British Thoracic Society Interstitial Lung Disease Registry Project

Management Protocol

Introduction

The principal objective of the British Thoracic Society is to improve the care of people with respiratory and associated disorders and the Society works to achieve this through a programme of clinical guideline development, quality improvement activities including clinical audit, development of educational resources, the promotion of respiratory research and public awareness activities.

Purpose of the project

The BTS Interstitial Lung Disease Registry launched in February 2013 and initially involves two elements:  Idiopathic Pulmonary Fibrosis Register  Sarcoidosis Register

In contrast to and chronic obstructive pulmonary disease (COPD), which primarily affect the airways, diffuse (or interstitial) lung diseases (ILD) primarily involve the lung tissue (parenchyma). They thereby compromise a major function of the lungs, which is to permit oxygenation of the blood and other organs, and may lead to severe breathlessness and incapacity, respiratory failure and death.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause characterised by variable degrees of inflammation and scarring. The aetiology of IPF is not known but it is not caused by smoking. The true incidence of IPF is unknown, but it is estimated that annually there are 5000 new cases of IPF, 5000 deaths due to IPF and approximately 15000 people in the UK have a diagnosis of IPF at present. Importantly it is now clear that the incidence of IPF is rapidly climbing with a 35% increase in diagnosed cases between 2000 and 2008. The average age at diagnosis is 70yrs, but the rising incidence has been shown to not be a consequence of an ageing population.

Sarcoidosis is a multisystem disease which may affect many organs, but involves the lungs in around 90% of patients. Sarcoidosis is the most common interstitial lung disease, typically accounting for around one third of the interstitial lung disease seen in a specialist respiratory clinic. The cause remains unknown; both genetic and environmental factors have been implicated. Further details about IPF and sarcoidosis are included at Annex 1.

Characteristics of the project

This project provides a means of national data collection for both IPF and sarcoidosis, through the development of the BTS online data collection system which has been used successfully since 2010 for the BTS national audit programme. The intention is to provide an easily accessed system for prospective data collection in a large number of patients so that the public health and epidemiological status of these conditions in the UK can be established.

The development of the BTS ILD Registry builds on work to date which has focussed on developing an understanding of the prevalence and service provision for these conditions, including:

 Publication of the BTS Guideline on Interstitial Lung Disease in 2008. The NICE Guideline on Idiopathic Pulmonary Fibrosis was published in 2013.

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V2.1 - February 2021  IPF survey and workshop: IPF is diagnosed almost exclusively in secondary care, and in contrast to North America (IPFnet), and to a lesser extent mainland Europe (eurIPFreg), there is no national registry of IPF in the UK. Since little is known with regard to the current variations in IPF diagnosis and management, BTS performed a national online survey of all chest in the UK. Invitations were sent to consultation chest physicians in 263 hospitals across the UK in late 2010/early 2011. Responses were received from 121 centres covering a total population of over 37 million people. BTS hosted a workshop in Spring 2011 for 25 clinicians and radiologists working in varied clinical settings within secondary care. The key clinical needs in IPF that could be addressed with a national registry were identified. The data derived from the survey and the workshop will be used to develop the national IPF registry.

 A Pilot Sarcoidosis Registry, developed following a national benchmarking study of ILD which included case studies in sarcoidosis. The retrospective pilot study aimed to evaluate the potential of a web-based registry, by recording demographic and clinical characteristics, follow up and treatment. 199 potential patients from specialist respiratory clinics at two hospitals were identified and 135 sets of case notes reviewed. Demographic and clinical data extracted from first and follow-up visits were entered over 12 weeks, with random data quality checks by at least one other author. General demographic data, biopsy, pulmonary and extra- pulmonary data, were added and data further analysed from two subsets of patients, namely those with cutaneous or neurological involvement. The data obtained have allowed characterisation of the demographics of this group of patients, as well as recording symptoms, investigations, treatment and outcome. The development of this registry represents a valuable resource for recording clinical data in sarcoidosis.

Data on demographics, method of diagnosis, markers of disease severity, and details of treatment and outcome are collected. The intended outcomes of the project include:  Refinement of the clinical characteristics, burden of disease (including its impact on health status and quality of life), and the course of the disease in the British population.  Provision of information which will allow clinicians to reduce delays in diagnosis and to make more informed decisions on the best management strategies.

In the longer term, it is intended that the quality of information provided to clinicians and patients with these conditions will be greatly improved, that guidelines for the diagnosis and management of these diseases will be refined, and robust audit tools developed for ongoing quality improvement activities in individual hospitals.

In due course it is envisaged that Registry data would provide a valuable resource that would enhance recruitment to multi-centre trials.

The development of the Registry within the British Thoracic Society ensures that there will be widespread participation in data collection from those working in respiratory medicine. The Society operates an effective system for communication and dissemination of findings to those who participate in its data collection initiatives, as well as to the wider BTS membership and the respiratory community as a whole, as part of ongoing education programmes (including e-learning), short courses, and BTS Summer and Winter Meetings.

British Thoracic Society Background information: July 2012

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ILD Registry Governance

The ILD Registry project is overseen by a small Steering Group, reporting to the Society’s Information Governance and Quality Improvement Committees. The Steering Group comprises consultant respiratory physicians, specialty trainees, a respiratory nurse, a patient representative, and representatives of appropriate patient charities. The latter group would ensure patient involvement in both streams of the Registry project.

The Society ensures that the ILD Registry Project adheres to the principles of the Data Protection Act 2018, and to the Government’s transparency agenda (as outlined in published guidance), and will ensure that the security of the online data collection system is maintained at all times.

The Steering Group membership and terms of references are enclosed at Annex 2.

The Society’s processes and procedures for handling sensitive information including patient identifiable data, are set out in the BTS Information Governance Policy document.

Patient data may only be entered into the ILD Registry with the informed consent of the patient. Electronic means may be used for seeking, confirming and recording informed consent, in accordance with the HRA and MHRA joint statement on seeking consent by electronic methods (September 2018).

The Registry database is held and administered at the British Thoracic Society (Head Office: 17 Doughty St, London WC1N 2PL).

The data controllers for the management of the Registry project are: Professor Monica Spiteri (clinical) Miss Sally Welham (administrative), Deputy Chief Executive, British Thoracic Society

Professor Spiteri is the applicant named on behalf of the Society in relation to the application for ethics approval for this project.

Mrs Sheila Edwards, Chief Executive, British Thoracic Society is the Data Custodian for the BTS ILD Registry Project.

The British Thoracic Society is registered with the Information Commissioner’s Office: registration number Z7560263.

British Thoracic Society ILD Registry Management information: September 2020

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V2.1 - February 2021 References

Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001;164:1885–1889

British Thoracic Society Interstitial Lung Disease Guideline Thorax 2008 63: v1-v58

Interstitial Lung Diseases. In: European Lung White Book 2003, pp75-83

De Vries J and Wimsberger RM. Fatigue, quality of life and health status in sarcoidosis. In: Sarcoidosis, European Respiratory Monograph 32 vol 10 2005 pp92-100

Macedo P, Coker RK, Partridge MR. Is there a uniform approach to the management of diffuse parenchymal lung disease (DPLD) in the UK?: A national benchmarking exercise. BMC Pulmonary Medicine 2007, 7:3

Coker RK, Wang C, Sepahzad A, Robert NJ, Partridge MR. Characterising sarcoidosis using a web- based registry: a pilot study. Thorax 2010 65 (Suppl IV): A26

V Navaratnam,K M Fleming, J West, C J P Smith, R G Jenkins, A Fogarty, R B Hubbard. Thorax, Vol 66, 2011. The rising incidence of idiopathic pulmonary fibrosis in the UK

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V2.1 - February 2021 Annex 1 Idiopathic Pulmonary Fibrosis (IPF)

The reported median survival in IPF is 3 years from diagnosis and IPF has a poorer prognosis than cancer of the colon, breast or ovary. There is no proven effective drug therapy for IPF, but combinations of corticosteroids, immunosuppressants and anti-oxidants are used to variable extents by clinicians. Lung transplantation is only feasible in a minority and even if listed, patients with IPF have the highest mortality of any group awaiting lung transplantation. The disease poses significant challenges for clinicians in that the diagnosis requires expert integration of clinical, radiological and, when available, pathological data. Diagnostic precision is critical to distinguish IPF from other interstitial lung diseases that my respond for example to corticosteroid therapy. Given the limited therapeutic options in IPF, best supportive care is recommended for all patients with IPF. This includes tailored oxygen therapy (short-burst, long-term domiciliary and ambulatory), pulmonary rehabilitation, and expert palliative care input. It is highly likely that novel, potentially expensive drugs will imminently be available for IPF [NICE pirfenidone health technology appraisal], in which case the precise patient groups that would benefit from these drugs will need to be defined.

The recent BTS survey confirmed that IPF represent a significant burden of disease. On average, clinicians estimate they are seeing over 40 patients with ILD a month (both new and follow up) of whom around 50% have IPF. However 60% of respondents had low confidence in estimating the true number of cases of IPF seen in clinics. With regard to the ability to accurately diagnose IPF, less than half of respondents (44%) had access to a multi-disciplinary meeting and only 35% had expert pulmonary radiology input to interpret HRCT scans. This variation in the diagnostic pathway directly impacts on the confidence with which clinicians are able to diagnose and therefore manage IPF. Recruitment to clinical trials is cited in the BTS guidelines as a key recommendation in the management of IPF, but only 35% of respondents had recruited patients to a trial in the last 5 years.

Based on the BTS survey and workshop, the following areas have been identified as areas of clinical need that would benefit from a national registry. 1. The diagnosis of IPF requires expert integration of clinical, radiological and when pathological data. The consistency and accuracy of this diagnostic process between clinical centres is not known, creates uncertainty in diagnosis and management and probably leads to variation in clinical practice. Clinicians would value the ability to compare diagnostic accuracy between their centre and nationally, with the aim of refining and changing practice if needed. 2. Best supportive care (BSC) for IPF is defined in the BTS ILD guideline and includes tailored oxygen therapy, pulmonary rehabilitation and palliative care. Capturing data on national delivery of BSC would help clinicians identify local shortfalls and improve patient care. 3. Lung transplantation is suitable for a small but important sub group of patients with IPF. There are no data to determine the number of patients that are eligible for transplant assessment or that are assessed but not listed. A registry would highlight variations in transplant referral. 4. Clinicians and patients recognise the value of recruitment to clinical trials in a disease of high mortality for which there is no effective therapy. A national registry of accurately phenotyped patients with ILD, would greatly enhance the UK recruitment rate to multi- centre trials. 5. Novel drugs for IPF will become available in the near future. Pirfenidone has very recently become the first drug to be licensed for use in IPF. The drug is likely to be expensive and therefore its use potentially restricted. A national registry will help identify the potential number of patients eligible for novel expensive drugs and the uptake and use these drugs.

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V2.1 - February 2021 Sarcoidosis

Prevalence ranges from 3 (in white populations) to 47 (in African Americans) per 100,000 population in North America, and 64 per 100,000 population in Scandinavia. Average incidence from radiographic population screening programmes in continental Europe is 10 per 100,000 population. UK general practice data suggest an incidence of around 3 per 100,000 person-years, similar to figures derived from New Mexico and Japan but lower than North American or European estimates. The disease is not only more prevalent in ethnic minorities such as Blacks and Afro-Caribbeans, but these groups also suffer more severe disease and a higher mortality.

Sarcoidosis is commoner in females; incidence peaks between the ages of 20 and 50 years with a smaller peak after the age of 60. There are no exact data European data on working days lost due to sarcoidosis, but many patients with active disease are unable to work because of exertional dyspnoea or other symptoms such as fatigue and joint pains. The course of sarcoidosis varies greatly; there is a high rate of spontaneous remission but chronic disease may occur in up to 30% of patients. To date it remains difficult to predict which patients will develop chronic, progressive severe disease.

Complications of sarcoidosis include , which is associated with increased mortality, fungal infections and aspergillomas, opportunistic infections resulting from immunosppressive therapy, and chronic fatigue which may be persistent and incapacitating. Overall mortality from sarcoidosis in large series is around 5%, the most common causes being severe parenchymal disease causing pulmonary fibrosis, and cardiac and neurological involvement. When required, treatment for active disease usually includes systemic corticosteroids with or without other immunosuppressive therapy such as methotrexate. Long term oxygen may be required; lung transplantation is reserved for those who have failed to respond to maximal therapy and is limited by organ availability.

Quality of life (QoL) and health status are important measures of disease impact and therapeutic outcome. While health status may indicate the presence of limitations, QoL also reflects the extent to which patients view these limitations as a problem in their daily life. Only one QoL measure has been employed in sarcoidosis patients, the WHOQOL-100, and studies have shown that it is reliable and valid in this group.

At least five measures of health status have been used in sarcoidosis studies. Four have shown to be of value for sarcoidosis (but in some cases require validation) include: the 36-item Short-Form Health Survey (SF-36); the Sarcoidosis Health Questionnaire (SHQ); the Symptom Impact Profile (SIP)and the St George’s Respiratory Questionnaire (SGRQ).

Over a decade ago in 1999 the American Thoracic and European Respiratory Societies identified key clinical questions which remain to be answered, including: determining the cause of sarcoidosis; identifying specific tests which doctors can use to predict progression; the optimal length of treatment; the role of current treatments; the discovery of new, less toxic treatments. The 2008 BTS ILD guidelines also identified the need to explore: the long-term effect of corticosteroid treatment on the natural history of the disease; whether steroid treatment is actually associated with a poorer outcome.

While the US ACCESS (A Case-Control Etiologic Study of Sarcoidosis) database serves to address some of these questions in relation to Northern American patients, to date there is no comparable database in the UK. It is likely that the variation in presentation of sarcoidosis between various countries, means that results from the North American ACCESS patients may not be applicable to the British population.

BTS – July 2012

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V2.1 - February 2021 Annex 2

BTS ILD REGISTRY STEERING GROUP

CONSTITUTION

1. TERMS OF REFERENCE

The BTS ILD Registry Steering Group is responsible for the management and supervision of the Society’s Interstitial Lung Disease Registry, which comprises two disease areas: idiopathic pulmonary fibrosis (IPF) and sarcoidosis.

The project aims to provide a means of national data collection for both IPF and Sarcoidosis, through the development of the BTS online data collection system, based on the successful audit programme. The Registry Programme will cover England, Scotland, Wales and Northern Ireland, although it is anticipated that in the early phases of development, participation in the Registry Programme will be limited to a relatively small number of hospitals in each country.

1.1 The Steering Group will meet a minimum of twice each year (with additional teleconferences if required) with the following remit:

 To provide advice to the Society on the development of the BTS Interstitial Lung Disease Registry Programme, which includes separate registers for IPF and sarcoidosis;  To oversee the content and direction of individual disease registers, including advice on ethical issues;  To advise on the development of online data collection system for each register;  To oversee the application for ethical approval for the ILD disease register;  To advise on communication and dissemination of information on each register to potential participants in the UK including the development of a network of ILD registry leads in centres across the UK;  To produce regular progress reports from the individual disease registers for: BTS Standing Committees (Board, IG) The Research and Ethics Committee (REC)  To advise on the content and format of reports to be produced from the data collected via the registry programme as feedback to participating centres and for publication, recognising that additional expertise will need to be obtained for data analysis, etc.  To advise on the criteria for approval of applications from ILD external bodies for access to the data collected by the BTS Registry programme;  To advise on potential expansion of activity to include bio banks;  To provide advice to the BTS Board and Information Governance Committee on possible additional sources of funding for the future development of the Programme.  To provide advice to the BTS Science and Research Committee on research opportunities presented by the Registry programme including sources of external research funding.  To provide advice to BTS Trustees and to BTS Head Office staff on issues related to the operation and management of the ILD registries as required.

2. MEMBERSHIP 2.1 The membership of the Steering Group comprises the following:

 The Chair, who will hold a place on the BTS Information Governance Committee;  Four consultant respiratory physicians;  Two specialty trainees

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V2.1 - February 2021  The Chair or a member of the BTS ILD SAG;  A respiratory nurse with an interest in ILD;  A lay/patient representative;  Representatives of appropriate patient charities

In addition to this, the Steering Group has the right to call on the expertise of specialist non-members as required (i.e. there is a provision to co-opt members whose expertise are required for a limited period of time).

2.2 All members, however selected and in whatever capacity, will normally serve for a maximum of 3 years from the date of taking up membership. The term of service is usually effective from the date of Society’s Annual General Meeting in December each year.

2.3 The Chair–Elect will be appointed in the third year of the Chair’s period of service, to allow handover, and will therefore expect to serve for no longer than 4 years, but exceptionally for 5 or 6 years. This will only occur if the Chair-Elect is already serving on the Committee at the time of the election.

2.4 Members of the Steering Group other than those who are members of the Group by virtue of their position as representative of an external organisation or member of the SAG, can apply to join by volunteering annually in response to a call for volunteers. This is circulated in the early summer each year to all BTS members. The call for volunteers will clearly state the vacancies that are available; the experience and special interests sought (if any) and the arrangements for selection. If there are more volunteers than places available, selection will be undertaken by the Chair of the Group and Honorary Secretary supported by the Chief Executive or Deputy CE, based on the provision by volunteers of a short CV and supporting statement.

2.5 All members of BTS Steering Groups must be members of the Society unless they have been nominated by an external organisation or are acting as lay representatives.

2.6 If a Steering Group wishes to involve a member with specific skills, and that person is not therefore likely to be a BTS member; or, if a Steering Group wishes to vary the membership as outlined above, this MUST be discussed first by the Chair with the BTS Board of Trustees, and agreement of Trustees obtained.

2.7 Every effort is taken to agree dates of meetings one year in advance and notify these to all members as soon as they have been agreed. Dates agreed in advance will only be changed if there are exceptional circumstances, and then at least 8 weeks’ notice will normally be given. If a member misses more than 2 meetings in succession, and there are no extenuating circumstances (in relation to sickness absence, for example), then the Society will ask that member to stand down.

2.8 All members are required to conduct themselves in accordance with the Society’s policies and general procedures (e.g. for travel expenses), and in particular in relation to the policy about relationships with the bio-medical and tobacco industries, and the associated Declarations of Interest Scheme (DoI) (see section 4, following). Members are especially asked to note that efforts should be made to return a completed DoI form before the end of January each year, or prior to the first meeting of the Committee in every calendar year, whichever is earlier. If a form has not been completed after a reminder has been given at that meeting, the member concerned will be asked to withdraw until the information has been provided.

2 STANDING ORDERS

3.1 Role of the Chair of the Steering Group The Chair of the Steering Group will be a member of the BTS Information Governance Committee and

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V2.1 - February 2021 will be the main link between the development and execution of the Society’s objectives for the Interstitial Lung Disease Registry and the detailed work of the Steering Group. The Chair will also provide an annual report to the BTS Quality Improvement Committee which will provide overall direction and guidance in relation to the Registry’s QI activities and its place within the wider BTS QI framework.

3.2 The Chair is responsible for the direction, conduct, moving forward and completion of Steering Group business, both during meetings and between the meetings. In this task s/he is supported by the Society’s staff (who provide a full secretariat service) and other members.

3.3 The Chair will approve the Steering Group agenda and draft minutes, which are prepared by BTS staff. S/he will also prepare and/or commission papers from other Group members or BTS staff and will chair the formal meetings of the Group and any ad-hoc meetings and teleconferences.

3.4 While BTS staff can draft follow-up correspondence and deal with queries arising from the work of the Group on an operational level from day to day, it is anticipated that the Chair will provide advice on content and professional issues involved and, in particular, deal with peers and external organisations in relation to all areas where clinical leadership is required.

3.5 The Chair has an important role in ensuring that Declaration of Interest forms from all Committee members are scrutinised and any issue of concern discussed with the individual concerned and/or the Honorary Secretary. S/he must also ensure that at the beginning of each meeting members are asked to declare any additional recently-acquired interests, and is expected to exercise judgement in the conduct of Group business in the event of any potential conflicts of interest.

3.6 Succession planning for the Chair of the Group will take place as follows. In the spring of the year when the Chair’s 3 year term in office is due to end, the Society will advertise that a vacancy for the Chair of that Committee will be coming up. A job description will be available. Members of the Committee plus any other member of the Society will be invited to apply. All applicants will be required to send a short c.v. and a statement outlining why they are interested in the position and what they feel they can bring to the post. Applicants will be shortlisted (if necessary) and interviewed by the Chair of the Board of Trustees and the Honorary Secretary, supported by the Chief Executive or Deputy Chief Executive. The panel’s decision will be shared with the Officers’ Group for ratification and made known to the successful candidate so that the Chair-elect can spend the remainder of the year before taking up post shadowing the incumbent and receiving information and training about being a Trustee of the Society. The appointment will also be reported to the next scheduled meeting of the Board of Trustees.

3.7 Before a Chair is appointed, s/he will be asked to submit an updated Declaration of Interest form, if this is not already available. This will be submitted to the Chair of the Board of Trustees and Honorary Secretary for approval before the appointment is confirmed.

3.8 Frequency and conduct of meetings of the Committee The Committee will normally meet twice a year. Meetings will usually be held at the Society’s headquarters building in London. These meetings may be held by video/teleconference.

3.12 The BTS staff member responsible for the Group will draft an agenda and discuss with the Chair no later than 3 weeks before the date of the meeting. The agenda and papers will be sent by email to all members no later than 7 days (and preferably) 10 days before the meeting takes place. It is not good practice, and will not normally be possible, to table papers at meetings, especially those that contain detailed information except at the discretion of the Chair, and taking into account circumstances involved. Authors of papers are therefore asked to submit in time according to the date given by the secretariat, so that copying can take place.

3.13 A draft minute, including named action points, will normally be produced within 7-10 days of the meeting to be agreed by the Chair and then sent to members as an aide-memoire for those who may

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V2.1 - February 2021 have been asked to carry out actions, or for the information of those who were not able to attend.

3 CODE OF CONDUCT

4.1 The Society values the contribution of those members who serve on its various Committees, Advisory Groups and Working Parties. Without this service, it would not be possible to carry out the great variety of work that is undertaken and which contributes to the raising of standards of care for people with . BTS has a justifiably high reputation for the quality of its activities and the advice it gives to external bodies.

4.2 The Society is also proud to have been a pioneer in a number of areas, including its Declarations of Interest scheme, which has been replicated by a number of other Societies in recent years. The probity of our actions is underpinned by a number of policies and procedures which are kept under regular (annual) review.

4.3 To ensure effective functioning of the Declarations of Interest process the Chair should proactively manage declarations from Steering Group members. This will include:  Having declarations of interest as a standing item on all meeting agendas;  Formally asking members whether anything has changed since they submitted their last declaration;  Formally asking members at the start of each meeting whether there are any agenda items which may cause conflict or in which they have an interest;  Seeking advice when required from the Honorary Secretary or Chief Executive if there are any concerns about new items mentioned under declaration of interest.

4.4 Consequently, we ask all members of Committees, Advisory Groups and Working Parties to note and abide by the following policy and procedures documents:-

 BTS Policy on Biomedical Industries: Joint Working and Commercial Sponsorship and associated Declarations of Interest Scheme. This is reviewed annually by BTS Council and Trustees.  Endorsement Policy (reviewed in June 2020)  Media policy (reviewed in October 2020)  Travel and subsistence policy (reviewed annually by Honorary Treasurer and Chief Executive)

These documents can all be found on the BTS website in the “governance” pages of the section entitled “About BTS”

Date of production/revision: February 2021 By: Deputy Chief Executive Review date: July 2021

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