Early health technology assessment (eHTA) approaches focused on human stem cell-related technologies: a scoping review protocol

Abstract

Introduction

The growing advancement of innovative stem cell technologies requires careful evaluation of their economic, clinical and societal impacts. Early economic evaluations are essential for developing new medical technologies and supporting key decisions about commercialisation and market access. This scoping review explores Early Health Technology Assessment (eHTA) approaches specifically related to human stem cell technologies. By examining how eHTA can support the commercialisation of these therapies, we aim to clarify its role in optimising resource allocation and enhancing both the clinical and societal benefits of stem cell technologies.

Methods and analysis

To explore the use of eHTA in the development of stem cell-related technologies, a scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Scoping Review Extension guidelines. Systematic searches were conducted across scientific databases (MEDLINE, International HTA database, EconLit, PAIS Index and EconPapers), grey literature sources (Overton) and through hand-searching to identify eligible articles published from inception to 14 April 2026. No limits were imposed on language. Reviewers will independently record data from eligible studies using a standard data abstraction form. The gathered information will be synthesised both quantitatively and narratively.

Ethics and dissemination

Formal ethical approval is not required, as this study does not involve the collection of primary data. The findings will be shared through professional stem cell networks, published in national and international health technology assessment conference proceedings and submitted for open-access, peer-reviewed publication.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• The narrative synthesis will highlight the important role of Early Health Technology Assessment in guiding the future of stem cell technologies by providing comprehensive insights into economic sustainability, commercialisation and clinical and societal impacts.

• This study will actively involve patients with lived experiences in disseminating results. They will identify key stakeholders, suggest dissemination methods, prioritise findings and cocreate communication messages.

• Our search strategy will encompass peer-reviewed academic publications in all languages, as well as policy documents and grey literature databases.

• Non-English studies will be translated using Google Translate, which may result in suboptimal translations for data abstraction.

Introduction

In recent years, there has been a notable shift towards using early-stage health economic models to guide product development, market entry and pricing strategies. These early economic evaluations play a critical role in determining the commercial potential of new medical technologies, allowing companies to make informed decisions about whether to continue or halt development based on projected outcomes.¹ With a vast number of new health technologies emerging annually, only a select few reach the market and prove to be cost-effective.² Given the limited resources available in healthcare, conducting economic assessments as part of health technology evaluations becomes essential for optimising resource allocation.³ Moreover, integrating economic evaluations during the development phase of health technologies offers valuable insights that can influence investment decisions and the direction of further research, reflecting the increasing interest in early-stage economic assessments over the past few decades.^{4 5} Globally, billions of dollars are allocated to developing medical products, amid mounting pressure to optimise returns on these investments. Specifically, governmental bodies require information regarding the advantages of using public resources, corporations seek comprehensive data to effectively manage their product development portfolios and universities may need to align their research programmes to enhance societal benefits.^{6 7}

Early Health Technology Assessment (eHTA) is a proactive method for evaluating the potential value, feasibility and impact of emerging health innovations during the translational phase.⁸ The eHTA framework is defined as ‘a systematic approach to guide early evidence generation and synthesis to assess and demonstrate a technology’s potential value to payers, patients, providers and other healthcare interest holders, as well as to inform go/no-go decisions at an early stage of development.⁹ eHTA extends beyond economic modelling to encompass clinical safety and efficacy, economic feasibility and social and ethical considerations. These considerations encompass equity, accessibility, cultural acceptability and the facilitators and barriers to implementation, including existing regulatory pathways and workforce readiness.^{8 10 11}

Over the past few decades, stem cells have emerged as a novel and promising avenue in regenerative medicine, with research spanning both animal models and preliminary clinical trials. Stem cells are the fundamental building blocks of tissues and organs due to their distinctive ability to self-renew and differentiate into multiple cell lineages.¹² Stem cell potency refers to their ability to differentiate into various cell types. Totipotent stem cells can form all embryonic and extraembryonic tissues. Pluripotent cells differentiate into three germ layers but not extraembryonic types. Multipotent cells are limited to specific germ-line tissues, whereas unipotent cells are found in adult organs and are committed to a single lineage.^{12 13} Embryonic stem cells are pluripotent; however, they are constrained by legal and ethical considerations, thereby rendering induced pluripotent stem cells a more favourable alternative. These reprogrammed somatic cells can differentiate into various cell types, thereby supporting clinical and research applications without the ethical dilemmas associated with embryonic stem cells.¹⁴ Stem cells can be extracted from different sources, including bone marrow,¹⁵ amniotic cells,¹⁶ adipose tissue,¹⁷ umbilical cord¹⁸ and placental tissue.¹⁹ Organ bioengineering is an emerging, rapidly advancing application of stem cell technology with significant clinical and research implications.¹³ However, numerous technological developments are required before this technology can be widely implemented clinically.²⁰

As stem cell technologies continue to advance and enter various stages of clinical application, eHTA provides a systematic framework for assessing their safety, efficacy and economic implications before widespread adoption. This proactive approach not only enhances the understanding of the impact of stem cell technologies on patient outcomes and healthcare costs but also facilitates the alignment of research and clinical practices with societal needs. Ultimately, eHTA serves as a vital tool in navigating the complex landscape of stem cell technologies, ensuring that investments are justified and that emerging technologies are effectively integrated into healthcare systems. This review aims to provide a comprehensive assessment of the literature on eHTA approaches, with a specific focus on stem cell-related technologies. The objectives will be to (1) determine if and to what extent eHTA was previously used to guide the development and adoption of stem cell technologies, (2) characterise the approaches and methods used as part of the eHTA and (3) classify key value drivers such as clinical efficacy, safety, economic feasibility and ethical implications.

Methods and analysis

This article outlines the protocol for a scoping review currently underway. The review is being conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews²¹ and follows Arksey and O’Malley’s modified six-step framework.^{22 23} The reporting of this review is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) standards.²⁴

Information sources and search strategy

To identify relevant studies, a systematic search was conducted by a research librarian (JB) across MEDLINE (Ovid), the International HTA database, EBSCOhost EconLit, ProQuest PAIS Index, EconPapers and Overton databases from inception to 31 July 2025. The search terms were peer-reviewed by an independent librarian using the Peer Review of Electronic Search Strategies (PRESS) checklist,²⁵ resulting in the addition of new search terms and an update to the search on 14 April 2026. These databases were selected because they contain the most articles related to health economics and public health. The database search was complemented with a hand search of the reference lists of included reviews.

The search strategy began with two primary concepts: ‘stem cells’ and ‘early health technology assessment’. The latter concept was subsequently expanded to encompass the breadth of health technology assessment and early economic modelling. ‘Stem cells’ refer to undifferentiated cells that are present in the embryonic, fetal and adult stages of life and give rise to differentiated, specialised cells that are building blocks of tissue and organs.¹² We used the Ijzerman et al definition of eHTA, ‘all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty’.¹ Our search strategy imposed no restrictions on language and encompassed all peer-reviewed academic publications, books, editorials and commentary papers.²⁶

The keywords ‘stem cells’, ‘stem cell transplantation’, ‘early HTA’, ‘early economic evaluation’, ‘societal impact’, ‘safety’, ‘clinical impact’, ‘patient participation’, ‘intersectoral collaboration’, ‘delivery of healthcare’, ‘health inequities/disparity’ and ‘return on investment’ were used as search terms. These search terms were customised to align with the specific search functionalities of each electronic database (for instance, wildcards (*), truncations and the capacity to execute complex searches). A comprehensive search strategy has been developed for Medline (Ovid interface), as outlined in online supplemental appendix 1.

Eligibility criteria

A screening checklist was developed to guide this scoping review. A ‘no’ response to any study inclusion criteria (online supplemental appendix II) is grounds for exclusion from the scoping review. We will include any intervention self-identified as a ‘stem cell’ technology, and no experimental validation of stemness (self-renewal and differentiation) is required for inclusion. Publications were included if they mentioned eHTA or early economic evaluations and employed a systematic approach (framework) to evaluate eHTA for health technologies during the preclinical (in vitro or in vivo animal studies) or early clinical (entered human testing but is still in the initial phases of clinical trials (Phase 1 trials—focus on safety, dosing, tolerability, or Phase 2 trials—focused on effectiveness and safety) stages of development.⁹ During the preclinical stages of development, ‘very early HTA’ reflects basic research on mechanisms, while ‘early HTA’ reflects translational research, proof of principle and prototype product development. Studies that mention the use of eHTA or early economic evaluations but lack explicit details regarding what phase of development eHTA was performed could be included based on reviewer consensus if the study presents a structured analysis using eHTA methodology. Additionally, any article that uses emerging stem cell technologies, including transplantation, will be considered. Studies must also clearly present their analytical methodology and assess outcomes related to clinical efficacy, safety, economic feasibility and the ethical implications of stem cell-related technologies. No limits were placed on study design or language. Non-English studies will be translated by the authors, and translation software (Google Translate) will be used when necessary.²⁷ Where possible, articles with no available full text will be requested through the listed author contact information, through inter-library loan, or purchased from the publisher. In cases where articles couldn’t be retrieved, they were excluded from the assessment.

Study selection and screening process

The selection and screening of studies involves several stages, including a thorough literature search, refinement of the search strategy and review of articles for eligibility. Four reviewers (TF, SH, AA and US) are currently independently assessing titles and abstracts for inclusion, using the Covidence software platform designed for literature reviews.²⁸ The reviewers will obtain the full texts of studies that meet the eligibility criteria and assess their suitability using a standardised inclusion screening checklist. Any disagreements among reviewers will be resolved through discussion, with additional input from another author (VR) as needed. Inter-rater reliability will be assessed using Cohen’s kappa coefficient after reviewing titles and abstracts and following full-text evaluations.

Data abstraction

The reviewers (TF, SH, AA and US) will independently extract data from eligible full-text studies using a standardised data extraction tool in Covidence (online supplemental appendix III).²⁸ The tool extracts essential information from primary research reports, encompassing study characteristics such as author, publication year, country, study design and study objectives. It also captures details regarding the use of stem cell technology (target population, disease classification), types of stem cells (induced pluripotent, embryonic, somatic, perinatal or other (eg, mesenchymal, haematopoietic), origin of stem cells, eHTA context (funding sources, target audience or economic perspective (health system, payer, provider or societal), who initiates the evaluation, who commissions it, why an evaluation is needed and who conducts the evaluation), eHTA quantitative methodology, the stage of eHTA (very early (basic research), early stage (translational research) or other (early clinical research) and key value drivers, namely clinical efficacy, safety, economic feasibility, ethical considerations or other value drivers. Funding sources will be classified as academic institutions, public research funding, health system-based funding, research networks, non-profit organisations, state or provincial agencies or funding sources not reported. When a publication does not specify an economic perspective or clearly identify its target audience, reviewers will use their discretion to determine the intended audience. Any disagreements among reviewers will be addressed through consensus.

Collating, summarising and reporting the results

Data will be analysed and summarised descriptively. The study characteristics will be presented in tabular or graphical formats, along with a narrative summary. A narrative synthesis will be employed to outline the characteristics of the eHTA studies. The process of this narrative synthesis includes three stages: (1) developing the preliminary synthesis, (2) comparing themes within and across studies and (3) classifying themes (figure 1).²⁹ In accordance with our objectives, the narrative synthesis will detail emerging stem cell technologies documented in the literature, the eHTA methodologies used and the primary value drivers.

Figure 1. Narrative synthesis process. Diagram illustrating the three stages of the narrative synthesis process: (1) developing the preliminary synthesis, (2) comparing themes within and across studies and (3) classifying themes.

Patient and public involvement

In this study, patients with lived experiences (PWLE) will be actively engaged in the reporting and dissemination of results. They will serve to identify key stakeholders interested in the technology and highlight appropriate methods for disseminating the findings. Their involvement will help determine which findings should be prioritised for communication, codevelop an effective communication message, select appropriate dissemination settings and identify the most effective formats, such as presentations, pamphlets or social media infographics.

Ethics and dissemination

Formal ethical approval is not required, as this study does not involve the collection of primary data. The findings will be shared through professional stem cell networks, published in national and international health technology assessment conference proceedings and submitted for open-access, peer-reviewed publication.

Discussion

This scoping review will investigate eHTA approaches related to human stem cell technologies, an area of growing significance given rapid advances in regenerative medicine and the complexities of evaluating these innovative interventions. Stem cell technologies have the potential to significantly impact healthcare systems, potentially leading to a paradigm shift in patient care and treatment methods. eHTA, as a methodology, has been underused in bringing stem cell-related technologies to market and in investigating their return on investment. Our search strategy included peer-reviewed academic publications in all languages, as well as policy documents and grey literature databases. Additionally, our use of PRESS has enabled us to develop a search strategy with well-defined concepts that reflect the evolving use of eHTA in the literature. Our use of Google Translate will enable us to maximise the number of publications and translate full-text non-English studies; however, this may result in suboptimal translations for data abstraction.²⁷ To address the suboptimal translations, we will use a dual-extraction process, resolving disagreements by consensus. This review emphasises the importance of actively involving PWLE in disseminating research findings. PWLE are crucial for identifying key stakeholders, prioritising information and selecting the most effective communication methods, such as presentations, pamphlets or social media infographics. As the healthcare landscape evolves and numerous products compete for market entry, eHTA becomes an essential tool for stakeholders, including healthcare providers, policymakers and investors, to assess potential value before making significant investments. It helps bridge the divide between the scientific exploration of stem cell innovations and their practical application within healthcare systems. This alignment is critical, especially when funding constraints necessitate more refined resource allocation strategies. This proactive approach not only enhances the ability to manage uncertainties associated with these complex interventions but also ensures that investment decisions align with expected health outcomes, such as improved quality of life, increased survival and cost-effectiveness. Such alignment can significantly enhance the sustainability of healthcare systems, especially when implementing costly yet potentially transformative stem cell technologies.

Our review will highlight potential limitations in the existing literature on eHTA techniques, specifically those related to stem cell technologies. Engaging interest holders, including patients, clinicians and payers, during the assessment process could further enhance the relevance and applicability of eHTA findings, ultimately leading to more informed decision-making in healthcare settings. This scoping review will highlight the need for adopting robust eHTA methodologies to effectively evaluate stem cell-related technologies. As investments in these promising interventions continue to grow, it is crucial that future research focuses on refining assessment strategies, standardising metrics and incorporating a broader range of perspectives from interested stakeholders. By doing so, we can ensure that the potential benefits of stem cell technologies are realised in practice, thereby leading to improved health outcomes and optimised resource utilisation in healthcare systems.