A Pilot Randomized Controlled Trial to Evaluate an Advanced Borderless Dressing (ALLEVYN LIFE Non-Bordered) in the Treatment of Chronic Ulcers
Phase: NA
Conditions: Pressure Ulcer, Leg Ulcer, Diabetic Foot Ulcer
Sponsor: Smith & Nephew, Inc.

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A Pilot Randomized Controlled Trial to Evaluate an Advanced Borderless Dressing 
(ALLEVYN™ LIFE Non-Bordered) in the Treatment of Chronic Ulcers 
Study Number: 
CT1603ALF 
Sponsor Name & Address: 
Smith & Nephew, Inc. 
5600 Clearfork Main Street 
Fort Worth, Texas 76109 
Test and Comparator 
Product(s): 
Test Article: ALLEVYN LIFE Non-Bordered 
Comparator Article: Standard Care 
Protocol Author(s): 
Stewart Richmond, PhD  
Michael Robinson, MMathStat  
Darrell Lange, PhD  
Protocol Version  
1.0, 27Mar2017 

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1. SIGNATURES 
1.1 
INVESTIGATOR’S AGREEMENT 
I have read the attached protocol entitled “A Pilot Randomized Controlled Trial to Evaluate an 
Advanced Borderless Dressing (ALLEVYN™ LIFE Non-Bordered) in the Treatment of Chronic 
Ulcers,” version 1.0, dated 27 Mar 2017, and agree to abide by all provisions set forth therein.  
I agree to comply with the requirements stipulated in Section 21.3 (Principal Investigator 
Obligations) of the protocol. 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the conduct of the described clinical investigation without the prior 
written consent of Smith & Nephew, Inc.  
 
 
Signature 
 
 
 
Name of Principal Investigator (print) 
 
 
Date 

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2. SYNOPSIS 
 
 
 
 
Financial Disclosure Information for U.S. FDA Submission 
to be Obtained? 
 
Yes 
X 
No 
 
 
 
 
 
 
 
 
Investigational Products: 
ALLEVYN LIFE Non-Bordered 
Product Used in Study: 
ALLEVYN LIFE Non-Bordered is a borderless, multilayer 
foam dressing with a silicone adhesive.  
Active Ingredients: 
NA 
 
 
 
 
 
 
 
 
Objective(s): 
The primary objective is to estimate the effect of treatment 
with Allevyn Life Non-Bordered (ALNB) on Health-
Related Quality of Life (HRQoL) in subjects with chronic 
ulcers, measured using the Cardiff Wound Impact Schedule 
Physical Symptoms and Daily Living (CWIS-PSDL) scale, 
compared to subjects receiving SC alone, over a six week 
treatment period. 
Secondary objectives of this study are: 
1) To estimate the effects of treatment with ALNB, 
when compared with SC alone, on: 
a. HRQoL measured by the CWIS-PSDL scale 
at three and twelve weeks, and CWIS well-
being (WB), social life (SL); global quality 
of life (GQ); and satisfaction with quality of 

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life (SQ) scales; at three, six, and twelve 
weeks 
b. Ulcer progression (including undermining, 
necrotic tissue type and amount, exudate 
type and amount, skin color surrounding the 
wound, granulation tissue, epithelialization, 
condition of peri-wound, ulcer dimensions 
and healing status) at three, six, and twelve 
weeks 
2) Health care resource use related to the reference 
ulcer (including number and cost of dressings used, 
time in hospital, number and cost of additional 
treatments, procedures, and investigations) over 
twelve weeks 
The exploratory objectives of this study are to compare 
differences between ALNB and SC in dressing performance 
(including wear time, leakage, odor control, and absorption 
under compression) and usability (including comfort and 
ease of application/removal together with associated pain) 
at three, six, and twelve weeks. 
Study Population: 
Adults aged 18 years and older with moderate to highly 
exuding chronic ulcers.  

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Structure: 
Parallel Group  
Duration of Treatment: 
Up to 12 weeks 
Duration of Assessment: 
Up to 12 weeks 
 
 
 
 
Multi-Center: 
X 
Yes 
Number of Centers: Up to 6 
 
 
No 
 
 
 
 
 
 
 
 
 
 
Blinding: 
X 
None 
 
Subject-Blind 
 
 
Observer-Blind 
 
Double-Blind 
 
 
 
 
 
 
 
 
 
Randomization: 
X 
Yes 
Group Assignment Ratio: 5:3 in favor of ALNB 
(ALNB n = 25; SC n = 15)  
Stratified by wound type: diabetic foot ulcer 
(DFU), leg ulcer (LU) and pressure ulcer (PU).  
 
 
No 
 
 
 
 
 
 
 
 
 
Concurrent Comparator: 
Standard Care (SC) 
 
 
 
 
 
 
 
 
Estimated Total Sample Size: 
A minimum of 40 randomized subjects. 
Statistical Rationale  
 
Yes  
Provided: 
X 
No 
Subject Population: 
Adult subjects (≥ 18 years of age) presenting with a moderate 

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to highly exuding chronic ulcer that, in the opinion of the 
Investigator, would benefit from a protective dressing but 
does not require topical antimicrobial treatment. Chronic 
ulcers will include leg ulcers (LU) of any etiology, pressure 
ulcers (PU), and nonischemic diabetic foot ulcers (DFU).  
 
 
 
 
Variable(s): 
PRIMARY: 
The change in CWIS-PSDL scale score between baseline and 
six weeks in each treatment group. 
 
KEY 
SECONDARY: 
Subject-reported HRQoL variables (measured using the 
CWIS) to be compared between groups for change over 
three, six, and twelve weeks for the domains of CWIS-SL, 
CWIS-WB, and CWIS-GQ and at 3 and 12 weeks for CWIS-
PSDL.  
 
SECONDARY 
Ulcer progression variables to be compared between groups 
at three, six, and twelve weeks including: 
 Modified Bates-Jensen Wound Assessment Tool 
o Undermining  
o Necrotic tissue type  
o Necrotic tissue amount 
o Exudate type 
o Exudate amount 
o Skin color surrounding the wound 
o Granulation tissue 
o Epithelialization 
 Condition of peri-wound 
 Ulcer dimensions 
 Ulcer healed status 
 
Healthcare resource use variables (to be compared between 
groups over the entire twelve week study period) including: 

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 Dressings used (number and type for both primary and 
secondary dressings), including use of compression 
therapy 
 Healthcare consultations (number and type) 
 Time spent by health care providers (HCP) in 
treating/caring for reference ulcer  
 Time in hospital (nights spent as an inpatient due to 
reference ulcer) 
 Interventions/procedures related to the reference ulcer 
(number and type), including debridement of the ulcer 
(curette, scissors, scalpel, forceps, other) 
 Concomitant therapies/treatments (number and type) 
used on the reference ulcer 
 
 
EXPLORATORY: Further exploratory data will be gathered for dressing 
performance and usability/acceptability and compared 
between groups, where appropriate. Relevant variables will 
include: 
 Dressing wear time (days) 
 Dressing leakage (HCP-assessed) 
 Ease of dressing application/removal (HCP-assessed) 
 Dressing use (whether dressing was cut and adherence 
following repositioning) 
 Odor control of dressing (HCP-assessed) 
 Absorption under compression (HCP-assessed for 
subjects with LU requiring compression). 
 Reason for dressing change (HCP-assessed) 
 Pain on dressing removal (subject-reported) 
 Comfort during wear (subject-reported) 

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SAFETY: 
Safety data will be gathered throughout the twelve weeks of 
the study, including: 
 Adverse events 
 Device deficiencies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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3. CONTENTS 
3.1 
TABLE OF CONTENTS 
1. 
SIGNATURES .......................................................................................................................2 
1.1 
Investigator’s Agreement ...........................................................................................2 
1.2 
Sponsor Approval .......................................................................................................3 
1.3 
Quality Assurance Signature ......................................................................................4 
2. 
SYNOPSIS ..............................................................................................................................5 
3. 
CONTENTS .........................................................................................................................11 
3.1 
Table of Contents ......................................................................................................11 
3.2 
Table of Tables .........................................................................................................12 
3.4 
List of Abbreviations ................................................................................................13 
4. 
INTRODUCTION ...............................................................................................................15 
4.1 
Background ...............................................................................................................15 
4.2 
Safety Considerations ...............................................................................................16 
5. 
OBJECTIVES ......................................................................................................................18 
5.1 
Primary .....................................................................................................................19 
5.2 
Key Secondary ..........................................................................................................19 
5.3 
Secondary .................................................................................................................19 
5.4 
Exploratory ...............................................................................................................19 
5.5 
Safety ........................................................................................................................20 
5.6 
Claims .......................................................................................................................20 
6. 
STUDY PRODUCT .............................................................................................................20 
6.1 
Identification .............................................................................................................20 
6.2 
Product Use ...............................................................................................................24 
6.3 
Packaging and Labeling ............................................................................................26 
6.4 
Product Accountability Procedures ..........................................................................27 
7. 
SUBJECTS ...........................................................................................................................28 
7.1 
Subject Population ....................................................................................................28 
7.2 
Inclusion Criteria ......................................................................................................28 
7.3 
Exclusion Criteria .....................................................................................................29 
7.4 
Screening Log ...........................................................................................................30 
7.5 
Enrollment ................................................................................................................30 
7.6 
Withdrawal ...............................................................................................................30 
8. 
STUDY DESIGN .................................................................................................................31 
8.1 
Study Design .............................................................................................................31 
8.2 
Rationale ...................................................................................................................32 
8.3 
Methods Used to Minimize Bias ..............................................................................33 
9. 
STUDY PROCEDURE .......................................................................................................33 
9.1 
Informed Consent .....................................................................................................33 
9.2 
Visits and Examinations ...........................................................................................34 
9.3 
Discontinued Subjects ..............................................................................................46 

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9.4 
Subject Pregnancy ....................................................................................................47 
9.5 
Study Methods and Measurements ...........................................................................47 
9.6 
Health-Related Quality of Life .................................................................................54 
10. STATISTICAL DESIGN ....................................................................................................55 
10.1 
Evaluability ...............................................................................................................55 
10.2 
Efficacy .....................................................................................................................56 
10.3 
Safety ........................................................................................................................61 
11. SAMPLE SIZE JUSTIFICATION ....................................................................................62 
12. ADVERSE EVENTS AND DEVICE DEFICIENCIES ...................................................62 
12.1 
Definitions ................................................................................................................62 
12.2 
Reporting Procedures ...............................................................................................65 
12.3 
Unblinding of Test Article ........................................................................................67 
12.4 
Follow-up of Subjects with Adverse Device Effects ................................................67 
13. INVESTIGATOR OBLIGATIONS ...................................................................................67 
14. SPONSOR AND MONITOR RESPONSIBILITIES .......................................................67 
15. PROTOCOL AMENDMENTS ..........................................................................................68 
16. CONFIDENTIALITY OF THE STUDY ..........................................................................68 
17. STATEMENTS OF COMPLIANCE ................................................................................69 
18. END OF STUDY ..................................................................................................................69 
19. PUBLICATION POLICY ..................................................................................................69 
20. REFERENCES ....................................................................................................................71 
21. APPENDICES ......................................................................................................................72 
21.1 
Instructions For Use ..................................................................................................72 
21.2 
Cardiff Wound Impact Schedule ..............................................................................75 
21.3 
Principal Investigator Obligations ............................................................................79 
3.2 
 TABLE OF TABLES 
Table 6.1.1-1: ALLEVYN Life Non-Bordered Dressings for Evaluation .................................... 23 
Table 9.2-1: Study Plan ................................................................................................................. 35 
Table 12.1-1: Categories of Adverse Event .................................................................................. 63 
Table 12.2-1: Contact Information for Reporting of Unanticipated Serious Adverse Device 
Effects ........................................................................................................................................... 67 
3.3 
TABLE OF FIGURES  
Figure 6.1.1-1: ALLEVYN Life Non-Bordered Dressing structure ............................................. 22 
Figure 6.1.1-2: Wound contact layer, showing regular perforation .............................................. 22 
Figure 6.1.1-3: ALLEVYN LIFE Non-Bordered Dressings ........................................................ 23 
Figure 6.2.2-1: ALNB ApplCT160ication .................................................................................... 25 
Figure 6.2.3-1: Instructions for changing ALNB.......................................................................... 26 
Figure 8.1-1: Basic overview of study design (live phase) ........................................................... 32 
Figure 12.2-1: Evaluation of an Adverse Event by the Investigator ............................................. 66 

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3.4 
LIST OF ABBREVIATIONS  
Abbreviation 
Definition 
ABI 
Ankle Brachial Index 
ADE 
Adverse Device Effect(s) 
AE 
Adverse Event(s) 
ALNB 
ALLEVYN LIFE Non-Bordered 
ASADE 
Anticipated Serious Adverse Device Effect(s) 
cm 
centimeter 
CWIS 
Cardiff Wound Impact Schedule 
DevD 
Device Deficiency(ies) 
DFU 
Diabetic Foot Ulcer 
eCRF 
Electronic Case Report Form 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GQ 
Global Quality of Life 
HCP 
Health Care Provider 
HRQoL 
Health-Related Quality of Life 
IAD 
Incontinence-Associated Dermatitis 
IRB 
Independent Ethics Committee 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
ITD 
Intertriginous Dermatitis 
LTFU 
Lost To Follow-Up 
LU 
Leg Ulcer 
MARSI 
Medical Adhesive-Related Skin Injury 
MASD 
Moisture-Associated Skin Damage 

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Abbreviation 
Definition 
MedDRA 
Dictionary for Medical Drug Regulatory Activities  
MVP 
Moisture Vapor Permeable 
NPUAP 
National Pressure Ulcer Advisory Panel 
PMS 
Post-Marketing Surveillance 
PP 
Per-Protocol set 
PSDL 
Physical Symptoms of Daily Living 
PU 
Pressure Ulcer 
QoL 
Quality of Life 
RCT 
Randomized Clinical Trial 
SADE 
Serious Adverse Device Effect(s) 
SAE 
Serious Adverse Event(s) 
SAF 
Safety Analysis Set 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System Software, Cary, NC, USA 
SC 
Standard Care 
SL 
Social Life 
S&N 
Smith & Nephew Inc. 
SOP 
Standard Operating Procedure 
SQ 
Satisfaction with Quality of Life 
UADE 
Unanticipated Adverse Device Effect(s) 
USADE 
Unanticipated Serious Adverse Device Effect(s) 
VLU 
Venous Leg Ulcer 
WB 
Well Being 

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4. INTRODUCTION 
4.1 
BACKGROUND  
Chronic wounds, including leg ulcers (LU), diabetic foot ulcers (DFU), and pressure ulcers (PU), 
significantly impact patients’ quality of life. These chronic wounds fail to heal and remain stuck 
in an inflammatory phase. In developed countries, the incidence of chronic wounds has increased 
in recent years1, possibly due to an aging population with an abundance of concurrent illnesses 
such as diabetes, hypertension, obesity, and peripheral vascular disease. 
In the United Kingdom, it is estimated that 15 to 18 out of 1000 people suffer from VLU; the 
cost to treat these and other chronic wounds was between £2-3 billion in 20062. More recent 
estimates put the annual cost of treating chronic wounds in the US at $6-15 billion3, however, a 
2010 report4 puts the cost of treating DFU alone at $39 billion.  
Closure of complex wounds, including chronic wounds, post-surgical wounds, and trauma 
wounds is often achieved through secondary intention. Although these wound types have 
different etiologies and underlying pathophysiology, their treatment follows a similar course. 
Wound closure by secondary intention can be supported by a wide range of wound dressings 
designed specifically for this purpose. An ideal dressing must provide the following at a 
minimum: 
• 
a barrier to exogenous contamination and infection  
• 
adequate management of wound exudate 
• 
maintenance of a moist wound healing environment 
Failure of a dressing to deliver these fundamental features will negatively impact the ability of a 
complex wound to heal and may allow the wound to deteriorate. Failure to prevent 
contamination may allow a wound to become infected. Inability to manage moderate to high 
exudate volume may lead to maceration of the peri-wound skin, which can lead to further wound 
breakdown if untreated. At the same time, a dressing should not allow a wound to dry out; the 
dressing should maintain a moist wound healing environment. The consequences of wound 

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deterioration vary, but can result in protracted wound healing or may cause an otherwise 
preventable hospital episode for surgical management or closure.  
This study will focus on the use of ALLEVYN LIFE™ Non-Bordered (ALNB) in the treatment 
of chronic wounds. ALNB is a new multilayer foam dressing that is intended to provide an 
optimal moist wound healing environment to promote the healing of moderate and highly 
exuding wounds.  
ALNB is the latest addition to the ALLEVYN LIFE range of dressings, which were first 
launched in 2012. The introduction of ALNB recognizes the fact that clinicians sometimes prefer 
using a non-bordered absorbent product with wounds that require a secondary dressing, e.g. 
compression bandaging for leg ulcers.  
While the present study will be the first clinical trial to evaluate the actual use of ALNB in 
clinical practice, the original ALLEVYN LIFE dressing has been used in several clinical studies. 
The results of these suggest that ALLEVYN LIFE supports good wound progression, wound 
granulation, healthy condition of the surrounding skin, and patient satisfaction5. 
Because medical devices are designed to improve the patient’s quality of life6, the primary 
outcome in the study will be the differences in Health-Related Quality of Life (HRQoL) between 
subjects treated with ALNB and Standard Care (SC) for subjects with moderate to highly 
exuding chronic wounds. The subjects will be surveyed using the Cardiff Wound Impact 
Schedule (CWIS)7 which measures the impact of chronic wounds on physical symptoms, daily 
living, social life, and well-being.  
A summary of known and potential risks and benefits to humans of the test article can be found 
in the Package Insert (ALLEVYN LIFE Non-Bordered).  
4.2 
SAFETY CONSIDERATIONS 
Precautions for the use of ALNB, as specified in the current Instructions for Use (IFU), are: 
 Do not use with oxidizing agents such as hypochlorite solutions (e.g. EUSOL) or 
hydrogen peroxide, as these can reduce the absorbency of the dressing. 

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 If reddening or sensitization occurs discontinue use. 
 Single-use only; if used on more than one subject, cross contamination or infection may 
occur. 
 Once the pouch is opened, do not retain unused dressings for application at a later date. 
Risks associated with the use of ALNB within the present study will be mitigated as follows: 
 Study personnel will be trained in the correct use of ALNB prior to applying the dressing 
to the wounds of study subjects. 
 Study personnel will be trained on the study protocol. 
 Study personnel will be directed to carefully follow the inclusion and exclusion criteria 
for participation in the study when assessing the subject eligibility. 
 Study personnel will be directed to read and follow the IFU. 
4.2.1 Benefits 
ALNB is a multilayer dressing with a silicone gel adhesive that provides an optimal moist wound 
healing environment to promote the healing of moderate and highly exuding wounds. 
The absorbent pad is composed of a foam layer and a lock-away core made from superabsorbent 
material. The silicone adhesive layer is gentle, even to fragile skin, and makes it easy to apply, 
reposition, and remove. A breathable opaque outer film helps mask exudate, prevent bacterial 
contamination, and is showerproof when used with appropriate secondary retention. 
4.2.2 Hazards/Harms 
This will be the first study to evaluate the use of ALNB in clinical practice; there is currently no 
direct clinical evidence concerning the safety of ALNB.  
ALLEVYN LIFE has been used widely over the last four years and has been shown to be 
equivalent to ALNB with regard to materials and fluid handling properties (see Section 6). 
Published clinical studies with ALLEVYN LIFE, risk management reports, and post-marketing 

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surveillance (PMS) data consistently indicate that the risk of adverse events is low and that 
reactions which do occur are generally local to the application site and are mild in severity. 
Adverse events are well characterized and are manageable in the majority of cases. As such, 
ALLEVYN LIFE demonstrates an acceptable benefit-risk profile.  
Because of the similarities between ALLEVYN LIFE and ALNB, the anticipated medical 
benefits of ALNB are also expected to outweigh risks. There are some differences between the 
two products, including:  
 ALNB can be cut to size without compromising its performance characteristics 
 ALNB does not incorporate a change indicator, as this would be obscured by any 
secondary dressing 
 ALNB includes a lower tack adhesive, to serve as a ‘third hand’, and enable the dressing 
to be removed and repositioned more easily 
 ALNB requires the use of a secondary dressing to aid retention 
The use of a lower tack adhesive with ALNB may positively impact safety by lowering the 
incidence and severity of skin stripping resulting from its use. Unlike ALLEVYN LIFE, ALNB 
requires a secondary dressing to aid retention. Choice of ancillary dressing, together with 
associated risks relating to this secondary device, will be carefully monitored during this study.  
There are no anticipated Serious Adverse Device Effects (SADE) associated with the use of 
ALNB.  
5. OBJECTIVES 
The aim of this pilot randomized controlled trial (RCT) is to gather preliminary clinical, health 
economic and safety data on the use of ALNB in the treatment of chronic wounds, for post-
market surveillance and to assist with planning future research concerned with the efficacy and 
cost-effectiveness of ALNB. 

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5.1 
PRIMARY 
The primary objective is to estimate the effect of treatment with ALNB on HRQoL in subjects 
with chronic ulcers, measured using the CWIS-PSDL (Physical Symptoms of Daily Living) 
scale, compared to subjects receiving SC alone, over a six-week treatment period. 
5.2 
KEY SECONDARY 
To estimate the effects of treatment with ALNB, when compared with SC alone, on HRQoL 
measured by the CWIS-PSDL scale at three and twelve weeks, and CWIS well-being (WB), 
social life (SL); global quality of life (GQ); and satisfaction with quality of life scales (SQ); at 
three, six, and twelve weeks. 
5.3 
SECONDARY  
Secondary objectives of this study are: 
o Ulcer progression (including undermining, necrotic tissue type and amount, 
exudate type and amount, skin color surrounding the wound, granulation tissue, 
epithelialization, condition of peri-wound, ulcer dimensions and healing status) at 
three, six, and twelve weeks 
o Healthcare resource use related to the reference ulcer (including number and cost 
of dressings used, consultations and time used by healthcare professionals (HCP), 
time in hospital, number and cost of additional treatments, procedures, and 
investigations) over twelve weeks 
5.4 
EXPLORATORY 
The exploratory objective of this study is to compare differences between ALNB and SC in 
dressing performance (including wear time, leakage, odor control, and absorption under 
compression) and usability (including comfort and ease of application/removal together with 
associated pain) at three, six, and twelve weeks 

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5.5 
SAFETY 
Safety data will be gathered throughout the twelve weeks of the study including: 
 Adverse events 
 Device deficiencies 
5.6 
CLAIMS 
The study is a pilot RCT, which will enroll a small sample of subjects with a range of chronic, 
moderate to highly exuding ulcer types: LU (arterial/mixed etiology leg ulcers or venous leg 
ulcers requiring compression therapy), PU, and non-ischemic DFU. Data generated from this 
study are unlikely to be sufficient to demonstrate any statistically significant difference in 
observed clinical outcomes between devices. Nevertheless, this study will generate the first 
comparative clinical, economic, and safety data for use of ALNB in subjects, and will extend 
current evidence for the ALLEVYN LIFE product range. 
This pilot RCT may provide preliminary data as supporting evidence for the existing product 
claims.  
6. STUDY PRODUCT 
6.1 
IDENTIFICATION  
6.1.1 Test Product: ALLEVYN LIFE Non-Bordered 
Intended use 
ALNB is intended for use in wound management by secondary intention on shallow, granulating 
wounds, chronic and acute exudative wounds, full- and partial-thickness wounds including: 
 Pressure ulcers 
 Leg ulcers 
 Diabetic foot ulcers 
 Surgical wounds 
 First- and second-degree burns 

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 Skin graft donor sites 
 Skin tears 
 Fungating wounds 
The present study aims to evaluate the use of ALNB for adult (≥ 18 years of age) subjects with 
moderate to highly exuding chronic ulcers that, in the opinion of the Investigator, would benefit 
from a protective dressing but do not require a topical antimicrobial treatment, limited to: 
 Pressure ulcers, excluding Stage 1. Inclusion of other stages, including “unstageable”, 
depends on the level of exudate and lack of infection. 
 Non-ischemic diabetic foot ulcers (Wagner Grade 1 or 2) 
 Leg ulcers  
Dressing description 
ALNB is a quadrilobed or rectangular shaped exudate management wound dressing which is a 
new variant of ALLEVYN LIFE. ALNB is a non-bordered dressing, allowing it to be cut to the 
shape of the wound before use. ALNB uses a low-tack silicone adhesive. ALNB incorporates an 
opaque, moisture-vapor permeable (MVP) top film that allows for some masking of the exudate 
penetration.  
Construction of ALNB 
ALNB is a composite dressing; it is made up of 4 layers (see Figure 6.1.1-1), including the MVP 
top film, a superabsorbent layer, a foam layer, and a wound contact layer (see Figure 6.1.1-2). 
The wound contact layer is perforated to allow the transfer of exudate from the wound into the 
dressing.  

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Figure 6.1.1-1: ALLEVYN Life Non-Bordered Dressing Structure 
 
Figure 6.1.1-2: Wound Contact Layer, Showing Regular Perforation 
 
The device is fitted with handles to protect the silicone wound contact layer prior to application 
and to facilitate application of the dressing to the wound. The handles are removed during the 
application process. 
Manufacturer and available sizes  
ALNB is manufactured by Smith & Nephew Medical Limited, 101 Hessle Road, Hull, HU3 
2BN, England.  
ALNB is available in three sizes (see Table 6.1.1-1). Shapes and relative sizes are shown in 
Figure 6.1.1-3. 
Wound contact layer 
Foam layer 
Superabsorbent layer 
Top film 
Wound contact layer 
Top film 

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Table 6.1.1-1: ALLEVYN Life Non-Bordered Dressings for Evaluation 
Product Code 
Dressing Size and Packaging 
66801748 
10.5 x 10.5 cm Dressing; Carton of 10 
66801749 
16 x 16 cm Dressing; Carton of 10 
66801751 
10 x 20 cm Dressing; Carton of 10 
 
Figure 6.1.1-3: ALLEVYN LIFE Non-Bordered Dressings (Not Actual Size) 
 
Number of investigational devices used on each subject 
ALNB is designed to be worn for up to seven days. Subjects randomized to ALNB will have 
their dressings changed according to individual clinical need (see Section 6.2). The total duration 
of treatment with ALNB will also depend on factors such as wound healing, topical wound 
treatments, or suitability of continued treatment with ALNB. If the wound does not heal, the 
maximum study treatment period will be twelve weeks. Thus, the number of ALNB dressings 
used by each subject will differ. 

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6.1.2 Comparator Products 
Subjects allocated to the comparator arm of the study shall receive SC, defined as any protective 
wound dressing(s) which, in the opinion of the Investigator, would be beneficial in treating the 
wound, other than: 
 variants of ALLEVYN 
 topical antimicrobials, such as Acticoat™, Iododsorb™, silver products, etc. 
 negative pressure wound therapy 
Standard care should correspond as closely as possible to normal clinical practice, and dressings 
used routinely within each individual research site. 
6.1.3 Ancillary Product 
At Smith & Nephew’s discretion, the following ancillary products may be made available to 
research sites for use on study subjects during this study – OPSITE™, PROFORE™, 
DURAFIBER™, and INTRASITE™. However, this study does not require any particular 
ancillary dressing to be used to secure ALNB. Rather, selection of ancillary dressings should be 
determined based on clinical requirements.  
Per the IFU, physicians may use INTRASITE under ALNB, as clinically warranted.  
6.2 
PRODUCT USE 
6.2.1 HCP Training 
Study center personnel with responsibilities for the medical care of subjects and/or application of 
the investigational product (ALNB) will be trained on the use and application of ALNB prior to 
enrolling subjects into the study. HCP training will only occur following completion of the 
clinical trial agreement. HCP training will involve a presentation on the correct application and 
use of ALNB, including frequency of dressing change. ALNB is a moderate to highly absorbent 
dressing which can be worn for up to seven days and should be changed as directed in the 
product IFU (see Sections 6.2.3 and 21.1), rather than due to routine schedule or convenience.  

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6.2.2 Application 
Application of the product will follow the directions from the product IFU (Figure 6.2.2-1). 
Figure 6.2.2-1: ALNB Application 
 
Study subjects will not be trained or expected to apply or change their own dressings. All 
dressing changes should occur at the Investigator site.  
6.2.3 Dressing Change  
HCP will be instructed to follow directions given in the product IFU (Figure 6.2.3-1) when 
changing ALNB. 

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Figure 6.2.3-1: Instructions for changing ALNB 
 
6.2.4 Storage of ALNB 
ALNB should be stored in a dry place, at less than 77°F (25°C), and away from sunlight.  
6.2.5 Concomitant Dressings 
With the exception of dressing/bandaging placed over ALNB for secondary retention or 
compression, the only other dressings that are permitted to come into contact with the wound bed 
and for use in conjunction with ALNB within the study are: 
 Intrasite Gel for necrotic and sloughy wounds  
 Durafiber for deeper wounds (Durafiber Ag should not be used due to its antimicrobial 
action). 
6.3 
PACKAGING AND LABELING 
Packaging and labeling will be prepared to meet regulatory requirements. 

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6.3.1 Test Product 
Smith & Nephew will supply each site with ALLEVYN LIFE Non-Bordered for use during the 
study. All test articles will be supplied in standard commercial packaging, clearly showing the 
batch number and expiry date. A label with the following information will be affixed to the 
ALNB packaging without obscuring any regulatory text:  
• 
Smith & Nephew, Inc. Fort Worth, Texas 
• 
Study Number 
• 
Store at room temperature 
• 
For Investigational Use Only 
6.3.2 Comparator Article 
SC, as defined in Section 6.1.2., will serve as the control treatment. Dressings used as SC will be 
those used routinely by the participating research site. Participating sites will acquire these 
routine dressings for use during the study.  
Due to the variability in the product that will be used in the comparator group, S&N will not 
supply or label these dressings.  
6.3.3 Ancillary Products  
Any ancillary products supplied by Smith & Nephew will not be labeled.  
6.4 
PRODUCT ACCOUNTABILITY PROCEDURES 
The Sponsor will keep a detailed record of all ALNB dressings supplied to each site. 
Confirmation of receipt by the Investigator will also be retained. 
The receipt and dispensing of each dressing will be recorded on appropriate accountability forms 
available for verification by the Sponsor or its designated representative at each monitoring visit. 
Overall accountability for the accuracy of these records is the responsibility of the Investigator or 
designated individual maintaining the inventory, which shall include details of receipt, use, 

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waste, returns, and collection, etc., of product supplies. Used dressings will be appropriately 
destroyed per local requirements for clinical waste by the site staff without verification by the 
study monitor. 
All cartons will be clearly identified per the labeling in Section 6.3. The Study Monitor will 
ensure that the procedures and records are in place for appropriate reconciliation of all test 
articles. As part of monitoring, the Study Monitor will check that the site personnel are following 
the procedures and completing all of the necessary documentation. 
In addition, any ancillary products (PROFORE, INTRASITE, etc.) supplied to the site by the 
Sponsor will require appropriate accountability.  
7. SUBJECTS 
7.1 
SUBJECT POPULATION 
Approximately 40 adult subjects (18 years of age or older) with a moderate to highly exuding 
chronic ulcer that requires a dressing, but which does not, in the opinion of the Investigator, 
require topical antimicrobial treatment, will be recruited.  
Chronic wounds will include LU (arterial/mixed etiology leg ulcers or venous leg ulcers 
requiring compression therapy), PU, and non-ischemic DFU. For subjects with multiple ulcers, 
the largest ulcer meeting the inclusion/exclusion criteria will be studied as the reference ulcer. 
The following minimum numbers of wound types will be enrolled in each study group:  
 ALNB: 5 DFU, 5 PU, 5 LU  
 SC: 3 DFU, 3 PU, 3 LU. 
7.2 
INCLUSION CRITERIA 
1. The subject must provide informed consent to participate in the study; see Section 9.1. 
2. The subject must be eighteen (18) years of age or older. 
3. The subject must be willing and able to make all required study visits. 

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4. The subject must be able to follow instructions and be deemed capable of completing the 
CWIS questionnaire. 
5. The subject must present with a chronic (≥ 4 weeks duration) ulcer which meets all of the 
following criteria: 
(a) The ulcer is classified as either: 
 a pressure ulcer 
 a non-ischemic diabetic foot ulcer 
 a leg ulcer (arterial/mixed etiology leg ulcers or venous leg ulcers requiring 
compression therapy) 
(b) The ulcer is, in the opinion of the Investigator, moderate to highly exuding. 
(c) The ulcer would, in the opinion of the Investigator, benefit from a protective dressing.  
(d) The ulcer is not infected based on clinical signs/symptoms. 
6.  A subject with a DFU must have an ankle-brachial index (ABI) of 0.7 or greater, as 
measured within 30 days of the Screening Visit. 
Subjects with a VLU that will use compression therapy should have an ABI that meets the 
requirements of the IFU for the selected compression device.  
7.3 
EXCLUSION CRITERIA 
1. Contraindications or hypersensitivity to the use of the ALLEVYN LIFE Non-Bordered, 
comparator, ancillary products, or their components.  
2. Participation in the treatment period of another clinical trial within 30 days of Visit 1 or 
planned participation overlapping with this study. 
3. The subject’s reference ulcer is being treated with a topical antimicrobial dressing. 

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4. Subjects with skin features (e.g. tattoos, skin color, pre-existing scarring) which, in the 
opinion of the Investigator, could interfere with the study assessments. 
5. Subjects who have participated previously in this clinical trial. 
6. Subjects with a history of poor compliance with medical treatment. 
7. Subjects with a medical or physical condition that, in the opinion of the Investigator, would 
preclude safe subject participation in the study. 
7.4 
SCREENING LOG 
Participating study sites are required to document all screened subjects initially considered for 
inclusion in this study (i.e. a subject who gives informed consent). If a subject is excluded from 
the study, the reasons for exclusion will be documented in the subject's source documents and 
noted on the Screening Log.  
7.5 
ENROLLMENT 
The point of enrollment in the study is when the subject has signed and dated the informed 
consent document and met all the eligibility criteria. 
The anticipated enrollment period is approximately nine (9) months. 
7.6 
WITHDRAWAL 
Subjects may be withdrawn early from study treatment for the following reasons: 
 Closure of the reference ulcer. 
 If the subject misses two (2) consecutive dressing changes/study visits, interrupting 
treatment for longer than seven (7) days. 
 At the discretion of the Investigator due to: 
o A change in treatment that is clinically warranted 
o An adverse event (AE) 

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o Any other significant reason identified by the Investigator 
Subjects may be withdrawn entirely from the study for the following reasons: 
 At their own request (i.e. withdrawal of consent). 
 Failure to complete the CWIS appropriately at Visit 1. 
 At the discretion of the Investigator due to: 
o Concurrent illness 
o Adverse device effects (ADE) 
o Non-compliance (e.g. did not follow instructions). 
o Lost to follow-up (LTFU) 
o Any other significant reason identified by the Investigator 
Where subjects withdraw consent, the Investigator should make a reasonable effort to ascertain 
the reason(s), while fully respecting the subject’s privacy. 
Subjects withdrawn from the study because the CWIS is not complete will be replaced by 
enrolling a new study subject.  
 
8. STUDY DESIGN 
8.1 
STUDY DESIGN 
This is a randomized, parallel group study. Subjects will be randomly assigned in a 5:3 ratio of 
ALNB:SC. Subjects will be stratified by ulcer type (PU, DFU, LU).  
Participation in the study will last up to 12 weeks. Subjects will be required to make at least one 
visit per week to the research site. The primary clinical endpoint will be six (6) weeks from 
enrollment, with clinical data also collected at three (3) and twelve (12) week follow-up visits. 
Health care resource use data will be gathered and compared over the entire twelve week study 
period. 

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Figure 8.1-1: Overview of Study Design  
 
8.2 
RATIONALE  
This post-market clinical study is required for regulatory purposes and will be the first clinical 
evaluation of ALNB following its launch. This pilot study will gather preliminary data regarding 
the use of this new dressing in subjects with chronic, moderate to highly exuding ulcers in an 
outpatient clinical care setting. Both subject population and setting were selected due to market 
considerations. When compared to SC, this study will provide important evidence to support 
product claims, reinforce continuing regulatory approval, and provide both an estimate of effect 
size and test of study feasibility to guide the development of potential future full-scale RCT 
testing the efficacy and cost-effectiveness of ALNB. 
The impact of treatment on HRQoL is a common outcome across a wide range of health 
interventions and medical conditions, including advanced wound care. The CWIS was chosen for 
use in this study due to its focus on the quality of life in subjects with chronic wounds, and 
supporting evidence for reliability and validity. Within this self-reported questionnaire, the 

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CWIS-PSDL scale was selected as the primary outcome measure due to relevance to key product 
claims for ALNB, including those concerning fluid handling/leakage, pain, comfort, and odor 
control.  
In addition to evaluating the impact on quality of life, this study will also seek to estimate the 
effects of ALNB on ulcer progression, healthcare resource use, gather safety data, and explore 
dressing performance. 
8.3 
METHODS USED TO MINIMIZE BIAS  
Blinding of subjects and HCP to treatment allocation is not possible due to obvious physical 
differences in the appearance of dressings and sterile packaging. Bias reduction will consist of 
subjects randomly allocated to the two groups, ALNB and SC, to control for the influence of 
extraneous variables on treatment outcomes. In this way, no Investigator will be able to direct a 
particular subject to a particular treatment. Baseline procedures and assessments are performed 
prior to assigning the subject to a treatment group. SC was selected as the comparator treatment, 
rather than a specific competitor dressing, together with the recruitment of subjects from multiple 
treatment facilities to widen the generalizability of results to normal clinical practice. 
Unequal allocation of subjects in favor of ALNB will ensure that twenty-five (25) subjects 
receive treatment with ALNB, which is viewed as a reasonable minimum requirement in 
providing basic safety data for the primary dressing of interest. Additionally, treatment allocation 
will be stratified by ulcer type to safeguard against major imbalances in clinical characteristics at 
baseline and aid comparability between groups. 
9. STUDY PROCEDURE 
9.1 
INFORMED CONSENT 
Before conducting any study procedures or examinations, the purpose and nature of the study 
will be explained to the subject in their native language. The subject will then read, sign, and 
date the Institutional Review Board (IRB)-approved informed consent document (see below for 
difficulties with reading and writing). Additionally, the individual who obtains consent from the 

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subject will sign and date the informed consent document. A photocopy of the signed informed 
consent document will be provided to the subject and a copy will be placed in the subject’s 
medical record, with the original filed in the Investigator site file (ISF). Any additional 
requirements required by the IRB will be followed.  
Subjects lacking mental capacity 
The minimum age for participation in the study is eighteen (18) years. Adults who lack the 
mental capacity to understand study information and provide informed consent without 
assistance from a legally appointed representative will not be permitted to take part in the study. 
This criterion is necessary due to demands of study participation, including completion of self-
reported outcome measures. 
Difficulties with reading or writing 
If the subject is unable to read or write, the informed consent document and associated study 
information will be read aloud to the subject in the presence of an independent witness. If 
possible, the subject shall sign and personally date the informed consent form. Where this is not 
possible the subject will provide verbal consent to participate in the study. The witness will then 
personally sign and date the informed consent form, attesting that the information was accurately 
explained and that the informed consent was freely given. 
9.2 
VISITS AND EXAMINATIONS 
9.2.1 Summary 
For a summary of the required procedures by visit, see Table 9.2-1. 

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Table 9.2-1: Study Plan  
Procedure 
Key Visits 
 
Other Visits 
Visit 1 
(Baseline) 
Visit 2  
(Day 21±3) 
and 
Visit 3 
(Day 42±4) 
End of 
Study 
Visit 
(Day 84±4) 
Routine 
Dressing 
Changes 
Treatment 
D/C  
(before end 
of study) 
Informed Consent 
√ 
 
 
 
 
Demographics/Medical 
History 
√ 
 
 
 
 
Concomitant Medication 
√ 
√ 
√ 
√ 
√ 
CWIS  
√ 
√ 
√ 
 
√ 
Ulcer Assessment 
√ 
√ 
√ 
√ 
√ 
ABI 
√1 
 
 
 
 
Verify Inclusion/Exclusion 
√ 
 
 
 
 
Allocate Study ID Number 
√ 
 
 
 
 
Randomize 
√ 
 
 
 
 
Photograph Ulcer 
√ 
√ 
√ 
√2 
√ 
Photograph Dressing 
√3 
√ 
√ 
√3 
√3 
Dressing Change 
 
√ 
 
√ 
 
Complete Questions about 
Dressing (Subject and 
Investigator) 
√ 
√ 
√ 
√ 
√ 
Pain scale 
 
√ 
√ 
√ 
 
Record Adverse Events 
(AE) 
√ 
√ 
√ 
√ 
√ 
Record Device Deficiencies 
(DevD) 
√ 
√ 
√ 
√ 
√ 
Complete Exit Form 
 
 
√ 
 
 
1 If not obtained within last 30 days for DFU/LU subjects 
2 Only if AE related to ulcer is observed 
3 Only if DevD observed

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9.2.2 Visit 1 – Initial Visit (Baseline, Day 1) 
1. 
Obtain written informed consent from the subject as detailed in section 9.1. 
2. 
Obtain demographic information, relevant medical history, and relevant concomitant 
medications.  
3. 
Screen the subject against protocol inclusion and exclusion criteria.  
4. 
Provide the subject with a copy of the CWIS, and allow sufficient time to complete it. 
Staff should not assist the subject with the questionnaire, other than to instruct the 
subject to complete all questions. Ensure that the subject has completed the CWIS 
questionnaire appropriately, providing a single valid response for each item of the 
questionnaire.  
NOTE: subjects who cannot read/write may have the CWIS read aloud to them and the 
subject’s responses recorded. Ensure this process is noted in the source documents.  
5. 
Complete an ulcer assessment (see Section 9.5.1) including ulcer classification, i.e. 
pressure ulcer staging or Wagner classification for DFU (see Section 9.5.5). 
6. 
If the reference ulcer is a DFU or LU, determine ABI. Values obtained within the last 
30 days may be used to qualify the subject.  
Note for DFU subjects: Subjects with a DFU and an ABI value less than 0.7 may not 
be enrolled.  
VLU subjects that will use compression during the study should have an ABI that 
meets the requirements stated in the IFU for the selected compression device.  
7. 
Assign the subject a study number and allocate the subject to either the ALNB 
(experimental) or SC (comparator group) according to the randomization schedule 
provided by SealedEnvelope.  

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8. 
Photograph the ulcer. Ensure that the calibration ruler with subject’s initials and visit 
date is visible in the image. If the ulcer is debrided, take a photograph of the ulcer 
immediately prior to and following debridement. Record any debridement and the 
method of debridement in the electronic Case Report Form (eCRF). 
9. 
Apply dressing according to randomization: 
 For subjects allocated to the ALNB group, apply ALNB as instructed in 
Section 6.2.2.  
 For subjects allocated to SC, apply a suitable dressing per dressing IFU. 
10. 
Record details of all dressings used for all subjects, (e.g. brand, size, etc.) as well as 
any treatment applied underneath the dressing, such as Durafiber or Intrasite gel. 
11. 
Assess the ease of applying the dressing (Section 9.5.7), including remains in place 
and repositioning (if applicable).  
12. 
Instruct the subject to carefully follow the ulcer care instructions until the next 
dressing change and provide information concerning arrangements for future study 
visits. 
13. 
Record the total time that the subject spent at the visit (start to finish of ulcer care 
procedures).  
14. 
If any AE or DevD are observed or reported after application of study product, they 
must be reported as instructed in Section 12 (Adverse Events and Device 
Deficiencies). In addition to photographing the ulcer (as above), photograph the 
dressing if reporting a device deficiency. 
9.2.3 Routine Dressing Changes 
As ALNB has a maximum recommended wear time of 7 days, routine dressing changes will 
occur between scheduled Study visits 2, 3, and the End of Study Visit. The number of these visits 
will vary from subject to subject, based on clinical judgment. These visits will involve subjects 

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returning to an on-site visit. Dressings should not be given to study subjects; the dressing should 
only be changed by an HCP at a visit.  
1. 
Question subjects regarding any changes in health or concomitant treatment. 
2. 
Ask the subject to assess the comfort of wearing the dressing since the last visit (see 
Section 9.5.8). 
3. 
Assess the movement of the dressing (see Section 9.5.9). 
4. 
Remove the old dressing and inspect the ulcer. Complete an ulcer assessment (see 
Section 9.5.1). 
5.  
Assess the level of pain experienced by the subject when the dressing is removed (see 
Section 9.5.6). 
6.  
Assess the ease of dressing removal, leakage, and absorption under compression (see 
section 9.5.10).  
7. 
If any adverse events or device deficiencies are observed or reported, they must be 
recorded as instructed in Section 12 (Adverse Events and Device Deficiencies).  
NOTE: Photograph the ulcer only if reporting an AE or DevD. 
8.  
Redress the ulcer, if clinically indicated per the subject’s randomization assignment:  
• 
For subjects allocated to the experimental group, apply ALNB as supplied for use 
in the study, cutting the dressing to size if required and securing with a suitable 
secondary dressing.  
• 
For subjects allocated to SC apply a suitable protective dressing, other than 
ALLEVYN LIFE/ALNB.  
9. 
Record details of all dressings used for all subjects, (e.g. brand, size, etc.) as well as 
any treatment applied underneath the dressing, such as Durafiber or Intrasite gel.  
For subjects randomized to ALNB, record whether or not the dressing was cut to a 
smaller size.  

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10. 
Assess the ease of applying the dressing (see Section 9.5.7), including remains in place 
and repositioning (if applicable). 
11. 
Instruct the subject to carefully follow the ulcer care instructions until the next 
dressing change and provide information concerning arrangements for future study 
visits. 
12. 
Record the total time that the subject spent at the visit (start to finish of ulcer care 
procedures). 
13. 
If any AE or DevD are observed or reported after application of study product, they 
must be reported as instructed in Section 12 (Adverse Events and Device 
Deficiencies). 
9.2.4 Visit 2 (Day 21 ± 3 days) and Visit 3 (Day 42 ± 4 days) 
Visits 2 and 3 will consist of an on-site visit. These visits should coincide with the normal timing 
of dressing changes, i.e. seven (7) days or fewer for ALNB.  
Subjects who have already had their treatment discontinued/been withdrawn from treatment and 
no longer require a dressing change shall be followed up either by an on-site visit or by 
telephone. In such cases, the main purpose will be to collect CWIS outcome data and any data 
related to AE (if applicable).  
1. 
Question subjects regarding any changes in health or concomitant treatment.  
2. 
All subjects must complete the CWIS, including those withdrawn from treatment 
unless they have been withdrawn from the study.  
Give the subject a printed copy of the CWIS and allow sufficient time to complete it. 
Assist with completion if asked. For any subject followed up by telephone, read the 
complete CWIS and record the subject’s responses accurately. Ensure that the subject 
has completed the CWIS appropriately. A single valid response should be recorded for 
each item.  

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NOTE: subjects who cannot read/write may have the CWIS read aloud to them and the 
subject’s responses recorded. Ensure this process is noted in the source documents.  
3.  
Ask the subject to assess the comfort of wearing the dressing since the last visit (see 
Section 9.5.8). 
4.  
Assess the movement of the dressing (see Section 9.5.9). 
5. 
Remove the old dressing and inspect the ulcer. Complete an ulcer assessment (see 
Section 9.5.1). 
Notes: 1) A full ulcer assessment is not necessary if the subject has already been 
discharged or withdrawn from treatment. 
     2) Not applicable if this visit is completed via a phone call.  
6. 
Assess the level of pain experienced by the subject when the dressing is removed (see 
Section 9.5.6). 
7. 
Assess the ease of dressing removal, leakage, and absorption under compression (see 
section 9.5.10)  
8. 
Take a photograph of the ulcer, showing the ruler as supplied. Record any debridement 
and the method of debridement, and take a photograph of the ulcer immediately prior 
to and following debridement.  
Photograph the used dressing on both sides, together with any secondary dressing. 
Note: Photographs are not necessary if the subject was discharged or withdrawn from 
treatment at a previous visit. 

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9. 
Redress the ulcer, if clinically indicated, using an appropriate dressing according to 
group allocation: 
For subjects allocated to the experimental group, apply ALNB as supplied for use in 
the study, cutting the dressing to size if required and securing with a suitable 
secondary dressing.  
For subjects allocated to SC apply a suitable protective dressing, other than 
ALLEVYN LIFE/ALNB.  
10. 
Record details of all dressings used for all subjects, (e.g. brand, size, etc.) as well as 
any treatment applied underneath the dressing, such as Durafiber or Intrasite gel.  
For subjects randomized to ALNB, record whether or not the dressing was cut to a 
smaller size. 
11. 
Assess the ease of applying the dressing (see Section 9.5.7), including remains in place 
and repositioning (if applicable). 
12. 
Instruct the subject to carefully follow the ulcer care instructions until the next 
dressing change and provide information concerning arrangements for future study 
visits. 
13. 
Record the total time that the subject spent at the visit (start to finish of ulcer care 
procedures). 
14.  
If any AE or DevD are observed or reported, they must be recorded as instructed in 
Section 12 (Adverse Events and Device Deficiencies).  
 
9.2.5 End of Study Visit – Week 12 (84 ± 4 days) 
The End of Study Visit will consist of an on-site visit. This should coincide with the normal 
timing of dressing changes, i.e. seven (7) days or fewer for ALNB. 

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Subjects who have already had their treatment discontinued/been withdrawn from treatment shall 
be followed-up either by an on-site visit or by telephone. Obtain information about adverse 
events and responses to the CWIS.  
1. 
Question subjects regarding any changes in health or concomitant treatment.  
2. 
All subjects must complete the CWIS, including those withdrawn from treatment 
unless they have been withdrawn from the study.  
Give the subject a printed copy of the CWIS and allow sufficient time for them to 
complete it. Assist with completion if asked. For any subject followed up by telephone 
(see above), read the complete CWIS and record the subject’s responses accurately. 
Ensure that the subject has completed the CWIS appropriately. A single valid response 
should be recorded for each item of the CWIS.  
NOTE: Subjects who cannot read/write may have the CWIS read aloud to them and 
the subject’s responses recorded. Ensure this process is noted in the source documents. 
3. 
Ask the subject to assess the comfort of wearing the dressing since the last visit (see 
Section 9.5.7). 
4. 
Assess the movement of the dressing (see Section 9.5.9). 
5. 
Remove the old dressing and inspect the ulcer. Complete an ulcer assessment (see 
Section 9.5.1).  
Note: A full ulcer assessment is not necessary if the subject has already been 
discharged or withdrawn from treatment. 
6. 
Assess the level of pain experienced by the subject when the dressing is removed. (see 
Section 9.5.6). 
7. 
Assess the ease of dressing removal, leakage, and absorption under compression (see 
section 9.5.10)  

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8. 
Take a photograph of the ulcer, showing the ruler as supplied. Record any debridement 
and the method of debridement, and take a photograph of the ulcer immediately prior 
to and following debridement.  
Photograph the used dressing on both sides, together with any secondary dressing. 
Note: Photographs are desirable, but not necessary if the subject has been discharged 
or withdrawn from treatment. 
9. 
Exit the subject from the study.  
The subject will be returned to SC and the Investigator will advise him/her of 
subsequent therapy and/or procedures necessary for their medical condition. 
10. 
Record the total time that the subject spent at the visit (start to finish of ulcer care 
procedures). 
11. 
If any AE or DevD are observed or reported, they must be recorded as instructed in 
Section 12 (Adverse Events and Device Deficiencies).  
9.2.6 Treatment Discontinuation 
A subject may be withdrawn from treatment early and discharged from care (see Sections 7.6 
and 9.3) prior to follow-up at Visit 2, Visit 3, or the End of Study Visit. However, these subjects 
will still be retained as active study participants, even though their study treatment has ended. 
When this occurs, the subject will continue as an active participant for the remainder of the 
twelve (12) week study period, completing all remaining study visits (either by attending site 
appointments or by telephone if necessary), to gather complete CWIS data. 
1. 
Question subjects regarding any changes in health or concomitant treatment. 
2. 
Give subject given a copy of the CWIS and allow sufficient time for them to complete 
it. Assist with completion if asked. For any subject followed up by telephone (see 
above), read the complete CWIS and record the subject’s responses accurately. Ensure 
that the subject has completed the CWIS appropriately. A single valid response should 

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be recorded for each item of the CWIS.  
NOTE: subjects who cannot read/write may have the CWIS read aloud to them and the 
subject’s responses recorded. Ensure this process is noted in the source documents.  
3. 
Ask the subject to assess the comfort of wearing the dressing since the last visit (see 
Section 9.5.8). 
4.  
Assess the movement of the dressing. (see Section 9.5.9). 
5. 
Remove the old dressing and inspect the ulcer. Complete an ulcer assessment (see 
Section 9.5.1). 
Notes: 1) A full ulcer assessment is not necessary if the subject has already been 
discharged or withdrawn from treatment. 
2) Not applicable if this visit is completed via a phone call.  
6. 
Assess the level of pain experienced by the subject when the dressing is removed. (see 
Section 9.5.6). 
7. 
Assess the ease of dressing removal, leakage, and absorption under compression (see 
section 9.5.10). 
8. 
Take a photograph of the ulcer, showing the ruler as supplied. Record any debridement 
and method of debridement, and take a photograph of the ulcer immediately prior to 
and after debridement.  
Photograph the used dressing on both sides, together with any secondary dressing. 
9. 
If any AE or DevD are observed or reported, they must be recorded as instructed in 
Section 12 (Adverse Events and Device Deficiencies).  
Photograph the dressing only if reporting a device deficiency.  

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10. 
Redress the ulcer, if clinically indicated, using an appropriate dressing.  
Do not apply any dressing supplied by S&N for use within the study, as the study 
treatment is being discontinued. 
11. 
Record details of any new dressings applied and complete all remaining items in the 
eCRF. 
12. 
Instruct the subject on the need to continue as a participant in the study, providing 
important information about their health and quality of life, until the End of Study 
Visit (84 ± 4 days from Visit 1). 
13. 
If ongoing treatment is clinically indicated, continue to provide the subject with SC for 
the remainder of the study. 
14. 
Record the total time that the subject spent at the visit (start to finish of ulcer care 
procedures). 
9.2.7 Unscheduled Visits 
Any visits to the research site due to the reference ulcer will be captured as a Routine Dressing 
Change Visit (Section 9.2.3). Visits to the research site for other reasons may be captured as an 
Unscheduled Visit at the discretion of the Investigator with all information recorded in the source 
documents and on the Unscheduled Visit eCRF.  
9.2.8 Concomitant Treatment 
A concomitant treatment is any drug, substance or device administered at any time from 
enrollment into the study through the last study visit.  
9.2.8.1 
Concomitant Treatments Restricted During the Study  
The following treatments are not permitted: 
 Anything under the dressing other than Intrasite or Durafiber.  

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 Oxidizing agents such as hypochlorite solutions (e.g. EUSOL) or hydrogen peroxide in 
conjunction with ALNB, as these can reduce the absorbency of the dressing. 
 Negative pressure wound therapy 
9.2.8.2 
Recording Concomitant Treatments in the eCRF  
Concomitant treatments meeting the following criteria will be recorded on the eCRF:  
• 
All current and past reference ulcer treatments 
• 
Concomitant treatments used to treat the reference ulcer (e.g. systemic antibiotics for a 
reference ulcer infection) and the peri-ulcer area (such as treatment for erythema, 
irritation, itching), together with the indication for the medication. 
• 
Concomitant medications used to treat all Serious Adverse Events (SAE), ADE, Serious 
Adverse Device Effects (SADE) and Unanticipated Adverse Device Effects (UADE).  
Adverse device effects related to administration of these treatments must be documented in the 
appropriate eCRF. 
9.3 
DISCONTINUED SUBJECTS 
Discontinued subjects are those who voluntarily discontinue participation in the study, who are 
withdrawn from the study for reasons of safety or non-compliance, or who are withdrawn from 
the study for failure to complete the CWIS at Visit 1. Where possible, the End of Study Visit 
should be completed for all subjects who discontinue the study early. When consent is 
withdrawn, the date of and reason for discontinuation should be captured.  
Subjects may be discontinued from the study at any time if, in the opinion of the Investigator, 
their continued participation in the study poses a risk to the subject. Additionally, subjects may 
be discontinued from the study for the following reasons: 
• 
Adverse device effects 
• 
Lost to follow-up 

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• 
Subject decision unrelated to an adverse device effect 
• 
Noncompliance (e.g. did not follow instructions, took disallowed medications, did not 
communicate with the site staff) 
• 
Other 
If appropriate, the Investigator will advise the subject of subsequent therapy and/or procedures 
necessary for their medical condition, which will consist of SC. 
Note that subjects who are withdrawn only from treatment will not automatically discontinue 
participation in the study, see Section 7.6. 
9.4 
SUBJECT PREGNANCY 
Women of child-bearing potential are not excluded from the study. However, if a woman 
becomes pregnant during the study, S&N must be contacted immediately. Pregnancy is not 
reportable as an adverse event; however, complications related to the pregnancy may be 
reportable as determined on a case-by-case basis. Pregnancy-related information will be 
collected until the end of the pregnancy. 
9.5 
STUDY METHODS AND MEASUREMENTS 
9.5.1 Ulcer Assessments 
Modified Bates-Jensen Wound Assessment Tool 
1. 
Undermining: Assess by inserting a cotton-tipped applicator under the wound edge; advance it as far as it will 
go without using undue force; raise the tip of the applicator so it may be seen or felt on the surface of the skin; 
mark the surface with a pen; measure the distance from the mark on the skin to the edge of the wound. 
Continue process around the wound. Then use a transparent metric measuring guide with concentric circles 
divided into 4 (25%) pie-shaped quadrants to help determine the percent of wound involved. 

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2. 
Necrotic Tissue Type: Pick the type of necrotic tissue that is predominant in the wound according to color, 
consistency, and adherence using this guide 
White/gray non-viable tissue 
= 
May appear prior to wound opening; skin surface is white or 
gray. 
Non-adherent, yellow slough 
= 
Thin, mucinous substance; scattered throughout wound bed; 
easily separated from wound tissue. 
Loosely adherent, yellow 
slough 
= 
Thick, stringy, clumps of debris; attached to wound tissue. 
Adherent, soft, black eschar 
= 
Soggy tissue; strongly attached to tissue in center or base of 
wound. 
Firmly adherent, hard/black 
eschar 
= 
Firm, crusty tissue; strongly attached to wound base and edges 
(like a hard scab). 
 
3. 
Necrotic Tissue Amount: Use a transparent metric measuring guide with concentric circles divided into 4 
(25%) pie-shaped quadrants to help determine the percent of wound involved. 
4. 
Exudate Type: Before assessing exudate type, gently cleanse wound with normal saline. Pick the exudate 
type that is predominant in the wound according to color and consistency, using this guide: 
Bloody 
= 
Thin, bright red 
Serosanguinous 
= 
Thin, watery pale red to pink 
Serous 
= 
Thin, watery, clear 
Purulent 
= 
Thin or thick, opaque tan to yellow 
Foul purulent 
= 
Thick, opaque yellow to green with offensive odor 
 
5. 
Exudate Amount: Use a transparent metric measuring guide with concentric circles divided into 4 (25%) pie-
shaped quadrants to determine the percent of wound area involved with exudate. Use this guide: 
None 
= 
Wound tissues dry. 
Scant 
= 
Wound tissues moist; no measurable exudate. 
Small 
= 
Wound tissues wet; moisture evenly distributed in wound; drainage involves < 25% 
dressing. 
Moderate 
= 
Wound tissues saturated; drainage may or may not be evenly distributed in wound; 

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drainage involves > 25% to < 75% dressing. 
Large 
= 
Wound tissues bathed in fluid; drainage freely expressed; may or may not be evenly 
distributed in wound; drainage involves > 75% of dressing. 
 
6. 
Skin Color Surrounding Wound: Assess tissues within 4cm of wound edge. Dark-skinned persons show the 
colors "bright red" and "dark red" as a deepening of normal ethnic skin color or a purple hue. As healing 
occurs in dark-skinned persons, the new skin is pink and may never darken. 
7. 
Granulation Tissue: Granulation tissue is the growth of small blood vessels and connective tissue to fill in 
full thickness wounds. Tissue is healthy when bright, beefy red, shiny and granular with a velvety appearance. 
Poor vascular supply appears as pale pink or blanched to dull, dusky red color. 
8.   Epithelialization: Epithelialization is the process of epidermal resurfacing and appears as pink or red skin. In 
partial thickness wounds, it can occur throughout the wound bed as well as from the wound edges. In full 
thickness wounds, it occurs from the edges only. Use a transparent metric measuring guide with concentric 
circles divided into 4 (25%) pie-shaped quadrants to help determine the percent of wound involved and to 
measure the distance the epithelial tissue extends into the wound. 
 
Item 
Assessment 
1. Undermining 
1 = None present 
2 = Undermining < 2 cm in any area 
3 = Undermining 2-4 cm involving < 50% wound margins 
4 = Undermining 2-4 cm involving > 50% wound margins 
5 = Undermining > 4 cm or Tunneling in any area 
2. Necrotic Tissue 
Type  
1 = None visible 
2 = White/grey non-viable tissue &/or non-adherent yellow slough 
3 = Loosely adherent yellow slough 
4 = Adherent, soft, black eschar 
5 = Firmly adherent, hard, black eschar 
3. Necrotic Tissue 
Amount  
1 = None visible 
2 = < 25% of wound bed covered 
3 = 25% to 50% of wound covered 
4 = > 50% and < 75% of wound covered 
5 = 75% to 100% of wound covered 

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Item 
Assessment 
4. Exudate Type 
1 = None  
2 = Bloody  
3 = Serosanguinous: thin, watery, pale red/pink 
4 = Serous: thin, watery, clear 
5 = Purulent: thin or thick, opaque, tan/yellow, with or without odor  
5. Exudate Amount 
1 = None, dry wound 
2 = Scant, wound moist but no observable exudate 
3 = Small 
4 = Moderate 
5 = Heavy 
6. Skin Color 
Surrounding 
Wound 
1 = Pink or normal for ethnic group 
2 = Bright red &/or blanches to touch 
3 = White or gray pallor or hypopigmented 
4 = Dark red or purple &/or non-blanchable 
5 = Black or hyperpigmented 
7. Granulation 
Tissue 
1 = Skin intact or partial thickness wound 
2 = Bright, beefy red; 75% to 100% of wound filled &/or tissue overgrowth 
3 = Bright, beefy red; < 75% & > 25% of wound filled 
4 = Pink, &/or dull, dusky red &/or fills < 25% of wound 
5 = No granulation tissue present  
8. Epithelialization 
1 = 100% wound covered, surface intact 
2 = 75% to < 100% wound covered &/or epithelial tissue extends to > 0.5 cm into wound 
bed 
3 = 50% to < 75% wound covered &/or epithelial tissue extends to < 0.5 cm into wound 
bed 
4 = 25% to < 50% wound covered 
5 = < 25% wound covered 
 
Condition of peri-wound  
 Normal 
 Erythematous 
 Edematous 
 Eczematous 
 Excoriated 
 Macerated 

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 Indurated 
Ulcer length/width/depth  
 Using a ruler, obtain the greatest length and width of the ulcer as well as the deepest 
depth.  
Healing status 
 Healed (100% re-epithelialized, no drainage, no need for a dressing)  
 Not healed  
Level of odor 
 none 
 mild 
 moderate 
 strong 
9.5.2 Photographs  
Photograph the ulcer and/or dressing (per visit instructions). Ensure that the paper ruler has the 
subject number and the date clearly written. The paper ruler should be laid flat next to the ulcer, 
preferably on the intact skin.  
The image should be framed such that the entire reference ulcer/dressing nearly fills the frame. 
Ensure that identifying information, such as the subject’s face, are not visible in the photograph. 
After obtaining the image, ensure that the image is clear (in focus) and that there is sufficient 
light to clearly see the ulcer/dressing. Follow sponsor instructions for sending the images to the 
sponsor.  
9.5.3 Ankle Brachial Pressure Index (ABI) 
The ABI of each subject must be taken at the initial assessment date, or if there is an ABI result 
within 30 days of Visit 1 this can be used to confirm eligibility. ABI should be determined per 
the site’s standard procedure.  

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9.5.4 Biological Samples 
This study does not require the collection of any biological samples.  
9.5.5 Ulcer Classification 
9.5.5.1 
Pressure Ulcers8 
Stage 1 Pressure Injury: Non-blanchable erythema of intact skin 
Intact skin with a localized area of non-blanchable erythema, which may appear different in darkly pigmented 
skin. Presence of blanchable erythema or changes in sensation, temperature, or firmness may precede visual 
changes. Color changes do not include purple or maroon discoloration; these may indicate deep tissue pressure 
injury. 
Stage 2 Pressure Injury: Partial-thickness skin loss with exposed dermis 
Partial-thickness loss of skin with exposed dermis. The ulcer bed is viable, pink or red, moist, and may also 
present as an intact or ruptured serum-filled blister. Adipose (fat) is not visible and deeper tissues are not 
visible. Granulation tissue, slough, and eschar are not present. These injuries commonly result from adverse 
microclimate and shear in the skin over the pelvis and shear in the heel. This stage should not be used to 
describe moisture associated skin damage (MASD) including incontinence associated dermatitis (IAD), 
intertriginous dermatitis (ITD), medical adhesive-related skin injury (MARSI), or traumatic wounds (skin 
tears, burns, abrasions). 
Stage 3 Pressure Injury: Full-thickness skin loss 
Full-thickness loss of skin, in which adipose (fat) is visible in the ulcer and granulation tissue and epibole 
(rolled wound edges) are often present. Slough and/or eschar may be visible. The depth of tissue damage 
varies by anatomical location; areas of significant adiposity can develop deep wounds. Undermining and 
tunneling may occur. Fascia, muscle, tendon, ligament, cartilage and/or bone are not exposed. If slough or 
eschar obscures the extent of tissue loss this is an Unstageable Pressure Injury. 
Stage 4 Pressure Injury: Full-thickness skin and tissue loss 
Full-thickness skin and tissue loss with exposed or directly palpable fascia, muscle, tendon, ligament, cartilage 
or bone in the ulcer. Slough and/or eschar may be visible. Epibole (rolled edges), undermining and/or 
tunneling often occurs. Depth varies by anatomical location. If slough or eschar obscures the extent of tissue 
loss this is an Unstageable Pressure Injury. 
Unstageable Pressure Injury: Obscured full-thickness skin and tissue loss 
Full-thickness skin and tissue loss in which the extent of tissue damage within the ulcer cannot be confirmed 
because it is obscured by slough or eschar. If slough or eschar is removed, a Stage 3 or Stage 4 pressure injury 
will be revealed. Stable eschar (i.e. dry, adherent, intact without erythema or fluctuance) on the heel or 
ischemic limb should not be softened or removed. 

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9.5.5.2 
Diabetic Foot Ulcers 
Wagner Classification of Diabetic Foot Ulcers 
Grade 0: No open lesions; may have deformity or cellulitis 
Grade 1: Superficial diabetic ulcer (partial or full thickness) 
Grade 2: Ulcer extension to ligament, tendon, joint capsule, or deep fascia without abscess or 
osteomyelitis 
Grade 3: Deep ulcer with abscess, osteomyelitis, or joint sepsis 
Grade 4: Gangrene localized to portion of forefoot or heel 
Grade 5: Extensive gangrenous involvement of the entire foot 
9.5.6 Ulcer Pain Scale 
The level of pain associated with removing the dressing from the reference ulcer will be assessed 
at each study visit. The subject will be asked to rate the level of pain when the dressing is 
removed on a scale of 0 to 10 (no pain to worst pain). The pain measure will be recorded as a 
whole number only.  
9.5.7 Dressing Application 
1. How easy was it to apply the dressing?  
Very Easy/Easy/Neither Easy nor Difficult/Difficult/Very Difficult.  
If Difficult or Very Difficult, provide details. 
2. Did the dressing stay in place (without assistance) on the ulcer until secondary retention was 
applied?  
Yes/No 
3. Did the dressing need to be repositioned before application of secondary retention?  
Yes/No.  
If yes, was adherence to the ulcer affected after repositioning?  
Yes/No 

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9.5.8 Dressing Comfort 
How comfortable was the dressing to wear?  
Very comfortable/Comfortable/Neither Comfortable nor Uncomfortable/Uncomfortable /Very Uncomfortable  
If Uncomfortable or Very Uncomfortable, list the reason. 
9.5.9 Dressing Movement 
Has the dressing moved/shifted since the last visit?  
Yes/No  
If yes, explain. 
9.5.10 Dressing Removal 
1. How easy was the dressing to remove?  
Very Easy/Easy/Neither Easy nor Difficult/Difficult/Very Difficult  
If Difficult or Very Difficult, provide details. 
2. Did the dressing leak since the last visit?  
Yes/No 
3. For VLU under compression, did the dressing absorb exudate since the last visit?  
Yes/No  
If no, record observation.  
9.6 
HEALTH-RELATED QUALITY OF LIFE  
Changes in subject-reported HRQoL are an important consideration for any post-marketing 
clinical follow-up study.  
This CWIS considers the impact of chronic wounds (leg ulcers and diabetic foot ulcers) on 
HRQoL, as measured by three domains: 
 Physical symptoms and daily living (24 items) 

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 Social life (14 items) 
 Well-being (7 items) 
Corresponding scales provide scores between 0 and 100. Each scale has been shown to have 
good internal consistency, reproducibility, and discriminative validity.  
This instrument also includes two further single item ‘global’ scales for HRQoL and satisfaction 
with the quality of life. However, their sensitivity and value in detecting change are unclear in 
reported literature. 
subject 
10. STATISTICAL DESIGN 
There will be a formal Statistical Analysis Plan (SAP); the following is a brief description of the 
summaries and analyses to be described in this plan.  
Unless otherwise stated, all significance tests and hypothesis testing will be two-sided, 
performed at the 5% significance level. Resulting p-values will be quoted and 95% two-sided 
confidence intervals will be generated where appropriate. All analyses will be performed in SAS 
v9.4, or later. 
Where data summaries are specified, categorical and ordinal variables will be summarized using 
frequency distributions, which will detail the number and percentage of subjects that fall into 
each category. Continuous variables will be summarized using the following summary statistics: 
mean, median, standard deviation, minimum and maximum values, and number of observations. 
10.1 
EVALUABILITY 
All subjects who provide informed consent are considered study participants. Study populations 
are defined as follows: 
 Safety population (SAF): all subjects who receive study treatment. This population will 
be used for summaries of disposition of the subjects, protocol deviations/violations, and 
safety. 

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 Full analysis set (FAS): following the intention to treat principle all randomized subjects 
who receive study treatment and attend at least one post-baseline assessment will be 
included. This population will be used for the primary analysis of baseline characteristics, 
primary variables, secondary variables and exploratory variables.  
 Per protocol (PP) population: includes all subjects in the FAS population who have no 
significant protocol deviations, meet the inclusion/exclusion criteria, and did not 
withdraw early (except for closure at any time). This population will be used for 
supportive evidence of the primary variable. 
10.2 
EFFICACY  
10.2.1 Primary Efficacy 
The primary objective of the study is to compare HRQoL in subjects with chronic wounds. The 
primary efficacy variable used to measure this objective will be the change from baseline in the 
CWIS-PSDL scale, over a six week treatment period. 
The CWIS-PSDL scale is a 24 item questionnaire split into uses a 5 category Likert scale to 
answer each item with a 1 - 5 score assigned to each category. The first 12 items focus on 
whether the subject has experienced any of the items over the past 7 days [Not at all/Not 
applicable – 5, Seldom – 4, Sometimes – 3, Frequently – 2, Always – 1]. The last 12 items focus 
on how stressful the experience of the items has been over the past 7 days [Not at all/Not 
applicable – 5, Slightly – 4, Moderately – 3, Quite a bit – 2, Very applicable – 1]. These scores 
are then transformed into a 0-100 scale at each time point, where a high score represents a 'good' 
HRQoL and a low score represents a 'poor' HRQoL, using the following formula: 
ܲܵܦܮ ܵܿ݋ݎ݁ൌ ܵݑ݉ ݋݂ ݅ݐ݁݉ ݏܿ݋ݎ݁ݏെ24
96
 ൈ100 

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The increase in CWIS-PSDL score between baseline and 6 weeks will be derived as follows:  
ܲܵܦܮ ݏܿ݋ݎ݁ ݅݊ܿݎ݁ܽݏ݁ ൌ ሺ ܵܿ݋ݎ݁ ܽݐ 6 ݓ݁݁݇ݏെ ܵܿ݋ݎ݁ ܽݐ ܾܽݏ݈݁݅݊݁ ሻ 
Subject responses to individual items at each assessment will be summarized as ordinal variables 
by treatment, wound type (and overall) and level of exudate at baseline.  
The CWIS-PSDL score at Baseline and 6 weeks will be summarized as a continuous variable by 
treatment, wound type (and overall) and level of exudate at baseline. 
The increase in CWIS-PSDL score between the Baseline and 6 weeks will be summarized as a 
continuous variable by treatment, wound type (and overall), baseline mobility, and level of 
exudate at baseline. 
For the primary analysis, an ANCOVA model will be fit to the FAS population with the increase 
in CWIS-PSDL score between the Baseline and 6 weeks as the dependent variable, treatment 
(ALNB or SC) and center will be included in the model as fixed effects and subject will be 
included as a random effect. The covariates for the model to be considered will be wound type, 
baseline CWIS-PSDL score, baseline exudate level, baseline mobility, and baseline wound area.  
The null hypothesis will be that there is no difference between the treatments in the increase 
from baseline to 6 weeks in the CWIS-PSDL score. An estimate of the LS mean difference 
between the treatments (ALNB – SC) for the CWIS-PSDL score will be reported, along with the 
corresponding 95% confidence interval and p-value.  
If the assumptions of ANCOVA are not met then a non-parametric analysis will be considered 
the primary analysis for this variable. A Wilcoxon Rank-Sum test will be used to test for a 
difference in the increase from baseline score between the two treatments and the Hodges-
Lehmann estimate of the median difference will be reported with the corresponding 95% 
confidence interval. 
This analysis will be repeated using the per-protocol population and used as supportive evidence 
to the primary analysis. Any further sensitivity analyses and discussion of methods of handling 
missing data will be defined in the SAP. 

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10.2.2 Secondary Efficacy 
Various secondary efficacy variables will also be assessed for differences between the treatment 
and comparator arms. These are listed below and further details will be included in the SAP. 
10.2.2.1 
Key Secondary 
Health-related quality of life (HRQoL) 
Subject-reported HRQoL variables (measured using the CWIS) include: 
 The increase in CWIS-PSDL scale scores from baseline to three and twelve weeks 
(separately). This will be analyzed in the same way as described in the primary efficacy 
analysis. 
 Increase from baseline scores to three, six, and twelve weeks will be calculated and analyzed 
separately in the same way as described in the primary efficacy analysis, for the following 
variables: 
o CWIS-SL scale 
o CWIS-WB scale 
o CWIS-GQ scale 
o CWIS-SQ scale 
10.2.2.2 
Secondary 
Ulcer progression 
Ulcer progression variables will be summarized by treatment group at three, six, and twelve 
weeks. 
Part of the assessment of ulcer progression will be done using a modified version of the Bates-
Jensen Wound Assessment tool with the following variables being assessed (see section 9.5.1 for 
the scales used): 
 Undermining 

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 Necrotic tissue type  
 Necrotic tissue amount 
 Exudate type 
 Exudate amount 
 Skin color surrounding the wound 
 Granulation tissue 
 Epithelialization 
Other assessments of ulcer progression to be summarized include: 
 Condition of peri-wound (categorized as Normal, Erythematous, Edematous, 
Eczematous, Excoriated, Macerated, Indurated) and the condition of peri-wound at each 
post-baseline time point cross-tabulated with condition of peri-wound at baseline to be 
summarized separately. 
 Ulcer length/width/depth will be used to derive area and volume. These variables will 
then be used to derive the reduction in area, depth, and volume from baseline to three, six 
and twelve weeks. The reduction in each dimension at each assessment will be analyzed 
as the dependent variable in separate linear regression models. An estimate of the 
difference between treatments in the reduction from baseline area, depth, and volume 
(separately) will be reported with the corresponding 95% confidence interval. 
 Reference ulcer healed (100% re-epithelialized, no drainage, no need for a dressing) will 
be summarized at each assessment (at three, six, and twelve weeks) and analyzed using 
separate logistic regression models with whether the reference ulcer was healed or not at 
the assessment as the dependent variable. 
Healthcare resource use 
The following Healthcare resource variables will be summarized by treatment groups and overall 
at twelve weeks: 

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 Number and type of dressings used (both primary and secondary dressings), including 
use of compression therapy 
 Number of outpatient visits 
 Amount of time in hospital (nights spent as an inpatient) 
 Number and type of interventions/procedures including debridement of ulcer (curette, 
scissors, scalpel, forceps, other) 
 Number and type of concomitant therapies/treatments 
10.2.3 Exploratory Efficacy 
The following exploratory analysis has been planned for three, six, and twelve weeks (unless 
otherwise stated): 
 Dressing wear time (days) will be summarized per subject and overall by treatment group 
and an estimate of the difference in wear time between treatment groups will be reported 
with the corresponding 95% confidence interval at twelve weeks only. 
 Dressing leakage will be summarized by treatment group and overall 
 Ease of dressing application/removal will be summarized by treatment group and overall 
 Dressing use (whether dressing was cut and adherence following repositioning) will be 
summarized by treatment group and overall 
 Odor control of dressing will be summarized by treatment group and overall 
 Absorption of exudate under compression will be summarized by treatment group and 
overall 
 Reason for dressing change will be summarized by treatment group and overall 
 Pain on dressing removal will be summarized by treatment group and overall and an 
estimate of the difference between treatment groups will be reported with the 
corresponding 95% confidence interval 
 Comfort during wear will be summarized by treatment group and overall 

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10.3 
SAFETY  
All safety analyses and summaries will be conducted using the Safety Population. Unless 
otherwise stated, all safety summaries will be presented by treatment and overall.  
Extent of Exposure 
The duration of treatment will be summarized. 
Adverse Events 
Adverse events will be coded and grouped by system organ class using the Dictionary for 
Medical Drug Regulatory Activities (MedDRA). 
The number of subjects reporting: adverse events, serious adverse events, severe adverse events, 
device-related adverse events, serious device-related adverse events, unexpected adverse events, 
and serious unexpected adverse events will be summarized. In addition, for each adverse event, 
the following will be summarized: severity, treatment, the relationship to the investigational 
device, the possible cause if related, outcome and duration of the resolved adverse events and the 
duration of the adverse events at trial discontinuation. 
The proportion of subjects with a device-related adverse event will be compared between 
treatments using Fisher’s exact test. In addition, the percentage of serious device-related adverse 
events and the corresponding 1-sided upper 95% confidence limit will be detailed assuming a 
Poisson distribution for serious device-related adverse events separately for each treatment.  
The number and proportion of subjects reporting treatment-emergent adverse events split by 
treatment separately by system organ class and preferred term will be summarized by: 
1. Their relationship with the investigational device (not related or related). If the relationship 
is missing, the adverse event will be assumed to be treatment-related and a footnote will be 
added to the table. If a subject experiences more than one preferred term within a system 
organ class, then the relationship at the system organ class level for that subject will be 
reported according to their most related relationship for each preferred term. 
2. The severity of the adverse event (mild, moderate or severe). 

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3. Whether or not the adverse event is serious 
4. The adverse event outcome. 
5. Whether or not the adverse event is expected or unexpected. 
11. SAMPLE SIZE JUSTIFICATION 
Since there is no previous data upon which to base a sample size calculation, no statistical 
justification for the sample size is provided. Twenty-five (25) subjects were desired for the 
ALNB group; a 5:3 randomization ratio was selected so that approximately forty (40) subjects 
would be enrolled into the study. This number of subjects is based on feasibility only. 
12. ADVERSE EVENTS AND DEVICE DEFICIENCIES 
12.1 
DEFINITIONS 
The different categories of adverse events are shown in table 12.1-1 below. The definitions for 
each of these categories are given in the subsequent sections (see reference within the table).  

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Table 12.1-1: Categories of Adverse Event 
 
NOT DEVICE-
RELATED 
DEVICE-RELATED 
NON-
SERIOUS 
ADVERSE EVENT  
(AE) (SEE 12.1.1) 
ADVERSE DEVICE EFFECT  
(ADE) (SEE 12.1.2) 
SERIOUS 
SERIOUS ADVERSE 
EVENT  
(SAE)  
(SEE 12.1.3) 
SERIOUS ADVERSE DEVICE EFFECT 
(SADE) (SEE 12.1.3) 
ANTICIPATED 
UNANTICIPATED 
ANTICIPATED SERIOUS 
ADVERSE DEVICE EFFECT  
(ASADE) (SEE 12.1.4) 
UNANTICIPATED SERIOUS 
ADVERSE DEVICE EFFECT  
(USADE) (SEE 12.1.4) 
12.1.1 Adverse Event 
An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use 
of an investigational medicinal product or device, whether or not considered causally related to 
that product/device. An AE can be any unfavorable and unintended sign (for example, an 
abnormal laboratory finding), symptom, or disease. 
AE is used both to refer to AE which are not serious or device related and as an umbrella term 
referring to adverse events of all classifications.  
12.1.2 Adverse Device Effect (ADE) 
An Adverse Device Effect (ADE) is an adverse event that, in the opinion of the Investigator, is 
related to the investigational or comparator device:  
• 
Not Related – An AE is considered to be not related to the use of the test article when 
the effect is DEFINITELY UNRELATED or UNLIKELY to have any relationship to 
the use of the test article; 
• 
Related – An AE is considered to be related to the use of the test article when there is a 
POSSIBLE, PROBABLE, or DEFINITE relationship between the AE and the use of the 
test article. 

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AE related to the use of S&N ancillary products will be reported as ADE. 
An ADE is further categorized depending on whether the criteria in section 12.1.3 and 12.1.4 are 
met.  
12.1.3 Seriousness  
An AE and an ADE are considered “serious” if, in the view of either the Investigator or the 
sponsor, it: 
• 
Results in death 
• 
Is life-threatening (NOTE: The term “life-threatening” in the definition of “serious” refers 
to an event/reaction in which the subject was at risk of death at the time of the 
event/reaction; it does not refer to an event/reaction which hypothetically might have 
caused death if it were more severe) 
• 
Requires in subject hospitalization or results in prolongation of existing hospitalization 
• 
Results in persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• 
Is a congenital anomaly/birth defect 
• 
Is a medically important event or reaction 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious such as important medical events that might not be immediately life-
threatening or result in death or hospitalization but might jeopardize the subject or might require 
intervention to prevent one of the other outcomes listed in the definition above. Examples of 
such events are intensive treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias, or convulsions that do not result in hospitalization; or development of drug 
dependency or drug abuse. 

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12.1.4 Anticipated/Unanticipated Serious Adverse Device Effect (ASADE/USADE) 
A USADE is a serious ADE that meets any of the above definitions but is also considered, by the 
Investigator, to be caused by or related to the investigational device, not previously identified in 
nature, severity or degree in the ALLEVYN LIFE Non-Bordered Instructions for use. An 
ASADE is a serious ADE that does not meet the criteria for a USADE.  
12.1.5 Severity  
The severity of every AE will be assessed by the Principal Investigator (PI). AE should be 
classified as mild, moderate, or severe, regardless of whether or not the AE are considered to be 
serious or non-serious. The classification should be based on the following definitions: 
• 
Mild – An event is mild if the subject is aware of, but can easily tolerate the sign or 
symptom; 
• 
Moderate – An event is moderate if the sign or symptom results in discomfort 
significant enough to cause interference with the subject’s usual activities; 
• 
Severe – An event is severe if the sign or symptom is incapacitating and results in the 
subject’s inability to work or engage in their usual activities. 
12.1.6 Device Deficiency (DevD) 
A DevD is an inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, safety or performance. DevD include malfunctions, use errors and inadequate 
labeling.  
12.2 
REPORTING PROCEDURES 
AE of any kind and DevD will be recorded in the applicable forms, eCRF, and source notes. The 
Investigator will evaluate all AE for relationship to the device, seriousness, and severity. ADE, 
SAE, and DevD will be entered into the eCRF and reported to the Sponsor within 24 hours of the 
Investigator being informed about the event (Figure 12.2-1). Updates to submitted information 

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will be recorded in the eCRF within 24 hours of the information being available to the 
Investigator. Ensure that for a device that causes an ADE/DevD, that the device information 
(Product Name, Product Code, Lot #, Expiration Date, and Size) are entered in the eCRF. 
All SAE and ADE will be reviewed by a medically qualified person appointed by the Sponsor to 
determine which, if any, meet criteria for expedited reporting to the regulatory authorities.  
The Investigator will inform the IRB of adverse events according to the IRB requirements.  
Figure 12.2-1: Evaluation of an Adverse Event by the Investigator 
 
Site aware 
of AE 
Record in 
Source  
Investigator assess seriousness and 
relationship to device 
Serious or 
device-related 
NOT Serious or 
device-related 
IMMEDIATELY complete 
eCRF to alert S&N 
Complete eCRF to 
usual timescales 

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Table 12.2-1: Contact Information for Reporting of Unanticipated Serious Adverse Device 
Effects 
Darrell Lange, PhD  
Business Phone 
817-302-3959 
Senior Study Manager 
Mobile Phone 
817-707-6219 
 
email address 
darrell.lange@smith-nephew.com 
Innes Cargill, PhD 
Business Phone 
817-302-3913 
Medical Monitor 
Mobile Phone  
254-681-1010 
 
email address 
innes.cargill@smith-nephew.com 
12.3 
UNBLINDING OF TEST ARTICLE 
Not applicable, as the study is not blinded.  
12.4 
FOLLOW-UP OF SUBJECTS WITH ADVERSE DEVICE EFFECTS 
For subjects who are experiencing ongoing unresolved ADE at the time of their study completion 
or early discontinuation from the study, it is recommended that the Investigator schedule an 
appropriate follow-up visit to determine the outcome of the event. Any additional data must be 
documented and available to the sponsor who will determine whether the data need to be 
documented within the Clinical Study Report. 
13. INVESTIGATOR OBLIGATIONS 
The PI will comply with the commitments outlined in the Investigator’s Agreement Form 
provided by the Sponsor, with Good Clinical Practice (GCP), and all applicable regulatory 
requirements as outlined in Section 21.3 of this protocol. 
14. SPONSOR AND MONITOR RESPONSIBILITIES 
The Sponsor will designate a monitor to conduct the appropriate site visits at the appropriate 
intervals. The clinical investigation will be monitored to ensure that the rights and wellbeing of 
the subjects are protected; the reported data are accurate, complete, and verifiable from the 

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source documents; and the study is conducted in compliance with the currently approved 
protocol, with current GCP, and with applicable regulatory requirements. 
Detailed monitoring requirements will be documented in the Monitoring Plan for this study. All 
studies will have a site initiation visit. Monitoring will be conducted periodically while the 
clinical study is ongoing. Monitoring methods may include site visits, telephone, written, and fax 
correspondence. The Study Manager and/or assigned study monitor will contact each site at 
appropriate intervals. The Study Manager will determine the frequency of site visits. Close-out 
visits will take place after the last visit of the last subject.  
15. PROTOCOL AMENDMENTS 
Amendments should be made only in exceptional cases once the study has started. Protocol 
amendments must be approved prior to submission to the IRB. Once approved by the IRB the 
changes then become part of the protocol. 
16. CONFIDENTIALITY OF THE STUDY 
The existence of this clinical study is confidential and should not be discussed with persons 
outside of the study. You shall not use the confidential information for any purpose other than 
the study. The foregoing obligations of confidence and non-use assumed by you shall not apply 
to (a) information which at the time of disclosure is in the public domain; (b) information which 
thereafter lawfully becomes part of the public domain other than through disclosure by or 
through you; (c) information which, as evidenced by your written records, was known by you 
prior to S&N’s disclosure; (d) information which is lawfully disclosed to you by a third party, 
not under any obligation of confidence to S&N; or (e) information which is required to be 
disclosed by law or government regulatory agency, provided reasonable advance notice of such 
disclosure is given to S&N. 

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17. STATEMENTS OF COMPLIANCE 
This clinical study will be performed in compliance with the ethical principles of the Declaration 
of Helsinki; ISO 14155: Clinical investigation of medical devices – Good Clinical Practice9; 
effective for studies commencing after July 1996.  
This clinical study will not commence until the required approval/favorable opinion from the 
IRB or regulatory authority has been obtained. Any additional requirements imposed by the IRB 
or regulatory authority will be followed.  
Public/Products Liability Insurance has been purchased by Smith & Nephew plc. Worldwide and 
incorporates coverage for personal injury in respect of clinical studies. The Sponsor agrees to 
operate in good faith the per the ABHI (Association of British Healthcare Industries) guidelines 
regarding compensation for injury arising in the course of clinical studies. 
18. END OF STUDY 
The end of the study is defined as the last visit of the last subject undergoing treatment in the 
study. ALLEVYN LIFE Non-Bordered is a commercially available product and therefore should 
be available to subjects after their participation in this study. Subjects may participate for a 
maximum total duration of 88 (84 ± 4) days. 
Should circumstances arise which require the termination of the entire study prior to its planned 
completion (e.g. safety concerns) or circumstances arise which mean the end of the participation 
of an individual site (e.g. departure of Investigator, non-compliance) then this will be undertaken 
according to the SOPs of the Sponsor.  
19. PUBLICATION POLICY 
An analysis of the results of the study submitted by the Investigator will be prepared by the 
Sponsor in the form of an internal clinical study report. These results are primarily intended for 
regulatory purposes, rather than external publication. Further details regarding the publication 
policy for this study can be found in the Clinical Trial Agreement. By signing the Clinical Trial 

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Agreement the Principal Investigator agrees to comply with the terms and conditions contained 
therein. 
 
 

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20. REFERENCES 
1. 
Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, et al. Human skin wounds: 
a major and snowballing threat to public health and the economy. Wound Repair Regen. 
2009;17:763–71. 
2. 
Posnett J, Franks PJ. The burden of chronic wounds in the UK. Nurs Times. 2008;104:44–
5.  
3. 
Markova A, Mostow EN. US skin disease assessment: ulcer and wound care. Dermatol 
Clin. 2012;30:107–11.  
4. 
Driver VR, Fabbi M, Lavery LA, Gibbons G. The costs of diabetic foot: the economic case 
for the limb salvage team. J Am Podiatr Med Assoc. 2010;100:335–41. 
5. 
Drysdale K, Rossington A, Winter R. Clinical performance and positive impact on patient 
wellbeing of ALLEVYN™ Life. Wounds UK 2013;9:91-95.  
6. 
BSI Group. The Post-Market Priority. Understanding and Meeting Demand for Effective 
Post-Market Clinical Follow-Up-Whitepaper. 2014 
7. 
Price P, Harding K. Cardiff wound impact schedule: the development of a condition-
specific questionnaire to assess health-related quality of life in patients with chronic 
wounds of the lower limb. Int Wound J 2004;1:10–17. 
8. 
National Pressure Ulcer Advisory Panel (http://www.npuap.org/resources/educational-and-
clinical-resources/npuap-pressure-injury-stages) Accessed on 15Feb2017. 
9. 
ISO 14155:2011 Clinical investigation of medical devices for human subjects – good 
clinical practice. 
 
 
 

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21. APPENDICES 
21.1 
INSTRUCTIONS FOR USE 
Revision 9: 24th October 2016 
 

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circulate without written authorization from the appropriate Smith & Nephew personnel 
 
 
 

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21.2 
CARDIFF WOUND IMPACT SCHEDULE 
 

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circulate without written authorization from the appropriate Smith & Nephew personnel 
 

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21.3 
PRINCIPAL INVESTIGATOR OBLIGATIONS 
An Investigator is responsible for:  
1. General Responsibilities: [21 CFR §812.100] 
a. Ensuring that an investigation is conducted according to the signed agreement, the 
investigational plan, and applicable FDA regulations.  
b. Protecting the rights, safety, and welfare of those under the Investigator’s care.  
c. The control of devices under investigation. 
2. Specific Responsibilities: [21 CFR §812.110] 
a. An Investigator may determine whether potential participants would be interested in 
participating in an investigation, but shall not request written informed consent of any 
participant to participate, and shall not allow any participant to participate before 
obtaining IRB and FDA approval.  
b. An Investigator shall conduct an investigation in accordance with the signed agreement 
with the sponsor, the investigational plan, this part and applicable FDA regulations, and 
any conditions of approval imposed by an IRB or FDA.  
c. An Investigator shall permit an investigational device to be used only with participants 
under the Investigator’s supervision. An Investigator shall not supply an investigational 
device to any person not authorized under this part to receive it.  
d. A clinical Investigator shall disclose to the sponsor sufficient accurate financial 
information to allow the applicant to submit complete and accurate certification or 
disclosure statements required under part 54 of this chapter. The Investigator shall 
promptly update this information if any relevant changes occur during the course of the 
investigation and for 1 year following completion of the study.  
e. Upon completion or termination of a clinical investigation or the Investigator’s part of an 
investigation, or at the sponsor’s request, an Investigator shall return to the sponsor any 
remaining supply of the device or otherwise dispose of the device as the sponsor directs.  
3. Investigator Records: [21 CFR §812.140(a)] 
 
a. A participating Investigator shall maintain the following accurate, complete, and current 
records relating to the Investigator’s participation in an investigation:  
i. 
All correspondence with another Investigator, an IRB, the sponsor, a monitor, or 
FDA, including required reports. 
ii. 
Record of receipt, use, or disposition of a device that relate to: 
1. The type and quantity of the device, the dates of its receipt, and the batch 
number or code mark. 
2. The names of all persons who received, used, or disposed of each device. 

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3. Why and how many units of the device have been returned to the sponsor, 
repaired, or otherwise disposed of. 
b. Records of each participant’s case history and exposure to the device. Case histories 
include case report forms and supporting data including, for example, signed and dated 
consent forms and medical records including, for example, progress notes of the 
physician, the individual’s hospital chart(s), and the nurses’ notes. Such records shall 
include: 
i. 
Documents evidencing informed consent and, for any use of a device by the 
Investigator without informed consent, any written concurrence of a licensed 
physician and a brief description of the circumstances justifying the failure to obtain 
informed consent. The case history for each individual shall document that informed 
consent was obtained prior to participation in the study. 
ii. 
All relevant observations, including records concerning adverse device effects 
(whether anticipated or unanticipated), information and data on the condition of each 
participant upon entering, and during the course of, the investigation, including 
information about relevant previous medical history and the result of all diagnostic 
tests. 
iii. 
A record of exposure of each participant to the investigational device, including date 
and time of each use, and any other therapy. 
c. The protocol, with documents showing the dates of and reasons for each deviation from 
the protocol. 
d. Any other records that FDA requires to be maintained by regulation or by specific 
requirement for a category of investigations or a particular investigation. 
4. Retention period: [21 CFR §812.140(d)] 
a. An Investigator or sponsor shall maintain the records required by this subpart during the 
investigation and for a period of 2 years after the latter of the following two dates: The 
date on which the investigation is terminated or completed, or the date that the records are 
no longer required for purposes of supporting a premarket approval application or a 
notice of completion of a product development protocol.  
5. Records Custody: [21 CFR §812.140(e)] 
a. An Investigator or sponsor may withdraw from the responsibility to maintain records for 
the period required in 21 CFR §812.140(d) and transfer custody of the records to any 
other person who will accept responsibility for them under 21 CFR §812.140, including 
the requirements of 21 CFR §812.145.  
b. Notice of a transfer shall be given to FDA not later than 10 working days after the 
transfer occurs.  
6. Inspections: [21 CFR §812.145] 

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a. An Investigator who has authority to grant access shall permit authorized FDA 
employees, at reasonable times and in a reasonable manner, to enter and inspect any 
establishment where devices are held (including any establishment where devices are 
manufactured, processed, packed, installed, used, implanted or where records of results 
from use of devices are kept).  
b. An Investigator shall permit authorized FDA employees, at a reasonable time and in a 
reasonable manner, to inspect and copy all records relating to an investigation.  
c. An Investigator shall permit authorized FDA employees to inspect and copy records that 
identify participants, upon notice that FDA has reason to suspect that adequate informed 
consent was not obtained, or that reports required to be submitted by the Investigator to 
the sponsor or IRB have not been submitted or are incomplete, inaccurate, false, or 
misleading.  
d. An Investigator shall prepare and submit the following complete, accurate, and timely 
reports:  
i. 
An Investigator shall submit to the sponsor and to the reviewing IRB a report of any 
unanticipated adverse device effect occurring during an investigation as soon as 
possible, but in no event later than 10 working days after the Investigator first learns 
of the effect. 
ii. 
An Investigator shall report to the sponsor, within 5 working days, a withdrawal of 
approval by the reviewing IRB of the Investigator’s part of an investigation. 
iii. 
An Investigator shall submit progress reports on the investigation to the sponsor, the 
monitor, and the reviewing IRB at regular intervals, but in no event less than yearly. 
iv. 
An Investigator shall notify the sponsor and the reviewing IRB [21 CFR §56.108(a) 
(3) and (4)] of any deviation from the investigational plan to protect the life or 
physical well-being of a participant in an emergency. Such notice shall be given as 
soon as possible but in no event later than 5 working days after the emergency 
occurred. Except in such an emergency, prior approval by the sponsor is required for 
changes in or deviations from a plan, and if these changes or deviations may affect 
the scientific soundness of the plan or the rights, safety, or welfare of human 
participants, FDA and IRB in accordance 21 CFR §812.35(a) also is required. 
v. 
If an Investigator uses a device without obtaining informed consent, the Investigator 
shall report such use to the sponsor and the reviewing IRB within 5 working days 
after the use occurs. 
vi. 
An Investigator shall, within 3 months after termination or completion of the 
investigation or the Investigator’s part of the investigation, submit a final report to 
the sponsor and reviewing IRB. 

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vii. 
An Investigator shall, upon request by a reviewing IRB or FDA, provide accurate, 
complete, and current information about any aspect of the investigation. 
viii. 
HIPAA Authorization: For studies conducted in the US only, obtain written HIPAA 
authorization (or provide a waiver) for use and disclosure of protected health 
information (PHI) from each study participant (or legal representative) enrolled in 
the study using your current authorization form before performing any study-specific 
procedures on the study participant.