to inform developers of health technologies: a proposed framework and application to diagnostic technologies
Creators: name: Bouttell, Janet
Publisher: name: University of Glasgow
Year: 2021
Subjects: subject: early health technology assessment; developer-focused health technology assessment; early HTA.

description: Key points • This thesis aimed to develop a framework to help people undertaking health technology assessment of health technologies in development (termed ‘analysts’) approach their work. • It used a literature review and learning from five case studies to develop a framework which described the features of this type of health technology assessment, a generic process for undertaking the work and described which methods might be appropriate. Although the case studies are all diagnostic technologies, the framework would be appropriate for those working with small and medium-sized developers of any type of health technology. • Analysts need to be aware that HTA for developers of health technologies and their investors (termed ‘developers’) is different to HTA undertaken later in the technology’s lifecycle. Compared to HTA undertaken at market access stage, HTA undertaken to inform developers (termed ‘development-focused HTA’ or ‘DF-HTA’) informs a broader range of decisions and has to deal with a greater level of uncertainty, as the precise use of the technology may not yet be known and there is likely to be little evidence specific to the technology. • Although the process of DF-HTA will be familiar to analysts in that it involves the assessment of clinical and economic value, DF-HTA is more iterative in nature and does not have strict methodological guidelines to follow, as is often the case for HTA at market access stage. Analysts can take a more positive stance and put themselves in the shoes of the developer to consider what analysis would be useful to the developer at this stage of development. • The methods would be familiar to those carrying out health technology assessment but need some modification when the work is to inform developers. This is particularly relevant when resources for analysis are constrained, which is often the case when assessing technologies in development, many of which are likely to fail. In practice, this means that methods may be simpler. There is also more emphasis on methods of stakeholder consultation as a result of the lack of clinical evidence. • The framework would benefit from validation through prospective use in further case studies by external groups of analysts. This is particularly important because much HTA work undertaken for commercial developers is not published due to commercial sensitivity. Background and aims The development of health technologies is expensive and high risk, as many technologies in development fail to achieve commercial success. There are many choices to be made during the development process and the decisions made at this time are likely to influence the future success of the technology. It has been suggested that health technology assessment (HTA) undertaken during the development process may help to reduce the risk of failure or to accelerate failure and reduce research waste. The form of HTA used to inform developers about some of the decisions they need to make during the development process has been termed ‘Early HTA’. However, the current ‘Early HTA’ literature includes work which is not intended to directly inform developers (such as HTA accompanying managed access agreements) and much of the HTA that is conducted to inform developers is not published. As a result, there is a lack of clear guidance for the analyst on how to approach HTA to inform developers of medical technologies. This thesis proposes a framework to aid analysts (people undertaking HTA assessments) who are working with developers of medical technologies. The term developers is used throughout to describe the individuals or companies who are developing a medical technology and their investors/funders. Large pharmaceutical and medical device companies tend to have in-house HTA resource (often termed Health Economics and Outcome Research (HEOR) or market access teams). For this reason, the framework is aimed primarily at academic and consultant analysts working with small or medium-sized enterprises (SMEs). The framework comprises three sections: features, process and methods of HTA to inform developers (termed development-focused or DF-HTA). Features means the characteristics of DF-HTA. Process describes the broad activities of DF-HTA. Methods describes the analytical approach to those activities or how the analyst would undertake the activity. The framework was developed alongside five case studies in the assessment of diagnostic technologies which are included to illustrate the framework of features, process and methods. Methods A pearl-growing literature review was undertaken in October 2017 and refreshed in February 2019. Pearl-growing involves searching the citations and references of articles of interest until no further papers are being retrieved. The aim was to retrieve literature which informed an understanding of early health technology assessment and included both methods papers and applied studies. An iterative process was undertaken to develop a framework of DF-HTA including features, process and methods. An initial list of features of DF-HTA was developed then refined and expanded using an iterative process informed by the content of articles identified as being particularly informative and the experience of undertaking the case studies. Frameworks for the process of DF-HTA identified in the literature review were used as the basis for the development of a generic process of DF-HTA. Methods useful for DF-HTA were extracted from review articles. Methods of research and development or other commercial activities were excluded. Terminology was streamlined where similar terms were describing the same method. Five case studies were used to illustrate the framework of DF-HTA. For each of the case studies the features were compared to the list of features and areas of non-conformity identified and discussed. The process of DF-HTA included clinical value assessment in all cases and economic value assessment in four of the five case studies. Methods were selected from the methods identified as useful for DF-HTA. Results A total of 152 early HTA papers were identified of which 88 were judged to be aimed at informing developers. These comprised 56 methods, 61 applied and 35 methods and applied papers in early HTA of which 43 methods, 25 applied and 20 methods and applied were aimed to inform developers. A proposed framework of DF-HTA was developed including the features, a generic process and a range of methods suitable for DF-HTA. Ten features characterising DF-HTA were identified including six which had not been previously identified: audience; timing; decisions informed; available evidence; underlying user objective; decision space; business model; resources for analysis; stance of analysis and burden of proof. The proposed generic process of DF-HTA comprises two core aspects of DF-HTA identified in all the frameworks found in the literature – clinical value assessment and economic value assessment. Clinical value assessment considers what impact the technology might have on clinical practice and ultimately upon health (and wider social) outcomes. Economic value assessment builds on the clinical value assessment to consider the economic impact of changes in healthcare resource use and other economic value drivers such as productivity effects. Eight broad groups of methods useful in DF-HTA were identified from review articles: care pathway analysis; qualitative methods of stakeholder interaction; literature review; multi-criteria decision analysis; discrete choice experiments; expert opinion and elicitation; cost effectiveness analysis and value of information analysis. The framework was illustrated using the case studies. The features of DF-HTA were evident in three case studies of technologies in development but not in two case studies concerning technologies already in clinical use. The process and methods used in the case studies aligned with the generic process of DF-HTA. All the case studies began with a clinical value assessment using decision models to map the existing and potential clinical pathways. For the three DF-HTA case studies parameter estimates came from the literature and expert opinion initially supplemented by evidence from small clinical studies specific to the technology where this was available. The case studies show that an initial clinical model is able to distinguish technologies with potential value from those with little potential value. Cost-effectiveness or cost consequence models were able to identify potential economic value, indicate design factors which required clarification before further development and identify parameters likely to have a significant impact on potential economic value. The two case studies which involved technologies which were already in clinical use were able to show, using similar methods to DF-HTA and in situations where evidence was limited, cost savings and consequences of expanding a testing programme and introducing a triage test. These case studies demonstrate the need for alternatives to cost-effectiveness using methods appropriate at market access/adoption stage when resources are limited. Conclusion The main contribution of the thesis was to propose a framework of features, process and methods of DF-HTA. A secondary contribution was to provide five empirical examples, three in DF-HTA and two in early economic evaluation of diagnostic technologies. The case studies use simple models that can be readily used to provide an indication of the potential value of a technology whilst it is under development or during some form of expedited review. The main limitation concerns the likely incompleteness and unrepresentativeness of HTA studies to inform developers in the academic literature. This is because of commercial confidentiality and a lack of an incentive to publish. This thesis suggests that developers should be encouraged to consult an HTA practitioner at an early stage in the development. Where development is technology-driven (i.e. the technology is developed without a precise clinical need identified), DF-HTA can help developers to ‘position’ their technology, articulate value propositions and engage with stakeholders. This process can sometimes change the design or intended direction of the technology in development and can inform evidence generation strategy. For analysts, the framework should provide guidance on the nature, process and methods of HTA to meet the needs of the developer. For policy-makers the thesis suggests that it is possible and desirable to encourage the articulation of a value proposition (particularly for translational research) within funding applications. It is also essential to support translational research bodies which facilitate links between commercial entities, academic and clinical researchers, clinicians, regulators and reimbursement agencies. Policy-makers may also wish to fund the development of full disease models which could be used to rapidly and robustly evaluate any proposed technology (in technology-driven development) as well as determining areas of greatest need to inform specific calls for innovation (needs-driven development). Further research exploring the features of in-house and unpublished DF-HTA and the usefulness of this framework of DF-HTA to developers and analysts would be valuable. The decision-making process for the adoption of many technologies is not clear and transparent and research into the evidence relied upon by decision-makers in different settings would be useful. The extent to which full disease models have been or could be used to assess the value proposition for innovative technologies would also be a useful area of research.