Abstract
Aim: Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells. They offer groundbreaking new opportunities for the treatment of disease and injury. However, ATMP adoption requires adjustments to current clinical practices and frameworks. This study investigates the readiness of the Irish healthcare system to adopt licensed ATMPs.
Materials & methods: Scoping review, guided by the preferred reporting items for systematic reviews and meta-analyses – scoping review extension. A systematic search of English articles from 2013 to 2023 (published and grey literature) will be conducted.
Results: Findings will be presented via narrative summary, graphical and tabular formats.
Discussion: Review findings will be discussed in the context of recommendations that will inform national policy and strategy on the adoption of ATMPs in Ireland.
Keywords: : advanced therapies, ATMPs, gene therapy, healthcare systems, institutional readiness, regenerative medicine
Plain Language Summary
This study examines whether Ireland’s healthcare system is ready to use new kinds of medicines called advanced therapy medicinal products (ATMPs). These medicines are made from genes, tissues or cells and can be effective in treating certain diseases. However, delivering these medicines might mean changing current practices in clinics and hospitals.
A scoping review will examine publications from 2013 to 2023 that focus on this topic. Results will be reported via narrative summary, graphs and tables. A discussion of the findings will be completed to inform recommendations for preparing the Irish healthcare system to deliver ATMPs.
Ethics and dissemination: Ethical approval is not required for this scoping review. Findings will be disseminated through publication, stakeholder meetings and public engagement.
Plain language summary
Article highlights.
Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells.
The Irish healthcare system’s readiness for adopting ATMPs is unclear and, to the best of the authors’ knowledge, has not been explored previously.
A scoping review was chosen as the best way to investigate this topic.
This scoping review protocol aims to detail the aims of this scoping review and how it will be structured.
The scoping review detailed in this scoping review protocol aims to assess the readiness of the Irish Healthcare system to adopt licensed ATMPs and identify necessary changes required to strategically position the Irish healthcare system for future ATMP adoption.
This scoping review will be in accordance with the Joanna Briggs Institute PRISMA-Scr approach.
Both published and grey literature in English from 2013 to 2023 will be considered.
The population, concept, context (PCC) framework will dictate eligibility for inclusion to the review.
A previously published framework on ATMP adoption will be used to specify the concept of ‘institutional readiness’.
We anticipate that the results of this review will help identify gaps in current research relating to the adoption of ATMPs within the Irish healthcare system.
We anticipate that these results will also inform future national policy relating to the adoption of ATMPs within the Irish healthcare system.
Results will be summarized descriptively using a narrative approach and using summary tables.
The findings of the research will be submitted to relevant peer-reviewed journals for publication.
1. Rationale
Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells [1]. ATMPs aim to cure rather than manage chronic conditions [2]. The scope of technology employed in these therapies is wide ranging, from the use of stem cells, gene editing and therapy and novel biomaterials [3,4]. For diseases where there is an unmet clinical need, ATMPs can potentially offer patients enduring remission [5]. Delivery of ATMP treatments differ from current, established practices in several ways. These therapies are frequently once-off, highly personalized and are limited to specific populations. Further, the use of live tissues makes it more difficult to standardize and measure clinical outcomes through conventional trials procedures [6]. As these therapies are so different to conventionally offered treatments, adaptions are needed across many systems. For example, it is uncommon for clinical staff to have received formal education or training in regenerative medicine and is therefore crucial prior to ATMP clinical rollout [7].
There has been recent accelerated growth and development in this field; with this arises a need for adaptive clinical practice. Healthcare systems must be ready to adopt these scientific advancements and provide access to these therapies in a safe, patient-centered and efficient manner [8]. ATMP translation requires multidisciplinary stakeholders not just from medical specialities but from other fields such as engineers, biomedical scientists, laboratory medicine specialists and qualified persons [9]. The involvement of patients [10], patient charities and patient organizations are also crucial. Furthermore, ATMPs require specialist manufacturers and facilities with clinical and commercial use permissions, and practitioners with specialized knowledge [11]. Webster and Gardner have previously explored difficulties in translating ATMP knowledge to practice in the UK [12–14]. A hospital, for example, requires access to a Good Manufacturing Practice-licensed facility [15], specialized training for staff [9] and protocols for outcome monitoring and cost evaluations [14]. The adaptations required of healthcare facilities to successfully adopt ATMPs in relation to their current standing, and extent of required changes, can be termed ‘institutional readiness’ [14].
A framework, previously published by Umemura & Morrison [2], which outlines the sociotechnical configurations for clinical therapies will be used to define categories of readiness, specifically: markets and practices, healthcare and physical infrastructure, production systems, government bodies and regulators, human capital and networks, regulations and policies, technology, cultural and symbolic meanings. This perspective is in line with contemporary research on sociotechnical systems [16,17], emphasizing the need for comprehensive adjustments throughout a system to facilitate the adoption of a new technology.
Point-of-care manufacturing, widely and increasingly considered a viable option for the adoption of ATMPs into healthcare systems, involves the production of cell and gene therapies onsite or within close proximity to the hospital or clinic that they will be delivered to patients in [18]. Numerous benefits present with this centralized manufacturing approach including the maintenance of the integrity and quality of time-sensitive products such as ATMPs as well as lower logistical costs involved in the transportation of these finite products [19].
The Irish healthcare system differs from those in other European countries in several ways. The Irish healthcare system is made up of both public and private sectors. Using a means-tested model, some people in Ireland receive care that is government reimbursed whereas others access healthcare on a ‘fee for service’ basis. Additionally, around one quarter of acute care hospitals in Ireland are private healthcare institutions. Ireland does not have ATMP launch, catalyst and adoption capacities comparable to countries like the UK, making it increasingly difficult to create cohesion between the available services and industries involved.
To the best of our knowledge, there are no existing reviews examining current adoption of ATMP technologies within the Irish healthcare system, a gap which our work will address. Utilizing Umemura & Morrison’s previously published framework within our scoping review presents a novel application of this approach within ATMP research to assess Irish institutional readiness. In doing so, necessary changes required to strategically position the Irish healthcare system for future ATMP adoption will be identified.
This scoping review will also support and inform parallel mixed-methods research on this topic which is also being conducted at the clinical research facility. In this case, a scoping review is the preferred method of evidence synthesis as we wish to explore the depth of the literature relevant to the Irish healthcare context, summarize available information and identify gaps for future research.
1.1. Review question
What is the current level of readiness within the Irish health system to adopt licensed ATMP technologies?
2. Materials & methods
This protocol was drafted using the preferred reporting items for systematic reviews and meta-analysis protocols extension for scoping reviews (PRISMA-ScR) [20]. The review itself will be conducted in accordance with Joanna Briggs Institute (JBI) methodology for scoping reviews [21].
3. Eligibility criteria
The (population, concept, context) framework will dictate eligibility for inclusion to the review as it is specifically relates to scoping review methodology [22].
3.1. Population
As such, this scoping review will not discuss the actors delivering ATMPs, but pertains to the delivery itself of ATMPs.
3.2. Concept
The concept for consideration is the environment most suited to quality ATMP service provision in Ireland. This will be assessed qualitatively, through identifying current facilitators and barriers to achieving institutional readiness. A previously published framework on ATMP adoption will be used to specify this concept of readiness, specifically exploring:
Markets and practices
Healthcare and physical infrastructure
Production systems
Government bodies and regulators
Human capital and networks
Regulations and policies
Technology
Cultural and symbolic meanings [2].
3.3. Context
The Irish healthcare system is the context which will be considered. All healthcare sites will be considered (for example, public and private healthcare institutions).
4. Information sources
4.1. Source types
Both published and grey literature in English from 2013 to 2023 will be considered. Limiting the timeframe to ten years accounts for the emerging landscape of ATMP technology. The review will include:
Quantitative and qualitative primary research published in peer-reviewed academic journals.
Literature reviews published in peer-reviewed academic journals.
Opinion pieces published in peer-reviewed academic journals.
Reports published by Irish government-funded healthcare organizations, for example from the Health Service Executive.
Reports from pharmaceutical and biotechnology companies.
Non-governmental organization reports and outputs.
Patient representative organization reports.
We will assess the information quality of each qualitative information source included in our scoping review using the GRADE-CERQual framework [23].
4.2. Databases
Pubmed, Web of Science, Medline, Embase, Cochrane library, Cinahl, Scopus, the Joanna Briggs Institute and Google.
For grey literature, a general Google search will be used and limited to 250 results. Authors of included publications will also be contacted to provide further context to included data and for signposting to other potential sources of evidence. These authors will not be formally interviewed.
5. Search Strategy & Terms
The search strategy aims to find published and unpublished materials using a three-step search strategy.
-
1.
Initial limited search of at least two appropriate databases.
-
2.
Analysis of text words contained in the title and abstracts of retrieved papers and index of terms. A second systematic search using all identified key words and index terms across all included databases (Table 1).
-
3.
The reference lists of all included studies will be searched.
Table 1.
Search string for Embase.
| #9 | #3 AND #8 |
| #8 | #4 OR #5 OR #6 OR #7 |
| #7 | ‘advanced therap* treatment cent*’:ti,ab,kw |
| #6 | ((‘health system*’ OR ‘healthcare system*’ OR ‘healthcare system*’ OR ‘health service*’ OR ‘healthcare service*’ OR ‘healthcare service*’ OR ‘health organi?ation*’ OR ‘healthcare organi?ation*’ OR ‘healthcare organi?ation*’ OR ‘health surveillance system?’) NEAR/3 (readiness OR preparedness OR ability OR consideration* OR challenge* OR adopt* OR affordability)):ti,ab,kw |
| #5 | ((institutional OR organisation* OR organization* OR system*) NEAR/3 (readiness OR preparedness OR fit OR consideration* OR adopt* OR affordability)):ti,ab,kw |
| #4 | ‘healthcare system'/mj |
| #3 | #1 OR #2 |
| #2 | (‘gene therap*’ OR ‘molecular therap*’ OR ‘cell therap*’ OR ‘gene/cell therap*’ OR ‘cell engineering’ OR ‘advanced therap*’ OR tissue-engineering OR ‘Regenerative Medicines Advanced Therap*’ OR RMATs OR ‘ATMP*’):ti,ab,kw |
| #1 | 'gene therapy'/de OR 'cell therapy'/exp OR 'cell engineering'/de |
Search string considers articles from 2013 to 2023.
6. Results
Steps one and two (above) have already been completed in a pilot capacity. Google Scholar and Embase (Table 1 for sample search strategy) were searched to identify relevant primary and secondary terms. Keywords from articles were also scanned and terms were extracted from them to guide our search, including MeSH terms. Reviewers (Isabella Devine, Clarice O'Brien and Gerry Hughes) and the subject librarian (David Mockler) discussed and agreed on selected terminology.
We anticipate that the results of the completed scoping review will identify gaps in the published research and grey literature, potentially informing future research. It is also anticipated that information found on the readiness of the Irish healthcare system to adopt ATMPs will inform future policy making. The findings of the research will be submitted to relevant peer-reviewed journals for publication.
6.1. Data management
Article hits will be imported to Covidence® and de-duplicated. Title and abstract screening will be conducted by two independent reviewers (ID and CoB).
6.2. Selection of sources
Included records will be imported to EndNote® and full texts will be independently reviewed (ID, CoB) for assessment of eligibility. Reasons for exclusion will be recorded. Reviewers will reach consensus through discussion; if consensus cannot be reached, a third reviewer (GH) will contribute to the discussion.
The selection process and results will be documented and illustrated with a PRISMA flow diagram [24].
6.3. Data Extraction & Charting
Two independent reviewers (ID and CoB) have developed a data extraction tool in line with the JBI scoping review data extraction guidelines [21]. (Table 2). Specific study details such as year, authors, origin/country of origin, aims, population, concept, context, methods and findings will be recorded. The data extraction chart will be modified as needed during the extraction process. Any revisions to the chart will be recorded and reported in the review. Any disagreements will be resolved via discussion or inclusion of a third reviewer (GH) if necessary. Authors will be contacted where further information or context is required.
Table 2.
Data extraction tool.
| Scoping review details |
|---|
| Title |
| Objectives |
| Questions |
| Eligibility |
| Population |
| Concept |
| Context |
| Types of evidence source |
| Evidence source details and characteristics |
| Citation Details (authors, date, title, journal, volume, issue, pages) |
| Country |
| Context |
| Participants |
| Methodology |
| Details/results extracted from source of evidence |
| Key findings |
| Recommendations |
6.4. Data items
Qualitative data will be extracted in accordance with the Umemura and Morrison ATMP adoption framework [2] (Table 3). As more information becomes available, subheadings or further headings may be added. Any changes made will be recorded and reported in the review.
Table 3.
Data items.
| Concept heading | Relevant finding |
|---|---|
| Markets and practices | |
| Healthcare & physical infrastructure | |
| Production system | |
| Government bodies & regulators | |
| Human capital & networks | |
| Regulations & policies | |
| Technology | |
| Cultural & symbolic meanings |
Concept headings are guided by Umemura & Morrison (2021) paper.
6.5. Data synthesis
Data from all eligible full texts will be summarized descriptively using a narrative approach and using summary tables.
6.6. Patient & Public Involvement
This scoping review will be conducted in parallel with further qualitative research for the purpose of knowledge translation and quality improvement at the clinical research facility. This overall research package is guided by a steering committee, on which there are two patient representatives.
7. Discussion
The discussion section will relate the objectives of the scoping review to the overall findings. Review findings will be discussed in the context of recommendations to inform future research, national policy and strategy on the adoption of ATMPs in Ireland. The authors will also consider the strengths and limitations of the scoping review, as below, within the discussion.
7.1. Strengths & Limitations of this study
This protocol outlines a rigorous, evidence-based approach to a scoping review; protocol visibility is important to inform the wider research community of this work.
The Irish healthcare system readiness for adopting ATMPs is unclear and, to the best of the authors’ knowledge, has not been explored previously.
A previously published framework will specify the concept of ‘readiness’.
Parallel mixed methods research into ATMP knowledge translation and quality improvement activities at the Wellcome-HRB Clinical Research Facility at St James’s Hospital Dublin (CRF) will be informed by this review.
Both academic and nonacademic sources will be included, providing a comprehensive overview of the current evidence base.
We will assess the information quality of each qualitative information source included in our scoping review using the GRADE-CERQual framework.
Publication bias may affect the results as this is an emerging field of research.
8. Conclusion
By utilizing the readiness framework from Umemura and Morrison [2], these findings will be specific for ATMP technologies and relevant to the Irish context.
9. Future perspective
It is expected that results generated from this scoping review will inform national policy on ATMP adoption in Ireland.
Funding Statement
Pfizer Global Quality Improvement Grant. Grant number: 76768559. G Hughes has received previous grant funding and honoraria from Pfizer.
Author contributions
I Devine – data curation, investigation, methodology, writing – original draft. C O'Brien – data curation, investigation, methodology, writing – original draft. G Hughes – conceptualization, funding acquisition, investigation, methodology, project administration, supervision, validation, writing – review & editing. D Mockler – data curation, investigation, methodology. C Kennedy – conceptualization, funding acquisition, methodology, supervision, validation, writing – review & editing. M Hennessy – conceptualization, funding acquisition, methodology, supervision, validation, writing – review & editing.
Financial disclosure
Pfizer Global Quality Improvement Grant. Grant number: 76768559. G Hughes has received previous grant funding and honoraria from Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Competing interests disclosure
The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.
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