EUROPEAN  TISSUE  REPAIR  SOCIETY

ETRS Working Groups: Draft Statements
Keith Harding, ETRS Working Group Coordinator

The ETRS is one of the oldest established societies in the field of tissue repair. Continuing its policy of undertaking new initiatives in this area, a num-ber of working groups were set up for the purpose of generating draft statements on important aspects of wound healing.

Meetings were held in Vienna in 2002 and in Berlin in 2003 with the generous support of an unrestricted educational grant from Johnson & Johnson and the organizational skills of MEP Ltd. As a result of these meetings, and subsequent work, I attach the draft statements to this document and would urge you to provide us with comments, observations and constructive criticism.

It is recognised that these draft statements have the potential for further refinement but we feel that the creation of these draft statements are an important step forward in raising the standards of professionalism associated with wound healing research and clinical practice.

I would like to thank everyone involved in this initiative who have given so enthusiastically their time, ideas and experience in this area.

There are a number of further stages in this initiative, and these include:

1) Receiving comments from all members of ETRS,
2) Amendments of the draft statements in the light of comments received,
3) Obtain approval from the ETRS Board for continuing and expanding the work of the working group,
4) Obtain approval from ETRS Board for the final version of statements produced,
5) Inform and engage other societies in commenting on or adopting the statements produced,
6) Hopefully produce internationally agreed statements at the next ETRS Annual Meeting which will be part of the WUWHS meeting in Paris in 2004.

I do hope you will take the opportunity to participate in this worthwhile but challenging exercise.

Keith Harding
ETRS Working Group Coordinator

Draft Statements

A1) Developing standards for in vitro models of wound healing

Such models have definite value in research but attention is needed in the following areas:

1.1 Redefining Laboratory Models
Where possible in vitro models should have relevance to the clinical situation, specific disease or pathological process.

1.2 Reproducibility and standardisation
Standardisation is the key to the development and extension of existing models to enable comparison of data generated in academic, commercial and other laboratories. Consider using the frame work of existing international standard testing as a basis for developing work in this area.

1.3 Refining Current Model Systems
All in vitro models are by definition limited in some way. Current models should be extended by the use of disease and age specific cellular populations and environmental conditions that reproduce the in vivo situation.

B1) Standards for Clinical Care of Patients with Wounds

1.1 It should be recognised that provision of care to patients with wound will be influenced by:

a) Health care systems operating in different countries.
b) Local availability of services and expertise.
c) Controlled availability of treatments due to cost, regulations and formularies.
d) Existence of local, national and international guidelines (e.g., IWGDF, EPUAP).

1.2 The diversity of types of chronic wounds seen in clinical practice is such that in this document, in addition to some generic aspects of patient care, specific attention is paid to the management of lower limb ulceration.

2) Training
2.1 All patients with a chronic wound should be managed by an appropriately trained health care professional.
2.2 Training should include a Board certified educational programme for all professionals involved in the provision of wound care.

3) Diagnosis and Treatment
3.1 All patients should have rapid access to a specialist if:

a) the diagnosis is unclear
b) appropriate therapy is not available
c) wound healing is likely to be compromised by underlying disease
d) wound healing is not progressing as expected

4) Documentation and Audit
4.1 Adequate and accurate documentation of all patients with wounds should take place. This should include core information with additional information recorded depending on the wound type.
4.2 Core information should be recorded at least monthly and include:

a) Wound size by:
i) Tracing
ii) Measurement
iii) Photography

b) Wound bed colour (black, green, yellow, pink, red):
i) % of wound bed
ii) Photography

c) Wound depth using grading scale of initial assessment and detailing tissue at wound base

d) Surrounding skin
i) Healthy
ii) Unhealthy
e) Exudate – Composition and Volume
i) Nil
ii) Normal
iii) Excessive
f) Pain – continuous/dressing change/occasional
g) An evaluation of treatment effect with the outcome graded as wound:
i) Healing
ii) Static
iii) Deteriorating

h) The reason for non-healing indicated, e.g., infection, and the reason for treatment changes documented.

5) Wound Cleansing
5.1 Cleansing is defined as the irrigation of wounds with fluids e.g. water, normal saline or Ringer’s solution.
5.2 The role of antiseptics in treating infection requires further evaluation to clearly define their potential benefit in this area. If such agents are used they should have the following characteristics:

a) Broad spectrum efficacy,
b) No tendency for resistance,
c) Not harmful to healing,
d) Long term efficacy,
e) Non-allergenic or irritating,
f) Cost effective,
g) Simple to use.

5.3 Wound cleansing is not always necessary.

6) Debridement
6.1 Debridement is defined as the removal of non-viable tissue.

a) Debridement should only be undertaken by suitably trained qualified staff working within the limits of their ability and training.

b) There should be consistent documentation of the wound condition before and after debridement.

c) Debridement techniques may differ according to wound type:
i) In diabetic and neuropathic foot ulcers sharp debridement should be to bleeding and viable tissue
ii) In ischaemic ulceration debridement should only be performed following revascularisa-tion unless needed acutely to deal with infection
iii) Pressure ulcers usually require progressive debridement using a variety of techniques
iv) In venous leg ulcers formal sharp debridement is rarely required and the principles of wound bed preparation may be more appropriate

7) Advanced Treatments
7.1 The definition of advanced treatments will depend on availability, experience, financial incentives and reimbursement rules of individual health care systems.
7.2 ‘Advanced’ treatments with proven efficacy should be:
a) Considered when a wound is not healing within an agreed and acceptable time frame. Such patients should be referred to secondary centres if possible.
b) Advanced treatments should not be unreasonably denied to patients if there is a sound justification for their use.

8) Compression Therapy and Vascular Assessment for Patients with Lower Limb Ulcers
8.1 All patients receiving compression therapy should undergo adequate arterial assessment. Assessment should include:

a) History
b) Examination
c) Ankle brachial pressure index (ABPI)

8.2 Patients with a normal ABPI and clinical features suggestive of venous disease should be treated with compression therapy in line with the International Leg Ulcer Advisory Board as set out in the European Wound Management Association Position Paper on Compression Therapy.
8.3 It is essential to localise the site of venous abnormality in lower limb and differentiate between superficial and deep venous disease.
8.4 Further vascular assessment and/or investigations of both the arterial and venous systems should be performed if the ulcer is recurrent or non-healing.
8.5 These investigations would determine the need for further intervention including surgical, radiological and pharmacological treatments.
8.6 Patients with abnormal ABPI or examination features suggesting arterial disease should undergo further arterial investigation.
8.7 In patients with Diabetes Mellitus additional care should be taken and further arterial investigations undertaken such as toe pressures or TcPO2 measurements.
8.8 In complicated ulcers Doppler assessment and ABPI should be repeated at least three monthly and should be repeated for patients continuing to receive compression therapy after ulcer healing.

ETRS Working Groups

C1. Standards for Clinical Trials in Wound Healing
1.2 Overall Study Design
a) Inclusion and exclusion criteria and stratification of risk factors should be used to make studies as ‘inclusive’ as possible to allow for valid comparisons between groups to be more representative of the presenting population.
b) Generic and wound specific risk factor scales should be established to allow stratification of patients (in order to reduce bias). A scale such as the one included in Table 1 could form the basis of an agreed framework for the information that should be documented about the patients involved in trials, as well as calculating an ‘at-risk score’ that could be used for classification purposes.
c) Trials should use standard protocols and documentation to describe wounds and record progress.
d) Trials should not function in isolation. Trial design should consider the context in which health care is delivered. The following acronym (‘FRIPP’) may help to clarify the points to be considered:

Feasibility
(Is the study feasible with healthcare settings across a number of countries?)

Reality
(How closely does the trial reflect the reality of health care delivery?)

Implication
(What is the implication for a healthcare system if the findings are positive?)

Prospective
data collection in ‘post’ trial phase (investigators should report health status data for a post trial phase to confirm safety and health outcome data.)

Publication
(Will the study be good enough to warrant publication, which is to be strongly encouraged?)
e) Early involvement of appropriately qualified health care professions and statisticians is necessary for effective trial design.
f) Trial design and execution should follow national and international guidelines for quality assurance purposes.

2. Size and Power
2.1 Studies should be of a sufficient size and power to detect differences between groups based on:
i) Endpoints used
ii) Primary aim of study
iii) Expected attrition rate
iv) Allowance for uncontrolled variables
v) Allowance for ‘centre’ effects/population effects
vi) Encourage multi-centre studies once pilot data is available
If trials have to be amended once they have started (e.g., to help recruitment rates) the impact on trial size must be considered.

2.2 Care should be taken to avoid/reduce bias:
i) Using an independent randomisation system
ii) If at all possible double blinding should be the gold standard, but blinded assessment should be the minimum acceptable standard
Double Blinded Best
Single Blinded Ø
Blinded Assessment Minimum
iii) Analysis should be completed blind to group allocation
iv) Careful validation of data at end of study
v) Use of stratification to avoid bias in group characteristics
vi) Reporting the possible cumulative bias within a study involving a number of patient characteristics, which may not be significantly different on an individual basis.

3. Interventions
a. The ‘standard’ treatment is the best current therapy as defined by international consensus guidelines or where this is not available by best current practice as agreed by specialist groups.
b. The standard treatment must be described in the protocol.
c. ‘Placebo’ (defined as no-treatment) is not acceptable as a comparative therapy.
d. The time period for the intervention should be based on the primary end point, this justification should include the wound type, risk factors and patient population; this justification should be clearly defined in the protocol.
e. Interventions should include a run-in period to avoid centre effects and a follow-up period beyond the official study period to assess the quality and durability of healing.

4. Results/Data Interpretation
a. The endpoint to be used will depend on the type of intervention investigated (including surrogates).
b. Alternatives to healing are acceptable as endpoints, especially in groups where healing is not the main focus (e.g., palliative care). Where other endpoints are used (e.g., debridement, reduction of bacterial burden) then patients should be followed to healing to ensure that healing is not negatively affected.
c. Intention to Treat (ITT) and Per Protocol analysis must be presented.
d. Data should be analysed by both Internal and External statisticians.
e. Results of studies should be published whenever possible, including those with negative findings.

ETRS Working Groups – Recommendations:
1. Post draft statements on ETRS Website,
2. Publish draft statements in ETRS Bulletin,
3. Take comments from ETRS members,
4. Obtain approval from ETRS Board for setting up working groups to continue and expand work,
5. Agree final wording of statements by ETRS Board,
6. Inform and engage other societies in commenting on statements, and
7. Seek adoption by other societies at WUWHS meeting July 2004.

ETRS Working Groups: