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Reporting standards of studies and papers on the prevention

and management of foot ulcers in diabetes: required details
and markers of good quality
William J Jeffcoate, Sicco A Bus, Frances L Game, Robert J Hinchliffe, Patricia E Price, Nicolaas C Schaper, on behalf of the International Working
Group on the Diabetic Foot and the European Wound Management Association

The evidence base for many aspects of the management of foot ulcers in people with diabetes is weak, and good- Lancet Diabetes Endocrinol 2016;
quality research, especially relating to studies of direct relevance to routine clinical care, is needed. In this paper, we 4: 781–88

summarise the core details required in the planning and reporting of intervention studies in the prevention and Published Online
May 10, 2016
management of diabetic foot ulcers, including studies that focus on off-loading, stimulation of wound healing,
http://dx.doi.org/10.1016/
peripheral artery disease, and infection. We highlight aspects of trial design, conduct, and reporting that should be S2213-8587(16)30012-2
taken into account to minimise bias and improve quality. We also provide a 21-point checklist for researchers and for Foot Ulcer Trials Unit,
readers who assess the quality of published work. Department of Diabetes and
Endocrinology, Nottingham
University Hospitals Trust,
Introduction conducted and submitted for publication. Finally,
Nottingham, UK
Foot ulcers pose an enormous problem for people with through doing repeated systematic reviews, we found (Prof W J Jeffcoate MRCP);
diabetes,1 and their prevention and management are that existing tools for assessing the literature do not fully Academic Medical Centre,
undermined by the scarcity of evidence on which to base meet the needs of research in this complex clinical area; University of Amsterdam,
Amsterdam, Netherlands
treatment choices. Many systematic reviews2–7 have therefore, we also include a checklist as both a guide to
(S A Bus PhD); Derby Teaching
repeatedly drawn attention to the urgent need for higher- authors and a tool for readers to assess the quality of Hospitals, National Health
quality studies in both prevention and management. reported work. Service Foundation Trust,
Despite this call for action and the escalating size of the This definition of standards for the design and Derby, UK (Prof F L Game FRCP);
St George’s Vascular Unit,
clinical problem, the number of reports of high-quality reporting of research into disease of the foot in diabetes St George’s Hospital, London,
research into interventions for diabetic foot ulcers has is limited to interventions designed to improve either UK (Prof R J Hinchliffe MD);
remained low.2–6 the prevention or the management of foot ulcers, and Department of Vascular
There is no shortage of guidance available on the excludes other forms of diabetic foot disease. Although Surgery, University of Bristol
and Bristol Royal Infirmary,
general principles of trial design, conduct, and reporting, consideration is given to studies targeting different Bristol, UK (Prof R J Hinchliffe);
and researchers are already encouraged to use one of pathogenic factors (eg, neuropathy, deformity, peripheral Vice-Chancellors’ Office, Cardiff
several checklists when planning and conducting their artery disease, and infection), we primarily focus on University, Cardiff, UK
research. These include the CONSORT statement for research that is of direct clinical relevance. These (Prof P E Price PhD); and
Maastricht University Medical
randomised trials,8 STROBE for epidemiological guidelines do not include work on specific underlying Centre, Maastricht,
studies,9 and PRISMA for systematic reviews and meta- biological mechanisms or processes, observational (non- Netherlands
analyses.10 Systems for scoring studies of different interventional) research, or work in animal models. The (Prof N C Schaper MD)
design11 and guidance on the assessment of published paper is also limited to studies of efficacy and Correspondence to:
evidence—notably, the GRADE system12—also exist. effectiveness, and does not consider health-economic Prof William J Jeffcoate, Foot
Ulcer Trials Unit, Department of
These principles have been incorporated into two aspects. Diabetes and Endocrinology,
guidance documents for studies of chronic wounds Nottingham University Hospitals
published by the European Wound Management Core details for reports of intervention studies Trust, Nottingham NG5 1PB, UK
Association (EWMA),13,14 but no guidelines have so far Many details should be documented in intervention wjeffcoate@futu.co.uk

been produced that are specific for studies in the
complex clinical area of foot ulcers in diabetes. Part of
the reason for this lies in the large number of overlapping
processes involved in the development and presentation
of foot ulcers and in their protracted healing, and their
effects on all aspects of trial design.
Therefore, in this paper, we outline standards for the
design and reporting of studies of foot ulcers in diabetes,
although this paper is intended to be read in conjunction
with the less specific reports published by the EWMA.13,14
These standards are directed at those who design and
undertake the research, and those who read and assess
the reports. We hope that by defining the criteria that
need to be specified in research articles, this paper will
lead to an improvement in the quality of the research
studies, but they vary depending on the specific area of
research. They also vary between studies of ulcer
prevention and management (table 1), and between
studies concerning off-loading, associated peripheral
artery disease, and infection (table 2). The details of
studies can be divided into those relating to the
population (whether of the person, the limb, or the
ulcer), interventions, and outcomes, and they will vary
according to the primary objective or area of interest of
the study. The items listed in tables 1–2 should be
considered as essential for inclusion in reports, even
though the detail for each report will vary with the study
type. Failure to include some or many of these details is
the reason that so few high-quality papers have been
identified in systematic reviews.2–7

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Prevention of foot ulcers in diabetes
Population*
Person • Age, sex, and ethnicity
• Diabetes type, duration, and adequacy of glycaemic control
• Comorbidities (eg, established renal failure, heart failure, immobility, impaired vision)
• Ulcer risk classification: low, medium, or high
• Ambulatory status
• Educational status, socioeconomic status, and capacity for self-care (for studies on
education)
Limb • Peripheral artery disease: minimal assessment by palpation of pulses and ankle-brachial
pressure index, or toe blood pressure, or both
• Neuropathy: minimal assessment by determining loss of protective sensation (eg, with
a 10 g monofilament or vibration perception)
• Foot deformity (type or severity, or both)
• History of previous foot ulceration and amputation
Ulcer Not applicable
Interventions • All interventions: details of interventions (including duration and frequency); person
or team providing foot care; setting of the study
• Footwear: details on design, customisation, and materials used; evidence of
pressure-reducing efficacy if study relates to plantar ulceration
• Education or behavioural change: whether aimed at patients, carers, or health-care
professionals
• Surgery: evidence of pressure-reducing efficacy if study relates to plantar ulceration
Outcomes
Foot and limb • Ulcer (defined according to existing guidelines) incidence expressed as a proportion of
a population by a fixed time, or time to ulceration, or both
• First ever ulcer
• Recurrent ulcer (specified as being at the same site as a previous ulcer) or ulcer at a
different site
• Adherence to the intervention (eg, wearing footwear, self-care, or education,
preferably measured objectively)
• Foot pressure reduction (following provision of footwear or surgical interventions,
or both)
• Ambulatory activity level (for footwear studies), expressed as quantitatively as possible
• False-positive and false-negative outcomes (in diagnostic self-care studies)
• Amputation (major or minor, defined according to existing guidelines)
Person • Survival
• Ulcer-free survival (days)
• Health-related quality of life
• Adverse events or adverse device effects, or both
Surrogate • Potential surrogate outcome measures for studies in which ulcer incidence is not the
primary outcome
• Incidence of pre-ulcerative lesions (eg, hyperkeratotic tissue, haemorrhage, blister,
inflammation, each of which require definition)
• Change in plantar foot pressures
• Change in adherence
• Knowledge and behaviour (patient, carer, health-care professional)
• Foot examination skill (patient, carer, health-care professional)
• Patient satisfaction and wellbeing
IWGDF=International Working Group on the Diabetic Foot. *The detail recorded on each individual is dependent on sample size. It can be assumed, in very large prevention studies, that the sample is
representative of the total at-risk population and the need for detail is less.
Table 1: Core details for the reporting of intervention studies
The protocol and report should include definitions of key
terms appropriate to the study, such as “ulcer”, “healing”,
“deformity”, “peripheral artery disease”, “neuropathy”, and
“infection”. When relevant, the definition should be
accompanied by the criteria or the tests used to make the
782
Management of existing diabetic foot ulcers
• Age, sex, and ethnicity
• Diabetes type, duration, and adequacy of glycaemic control
• Comorbidities (eg, established renal failure, heart failure, immobility, impaired vision)
• Peripheral artery disease: minimal assessment by palpation of pulses and
ankle-brachial pressure index
• Neuropathy: minimal assessment by loss of protective sensation (eg, with a 10 g
monofilament or vibration perception)
• Foot deformity (type or severity, or both)
• History of previous foot ulceration and amputation
• Number of active ulcers
• Site of index ulcer
• Duration of index ulcer
• Type or classification of index ulcer (where appropriate)
• Area and depth of index ulcer
• Presence or absence of infection
Many potential interventions are possible, and these can be administered
systemically, regionally, or topically. For each intervention, sufficient information
should be provided to define
• its nature (including source)
• route, frequency, and duration of delivery
• person administering the delivery: professional, non-professional carer, the patient
• place of delivery: home, community clinic, surgery, hospital, specialist centre
• Ulcer healing (defined according to existing guidelines—eg, IWGDF)—the number or
percentage of index ulcers healed by a fixed time, or time to healing
• Healing following local surgery, including operative debridement
• Amputation (major or minor, defined according to existing guidelines)
• Failure to heal by a fixed time
• Survival
• Being ulcer free or amputation free, or both, at a fixed time after presentation
• Ulcer-free survival (days)
• Adverse events or adverse device effects, or both
• Health-related quality of life
• Change in ulcer area over a given period of time
• Change in ulcer appearance, biochemistry, histology, or other laboratory measure of
wound bed status
diagnosis. To facilitate uniform reporting that renders
comparison of studies possible, researchers are advised to
use the set of core definitions on patient characteristics,
treatment, and outcome provided by the International
Working Group on the Diabetic Foot (IWGDF).15
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Off-loading Peripheral artery disease Infections

Population No additional details • Smoking status
• Ambulatory status
• Previous interventions for peripheral artery disease
• History of related disease (eg, coronary artery disease,
heart failure, cerebrovascular disease)
• Other relevant comorbidities (eg, renal disease, depression)
• Relevant cardiovascular drugs
• Limb symptoms: none, atypical (weakness or limping),
intermittent claudication, and rest pain
• Toe systolic pressure, toe-brachial pressure index, or tcpO2
• Arterial pulse waveform
• Anatomical distribution of the vascular disease in the leg
• Number of active ulcers
• Site of index ulcer
Interventions • Details on non-surgical device, application method, No additional details
material use, and frequency of replacement
• Specific design details of the foot–device interface
• Person applying the device: the patient, a
non-professional carer, or a health-care professional
• Details of surgical intervention
• Evidence of pressure-reducing efficacy if study is on
plantar ulceration
Outcomes • Ulcer healing • Number of participants alive with an intact foot
• Adherence to the use of non-surgical removable • Description of outflow in the foot (in case of surgical or
interventions endovascular interventions)
• Foot pressure (for footwear and surgical • Ulcer healing
interventions) • Measures of the effectiveness of the vascular intervention
• Ambulatory activity level (eg, toe pressures and tcpO2)
• Number of patients with minor and with major
amputations
• Preceding antimicrobial use (type, route, duration, and
time before presentation)
• Immunosuppression
• Infection type (using IDSA or PEDIS grading): none,
mild, moderate, or severe
• Involvement of bone or joint
• Description of how samples were obtained for
microbiological examination
• Type of and results of microbiological examination
(Gram stain and susceptibility)
• Surgery undertaken before or in association with
antimicrobial administration
• Any other relevant intervention (including wound
debridement, cleansing, and antiseptic use) undertaken
before or in association with antimicrobial
administration
• Antimicrobial regimen: route of delivery, agents, and
duration
• Resolution of infection (which should be defined) at a
prespecified time after stopping antimicrobial treatment
• Clinical or laboratory signs of persistent infection at the
end of antimicrobial treatment
• Number and type of surgical procedures, including
amputation (with level of amputation defined according
to existing guidelines)
• Days of antimicrobial use, antimicrobial-free days, and
days of hospital admission
• Prevalence of antimicrobial resistance after treatment

IDSA=Infectious Disease Society of America. PEDIS=perfusion, extent, depth, infection, and sensation. tcpO2=transcutaneous partial pressure of oxygen.

Table 2: Additional core details for the reporting of intervention studies in the management of existing diabetic foot ulcers

Studies of foot ulcer prevention
Population
Table 1 summarises the core data to be considered in the
design and reporting of prevention studies. The
population details can be divided into those relating to the
person, the limb, and the ulcer. The minimum
requirements for the person details are age, sex, and
ethnicity, because all three are relevant to the onset of
new ulcers, which are more common in men, in older
people, and in white individuals.16 The presence of
relevant comorbidities—eg, established renal failure,
heart failure, immobility, impaired vision, or a
combination of these—should also be reported.
Participants should be classified as being at low, medium,
or high risk of new ulceration using a scheme such as
that adopted by the IWGDF,17 in which the classification
of risk is based on the presence of neuropathy, peripheral
artery disease or foot deformity, previous history of foot
ulceration, or amputation. Because a very large sample
size might be required to study prevention in low-risk
populations, the usual practice is to base research on
populations at high risk. The group with the highest risk
includes those who have had an ulcer previously; the
incidence of ulcer recurrence is roughly 30–40% in the
first 12 months after healing.18,19
Other details will depend on the focus of the study (eg,
whether it is concerned with education, footwear, or the
correction of risk factors such as deformity, use of
footwear, or peripheral artery disease). Educational
studies require documentation of educational status; in
studies of self-care behaviour, the capacity for self-care
should be described. Documentation of socioeconomic
status might also be relevant if it is feasible.
The volume and precision of data collection is affected
by the size of the study population. The incidence of new
ulceration in an unselected population with diabetes is
low (eg, roughly 2% per year in a low-risk population in
the UK); thus, a large sample size is required for studies
examining the effect of an intervention on ulcer incidence
in such a population—approximately 10 000 individuals
are needed to show a reduction in ulcer incidence to
1·5%, depending on study duration, anticipated
withdrawals, and power. The amount of baseline data that
can be reliably obtained from such a large study
population is necessarily limited, by contrast with smaller
studies in which more detailed data can be recorded.
Interventions
Various interventions can be explored with respect to
prevention (table 1), and their description should be

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detailed enough to enable another researcher to replicate
the study. In studies of footwear, for example, it is not
sufficient to simply state that the intervention was custom
made; details of the customisation must be provided.
As in studies of ulcer management (discussed below),
studies of ulcer prevention should specify the approach
for usual foot care in diabetes in the comparator group,
including the frequency of routine surveillance to
document the degree of ulcer risk, the approach to
mitigate risk factors (eg, deformity, abnormal pressure
loading, and peripheral artery disease), the provision of
foot-care education, the frequency of surveillance for
those at moderately increased risk, and the frequency of
surveillance for those at greatly increased risk.
Outcomes
The outcomes for the foot or limb or for the person can
be direct or surrogate (table 1). In prevention studies, the
primary outcome measure is preferably the incidence of
new ulceration, expressed as the proportion of the
population (in both absolute numbers and percentages)
who have a new ulcer by a fixed time, or as the time to
new ulceration, or both. Ulcer definition is a minimal
requirement. If more than one ulcer risk group is
included, outcomes should be reported for each group
separately. In some instances, it will also be important to
record the ulcer type and site, and whether the ulcer
occurs at the same site as the previous ulcer (ie, a
recurrence) or at a new site.
Other prevention studies use surrogate outcome
measures—eg, change in foot self-care (for educational,
behavioural, or other psychological intervention studies
directed at patients), change in foot examination skill or
frequency (for patients or health-care professionals), and
change in foot pressure (for footwear studies). Studies of
the effect of footwear or surgery on plantar foot ulcer
incidence should provide evidence of the efficacy of these
interventions to reduce pressure underneath the foot,
based on barefoot or in-shoe measures made with a
validated plantar pressure measurement system.
Additionally, footwear studies should provide data for
adherence to wearing the prescribed shoe using diaries
or, preferably, wearable technology such as activity and
footwear use monitors. For self-care management, data
for adherence and false-positive and false-negative
outcomes in seeking professional help are important,
because they can contribute to the cost-effectiveness and
acceptance of the intervention in clinical practice.
Studies of the management of existing diabetic foot
ulcers
Population
When the population studied is a mixed one (eg, studies
including both venous ulcers of the lower leg and diabetic
foot ulcer, or studies including people with and without
diabetes), the subpopulation of interest—ie, those with
diabetic foot ulcers—needs to be separately described and
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analysed, with specific reference to sample size, baseline
characteristics, withdrawals, and outcome. History of
previous ulceration or amputation might also be important
and should be specified in studies that include recurrence
or new ulceration as an endpoint. The setting of the study
(eg, primary, secondary, or tertiary care; one or multiple
centres) should be described to indicate the generalisability.
In addition to core population details—including age,
sex, ethnicity, and the type and duration of diabetes and
comorbidities—the extent of coexisting neuropathy (ie,
reduced sensation), peripheral artery disease, and foot
deformity should be documented because they can all
contribute to ulcer onset. Although several different
tests are used in clinical practice to define neuropathy
(eg, tests of 10 g monofilament, light touch, pain, and
vibration), there is no standard criterion for every
circumstance. The minimum requirement is usually
accepted as foot sensation documented with a 10 g
monofilament, although some researchers might use a
different stimulus (eg, vibration perception). At present,
the minimum details accepted for defining the presence
of peripheral artery disease in an ulcer study are pulse
palpability and the ankle-brachial pressure index.
However, neither of these measures is without flaws,
and further tests might be necessary, depending on the
nature of the study (table 2). In studies in which the
primary focus is interventions for peripheral artery
disease, the population needs to be defined with more
precise anatomical and functional markers (table 2). In
studies involving vascular interventions on both legs,
one limb should be chosen as index leg and only the
findings of this leg should be reported. There is no
accepted way of documenting the degree of foot
deformity in clinical practice; therefore, the inclusion of
foot deformity is inevitably subjective. However, if foot
deformity is relevant, then its nature and severity should
be described.
The ulcer needs to be described, and several classification
schemes are available for the documentation of ulcer
characteristics.20 Not all of these schemes include all the
details required for all studies. Reports should, however,
specify the number of active ulcers; the site, duration, type,
area, and depth of the index ulcer; and the presence or
absence of infection (table 1). People often have more than
one ulcer, and those who do have a worse overall prognosis
than do those who have only one ulcer. In individuals with
multiple ulcers, one ulcer should usually be selected for
the study (ie, the index ulcer). The index ulcer is usually
the largest or the one judged the most clinically important,
even though this definition depends on the chosen study
criteria. In studies in which the endpoint is healing of all
ulcers (and the foot being ulcer free), then all ulcers are
considered together as a group.
Increased area and depth of the ulcer are associated
with healing delay, and both need to be documented, as
do the methods used to determine them. Area is usually
documented after debridement but this needs to be
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stated. Ulcer depth is best classified by anatomical depth
(as in the University of Texas, IWGDF, and SINBAD
[site, ischaemia, neuropathy, bacterial infection, area,
and depth] classification systems20) rather than in
millimetres. The anatomical site should be specified
because this affects the choice of intervention and the
rate of healing.
For studies in which infection is the primary interest,
the population needs to be carefully defined (table 2). The
diagnosis of infection is primarily clinical and is based on
the criteria of the Infectious Diseases Society of America21
and the IWGDF.22 In most cases, studies will be concerned
with the treatment of clinically overt foot infection. Such
studies can select those with either soft tissue infection
alone or soft tissue infection combined with osteomyelitis;
the criteria used to define or exclude any osteomyelitis
must be stated. Studies may or may not include ulcers
that are infected at recruitment, but if they do, the
definition and severity of infection need to be described.
When assessing the effectiveness of new treatments
for wound care and off-loading in cases of so-called hard-
to-heal ulcers, it is becoming more common to specify
that a study ulcer has failed to heal despite management
in a specialist centre according to accepted principles of
good standard care (see below). As such, the duration of
the ulcer needs to be defined, and the ulcer needs to have
persisted without decreasing by more than a stated
percentage in cross-sectional area (40% or 50%) or other
aspect of size (eg, diameter, depth, or volume). The logic
for this requirement is that, in most cases, new (and
often expensive) treatments should not be used for ulcers
that are likely to heal with good standard care. The
adopted principles of good standard care should be
described (see below).
Nevertheless, so-called hard-to-heal ulcers might
include ulcers that have sometimes been present for very
long periods, and their failure to heal might derive from
a complex interaction between biological, social, and
personal factors. In such cases, the chances of one
treatment being shown to be effective might be reduced,
and this issue can be circumvented by including an
upper limit for ulcer duration (such as 12 or 24 months).
Interventions
The management of diabetic foot ulcers is multifaceted,
and the intervention to be tested should usually be
provided in addition to general good standard care. The
design of many studies will involve the comparison of
outcome in those receiving the intervention plus good
standard care with the outcome in a similar group
receiving a different intervention plus good standard care
or a group receiving good standard care alone.
Occasionally, the comparator group might be managed
with so-called usual care, implying that no effort has been
made to ensure that such care fulfils all the criteria of
good standard care. Although this is not ideal, it might be
a pragmatic solution, particularly in a study designed to
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Personal View
document effectiveness in a large population as opposed
to efficacy in a smaller, more tightly defined, one.
The principles of good standard care include a formal
assessment of the ulcer and surrounding skin at each
clinic review; provision of any necessary off-loading, with
detailed description of the type and assessment of its
effectiveness; debridement of the wound surface, which
can be surgical (either in the clinic or in an operating
room) or non-surgical; selection of appropriate dressing
products; appropriate antimicrobial therapy (for clinically
infected wounds only); attention to nutrition and self-care;
attempt to achieve optimal glycaemic control; assessment
for peripheral artery disease, with consideration of
revascularisation where appropriate; and continued close
observation with appropriate adjustment of management.
Outcomes
The outcome that most people want is to survive, have
improved quality of life, optimal mobility, and be ulcer
free as soon as possible—without the need for surgery or
hospital admission—and without recurrence (table 1).
Therefore, overall long-term outcome of the intervention
might be survival (at a fixed time) without continuing
ulceration and with unaided mobility intact. The use of
quality-of-life measures should also be considered.
If a person undergoes surgery, its nature needs to be
defined: surgical debridement with or without local
intervention such as grafting, minor amputation (defined
as transverse removal of part of the lower limb below the
ankle joint),15 and major amputation (transtibial, through
knee, or transfemoral).15 The extent of any postoperative
morbidity (eg, wound infection or transfer ulceration)
should be documented. When surgical or endovascular
procedures are assessed, 30 day mortality and preferably
also long-term mortality should be reported. The incidence
of major amputation should never be considered in
isolation from death, because there are many people who
die during follow-up and who would have had a major
amputation if their overall prognosis was not so poor.
Early major amputation is recognised to be the best
treatment for some individuals, and while the incidence
of limb loss through amputation should be recorded,
death during the study, both with and without preceding
major amputation, also needs to be documented. The
term limb salvage (which means survival without major
amputation) has become popular in some specialty areas,
but it is poorly defined and is therefore not recommended.
The preferred term is amputation-free survival.
Ulcer healing is usually defined as complete epi-
thelialisation after removal of callus without discharge,
which is maintained for a minimum of 2 weeks (as
required by the US Food and Drug Administration). Any
ulcer that occurs after the time specified is regarded as a
recurrence. It is important to also specify whether healing
follows a surgical procedure (such as flap or grafting) or
whether it is by secondary intention. Healing can be
recorded as the number (or percentage) of index ulcers
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healed by a fixed time from randomisation (or the start of
the observation period in non-randomised studies), or as
the time to healing. The term “rate of healing” is
ambiguous because it can refer to the incidence of
healing, the time to healing, or the percentage reduction
in cross-sectional area and should therefore be avoided. A
further problem inherent in the use of either the number
(or percentage) of ulcers healed by a fixed time or the time
to healing is that these metrics are directly related to
baseline ulcer area, because larger ulcers take longer to
heal. It is therefore important to ensure that intervention
and control groups include near-equal numbers of ulcers
of different sizes.
Change in ulcer area can be used as a surrogate
endpoint, but measurement of ulcer area presents its
own problems. The contour of the foot underlying an
ulcer is nearly always curved, meaning that measure-
ments taken from digital images are not precise.
Therefore, the methods used to measure cross-sectional
area need to be documented. Newer commercial imaging
systems are increasingly used, and some might allow the
assessment of changes in ulcer volume; however, they
tend to be expensive. Several other ulcer-related outcomes
can be used as surrogate endpoints, including measures
of clinical wound appearance and status, especially in
shorter-term studies.
For studies focused on infection, the choice of outcome
will be determined by the study design and, in particular,
whether the aim is to assess the use of a non-surgical
antimicrobial treatment without surgery or an
intervention that combines the two. The aim of most
such studies will be the resolution of infection, defined
as the disappearance of, or sufficient improvement in,
signs and symptoms related to the infection such that no
further treatment is required. Ulcer healing is not a
specific measure of the resolution of infection.
Resolution of infection can be achieved either by the use
of non-surgical antimicrobial treatment (including
antibiotics via topical, local, or systemic routes) or by
antimicrobial therapy in combination with surgery. If
the study aims to assess an antimicrobial regimen, then
the use of surgery might be considered as an outcome
(indicating incomplete effect), whereas in studies of a
combined approach, the use of surgery might simply be
a detail of the intervention. When assessing non-surgical
interventions (eg, an antibiotic regimen), the resolution
of infection can be determined at different stages—at
specified points during treatment, at the end of
treatment, or at a specified time after the end of
treatment (usually called test of cure). Such studies often
also include microbiological outcomes, but consideration
of these is beyond the scope of this paper. Moreover, the
eradication of clinical infection cannot be defined by the
results of microbiological testing.
In studies of peripheral artery disease, the outcomes
will be specific to revascularisation (eg, outflow in the
foot), even though ulcer healing might be used as a
786
secondary outcome measure (table 2). Of note, none of
the existing classifications for the effects of peripheral
artery disease is entirely appropriate for people with
diabetic foot ulcers.
All intervention studies should include a formal
documentation of adverse events and adverse device
effects, regardless of whether they are serious. Adverse
events might include, but are not restricted to, hospital
admissions, infection, onset of an acute Charcot foot,
new ulcer formation, amputation, death, and—especially
in the case of off-loading interventions—falls, abrasions,
hyperkeratosis, and blisters.
The efficacy or effectiveness of an intervention cannot
be assessed unless the completeness of intervention
delivery is documented. One example relates to the use
of off-loading, in which it can be important to show not
only that off-loading has been prescribed, but also that it
is effective in terms of reducing the forces applied to the
foot or to the healing wound and that the device is
worn as prescribed (ie, compliance, adherence, or
concordance).
Markers of good quality
Some of the details in the above sections should be used
to define the quality of the resulting publication. Quality
largely refers to the extent to which a study and its report
are free from bias—ie, the reported observations and
conclusions are most probably the result of the
intervention and unlikely to have been affected by other
factors. To help with the assessment of quality, we
provide a checklist for intervention studies of diabetic
foot ulcers (panel). Many criteria listed are relevant to the
management of chronic wounds, as detailed in the two
publications by the EWMA.13,14 Many criteria in this
checklist also overlap with those in the CONSORT
guidelines,8 which are widely applied by journal editors
when considering papers for publication.
In addition to providing guidance to investigators on
the design and reporting of research in this area, the aim
of this checklist is to include criteria that can be used to
grade the quality of the report and thereby give an
indication of its potential relevance to routine clinical
practice. The ability to grade publications in this way is of
great importance in the assessment of individual
publications and also for the conduct of systematic
reviews. Several generic scoring schemes already exist
but, in our own experience, these schemes do not apply
well to studies of diabetic foot ulcers.
The criteria are divided into four main groups: study
design, study conduct, outcomes, and study reporting.
The intention is that the desired answer for each item is
“yes”, and that each scores one point. Criteria have yet to
be established to determine how the resultant scores
(maximum 21) can be stratified into appropriate levels of
quality. The complete checklist is shown in the panel,
although some notes regarding the interpretation and
use of several criteria are provided below.
www.thelancet.com/diabetes-endocrinology Vol 4 September 2016

Study design: choice of study population (item 2)
If the study is being assessed from the point of view of
clinical care, the following principles apply, even though
some exceptions exist. First, the participants should be
patients with diabetes who are at risk of developing a
diabetic foot ulcer (for prevention studies) or whose
disease is complicated by a diabetic foot ulcer (for
intervention studies). Second, if more than one foot ulcer
is present, only one (a specified index ulcer) should be
included per participant. Third, the type of ulcer chosen
for a study of treatment should be appropriate for the
type of intervention. This is relevant because many trials
of new interventions were done in people with
uncomplicated neuropathic ulcers, for which a cheap
and effective treatment already existed (ie, off-loading).
In practice, a new (and usually expensive) treatment will
be reserved for ulcers that have failed to heal despite
administration of good standard care in expert centres.
Therefore, the effectiveness of new treatments should, in
most cases, be assessed in participants with so-called
hard-to-heal ulcers. To that end, the term “hard-to-heal”
requires a definition.
Study design: definition of other aspects of care (item 5)
When an intervention is administered for the prevention
or treatment of diabetic foot ulcers, it will inevitably be
given in conjunction with other aspects of care (usual
care or optimised, good standard care; see above). The
components of other aspects of care must be described.
Study conduct: retention and attrition (item 13)
Many participants are lost to follow-up from studies of
diabetic foot ulcers, not least because the population
susceptible to foot disease is also prone to other
complications of diabetes and comorbidities, and
intercurrent illness is not uncommon. The longer the
study duration, the higher the likelihood of intercurrent
illness and thus loss to follow-up. If the primary outcome
is based on ulcer healing, then the duration of the
intervention is likely to last for 16, 20, or 24 weeks. If the
primary endpoint is ulcer development in a prevention
study, follow-up might be much longer. The lower the
rate of retention (ie, the higher the rate of attrition or loss
to follow-up), the greater the likelihood of bias in any
observations made. There is no consensus on the rate of
retention or attrition that is acceptable in this population
in studies of different duration but, in our opinion, the
rate of attrition should be no greater than 25% in studies
of ulcer management with an intervention phase of
20 weeks or more.
Outcomes: performance in the control group (item 16)
Some expensive new interventions have acquired wide-
spread adoption as a result of studies that would now be
regarded as flawed. In some cases, the apparent benefit
of the new intervention was based on a significant
difference from the comparator group, when the
www.thelancet.com/diabetes-endocrinology Vol 4 September 2016
Personal View
Panel: 21-point scoring system for reports of clinical studies of the prevention and
management of disease of the foot in diabetes
The desired answer for each question is intended to be “yes”, and each scores one point.
Study design
1 Are appropriate definitions included for the terms “ulcer”, “healing”, and all other
required aspects of the population and the outcomes?
2 Was the choice of study population appropriate for the chosen intervention and the
stated conclusions?
3 Was there a control population that was managed at the same time as those in the
intervention group or groups?
4 Is the intervention sufficiently well described to enable another researcher to replicate
the study?
5 Are the components of other aspects of care described for the intervention and
comparator groups?
6 Were the participants randomised into intervention and comparator groups?
7 Were the participants randomised by an independent person or agency?
8 Was the number of participants studied in the trial based on an appropriate sample
size calculation?
9 Was the chosen primary outcome of direct clinical relevance?
10 Was the person who assessed the primary outcome or outcomes blinded to group
allocation?
11 Were either the clinical researcher who cared for the wound at research visits or the
participants blinded to group allocation?
Study conduct
12 Did the study complete recruitment?
13 Was it possible to document the primary outcome in 75% or more of those recruited?
14 Were the results analysed primarily by intention-to-treat analysis?
15 Were appropriate statistical methods used throughout?
Outcomes
16 Was the performance in the control group of the order that would be expected in
routine clinical practice?
17 Are the results from all participating centres comparable? Answer “yes” if the study
was done in only one centre.
Study reporting
18 Is the report free from errors of reporting—eg, discrepancies between data reported in
different parts of the report?
19 Are the important strengths and weaknesses of the study discussed in a balanced way?
20 Are the conclusions supported by the findings?
21 Is the report free from any suggestion that the analysis or the conclusions could have
been substantially influenced by people with commercial or other personal interests in
the findings?
difference could be accounted for by poor performance
in the comparator group receiving usual care. It is
therefore essential to scrutinise outcome in the
comparator group and to check that performance is
similar to that used as the basis for sample size
calculation.
Conclusions
The paper is based on expert opinion and summarises the
points that should be included in the design and reporting
of clinical studies of the complex processes involved in the
prevention and management of foot ulcers in diabetes. It
787
 Personal View
is directed both at researchers planning clinical research
in this area and at those who read and assess the reports of
such work. It does not include detail on some fundamental
aspects of trial design, which are covered in previous
publications by the EWMA.13,14 Finally, it is also intended to
be used as a template, which will need further details for
studies in some subspecialty areas.
The production of lists of required data is fraught with
difficulty, not least because the details required for one
type of study might sometimes be different from those
required in another type, even in the same specialty. It is
this difficulty that results in tables 1–2 being entitled
“core details” because it is not possible to be more
dogmatic. This is most true in the subspecialty areas of
off-loading, peripheral artery disease, and infection. For
each of these, as well as for research relating to specific
interventions in wound healing, the lists provided will
ultimately serve as a spine that can be used for the more
detailed guidance required by those working in the area.
In addition to highlighting the core details for points to
be considered in trial design and reporting, we have
included a checklist of 21 items that can be used to assess
the quality of work in the specialty of diabetic foot ulcers
(panel). The higher the score achieved, the greater the
chance that the reported study is free from bias and is
relevant to clinical practice. This checklist aims to provide
equal weight to aspects of study design, conduct, and
reporting, and should also be considered as a tool for the
conduct of systematic reviews in this complex clinical
area. If these criteria are adopted in future reports, it is
hoped that there will be overall improvement in the
quality of published work in a clinical field for which the
evidence base is weak at present.
Contributors
WJJ, SAB, FLG, PEP, and NCS produced the first version of the
manuscript in its final form. All authors were involved in discussions
leading to the drafting of this manuscript and revision of the manuscript,
and approved the final version for publication.
Declaration of interests
We declare no competing interests.
Acknowledgments
We are indebted to many colleagues who have participated in the process
leading to the development of this paper and who have commented on
its near-final versions. These include other members of the 2015
International Working Group on the Diabetic Foot systematic review
groups on prevention, wound healing, peripheral artery disease,
infection, and off-loading. We are also grateful to the European Wound
Management Association for supporting and endorsing this initiative.
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