Australian Idiopathic Pulmonary Fibrosis Registry: Vital lessons from a national prospective collaborative project YUBEN MOODLEY,1 NICOLE GOH,2 IAN GLASPOLE,2 SACHA MACANSH,3 E HAYDN WALTERS,4 SALLY CHAPMAN,5 PETER HOPKINS,6 PAUL N REYNOLDS,5 CHRISTOPHER ZAPPALA,7 WENDY COOPER,8,9,10 ANNABELLE MAHAR,8,9 SAMANTHA ELLIS,2 SAMUEL MCCORMACK,11 WILLIAM DARBISHIRE,3 RICHARD WOOD-BAKER,4 TAMERA J. CORTE12,9 AND AUSTRALIAN IPF REGISTRY STEERING COMMITTEE 1
Royal Perth Hospital, University of Western Australia, Perth, 2Department of Respiratory Medicine, The Alfred Hospital, Melbourne, 3Lung Foundation Australia, Brisbane, 4Department of Medicine, University of Tasmania, Hobart, Tasmania, 5 Respiratory Medicine, Royal Adelaide Hospital, Adelaide, South Australia, 6Thoracic Medicine, The Prince Charles Hospital, Brisbane, 7Respiratory Medicine, Royal Brisbane & Women’s Hospital, Brisbane, Queensland, 8Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, 9Sydney Medical School, University of Sydney, 10School of Medicine, University of Western Sydney, and 11Radiology Department and 12Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, Australia
There is little Australian epidemiologic data on idiopathic pulmonary fibrosis (IPF), a relatively uncommon but devastating disease. The vast geographic distances in Australia have been a major impediment for collaborative research into IPF. A collaborative national effort, the Australian IPF Registry, has been formed, launched and is recruiting successfully (n = 359, January 2014). Our experience provides unique insights for others wishing to set up IPF registries and in time for a global IPF registry. Key words: Australia, epidemiology, idiopathic pulmonary fibrosis, natural history, registry. Abbreviations: 6MWT, 6-min walk test; ATS, European Respiratory Society ; ERS, American Thoracic Society; HRCT, highresolution computed tomography; IPF, idiopathic pulmonary fibrosis; IQR, interquartile range; LFA, Lung Foundation Australia; SpO2, saturation of oxygen.
We report the successful establishment of the Australian Idiopathic Pulmonary Fibrosis (IPF) Registry, and its initial findings. IPF is a severe and progressive fibrosing lung disorder with a median survival from diagnosis of 3–5 years.1 Previously considered rare, the incidence of IPF appears to be increasing with estimates of incidence ranging from 4/100 000 in persons aged 18–34 years to >200/100 000 among those aged above 75 years.2–6 The relatively low prevalence of IPF has historically limited large epidemiological, clinical and basic science research into the Correspondence: Tamera J. Corte, Respiratory Medicine Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia. Email: [email protected]
Received 13 March 2014; Invited to revise 5 May 2014 and 18 June 2014; Revised 26 May 2014 and 18 June 2014; Accepted 18 June 2014 (Associate Editor: Toby Maher). Article first published online: 14 August 2014 © 2014 Asian Pacific Society of Respirology
condition. Expert groups have called for a collaborative and systematic approach to this disorder.7,8 In particular, due to the large geographic distances in Australia, collaborative IPF studies have traditionally been considered impossible. The Australian IPF Registry addresses at a national level the epidemiology and natural history of IPF for the first time. The Australian IPF Registry aims to facilitate collaborative research into IPF. In particular, it aims to provide further insight into the epidemiology of IPF in Australia, including the incidence, prevalence and natural history of the disease, the quality of life of these patients with IPF, the local management of IPF and comorbidities and complications of IPF. The Lung Foundation Australia (LFA) established the Australian IPF Registry in February 2012, utilizing philanthropic and pharmaceutical funding in the form of unrestricted educational grants. A multidisciplinary Steering Committee was formed comprising of respiratory physicians, histopathologists and radiologists. Responsibility for administration and intellectual property of the Australian IPF Registry resides with the LFA. Ethics approval was obtained at a national level with subsequent local ethics approval at institutions where the Registry coordinators and principal investigators are located. The Steering Committee’s plans, directions and advice are enacted by a full-time project manager who oversees Registry operations, governance and reporting on a national level. Each state has a parttime Registry coordinator who undertakes the day-today tasks including consent and data collection and entry in each state. The Registry coordinator fosters relationships with both participants and clinicians to ensure that maximum high-quality data are collected. A part-time Registry data manager works to improve data quality and accuracy. Respirology (2014) 19, 1088–1091 doi: 10.1111/resp.12358
Australian IPF registry Table 1 Australian IPF Registry data collection Data source
1 Participant questionnaire
Initial collection only Baseline and every 6 months
2 Physician questionnaire
Repeated every 6 months but collecting distinct information for every patient visit during this time Ongoing although new investigations are identified every 6 months by the physician
3 Clinical investigations
4 Expert panel review
Participants with a HRCT scan and/or surgical biopsy
Data content collected • Demographic information • Smoking history • Family history • Environmental and occupational exposures • Medication and treatment exposures • Medical and occupational history Longitudinal data collection on: • Smoking • Medications • Shortness of breath • Cough and wheeze • Gastro-oesophageal reflux • University of California San Diego Shortness of Breath Questionnaire • St George’s Respiratory Questionnaire • Anxiety and depression score • Sleepiness and tiredness • Additional symptoms • Reason for visit • Oxygen saturation • Respiratory and cardiovascular examination • Extremities/joints/skin/lymphatics • Pulmonary function tests • HRCT scan • Chest X-ray • 6MWT • Blood tests including autoimmune serology • Echocardiography • Bronchoscopy • Overnight oximetry/sleep study • Lung biopsy • Right heart catheter • Bone density scan • Cardiopulmonary exercise test • Radiology panel review • Histopathology panel review • Multidisciplinary panel review
6MWT, 6-min walk test; HRCT, high-resolution computed tomography; IPF, idiopathic pulmonary fibrosis.
Remote-access technology facilitates data collection, while ensuring high-level security. The Registry server is securely hosted by a commercial organization (NicheIT, Sydney, NSW, Australia). Filemaker Pro software (Filemaker Inc., Santa Clara, CA, USA) was selected for its ability to provide aWeb-based interface allowing the Registry coordinators from each state to enter and access data remotely and simultaneously. This was considered a cost-effective and flexible platform option allowing database changes to be made in the live environment. Participants are identified by physicians throughout the six states and two territories of Australia, and a member of the clinical team informs the local Registry coordinator who obtains written informed patient consent. Potential participants over 18 years of age are included if their physician has diagnosed definite, probable or possible IPF and they are able to complete the questionnaires. The diagnosis of IPF is reviewed by © 2014 Asian Pacific Society of Respirology
a central multidisciplinary panel, whereby a consensus diagnosis is made according to the 2011 American Thoracic Society/European Respiratory Society Diagnostic Guidelines. It is estimated that there are 840– 6300 persons with IPF in Australia (based on a prevalence of 4–30/100 000 in the total population of 21 million). We aim to recruit a minimum of 600 persons to the IPF Registry by mid-2015. The data dictionary was determined by the Steering Committee following international collaboration with established IPF research centres. Data are collected at baseline and longitudinally every 6 months from both the participant and their physician, who identifies any investigations that have been performed in the preceding 6 months (Table 1). Research proposals to use Registry data are considered for approval by a research subcommittee, which provides a summary and recommendations to the Steering Committee. A strict set of operating princiRespirology (2014) 19, 1088–1091
1090 ples are applied to data access requests and approval is only granted subject to obtaining relevant ethics committee approval. Seven research applications to use Registry data have been approved by the Steering Committee, of which four are already underway. Following its launch in February 2012, as of January 2014, the Registry has 359 participants consented. Delay in recruitment occurred in some states due to delays in ethics approvals and delays in appointment of the local Registry coordinator. All states and territories in Australia are now actively recruiting patients. Three hundred and fifty-nine participants (237 male; mean age 71.0 ± standard deviation 8.2 years) have been consented into the Registry, 292 (81.3%) participants have a completed initial questionnaire and 164 (45.7%) have a completed physician questionnaire to date. Eighty-four (29.9%) are never smokers, 190 (67.6%) are ex-smokers and 7 (2.5%) are current smokers. Baseline pulmonary function includes: mean forced vital capacity % predicted 81.8 ± 22.7% (n = 203); Forced expiratory volume in 1 s % predicted 85.2 ± 17.4% (n = 203); diffusion capacity of carbon monoxide % predicted 47.1 ± 17.4% (n = 184); and total lung capacity % predicted 71.5 ± 17.9% (n = 80). Median 6-min walk test distance was 447 m (interquartile range (IQR) 360, 485; n = 87), resting saturation of oxygen (SpO2) was 95.0% (93.0, 97.0, n = 85) and end-exercise SpO2 86% (81.0, 92.0; n = 81). Participants had an impaired quality of life and significant breathlessness at baseline, with a median University of California San Diego Shortness of Breath Questionnaire score of 40 (IQR 17, 69); and the median anxiety and depression components of the Hospital Anxiety and Depression Score was 5.0 (IQR 2,8; n = 268) and 4.0 (IQR 2,7; n = 274), respectively (n = 268). The St George Respiratory Questionnaire showed significant abnormality in the mean total score (47.0 ± 20.7) as well as the symptom (49.5 ± 22.1), activity (61.4 ± 23.9) and impact (37.5 ± 22.9) scores. Because of its relatively low prevalence of IPF, and the dispersed nature of our population, it has been difficult to perform quality research studies into this relatively uncommon disorder in Australia. This has led to a worldwide initiative to develop compatible registries to aid research and collaborations in interstitial lung diseases.7,8 The Australian IPF Registry was the first IPF registry to commence operating on a national level. Our data demonstrate that Australian IPF patients are similar to other reported studies in terms of demographic and baseline physiology. We hope that sharing this unique experience will guide the development of similar registries in the international respiratory community. Governance of any registry and its data is vitally important to the utility and outcome of the database. The Australian IPF Registry is under the governance of the independent national organization, the LFA. We found that this has been a major advantage, in terms of credibility, lack of interstate rivalry, administration, financial support and fundraising. The LFA works with the Steering Committee to ensure optimal running of the Registry. The role of Respirology (2014) 19, 1088–1091
Y Moodley et al.
the Steering Committee is complemented by the organizational infrastructure, expertise and support of the LFA. Financial support is an ongoing challenge for any national registry. The initial cost of setting up the Registry was met by the LFA, and the first 2 years were funded by philanthropic and pharmaceutical sources. Funding sources for the next stage of the Registry include pharmaceutical and philanthropic sources as well as research grants. In our experience, useful and significant progress can be made with relatively modest initial funding, which allows some momentum in discussion with potential partners about leveraging more funds. It is a challenge to ensure ongoing enthusiasm for recruitment. In Australia, the national ethics approval form is not recognized in all states, and multiple local institutional ethics approvals are also required. In countries with national ethics approval systems, this may be a more straightforward process. In our experience, Registry staff and the principal investigators working closely with physicians at a national, state and institutional level has encouraged referral to the Registry. While other viable registry models have managed recruitment and data entry at local specialist referral centres, our model involves central referral of potential participants from a wide spectrum of clinical settings to a local coordinator for each state and territory. We have found that our centralized administrative model focuses interest and streamlines the training of the dispersed staff doing the patient consent and data entry. We envisage that our experience will lay the basis for other registries to follow and in time a globalregistry for IPF, and possibly extending to all interstitial lung disease. This would involve the integration of registries with common data sets from around the world. The planning and establishment of any national registry should include preparation for being part of a global network and plan accordingly.
Acknowledgements The Registry is generously supported by the Royal Hobart Hospital Research Foundation, philanthropic sources and grants from InterMune and Boehringer Ingleheim. The authors acknowledge the ongoing work of the Registry coordinators whose efforts have facilitated the development of the Australian IPF Registry, Heather Chaplin, Joanne Fuller, Mary McAlister, Emily Stevens, Karen Symons, Susanne Webster and Data Manager Susan E. Smith.
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