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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 Jecoate, Sicco A Bus, Frances L Game, Robert J Hinchlie, 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 goodquality research, especially relating to studies of direct relevance to routine clinical care, is needed. In this paper, we
summarise the core details required in the planning and reporting of intervention studies in the prevention and
management of diabetic foot ulcers, including studies that focus on o-loading, stimulation of wound healing,
peripheral artery disease, and infection. We highlight aspects of trial design, conduct, and reporting that should be
taken into account to minimise bias and improve quality. We also provide a 21-point checklist for researchers and for
readers who assess the quality of published work.

Introduction
Foot ulcers pose an enormous problem for people with
diabetes,1 and their prevention and management are
undermined by the scarcity of evidence on which to base
treatment choices. Many systematic reviews27 have
repeatedly drawn attention to the urgent need for higherquality studies in both prevention and management.
Despite this call for action and the escalating size of the
clinical problem, the number of reports of high-quality
research into interventions for diabetic foot ulcers has
remained low.26
There is no shortage of guidance available on the
general principles of trial design, conduct, and reporting,
and researchers are already encouraged to use one of
several checklists when planning and conducting their
research. These include the CONSORT statement for
randomised trials,8 STROBE for epidemiological
studies,9 and PRISMA for systematic reviews and metaanalyses.10 Systems for scoring studies of dierent
design11 and guidance on the assessment of published
evidencenotably, the GRADE system12also exist.
These principles have been incorporated into two
guidance documents for studies of chronic wounds
published by the European Wound Management
Association (EWMA),13,14 but no guidelines have so far
been produced that are specic 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
eects 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 specic 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 dening the criteria that
need to be specied in research articles, this paper will
lead to an improvement in the quality of the research

conducted and submitted for publication. Finally,

through doing repeated systematic reviews, we found
that existing tools for assessing the literature do not fully
meet the needs of research in this complex clinical area;
therefore, we also include a checklist as both a guide to
authors and a tool for readers to assess the quality of
reported work.
This denition of standards for the design and
reporting of research into disease of the foot in diabetes
is limited to interventions designed to improve either
the prevention or the management of foot ulcers, and
excludes other forms of diabetic foot disease. Although
consideration is given to studies targeting dierent
pathogenic factors (eg, neuropathy, deformity, peripheral
artery disease, and infection), we primarily focus on
research that is of direct clinical relevance. These
guidelines do not include work on specic underlying
biological mechanisms or processes, observational (noninterventional) research, or work in animal models. The
paper is also limited to studies of ecacy and
eectiveness, and does not consider health-economic
aspects.

Core details for reports of intervention studies

Many details should be documented in intervention
studies, but they vary depending on the specic area of
research. They also vary between studies of ulcer
prevention and management (table 1), and between
studies concerning o-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 12 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
identied in systematic reviews.27

www.thelancet.com/diabetes-endocrinology Published online May 10, 2016 http://dx.doi.org/10.1016/S2213-8587(16)30012-2

Lancet Diabetes Endocrinol 2016

Published Online
May 10, 2016
http://dx.doi.org/10.1016/
S2213-8587(16)30012-2
Foot Ulcer Trials Unit,
Department of Diabetes and
Endocrinology, Nottingham
University Hospitals Trust,
Nottingham, UK
(Prof W J Jeffcoate MRCP);
Academic Medical Centre,
University of Amsterdam,
Amsterdam, Netherlands
(S A Bus PhD); Derby Teaching
Hospitals, National Health
Service Foundation Trust,
Derby, UK (Prof F L Game FRCP);
St Georges Vascular Unit,
St Georges Hospital, London,
UK (Prof R J Hinchliffe MD);
Department of Vascular
Surgery, University of Bristol
and Bristol Royal Infirmary,
Bristol, UK (Prof R J Hinchliffe);
Vice-Chancellors Office,
Cardiff University, Cardiff, UK
(Prof P E Price PhD); and
Maastricht University Medical
Centre, Maastricht,
Netherlands
(Prof N C Schaper MD)
Correspondence to:
Prof William J Jeffcoate, Foot
Ulcer Trials Unit, Department of
Diabetes and Endocrinology,
Nottingham University
Hospitals Trust, Nottingham
NG5 1PB, UK
wjeffcoate@futu.co.uk

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Prevention of foot ulcers in diabetes

Management of existing diabetic foot ulcers

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 classication: low, medium, or high
Ambulatory status
Educational status, socioeconomic status, and capacity for self-care (for studies on
education)

Age, sex, and ethnicity

Diabetes type, duration, and adequacy of glycaemic control
Comorbidities (eg, established renal failure, heart failure, immobility, impaired vision)

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 monolament or vibration perception)
Foot deformity (type or severity, or both)
History of previous foot ulceration and amputation

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
monolament or vibration perception)
Foot deformity (type or severity, or both)
History of previous foot ulceration and amputation

Ulcer

Not applicable

Number of active ulcers

Site of index ulcer
Duration of index ulcer
Type or classication of index ulcer (where appropriate)
Area and depth of index ulcer
Presence or absence of infection

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 ecacy if study relates to plantar ulceration
Education or behavioural change: whether aimed at patients, carers, or health-care
professionals
Surgery: evidence of pressure-reducing ecacy if study relates to plantar ulceration

Many potential interventions are possible, and these can be administered

systemically, regionally, or topically. For each intervention, sucient information
should be provided to dene
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

Population*

Outcomes
Foot and limb Ulcer (dened according to existing guidelines) incidence expressed as a proportion of
a population by a xed time, or time to ulceration, or both
First ever ulcer
Recurrent ulcer (specied as being at the same site as a previous ulcer) or ulcer at a
dierent 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, dened according to existing guidelines)

Ulcer healing (dened according to existing guidelineseg, IWGDF)the number or

percentage of index ulcers healed by a xed time, or time to healing
Healing following local surgery, including operative debridement
Amputation (major or minor, dened according to existing guidelines)
Failure to heal by a xed time

Person

Survival
Ulcer-free survival (days)
Health-related quality of life
Adverse events or adverse device eects, or both

Survival
Being ulcer free or amputation free, or both, at a xed time after presentation
Ulcer-free survival (days)
Adverse events or adverse device eects, or both
Health-related quality of life

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,
inammation, each of which require denition)
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

Change in ulcer area over a given period of time

Change in ulcer appearance, biochemistry, histology, or other laboratory measure of
wound bed status

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 denitions of key

terms appropriate to the study, such as ulcer, healing,
deformity, peripheral artery disease, neuropathy, and
infection. When relevant, the denition should be
accompanied by the criteria or the tests used to make the
2

diagnosis. To facilitate uniform reporting that renders

comparison of studies possible, researchers are advised to
use the set of core denitions on patient characteristics,
treatment, and outcome provided by the International
Working Group on the Diabetic Foot (IWGDF).15

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O-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

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)

Interventions

Details on non-surgical device, application method, No additional details

material use, and frequency of replacement
Specic design details of the footdevice interface
Person applying the device: the patient, a
non-professional carer, or a health-care professional
Details of surgical intervention
Evidence of pressure-reducing ecacy if study is on
plantar ulceration

Outcomes

Ulcer healing
Adherence to the use of non-surgical removable
interventions
Foot pressure (for footwear and surgical
interventions)
Ambulatory activity level

Number of participants alive with an intact foot

Description of outow in the foot (in case of surgical or
endovascular interventions)
Ulcer healing
Measures of the eectiveness of the vascular intervention
(eg, toe pressures and tcpO2)
Number of patients with minor and with major
amputations

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 dened) at a
prespecied 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 dened 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 comorbiditieseg, established renal failure,
heart failure, immobility, impaired vision, or a
combination of theseshould also be reported.
Participants should be classied 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 classication
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 3040% in the
rst 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 aected
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 eect of an intervention on ulcer incidence
in such a populationapproximately 10 000 individuals
are needed to show a reduction in ulcer incidence to
15%, 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
sucient 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 xed time, or as the time to
new ulceration, or both. Ulcer denition 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
measureseg, 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 eect of footwear or surgery on plantar foot ulcer
incidence should provide evidence of the ecacy 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-eectiveness 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 interestie, those with
diabetic foot ulcersneeds to be separately described and
4

analysed, with specic reference to sample size, baseline

characteristics, withdrawals, and outcome. History of
previous ulceration or amputation might also be important
and should be specied 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 detailsincluding age,
sex, ethnicity, and the type and duration of diabetes and
comorbiditiesthe 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 dierent
tests are used in clinical practice to dene neuropathy
(eg, tests of 10 g monolament, 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
monolament, although some researchers might use a
dierent stimulus (eg, vibration perception). At present,
the minimum details accepted for dening 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 aws,
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 dened 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
ndings 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 classication
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 denition 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 classied by anatomical depth

(as in the University of Texas, IWGDF, and SINBAD
[site, ischaemia, neuropathy, bacterial infection, area,
and depth] classication systems20) rather than in
millimetres. The anatomical site should be specied
because this aects the choice of intervention and the
rate of healing.
For studies in which infection is the primary interest,
the population needs to be carefully dened (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 dene or exclude any osteomyelitis
must be stated. Studies may or may not include ulcers
that are infected at recruitment, but if they do, the
denition and severity of infection need to be described.
When assessing the eectiveness of new treatments
for wound care and o-loading in cases of so-called hardto-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 dened, 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 eective 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 dierent 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 eort has been
made to ensure that such care fulls all the criteria of
good standard care. Although this is not ideal, it might be
a pragmatic solution, particularly in a study designed to

document eectiveness in a large population as opposed

to ecacy in a smaller, more tightly dened, 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 o-loading, with
detailed description of the type and assessment of its
eectiveness; 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 possiblewithout the need for surgery or
hospital admissionand without recurrence (table 1).
Therefore, overall long-term outcome of the intervention
might be survival (at a xed 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
dened: surgical debridement with or without local
intervention such as grafting, minor amputation (dened
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 dened and is therefore not recommended.
The preferred term is amputation-free survival.
Ulcer healing is usually dened as complete epithelialisation 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 specied is regarded as a
recurrence. It is important to also specify whether healing
follows a surgical procedure (such as ap 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 xed 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 xed 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 dierent 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 measurements 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, dened
as the disappearance of, or sucient improvement in,
signs and symptoms related to the infection such that no
further treatment is required. Ulcer healing is not a
specic 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 eect), 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 dierent stagesat
specied points during treatment, at the end of
treatment, or at a specied 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 dened by the
results of microbiological testing.
In studies of peripheral artery disease, the outcomes
will be specic to revascularisation (eg, outow in the
foot), even though ulcer healing might be used as a
6

secondary outcome measure (table 2). Of note, none of

the existing classications for the eects 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
eects, 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, andespecially
in the case of o-loading interventionsfalls, abrasions,
hyperkeratosis, and blisters.
The ecacy or eectiveness of an intervention cannot
be assessed unless the completeness of intervention
delivery is documented. One example relates to the use
of o-loading, in which it can be important to show not
only that o-loading has been prescribed, but also that it
is eective 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 dene the quality of the resulting publication. Quality
largely refers to the extent to which a study and its report
are free from biasie, the reported observations and
conclusions are most probably the result of the
intervention and unlikely to have been aected 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 stratied 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.

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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 specied 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 eective treatment already existed (ie, o-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 eectiveness 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 denition.

Study design: denition 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 dierent 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.

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 denitions 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 suciently 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 reportingeg, discrepancies between data reported in
dierent 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 ndings?
21 Is the report free from any suggestion that the analysis or the conclusions could have
been substantially inuenced by people with commercial or other personal interests in
the ndings?

dierence 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.

Outcomes: performance in the control group (item 16)

Some expensive new interventions have acquired widespread adoption as a result of studies that would now be
regarded as awed. In some cases, the apparent benet
of the new intervention was based on a signicant
dierence from the comparator group, when the

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

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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
diculty, not least because the details required for one
type of study might sometimes be dierent from those
required in another type, even in the same specialty. It is
this diculty that results in tables 12 being entitled
core details because it is not possible to be more
dogmatic. This is most true in the subspecialty areas of
o-loading, peripheral artery disease, and infection. For
each of these, as well as for research relating to specic
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 eld for which the
evidence base is weak at present.
Contributors
WJJ, SAB, FLG, PEP, and NCS produced the rst version of the
manuscript in its nal form. All authors were involved in discussions
leading to the drafting of this manuscript and revision of the manuscript,
and approved the nal version for publication.

10

11
12

13

14

15

16

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-nal 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 o-loading. We are also grateful to the European Wound
Management Association for supporting and endorsing this initiative.

17

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