Download Part Two: blood sample for Pro-NT BNP, other novel markers and DNA

XXXXXXXX HOSPITAL
Research Protocol Version 1, XXXXXXX date
AUSTRALIAN SCLERODERMA SCREENING PROGRAM (ASSP)
1.0
SCLERODERMA GENERAL OVERVIEW ............................................................... 2
2.0
AUSTRALIAN SCLERODERMA INTEREST GROUP ............................................. 3
3.0
THE AUSTRALIAN SCLERODERMA SCREENING PROGRAM (ASSP) AND
RESEARCH PROJECT ........................................................................................... 4
3.1 ASSP primary aims: ......................................................................................... 5
3.2 ASSP secondary aims: ..................................................................................... 5
4.0
ASSP RESEARCH COMPONENT .......................................................................... 5
4.1 Two part research component .......................................................................... 5
Part One: use of de-identified data ................................................................... 5
Part Two: blood sample for Pro-NT BNP, other novel markers and DNA .......... 6
4.2 Elements of the screening program .................................................................. 8
History and clinical examination........................................................................ 9
Investigations ................................................................................................... 9
4.3 Criteria for participation in research component.............................................. 10
Inclusion Criteria ............................................................................................. 10
Exclusion Criteria ........................................................................................... 10
4.4 Recruitment to the research ........................................................................... 10
4.5 Ethics approval ............................................................................................... 12
4.6 Governance and staffing ................................................................................ 12
4.7 Statistical Analyses......................................................................................... 12
4.8 Funding .......................................................................................................... 12
4.9 Publication of results ...................................................................................... 12
REFERENCES ................................................................................................................... 13
APPENDIX ONE:
APPENDIX TWO:
APPENDIX THREE:
APPENDIX FOUR:
APPENDIX FIVE:
APPENDIX SIX:
APPENDIX SEVEN:
APPENDIX EIGHT:
ASSP DATASET
FLOW CHART FOR USE OF GENETIC MATERIAL
INCLUSION CRITERIA
PARTICIPANT INFORMATION AND CONSENT FORM
CORRESPONDENCE WITH REFERRING PHYSICIANS
LETTER CONFIRMING APPOINTMENT TIME
BROCHURE ON SCREENING PROGRAM
ROUTINE SCREENING FORMS
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1.0 SCLERODERMA GENERAL OVERVIEW
Scleroderma is a rare, chronic disease characterized by excessive deposits of
collagen. Collagen is the main protein of connective tissue in animals. It has great
tensile strength, and is the main component of cartilage, ligaments, tendons, bone
and teeth. Collagen is responsible for skin strength and elasticity, it strengthens
blood vessels and plays a role in tissue development. Systemic sclerosis (SSc) is
generalised disease of excess collagen deposition which can affect various parts of
the body. SSc is often linked with mixed connective tissue disease (MCTD) which
is a human autoimmune disease in which the immune system attacks the body.
SSc can also affect connective tissue in the pulmonary arteries, the blood vessels
that carry blood away from the heart and to the lungs, severely restricting the flow
of blood from the heart to the lungs, and increasing the pressure in the pulmonary
arteries resulting in Pulmonary Arterial Hypertension (PAH). The heart must
pump against this increased pressure to maintain blood flow to the lungs and then
to the rest of the body. The heart adapts to this increased pressure by gradually
becoming larger, particularly on its right side. However, this is only a short term
solution and the heart eventually fails to pump efficiently. As a result, the body
does not receive sufficient oxygen supply from the blood to fulfil all its needs and
the patient may experience shortness of breath, dizziness, fainting, and other
symptoms, all of which are exacerbated by exertion. This complication is
particularly common in the limited form of SSc which is a more slowly progressive
form with less extensive involvement. Nonetheless, it may also occur in patients
with the more rapidly progressive, diffuse form.
The disease process in the pulmonary arteries which leads to PAH can sometimes
occur over several years. The signs and symptoms of this disease are often hard to
distinguish from other diseases or conditions, particularly in the early stages. This
frequently delays the formal diagnosis of PAH. During this time, symptoms such as
unexplained tiredness and breathlessness are experienced. These symptoms are
generally first only noticed during physical activity, but as the disease progresses
they are present all the time, even when resting. Understandably this impacts
greatly on daily life, limiting daily activities. More importantly the disease can lead
to right-sided heart failure.
Scleroderma and connective tissue disease can also contribute to a disease of the
lung tissue called Interstitial Lung Disease (ILD). In ILD, the walls of the air sacs in
the lung and the lung tissue become inflamed. If this inflammation continues then
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scarring, otherwise know as fibrosis, occurs and the lung becomes stiff. Symptoms
of ILD are similar to the breathlessness of PAH; however there may also be a
cough that can become quite distressing for patients.
PAH and ILD are recognised as the number one cause of death in patients with
scleroderma [1]. Reports of the prevalence of SSc and of PAH associated with SSc
vary. It has been estimated that in Australia, the point prevalence of SSc is
approximately 2300 patients [2] and that SSc PAH in Australia could be expected
to affect approximately 600 patients [3], confirmed by a study that found the
prevalence of PAH within the SSc or MCTD population to be 26% [4]. However
there is evidence that PAH is under-diagnosed, with recent studies suggesting
more than 13% of patients followed up in a community rheumatology setting had
undiagnosed PAH prior to formal assessment [4].
As well as the condition often being silent until late in the disease, it may not be
detected in investigations such as the echocardiogram (ECHO), if there is no minor
leakiness of the tricuspid valve on the right side of the heart (approximately 25% of
people) or if the technicians performing the investigations do not have the specific
skills required for detecting PAH.
There is now effective treatment available [5-8] which will reduce the severity of the
complications of this disease if provided early in the illness, so timely and ongoing
screening for SSc patients is currently recommended by the British Thoracic
Society [9]
and the Royal Free Hospital Connective Tissue Disease Clinic. A
screening trial for patients with SSc has been underway in Perth, Western Australia
since April 2005 and had screened over 100 patients in the first 12 months. Twenty
six (22%) of 119 patients were thought likely to have PAH based on ECHO
findings, of these 21 (81%) had the limited form of SSc. Of the 26 patients, 13
(11%) had PAH confirmed on Right Heart Catheter, with PAH defined as mean
pulmonary artery pressure >25 mmHg. There are currently several international
groups who have established databases and registries such as PHAROS
(Pulmonary Hypertension Registry of Scleroderma), the EUSTAR data base, SSc
QuERI (Toronto) and the Scleroderma Clinical Trials Consortium.
2.0 AUSTRALIAN SCLERODERMA INTEREST GROUP
The Australian Scleroderma Interest Group (ASIG) was formed in November 2005
to bring together physicians interested in improving the care of patients with
Systemic Sclerosis (SSc) by better management of its complications, especially
pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). Given the
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evidence of the benefits of screening and the current lack of facilities to provide this
service, the group determined that it would establish designated screening centres
around Australia so that all patients in Australia with a diagnosis of SSc or Mixed
Connective Tissue Disease (MCTD) could have access to high quality annual
screening for the presence of disease-related cardio-respiratory complications,
regardless of whether respiratory symptoms were present.
3.0 THE AUSTRALIAN SCLERODERMA SCREENING PROGRAM
(ASSP) AND RESEARCH PROJECT
The ASSP is the result of a collaboration between members of ASIG from across
Australia and currently comprises the following physicians:

Dr Wendy Stevens, St Vincent’s Health, Victoria

Dr Joanne Sahhar, Monash Medical Centre, Victoria

Assoc Prof Susanna Proudman, Royal Adelaide Hospital, South Australia

Dr Janet Roddy, Royal Perth Hospital, Western Australia

Assoc Prof Peter Youssef, Royal Prince Alfred, New South Wales

Assoc Prof Peter Nash, Sunshine Coast Rheumatology, Queensland

Assoc Prof Kathleen Tymms, Canberra Rheumatology ACT

Dr Jane Zochling, Menzies Institute, Tasmania

Assoc Prof Les Schrieber, Royal North Shore Hospital, New South Wales

Assoc Prof Allan Sturgess, St George Hospital, New South Wales

Assoc Prof Gabor Major and Assoc Prof Glenn Reeves, John Hunter
Hospital, New South Wales

Assoc Prof Catherine Hill, Queen Elizabeth Hospital, South Australia

Dr Vivek Thakkar, Liverpool Hospital, New South Wales

Dr Gemma Strickland, St Vincent’s Health, Victoria
With assistance from:

Prof David Celermajer (cardiologist), Royal Prince Alfred, New South
Wales

Dr Mandy Nikpour (rheumatologist and epidemiologist), St Vincent’s
Health, Victoria
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3.1

ASSP primary aims:
To increase the rate of screening for cardiopulmonary complications in
SSc and MCTD, by establishing screening centres around Australia
staffed by clinicians with expertise in the disease.

To ensure screened patients receive appropriate and timely treatment
according to evidenced based practice.
3.2

ASSP secondary aims:
To promote the adoption of best practice guidelines for the assessment of
PAH and ILD associated with SSc or MCTD into routine clinical practice.

To create a system to link data collected from the screening centres in deidentified form to be used for investigating whether there are predisposing
factors associated with the progression of SSc.
To achieve the secondary aims a research component of the program is
proposed.
4.0 ASSP RESEARCH COMPONENT
4.1
Two part research component
Part One: use of de-identified data
As a part of standard care, each screening centre will collect routine clinical data
according to a defined dataset (see Appendix 1) as well as a history from the
referring physician. Patients will be asked to consent to the use of this data in deidentified form.
For patients who have not consented to the research component of the project, the
dataset will be on a form that will be located on the local hospital server so that it
can be completed and printed off for inclusion in the patient record.
The dataset will also be located within a custom made application on a secure
server within a public hospital setting. Negotiations are currently underway for this
to be based at St Vincent’s Health, Victoria. Clinicians from around Australia will be
able to access the form via a secure log-in to enter data while seeing consented
patients, as well as edit data later on as test results become available. Clinicians
will only have access to their own patient data and they will also be able to print off
a copy of the form to store in paper format in the patient’s hospital file.
The full or aggregated database will only be able to be accessed by the ASIG
Project Officer, ASIG Data Manager and the IT Manager. Each patient will be
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assigned a unique code when entered into the database, so that when the data is
aggregated there will not be any identifying information visible. The link between
the unique code and patient identification will be kept in a secure location by the
lead researcher at each site. The aggregated database with de-identified data will
be in a format that can be exported to a statistical software package to enable
statistical analysis.
The security for the server will be the same as that for all files stored electronically
within St Vincent’s Health with data backed up daily.
Part Two: blood sample for Pro-NT BNP, other novel markers and DNA
To assist in assessing predisposing factors, patients will be asked to consent to
extra blood which will usually be taken at the same time as routine tests. The two
extra samples of 10ml each will be examined to explore links to the progression of
SSc, specifically:

The whole blood in one tube will be spun to collect the serum. ‘Markers’ in
blood serum sometimes indicate that disease is present or help predict how
severe the disease will be in the future. Researchers often make new
discoveries about the body and new or ‘novel markers’ become recognised.
Pro-NT BNP is a novel marker that is associated with heart disease
including PAH, that is rapidly becoming part of standard care; however as it
is not routine at all hospitals yet the sample may need to be transported to
another hospital for analysis. It is planned to have this test performed once
funding for the kits becomes available.
The researchers would like to store the remainder of this blood serum
sample for up to ten years to explore links with other known novel markers
in the future. This blood sample will be collected at each screening visit.

The whole blood in the second tube will be spun down to collect the buffy
coat from which DNA is extracted. Similarly, researchers often make new
discoveries about the genes associated with disease, so the second sample
will also be stored for up to ten years to serve as a DNA bank for analyses
by the current research team of potentially relevant genes related to SSc as
they emerge in the future. This sample will only be collected once.
The use of a portion of the patient’s blood for extraction and storage of
DNA:
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DNA will be stored and serve as a DNA bank for studies of potentially
relevant genes as they emerge by members of the ASIG project. Any
studies would require the permission of the Custodian of the DNA bank and
database, Dr XXXXX, and approval from the ASIG Blood Research
Committee as well as Institutional Ethics Committee. The use of database
material will be controlled according to a flow chart (see Appendix 2) that
has been devised according to current NHMRC guidelines. The key
attributes of this scheme are: 1) the identification code is kept separate from
the material; 2) there is a designated custodian and 3) there is a committee
to determine usage of the material. Nevertheless, the ‘right to know’ of
patients that the DNA could be used in future studies is addressed in the
patient information sheet. The samples will be de-identified and at no time
will patients be contacted based on the results of their genetic analysis.
Patients will also be asked if they wish to be contacted if clinically relevant
genetic information is uncovered.
Patients will be asked to consent to Part 2 of the research separately from Part 1
(the use of routine clinical data) and will have the option to consent to have their
data being included but not to have the extra blood samples taken and stored.
Blood samples collected by centres associated with the Australian Scleroderma
Interest Group (ASIG) are frozen and sent to the Arthritis Research Laboratory
(ARL) located at The Queen Elizabeth Hospital, Woodville South, SA for storage.
Proposed studies using the DNA sample:
1.
A comprehensive analysis of the immunogenetics of scleroderma.
To undertake this genetic study the DNA samples will be sent to Prof Matt Brown's
laboratory in the Diamantina Institute for Cancer, Immunology and Metabolic
Medicine in Queensland for analysis. All samples will remain de-identified, labelled
only with the ASIG unique ID number.
ASIG will be genotyping common variants (single nucleotide polymorphisms
(SNPs)) in genes previously associated with immunological diseases.
Individually these genes have little predictive value for disease, and the utility
of the genetic findings in clinical diagnosis is currently uncertain; however by
analysing the samples of a large group of patients for whom extensive data
is available in the ASIG database it is hoped to explore links between genes
and disease onset and progression.
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ASIG will not be testing rare variants known to have strong disease
associations in humans as the SNPs selected were chosen to identify lower
penetrance moderate and common variants, rather than as a screen for
monogenic diseases.
2. Genetics of Scleroderma
As with the immunogenetics study, the de-identified DNA samples with only ASIG
IDs as labels will be sent to Professor Matt Brown’s laboratory.
The study has two parts. First is to identify genetic factors involved in scleroderma
by sequencing a nucleotide (exon 37) of the fibrillin gene in a large case collection.
The study will compare mutations associated in scleroderma patients against that
of healthy controls who have already been sequenced by Professor Brown’s group,
and healthy controls of white European descent for whom exome sequence data is
already publicly available.
Second, a genome-wide association study (GWAS) and meta-analysis of available
GWAS data will be undertaken. Case data from the ASIG cohort will be compared
with common control data publicly available, including from Australian cohorts such
as the Older Age Twin Study, which have been genotyped using the same chips.
The GWAS data will be analysed as per a typical GWAS on its own, then metaanalysed with the available GWAS data from European and North American
Cohorts in order to increase the power of the study. This dataset will represent the
largest available scleroderma GWAS, and is very likely to identify further genetic
factors involved in the disease.
4.2
Elements of the screening program
There are three parts to the screening – history, clinical examination and
investigations – and the process for this will be the same regardless of whether
patients choose to participate in the research. As stated above, routine clinical data
defined in the dataset will be recorded in patients’ files as per standard practice;
however for those who have consented to the research an online version will also
be created for entry into the aggregated database.
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Baseline data will be collected at the first appointment and the patient will be
contacted for review every 12 months; however not all investigations will be
repeated annually.
History and clinical examination
A clinician with a special interest in the management of SSc and/or PAH who will
be a member of the research team will take a history and then complete a clinical
examination. The clinician may be assisted by a registrar and/or research nurse.
The patient will have received an information pack (includes symptom
questionnaire, past medical history questionnaire and Quality of life Questionnaires
including HAQ, SF-36, sHAQ, PROMIS-29, FACIT-fatigue and dyspnoea, UCLA
SCTC GIT) that they are encouraged to complete and bring to the first appointment
for discussion with the clinician. This assessment will usually take place in the
public hospital outpatient setting, with the exception of private patients already
being seen by a research clinician who can undertake this assessment in the
private rooms during the course of routine care. After the assessment, the clinician
will refer patients for investigations.
The history will include:

demographics and social data

current health

past disease – diagnosis, organ involvement, treatment
The clinical examination will include:

Current symptoms

Body mass index, blood pressure

Skin Score

Examination of the cardiorespiratory system
Investigations
The investigations will be conducted within the public hospital according to
standard care with recommendations for the timing of repeat tests determined after
assessment of the results. A standard set of screening investigations would
include:

Lung function tests (spirometry and diffusing capacity)

Electrocardiograph (ECG)
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
Echocardiogram (Echo)

Chest Xray

Six minute walk test

Blood test for full blood count, renal and liver function, muscle enzymes and
autoantibody screen

Urine test

High-resolution computed tomography (HRCT) may be performed if
abnormalities are detected on lung function testing
The screening centre will be staffed by highly skilled technicians who have the
training and expertise to detect PAH and ILD.
The patient will not incur any costs if they choose to participate in the research, and
they will have no out of pocket expenses from the screening program.
4.3
Criteria for participation in research component
Inclusion Criteria

Patients eligible for and participating in the screening program (aged
greater than 18 years with a clinical diagnosis of SSc or MCTD according
to either the American College of Rheumatology criteria or the LeRoy
criteria for limited or diffuse scleroderma – see Appendix 3)

Screening program patients who are willing to participate and have signed
the consent form – see Appendix 4.
Exclusion Criteria

Patients unable to be screened due to
-
Difficulty accessing a screening centre because of geographic
isolation or poor mobility.
-
Factors likely to limit compliance with screening requirements.
-
Factors likely to render screening investigations unsafe (modified
protocol may be permitted).

4.4
Patients do not wish to participate in research component
Recruitment to the research
All doctors in Australia caring for patients with SSc and MCTD will be invited to
refer their patients to the most convenient screening centres using a preformatted
referral form – see Appendix 5, Parts a and b. Referrals may come from
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rheumatologists, cardiologists, respiratory physicians, immunologists or general
practitioners. In the invitation, the physician will be informed of the benefits of the
screening program and what the program involves, be requested to supply relevant
patient history from the file, and asked to consider the agreement for ongoing
management. Physicians will also be told of the research component to the
screening program and that participation in this is optional for the patient. Referring
doctors will receive the results of the screening on a standard from – see Appendix
5 Part c.
Information on the screening program and research component will also be
disseminated to patients through support groups such as Scleroderma Australia
and the Arthritis society so that patients can approach their physician to discuss the
benefits of participation if they are interested.
Once a referral to the screening program is made the patient will be asked to ring
the screening centre to make an appointment. The patient will receive a letter
confirming the appointment time and informing them of the optional research
component – see Appendix 6. The letter will be accompanied by an information
pack which will include:

A brochure describing PAH and the investigations that are routinely
conducted as part of the screening program – Appendix 7

A symptom questionnaire based on the Vital Activities and Lifestyle Index
that patients are encouraged to complete before attending the first
appointment, that are all part of routine care – Appendix 8.

The Plain Language Statement and Consent Form for the research
component of the program. This will ensure that patients have time to
consider whether they have any queries about the research before
deciding whether they wish to participate - Appendix 4.
Cardio-respiratory complications can occur at any stage in the disease. PAH often
occurs after 10 years of disease duration. We are therefore keen to recruit both
recently diagnosed scleroderma patients and those with more long standing
disease into this project therefore the baseline appointment will review the patient
history and for research participants, the past information on the progress of the
disease will also be entered on the web based database. This process will ensure
that investigations are not repeated before there is a clinical need to do so, and
that all investigations are performed according to the standard now accepted as
best practice.
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4.5
Ethics approval
Researchers attached to each of the screening centres will be responsible for
obtaining ethics approval from their local Human Research Ethics Committee for
the research component of the screening program. Each centre will use the same
research protocol with the only variations being information that is site specific –
names and contact details of researchers. All sites have obtained approval for the
project as at 2009.
4.6
Governance and staffing
The Australian Scleroderma Interest Group (ASIG) is a committee formed under
the auspice of the Australian Rheumatology Association (ARA). All researchers on
the project are members of the committee and of the ARA, with the exception of
the cardiologist and respiratory physicians who are co-opted members. The
committee meets regularly by teleconference or face to face and meetings are coordinated by the Chair. One staff member, employed as a Project Officer, reports to
the committee and manages the implementation of the research protocol with the
assistance of the committee members who all donate their time to the project
voluntarily.
4.7
Statistical Analyses
The data will be analysed to produce descriptive statistics. Tests for
correlations between clinical and genetic findings will be determined by the
type and distribution of the data. Power calculation: not applicable.
4.8
Funding
Funding for the screening program and research component has been provided by
Actelion Australia as an unrestricted educational grant. The funding covered the
cost of the project for the initial three years (2007-2009) and this has been
extended on a yearly basis since 2012. Further funding will be sought to extend the
program.
4.9
Publication of results
Findings of the research will be published in de-identified form in medical journals
and a summary will be available for participants through patient support groups
such as Scleroderma Australia.
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REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
Mukerjee D, St George D, Coleiro B, Knight C, Denton CP, Davar J, Black CM,
Coghlan JG. Prevalence and outcome in systemic sclerosis associated pulmonary
arterial hypertension: application of a registry approach. Ann Rheum Dis
2003;62(11):1088-93.
Englert H, Small-McMahon J, Davis K, O'Connor H, Chambers P, Brooks P.
Systemic sclerosis prevalence and mortality in Sydney 1974-88. Aust N Z J Med
1999;29(1):42-50.
Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, Rich S,
Barst RJ, Barrett PS, Kral KM, et al. Continuous intravenous epoprostenol for
pulmonary hypertension due to the scleroderma spectrum of disease. A randomized,
controlled trial. Ann Intern Med 2000;132(6):425-34.
Wigley FM, Lima JA, Mayes M, McLain D, Chapin JL, Ward-Able C. The prevalence
of undiagnosed pulmonary arterial hypertension in subjects with connective tissue
disease at the secondary health care level of community-based rheumatologists (the
UNCOVER study). Arthritis Rheum 2005;52(7):2125-32.
Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, Nikkho S,
Speich R, Hoeper MM, Behr J, et al. Inhaled iloprost for severe pulmonary
hypertension. N Engl J Med 2002;347(5):322-9.
Williams MH, Das C, Handler CE, Akram MR, Davar J, Denton CP, Smith CJ, Black
CM, Coghlan JG. Systemic sclerosis associated pulmonary hypertension: improved
survival in the current era. Heart 2006;92(7):926-32.
Joglekar A, Tsai FS, McCloskey DA, Wilson JE, Seibold JR, Riley DJ. Bosentan in
pulmonary arterial hypertension secondary to scleroderma. J Rheumatol
2006;33(1):61-8.
Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A,
Roux S, Leconte I, et al. Bosentan therapy for pulmonary arterial hypertension. N
Engl J Med 2002;346(12):896-903.
British Cardiac Society Guidelines and Medical Practice Committee.
Recommendations on the management of pulmonary hypertension in clinical
practice. Heart 2001;86:i1-i13.
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Appendix One
APPENDIX ONE: ASSP DATASET
SYSTEMIC SCLEROSIS DATA ENTRY SHEETS
First visit – PART I & Part II
Annual review – PART II only but confirm ‘patient data’.
Where there are options please circle appropriate response or use drop down
box if entered electronically.
Appendix One
Appendix One
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Appendix One
Appendix Two
APPENDIX TWO: FLOW CHART FOR THE USE OF GENETIC MATERIAL
Custodian of database: Dr Wendy Stevens
Committee to consider projects that use database material: Drs S Proudman, Dr W Stevens,
Dr J. Sahhar, Dr J. Roddy, A/Prof P. Nash, A/Prof P Youssef.
Blood
Coded
Storage of Code
(Dr XXXX)
Committee determines access.
If for research purposes, specific
projects must be approved by the
Research Ethics Committee
Storage of Blood/DNA
with coded identifier
Appendix Three
APPENDIX THREE: INCLUSION CRITERIA
(a)
American College of Rheumatology (ACR) criteria for systemic sclerosis
Clinical Features - Classification Related
Major criterion:
Proximal scleroderma: symmetric thickening, tightening, and induration of the skin
proximal to the metacarpophalangeal or metatarsophalangeal joints
Minor criteria:
1. Sclerodactyly: above skin changes, limited to the fingers.
2. Digital pitting scars or loss of substance from the finger pad: Depressed areas at tips
of fingers or loss of digital pad tissue as a result of ischemia
Investigations - Classification Related
3. Bibasilar pulmonary fibrosis: Bilateral reticular pattern of linear or lineonodular
densities most pronounced in basilar portions of the lungs on standard chest
radiograph; may assume appearance of diffuse mottling or “honeycomb lung”. These
changes should not be attributable to primary lung disease.
Presence of the major criterion or 2 of the 3 minor criteria indicates systemic
sclerosis.
(Adapted from the Subcommittee for Scleroderma Criteria of the American
Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary
Criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum
23:581-90, 1980).
(b)
Systemic Scleroderma subsets according to LeRoy et al.
[20<http://dermatology.cdlib.org/DOJvol8num1/reviews/scleroderma/haustein.html#20> ]
Limited Cutaneous SSc




Raynaud's phenomenon for years at presentation
Skin sclerosis limited to hands, feet, face, and forearms, or absent
Significant late incidence of pulmonary hypertension, trigeminal neuralgia,
calcinosis, and telangiectasia
Dilated nailfold capillary loops, usually without capillary dropouts
Diffuse cutaneous SSc






Onset of Raynaud's phenomenon within 1 year of onset of skin changes
Truncal and acral skin involvement
Presence of tendon friction rubs
Early and significant incidence of interstitial lung disease, oliguric renal failure,
diffuse gastrointestinal disease, and myocardial involvement
Presence of anti-DNA topoisomerase I (anti-Scl-70) antibodies
Absence of anticentromere antibodies
Appendix Three

Nailfold capillary dilatation and destruction (detected by widefield nailfold
capillaroscopy)
Appendix Four
HOSPITAL XXXX
PARTICIPANT INFORMATION AND CONSENT FORM
Protocol No. XXXX
Version XXXX, Dated XXXX
Site: XXXX
Full Project Title:
Australian Scleroderma Screening Program
Researchers at St Vincent’s Health: XXXX
Associate Researcher in the national collaboration: XXXX
This Participant Information and Consent Form is 7 pages long. Please make sure you
have all the pages.
1.
Your Consent
You are invited to take part in this research project because you have either Scleroderma
(SSc) or Mixed Connective Tissue Disease (MCTD). The Participant Information section
contains detailed information about the research project. Its purpose is to explain to you
as openly and clearly as possible all the procedures involved in this project before you
decide whether or not to take part in it.
Please read this Participant Information carefully. Feel free to ask questions about any
information in the document. You may also wish to discuss the project with a relative or
friend or your local health worker. Feel free to do this.
Once you understand what the project is about and if you agree to take part in it, you
will be asked to sign the Consent Form. By signing the Consent Form, you indicate that
you understand the information and that you give your consent to participate in the
research project.
You will be given a copy of the Participant Information and Consent Form to keep as a
record.
2.
Purpose and Background
Scleroderma (Systemic Sclerosis) is a rare, chronic disease characterized by excessive
deposits of collagen in the connective tissue which can affect various parts of the body.
SSc can also affect connective tissue in the pulmonary arteries, the blood vessels that
carry blood away from the heart and to the lungs, restricting the flow of blood from the
heart to the lungs, and increasing the pressure in the pulmonary arteries resulting in
Pulmonary Arterial Hypertension (PAH).
Previous research has suggested that some patients with Scleroderma or Mixed
Connective Tissue Disease may develop these complications which can impact on their
heart and lungs and long term health. In the early stages the complications are difficult
to detect however there is now effective treatment available which will reduce the
severity of the symptoms if provided early in the illness. Therefore screening centres are
being established around Australia and all patients confirmed to have either Scleroderma
or Mixed Connective Tissue Disorder will be encouraged to use the service.
Those patients who do attend for annual screening at one of the Australian Scleroderma
Screening Centres will be invited to participate in a research project. The physicians who
Participant Information and Consent Form Version
XXXXX
Page 1 of 7
Appendix Four
are setting up the centres would like to use the health information that is collected during
routine care at the centre, so that the information can be examined to better understand
why some people develop the serious complications.
Patients will also be asked if they are willing to provide two extra blood samples that are
NOT part of routine care, but will also be used to understand why some people develop
the serious complications. One sample will be spun in a lab to collect the sera and it will
be used to test for markers in the blood that sometimes indicate that disease is present
or help to predict how severe the disease will be in the future. BNP is a marker that can
sometimes indicate that the heart is under some strain. It is thought that BNP may be
raised in patients with scleroderma or mixed connective tissue disease who have
pulmonary hypertension. With ongoing medical research new markers may be recognised
so the researchers would like to store the remainder of this sample for future testing.
The other sample will be used to explore links between your genes and how your illness
progresses. Genes that are found in the blood are different for each person and they
provide instructions for processes in the body. To perform this test, genetic material
(DNA) is extracted from the blood cells. We are asking your permission to store some of
the excess DNA for future studies of genes which future research suggests are related in
some way to arthritis. The study does not involve storage of any living cells. Any future
studies which did occur with the stored DNA would require the permission of the
Custodian of the DNA bank of blood collected from St Vincent’s Hospital patients (Dr W
Stevens) and be reported to the Research Ethics Committee before they could proceed.
The blood samples will be labelled only with your unique study code. The sera sample will
be stored in 3 smaller tubes. One of the sera tubes will be stored at XXXXX Hospital to
be used for blood marker studies involving only the scleroderma patients who attend
XXXXX. The other sera sample and the genetic sample will both be transported to the
Arthritis Research Laboratory in Adelaide for storage and future analysis with blood from
other sites participating in the national study. The blood samples will be compared with
samples from other people to help researchers understand why some people with SSc
develop serious complications.
As you have made an appointment at the XXXXX screening centre, you have received
this invitation. If you choose not to participate in the research your attendance at the
screening centre will not be affected, and the ongoing management of your illness will
proceed as per standard care.
3.
Procedures
Participation in this project will involve:

The use of your de-identified health information (information about you that does not
include your name, address, date of birth or anything that would allow someone to
know who you are) that will be collected as a part of routine care at the screening
centre located at St Vincent’s Health. If you consent to this, there will be no change
in the way your screening is conducted or the ongoing management of your illness.
This de-identified data may be entered into international databases for studies of long
term outcomes of patients with scleroderma. You will also be asked to complete a
symptoms and quality of life questionnaires. These will allow your doctor to assess
your health history, current health and general wellbeing. The questionnaires may
take from 15 to 20 minutes to fill during the first visit and about 10 minutes for
subsequent annual visits.
 Two extra blood samples taken at the time of the routine screening procedure. You will
be asked to consent to this procedure separately and have the option of with-holding
Participant Information and Consent Form Version
XXXXX
Page 2 of 7
Appendix Four
consent to the extra blood samples but still including your information in the research.
The consent includes taking two samples, one of 10 ml (approximately 2 teaspoons
full) and one of 16ml (approximately 3 teaspoons) at the same time as the routine
test for the screening program which is 20 ml. This means one procedure will be
performed and from this collection three separate samples will be taken totalling 46
ml. The BNP test will be performed when the next batch is processed; however the
researchers would like to store the other sera samples for testing in the future.
Researchers often make new discoveries about genes, so they would like to keep the
sample rather than asking you to repeat it again at a later date and this means it may
be stored for several years. The research on your blood will only be related to finding
out more information about Scleroderma.
4.
Possible Benefits
Possible benefit from the research part of the program is knowing that you are
contributing to a project that may be able to predict the characteristics of people who are
likely to go on to develop the serious complications. Depending on the stage of your
illness this may not provide a direct benefit to you; however it may benefit others
diagnosed with your illness in the future.
5.
Possible Risks
As the procedures to be performed are all part of routine care there are no additional
risks or side effects, other than that experienced during the taking of the routine blood
test. This would be possible discomfort and pain, minor bruising, and swelling at the site
of the needle prick.
Your health information will be stored securely with access limited to research staff and
in a format that would make identification of you extremely unlikely. All reports on the
findings of the research will be on information that is grouped together so that it will be
impossible to identify individuals.
6.
Alternatives to Participation
If you choose not to participate you can still participate in the screening program.
7.
Privacy, Confidentiality and Disclosure of Information
Your health information that will be used in the research will not include anything that
easily identifies you; however your information will be linked to a unique code. There are
two reasons why this is done. Firstly it means that we can link your information from
each annual visit to compare how your health is over time and the progression of any
symptoms that may develop. The second reason is that at some point in the future if
during our research we become aware of any clinical concerns regarding your health we
would be able to let your treating doctor know of these concerns so that he or she can
advise you on the best treatment options. Your health information will be stored
electronically with information collected from other screening centres around Australia. It
will be stored on a secure computer associated St Vincent’s Health.
The link between your unique code and your identifying information will be kept in a
separate place from the health information. Access to the health information will be
limited to those directly involved in the research. Your data will be kept confidential in
accordance with the standards followed by medical researchers in compliance will all
applicable privacy laws.
This project started in 2007 and has funding committed until 2014. The researchers
continue to seek funding grants and if ongoing funding is made available the project will
continue as long as the information collected is relevant for researching this illness.
Participant Information and Consent Form Version
XXXXX
Page 3 of 7
Appendix Four
Research like this is called a longitudinal study, which means that the information may
be able to provide valuable findings that will help patient care for many years.
We would like to keep your unused stored blood samples for up to ten years so they can
be used in scleroderma research. One sera sample will be stored at St Vincent’s Hospital
and Dr Stevens will seek approval from the HREC before using it in any scleroderma
research projects. The other serum and genetic blood samples will be stored at the
Arthritis Research Laboratory, Adelaide. The National research collaboration has approval
to use the sera for any scleroderma research projects conducted by the researchers in
the collaboration, however approval from the HREC will be sought for all genetic studies.
All samples will be labelled only with your unique code.
Any information obtained in connection with this project and that can identify you will
remain confidential. It will only be disclosed with your permission, except as required by
law.
The researchers plan to publish the results of this research for scientific purposes but
your identity will not be given.
8.
Results of Project
The researchers intend to publish the results of this study in scientific journals.
Participants will be able to request that they receive copies of these publications. A
summary of the findings will also be provided to Scleroderma Australia, the national
support group for distribution to any interested participants or patients.
9.
Further Information or Any Problems
This research is a collaboration set up by a group of doctors from around Australia. If you
require further information or if you have any problems concerning this project, you can
contact the principal researcher located at St Vincent’s Hospital, Dr Wendy Stevens, on
Ph: 9288 2211. For your information the other doctors involved in this project are:
Dr Joanne Sahhar, Monash Medical Centre, VIC
A Prof Susanna Proudman, Royal Adelaide Hospital, SA
Dr Janet Roddy, Royal Perth Hospital, WA
Assoc Prof Peter Youssef, Royal Prince Alfred, NSW
A Prof Peter Nash, Sunshine Rheumatology, QLD
A Prof Allan Sturgess, St George Hospital, NSW
A Prof Kathleen Tymms, Canberra Rheumatology, ACT
A Prof Catherine Hill, Queen Elizabeth Hospital, SA
A Prof Jane Zochling, Menzies Institute, TAS
Dr Gabor Major and A Prof Glenn Reeves, John Hunter Hospital, NSW
Dr Vivek Thakkar, Liverpool Hospital, NSW
A Prof Les Schrieber, Royal North Shore Hospital, NSW
10.
Complaints
If you have any complaints about any aspect of the study or the way in which it is being
conducted you may contact the Patient Representative at XXXXX on Telephone XXXXX.
Participant Information and Consent Form Version
XXXXX
Page 4 of 7
Appendix Four
You will need to tell the Patient Representative the name of the person who is noted
above as principal investigator.
11.
Participation is Voluntary
Participation in any research project is voluntary. If you do not wish to take part you are
not obliged to. If you do consent to any aspect of this research you can change your
mind later. This means that you can ask that your health information that has not been
processed be removed from the research, or that your stored blood sample be destroyed.
You can also provide consent to the blood test at some time in the future if you decide
that you would like to do this later. Any changes to your consent to the research will not
in any way change your involvement in the screening program, the ongoing management
of your illness or your relationship with XXXXX.
Before you make your decision whether to participate, a member of the research team
will be available to answer any questions you have about the research project. You can
ask for any information you want. Sign the Consent Form only after you have had a
chance to ask your questions and have received satisfactory answers.
If you decide to withdraw from this project, please notify a member of the research team
before you withdraw. This notice will allow that person or the research supervisor to
inform you if there are any health risks or special requirements linked to withdrawing.
12. Research Participant Rights
If you have any questions about your rights as a research participant, then you may
contact the Executive Officer Research at XXXXXon Telephone: XXXXX.
12.
Ethical Guidelines
This project will be carried out according to the National Statement on Ethical Conduct in
Research Involving Humans (June 1999) produced by the National Health and Medical
Research Council of Australia. This statement has been developed to protect the interests
of people who agree to participate in human research studies.
The ethical aspects of this research project have been approved by the Human Research
Ethics Committee of XXXXX.
13.
Reimbursement for your costs
You will not be paid for your participation in this project.
Participant Information and Consent Form Version
XXXXX
Page 5 of 7
Appendix Four
XXXX HOSPITAL
CONSENT FORM Protocol NO. XXXXX
Version XXXXX, Dated XXXXX
Site: XXXXX
Full Project Title: Australian Scleroderma Screening Program
I have read, or have had read to me, and I understand the Participant Information
Version XXXXX.
I freely agree to participate in the following parts of the project according to the
conditions in the Participant Information (place a cross in the box for items for which you
are willing to consent):

Use of de-identified health information

A blood sample to be stored at XXXXXuntil it is used in blood marker studies
specifically related to understanding the disease of scleroderma
yes
yes
no

A blood sample to be tested for blood markers including BNP protein level with the
remainder to be stored for several years for testing for other new blood markers,
specifically related to understanding the disease of scleroderma and conducted by
members of the ASIG research team
yes
no

A blood sample to be stored for several years and used for genetic research
specifically related to understanding the disease of scleroderma and conducted by
members of the ASIG research team
yes
no

I wish to be contacted in the future if genetic information is uncovered which may
be important for my future health.
yes
no
I will be given a copy of the Participant Information and Consent Form to keep
The researcher has agreed not to reveal my identity and personal details if information
about this project is published or presented in any public form.
Participant’s Name (printed) ……………………………………………………
Signature
Date
Name of Witness to Participant’s Signature (printed) ……………………………………………
Signature
Date
Declaration by researcher*: I have given a verbal explanation of the research project, its
procedures and risks and I believe that the participant has understood that explanation.
Researcher’s Name (printed) ……………………………………………………
Signature
Date* A senior member
of the research team must provide the explanation and provision of information
concerning the research project.
Participant Information and Consent Form Version
XXXXX
Page 6 of 7
Appendix Four
Note: All parties signing the Consent Form must date their own signature.
Participant Information and Consent Form Version
XXXXX
Page 7 of 7
Appendix Four
XXXX HOSPITAL
REVOCATION OF CONSENT FORM
(To be used for participants who wish to withdraw from the project.)
Protocol NO. XXXX
Version XXXX, Dated XXXX
Site: XXXX
Full Project Title: Australian Scleroderma Screening Program
I hereby wish to WITHDRAW my consent to participate in the research proposal
described above and understand that such withdrawal WILL NOT jeopardise any
treatment or my relationship with XXXX.
Participant’s Name (printed) …………………………………………………….
Signature
Participant Information and Consent Form Version
Date
XXXXX
Page 8 of 7
Appendix 5 - Version 1, Dated 23rd February 2007
APPENDIX FIVE: CORRESPONDENCE WITH REFERRING PHYSICIANS
APPENDIX 5a: Letter inviting physicians to refer to screening centre
AUSTRALIAN SCLERODERMA INTEREST GROUP
RESEARCH PROJECT
XXXXX HOSPITAL
Dear Colleague,
The Australian Scleroderma Interest Group (ASIG) was formed in November 2005 to
bring together physicians interested in research and management of patients with
Systemic Sclerosis (SSc) with a focus on pulmonary arterial hypertension (PAH) and
interstitial lung disease (ILD). ASIG is in the process of establishing designated
screening centres around Australia so that all patients in Australia with a diagnosis of
SSc or Mixed Connective Tissue Disease (MCTD) can have access to high quality
annual screening for the presence of disease-related cardio-respiratory
complications, regardless of whether respiratory symptoms are present. This practice
is currently recommended by the British Thoracic Society [9] and the Royal Free
Hospital Connective Tissue Disease Clinic. There are three components to the
screening which are all part of routine care - an interview to take a history, a clinical
examination and investigations based on the protocol developed by The Australian
Scleroderma Interest Group. It is important to standardise these procedures eg.
ECHO to maximise diagnostic accuracy.
The benefit to the patient includes echocardigraphy and pulmonary function testing
as indicated yearly with no out of pocket expense, with all patients being returned to
the care of their referring Rheumatologist with a results report.
All patients undergoing screening will be invited to participate in a research
component of the project that has two parts and will be under ARA governance. The
first is consent to the collection of their de-identified data that will be aggregated with
data from other centres around Australia. This will enable powerful statistical
analyses to explore predisposing factors linked to the progression of the disease.
The second part is consent to two extra blood samples that are not part of routine
care (for DNA analysis and serum for novel markers), that will be used to examine
potential links between these markers and disease outcomes. Involvement in the
research is optional and patients may consent to the use of their data but not the
extra blood test. Patients will be informed of the research component when their
screening appointment is confirmed. The research protocol has received ethics
approval from XXXX Health Human Research Ethics Committee.
We would like to continue to follow these patients on an annual basis to look at
predictors for development of cardiorespiratory disease. However we do not intend to
take over their day to day management and copies of all tests will be sent to you and
you would be consulted if any significant abnormalities were detected that may
require further investigation or management prior to this being instituted.
We would like to encourage you to discuss the benefits of this screening program
with your existing and recently diagnosed SSc patients. If you wish to proceed with a
referral, please complete the attached sheets, including a signed treatment
agreement.
Appendix 5 - Version 1, Dated 23rd February 2007
If you have any queries we would be delighted to discuss this program further. You
can contact Dr XXXX on XXXX.
Yours sincerely,
Dr XXXX
Consultant Rheumatologist
References
Gibbs JSR. Recommendations on the manangement of pulmonary hypertension in clinical practice.
Heart 2001;86 (Suppl 1): I1-I13.
Mukerjee D et al. Prevalence and outcome in systemic sclerosis assocaited pulmonary arterial
hypertension: application of a registry approach. Ann Rhuem Dis 2003;62: 1088-1093.
Appendix 5 - Version 1, Dated 23rd February 2007
APPENDIX 5b: Form for referral to screening centre
REFERRAL TO AUSTRALIAN SCLERODERMA SCREENING PROGRAM
XXXX HOSPITAL
To: Dr XXXX
Consultant Rheumatologist
Patient details:
Name:
Address:
Telephone:
Date of Birth:
Referring Doctor:
Name:
Address:
Telephone:
Provider Number:
Disease subset:
Diffuse SSc
Limited SSc
MCTD
ANA titre:
_________
ANA pattern: _______
Scl70:
_________
Other antibodies:
_________
Treatment agreement: Could you please tell us how you would like the ongoing
management of your patient to be arranged by ticking the appropriate boxes
below.

Basic screening (clinical assessment, pulmonary function tests, ECG
echocardiogram, chest xray, bloods, urinalysis, 6MWT)
Yes

Further assessment if indicated (eg right heart catheter, high resolution
CT scan chest)
Yes

Consult me before proceeding
Management of pulmonary hypertension, if identified
Yes

No
No
Consult me to discuss treatment
Management of interstitial lung disease, if identified
Appendix 5 - Version 1, Dated 23rd February 2007
Yes

No
Consult me to discuss treatment
Would you like to be notified when we contact your patient for their annual
screen? Please note that frequency of investigations will vary according to
risk as determined by results screening.
Yes
No
Signed Treatment Agreement:
I would like my patient to be enrolled in the Australian Scleroderma Screening
Program with future management of my patient to occur according to the above
options that I have selected. I am aware that my patient will be asked whether they
wish to participate in the research component of the project, but if they do not wish to
participate in the research, the screening will proceed as per standard clinical care.
Signature:
Date:
* Could you please attach copies of PFT, ECHO, Xray, HRCT scan of chest
performed in the last two years, if available?
Your patient will be notified by mail of appointment times and sent more information
about the programme
Office use:
Screening number assigned:
Dates of PFT:
Echo:
6MWT:
clinic review:
Appendix 5 - Version 1, Dated 23rd February 2007
APPENDIX 5c: SUMMARY OF RESULTS LETTER TO BE SENT TO REFERRING
PHYSICIAN
AUSTRALIAN SCLERODERMA INTEREST GROUP
SCREENING PROGRAM BASED AT
XXXX HOSPITAL
Summary of results
Date:
Visit number:
Referring doctor’s name and address:
Patient’s name address and date of birth:
Procedures performed:
Results:
Symptom questionnaire
Physical examination
Pulmonary function tests
Echocardiogram
ECG
Chest Xray
Six minute walk test
Implication of results
Following these assessments, we believe that your patient:
Interstitial Lung Disease

Mild

Moderate

Severe
Pulmonary hypertension

Low risk

Moderate risk

High risk - requires further confirmation with RHC

Has…..
Recommendation:
Should have repeat testing in __ Months with PFT
Echo
Further assessment with......................
Treatment for
should be considered..................
Appendix 5 - Version 1, Dated 23rd February 2007
Please note, if the above indicates further assessment or treatment is required you will be
contacted by Dr XXXX before this proceeds according to the treatment agreement, however
you can contact Dr XXXX at any time if you wish to discuss the progress of your patient.
Signature: __________________
Dr XXXX
Consultant Rheumatologist
Appendix Six
APPENDIX SIX: LETTER CONFIRMING APPOINTMENT TIME
XXXX Hospital Letterhead
Dear ____,
We have received a request for you to attend the Scleroderma screening clinic based at
XXXX Hospital Melbourne. This letter is to confirm your appointment at the Clinic Your
appointment is for:
Day,and Date
Location
Doctor
Enclosed with this letter you will find:



A brochure that provides information about Scleroderma, the complications that
patients sometimes experience and the importance of screening for these
complications. The tests that will be conducted are also explained.
A symptom questionnaire that we would ask you to read and fill out as much as
possible before your appointment. However if you find any of it difficult to complete do
not be concerned you can be assisted at your appointment.
Information on a research project that the group of doctors who have set up the
screening centres around Australia are also involved in. This project hopes to learn
more about the disease of Scleroderma and how the doctors can provide better care
for their patients. Patients who consent to involvement in the research will receive
exactly the same care as those who choose not to participate. We would ask that you
read the Patient Information and Consent form for the research project so that you
can consider whether you would like to participate in the project. If you would like to
participate you will be asked to sign the form during your visit; however there will be a
chance to ask any questions you may have before you make a decision.
Please bring to your appointment any previous Xrays you have of your chest or lungs.
If you have any queries about your appointment please contact the Scleroderma Nurse –
XXXX on XXXX.
Yours sincerely,
Scleroderma Nurse
XXXX HOSPITAL
Appendix Seven
APPENDIX SEVEN: BROCHURE ON SCREENING PROGRAM
Appendix Seven
Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
Australian Scleroderma Screening Program
4.10 PATIENT QUESTIONNAIRE FOR THE FIRST APPOINTMENT
Thank you for completing this form before your appointment. We ask that you read
carefully the instructions and fill in all of the sections below. Your Doctor will discuss the answers
with you, so if you are unsure do not worry – just skip that question and move onto the next.
4.11 1.
YOUR PERSONAL INFORMATION
Date: … / … / …
Surname:
Date of birth:
Address:
Phone (H):
Phone (W):
Phone (M):
Email address:
Referring doctor/physician involved in care:
Name:
Address:
First name:
Gender:
Male
Female
Medicare number:
Name of your Rheumatologist:
GP if not referring doctor:
Name:
Address:
Phone:
Phone:
Have you received information about the option to participate in the research?
Yes
No
(Please note, you will have a chance to discuss this with the doctor before you make a decision)
Can you give us the name, address and phone number of a person not living with you who we can
contact if you move from your current address?
4.12
ASSP First visit : Patient Questionnaire - Version 1 dated 1st May 2014
Page 18 of 66
Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
4.13 2.
YOUR BACKGROUND INFORMATION
Your country of birth:
Your mother’s country of birth:
Are you confident reading English?
Your father’s country of birth:
Yes
No
What is your cultural/ethnic background?
Aboriginal or Torres Strait Islander
Caucasian
Black African-American
Asian
Hispanic
Other
If other, please specify:
Has any first degree relative (parent, sibling) had:
Heart Disease?
Yes
No
Stroke?
Yes
No
Do you know if anyone else in your family has/had Scleroderma?
Diabetes?
Yes
No
Yes
No
If yes, tick for each relative:
Relativ
e
1
Gender
Male
Female
From which
side?
Father
Mother
Relationship with you
Parent
Grandparent
2
Male
Female
Father
Mother
Parent
Grandparent
3
Male
Female
Father
Mother
Parent
Grandparent
4
Male
Female
Father
Mother
Parent
Grandparent
Sibling
Aunt/Uncle
Cousin
Sibling
Aunt/Uncle
Cousin
Sibling
Aunt/Uncle
Cousin
Sibling
Aunt/Uncle
Cousin
What is your current marital status?
single
married or defacto
At this time, are you working?
part time
full time
student
separated
unemployed
home-duties (full time)
divorced
widowed
disability preventing work
retired
If working, what is your current occupation?
What was your occupation when you were first diagnosed with Scleroderma?
Please tick up to 3 of the main industries you worked in prior to your diagnosis:
ASSP First visit : Patient Questionnaire - Version 1 dated 1st May 2014
Page 19 of 66
Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
Petrochemical
Agriculture
Automotive
Manufacturing
Electrical
Computing/electronic
Textile
Driving
Beauty
Nursing
Cleaning
Teaching/education
Other (specify):
What is your highest level of education?
Primary school
Degree
Other, please specify:
Secondary school
Have you ever been pregnant (if female)?
Mining
Plumbing
Construction
Laboratory
Health care
Retail
Trade qualification
Yes
If yes, HOW MANY TIMES have you been pregnant?
Please tick your response for each pregnancy:
Pregnancy 1
Live birth
If live birth, what is the sex of baby?
Diploma
No
Male
Female
Which year?
Stillborn
Miscarriage
If miscarriage, when is the trimester of loss?
1
2
3
Which year?
Pregnancy 2
Live birth
If live birth, what is the sex of baby?
Male
Female
Which year?
Stillborn
Miscarriage
If miscarriage, when is the trimester of loss?
1
2
3
Which year?
Pregnancy 3
Live birth
If live birth, what is the sex of baby?
Male
Female
Which year?
Stillborn
Miscarriage
If miscarriage, when is the trimester of loss?
1
2
3
Which year?
ASSP First visit : Patient Questionnaire - Version 1 dated 1st May 2014
Page 20 of 66
Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
Use back of paper for further pregnancy information…
Have you had any exposure to any of the following BEFORE scleroderma was diagnosed?
Vinyl chloride
Appetite suppressant
Organic solvents
Other please specify:
Epoxy resin
L-tryptophan
Silica dust
None of these
3.
THE HISTORY OF YOUR SCLERODERMA
Please answer as much of this as you are able to.
Have you been told you have:
ASSP First visit : Patient Questionnaire - Version 1 dated 1st May 2014
Page 21 of 66
Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
Diffuse scleroderma
Limited scleroderma
Mixed connective tissue
disease
Have you ever had Raynaud’s phenomena (fingers changing to white/blue in the cold)?
Yes
No
If yes, when did you first start to get Raynaud’s phenomena (month/year):
Have you noticed thickening of your skin?
Yes
No
If yes, when did this start (month/year):
When was the first time (month/year) your fingers became swollen and never returned to normal?
Other than Raynaud’s phenomena, what was the first symptom of scleroderma (please tick one):
swollen fingers
pleuropericarditis
Sjogrens (dry mouth and eyes)
telangiectasia
if other, please specify:
joint/tendon involvement
gastrointestinal problems
pulmonary arterial
hypertension
calcinosis
muscle disease
vascular/digital ulcers
scleroderma renal crisis
severe reflux
When did you first had the above change/s (month/year)?
When was your scleroderma first diagnosed (month/year)?
Who first diagnosed the scleroderma?
PRIOR TO THIS VISIT
Have you ever had a gastroscopy (camera to look in your stomach)?
Yes
No
If yes, when was this done (month/year)?
Have you had lung function tests?
Yes
No
If yes, when was this done (month/year)?
Where was the test done?
Have you had an echocardiogram?
Yes
No
If yes, when was this done (month/year)?
Where was the test done?
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Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
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Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
4.
YOUR SCLERODERMA PAST HISTORY
Please tell us if you have ever had any of the following. If you answer “Yes”, please write AGE or
YEAR when it began below:
GAVE (Gastric antral vascular ectasia , also
called watermelon stomach)
Yes
No
If yes, Age or Year:
Reflux Oesophagitis
Yes
No
If yes, Age or Year:
Oesophageal Stricture
Yes
No
If yes, Age or Year:
Oesophageal Dysmotility
Yes
No
If yes, Age or Year:
Small bowel involvement by scleroderma
Yes
No
If yes, Age or Year:
Episode of Bowel Pseudo-obstruction
Yes
No
If yes, Age or Year:
Pulmonary Arterial Hypertension (PAH)
Yes
No
If yes, Age or Year:
Pulmonary Fibrosis or Interstitial Lung
Disease (ILD)
Heart Problems related your scleroderma:
Yes
No
If yes, Age or Year:
Yes
No
If yes, Age or Year:
Please specify type of heart
problem:
Renal Crisis due to scleroderma
Yes
No
If yes, Age or Year:
Primary Biliary Cirrhosis
Yes
No
If yes, Age or Year:
Muscle involvement by scleroderma
Yes
No
If yes, Age or Year:
Inflammatory arthritis
Yes
No
If yes, Age or Year:
Digital Ulcers
Yes
No
If yes, Age or Year:
Digital Gangrene/Amputation
Yes
No
If yes, Age or Year:
Cancer
Yes
No
If yes , please answer below:
Site of cancer 1:
Type of cancer 1:
Age or Year:
Site of cancer 2:
Type of cancer 2:
Age or Year:
Site of cancer 3:
Type of cancer 3:
Age or Year:
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Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
5.
TREATMENT
Please write below all the drugs or medicines you have taken over the last week for any condition.
Include all drugs, pills, medicines bought with or without prescription, including birth control pills,
hormone replacement, arthritis tablets, aspirin, natural therapies and any others.
Name of medicine
How much is the
dose?
How many per day?
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Have you ever had any of the following (please tick as many as you can)?
Prednisolone
Antibiotics to control my
diarrhoea
Methotrexate
Mycophenolate
Azathioprine
Feeding through my veins
Iloprost infusions
Cyclophosphamide
Home oxygen
Penicillamine
Are there any other drugs or therapies you can remember having for your scleroderma (please list
below):
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Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
Have you ever had any of the following (please tick and write year)?
Sympathectomy
Age or Year:
Coronary artery bypass
Age or Year:
Right heart cathether
Age or Year:
Heart valve surgery
Age or Year:
Coronary artery stent
Age or Year:
Have been admitted to the hospital in the last 12 months?
Operation for peripheral vascular disease
Stent
Age or Year:
Angioplasty
Age or Year:
Bypass
Age or Year:
Yes
No
If yes, please list details of your admission:
Admission #
Reason for admission
Date
Number of days
in hospital
1
2
3
4
5
6
7
Please use the back of this sheet if you need more space
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Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
6.
YOUR CURRENT SYMPTOMS
Can you please indicate with a tick if you have experienced any of the following over the last year?
Raynaud’s (fingers changing to white/blue
in the cold)
Ulcers on the fingers
Ulcers elsewhere on the hands
Episodes of heart burn/acid reflux
Difficulty swallowing
Bloating after meals
Do you have episodes of vomiting?
Yes
No
Yes
Yes
No
No
Yes
No
Yes
No
Yes
No
If yes, how many ulcers?
If yes, how many ulcers?
If yes, how often?
Occasional
Regular
If yes, is it due to any of the
following?
just dry foods
all solids
both liquids and solid
If yes, how often?
Once per day
Once per week
Once per month
Please tick the number of times per
day:
0-1
4-10
1-3
>10
Yes
No
Constipation
Yes
No
Diarrhoea
Yes
No
Anal incontinence
Yes
No
High blood pressure
Yes
No
Angina
Yes
No
If yes, what month and year?
Heart attack
Yes
No
If yes, what month and year?
High cholesterol
Yes
No
If yes, what month and year?
Stroke/TIA
Yes
No
If yes, what month and year?
Diabetes
Yes
No
If yes, what month and year?
Palpitations (heart pounding)
Yes
No
If yes, what month and year?
Asthma/Wheezing
Peripheral vascular disease
DVT/Clot in leg
Yes
Yes
Yes
No
No
No
If yes, what month and year?
If yes, what month and year?
Pulmonary embolus (blood clot in lung)
Yes
No
If yes, what month and year?
Emphysema
Yes
No
If yes, what month and year?
Impotence
Yes
No
Dry eyes
Yes
No
Dry mouth
Yes
No
Number of bowel actions per day
ASSP First visit : Patient Questionnaire - Version 1 dated 1st May 2014
If yes, what month and year?
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Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
Have you ever smoked?
No
Are you a current smoker?
No
Yes
Yes
If yes, year first started:
If yes, average smoked per day now:
If no, proceed to the next question.
If you have stopped smoking, average per day while a smoker:
And if you have stopped smoking, year stopped:
Do you currently drink alcohol?
Yes
No
If yes, how many standard drinks do you have per week now?
If not sure, list type of alcohol and number of glasses/bottles below
Do you use drugs not sold in stores?
Yes
No
When you get up in the morning do you feel stiff?
Yes
No
If yes, how long is it until you are as limber as you will be for that day? Please write:
Number of minutes:
OR
Number of hours:
Which of the following best describes you TODAY? Please tick only one.
I can do everything I want to do
I can do most of the things I want to do, but have some limitations
I can do some, but not all, of the things I want to do and I have many limitations
How do you feel TODAY compared to ONE MONTH AGO? Please tick
only one.
Much better today than one month ago
Better today than one month ago
The same today as one month ago
Worse today than one month ago
Much worse today than one month
How SATISFIED are you with your ability to do your usual activities? Please tick only one.
Very satisfied
Somewhat satisfied
Somewhat dissatisfied
Very dissatisfied
4.14
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Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
7.
YOUR CURRENT BREATHING
Can you please indicate the response that applies to you in the last month?
After climbing JUST one flight of stairs would you describe your breathing as:
0
0.5
1
2
3
4
5
6
7
8
9
10
no breathlessness
very, very slight (just noticeable)
very slight
slight
moderate
somewhat severe
severe
very severe
very, very severe (almost maximal)
most severe breathlessness
Are you breathless when you do any of the following?
1.
2.
3.
4.
4.
5.
6.
Walking on flat
Walking up incline
Showering
Dressing
Housework
All the time
All the time
All the time
All the time
All the time
Most of the time
Most of the time
Most of the time
Most of the time
Most of the time
Has your Raynaud’s phenomena been worse in the last month?
Sometimes
Sometimes
Sometimes
Sometimes
Sometimes
Yes
Never
Never
Never
Never
Never
No
How many times do you experience Raynaud’s per week:
Have you been more breathless in the last month?
Has your skin thickening been worse in the last month?
Yes
Yes
No
No
Has your skin been itchy in the last month?
0
no itch
1
very slight itch
2
slight
3
moderate
4
somewhat severe
5
severe
6
7
very severe
8
9
very, very severe (almost maximal)
10
maximal itch
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Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014
8.
YOUR PAST HEALTH HISTORY
Please list below all operations you have ever had. Please write N/A on the following box if there is
none.
Operation
1.
Year
Surgeon
Hospital, City State
2.
3.
4.
5.
Please use the back of this sheet if you need more space
Please list below all major illnesses or admissions to a hospital (other than for operations). Please
write N/A on the following box if there is none.
Illness or reason for hospitalisation
1.
Year
Hospital, City State
2.
3.
4.
5.
Please list any major medical problems you have had other than scleroderma. Please write N/A on
the following box if there is none.
Medical problems
1.
Year
2.
3.
4.
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Appendix Eight –UCLA SCTC GIT 2.0
4.15 9. THE LEVEL THAT YOUR ILLNESS AFFECTS YOUR LIFE
Please cross out the numbered box below each item to indicate the level it applies to you.
a.
We are interested in learning whether or not you are affected by pain because of your illness.
How much pain have you had because of your illness IN THE PAST WEEK?
VERY SEVERE
PAIN
NO PAIN
0
1
2
3
4
5
6
7
8
9
10
b. IN THE PAST WEEK how much have your intestinal problems affected your daily activities?
INTESTINAL PROBLEMS
DO NOT LIMIT ACTIVITIES
0
c.
1
2
3
VERY SEVERE
LIMITATION
4
5
6
7
8
9
10
IN THE PAST WEEK how much has your breathing problems interfered with you daily
activities?
BREATHING PROBLEMS
DO NOT LIMIT ACTIVITIES
0
1
2
3
VERY SEVERE
LIMITATION
4
5
6
7
8
9
10
d. IN THE PAST WEEK how much has your Raynaud’s interfered with your daily activities?
RAYNAUD’S DOES
NOT LIMIT ACTIVITIES
0
e.
1
2
VERY SEVERE
LIMITATION
3
4
5
6
7
8
10
IN THE PAST WEEK how much have your finger ulcers interfered with your daily activities?
FINGER ULCERS
DO NOT LIMIT
0
f.
9
1
VERY SEVERE
LIMITATION
2
3
4
5
6
7
8
9
10
Overall, considering how much pain, discomfort, limitations in your daily life and other changes
in your body and life, how severe would you rate your disease today?
NO
DISEASE
0
VERY SEVERE
LIMITATION
1
2
3
4
5
ASSP First visit : Patient Questionnaire - Version 1 dated 1st May 2014
6
7
8
9
10
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Appendix Eight –UCLA SCTC GIT 2.0
Please complete the extra sheets for HAQ (health assessment questionnaire) and SF-36 Health Survey which
are standard questionnaires that we would like to use so that we can compare the impact of this illness with
people who have other health issues.
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