A LONG-TERM, PROSPECTIVE, OBSERVATIONAL COHORT STUDY OF THE SAFETY AND EFFECTIVENESS OF ETANERCEPT IN THE TREATMENT OF PAEDIATRIC PSORIASIS PATIENTS IN A NATURALISTIC SETTING: A POST-AUTHORISATION SAFETY STUDY (PASS)
Conditions: Psoriasis
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) DRUG STUDY PROTOCOL 
A LONG-TERM, PROSPECTIVE, OBSERVATIONAL COHORT STUDY OF THE 
SAFETY AND EFFECTIVENESS OF ETANERCEPT IN THE TREATMENT OF 
PAEDIATRIC PSORIASIS PATIENTS IN A NATURALISTIC SETTING:  
A POST-AUTHORISATION SAFETY STUDY (PASS)
Compound Number:
PF-05208752
Compound Name:
Enbrel (etanercept)
Study Number:
B1801035
Version and Date:
Original - 27 February 2009
Amendment 1 – 14 May 2009
Amendment 2 – 05 March 2010
Amendment 3 – 22 June 2011
Amendment 4 – 09 April 2012
Amendment 5 – 01 July 2013
Amendment 6 – 01 July 2014

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TABLE OF CONTENTS 
LIST OF TABLES ...........................................................................................................................4 
1. INTRODUCTION .......................................................................................................................7 
1.1. Background and Rationale ..............................................................................................8 
2. STUDY OBJECTIVES AND ENDPOINTS ...............................................................................9 
2.1. Endpoints .......................................................................................................................10 
2.1.1. Safety Endpoints ...............................................................................................10 
2.1.1.1. Serious and Opportunistic Infections ..............................................10 
2.1.1.2. Malignancies ...................................................................................11 
2.1.1.3. Other SAEs ......................................................................................11 
2.1.2. Effectiveness Endpoints....................................................................................11 
2.2. Concomitant Medications .............................................................................................12 
3. STUDY DESIGN.......................................................................................................................12 
4. STUDY POPULATION ............................................................................................................13 
4.1. Registry Enrolment .......................................................................................................13 
4.1.1. Geographical Scope of Registry .......................................................................13 
4.1.2. Physician Enrolment .........................................................................................13 
4.1.3. Patient Enrolment .............................................................................................13 
4.2. Inclusion Criteria ...........................................................................................................14 
4.3. Exclusion Criteria ..........................................................................................................15 
5. STUDY TREATMENT AND DURATION .............................................................................15 
6. STUDY PROCEDURES ...........................................................................................................16 
6.1. Schedule of Assessments ..............................................................................................16 
6.2. Data Collection ..............................................................................................................16 
6.2.1. Baseline Visit ....................................................................................................17 
6.2.2. Follow-up Visit .................................................................................................18 
FOLLOW-UP: YEAR 1 THROUGH 2 ......................................................................18 
FOLLOW-UP: YEAR 3 THROUGH YEAR 5 ..........................................................18 
6.2.3. Patient Withdrawal ...........................................................................................19 
7. DATA ANALYSIS/STATISTICAL METHODS .....................................................................20 
7.1. General considerations ..................................................................................................20 

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7.2. Sample Size Calculation ................................................................................................20 
7.3. Baseline Assessment .....................................................................................................20 
7.4. Primary Analyses ..........................................................................................................21 
7.5. Missing Data .................................................................................................................22 
7.6. Limitations of the Registry ............................................................................................22 
8. DATA COLLECTION AND DATA MANAGEMENT ...........................................................23 
8.1. Operations .....................................................................................................................23 
8.2. Required Documentation ...............................................................................................23 
8.3. Data Entry .....................................................................................................................23 
8.4. Case Report Form ..........................................................................................................24 
8.5. Patient Files ...................................................................................................................25 
8.6. Record Retention ...........................................................................................................25 
8.7. Quality Assurance, and Inspection by Authorities ........................................................25 
9. ADVERSE EVENT REPORTING AND SERIOUS ADVERSE EVENT 
REPORTING .......................................................................................................................26 
9.1. Definitions .....................................................................................................................27 
9.2. Adverse Event and Serious Adverse Event Recording and Reporting .........................32 
10. ETHICS....................................................................................................................................35 
10.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..................35 
10.1.1. Study Approval ...............................................................................................35 
10.1.2. Amendments to the Protocol ..........................................................................36 
10.2. Ethical Conduct of the Study ......................................................................................36 
10.2.1. Guiding Principles ..........................................................................................36 
10.2.2. Opinion of External Experts and Scientific Boards ........................................37 
10.3. Patient Information and Consent .................................................................................37 
10.4. Patient Identification and Privacy ...............................................................................38 
10.5. Compensation to Patients and Physicians ...................................................................39 
11. COMMUNICATION AND PUBLICATION OF STUDY RESULTS...................................40 
11.1. Communication of Results by Pfizer ..........................................................................40 
11.2. Enrolment and Progress Reports .................................................................................41 
11.3. Annual Analyses and Reporting ..................................................................................41 
11.4. Final Analyses and Reporting .....................................................................................42 

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11.5. Reporting to the EMA .................................................................................................42 
12. REFERENCES ........................................................................................................................43 
LIST OF TABLES 
Table 0-1: Registry Flowchart .........................................................................................................6 
Table 2-1: Opportunistic Infections...............................................................................................11 

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LIST OF ABBREVIATIONS 
ADR
adverse drug reaction 
AE
adverse event
CHMP
Committee for Medicinal Products for Human Use
CRF
case report form
DMARDs
disease-modifying anti-rheumatic drugs
DSU
Drug Safety Unit
EC
Endpoint Committee
EDC
electronic data capture
EIU
exposure in-utero
EMA
European Medicines Agency
EU
European Union
FDA
US Food and Drug Administration
GPP
Good Pharmacoepidemiology Practices
ICF
informed consent form
ICH
International Committee on Harmonisation
IEC
independent ethics committee
ISPE
International Society for Pharmacoepidemiology
JC virus
John Cunningham virus
JIA
juvenile idiopathic arthritis
MedDRA
Medical Dictionary for Regulatory Activities
NICE
National Institute for Health and Clinical Excellence
NRP
national responsible person
PASS
post-authorisation safety study
PSUR
periodic safety update report
PUVA
psoralen ultraviolet A phototherapy
RA
rheumatoid arthritis
RMF
registry master file 
RP
registry physician
RSF
registry site file
SAE
serious adverse event
SAP
statistical analysis plan
SIR
standardized incidence ratio
SSC 
Scientific Steering Committee 
TB
tuberculosis
TNF
tumour necrosis factor
UV
ultraviolet
 
 

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Table 0-1: Registry Flowchart 
Data Collected
Study Interval
Enrolment
Year 1 – Year 2
Year 3 – Year 5a
Baseline
Every 3 months
(± 4 weeks)
Every 6 months
(± 4 weeks)
Visit ID
1
2 – 8
9 – 12
Informed consent/assent
X
Patient/legal representative contact information
X
X
X
Demographics
X
Medical history
X
Co-morbidities
X
X
X
Psoriasis history (including date of diagnosis, 
severity assessment, previous treatments)
X
Etanercept exposure
Xb
X
X
Treatment discontinuation
X
X
Other systemic psoriatic treatmentsb
X
X
X
Prior medications
X
Concomitant medications
X
X
X
Serious and pre-specified opportunistic 
infectionsc
Xb
X
X
Malignanciesc
X
X
X
Other adverse eventsc
X
X
Registry discontinuationd
0--------------------------------------------------X
a.
Patients enrolled after September 2013 may be followed for less than 5 years (i.e., until overall study 
completion in 2018)
b.    For patients being treated with etanercept prior to enrolment, details regarding etanercept dose and regimen, 
other systemic treatments, and serious and pre-specified opportunistic infections occurring since the first 
etanercept dose but before enrolment will be collected via retrospective medical record abstraction.
c.
Patients will be interviewed at the specified timepoints to determine if any of these events have occurred 
since the last evaluation.  However, the registry physician may report an event between evaluations if he 
becomes aware that such an event has occurred.
d.
Patients may discontinue from the registry at any time following enrolment.

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1. INTRODUCTION 
Psoriasis is a chronic, inflammatory, hyperproliferative skin disease with a genetic basis that 
affects approximately 2% of the world’s population.1,2 Dysregulation of T cell 
antigen-presenting cell interactions and over-expression of pro-inflammatory cytokines both 
play a central role in the pathogenesis of psoriatic skin lesions.3 The clinical course is 
unpredictable, but in the majority of cases, psoriasis is a chronic, remitting and relapsing 
disease. Plaque psoriasis presents with characteristic plaque-type lesions, which consist of 
sharply demarcated, dull red scaly plaques, often symmetrically distributed over the body, 
particularly on the extensor surfaces of limbs and on the scalp. 
The true incidence and natural history of paediatric psoriasis is poorly understood. It is 
reported that psoriasis represents 4.1% of all dermatoses seen in children under the age of 16 
in Europe and North America, and that 30% to 45% of affected patients recall signs of 
disease before adolescence.4,5 Data on childhood disease severity and treatment are also 
scarce.  One study reported that ~8% of children had severe disease requiring phototherapy 
or systemic psoriasis therapies.6 Quality of life in children and adolescents with severe 
psoriasis is reduced as the disfiguring consequences may cause severe psychological 
problems.7 The epidemiology and natural history of psoriasis is better understood in adults, 
for which treatment algorithms and clinical guidelines exist.8,9 In contrast, little is known 
about the disease in paediatric populations and we identified no treatment guidelines for 
paediatric psoriasis. A safe and efficacious treatment option for paediatric psoriasis patients 
with moderate-to-severe disease is thus an unmet medical need. 
Current first-line therapies for plaque psoriasis include emollients, salicylic acid, topical 
corticosteroids, vitamin D analogues (for children ≥ 6 years), coal tar, dithranol and 
tazarotene (a topical retinoid). Calcipotriene and corticosteroid formulations are approved for 
the treatment of mild to moderate plaque psoriasis but may be inadequate in the treatment of 
moderate to severe psoriasis. Narrow band ultraviolet (UV) B phototherapy or a 
psoralen/ultraviolet A (PUVA) combination is limited in children because of concerns of 
carcinogenicity and premature aging. PUVA is used in adolescents only when absolutely 
necessary, but remains contraindicated in young children. Additionally, light therapies 
require frequent office visits, interfering with school and work schedules. Systemic 
treatments used for severe forms of plaque psoriasis that are resistant to other therapies 
include acitretin, cyclosporin, methotrexate, and biological therapies, such as adalimumab, 
alefacept, efalizumab, infliximab, not all of which are indicated for use in children. 

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1.1. Background and Rationale 
Etanercept is a soluble tumour necrosis factor (TNF) receptor fusion protein previously 
indicated for the treatment of moderately to severe active rheumatoid arthritis, psoriatic 
arthritis, ankylosing spondylitis and plaque psoriasis in adults, as well as polyarticular 
juvenile idiopathic arthritis (JIA) (refer to Enbrel Summary of Product Characteristics, 
accessible at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Summary_for_the_public/human/000262/WC500027364.pdf). In November 1998, the US 
Food and Drug Administration (FDA) first approved etanercept for use in adults to reduce 
signs and symptoms of moderate to severe active rheumatoid arthritis (RA), in patients with 
an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). 
Etanercept was subsequently approved for the treatment of moderate to severe JIA in 
children and adolescents (4-17 years of age) intolerant or responding inadequately to 
methotrexate. In patients with JIA, etanercept has also shown a favourable long-term safety 
profile, as repeated etanercept treatment (0.4 mg/kg twice weekly) for up to 8 years did not 
reveal an increase in serious adverse events.10,11 Etanercept has shown a favourable 
risk-benefit profile in adults treated for moderate to severe plaque psoriasis and in patients as 
young as four years of age with JIA. 
As a consequence of clinical and post-marketing experience across indications, in both adult 
and paediatric populations, and with similar products, current U.S. product labelling for 
etanercept includes a black box warning addressing the risk of serious infections that may 
lead to hospitalisation or death, including tuberculosis and bacterial sepsis. Due to the 
mechanism of action, TNF blockade, and the role of TNF in normal immune and 
inflammatory response function, it is not surprising that the potential for an increased risk for 
opportunistic and/or serious infections is an ongoing safety concern. In addition, the activity
of TNF in preclinical models and potentially in humans theoretically raises the possibility 
that inhibition of this cytokine might potentiate the clinical risk of malignancy; however, 
clinical data regarding the risk of both lymphomas and solid tumours associated with the use 
of etanercept and related compounds have been inconsistent. The interpretation of 
malignancy risk is complicated by the fact that patients treated with etanercept (and other 
TNF inhibitors) may have an inherent predisposition to malignancy based upon their 
underlying disease and often receive other medications concomitantly, such as 
cyclophosphamide, that independently increase the risk of malignancy. 
A recent Phase 3 clinical study was performed in support of adding an indication for 
moderate to severe plaque psoriasis in children and adolescents. The study reported 
statistically significant improvement in disease severity but was limited, by design, to 
short-term safety outcomes.12 This 48 week randomised, placebo-controlled trial of the safety 
and efficacy of etanercept included 211 patients with moderate to severe plaque psoriasis 
between 4 and 17 years of age. During the first 12 weeks of the trial, patients received once 

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weekly injections of either placebo or 0.8mg/kg of etanercept, followed by an extension in 
which all patients received etanercept for 24 consecutive weeks.  At week 36, 138 of the 
patients were randomised to receive placebo or etanercept to investigate the effects of 
stopping and re-starting treatment. The study showed that at 12 weeks, 57% of patients 
achieved 75% improvement in the psoriasis area-and-severity index compared with 11% of 
the patients receiving placebo. After 36 weeks, 68% of etanercept patients achieved 
improvement.  Etanercept was well tolerated, and rates of infectious and non-infectious 
adverse events were comparable in the treatment and placebo arms. During the 
placebo-controlled stage of the study, there were no SAEs.  Four SAEs including three severe 
infections (gastroenteritis, gastroenteritis-associated dehydration, and pneumonia) occurred 
during open-label treatment of three patients. All events resolved without sequels.  Although 
no malignancies, opportunistic infections or cases of tuberculosis were reported during the 
study, it is also recognised that longer term data are required to better understand the risk of 
malignancy, the risk of serious infection, and other as yet unidentified events associated with
potentially chronic use. It is expected that as etanercept is not curative, patients will receive 
repeat courses when disease flares occur. The risks associated with this type of chronic 
repetitive administration in children and adolescents with plaque psoriasis are not fully 
understood. 
Following a positive recommendation from the CHMP in November 2008, on 22 December 
2008 the European Commission extended marketing authorisation of the use of etanercept for 
treatment of chronic severe plaque psoriasis in children and adolescents (8-17 years of age) 
who are inadequately controlled by, or are intolerant to, other systemic therapies or 
phototherapies. In August 2011, Commission approval was received for expansion of the 
paediatric plaque psoriasis indication to include patients from the age of 6 years.   
This registry constitutes a post-authorisation safety study (PASS) and is a condition of 
marketing authorization, to be conducted in compliance with Volume 9A of The Rules 
Governing Medicinal Products in the European Union (EU) (Guidelines on 
Pharmacovigilance of Medical Products for Human Use) and is intended to provide 
information regarding the long-term safety of etanercept use in paediatric patients with 
plaque psoriasis, as well as information regarding the use of etanercept in routine clinical 
practice.
2. STUDY OBJECTIVES AND ENDPOINTS 
The objectives of this study are to: 
Describe the risk of serious and pre-specified opportunistic infections (including 
tuberculosis) associated with current or recent treatment with etanercept in paediatric 
plaque psoriasis; 

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Describe the long-term risk of incident malignancy in paediatric plaque psoriasis 
patients who have ever received etanercept; 
Identify any new, serious potentially unrecognised adverse drug reactions (ADRs) by 
collecting serious adverse event data in this population; and
Assess effectiveness by describing patterns of treatment with etanercept, including 
premature discontinuation of etanercept and subsequent treatment with systemic 
therapies (including re-treatment with etanercept). 
2.1. Endpoints 
2.1.1. Safety Endpoints 
Any patient who receives at least one dose of etanercept will be included in the evaluation for 
safety. Whenever a patient or parent/legal representative reports an event of interest directly 
to site staff or CRO registry staff, the registry physician (RP) will be contacted and asked to 
review records and confirm the occurrence and characteristics of the event. If needed, the RP 
will obtain records from other health care providers who may have treated the event of 
interest. 
2.1.1.1. Serious and Opportunistic Infections 
Serious infections 
Serious infections are defined as any infections that are life-threatening or result in disability, 
and infections requiring intravenous antibiotic treatment and/or hospitalisation. Nosocomial 
infections that are included in the above definition will be categorized as such for purposes of 
analysis. 
Opportunistic infections 
Opportunistic infections of interest (i.e., pre-specified opportunistic infections) include the 
following listed infections and pathogens in Table 2-1.

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Table 2-1: Opportunistic Infections 
Bacterial
Fungal
Protozoan
Viral
Salmonella bacteraemia
Aspergillus sp. 
(Aspergillosis)
Cryptosporidiosis
Cytomegalovirus
Campylobacteriosis
Invasive Candida albicans 
Isosporiasis
Shigellosis
Coccidioidomycosis
Microsporidiosis
JC Virus (progressive 
multifocal 
leukoencephalopathy)
Mycobacterium 
tuberculosis
Cryptococcosis
Disseminated  or central 
nervous system herpes 
zoster
Mycobacterium avium 
Histoplasmosis
Acanthamoebiasis
Kaposi’s sarcoma 
(herpesvirus 8)
Mycobacterium kansasii 
Blastomycosis
Toxoplasmosis
BK virus
Syphilis/neurosyphilis
Paracoccidioidomycosis
Trypanosomiasis 
(Chagas disease)
Pseudomonas aeruginosa 
Sporotrichosis
Leishmaniasis
Acinetobacter baumannii
Penicilliosis
Listeriosis
Zygomycosis
Nocardiosis
Pneumocystosis
Legionellosis
Actinomycosis
Bartonellosis
2.1.1.2. Malignancies 
If a malignancy occurs, the registry will collect reports of all solid malignant tumours, 
including non-melanoma skin cancers, and malignant tumours of haematopoietic and 
lymphoid tissues. In order to meet the case definition for malignancy, a pathology report or a 
physician’s notation of specific tumour histology will be required.
2.1.1.3. Other SAEs and AEs 
Reports of all other SAEs and non-serious AEs that occur during follow-up will be collected 
and described.
2.1.2. Effectiveness Endpoints 
The primary focus of this registry is safety; it will not directly measure effectiveness 
endpoints. However, to the extent possible effectiveness (or lack of effectiveness) will be 

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inferred from patterns of treatment and re-treatment. The recommended course of etanercept 
treatment for paediatric psoriasis is for 24 weeks; physicians are advised to consider 
discontinuation of etanercept if a satisfactory response is not achieved by 12 weeks. If a 
patient receives etanercept for less than 24 weeks, the RP will be asked to report the reason 
for early discontinuation of therapy whether for positive (e.g., clearing of plaque psoriasis) or 
negative reasons (e.g., intolerance, adverse event, less than expected therapeutic effect). 
Treatment discontinuation for lack of desired therapeutic effect will, for purposes of analysis, 
serve as a proxy for treatment effectiveness. 
As etanercept is not a cure for this chronic condition, patients will likely require repeated 
courses of etanercept over time. For each subsequent course of etanercept, occurrence and 
reasons for premature discontinuation, i.e., less than 24 weeks, will be documented. If a 
subsequent course of systemic therapy does not include etanercept, the reason for that 
decision will also be documented. 
2.2. Concomitant Medications 
Treating physicians will report information regarding use of medications and other treatment, 
including topical medications, and other immunosuppressant and immune-modulator 
medications. 
The following information on other psoriasis treatments and concomitant medications will be 
included: 
Type of treatment (e.g., PUVA) or medication name 
Status of exposure to medication (i.e. current treatment, past treatment) 
Dose and duration of exposure 
Indication for use 
3. STUDY DESIGN 
This product registry is a multi-centre, long-term, prospective, observational, cohort study 
conducted to evaluate the long-term safety and effectiveness of etanercept prescribed by 
dermatologists to children for the treatment of plaque psoriasis. This registry constitutes a 
PASS and is a condition of marketing authorization, to be conducted in compliance with 
Volume 9A of The Rules Governing Medicinal Products in the European Union (EU) 
(Guidelines on Pharmacovigilance of Medical Products for Human Use). 
It is estimated that during the first 4 years following approval for treatment of plaque 
psoriasis in patients aged 8 through 17, etanercept will be prescribed for approximately 250 
patients throughout Europe.  The registry will target recruitment of 60 to 80 patients.

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The study will be performed by the CRO, with oversight of a project-specific Scientific 
Steering Committee (SSC), (refer to Section 10.2.2) and with guidance, input, review and 
approval by the Pfizer paediatric psoriasis registry project team. 
4. STUDY POPULATION 
4.1. Registry Enrolment 
4.1.1. Geographical Scope of Registry 
Paediatric plaque psoriasis is a rare disease for which actual prevalence data are sparse.  In 
order to optimize registry enrolment and reach recruitment goals, systematic selection of 
participating EU countries and dermatology clinics will be guided primarily by the following 
criteria: 
Country-specific prevalence of psoriasis (this may be suggested by clinical sites 
within the country that already participate in an adult psoriasis registry); 
Local availability of etanercept for use in paediatric plaque psoriasis; 
High market penetration of etanercept in the country for other indications, including 
adult plaque psoriasis. While this will not guarantee use among dermatologists for 
paediatric plaque psoriasis, we believe physicians with familiarity with etanercept are 
more likely to prescribe it for this indication. 
Due to the low prevalence of the disease in the paediatric population and the inability to 
predict the uptake of the product immediately after approval, committing to specific 
countries and sites is impractical at this time. It is currently estimated that a total of 11-15 EU 
countries and up to 100 dermatology clinics will be included; however, the number of 
countries and sites may be adjusted in order to meet enrolment objectives. 
Upon selection of each country, the Sponsor will notify the respective National Responsible 
Person (NRP) and the EMA. 
4.1.2. Physician Enrolment 
The Sponsor will recruit dermatologists within the selected EU countries who are likely to 
treat patients eligible for the registry such as those treating paediatric patients and those 
known to prescribe etanercept for adult plaque psoriasis. The enrolled physicians are 
hereafter referred to as “registry physicians” or RPs.
4.1.3. Patient Enrolment 
All paediatric patients undergoing treatment at any of the registry sites who meet the 
inclusion and exclusion criteria detailed above (see Section 4.2 and 4.3) may be included in 
the registry. Sites will be required to maintain a patient enrolment log of eligible patients at 
each treatment centre. This log will document how patients came to be included or excluded 

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from the registry, including patients identified by the site as initiating etanercept prior to 
registry enrolment, in order to assess the representativeness of the registry population. 
Patients treated with etanercept for plaque psoriasis but permanently discontinuing therapy 
prior to site participation in the registry are not eligible for inclusion. 
An independent ethics committee (IEC) must review and approve the protocol, informed 
consent form (ICF) and paediatric assent forms before any patients are enrolled.  Each patient 
and parent/legal representative must participate in the informed consent process and sign and 
date an ICF for this protocol before any data are collected and made accessible to the 
Sponsor.  As required by local regulations, investigators will obtain paediatric assent. 
Throughout this document, the requirements for informed consent also apply to assent. The 
registry will require that documentation of informed consent and assent be recorded in the 
source documents for each patient.
It is anticipated that in most, if not all, countries in which the registry will be conducted the 
following requirements for inclusion of paediatric patients will apply: 
Patients < 7 years of age: written parental consent only to participate 
Patients age 7 and ≤ 17: written parental consent and paediatric assent to participate
These requirements must be adjusted by country and site to comply fully with local 
regulations and ethics committee requirements, as needed, such as in countries where older 
adolescents (e.g., > 15 years) are expected to provide written informed consent similar to
adults, rather than assent. In some EU Member States, written informed consent from both
parents may be required. If a paediatric patient reaches 18 years of age during registry 
follow-up, he/she will be asked to sign the current IEC-approved ICF at that time. 
4.2. Inclusion Criteria 
To be eligible for registry enrolment, patients must meet all of the following criteria: 
Age ≤ 17 years at time of administration of the first dose of etanercept
Diagnosis of plaque psoriasis by a dermatologist 
Prior to enrolment, a clinical decision has been made to prescribe etanercept for the 
treatment of psoriasis 
Newly prescribed with initial etanercept or actively being treated with etanercept, 
regardless of length of treatment prior to study enrolment 
Capable and willing to provide paediatric assent, or written informed consent when 
applicable, and 
Parent(s)/legal representative of patient is capable and willing to provide written 
informed consent 

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Evidence of a personally signed and dated informed consent document indicating that 
the patient (or a legally acceptable representative) has been informed of all pertinent 
aspects of the study must exist. 
Please note:  Currently etanercept is approved for the treatment of severe plaque psoriasis in 
children and adolescents from the age of 6 years who are inadequately controlled by, or are 
intolerant to, other systemic therapies or phototherapies.  The registry protocol will not 
encourage use of etanercept at younger ages.  However if a doctor, in collaboration with the 
child’s parents, makes the independent clinical decision to prescribe etanercept to a child less 
than 6 years of age for severe plaque psoriasis, that child may be included in the registry. 
4.3. Exclusion Criteria 
Patients are not eligible for this registry if they meet any of the following criteria: 
Prior therapy with any biologic agent other than etanercept 
History of malignancy 
Unlikely to complete a minimum of two years of follow-up, based on physician’s 
judgment (i.e., social issues, family illness, plan to move out of area, living too far 
from the physician’s office to adhere to standard of care visit schedule)
Participation in any study involving any experimental drug or device within the last 
30 days or 5 elimination half-lives, whichever is greater 
Other severe acute or chronic medical or psychiatric condition or laboratory 
abnormality that may increase the risk associated with study participation or may 
interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the patient inappropriate for entry into this study. 
5. STUDY TREATMENT AND DURATION
There will be no dispensing of any study medication or protocol-specified procedures 
associated with participation in this registry. All medical treatment, including medications, is 
solely at the discretion of the treating physician in accordance with their usual care. 
The total duration of the registry is approximately 9 years, including approximately 4 to 5
years for patient enrolment and 4 to 5 additional years for follow-up on all enrolled patients. 
Dermatologists will enrol eligible patients who are current users of etanercept at any time 
after they initiate such treatment for plaque psoriasis. The Sponsor expects to enrol the first 
patient in Q4 2010, with all follow-up to be completed in 2018. Follow-up will occur every 3 
months during the first 2 years of the study and every 6 months thereafter (year 3 through the 
end of participation). Each patient is expected to participate for 5 years, or until the registry is 
completed in 2018, whichever comes first.    

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6. STUDY PROCEDURES  
6.1. Schedule of Assessments 
For the purpose of routine clinical care of chronic psoriasis, it is anticipated that follow-up 
with the treating physician will occur at least once every 3 months for the first two years after 
receiving the first dose of etanercept at which time RPs will collect follow up data.  
Alternatively, the patient and the parent/legal representative may be contacted by phone.  
Thereafter, data collection will take place every 6 months (also in conjunction with routine 
clinical visits) from year 3 through the end of follow-up, as shown in the registry flowchart.  
The registry will allow a window of ± 4 weeks around the date of the scheduled data 
collection. Infections, malignancies, SAEs, etanercept discontinuations and registry 
discontinuations may be reported at any time during follow-up. 
At each scheduled data collection point, the RP will record information on the registry 
outcomes of interest, comorbid medical conditions, medication use, and SAEs.  In order to 
maximise retention and capture relevant data, a highly structured approach to managing 
follow-up is planned. Centralised registry resources will proactively contact sites (quarterly 
during the first 2 years, semi-annually thereafter) in advance of scheduled data collection 
times to remind the RP to collect and report study data.  At that time, registry staff will 
update contact information regarding the patients and their physicians. If data has not been 
received within the expected timeframe, CRO will contact sites several times following the 
original due date. They will make every reasonable effort (including direct-to-patient calls) to 
obtain this data before considering a patient lost to follow-up.  For each site, the electronic 
data capture (EDC) system will also provide active, up-to-date workflow reports alerting 
them to upcoming and overdue timepoints. 
If, during the study period, the enrolled site is not actively following the patient, CRO will 
provide the enrolled site with the contact information for the patient’s primary health care 
provider (or other treating physician) and a standard form letter (with a paper copy of the 
questionnaire) that the site can fax/mail to the physician requesting the follow-up information 
on behalf of the registry.  The patient’s treating physician will be asked to complete the 
questionnaires and return them to CRO for data entry. 
6.2. Data Collection 
Data collection is designed to minimise the burden on the participating RPs and patients, and 
maximise retention.  Electronic case report form for data entry, are designed to elicit the 
specific desired data points. 
Data will be collected from the following sources: 

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Prospective data provided by the treating physicians (this may be multiple physicians 
including the prescribing dermatologist or RP, and other physicians responsible for 
the patient’s care over the course of the study);
Prospective data collected from patient interviews during the less frequent follow-up 
phase of the study. 
Retrospective data collected by medical record abstraction  
The RP will provide information on current prescriptions and status of each registry patient at 
enrolment and at each scheduled follow-up assessment.  Following enrolment in the registry, 
the RP will also provide information by retrieving medical record information at his/her own 
institution and other health care settings, as appropriate. Some patients may be undergoing 
active treatment with etanercept at the time of registry enrolment, and the lag between 
initiating etanercept treatment and active data collection as part of the registry will 
necessitate the abstraction of relevant safety-related and treatment pattern information from 
the medical record. The number of patients meeting this criterion is expected to be limited.
6.2.1. Baseline Visit 
During the enrolment visit, the site will be instructed to obtain additional information 
regarding the patient, including secondary contact information and contact information for 
the patient’s primary health care provider.
The following information will be collected: 
1. Date of informed consent(s)/assent 
2. Patient/legal representative contact information, including secondary contacts and 
primary health care provider details, if different than RP 
3. Demography [age, gender, weight, race/ethnicity (where allowed by local regulation)] 
4. Medical history/co-morbid medical conditions 
5. Plaque psoriasis history 
a.
Physician’s global subjective assessment of disease severity (four-point scale) 
b. Prior treatments or therapies, including topical agents and immunosuppressive 
therapies and the patient’s response to each.
6. Etanercept Treatment 
a.
Initial prescribed etanercept treatment regimen 
b. Date of first dose 
7. Concomitant medications, including immunosuppressants 
8. Retrospective medical record abstraction for patients with historical treatment with 
etanercept will also include: 
a.
Etanercept dosing history 
b. Use of additional systemic therapies since starting etanercept 
c.
Occurrence of serious and/or pre-specified opportunistic infections and SAEs

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Note: Due to the significance of the AEs of interest (serious and opportunistic infections and 
malignancies), it is considered highly likely that these events, if they occurred, would be 
documented in the medical record of the prescribing RP. Retrospective data for other SAEs 
overall, however, may not be consistently recorded; therefore, all retrospective SAEs will be 
collected but analysed separately. 
6.2.2. Follow-up Visit 
FOLLOW-UP: YEAR 1 THROUGH 2 
Regardless of the duration of etanercept exposure at the time of registry enrolment, all 
patients will be followed prospectively using the same schedule. During follow-up, the RP or 
other trained site staff will collect data during routine clinical visits. Routine clinical visits 
may not coincide with registry timepoints; therefore alternatively, the RP, trained site staff or 
CRO registry staff may administer follow-up questionnaires via phone interviews. 
The following data will be collected every 3 months (± 4 weeks) during the first 2 years of 
participation: 
1. Updated informed consent information (e.g., if patient turns 18 since last follow-up) 
2. Updated contact information 
3. Status of etanercept exposure (ongoing/completed/discontinued/reason for 
discontinuation) 
4. Requirement for additional psoriasis treatment 
a.
Continued etanercept  
b. Other systemic treatments 
c.
Use of topical agents 
d. Reason for treatment decision 
5. Physician’s global subjective assessment of plaque psoriasis severity
6. Changes in medical status, including new onset comorbid medical conditions 
7. Changes/additions to concomitant medications 
8. AEs as described in Section 2.1.1, Safety Endpoints 
a.
Serious and pre-specified opportunistic infections 
b. Malignancies 
c.
Other AEs 
FOLLOW-UP: YEAR 3 THROUGH YEAR 5/END OF FOLLOW-UP 
The following data will be collected every 6 months (± 4 weeks) during year 3 through the 
end of participation: 
1. Updated informed consent information (e.g., if patient turns 18 since last follow-up) 

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2. Updated contact information 
3. Status of etanercept exposure (ongoing/completed/discontinued/reason for 
discontinuation) 
4. Requirement for additional psoriasis treatment 
a.
Continued etanercept  
b. Other systemic treatments 
c.
Use of topical agents 
d. Reason for treatment decision 
5. Physician’s global subjective assessment of plaque psoriasis severity
6. Changes in medical status, including new onset comorbid medical conditions 
7. Changes/additions to concomitant medications 
8. AEs as described in Section 2.1.1, Safety Endpoints 
a.
Serious or pre-specified opportunistic infections 
b. Malignancies 
c.
Other AEs 
6.2.3. Patient Withdrawal 
Patients may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioural, 
or administrative reasons. Patients and/or their respective parents/legal representatives if 
minors have the right to withdraw from the registry at any time, without prejudice, and are 
not obligated to state their reasons for registry discontinuation. If a patient or parent/legal 
representative declares his or her wish to discontinue from the registry, the RP will complete 
a discontinuation CRF. All reasonable efforts will be made to establish whether the reason 
for discontinuation was related to a registry outcome of interest or other adverse event. The 
Sponsor reserves the right to suspend or terminate the registry or part of the registry at any 
time for any reason. 
Before considering a patient lost to follow-up, the RP/site staff will make all reasonable 
attempts to contact the patient or the parent/legal representative to ensure that a registry 
outcome of interest is not the underlying reason for the inability to contact the patient.  For 
each missed scheduled encounter with the RP, several attempts to reach the patient by phone, 
e-mail and post will be made with a minimum of three attempts and a period of 
approximately one week between attempts. If no response is received within a month of the 
follow-up timepoint, CRO registry staff will contact any other known healthcare providers to 
determine if the reason for failure to respond is health-related, and to determine the health 
status of the patient. If CRO is unable to obtain the follow-up data from the RP or other 
provider(s), they will contact the secondary patient contact to obtain vital status. The 
informed consent process and forms will describe these procedures, including the possibility 

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of contacting the patient’s non-RP health care providers. Data collected prior to loss to 
follow-up will be included in all analyses.
If the patient withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected. The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
7. DATA ANALYSIS/STATISTICAL METHODS 
The purpose of the registry is to assess the long-term safety of etanercept in paediatric 
patients with plaque psoriasis and to infer effectiveness by describing the pattern of treatment 
of psoriasis in this population. 
7.1.  General considerations 
All AE verbatim terms will be recorded and coded using MedDRA. Statistical analysis of all 
data will be performed using SAS® statistical software (SAS Institute, Cary, NC, USA). 
Frequencies of defined outcomes will be described. If possible, analyses will also be 
performed using the different etanercept treatment status (i.e., current/recent versus past 
treatment) and etanercept cumulative dose exposure groups. 
Analysis of the characteristics of patients enrolled in the registry and of those who did not 
consent to participate (to the extent feasible) will help evaluate whether there are any 
differences between registry enrolees and non-respondents, i.e., generalizability. 
Primary analyses will be limited to prospective data, i.e., events reported during participation 
in the registry. Serious and pre-specified opportunistic infections and malignancies reported 
as part of retrospective data collection will be summarized separately.  
7.2. Sample Size Calculation  
No formal sample size calculation will be used to manage enrolment in the study since the 
goal is to obtain participation by all eligible patients. Current available data are insufficient to 
project population based estimates of paediatric patients with severe psoriasis treated with 
conventional systemic therapy who are not well-controlled and may warrant further 
intervention such as that potentially afforded by etanercept. 
7.3. Baseline Assessment 
The demographic and clinical profile of the registry population will be described using 
baseline data.  Patient demographics, psoriasis severity, history of psoriasis and psoriasis 
treatment(s) prior to first etanercept administration will be summarized. Data will be 

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summarized overall and by status at enrolment to explore whether the patients treated prior to 
registry enrolment are different than the overall population. 
Continuous variables (e.g., age) will be reported as means and standard deviations.  
Categorical variables (e.g., gender) will be summarized as number and percentage (%) of the 
total registry population. 
7.4. Primary Analyses 
It is anticipated that the etanercept treatment status for each patient will change throughout 
follow-up.  A standard course of etanercept treatment is expected to last 24 weeks. Patients 
successfully responding to the first etanercept treatment course may be exposed to 
subsequent treatment (i.e., when patients experience a flare) and the time window between 
two (or more) consecutive courses of treatment may vary substantially. 
Patterns of treatment with etanercept will be described (to the extent possible) as follows: 
Frequency of premature discontinuation of etanercept (i.e., treatment course < 24 
weeks) 
Frequency of subsequent treatment with systemic therapies (including re-treatment 
with etanercept) 
Intervals between etanercept treatment and subsequent course of systemic therapy 
(including etanercept) 
Means and percentages of demographic and disease characteristics of patients who
experience and those who do not experience discontinuation of etanercept 
Frequency of discontinuation stratified by cumulative dose, duration of use, and other 
etanercept use patterns. 
Serious and Pre-specified Opportunistic Infections 
Time at risk of serious and pre-specified opportunistic infections will correspond to 
current/recent treatment with etanercept.  Current/recent etanercept treatment will be defined 
as time between the dates of first and last dose within a treatment course plus 28 days. Risk 
will be estimated as number of events over cumulative time at risk. Estimates of relative risk 
of these infections will be used to quantify any association between the study outcomes and 
current/recent treatment with etanercept. In order to calculate relative risk, incidence of 
infection during cumulative current/recent treatment with etanercept will be compared to 
incidence of infection during cumulative period without use of etanercept. 
Should any patient develop tuberculosis (TB) during the course of follow-up, the Sponsor 
will conduct standardised incidence ratio (SIR) analyses using geographically appropriate 
population based rates of TB applied to time at risk on etanercept. 
Analyses may include more than one episode of infection experienced by a single individual. 
Stratified analyses of the events of interest by etanercept dose, duration of treatment, and 

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number of treatment course (i.e., first, second, etc.) will be attempted, depending on the 
number of events reported. 
Malignancies 
Time at risk of incident malignancies will be defined as time since the date of first dose of 
etanercept treatment to the date of malignancy diagnosis or end of follow-up if no 
malignancy has been diagnosed. Long-term risk of incident malignancy in patients who have 
ever received etanercept will be estimated as number of events over the total time at risk.  
Should any patient develop cancer during follow-up, the Sponsor will calculate SIRs for 
malignancy (age and gender-adjusted) using geographically appropriate population-based 
norms. Although all malignancies reported throughout the study will be described, only the 
first diagnosis of malignancy occurring during the follow-up will be considered in the SIR 
analysis. 
Other SAEs 
Time at risk of all other SAEs will correspond to current/recent treatment with etanercept. 
Current/recent etanercept treatment will be defined as time between the dates of first and last 
dose within a treatment course plus 28 days. 
A descriptive analysis of SAEs will be conducted.  Any grouping and stratification will be 
dependent on the number and type of events reported. 
7.5. Missing Data 
Several attempts will be made to contact patients and to limit missing data. Some imputation 
(e.g., in order to estimate minimum and maximum exposure) may be required. Details on 
handling of missing data will be included in the statistical analysis plan (SAP). 
7.6. Limitations of the Registry 
The planned registry offers as strengths the long-term follow-up during and after treatment 
with etanercept in a population of paediatric psoriasis patients in the EU. Such a setting will 
allow fulfilment of the objectives of this registry. However, the registry also carries some 
limitations. As in any registry, lack of an internal ‘untreated’ contemporaneous comparator 
group may pose some challenges for the interpretation of data. In the evaluation of the risk of 
serious and pre-specified opportunistic infections, an attempt will be made to make 
comparisons within the registry population based on current/recent treatment and periods 
without etanercept treatment. However, such an approach is unfeasible when assessing risk 
of malignancies and appropriate external comparator groups will be needed to aid in the 
interpretation of the registry data. Generalizability of the results may be limited by the 
characteristics of the population that voluntarily enrol in the registry. Attempts will be made 

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to characterize and compare patients who refuse to participate with patients who agree to 
enrol in the registry. 
The registry will include patients who initiated etanercept prior to enrolment into the registry. 
There is the possibility that these patients, who must be considered actively treated at the 
time of enrolment, are substantively different than other patients who were prescribed 
etanercept at the same time, but did not tolerate therapy or experienced one or more relevant 
SAEs, potentially resulting in a differential depletion of susceptible (i.e., the effect whereby 
patients who remain on treatment are those who can tolerate them while those who are 
susceptible select themselves out of the population at risk). This could lead to an 
underestimation, or dilution, of the estimated risk of developing an adverse event associated 
with etanercept in the population with retrospective data collection.  
Generalizability of the results may be limited by the characteristics of the population that 
voluntarily enrol in the registry. Attempts will be made to characterize and compare patients 
who refuse to participate with patients who agree to enrol in the registry. 
8. DATA COLLECTION AND DATA MANAGEMENT 
8.1. Operations 
Each participating site will receive appropriate training, which describes all processes that 
the RP or representative must understand.  The information will outline all processes required 
for a clinic to become a registry site, enrolling patients, providing follow-up data on enrolled 
patients, maintaining registry documents or files, reporting adverse events and closing the 
registry. All site staff who participates in enrolling patients, collecting or entering data for the 
registry will be required to undergo appropriate training. 
8.2. Required Documentation 
The RP must provide the Sponsor with the following regulatory documents before enrolling 
any patients: 
Current signed and dated curricula vitae for the RP and site staff having significant 
responsibility (i.e., those related to determination of eligibility or safety) 
Copy of the IEC approval letter for the protocol and informed consent.  All written 
information provided to the patient must be approved by the IEC 
Copy of the IEC-approved informed consent document to be used
Copy of the protocol sign-off page signed by the investigator 
Fully executed site agreement 
8.3. Data Entry 
All data will be collected and entered by the RP/participating sites directly into the EDC 
system. All sites will be fully trained on using the on-line data capture system, including 

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eCRF completion guidelines and help files.  Sites will have the ability to add a new record, to 
search for and modify existing records, to search for patients for whom follow-up is due, to 
identify records with outstanding queries and to identify records that require signatures. 
Data collected by the RP, including data collected from interview of patients or their 
parents/legal representative will be entered into a validated database. All data entry will be 
conducted so that errors in data completeness, data validity, and data consistency are 
minimized. It is the RP’s responsibility to ensure the accuracy of the data provided to the 
registry by any site staff that is trained for registry data collection. 
On a regular basis, when analysis is planned and after quality assurance procedures have 
been completed, the database will be frozen and a dataset created so that no further changes 
take place and analysis can be implemented. 
8.4. Case Report Form 
As used in this protocol, the term case report form (CRF) should be understood to refer to 
either a paper form or an electronic data record or both, depending on the data collection 
method used in this study.  
A CRF should be completed for each included patient.  The completed original CRFs are the 
sole property of Pfizer and should not be made available in any form to third parties, except 
for authorized representatives of Pfizer or appropriate regulatory authorities, without written 
permission from Pfizer. 
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic / original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs is true. Any corrections to entries made in the CRFs, source 
documents must be dated, initialled and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital's or the physician's patient chart.  In 
these cases, data collected on the CRFs must match the data in those charts.  
In some cases, the CRF, or part of the CRF, may also serve as source documents. In these 
cases, a document should be available at the investigator’s site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document. 

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8.5. Patient Files 
The RP and trained staff at the registry sites will maintain files on each enrolled patient. In 
addition, all original source documentation is expected to be stored at the site for the longest 
possible time required by local applicable regulations. The RP will be instructed to notify 
Pfizer before any destruction of medical records of registry participants. If an RP becomes 
involved in follow-up with other clinicians, the associated documentation provided by other 
clinicians will be maintained in the patient’s registry file at the site.
8.6. Record Retention 
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating patients (sufficient 
information to link records, e.g., CRFs and hospital records), all original signed informed 
consent forms, copies of all CRFs, serious adverse event forms, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (e.g., letters, meeting minutes, telephone calls reports). The records should 
be retained by the investigator according to local regulations, or as specified in the Clinical 
Study Agreement, whichever is longer.  
The RP at each registry site will receive a registry site file (RSF) upon initiation of the 
Registry. This RSF will contain all documents necessary for the conduct of the registry and 
will be updated and completed throughout the study. The RSF must be available for review 
in the event the site is selected for monitoring, audits, or inspections and must be safely 
archived for at least 5 years after the completion the registry.  Documents to be archived 
include the patient enrolment log and the signed patient ICFs. In the event that archiving of 
the RSF is no longer possible at the site, the RP will be instructed to notify Pfizer. 
The study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer. The 
investigator must obtain Pfizer's written permission before disposing of any records, even if 
retention requirements have been met. 
8.7. Quality Assurance, and Inspection by Authorities 
The registry database will be housed at the CRO in a physically and logically secure 
computer system maintained by the CRO in accordance with its written security policy. The 
system meets approved established standards for the security of health information and is 
validated. The system also meets the standards of the International Committee on 
Harmonisation (ICH) guideline E6R1 regarding electronic study data handling and is 
available for audit upon request. Patient confidentiality will be strictly maintained. 
The protocol, each step of the data capture procedure, and the handling of the data, as well as 
the eventual registry report, is subject to independent clinical quality assurance audits. Audits 

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may be conducted by the Sponsor, or its designated organization, at any time during or after 
registry initiation to ensure the validity and integrity of the registry data. In addition, the 
Registry may be inspected by health authorities. 
9. ADVERSE EVENT REPORTING AND SERIOUS ADVERSE EVENT 
REPORTING 
ADVERSE EVENTS 
All observed or volunteered adverse events regardless of treatment group (if applicable) or 
suspected causal relationship to etanercept will be recorded on the adverse event page(s) of 
the case report form (CRF) as follows.  
For all adverse events, the investigator must pursue and obtain information adequate both to 
determine the outcome of the adverse event and to assess whether it meets the criteria for 
classification as a serious adverse event (see section "Serious Adverse Events”) requiring 
immediate notification to Pfizer or a Pfizer-designated representative.  For all adverse events, 
sufficient information should be obtained by the investigator to determine the causality of the 
adverse event.  The investigator is required to assess causality. For adverse events with a 
causal relationship to etanercept, follow-up by the investigator is required until the event or 
its sequels resolve or stabilize at a level acceptable to the investigator, and Pfizer concurs 
with that assessment. 
All AEs must be evaluated by the site and assessed for seriousness, as defined below in 
Section 9.1.
REPORTING PERIOD 
All reportable serious and non-serious AEs directly observed or reported by the patient or 
caregiver to the physician or other site personnel, from the time of enrolment (i.e., informed 
consent has been obtained and the patient has received at least one dose of etanercept) 
through patient discontinuation from the registry, end of the observation period, or 28 days 
after the last dose of etanercept, whichever is later, will be assessed and recorded, if 
applicable, within the CRF. If a patient was administered etanercept on the last day of the 
observation period, then the reporting period should be extended for 28 calendar days 
following the end of observation. The site will record the diagnosis, if available. If no 
diagnosis is available, the site will be instructed to record each sign and symptom as an 
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If the investigator becomes aware of a SAE occurring at any time after completion of the 
study and s/he considers the SAE to be related to etanercept, the SAE also must be reported 
to Pfizer Safety.  
Specific AE data (i.e., serious infections, pre-specified opportunistic infections, and 
malignancies) will be obtained at scheduled or unscheduled interviews based on information 
provided spontaneously by the patient (or parent) and/or by thorough questioning of the 
patient (or parent).  To elicit reports of these events, each interview will begin with simple 
open-ended questions and questions designed to collect information regarding the specific 
outcomes of interest.
If a patient is seen by a non-RP physician or hospitalised in relation to an AE, the RP or 
trained registry site personnel should, in a timely manner, make every effort to follow-up 
with the treating physician or relevant concerned health care provider to obtain all 
information necessary for the accurate reporting of the event. 
For instances where an event is reported by the patient and/or treated by a non-RP, registry 
staff will contact the treating physician or other health care provider as described and 
authorized by the informed consent, in order to obtain relevant information necessary for 
complete reporting of adverse events. 
9.1. Definitions 
An adverse event (AE) is any untoward medical occurrence in a patient administered a 
medicinal product; the event need not necessarily have a causal relationship with the 
treatment or usage. Examples of AEs include but are not limited to:   
Abnormal test findings (see below for circumstances in which an abnormal test 
finding constitutes an adverse event) 
Clinically significant symptoms and signs 
Changes in physical examination findings 
Hypersensitivity 
Progression/worsening of underlying disease 
Lack of efficacy 
Drug abuse 
Drug dependency 
Additionally, they may include the signs or symptoms resulting from: 
Drug overdose 
Drug withdrawal 

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Drug misuse 
Drug interactions 
Extravasation 
Exposure during pregnancy 
Exposure during breast feeding 
Medication error 
Occupational exposure 
ABNORMAL TEST FINDINGS 
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows:  
Test result is associated with accompanying symptoms, and/or 
Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or 
Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy, and/or 
Test result is considered to be an adverse event by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not
constitute an AE. Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
A serious adverse event (SAE) is any untoward medical occurrence at any dose that: 
Results in death. 
Is life-threatening as it occurred, i.e, the patient was at risk of death at the time of the 
event. This does not refer to an event which hypothetically might have caused death if 
it were more severe. 
Requires inpatient hospitalisation or prolongation of existing hospitalisation (see 
below for circumstances that do not constitute adverse events) . 
Results in persistent or significant disability/incapacity, defined as a substantial 
disruption of a patient's ability to conduct normal life functions. 
Results in a congenital anomaly or birth defect. 
Constitutes an important medical event, i.e, based upon appropriate medical 
judgement, event may jeopardise the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed above. 
HOSPITALIZATION 

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AEs reported from studies associated with hospitalization or prolongation of hospitalization 
are considered serious. Any initial admission (even if less than 24 hours) to a healthcare 
facility meets these criteria. Admission also includes transfer within the hospital to an 
acute/intensive care unit (e.g.,, from the psychiatric wing to a medical floor, medical floor to 
a coronary care unit, neurological floor to a tuberculosis unit). An emergency room visit does 
not necessarily constitute a hospitalization; however, an event leading to an emergency room 
visit should be assessed for medical importance. 
Hospitalization in the absence of a medical AE is not in itself an AE and is not reportable. 
For example, the following reports of hospitalization without a medical AE are not to be 
reported.  
• 
Social admission (e.g., patient has no place to sleep) 
• 
Administrative admission (e.g., for yearly exam) 
• 
Optional admission not associated with a precipitating medical AE (e.g., for elective 
cosmetic surgery) 
• 
Hospitalization for observation without a medical AE 
• 
Admission for treatment of a pre-existing condition not associated with the 
development of a new AE or with a worsening of the pre-existing condition (e.g., for work-
up of persistent pre-treatment lab abnormality) 
• 
Protocol-specified admission during clinical study (e.g., for a procedure required by 
the study protocol) 
If there is any doubt about whether the information constitutes an AE, the information will be 
treated as an AE. Medical and scientific judgment is exercised in determining whether an 
event is an important medical event. An important medical event may not be immediately 
life-threatening and/or result in death or hospitalization. However, if it is determined that the 
event may jeopardize the patient or may require intervention to prevent one of the other 
adverse event outcomes, the important medical event should be reported as serious. 
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. 
CAUSALITY ASSESSMENT 
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious). The investigator must record the causal relationship in the CRF, as appropriate, and 

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report such an assessment in accordance with the serious adverse reporting requirements if 
applicable.   
An investigator's causality assessment is the determination of whether there exists a 
reasonable possibility that etanercept caused or contributed to an adverse event. If the 
investigator's final determination of causality is unknown and the investigator does not know 
whether etanercept caused the event, then the event will be handled as related to etanercept 
for reporting purposes. If the investigator’s causality assessment is unknown but not related 
to etanercept this should be clearly documented in the CRF.  
Scenarios necessitating reporting to Pfizer Safety within 24 hours  
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication 
error, overdose, misuse, lack of efficacy, and occupational exposure are described below. 
EXPOSURE DURING PREGNANCY  
An exposure during pregnancy (EDP) occurs if: 
1. A female becomes, or is found to be, pregnant either while receiving or having been 
directly exposed to (e.g., environmental exposure) etanercept, or the female becomes, 
or is found to be, pregnant after discontinuing and/or being directly exposed to 
etanercept (maternal exposure). 
2. A male has been exposed, either due to treatment or environmental, to etanercept 
prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy (paternal exposure). 
As a general rule, prospective and retrospective exposure during pregnancy reports from any 
source is reportable irrespective of the presence of an associated AE and the procedures for 
SAE reporting should be followed.
If any study patient or study patient’s partner becomes, or is found to be, pregnant during the 
study patient’s treatment with etanercept, the investigator must submit this information to 
Pfizer within 24 hours of awareness of the pregnancy, irrespective of whether an adverse 
event has occurred, using the NIS AEM Report Form and the EDP Supplemental Form. 
Information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy). 
Follow-up is conducted to obtain general information on the pregnancy; in addition, follow-
up is conducted to obtain pregnancy outcome information on all EDP reports with an 
unknown outcome. The investigator will follow the pregnancy until completion or until 
pregnancy termination (e.g., induced abortion) and then notify Pfizer of the outcome. The 

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investigator will provide this information as a follow up to the initial EDP report.  In the case 
of a live birth, the structural integrity of the neonate can be assessed at the time of birth.  In 
the event of a termination, the reason(s) for termination should be specified and, if clinically 
possible, the structural integrity of the terminated fetus should be assessed by gross visual 
inspection (unless pre-procedure test findings are conclusive for a congenital anomaly and 
the findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (e.g., ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
procedures for reporting SAEs should be followed. 
Additional information about pregnancy outcomes that are reported as SAEs follows:  
• 
Spontaneous abortion includes miscarriage and missed abortion; 
• 
Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure to 
investigational product 
Additional information regarding the exposure during pregnancy may be requested.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (e.g., follow-up on 
preterm infants to identify developmental delays).   
In the case of paternal exposure, the study participant will be provided with the Pregnant 
Partner Release of Information Form to deliver to his partner.  It must be documented that the 
study participant was given this letter to provide to his partner 
EXPOSURE DURING BREASTFEEDING 
Scenarios of exposure during breastfeeding must be reported to Pfizer within 24 hours of 
awareness, irrespective of the presence of an associated AE. 
MEDICATION ERROR 
A medication error is any preventable event that may cause or lead to inappropriate 
medication use or patient harm while the medication is in the control of the health care 
professional, patient, or consumer. Such events may be related to professional practice, 
health care products, procedures, and systems including: prescribing; order communication; 
product labelling, packaging, and nomenclature; compounding; dispensing; distribution; 
administration; education; monitoring; and use.   

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Medication errors include: 
Near misses, involving or not involving a patient directly (e.g., inadvertent/erroneous 
administration, which is the accidental use of a product outside of labeling or 
prescription on the part of the healthcare provider or the patient/consumer) 
Confusion with regard to invented name (e.g., trade name, brand name) 
The investigator must submit the following medication errors to Pfizer within 24 hours of 
awareness, irrespective of whether an adverse event occurred: 
Medication errors involving patient exposure to the product, whether or not the 
medication error is accompanied by an AE 
Medication errors including potential medication errors or near misses that do not 
involve a patient directly.  When a medication error does not involve patient exposure 
to the product the following minimum criteria constitute a medication error report 
An identifiable reporter 
A suspect product 
A medication error including potential medication error or near miss 
LACK OF EFFICACY 
Reports of lack of efficacy to etanercept are to be submitted to Pfizer by the investigator 
within 24 hours of awareness, irrespective of the presence of an associated AE/SAE or the 
indication for use of etanercept. 
OVERDOSE AND MISUSE 
The investigator must submit reports of overdose and misuse associated with the use of 
etanercept to Pfizer within 24 hours of awareness, irrespective of the presence of an 
associated AE/SAE. 
OCCUPATIONAL EXPOSURE 
Reports of occupational exposure to etanercept are to be submitted to Pfizer by the 
investigator within 24 hours of awareness, irrespective of the presence of an associated 
AE/SAE. 
9.2. Adverse Event and Serious Adverse Event Recording and Reporting 
Complete training on AE and SAE reporting practices will be provided to each participating 
site. Any AE/SAE observed by or reported to site personnel by the patient that occurs from 
the time of enrolment through patient discontinuation from the registry, end of the 

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observation period,  or 28 days after last dose of etanercept, whichever is later, is potentially 
reportable.  The RP must instruct the patient to report AEs (including SAEs, AEs of special 
interest and non-serious AEs)(see list under Section 9.1) during this time period. 
Each AE is to be assessed to determine if it meets serious criteria.  If a SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate. 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event. An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization. However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition of SAE, the important medical event should be reported as serious. 
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. 
This study protocol may require review of the patient medical chart. Review of patient
medical charts for specific attribution of SAEs to Pfizer drugs will not be actively pursued.  
However, while the primary purpose of this study does not encompass assessment of drug-
related effects in individuals, the reviewer may identify an SAE with explicit attribution to a 
Pfizer drug via patient chart (and with an identifiable reporter).  Such SAEs must be reported 
to Pfizer or its representative for submission to regulatory authorities. Explicit attribution is 
not inferred by a temporal relationship between drug administration and an SAE but must be 
based on a definite statement of causality by a healthcare provider linking drug 
administration to the SAE. 
If there is a written notation in the medical chart indicating that a physician attributed a 
serious or non-serious adverse event to a Pfizer drug, Pfizer or its representative/the reviewer 
will record the event on the CRF, and report SAEs and non-serious AEs of interest, within 24 
hours of awareness, to Pfizer Safety using the NIS AEM Report Form.  
Scenarios involving drug exposure, including exposure during pregnancy, exposure during 
breast feeding, medication error, overdose, misuse, lack of efficacy and occupational 
exposure associated with the use of a Pfizer product must be reported, within 24 hours of 
awareness, to Pfizer Safety using the NIS AEM Report Form. 
For these safety events with an explicit attribution to or associated with use of, respectively, a 
Pfizer product, the data captured in the medical record will constitute all clinical information 
known regarding these adverse events.  No follow-up on related adverse events will be 
conducted. 

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SERIOUS ADVERSE EVENT REPORTING REQUIREMENTS 
If a SAE occurs, Pfizer is to be notified within 24 hours of awareness of the event by the 
investigator. In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be 
made immediately, irrespective of the extent of available AE information. This timeframe 
also applies to additional new information (follow-up) on previously forwarded SAE reports 
as well as to the initial and follow-up reporting of exposure during pregnancy, exposure 
during breast feeding and medication error cases.   
In the rare event that the investigator does not become aware of the occurrence of a SAE 
immediately (e.g., if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the SAE.
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the timeframes for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion. This information collected for SAEs is more detailed than that captured on 
the AE CRF.  In general, this will include a description of the AE in sufficient detail to allow 
for a complete medical assessment of the case and independent determination of possible 
causality. Information on other possible causes of the event, such as concomitant medications 
and illnesses must be provided. In the case of a patient death, a summary of available autopsy 
findings must be submitted as soon as possible to Pfizer or its designated representative.  
The CRO EDC System will include a AE/SAE CRF for site staff to record basic information 
for any reportable AEs noted by the site or reported to the site by the patient. Entry of the 
CRF will generate an automated notification to CRO’s registry staff to ensure appropriate 
follow up.   
Recording of AEs/SAEs on the CRF does not satisfy the requirements for expedited 
reporting of events for regulatory reporting purposes.   
The site is also required to fax a completed Non-Interventional Study (NIS) AEM Report 
Form to CRO each time a SAE or an AE of interest is reported. The document will then be 
transmitted to Pfizer’s Drug Safety Unit within 24 hours for further processing and 
evaluation. 
In case a pregnancy should be reported, site will complete a NIS AEM Report Form as well 
as the EDP Supplemental Form. Upon receipt of an automated email notification, if follow-
up required, the CRO will immediately contact the site and request that the required Form(s) 
containing the minimum information (reportable event, identifiable subject, identifiable 
reporter and exposure to etanercept), is faxed to the CRO without delay. Upon receipt of the 
Form(s), the CRO immediately faxes it (them) to Pfizer local Drug Safety Unit (DSU), even 

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if minimal information is missing. The CRO then forwards the information to the Medical 
Monitor at the CRO via email. 
All SAEs, pregnancies and AEs of interest (as listed under Section 9.1), and follow-up 
information must be reported within 24 hours by faxing a completed NIS AEM Report Form 
to the study center at CRO  and confirming by phone or e-mail that the fax was received.   
Additionally to the NIS AEM Report Form, pregnancy should also be reported using the 
EDP Supplemental Form. 
All NIS AEM Report Forms and EDP Supplemental Forms should be faxed to the study 
center at CRO. 
In order to maintain compliance with the EMA and other international regulatory bodies, 
sites may be further contacted by the registry staff or Pfizer safety personnel in order to 
collect additional information required to evaluate a potential SAE. 
It is the responsibility of the site to inform their IEC (or equivalent local body governing 
research) of relevant SAEs occurring at their site, according to local requirements. Pfizer or 
CRO will notify the sites of any emergent product-related safety issues in accordance with 
local requirements. 
COMMUNICATION OF ISSUES 
In the event of any prohibition or restriction imposed (e.g.,, clinical hold) by an applicable 
Competent Authority in any area of the world, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of etanercept, 
Pfizer should be informed immediately.   
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study patients against any immediate hazard, and of 
any serious breaches of this NI study protocol that the investigator becomes aware of. 
10. ETHICS 
10.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
10.1.1. Study Approval 
IEC approval consistent with local regulations will be obtained.  Prior to enrolment of 
patients at a given site, the registry protocol will be submitted together with its associated 
documents (e.g., ICF, questionnaires) to the responsible IEC for its review. The written 
favourable opinion/approval of the IEC will be provided to each RP, and a copy will be filed 
in the Registry Master File (RMF) maintained by CRO.

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Patient enrolment will not start at any site before the Sponsor has obtained written 
confirmation of a favourable opinion/approval from the concerned IEC. The IEC will be 
asked to provide documentation of the date of the meeting at which the favourable 
opinion/approval was given, and of the members and voting members present at the meeting.  
Written evidence of favourable opinion/approval that clearly identifies the registry, the 
protocol version, and the Patient Information and Consent Form version reviewed will be 
provided. 
Before implementation of any substantial changes to the protocol, protocol amendments will 
also be submitted to the relevant IEC in a manner consistent with local regulations. Pertinent 
safety information will be submitted to the relevant IECs during the course of the registry in 
accordance with local regulations and requirements. 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, and informed consent forms, and other relevant documents, 
e.g., recruitment advertisements, if applicable, from the IRB/IEC.  All correspondence with 
the IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should 
be forwarded to Pfizer.  
10.1.2. Amendments to the Protocol 
Once the protocol has been approved by the local site IRB, the site investigators will not 
modify it. The site investigators will be notified in writing of any amendment(s) to the 
protocol and/or the informed consent form or assent form. Changes to the protocol will be 
documented in written protocol amendments.  The protocol amendments will usually require 
submission to the Competent Authorities and to the relevant IECs for approval or favourable 
opinion.  In such cases, the amendment will be implemented only after approval or 
favourable opinion has been obtained. 
Any amendment that could have an impact on the patient’s agreement to participate in the 
registry, e.g., changing the nature of the data collected, requires the patient’s or parent/legal 
representative’s informed consent prior to implementation. 
10.2. Ethical Conduct of the Study 
10.2.1. Guiding Principles 
The registry will comply with VOLUME 9A of The Rules Governing Medicinal Products in 
the European Union - Guidelines on Pharmacovigilance for Medicinal Products for Human 
Use –Part 1 Section 7, Company-Sponsored Post-Authorisation Safety Studies.13
To ensure the quality and integrity of research, this registry will be conducted under the 
Guidelines for Good Pharmacoepidemiology Practices issued by the International Society for 

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Pharmacoepidemiology (ISPE), the Declaration of Helsinki and its amendments, and any 
applicable national guidelines.14,15
10.2.2. Opinion of External Experts and Scientific Boards 
A Scientific Steering Committee (SSC), consisting of 5-7 external advisors, will be identified 
and recruited to assist in the study execution and interpretation. Specifically, physicians with 
expertise relevant to this effort, e.g., dermatology, general paediatrics, will be recruited.  The 
Scientific Steering Committee will meet at pre-specified intervals and will be guided by a 
charter agreed upon at the start of the registry. They will review interim data on a regular 
basis to assess whether any developing safety signals are potentially associated with use of 
etanercept in this population. 
In addition, an Endpoint Committee (EC) comprised of three (3) dermatologists or 
paediatricians will ensure that all events reported to the registry are evaluated and classified 
in a systematic manner.  Two members will independently evaluate all reports of serious and 
pre-specified opportunistic infections, malignancies, and SAEs.  Any discordant evaluations 
will be referred to a third member for independent review. 
10.3. Patient Information and Consent 
An unconditional prerequisite for a patient’s participation in the registry is his or her 
informed consent. Since the registry will enrol children and adolescents, in most cases a 
written informed consent will be required from a parent/legal representative.  Underage 
patients, as defined by local regulations in each of the selected countries, will be required to 
provide assent for participation. Underage patients that reach the local legal age for providing 
informed consent during follow-up will be re-consented as soon as feasible, i.e., at the next 
follow-up timepoint. 
The RP will obtain informed consent for enrolment into the registry, including contact 
information for treating physician(s) other than the RP and permission to access hospital 
records, before any registry-related activities to collect data from or about that patient are 
carried out. Depending on the local regulations, the form may include consent for direct 
contact with the patient or parent/legal representative, and retrieval of information or 
supportive documentation from health care providers and/or administrative sources other 
than the RP. 
Upon recruitment, the RP will be required to provide patients or parents/legal representatives 
with an information sheet in their local language that contains adequate information on risks 
of registry participation, in this case, limited to communication of personal identifiers and 
health information. If local regulations allow, provision of verbal and written information for 
the purposes of obtaining consent may be performed by a trained designee of the RP. Since 

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the registry will enrol a paediatric population, the language used to describe the registry must 
be cognitively understandable to children and adolescents. 
The informed consent form must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements. The ICFs must be signed and personally dated by the 
patient, or a parent/legal representative, and the RP (or designee, if applicable). The signed 
and dated declaration of informed consent will remain at the RP’s clinic and must be safely 
stored, so that the forms are retrievable at any time for monitoring, auditing, and inspection 
purposes. A copy of the signed and dated information and consent form will be provided to 
the patient or parent/legal representative. 
Whenever important new information that may be relevant to patient’s consent becomes 
available, the written patient information sheet and any other written information provided to 
patients or parents/legal representatives will be revised and submitted to the IEC. The agreed 
upon and approved, revised information will be forwarded to each patient or parent/legal 
representative in the registry. The RP will explain to the patient and/or parent/legal 
representative the changes to the previous version. 
The investigator must ensure that each study patient, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation. The investigator, or a person designated by the 
investigator, will obtain written informed consent from each patient or the patient's legally 
acceptable representative before any study-specific activity is performed. The investigator 
will retain the original of each patient's signed consent form. 
The informed consent form used in this study, and any changes made during the course of the 
study, must be prospectively approved by both the IRB/IEC and Pfizer before use. 
10.4. Patient Identification and Privacy 
After providing written informed consent, each patient will be assigned a unique registry 
patient identification number to be used throughout the study. This unique registry patient 
identification number will consist of the protocol number, site number (four digits), and 
patient number (three digits). All parties will ensure protection of patient personal data and 
will not include patient names on any sponsor forms, reports, publications, or in any other 
disclosures, except where required by laws. In case of data transfer, Pfizer will maintain high 
standards of confidentiality and protection of patient personal data. 
Example: the
 patient enrolled at site 
 in country 
 in protocol B1801035  
Protocol No.
Site No.
Patient No.
B1801035
P
P
PP
PP
PPD
PP

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Should the patient be withdrawn from the registry, his or her unique patient identification 
number will not be reassigned. 
Each patient’s data collected in the registry will be stored under the unique registry patient 
identification number. To maintain privacy, personal contact information will be stored so 
that patients can be contacted regularly if necessary, but contact information will be stored 
securely and separately from all other data collected in the registry. Data protection and 
privacy regulations will be observed in capturing, forwarding, processing, and storing patient 
data. 
In accordance with local regulations in each of the registry countries, patients or parents/legal 
representatives will be informed about data-handling procedures and asked for their consent.  
Every effort will be made to protect participant confidentiality according to the Directive 
95/46/EC on the protection of individuals, and in compliance with Safe Harbour privacy 
principles.16,17
10.5. Compensation to Patients and Physicians 
One of the threats to any long-term cohort study is loss to follow-up.  The ability to retain 
patients and physicians over multiple years is essential to meet the registry's goals.  The 
study design has taken into account tracking and participation considerations that aim at 
maximising both aspects while preserving the validity of the registry. 
To maximise patient retention, it is important to develop and maintain rapport between the 
RP and the patients/parents. In addition, if approved by the IEC, retention strategies may 
include the provision of general (i.e., not etanercept-specific) educational materials about 
psoriasis, feedback to patients about the registry progress, and nominal cash compensation 
for time spent completing registry-related questionnaires. We anticipate that such 
compensation, which would have a maximum cumulative value of 50 euros (or local 
equivalent), would be dispersed over the course of the registry observation period.  It is 
important to emphasise that any such compensation would be independent of current 
psoriasis treatment; it is not an inducement to continue etanercept treatment but rather to 
maximise capture of follow-up information over the 5-year study, information that is critical 
for its success. Such patient remuneration would be explicitly explained in the informed 
consent, and would only occur with prior approval of local IECs. As a final strategy for 
registry enrolment and retention, we will also explore endorsement of local and national 
psoriasis patient groups. 
The physicians will be compensated for their time to complete the registry requirements, 
consistent with local prevailing conditions. This compensation schedule will also be subject 
to local ethical committee approval. 

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11. COMMUNICATION AND PUBLICATION OF STUDY RESULTS 
At the completion of the study, the final results will be disseminated publicly. Medically 
important findings that have public health impact identified prior to completion of the study 
will be communicated to regulatory agencies and the public according to regulatory and 
scientific guidance in a timely manner. 
The Sponsor's decision to publish or otherwise publicly communicate the results of this study 
will be made in accordance with all applicable laws, regulations, and sponsor policies 
regarding publication and communication of clinical study results. Publications will follow 
the International Committee of Medical Journal Editors guidelines18, STrengthening the 
Reporting of OBservational studies in Epidemiology (STROBE) guidelines19, and GPP.20
Scientific peers shall be informed of study results in a timely fashion by publication in the 
scientific literature and presentations at scientific conferences, workshops, or symposia.  
Presentations at meetings should not be considered as a substitute for publications in the 
peer-reviewed literature. Authorship of study reports will follow the guidelines established 
by the International Committee of Medical Journal Editors (http://www.icmje.org/). All 
authors should meet the criteria for authorship, and all people who meet the criteria should be 
authors.  Potential conflicts of interest, financial and non-financial, should be disclosed.  
If appropriate, methodology and special findings may be submitted for presentation. The 
publications will most likely include data from all registry sites.  
11.1. Communication of Results by Pfizer 
Pfizer fulfils its commitment to publicly disclose the results of studies through posting the 
results of this study on ClinicalStudyResults.org. Pfizer posts the results of studies that fall 
into either of the following categories: 
Studies that Pfizer registered on www.clincaltrials.gov regardless of the reason for 
registration; OR 
All other studies for which the results have scientific or medical importance as 
determined by Pfizer. 
Results are posted in two formats:   
The results of studies applicable under the US Food and Drug Administration 
Amendments Act of 2007 (FDAAA) and/or An Act Regarding Advertising by Drug 
Manufacturers and Disclosure of Clinical Trials (state of Maine Reporting 
Requirements) are posted on ClinicalTrials.gov in a tabular format called Basic 
Results.   

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The results of all required studies (even if not previously registered to 
ClinicalTrials.gov) and any voluntarily registered studies are posted on 
ClinicalStudyResults.org in a format called a Pharmaceutical Research and 
Manufacturers of America (PhRMA) website synopsis (PWS), the format established 
by the ICH-E3 Clinical Study Report (CSR) Synopsis. 
For studies involving a Pfizer product, the timing of the posting depends on whether the 
Pfizer product is approved for marketing in any country at the time the study is completed: 
For studies involving products already approved in any country and applicable under 
FDAAA and/or state of Maine, Pfizer posts results within one year of the primary 
outcome completion date (PCD).  For all other studies that do not involve a Pfizer 
product, Pfizer posts results one year from last patient last visit (LPLV);  
Primary Completion Date is defined as the date that the final patient was examined or 
received an intervention for the purposes of final collection of data for the primary outcome, 
whether the clinical trial concluded according to the pre-specified protocol or was 
terminated. 
Pfizer posts citations only for publications that are accessible in recognized (searchable) 
publication databases. Single-centre results publications for a multi-centre study are 
generally not posted because they may not accurately reflect the results of the study. 
11.2. Enrolment and Progress Reports 
The number and percentage of patients enrolled and patients discontinued from the registry 
will be summarized at periodic intervals, every six months for the first three years, and 
annually thereafter. Also, early identification of potential demographic and clinical 
differences between patients that enrol in the registry and those who choose not to enrol, or 
cannot be contacted, will be attempted. 
11.3. Annual Analyses and Reporting 
Annual reports will be generated beginning one year after start of enrolment (i.e., Q4 2010).  
The baseline characteristics of patients will be described. Demographic characteristics (e.g., 
age, gender) and disease characteristics (e.g., psoriasis treatment history, severity of 
psoriasis) will be presented using descriptive statistics for continuous variables or 
proportions for categorical variables. The median and mean follow-up time in the registry 
will be presented.  Analyses of the outcomes of interest will be performed, dependent on the 
quantity of data available. 

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11.4. Final Analyses and Reporting 
A final registry report will be prepared at closure of the registry database, when all data 
collection procedures are completed. The final report will encompass all planned analyses, 
including a description of the complete registry population and estimates of events rates, as 
described above and in the SAP. 
11.5. Reporting to the EMA 
Following Competent Authority acceptance and unless otherwise requested, Pfizer will 
provide interim progress reports annually and the final report at the completion of the nine 
year registry, to the EMA as part of the Periodic Safety Update Report (PSUR) and updated 
etanercept risk management plans. 
 
 

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12. REFERENCES 
                                                
1  
Koo J. Population-based epidemiologic study of psoriasis with emphasis 
on quality of life assessment. Dermatol Clin 1996;14:485-496.
2
Gelfand JM, Weinstein R, Porter SB, Neimann AL, Berlin JA, Margolis 
DJ.  Prevalence and treatment of psoriasis in the United Kingdom.  Arch 
Dermatol 2005;141:1537-1541.
3  
Granstein RD. New treatments for psoriasis. N Engl J Med
2001;345(4):248-55.
4
Beylot C, Puissant A, Bioulac P,Saurat JH, Pringuet R, Doutre MS. 
Particular clinical features of psoriasis in infants and children.  Acta 
Derm Venereol Suppl (Stockh) 1979;87:95-7.
5  
Raychaudhuri SP, Gross J.  A comparative study of pediatric onset 
psoriasis with adult onset psoriasis.  Pediatr Dermatol 2000;17(3):174-8.
6
Al-Fouzan AS, Nanda A.  A survey of childhood psoriasis in Kuwait.  
Pediatr Dermatol 1994;11(2):116-9. 
7  
Rasmussen JE. Psoriasis in children. Dermatol Clin 1986;(4):99-106. 
8  
NICE technology appraisal. Etanercept and efalizumab for the treatment 
of adults with psoriasis. Technology appraisal guidance 103, July 2006. 
Available from: 
http://www.nice.org.uk/guidance/index.jsp?action=download&o=33377 
.Accessed January 2009. 
9  
NICE technology appraisal. Infliximab for the treatment of adults with 
psoriasis Technology appraisal guidance 134, Jan 2008). Available from: 
http://www.nice.org.uk/guidance/index.jsp?action=download&o=38979 
Accessed January 2009. 
10
Lovell DJ, Giannini EH, Wallace CA, et al. Safety of over 8 years of 
continuous etanercept therapy in patients with juvenile rheumatoid 
arthritis. Ann Rheum Dis 2007; (Supplement II) 66.
11  Lovell DJ, Reiff A, Jones OY, et al. Long-term safety and efficacy of 
etanercept in children with polyarticular-course juvenile rheumatoid 
arthritis. Arthritis Rheum 2006;54:1987-94

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12  Paller AS, Siegfried EC, Langley RG et al for the Etanercept Paediatric 
Psoriasis Study Group. Etanercept treatment for children and adolescents 
with plaque psoriasis. N Engl J Med 2008;358:241-51. 
13  EudraLex VOLUME 9A of The Rules Governing Medicinal Products in 
the European Union - Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use. September 2008.  Available  at 
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol9_en.htm.
Accessed January  2009. 
14  International Society for Pharmacoepidemiology (ISPE). Guidelines for 
good pharmacoepidemiology practices (GPP), revision 2. April 2007. 
Available at 
http://www.pharmacoepi.org/resources/guidelines_08027.cfm.  Accessed 
January 2009. 
15  Declaration of Helsinki 59th World Medical Association  General 
Assembly, Seoul, October 2008. Available at 
http://www.wma.net/e/policy/b3.htm Accessed January 2009 
16  Directive 95/46EC of the European Parliament And The Council on the 
protection of individuals with regard to the processing of personal data 
and on the free movement of such data. Available at
http://ec.europa.eu/justice_home/fsj/privacy/docs/95-46-ce/dir1995-
46_part1_en.pdf Accessed January 2009 
17  International Safe Harbor Privacy Principles Safe Harbor Privacy  
Principles Issued by The U.S. Department Of Commerce on July 21, 
2000. Available at http://www.export.gov/safeharbor/ Accessed January 
2009
18  International Committee of Medical Journal Editors. Uniform 
requirements for manuscripts submitted to biomedical journals: writing 
and editing for biomedical publication. Updated October 2008. Available 
at: http://www.icmje.org/. Accessed January 2009. 
19     STROBE Statement: STrengthening the Reporting of OBservational 
studies in Epidemiology. March 30, 2008. Available at: 
http://www.strobe-statement.org/News%20Archive.html. Accessed 
January 2009. 
20  International Society for Pharmacoepidemiology (ISPE). Guidelines for 
good pharmacoepidemiology practices (GPP), ISPE Commentary. 
Pharmacoepi and Drug Safety 2008;17:200-8. 

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