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Translation of Wound Devices into Practice—A Myth? Translation … 289
multiple agencies although detailed requirements may well differ. Sale and use in
these territories, and sometimes even the performing of clinical trials, cannot be
carried out until the necessary approvals have been obtained and criteria satisfied.
Gaining Adoption and Usage of a Translated Product
or Therapy
It is tempting to believe as an innovator that once a product or therapy has successfully shown efficacy and gained regulatory approval through the steps above
which may take many years at significant cost that it can then be widely used and
adopted by all those who would benefit. However in most countries there are
usually additional hurdles to be overcome in order to allow clinicians and patients
to gain access to an approved product. This may well also apply to the use of an
existing approved product in a new indication or usage pattern.
The decision makers on allowing use and adoption can vary across different
territories as can who is the ultimate payer for the product. For example, in a system
that is public funded and free at point of delivery to the patient as in the UK, the
taxpayer ultimately covers all the cost although some prescription charges may exist
and some countries require patients to top up healthcare costs, so called co-pay. If
the system is largely an insurance based system as in the US then the individual
must self-insure the costs, perhaps with their employer. There are normally two
additional steps required for Governments or Insurance companies based on well
accepted principles. Firstly a payer will want to establish the health economic
benefit of the treatment which is does it demonstrate value for money? Secondl y
they will then wish to consider, based on the health economics and perhaps such
other factors as budget constraints, whether it should gain financial reimbursement
and be paid for by an insurer or national system. As the definitions beneath show,
these two factors are intimately linked.
Health
economics
Reimbursement Based on the health economics and value for money in relation to existing
Using resources efficiently to improve the population’s health. Health
economic analysis and evaluation compares the costs and consequences of
alternative courses of action. The cost effectiveness of an intervention or
programme is assessed to ensure maximum health gain from the fi nite
available resources (Majmudar et al. 2015)
comparators an assessment is used to determine whether a new
medicine/device should be reimbursed. This could include the cost of the
treatment and the time and other resources used to apply or deploy it
The interplay between the regulatory system and the reimbursement/health
economics is perhaps best illustrated in the European Union. With Medical devices
there is a common framework and mutual recognition of approvals for devices with
CE marks awarded in different countries and indeed for pharmaceuticals a single

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marketing authorisation route exists though national routes can still be followed.
However individual EU countries will have very different approaches to establishing health economics and reimbursement, perhaps even requiring additional
clinical studies. Most will have Health Technology Assessment (HTA) bodies to
assess these factors for their nations and whilst some harmonisation in approach
occurs via the European Network for Health Technology Assessment (EUnetHTA)
(Tafuri et al. 2020), and legislation is intended for 2025, national differences to
reimbursement and health economic decisions undoubtedly occur. Examples of
these HTA bodies in Europe are the French National Authority for Health (Haute
Autorité de Santé), the UK National Institute for Health and Care Excellence
(NICE) (Methods for the development 2012) the German Institute for Quality and
Efficiency in Health Car e (IQWIG). Interestingly the US lacks a single HTA
approach perhaps due to its decentralised insurance system, where each priva te and
public payer makes individual decisions and conducts its own negotiations with
manufacturers.
The ultimate effect and impact of this translational journey is that a well-ordered
route exists to allow clinical innovation to be used by all of the most beneficial
applications in clinical practice for patients. However due to local, national and
regional factors linked to health economics and reimbursement it may be that
adoption and use cannot occur for individual clinicians despite there being a
national regulatory approval that the product is safe and effective. With all this in
mind then before setting off on an innovation journey a company or innovator will
usually carry out a full business assessment of the potential of an intervention if its
safety and efficacy is validated and will factor in these health economic and
reimbursement criteria, identifying territories where initial translational activity can
benefit the maximum number of patients if effective. Just as national agencies carry
out assessments of the cost effectiveness of an intervention or programme so must
innovators.
Case Studies
To illustrate the above principles, case studies are presented below.
(i) Case Study of taking a previously used clinical practice and translating it
such that it can be used widely by more clinicians.
Negative Pressure Wound Therapy (NPWT) also referred to as vacuum
assisted closure (VAC).
NPWT is the use of suction on a wound ( acute or chronic) via a powered
pump or other suction method in combination with a wound contacting
dressing or filler and possibly tubing and a canister ( to collect exudate). The
use of various types of suction on skin and wounds for drainage and
improved healing is a practice that dates back many decades and centuries to

Translation of Wound Devices into Practice—A Myth? Translation … 291
the use of cupping and also post surgical wound drainage via hospital suction
such as that described by Chariker in 1989 (Chariker 1989). The translational
need was how to make NPWT available in the most reliable and repeatable
manner to the widest number of users. The VAC device (KCI Medical Ltd)
was launched in the 1990s bringing together the key elements of NPWT
envisaged by the clinical innovators such as Dr Louis Argenta and Dr
Michael Morykwas of Wake Forest University. These elements were the use
of a suction device/pump, a filler/dressing and tubing leading to a canister.
KCI developed these components as medical devices and had the system
registered using the processes described earlier as an off the shelf medical
device ( or combination of devices) that could be used ( for purchase or
rental) by clinicians. The clinical impact that NPWT had on a range of
wounds was significant (Novak et al. 2014) and initially was demonstrated in
acute wounds, allowing its use in hospitals where acute facilities could
choose to adopt and pay for this therapy based on the demonstrated cost
savings compared with alternative dressing regimens. However, its use in the
community and homecare took several years to be reimbursed (and even then
initially only in the US). This was despite the ever growing demand for
home‐based care from the Healthcare system and a wish to reduce the
unnecessary burden on hospital beds which NPWT in the home could help
support (Trueman 2008). Furthermore its value in chronic wounds, largely
treated in the community, became apparent. The reimbursement position in
Europe for example remains even now very complex varying among countries and also regions in countries. This lag or even refusal of reimbursement
between regions and countries is due to the differing economic assessment
processes or evidence needs overlaid on the structure of the healthcare
system for homecare patients across countries. In each country the patients
largely present the same with common needs and harmonised regulatory
approvals for products in place.
We learn here that clinical innovation building on current practices can be
diffused more widely by developing a product/protocol that ‘standardised’
the therapy and allows regulatory bodies to approve its use. However
national and regional reimbursement/health economic constraints may still
limit access by individual clinicians.
(ii) Case study of taking a natural treatment from Chinese Traditional Medicine
(Artemisinin) and combining it with known western drugs to develop a first
line treatment for malaria.
In the late 1960s and early 1970s the Chinese Government initiated a programme of work to look for malaria treatments partly for its own needs but
also to support the Government of Vietnam that was losing its soldiers to this
parasitic infection. The approach was to look for treatments based on natural
sources and using recipes defined in Chinese Traditional Medicine. At that
time Malaria was a deadly disease in South East Asia particularly China and
Vietnam as well as in many areas of the world. Professor Tu Youyou was

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appointed head of this team and from over 2000 Chinese TCM recipes
screened, they identified a potent and active extract from the plant sweet
wormwood (Artemisia Annua) (Valavanidis 2019). They developed, using
ethanol, a specialised extraction process which allowed retention of the
active properties and isolated what became named as artemisinin. It was
discovered during the “cultural revolution” at a time when fields of research
in China were limited and publication in foreign journals was not allowed.
Despite difficulties in getting the therapy progressed to human trial, it was
ultimately shown to be a highly safe and effective treatment. Gaining wider
global access or awareness of artemisinin was also challenging however once
it did then it rapidly became an important part of the armamentarium of
malaria treatmen ts firstly in China then more globally. The parasite had by
this time begun to show resistance to existing drugs and it was further
demonstrated that a rtemisinin or its derivatives when used in combination
with other treatments such as lumefantrine, mefloquine, amodiaquine,
sulfadoxine/pyrimethamine, piperaquine and chlorproguanil/dapsone was
highly effective against drug resistant malaria and quickly became the first
line therapy of choice popularly known as Artemisinin combination therapy
(ACT). These therapies continue to be improved (Lyu 2021;Tu2016).
What can we learn from this case study in relation to wound healing? Firstly,
in looking for solutions to clinical problems we need to be open minded to
translate possible therapies from a wide variety of sources such as traditional
Chinese medicine and proven practice. Secondly, as with the NPWT case,
then often to achieve a successful clinical end point perhaps a number of
existing known approaches will need to be combined to achieve a solution
that will be clinically successful and the idea of “combination” approaches is
a powerful one as demonstrated here. There can be few translational medical
innovations that have had as much impact as this one and it demonstrates that
“discovery”—the process of finding or learning rather than creating and
inventing—is as relevant and important in human health as creating new to
the world solutions.
(iii) Compression applied using bandages or hosiery to a limb, is a mainstay of
treating venous leg ulcers the underlying aim being to apply counter-pressure
to limbs with higher venous pressures. This practice was well known for
many years and accepted even though the healing rates of venous leg ulcers
was not satisfactory, it was variable between centres and the types of bandages, used based on publications: mostly such publications did not seek to
determine efficacy. This was to change once the Cochrane Wounds Group
initiated a systematic review and meta-analysis of randomised controlled
trials of published literature: such a review was a rigorous procedu re with
very clear aims and objectives, with a Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) and powerful statistical
routines. Existing databases were searched for publications to include only
those that clearly met with the defined aims. The evaluated evidence was
analysed and then distilled noting the bias involved before reaching

Translation of Wound Devices into Practice—A Myth? Translation … 293
conclusions with quantitative confidence. In its first publication, the
Cochrane Wounds Group reported that ‘some compression is better than no
compression’ to manage venous leg ulcers (Fletcher et al. 1997). That first
step led to more randomised controlled trials to test for efficacy as well as
Cochrane Reviews: their conclusions confirmed the value of compression
and its use empowering guidelines that recommend compression is the
mainstay of treatment (O’Meara et al. 2012). This led to a definition of
standard care for venous leg ulcers which is a key step as it permits the
valuation of diagno stics and adjuvants (Mani et al. 2016). The Cochrane
Wounds Groups works in many countries under the overarching umbrella of
the Cochrane Collaboration. This example illustrates successful adoption of
powerful experimental and analytical tools i.e., randomised controlled trials
and systematic reviews and meta-analysis with the support of a central
governmental agency. Clinical studies in this field are now better focused,
the findings have given guidance to the use of compression in managing
venous leg ulcers. The work is not complete since such situations as those
with misshapen legs, in warm humid climates need similar support, perhaps
calling for collaboration among centres with similar objectives. This begs the
question whether clinicians should take a global perspective into account
when drawing up guidelines?
(iv) The use of hyperbaric oxygen therapy commonly known as HBO or HBO T
to treat chronic wounds is another example to consider. HBOT is the process
of delivering oxygen at 2.4 atmospheric pressure, or slightly higher, to the
patient within an enclosed chamber. The procedure is laborious, the safety
issues are known and well published. The oxygen inspired is taken up by the
circulation of red blood cells as described in the Bohr–Bury equation, and
delivered to the wound site from tissues within. A large body of evidence
relating to wound healing as well as preventing amputation, swayed the
clinical public first one way and then the other till the early Cochrane Wound
Group publication on the efficacy of HBOT was available (Kranke et al.
2015). This work was regularly updated, the authors report that HBOT use to
treat the diabetic foot ulcer is safe, it benefits the reduction of major
amputations significantly, more than a minimum number of 30 sessions is
required. Brouwer (Bouwer et al. 2019) in a subsequent systematic review
and meta-analysis of a large number of trials and participants gave strong
support to HBOT use to treat the diabetic foot to reduce major amputation:
further their analysis of the absolute risk reduction permitted the inference
that the numbers needed to treat was seven to obtain the huge benefitof
reducing major amputations. Amputations to save limbs of diabetic patients
is the aim of all clinicians. These and another recent study (Sharma et al.
2021) examined the range of adverse events, the number of treatment ses-
sions and duration—the equivalent of dose and duration studies. There is a
growing consensus driven by data that HBOT is a complex approach which
benefits diabetic foot ulcer (DFU) management, its efficacy is best realised
when clinicians are able to pre-select their patients’ using data to better

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inform their clinical judgement. The overall cost needs to be manag ed:
society needs to ask itself if it wants to bring some level management to the
global challenge that is the diabetic foot. This question and nationally different responses to it as well as the availability of chambers has meant access
to HBOT is certainly not universal. These takeaway messages are confident;
the path of translation can be a long process but one which offers rewards to
patients.
Discussion
Truly successful innovations are those that can take a discovery, invention or an
adaptation of existing practice and translate that to meet a customer need. In our
own day to day lives each of us are customers as we make individual decisions
about those things we consume, wear, buy, read or even where we choose to study.
However, in relation to healthcare and medical innovation then defining who the
customer is for this can be difficult and elusive. Clearly the ultimate goal of medical
innovation is to sati sfy a patient or clinical need that is presently either unmet or
only poorly met. However, the patient is unlikely to be the primary decision maker
in choosing the product and in many cases depending on the healthcare funding
model, neither will they be directly paying for the product. So, who is the customer?
Is the customer the clinician? They are very likely to be pivotal in defining what
therapy or treatment they believe will be best to use for their individual patient or
patient group. However, they will be restricted and even prevented in making
choices based on procurement or health economic decisions made by others
nationally or locally e.g., the insurance or health system. In a network of needs and
requirements such as that in any global healthcare system it is clear therefore that in
clearing the various hurdles described in this chapter that there are a whole spectrum of customers and needs, starting with the regulators and moving all the way
through to the patient. Each participant or customer is aiming to play their part in
delivering an economic, efficient and effective clinical outcome by applying their
own decision criteria (e.g. is it safe? Is it economic? Is it easy to apply? Does it fit
with existing clinical practice?) And since the pandemic, how best to manage this
change?
For a successful translation of a discovery or innovation into practice then the
clinical innovator or the company, or a partnership of the two, must consider all of
these elements and aim to identify an optimum solution that satisfies all customers’
needs to an agreed level. To be single minded about only one dimension may mean
ultimately failing e.g., a protocol or therapy focussed only on maximising clinical
effectiveness may never be available widely if its health economics are not viable
and it will not be reimbursed. An example of this could be requiring twice daily
treatments in a patient’s own home in order to maximise the outcome when the
healthcare payer might never agree to fund such a care schedule. This is not to say
that a solution that merely satisfies the requirements of everyone (achieves the

Translation of Wound Devices into Practice—A Myth? Translation … 295
minimum hurdles) should be sought but that it is important that innovators should
be mindful of these conflicting tensions if choosing to maximise or focus on one
need.
We have seen in this chapter that successful innovations can be achieved in
medical practice not just by creating “new to the world” inventions but also by
building on already known and accepted treatments, practice or innovations.
Innovators can look to see what has been demonstrated and accepted as best
practice in achieving outcomes along the whole clinical pathway e.g., compression
of Venous Leg ulcers or offloading of diabetic foot ulcers. These can then be
translated alone or in combination (as with artemisinin) to new indications or
protocols to achieve improved outcomes. This approach has the advantage of
reducing the overall risk of a development, it builds on already proven and familiar
elements and improves the likelihood that the translation can be achieved and then
accepted and adopted. For example, in the case of NWPT, wound suction had
already been shown to have benefit in clinical practice (as by Chariker (1989)).
Therefore, adapting and improving the delivery of this method of care by making it
more widely available as an approved clinically studied medical device including
all the components a clinician needs was likely to have a better chance of becoming
more widely adopted. In the case of compression the dissemination of the existing
evidence bases and studies then extending this with powerful experimental and
analytical tools meant that its value overall became widely accepted.
We asked the question in this chapter whether the successful translation of
wound devices into practice was a myth? The route to achieve this is not
straightforward and to be successful in gaining widespread adoption an innovator
needs to consider many stages. These stem all the way from developing an intimate
understanding of the core, customer/clinical need and existing practice to the
development of evidence, regulatory approval and finally reimbursement for use.
The achievement of all of this is certainly not a myth but a well evidenced fact,
despite needing a lot of hard work and usually money, collaboration and time to
achieve it.
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Pain in Chronic Wounds: Mechanism
and Management
Aakansha Giri Goswami, Praveen Talawar, Somprakas Basu,
and Vijay Kumar Shukla
Abstract
Pain management in wound care is often underestimated as it could have a
ruinous effect on patients’ wound healing as well as the quality of life in general.
Pain from wounds is multidimensional, and it is the patient’s physiological and
psychosocial environments that influence excruciating experiences. Since the
origin and cause of pain differ in different wounds, accurate assessment, and
application of individualized strategies are key for comprehensive and effective
pain management. This chapter aims to provide a scientific guide to pain
management in chronic wounds while simultaneously acknowledging the fact
that every patient should have an individualized treatment plan, concurrently
emphasizing the need to ensure comprehensive patient as well as pain evaluation
with an ultimate goal to improve wound healing outcomes and emotional
well-being in patients enduring chronic wounds.
Keywords
Wound painChronic woundsWound pain assessmentWound pain
management
A. G. Goswami P. Talawar S. Basu (&)
All India Institute of Medical Sciences, Rishikesh, India
e-mail: somprakas.surg@aiimsrishikesh.edu.in
V. K. Shukla
Banaras Hindu University, Varanasi, India
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
R. Mani (ed.), Chronic Wound Management,
https://doi.org/10.1007/978-3-031-26110-7_15
297

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Introduction
Chronic wounds are an escalating problem worldwide. Due to the ambiguous definition of chronicity and underreporting of the issue, accurate estimation is difficult.
This contributes to inaccurate estimates of problem burden, health care planning, and
healthcare delivery services. With the availability of advanced health care facilities
and the resultant increase in life expectancy, its prevalence has doubled in the last two
decades (Sen et al. 2009). It is estimated that every 1 in 5 adults suffers from pain
globally and 10% are diagnosed with chronic pain every year (International Association for the Study of Pain | IASP [Internet] 2022). Pain is defined as “an unpleasant
sensory and emotional experience associated with actual or potential tissue damage
or described in terms of such damage” (Pain terms 1979). Chronic pain is any pain
that lasts longer than three months, the time frame corresponding to the definition of
chronic wounds. Pain is subjective, it also has a multivalent nature which makes it
difficult to quantify. This makes it hard to narrate it adequately as a measurable public
health concern. As a result of which it still does not invite significant public health
expenditure. Interestingly, the resultant psychological sequelae and the induced
morbidity are serious concerns that have got a wider impact on society and tend to
make it a global public health problem (Korula 2008).
The Burden of the Problem
The chronic wounds frequently encountered in daily practice include diabetic,
decubitus, and venous and arterial ulcers. Others are associated with cellulitis with
soft tissue necrosis, osteomyelitis, vasculitis, pyoderma gangrenosum, malignancy,
trauma, and various causes of cutaneous fistulae. Diabetic patients have a 2–3%
annual risk of developing diabetic foot ulcers (DFU) with an estimated lifetime risk
of 25% (Brem et al. 2006). The prevalence of diabetic foot worldwide ranges from
3 to 13% with a global average of 6.4% (Zhang et al. 2017). However, wound pain
in DFU is often underestimated and undertreated because of the erroneous belief
that diabetic patients with peripheral neuropathy do not experience pain in their
wounds. Recent studies have questioned this perception and currently, it is estimated that up to 85% of patients with DFU experience pain which is most commonly attributed to infection, ischemia, and arthropathy (Obilor and Adejumo
2015; Bradbury et al. 2011; Bengtsson et al. 2008).
About one-fourth of the patients hospitalized in health care facilities suffer from
pressure ulcers and more than fifty percent of these patients experience some type
of pain (Dallam et al. 1995; Woodbury and Houghton 2004). A study by Szor and
Bourguignon reported that as many as 84% of their subjects experienced pressure
ulcer-associated pain at rest, whereas 88% acknowledged cyclic acute wound pain
at dressing change (Szor 1999). A recent meta-analysis in patients with chronic
venous leg ulcers (VLU) concluded that 80% of these patients experienced
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