A new position document from the European Wound Management Association (EWMA) aims to investigate the barriers and possibilities of advanced therapies in next-generation wound management, including technologies based on cellular therapies, tissue engineering and tissue substitutes, which are all technologies associated with the clinical discipline of regenerative medicine. The article will summarise the document, which outlines new treatments based on physical therapies and the potential of sensors, software and internet technologies. The author hopes that this article will not only be interesting for scientists and clinicians, but also helpful for all the stakeholders in the field of wound management to build a better future for patients.
Major objectives
EWMA wishes to be on the forefront of the development of new, sustainable, costeffective, advanced therapies. The new document will examine how these therapies may support the continuous improvement of wound management, with regard to patients' quality of life, as well as providing more effective and efficient wound management. The document's objectives are to:
- review and discuss clinical experiences and the scientific evidence, where this is available
- provide an objective and exhaustive overview of the available therapies and their potential role in clinical practice, as well as recommendations for the implementation of these therapies in the different areas of wound management
- analyse and debate cost-effectiveness issues related to the included therapies
- discuss the regulatory framework for advanced therapies in Europe, and provide a point of referral for future discussions and negotiations with healthcare providers and payers.
Due to the lack of scientific documentation for many of these emerging therapies, the article will be based on the available literature, as well as expert opinions. It will include an evaluation of the potential for future use in clinical practice and call for research in recommended areas.
Defining advanced therapies
For the purposes of the position document, the definition for advanced therapies has been adopted as a basis for selecting relevant technologies for inclusion, and is as follows: the therapies related to chronic wound management can be defined as ‘advanced’ when they are based on novel principles and technologies or when they refer to a novel application of consolidated principles and technologies – including a singular mechanism of action or a strategy with different levels of action – on the proviso that some evidence has been produced in a measurable and comparable way by the manufacturers or developers. For the sake of this article, advanced therapies will be grouped according to their nature in four different categories: materials, cells and tissue engineering, physical and biophysical, and sensors and IT-related.
Based on an extensive review and critical reappraisal of the existing evidence, and of the problems related to the implementation of new technologies in wound healing, the authors responsible for the EWMA position document have agreed on a number of recommendations for future developments. The document is organised into six sections; four of which deal with the different areas of advanced therapies, and two dedicated to the economic and regulatory aspects of advanced therapies in wound management.
Development of new technologies
The development of new technologies is a time and resource-consuming process, often lasting several years. Thus, companies interested in developing and introducing new technologies and medical devices for wound healing to the market are advised to carry out preliminary consultations with an interdisciplinary team of stakeholders, including basic scientists, bioengineers and clinicians with a specific expertise in wound healing, in order to test the originality and applicability of their ideas and projects.
Health technology assessments
The limited financial resources in all healthcare systems across Europe, typically financed via a taxpayer system, emphasise the need for an adequate allocation of resources, based on updated evidence and principles of cost-effectiveness. Health technology assessments (HTAs) have become the standard approach whenever new technologies are proposed for introduction in the field. The fact is that HTA procedures vary from country to country or, in some cases, from region to region. As part of a rationalisation process, which should be promoted and endorsed by the EU in the framework of legislative action, HTA procedures should be defined and standardised across the continent. This would simplify the process of bringing new technologies from the lab to the patients. It would also reduce the amount of resources that companies have to invest in these procedures, eventually saving them from undertaking further research activities.
Implementation of new technologies in clinical practice
In order to bridge the gaps that develop between the realisation of new technologies and their implementation in clinical practice, it is important to define minimum standard requirements for testing and implementation in the field. These requirements must be related to the two former items in this article, tested under controlled conditions and follow the recommendations of ‘good clinical research’, but randomised controlled trials (RCTs) are the preferred approach. However, due to the cost and method-related difficulties linked with the organisation of an RCT, prospective observational trials may be considered, if they are independent and relevant for wound management.
Translational science
Despite the increasing number of options, in terms of variety and quality of technologies available for clinical use in wound management, there is a diffuse underuse of new technologies the moment they become available to clinicians. The implementation in clinical practice often does not meet the expectations of the manufacturers. One major component of this bias is related to the poor knowledge about the basic principles of the materials and technologies among healthcare professionals. Their level of knowledge may eventually be improved by translational science initiatives aimed at bridging the technological gap.
Need for investments in research
To sustain the growth of research and the development of new technologies for wound management, important economic resources are needed. Beyond the commercial interests of the industries in the field, institutions at the European level must also recognise the importance of investing in a field that will interest one out of four EU citizens over the coming decades.
Access to new technologies in EU
The possibility of making new technologies accessible varies significantly across the different countries in the EU, not only for the reasons highlighted later in this article. Another key factor in ensuring the accessibility of new technologies is that companies are willing to market new technologies in all European countries, despite the economic arguments for targeting certain countries before others. When new technologies are not available across European healthcare systems, this creates idiosyncrasies in the actual possibility of patients to be treated with new technologies. Companies are therefore advised to extend their diffusion of new technologies across Europe to the extent possible.
Regulatory controversies
Regenerative medicine is on the rise, and is about to shift focus from replacing and repairing tissue, to regenerating it. Although regenerative medicine is not yet a reality in wound management, the ongoing development of activities in the field of advanced therapy medicinal products (ATMPs) holds the realistic promise of revolutionising standard treatment. Gene therapies producing wound-healing factors may soon become reality and open new horizons for treatments. Most regenerative medicines are classed as ATMPs, and are confronted with high product and development standards. Thus, their development can be very challenging for companies due to the inert complexity of the products.
Detailed EU guidance related to emerging gene-editing technologies, in particular, is available, but for wound management, related indications are missing. It would be advisable to engage with regulatory authorities in the future, in order to make them aware of the challenges related to the development of medical products for wound management, as well as the lack of guidance. This would hopefully lead to the development of specific guidelines from which product developers could benefit in the future.
Definition of outcomes, direct and indirect costs
Cost studies vary in approach and quality. A wide variety of outcome measures and costs hinder comparisons of interventions and progress. There is an increasing need to clearly define outcomes, and direct and indirect costs that should be included in economic evaluations. Promoting research and clinical trials for advanced therapies, and involving health economists and health statisticians in the planning, execution and analysis of the studies is essential, with regard to ensuring the appropriate economic assessment of the impact of these interventions. Moreover, given the paucity of studies concerning the quality of life of patients, more analyses focusing on this dimension should be performed.
Telemedicine and wearables
There has been distinct growth in the wound-care-centred research field within telemedicine and wearables. These technologies enable physicians to cut down on in-person visits, remotely check on patients, track patient adherence to the therapy, detect the early stages of serious medical conditions and triage those who need immediate supervised care. While the application of such technology for diabetic foot care is still in its infancy, and its cost-effectiveness is still being debated, it is anticipated that general healthcare and chronic wound-care delivery will change dramatically in the near future. Thus, more research in this field is recommended to translate these telehealth technologies for better management of chronic wounds and improving patient-centred outcomes, including the number of in-person visits.
Evaluation of outcomes
A major challenge for a fair comparison between new technologies and conventional therapies is the lack of consensus and guidelines to standardise the reporting of outcomes. In addition, new outcomes that are more sensitive to new technologies should be defined and standardised; for example, the number of in-person visits for telehealth applications and the level of restriction in mobility during the wound-healing phase. Moreover, most research in the area of chronic-wound management is currently focused on wound outcomes during the wound-healing phase, not taking into consideration the high rate of recurrences. It is recommended that the time of recurrence for ulcers, as well as their frequency, are also taken into consideration when examining the effectiveness of new technologies.
