type 1 diabetes · 2020. 1. 11. · type 1 diabetes is a lifelong autoimmune disease that destroys...

Type 1 Diabetes Clinical Research Network Annual Report 2010/2011 Juvenile Diabetes Research Foundation

2 JDRF Australian Type 1 Diabetes Clinical Research Network – Annual Report 2010/2011

Table of Contents

Executive Summary ............................................................................................................ 3

Chairman’s message .......................................................................................................... 4

CEO’s message ................................................................................................................... 5

Type 1 diabetes ................................................................................................................... 6

The burden of type 1 diabetes............................................................................................ 6

How will a clinical research network help? ....................................................................... 7

Type 1 Diabetes Clinical Research Network ..................................................................... 8

Launching a national network ............................................................................................ 9

Objectives and outcomes ................................................................................................. 10

Objective 1 - Increasing clinical trial activity and capacity in Australia .............................. 10

Objective 2 - Facilitating patient involvement in Australian clinical trials ........................... 11

Objective 3 - Enhancing research collaboration ............................................................... 12

Clinical trials funded and/or supported ........................................................................... 13

Overview of supported trials ............................................................................................ 14

Looking to the future ........................................................................................................ 15

Governance and operations ............................................................................................. 16

CRN Executive Board ...................................................................................................... 16

CRN Committees ............................................................................................................ 16

Financial statements ......................................................................................................... 17

Statement of Comprehensive Income .............................................................................. 17

Statement of Financial Position ....................................................................................... 18

Financial commentary ..................................................................................................... 18

Accounting policies .......................................................................................................... 19

Director’s declaration ....................................................................................................... 19

Auditor’s opinion .............................................................................................................. 20


Executive Summary The Australian Type 1 Diabetes Clinical Research Network (CRN) was established in 2010/2011 to support the effective translation of laboratory research into clinical outcomes for the 122,300 Australians living with type 1 diabetes. Funded by the Department of Health and Ageing and administered by the Juvenile Diabetes Research Foundation (JDRF), the CRN has been established to provide a national clinical platform that funds clinical research and coordinates services, resources and trial participants. By laying this foundation, the CRN will increase clinical trial activity and capacity, facilitate patient involvement and enhance research collaboration and improve effectiveness. The CRN had a fruitful first year of operation, with a number of key developments occurring over the 2010/2011 period. These included –

The establishment of the CRN Executive Board with the induction of the Hon Dr Michael Wooldridge as Chairman.

A JDRF-led workshop of 20 key type 1 diabetes opinion leaders which took place in August 2010. Participants demonstrated overwhelming support towards the CRN.

Distribution of the first CRN Request for Application resulted in 23 letters of interest. Subsequent review identified three strong candidates for trial initiation funding, and a further two externally funded candidates for administrative support.

Launch of the CRN at Australian Parliament House, with special guests including the Hon Mark Dreyfus MP QC, Professor Warwick Anderson, and internationally recognised diabetes clinical researcher and pioneer of insulin pump technology, Professor Bill Tamborlane.

Review of existing network support models both locally and internationally and the integration of these insights into a draft CRN Charter and protocols. These will be reviewed and approved in 2011/2012.

A public presence was developed for the CRN including production of a publicly accessible website (www.t1dcrn.org.au) containing information about the CRN and lay summaries of supported programs.

A number of important activities are being planned for the 2011/12 financial year. These include overall approval of a Charter for CRN participants, completion of individual Funding Agreements and trial activation documents, and the development of a patient referral capability to support recruitment of participants to CRN-funded or -supported trials.

http://www.t1dcrn.org.au/


Chairman’s message

Type 1 diabetes is a cruel disease, striking young people and lasting a lifetime. While

classed as a chronic condition, many of the associated health complications are

acute and life threatening.

While the dream of researchers and the type 1 diabetes community is to find a cure, the

reality is we urgently need solutions for improving the day-to-day lives of people with the

disease. By doing this, we also reduce the long term costs – both personal and societal.

But taking these solutions from the lab bench to the patient is complex and expensive. Often

the process requires expertise or infrastructure that isn’t widely available. Finding research

partners and recruiting participants can be time consuming and challenging. This is why the

Australian Type 1 Diabetes Clinical Research Network (CRN) is so important.

The CRN aims to support the process and facilitate partnerships. By consulting both

researchers and patients, it will enable the development of a dynamic, yet sustainable,

network of support, information and infrastructure.

The Australian Government has demonstrated considerable insight by supporting this

innovative scheme, recognising that upfront support will provide an ongoing return on

investment.

The CRN would not be possible without the passion and expertise of the Juvenile Diabetes

Research Foundation. As the premier advocates for the type 1 diabetes community both in

Australia and around their world, they are uniquely placed to lead this program.

Finally, I would like to acknowledge the Australian type 1 diabetes research community,

without which this world-class program would not be possible. The quality of Australian

research is recognised internationally, and I am pleased to say it is now being acknowledged

at a local level.


CEO’s message

Establishment of the Type 1 Diabetes Clinical Research Network in Australia has

secured our international reputation as a leader in type 1 diabetes research and

provided a solid template for the extension of this model to other chronic conditions.

Australia has a proud history of research innovation. Our scientists and clinicians are

internationally recognised and the impact of their work can be seen in the volume of high

quality publications and citations. This is the foundation upon which the CRN has been built.

As we further grow and develop the CRN, benefits are already being seen. The financial and

managerial support provided for the five clinical trials outlined in this report will enable

patients to access cutting edge treatments whilst upskilling participating researchers and

clinicians.

The collegial workshops organised by JDRF under the auspices of the CRN have brought

together some of the best minds in the field and, for the first time, enabled a centralisation of

expertise and available infrastructure. This has already resulted in the development of new

partnerships and by enhancing the sharing of resources, reduced the need for duplicate

research infrastructure.

Other important benefits of the CRN will be seen in the long-term. As we grow research

capability, we will make a real contribution to the global understanding of type 1 diabetes and

position Australia as the ideal location for ongoing international research and investment.

This Annual Report provides a comprehensive profile of the objectives and significant

outcomes from the first year of the Australian Type 1 Diabetes Clinical Research Network. I

am proud to present this overview of work undertaken in 2010/2011 and look forward to

extending this important program in the coming years.

Mike Wilson

Chief Executive Officer Juvenile Diabetes Research Foundation


Type 1 diabetes Type 1 diabetes is a lifelong autoimmune disease that destroys the ability to produce insulin, a hormone which is vital for life. It is generally diagnosed in childhood but can arise at any age and is not preventable. The causes of the disease are not fully understood, but scientists believe that a person’s genes play a role, as well as a variety of potential environmental factors. People with type 1 diabetes must take insulin injections or receive a continuous infusion of insulin through a pump every day to stay alive. Current estimates show 122,300 Australians are living with type 1 diabetes, and with 6 new cases diagnosed every day, Australia has one of the highest per capita rates of type 1 diabetes in the world. It is the fastest growing chronic disease amongst Australian children, and incidence is increasing1.

The burden of type 1 diabetes A diagnosis of type 1 diabetes can reduce overall quality of life and life expectancy, but also imposes a significant financial burden on the individual, caregivers, and the health system.2 The chronic nature and relatively early onset of the condition means health expenditure includes not just long-term disease management but also treatment of common health complications including coma, blindness, kidney failure, stroke and amputation. The development of new treatments and therapies would not only improve the lives of people living with type 1 diabetes, but also reduce the significant financial and community costs associated with the disease.

1 Diabetes: Australian facts 2008. Diabetes series no.8. Australian Institute of Health and Welfare, Canberra 2008 2 Colagiuri A, Brnabic A, Gomez M, Fitzgerald B, Buckley A, Colagiuri R. Diabco$t Australia Type 1: Assessing the burden of Type 1 Diabetes in Australia. Diabetes Australia, Canberra 2009.


How will a clinical research network help? There is an exponential growth in type 1 diabetes clinical trials being conducted around the world, yet this is not being reflected in Australia. A search conducted by JDRF in early 2010 showed at least 153 clinical trials were actively recruiting people with type 1 diabetes internationally. Only nine of this type were recorded in Australia. Australian type 1 diabetes research is of very high quality, and this is demonstrated by high impact scientific output and above-average success in international peer-reviewed grant applications3. The challenge for clinical researchers lies with the transition of laboratory research into clinical trials. As Professor Warwick Anderson AM, CEO of the National Health and Medical Research Council stated at the 75th Anniversary NHMRC Symposium in 2011 “We need to learn how to accelerate the translation of research into how clinical care is offered to patients”. The establishment of a national clinical platform coordinating services, resources and trial participants will enable increased participation in international trials and establishment of local trials. It will also allow the type 1 diabetes community access to potentially life-saving novel therapies, reducing disease burden.

3 Australian Type 1 Diabetes Research Agenda - Partnering science, government and the community. 2nd Edition. Juvenile Diabetes Research Foundation. Sydney. 2010.


Type 1 Diabetes Clinical Research Network The Australian Type 1 Diabetes Clinical Research Network (CRN) was established to increase clinical trial activity in Australia and leverage existing investment in type 1 diabetes research in Australia. The activities of the CRN will also enable access to new therapies and treatments for the Australian type 1 diabetes community. The CRN works in partnership with researchers, clinicians, funding bodies and patient groups to integrate Australian capabilities in this field. It fulfils a key recommendation from the Type 1 Diabetes Research Agenda4, an initiative that mapped the Australian diabetes research landscape with input from over 100 of Australia’s best researchers. The primary objectives of the CRN are outlined below.

1) Increase clinical trial activity and capacity in Australia - Fund and support the implementation of local investigator-initiated trials - Build Australia’s capacity and competiveness in attracting industry and

internationally-sponsored clinical trials in type 1 diabetes to Australia - Facilitate and enhance the participation of healthcare professionals in clinical trials in

Australia

2) Facilitate patient involvement in Australian clinical trials - Increase patient and public awareness and understanding of clinical trials - Provide better access to and involvement of patients in type 1 diabetes clinical trials

in Australia

3) Enhance research collaboration - Improve the interaction and coordination between trial sponsors, trial sites, patients,

and existing trial support services. The CRN was established by a $5 million grant to JDRF from the Australian Government, subsequent to a personal pledge of $500,000 from JDRF President Dr Susan Alberti AO towards supporting clinical trial activity in Australia.

4 Australian Type 1 Diabetes Research Agenda - Partnering science, government and the community. 2nd Edition. Juvenile Diabetes

Research Foundation. Sydney. 2010.


Launching a national network The Australian Type 1 Diabetes Clinical Research Network was officially launched at Parliament House, Canberra in June 2011.

The launch included presentations from a number of eminent speakers including the Hon Mark Dreyfus QC MP, Cabinet Secretary and Parliamentary Secretary for Climate Change and Energy Efficiency, Chairman of the CRN the Hon. Dr Michael Wooldridge, Prof Warwick Anderson, CEO of National Health and Medical Research Centre (NHMRC) and Professor William V. Tamborlane MD, Professor of Paediatric Endocrinology and Deputy Director of the Yale Center for Clinical Investigations. Attendees also heard from Ellie and Casey McDonald-Smith - two special young women who live with type 1 diabetes every day.

In addition to launching the CRN, the first three research projects that would receive direct CRN support were announced and profiled. The launch generated significant interest amongst Australian politicians with over fifty Members and Senators attending. It also generated interest amongst the research and health communities (many of whom attended the event) as well as becoming the basis for outreach to the type 1 diabetes community and general media.

Message from Casey Macdonald-Smith, age 14 ‘Thank you for thinking of us and setting up the Type 1 Diabetes Clinical Research Network to take us closer to finding a cure for type 1 diabetes. My sister Ellie and I both have type 1 diabetes. Living with diabetes is not easy or fun and it frightens me about how I’m meant to always look after myself. I worry about the complications that I might get later on. I hope one day there is a cure, not just for me and Ellie, but for everyone else too – we don’t want other kids going through what we go through.’


Objectives and outcomes

Objective 1 - Increasing clinical trial activity and capacity in Australia The ultimate goal of the CRN is to increase the number of type 1 diabetes clinical trials involving Australian researchers and patients. Activities undertaken within Objective 1 aim to provide financial and managerial support to enable the activation of new studies and the local expansion of existing trials. In the longer term, this will grow to include the provision of enhanced infrastructure and resources for researchers considering clinical trial activity.

Outcomes 2010/2011

The first Request for Application (RFA) was widely distributed to the scientific community in November 2010. The excellent response to this letter resulted in the identification of strong candidates for CRN support, selected via a rigorous process that included both international scientific and lay review.

Three candidates were granted funding support through the CRN for trial initiation and development. The fourth (AdDit) trial was underway internationally with the establishment of 3 additional local sites and increased recruitment activities for the five existing sites. Although not funded by the CRN, the AdDit trial will be coordinated via the CRN to enable shared access to resources and support. In early 2011, another externally-funded trial, the Low Glucose Suspend Trial, was brought under the CRN umbrella (see page14 for more details on these trials).

Clinical Research Funding Agreements are currently being negotiated with recipient institutions, and are expected to be finalised by the end of 2011. These will include final budgets and agreed project milestones.

Establishment of the right organisational structure for the network is paramount to its long term viability and success. A review of existing network support models both locally and internationally has been completed by JDRF in 2010/2011 and has been used to draft the CRN Charter and ongoing protocols. These will be presented to the research community to be reviewed and approved in 2011/2012.


Objective 2 - Facilitating patient involvement in Australian clinical trials Objective 2 aims to increase awareness of the importance and benefits of clinical trials. This is of particular importance to members of the type 1 diabetes community who wish to participate in clinical trial activity and also to researchers looking to recruit patients. In addition to enhancing awareness, the CRN aims to develop structures that enable a simple and direct connection between trials and potential recruits.

Outcomes 2010/2011

The publicly accessible website (www.t1dcrn.org.au) was developed in 2010/11 and launched in conjunction with the launch of the CRN. This is the first phase of the website, designed to be a dynamic tool for virtual networking and information-sharing amongst both researchers and patients.

Lay summaries of CRN-funded clinical trials have been made available online and used as the basis of JDRF newsletter articles and media outreach.

Branding of the network is complete and officially titled the Australian Type 1 Diabetes Clinical Research Network. A logo has been developed and is used on all communication channels.

The CRN was extensively profiled in JDRF communications with both the type 1 diabetes community and healthcare professionals. This included media outreach, fact sheets, newsletters and reports.

Following discussions with JDRF International and JDRF Canada, detailed planning is underway for the development of an Australian Patient Referral Network. This online resource will further enable interactions between trial investigators and potential recruits.

http://www.t1dcrn.org.au/


Objective 3 - Enhancing research collaboration One of the operational challenges faced by researchers considering clinical trial activity is the coordination of trial sponsors, sites, patients and infrastructure. The CRN aims to alleviate this challenge by increasing collaboration and connecting researchers to available resources.

Outcomes 2010/2011

A JDRF-led workshop of 20 leading type 1 diabetes opinion leaders took place in Melbourne on the 6thAugust, 2010. Researchers discussed the framework of the CRN and clinical resource sharing. There was an overwhelming support towards the CRN and willingness to collaborate.

Strong relationships with key clinical research groups and individuals were established and strengthened in 2010/2011. In addition to ongoing dialogue with key opinion leaders in Australia and overseas, JDRF profiled the CRN at the 2010 Australian Diabetes Association/Australian Diabetes Educator Association National Conference in Sydney. This conference is the primary meeting for Australia diabetes clinicians and researchers, attracting around 1500 attendees

A detailed map of available clinical resources (such as DNA samples, patient databases) was developed and published by JDRF in 2011. Compiled with the assistance of the research community and funded by a partnership with the Macquarie Group Foundation, this valuable document5 provides universal visibility of resources that are currently available or are potentially accessible. It also provides recommendations for better placement of resources to support a critical mass of researchers.

A regular teleconference schedule has been established with the Canadian Clinical Trial Network to exchange current ideas in network implementation and explore the foundations for future collaborations.

5 Australian Type 1 Diabetes Research Resource Map. Juvenile Diabetes Research Foundation, Sydney 2011


Clinical trials funded and/or supported 2010/2011

Project Title Primary

Investigator Number of local sites

Trial participants

Establishment of a Paediatric Endocrine Database

A/Prof Maria Craig 24 (NSW, WA, VIC, SA, QLD, TAS, NT)

Over 8000 patients recruited into the database

Hypoglycaemia prevention with predictive suspension of insulin delivery

Prof Tim Jones 5 (WA, NSW, VIC, SA)

270 including control subjects

REMOVAL* Australian sub-

study Prof Alicia Jenkins 3

(NSW, VIC)

90 in addition to existing participants

Adolescent Type 1 Diabetes Cardio-renal Intervention Trial

(AdDit) *+

Prof Tim Jones 8 (WA, NSW, SA, VIC, QLD)

>1000

The Low Glucose Suspend

Trial+

Prof Tim Jones 1 (WA)

150

* International trials

+ Denotes study managed but not funded through the CRN


Overview of supported trials Establishment of the Paediatric Endocrine Database

The Australasian Paediatric Endocrine Group (APEG) represents health professionals caring for children and young people with diabetes. APEG applied for funding to establish a nationwide population-based clinical database focused on the paediatric population. Pockets of important data already exist but there is an urgent need for uniform collection and storage protocols, as well as establishment of a central information portal. The project will include registration of all new cases in children and young people (~1000/yr) as well as analysis of existing cases attending clinics (~8000 nationally). Ultimately, this database will facilitate research linkages and deliver an extremely valuable research resource.

Hypoglycaemia prevention with predictive suspension of insulin delivery

Low blood glucose levels or hypoglycaemia is a common side effect of insulin therapy. As well as being potentially life-threatening, the fear of hypoglycaemia often limits efforts to achieve optimal blood glucose levels. This trial aims to use continuous glucose sensors to analyse glucose level patterns around the clock. This information will be used to elucidate different causes of hypoglycaemia and enable development of technologies that can automatically suspend insulin delivery when hypoglycaemia is a risk. This approach is the first step toward the ultimate goal of a closed loop control or artificial pancreas.

The REMOVAL Australian Sub-study

Heart attacks, strokes and heart failure are common causes of death and disability in people with type 1 diabetes, and often occur at a younger age. The international REMOVAL (Reducing with Metformin Vascular Adverse Lesions in T1D) trial aims to test whether the use of an existing glucose control therapy (metformin) can be used in type 1 diabetes to prevent early blood vessel complications while helping to improve blood glucose and cholesterol, stabilise weight and prevent other complications. Investigators from the Australian arm of this study will use funding from the CRN to conduct a unique add-on study examining the specific effects of metformin on the heart. Results from this trial will provide important information about the potential for using existing treatment in a new and beneficial way.

The Adolescent Type 1 Diabetes Cardio-renal Intervention Trial (AdDiT)

The prognosis for young people diagnosed with type 1 diabetes during childhood remains poor and this may relate to the higher HbA1c levels encountered during puberty. Morbidity and mortality in these cases are overwhelmingly associated with long-term micro-vascular and macro-vascular complications. AdDiT aims to identify whether early interventional treatment with Statins and/or Angiotensin Converting Enzyme Inhibitors provides cardio-renal protection in high-risk subjects. This large-scale international trial was initiated in late 2010 and is coordinated by the University of Cambridge, UK. Australian trial sites form a significant proportion of patient recruitment. The Low Glucose Suspend Trial

The risk of recurrent and severe hypoglycaemia causes significant anxiety and emotional morbidity for children with type 1 diabetes and their families, particularly during the night. It is also is a limiting factor in the achievement of optimal glycaemic control and is associated with immediate and ongoing health complications. The use of traditional insulin pump therapy, where clinically applicable, has been shown to reduce the risk of hypoglycaemia when used correctly. A new generation of insulin pumps have recently been launched that include a low glucose suspend function. This function works in partnership with a continuous glucose monitoring system to automatically suspend insulin delivery when there is a risk of hypoglycaemia. This study aims to compare this new technology with traditional pump therapy and assess incidence of nocturnal hypoglycaemia and levels of hypoglycaemia awareness.


Looking to the future

1. Using insights gained from the JDRF review of existing clinical research network models, a draft CRN Charter will be presented for external discussion and approval at a meeting of key opinion leaders in November 2011.

The charter outlines:

The scope of the clinical activities that will be funded by the CRN

Operational and governance structures and their proposed roles and responsibilities

The process of administration and scientific review of clinical trials to be undertaken by the CRN

Budget allocation.

It is anticipated that both the CRN Charter and Funding Agreements will be finalised and approved by the end of 2011/2012.

2. Management of the approved clinical trials will continue with a focus on trial

activation, budget allocation and protocol development. Recruitment into CRN-funded clinical trials cannot commence until each of the project specific protocols (including all applicable project documents) have received Human Research Ethics Committee Approval by the applicable Institution. We are expecting this process to be completed in 2012.

3. Background studies are underway to investigate the potential of centralised

infrastructure support, such as the implementation of a national type 1 diabetes tissue bank.

4. Increased focus on the Patient Referral Network will enable the launch of this

valuable tool by the end of the 2012.


Governance and operations The CRN is funded by the Federal Department of Health and Ageing and administered by JDRF. In 2010/2011, JDRF employed an experienced Clinical Network Manager to coordinate the day-to-day activities of the CRN and guide the development of the final operational structure.

CRN Executive Board In 2010/2011, steps were taken to establish a CRN Executive Board with the appointment of the Hon. Dr Michael Wooldridge as Chairman. Dr Wooldridge was a Member of Federal Parliament for 15 years and a leader of the Opposition. He served as Health Minister, during which time he took an active interest in the development and implementation of medical research. In 2000, he was awarded the first Novo Nordisk International Health Policy Award by an international selection panel in recognition of his efforts to advance the cause of diabetes policy.

Mr Michael White was also appointed to the Board in 2010/2011. Based in the US, Mr White has a personal connection to type 1 diabetes and a deep understanding of all aspects of type 1 diabetes research gained from his time on the international JDRF International Lay Review panel and as Chair of the JDRF International Research Committee. It is anticipated that the CRN Executive Board will be expanded in 2011/2012.

CRN Committees As the operational structure of the CRN is finalised in the coming financial year, it has been proposed that a Network Steering Committee be established. Lead by a highly regarded local clinical researcher, this Committee will provide “on-the-ground” information and feedback as well as assisting with key operational decisions. It is also proposed that offshoots of this Committee will concentrate on separate areas such as training, marketing and sponsorship.


Financial statements Juvenile Diabetes Research Foundation International

Clinical Research Network (CRN)

Statement of Comprehensive Income For the period from 25 June 2010 to 30 June 2011

$

Revenue

Government Grant -

Interest Income 285,541

Total Revenue 285,541

Expenditure

Bank charges 46

Promotions & Communications 7,233

Travel & Accommodation 44,098

Legal & Consultant 36,057

Staff Costs 198,107

Total Expenditure 285,541

Co-ordinating Centre -

Clinical Site Delivery -

NET POSITION OF CRN -


Statement of Financial Position As at 30 June 2011

As at

30 June 2011

(audited)

$

Current Assets

Bank Account 586

Investments 5,000,000

Accrued Interest Income 147,075

Net GST -

Total Assets 5,147,661

Current Liabilities

Deferred Income 5,000,000

Accounts Payable 147,661

Total Liabilities 5,147,661

Net Assets

-

Accumulated Funds

Current period -

-

Total Accumulated Funds

-

Financial commentary The Statement of Comprehensive Income on page 17 outlines that the costs of the first period of operation of the Clinical Research Network (CRN) in Australia have been fully funded out of the interest earned on the funds provided by the Federal Government. This is because the first period has involved the launch of the network and the identification and selection of grants to be funded, but no contractual commitment or payments were made during the financial period 2010-2011. Total cost of operation for this period was $285,541. Costs related to Coordinating Centre activity and Clinical Site Delivery were not incurred as research program activity has not yet commenced. The assets of the CRN are dominated by the investment of the funds provided by the Federal Government. It is expected that these funds will be drawn down significantly during the financial year 2011-2012 as the first research payments are made to successful grant applicants. All excess funds provided by the Federal Government have been invested in secured term deposits with major banks with different maturity dates. Cash Balance Statement

Cash at bank as at 30 June 2011 amounted to $5,000,586 inclusive of cash investments. The cash was deposited with Westpac Banking Corporation and is available for future clinical research grants and administrative expenditure contracted by the project.


Accounting policies The above special purpose financial report, comprising the Statement of Comprehensive Income, Statement of Financial Position and cash balance statement, has been prepared in accordance with the historical cost convention.

Director’s declaration In the Directors’ opinion the financial statements and notes set out on pages 17, 18 and 19 give a true and fair view of the Clinical Research Network’s financial position as at 30 June 2011 and of its performance for the financial period ended on that date. This declaration is signed for and on behalf of the directors by:

Mike Wilson CEO and Managing Director

JDRF

Sydney, 20 December 2011


Auditor’s opinion

type 1 diabetes · 2020. 1. 11. · type 1 diabetes is a lifelong autoimmune disease that destroys...

Documents