Background: Early Health Technology Assessment (EHTA) is an evolving field in health policy which aims to provide decision support and mitigate risk during early medical device innovation. The clinician is a key stakeholder in this process and their role has traditionally been confined to assessing device efficacy and safety alone. There is however, no data exploring their role in this process and how they can contribute towards it. This motivated us to carry out a systematic review to delineate the role of the clinician in EHTA as per the PRISMA guidelines. Methods: A systematic search of peer reviewed literature was undertaken across PUBMED, OVID Medline and Web of science up till June 2018. Studies that were suitable for inclusion focused on clinician input in health technology assessment or early medical device innovation. A qualitative approach was utilised to generate themes on how clinicians could contribute in general and specific areas of EHTA. Data was manually extracted by the authors and themes were agreed in consensus using a grounded theory framework. The specific stages included: All stages of EHTA, Basic research on mechanisms, Targeting for specific product, Proof of principle and Prototype and product development. Bias was assessed utilising the NICE Qualitative checklist. Results: A total of 33 articles met the inclusion criteria for the review. Areas identified in which the clinicians could contribute to EHTA included: i) needs driven problem solving, ii) conformity assessment of MDs, iii) economic evaluation of MDs and iv) addressing the conflicts in interest. For clinicians' input across the various specific areas of EHTA, an innovation framework was generated based on the subthemes extracted. Conclusions: The following review has identified the various segments in which clinicians can contribute to EHTA to inform stakeholders and has also proposed an innovation framework.
Keywords: Health technology assessment; Medical device; Innovation; Needs analysis; Efficacy; Safety; Clinician; Clinical strategy; Framework
Electronic supplementary material The online version of this article (10.1186/s12913-019-4305-9) contains supplementary material, which is available to authorized users.
The medical device (MD) industry is one that is in the stage of accelerated growth globally. It currently has a compounded annual growth rate (CAGR) of 5.3% per annum and is projected to be worth 674.5 billion USD by 2022 [[
Taking this conundrum into consideration, several governmental organisations and researchers realised the necessity for decision support tools to be developed to provide innovation guidance for these SMEs during this time with high levels of uncertainty [[
Early health technology assessment (EHTA) is a field in its infancy within health policy. Its foundations lie in the pharmaceutical industry as a derivation of health technology assessment (HTA). HTA however had several shortcomings in informing the EMDI process. Firstly, it was crafted with the aim of assessing a technology after it was developed [[
As with HTA, initial studies describing EHTA positioned it as a manner of economic evaluation in the early stages of product development [[
The available evidence at present alarmingly suggests that decisions in the EMDI are taken without decision support and with motivations spanning from enthusiasm, a need to pioneer and responding to market competition [[
EHTA addresses this through a structured process which addresses multiple facets and stakeholders in the EMDI and therefore allows for risk mitigation [[
In addition, modern day EMDI is facing a climate where R&D is becoming more complex and resource intensive, healthcare budgets are shrinking and consumer demands are increasing [[
Furthermore, there is significant disconnect between the supply and demand side logics of the EMDI process as well. The supply side logic places emphasis on innovation policy outcomes, which considers wealth generation as a key consequence, whilst the demand side logic has a focus on health policy outcomes instead. EHTA helps bridge this gap between both these spectrums with the aim of bringing equilibrium to the process [[
To put EHTA in context, a brief understanding of medical device development is necessary. Medical device development is a multi-faceted process which takes a concept from ideation and translates it to a product which can be utilised by the end users. The process fosters interdisciplinary collaboration amongst various professionals (i.e. clinicians, engineers, business development executives) with the eventual goal of delivering a successful innovation outcome [[
To date, several authors have described a variety of conceptual models to describe the various stages in the process and how they interact [[
Graph: Fig. 1The medical device development process. The red outline illustrates the realm in which Early Health Technology Assessment (EHTA) occurs. The green outline illustrates the region where traditional clinical research influences the process. (Utilised with permission and adapted from Ijzerman and Steuten)
EHTA techniques are particularly of use during the periods of basic research and translational research (outlined in red). This is during a phase in the device life cycle where development is still ongoing and high-risk engineering and investment decisions are being made with a large level of uncertainty as to their future outcomes [[
A clinician is defined as 'an individual who utilises a recognised scientific knowledge base and has the authority to direct the delivery of personal health services to a patient' [[
Traditionally, clinicians have been the main triggers for the development of novel MDs and their role is deeply intertwined with the EMDI process [[
The available evidence however, does suggest that the clinician does serve a function beyond conformity assessment alone. For instance, several authors have emphasised that in early translational work, the first and most important decision which guides the process of medical innovation is whether the product has a clinical need [[
Furthermore, it should also be highlighted that early clinician involvement can avert potential reverberations later in the EMDI as well. For instance, regulatory bodies have linked the paucity of robust, high quality studies in the regulatory approval process to the lack of clinical evidence generation early in the innovation process as well [[
Considering these findings, it would be safe to assume that the clinician is a key stakeholder in the EMDI process and can further contribute to the EHTA process.
Recognising the intimate relationship between the clinician and the EMDI, we sought to understand the areas in which they could contribute to EHTA. The area of interest is outlined in red in Fig. 1. As part of the multidisciplinary team (MDT) overseeing the process, clinicians are in a pole position to influence the EMDI and additional value can only be anticipated with clarity in how they can contribute to the EHTA process. Despite this, there appears to be no data in the literature to provide guidance on the role of the clinician as well as how they can effectively contribute to this EHTA process.
Identifying this gap in knowledge was a primary motivation for us to carry out a qualitative methods systematic review to delineate the role of the clinician in the EHTA process. The primary objective of this review is to provide clarity and a framework to researchers in the field of EHTA regarding areas and manners in which the clinician could influence EHTA.
A search was carried out across 3 databases (PUBMED, OVID Medline and Web of science) by VS, RW and SK as per the PRISMA guidelines up till June 2018.
Theoretical and application studies were considered suitable for this systematic review. Application papers were defined as any studies which utilised empirical data in formulating their conclusions. All other papers were considered theoretical in nature. No exclusions were made for the year of publication. Articles of relevance identified from the reference lists of studies searched were suitable for inclusion in the review as well. Only articles in English were considered suitable for the following review.
The search strategy utilised is illustrated in Additional file 1. Search terms utilised include combinations of the following: medical device*, clinician*, health technology assessment and medical device development. Figure 2 depicts the flow of information through the various phases of the systematic review.
Graph: Fig. 2PRISMA flow chart for the study
Based on the search strategy employed in Additional file 1, no articles were found describing the specific role of the clinician in EHTA. As such, the inclusion criteria for the review was any article focussing on the role of the clinician in health technology assessment or early device innovation. This was confined to articles focusing on device development prior to the commencement of phase I trials as suggested by Markiewicz et al. [[
Citations were screened for suitability of inclusion in study and full text articles were ordered and read to determine short listing of the article for further review. Citations were screened by VS, RW, JAS and SK. Following shortlisting, the articles were read thoroughly by RW, VS, JAS and AN, and inclusion for the review was based on consensus.
Given the nature of the topic and the lack of available evidence, a qualitative approach was employed for evidence synthesis.
A grounded theory framework was employed to allow examination of the clinician's role in EHTA. This approach allows for development of theories and concepts grounded in the study data [[
Segments where clinicians could influence aspects of EHTA were defined as per the stages highlighted in red on Fig. 1 – an approach similar to the review carried out by Markiewicz et al. [[
Articles shortlisted for inclusion were read thoroughly by VS, RW and AN in tandem. In line with the objectives of the study, the articles were examined for references to the clinician's role in EMDI and the stage of EHTA (if available) it impacted upon. An initial thematic content analysis was then carried out by all three authors in tandem for each article in a systematic manner through immersion in the data, coding and subsequent data interpretation. This was to reduce researcher biases in summarising the content of the various sources of literature and increase credibility.
Reflexivity is a process which has been proposed during qualitative analysis procedures to aid in addressing self-bias, preferences and theoretical predispositions [[
Independent analyses were subsequently compared for commonalities and differences and a consensus summary for each article was compiled in Additional file 2.
Data items of interest included study design, year of publication, article type (theoretical or application), primary issue raised in the article, impact of issue in EHTA, stage of EHTA which the issue had significant impact on and supplementary issues described by the article.
Assessment of study quality was carried out by utilising the NICE (UK) Qualitative Appraisal Checklist (Attached as an Additional file 3). This is presented in Table 1. The assessment was carried out by RW, VS and SK individually and consensus was reached in discussion before an overall score was given for the quality of the study.
NICE qualitative appraisal checklist ratings for studies included in review
NICE Qualitative Assessment Tool Number of studies Percentage of all studies (%) Studies ++ 12 36.4 [ + 13 39.4 [ – 8 24.2 [
++ − all or most of the checklist criteria have been fulfilled and the conclusions of the study are unlikely to be altered by those criteria that have not been fulfilled, + some of the checklist criteria have been fulfilled and where they have not, the conclusions of the study are unlikely to be altered, − few or none of the criteria checklist have been fulfilled and the conclusions are very likely to be altered
Building on the initial thematic analysis carried out in 2.4 and documented in Additional file 2, a secondary thematic analysis was carried out to address the primary objectives of the systematic review (presented below). For this stage, studies were eligible for classification across multiple themes the summarised data was independently analysed by VS and RW and independent categories were identified.
Reflexivity was taken into consideration during the synthesis of results by using AN as a moderator for the themes generated in unison. He was involved in generating Additional file 2 and was thus aware of the general content of the included articles. He was also made to read seminal text of the clinicians role in early medical device innovation as well as EHTA so as to have a 'content expert' on the various roles of the clinician as well [[
These analyses were subsequently compared for commonalities and differences and recurring themes and subthemes were developed with AN in an attempt to establish data which was broad as well as theoretically grounded as well. Eventually, all themes and subthemes were generated following consensus between VS, RW and AN.
For the analysis, the two areas of interest were:.
This thematic area was focused on specific mechanisms through which the clinician can be engaged in EHTA and influence the EMDI process.
This thematic area focussed on the establishing a framework for the clinician to partake across the various phases of EHTA (all phases, basic research on mechanisms, targeting for specific product, proof of principle and prototype product development). The motivations behind this was to function as a guide for clinician integration at any phase of the EHTA process.
For the following systematic review, 33 articles met the inclusion criteria. 24.2% (n = 8) papers were application papers and 75.8% were theoretical papers. The years of publication ranged between 1996 to 2017. Data which was extracted from each of the papers is tabulated in Additional file 2 which was utilised to generate the themes and subthemes.
Table 2 contains a summary of the themes and subthemes to address the question of areas in which clinicians can contribute to the EHTA process and is graphically represented in Fig. 3. The means by which the clinician can contribute and interact in the EMDI process across the specific stages of EHTA is summarised in Table 3. Figure 4 further illustrates this as a framework to allow for ease of applicability of the findings.
Graph
Graph: Fig. 3Areas in which clinicians can contribute to EHTA. Percentages in themes (yellow) are in comparison to all studies (n = 33) included in the review. Sub theme (blue) values are for all studies included in the theme
Graph
Graph: Fig. 4Framework through which clinicians can contribute to the various stages of EHTA
As a whole, the themes and subthemes generated encompassed:
As a theme, the majority of studies (69.7%) described 'needs driven problem solving' as a key area of contribution by clinicians towards the EHTA process. The concept was also noted to have utility across all stages of the EHTA process with 15–27% of studies outlining its utility in some manner.
In terms of subthemes, assessing the 'clinical need' was given the highest level of importance with 45.5% of studies identifying it as an area of importance. In particular, the importance of this input seemed to be more impactful in the early stages of 'basic research on mechanisms' and 'targeting for a specific product' with between 15 and 27% of studies identifying it as 'part of a needs based approach to identifying problems' and 'needs based approach to targeting solutions with a MDT'.
In addition, 33.3% of studies in the review further highlighted the assessment of 'user needs' a sub theme of importance. Particularly 15.2% of the studies mentioned it to be of relevance across all stages of EHTA.
Finally, 33.3% of studies highlighted the assessment of 'manufacturer needs' as a subtheme of relevance.
33.3% of studies in this review identified 'conformity assessment' as a major theme with 18.2% of them suggesting a preponderance for it to be utilised in the 'prototype and product development phase'.
The subthemes generated highlighted the issue of clinical performance, safety and study design in particular.
15.2% of studies in the review identified 'economic evaluation' as a major theme. In addition, 9.1% have identified its area of importance to the stage of 'prototype and product development'.
9.1% of studies mentioned 'addressing COI' to be a major theme and a theme across all phases of EHTA.
The discussion will aim to expand on the findings of the review and attempts will be made to highlight specific methods through which the clinician can partake in the process as well.
The assessment of the clinical need is arguably one of the most important roles which the clinician must fulfil which impacts on all other aspects of EHTA.
The MD industry has historically been one which attempts to utilise technologies from other sectors to solve clinical problems. As such, the starting point often begins with a technological focus with hopes of translation to a device which solves a meaningful clinical issue [[
Given the privileged position and immersion they have in patient care, the clinician is in a unique position to understand the pain points and subsequently demarcate these accurately. In addition, they function as a valuable resource in the MDT by providing insight into the feasibility of a solution given their knowledge of its context in the cycle of care of the patient. This lays the foundations towards developing a technology which can holistically address these areas of concern in contrast to moulding a use case on the basis of the technology alone [[
Multiple resources are available to clinicians to establishing this clinical need and develop a statement of clinical need (SCN) to adequately define the scope of the clinical problem to be solved. Commonly utilised mechanisms include in depth reviews of the literature addressing the area of need, direct observations and interviews with key opinion leaders in the field [[
An in-depth discussion into the methods and areas of focus of the needs assessment is beyond the scope of this article. A thorough understanding of the factors to consider at this juncture can be sourced from the Stanford Biodesign model which articulates a clear approach to this process through their 'Identification phase' [[
The ability of users to contribute to the various phases of the EMDI has been well established in the literature and is known to ascribe value to the process [[
It must be borne in mind however, that users encompass a wide range of individuals spanning from clinicians to end users (i.e patients and their family members). Understanding their individual needs is imperative for a successful device development process, product quality and safety [[
Particular reference has to be made to the work of Shah et al. in their attempt to demarcate a framework through which user input can be elicited. These serve as excellent reference material for clinicians attempting to delineate user needs and integrate them into the device innovation process [[
In the EHTA process, clinicians can employ a variety of quantitative methods to assess this including interviews and surveys through study design from early stages in the design process. It must be mentioned however, that in assessing user needs, there is substantial bias towards considering the needs of clinicians in contrast to end users [[
Clinicians also need to have a thorough understanding of the value chain of the manufacturer involved in EMDI to generate the greatest impact during EHTA (i.e manufacturers business model,R&D process, regulatory strategy,go to market strategy) [[
A key advantage of this knowledge is the awareness it generates towards obtaining critical data which contributes towards this value chain during the EMDI process (i.e validating the value proposition of the MD, marketing information, forecasting adoption, price sensitivity) [[
'Conformity assessment', which entails characterising the clinical performance and safety of a device, is regarded as the core contributory area in EHTA for the clinician.
Historically, clinicians have been well-versed with conformity assessment by leveraging on their knowledge in specific areas of interest. The importance of demonstrating conformity assessment cannot be understated, as the MDs clinical utility, value proposition and the subsequent regulatory process hinge on it [[
In demonstrating performance, clinicians should be aware that the burden of proof is heavily dependent on the ability to demonstrate that the device can perform its purported claims adequately (and equally to a comparator if available) to the regulatory bodies [[
It must be mentioned however that displaying clinical performance is a very separate concept to demonstrating clinical effectiveness. Establishing effectiveness sets the bar higher for manufacturers in terms of having to demonstrate that the MD performs better than its available comparators [[
In establishing these endpoints, Hamilton offers valuable insight into the benefits of a thorough literature review prior to the commencement of the entire collaboration process for identification of useful outcome measures which can be utilised to characterise device performance [[
When discussing the evidentiary burden for medical devices, the risk profile of the device needs to be taken into consideration as well. For the various regulatory pathways, the level of evidence required for the devices varies significantly and this should be taken into consideration from the beginning in designing the feasibility studies. Essentially, this allows for extrapolation of the data from these studies to guide the design and pre-empt the logistical issues which may affect the pivotal trails for the device [[
For the clinician, there is also a necessity to prove through conformity assessment that the MD is safe for patients and does not pose any threat to their health.
The relevant information for these end points can be sourced from the IB provided by the manufacturer. This describes any prior adverse reactions encountered through device use and encompasses a risk management tool which outlines potential safety risks of the device to the patient and how to manage those risks as well. Further device specific risks can also be elicited from systematic review of the literature and device registries of similar or predicate devices [[
One of the findings of this study is in relation to considerations towards study design during the EHTA process. This is to be expected given the broad group of contrivances which are considered to be MDs which invariably impacts on conformity assessment. 15.2% of studies in this review identified 'study design to address device conformity' as a subtheme. This issue was further elaborated on in the framework generated too. The review identified the need for 'modified clinical trials to address the innovation framework' (3–18.2%), which highlighted the need for modified and adaptive trial designs to cope with the device specific peculiarities in assessing MDs.
There are a number of factors specific to MDs which enact this influence on study design. Firstly, MDs undergo cycles of rapid of change, between 18 and 24 months in duration, during their development. Subsequent iterations of the device often include updates of incremental innovation. As such, the right time to assess the device is often a subject of debate and confusion. In addition, it further raises questions of the generalisability of the MD being tested and the final product as well [[
In the context of these limitations, a move to address them must be propagated from angle of trial design itself. Industry generally has propagated the notion that the randomised controlled trial (RCT) is the design of choice to assess MDs. As can be discerned from the characteristics of MDs, the RCT for EHTA may not be the gold standard as it will provide only limited information as feedback into the early innovation process. With certain high-risk devices, the RCT itself may not be a feasible option and be unnecessary or inappropriate [[
The available evidence suggests that MD uptake has driven healthcare costs up globally [[
Traditionally, the responsibility of assessing value was left to physicians which understandably provided a myopic view of it [[
Furthermore, this evolution also seems to have detached the clinician from the evaluative process itself [[
Thankfully, to date, the focus and development of EHTA has been centred on economic evaluation. The literature describes techniques such as headroom analysis and return on investment (ROI), which can be easily incorporated into the EHTA process by clinicians. These methods however, are beyond the scope of the current article but the following articles provide valuable insight into the techniques and their relevance [[
The propensity for conflicts of interest (COI) to occur during participation in the EHTA process is one which is of significant concern to the clinician. 9.1% of studies mentioned 'Addressing COI' to be a major theme and a theme across all phases of EHTA.
COI is a necessary evil during the EHTA process and in collaborations between clinicians and industry. As demonstrated by the review, the role of the clinician in EHTA is one which is vital and as such, a move to completely remove the clinician from enterprise is one which is unfounded and unrealistic [[
Both Table 3 and Fig. 4 provide an overview of the framework which clinicians can utilise to contribute to the EHTA process. Although not exhaustive in nature, it provides direction of key issues for consideration.
Of note is 33.3% of studies identifying 'Adapt model to address the scope of early device innovation'. This theme illustrates the variable nature of the EHTA process in relation to the MD being innovated upon. Clinicians should be aware that the EHTA process is one which is in a constant state of flux and, is not one that is linear and stagnant. This theme highlights the need for clinicians to remain vigilant to these MD specific peculiarities, such as the risk profile of the device, and adapt the EHTA process as appropriate to address these.
One of the main limitations of this study is in the search strategy utilised. Although in line with the PRISMA guidelines, relevant information from grey document sources were not included in the search which may have provided a more holistic perspective of the clinician's role in the process. These issues can be averted with the utilisation of information specialists in the generation of a search strategy in future work on the issue.
The quality assessment using the NICE quality assessment tool was aimed to provide an overview of the quality for the studies included in this review. As can be garnered, nearly 24.2% were of low quality. This was mostly in relation to the opinion pieces and commentaries which were examined for inclusion. Given the nature of the topic however, we deemed it vital to get as much perspective on the early medical device innovation process to generate the aforementioned data. In addition, this is an issue traversed often in qualitative research. Furthermore, these studies remain valuable in generating the themes identified in our review.
In addition, investigator bias and reporting bias in generating themes is an aspect that needs consideration as well. Attempts were made to address this by recruiting an MDT, comprising of clinicians and biomedical engineers involved in the bio design process, for this review to generate themes and subthemes. It must be borne in mind however, that certain elements of the area of interest may be substantially over or under represented as a result.
Furthermore, the proportions generated for themes and subthemes in 3.2 and 3.3 be depended upon to classify the importance of issues hierarchically given the diversity of topics and the manners in which they have been generated. This is intended to provide an overview and justification for the selection of the themes.
One aspect of research direction that will benefit clinicians is the development of a specific framework for clinical trial design and adaptation for EHTA. Although our framework in Fig. 4 provides an overview of issues which can be addressed, there will be value in demarcating the exact factors which can be incorporated in trial design and how they feed back and add value to the EHTA process. This is one of the core focuses of future research of our group.
It should also be highlighted that previously, device innovation had a strong focus on 'supply side' factors in delineating lower cost, better efficacy and safety. Recently however, there has also been more interest in 'demand side' technologies which are more patient centric (i.e. non-invasive, telemonitoring) and less focussed on those historical tenets [[
Finally, another element that is also worth evaluating would be the cost effectiveness attached to the process of EHTA as a process itself. Given the large investment in time, resources and capital directed towards it, the value of the process itself is yet to be evaluated.
Involving the clinician will be an additional if not missing piece to the complex puzzle which is EHTA. As demonstrated by the findings of this review, areas in which clinicians can contribute include conformity assessment, needs based problem solving, economic evaluation and addressing issues of COI. In addition, this can take place across the various specific stages of EHTA as illustrated by the framework in Fig. 4. When carried out in a structured manner, one would anticipate that the feedback loop will allow for teams to pivot at a stage when it is technically feasible and affordable then at later phases where minimal change can be exerted over the technology or its applications. Furthermore, such an approach will aid in stakeholder making decisions on MD ventures in an informed manner as they are empowered with the knowledge to do so.
This research received no specific grant from any funding agency in the public, commercial or not- for – profit sectors.
No acknowledgements were applicable to the following systematic review.
VS, AN, RW,SK and JAS were involved in the conception, systematic review search, generation of themes, writing, editing and revisions of this manuscripts from conception till submission. FDSC, BV and EMW were involved in the writing, editing, and revisions of the manuscript from conception till submission. All authors have also read and approved the final manuscript.
All data generated or analysed during the study is included in this published article and in the supplementary data.
Not applicable.
Not applicable.
VS owns shares and works as a consultant for Biorithm Pte Ltd. AN, JAS and RW are employees of Biorithm Pte Ltd. SK, FDSC, BV and EMW, and have no competing interests.
Graph: Search strategy (DOCX 14 kb)
Graph: Data extracted from studies to delineate areas in which clinicians can contribute to the EHTA process. (DOCX 46 kb)
Graph: NICE qualitative appraisal checklist. (PDF 1073 kb)
• COI
- Conflict of information
• EHTA
- Early Health Technology Assessment
• EMDI
- Early Medical Device Innovation
• HTA
- Health Technology Assessment
• MD
- Medical device
• MDT
- Multi Disciplinary Team
• R&D
- Research and Development
• SME
- Small and Medium sized Enterprises
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