Assessing the burden and economic impact of idiopathic pulmonary fibrosis in Australia

Background:
Idiopathic pulmonary fibrosis (IPF) is the most frequent type of interstitial lung disease in older adults, characterised by progressive fibrosis and scarring of lung tissue, invariably leading to declining lung function, respiratory failure, and death. Treatment options for the disease are quite limited and only two recently introduced medications (pirfenidone and nintedanib) are known to slow disease progression but not cure the disease. IPF is associated with a high symptom burden, typically progressive shortness of breath and cough. There are limited treatment options. The disease typically has a high impact on health-related quality of life (HRQoL) and health resource utilisation.
There still exist many unknowns surrounding the aetiology, risk factors, pathophysiology, epidemiology, and economic burden of IPF, globally and by extension, in Australia. Given the expanding landscape of research on treatments for the disease and high costs associated with these, it is important to characterize the burden of the disease, both from a health and economic perspective, which will facilitate the formulation of policies to allow adequate resource allocation. This will facilitate access to health services and treatments for persons living with IPF.
Objectives:
The primary aims of this thesis were to:
1. Derive incidence, prevalence, and mortality estimates for IPF in Australia.
2. Systematically synthesise and meta-analyse data from available studies to assess health-related quality of life (HRQoL) of people living with IPF and the instruments used in this assessment.
3. Derive health state utility values (HSUVs) for a real-world Australian cohort of IPF patients using the EuroQoL’s five dimension – five level (EQ-5D-5L) instrument to evaluate the effects of IPF disease severity and other relevant factors on HSUVs.
4. Conduct a head-to-head comparison between the EQ-5D-5L and the Assessment of Quality of Life eight-dimension (AQoL-8D) instrument to assess the performance of the two instruments to derive HSUVs in an Australian cohort of persons living with IPF
5. Evaluate the trends in the utilization of pirfenidone and nintedanib in Australia since the initiation of subsidization under the Pharmaceutical Benefits Scheme (PBS).
6. Provide a comprehensive analysis of resource utilisation and costs for IPF in Australia from a societal perspective.
Thesis outline, methods, and summary of key results:
Chapter 1 presents a general overview of IPF along with health economic concepts relevant to this thesis. The studies included in this thesis form part of the QUality of LIfE and Costs AssociaTed with Idiopathic Pulmonary Fibrosis Study (QUIET-IPF) a project funded through the NHMRC Centre of Research Excellence in Pulmonary Fibrosis (CRE-PF) which uses the Australian IPF Registry (AIPFR) as the main platform for recruitment of participants.
Chapter 2 provides a brief summary of the methods, focusing on data sources and recruitment methods.
Chapter 3 presents first estimates of incidence, prevalence, and mortality for IPF in Australia for the period 1997-2015 and projected estimates for 2016-2025. We used a novel method, the Mortality and Incidence Analysis Model (MIAMOD). Data sources included general population and cause-specific (multiple cause) mortality data from the Australian Bureau of Statistics (ABS) for the period 1997-2015; and data from the AIPFR for the period 2012-2019. We found that overall crude and age-standardised estimates for mortality were 5.9 and 6.3 per 100,000 population; incidence, 10.4 and 11.2 per 100,000 population; and prevalence, 32.6 and 35.1 per 100,000 population. All estimates were higher in males than in females and persons older than 70 years accounted for approximately 82-83% of all deaths, incident, and prevalent cases. This study provided an alternative method to derive epidemiological estimates beyond the use of traditional methods. The prevalence estimates derived were used in the cost of illness analysis presented in Chapter 7. This study was published in Respirology in December 2021.
Chapter 4 presents a systematic review and meta-analysis investigating HRQoL in persons with IPF. In this study we reviewed 134 studies to evaluate the most frequent instruments used to measure HRQoL and also synthesised the HRQoL values for the most used instruments. There were a variety of instruments used to measure HRQoL, but most studies used non-IPF specific instruments namely St George’s Respiratory Questionnaire (SGRQ), Short Form 36 (SF36) and EuroQoL (EQ-5D). While our main interest was the EQ-5D, other instruments analysed demonstrated that deficits in HRQoL were mainly noted in physical domains in keeping with the physically debilitating aspects of the disease. This study also demonstrated that a diverse number of instruments are used to evaluate HRQoL. In view of this diversity, a standardised approach to measurement of HRQL for IPF is important to ensure that comparisons made are reliable. This study was published in European Respiratory Reviews in December 2020.
Given the health economic focus of this thesis, in Chapters 5 and 6 we focussed on HSUVs. Chapter 5 presents first HSUV estimates using the EQ-5D-5L for an Australian IPF cohort. We used survey data for a cohort of participants of the AIPFR to derive estimates. Mean HSUVs for all participants was 0.65 (95% CI: 0.61-0.70) and HSUVs decreased with increasing disease severity and in persons with more than two comorbidities. Given the frequency of multimorbidity in the elderly, our results indicated that managing comorbidities is important for favourable outcomes in persons with IPF. This study was published in Quality-of-Life Research in May 2021.
Chapter 6 presents the first comparison of EQ-5D-5L and the AQoL-8D’s performance in deriving HSUVs in an IPF population, using the same cohort of participants from the AIPFR. This study demonstrated that there was reasonable agreement between the two instruments. However, there were some fundamental differences, which led us to conclude that the EQ-5D-5L demonstrated superior performance when compared to the AQoL-8D in people with IPF. This may be attributable to the high symptom burden associated with IPF and the inherent sensitivity of the EQ-5D-5L to measure physical attributes of HRQoL. This study is currently under review with Quality-of-Life Research at the time of writing.
Chapter 7 presents an analysis of trends in prescription rates and costs of pirfenidone and nintedanib in Australia and provides preliminary estimates of the medication penetrance (the percentage of eligible people taking the medication) of the two medications to assess whether prescription rates were aligned to coverage. For this study we used publicly available data from the PBS and population estimates from the ABS. This study demonstrated that between 2017 and 2020, a total of 44,010 antifibrotic prescriptions were processed, with an associated cost of $131,377,951. NSW accounted for highest total costs and prescriptions, however when standardised to the relevant population size, the ACT accounted for the highest prescriptions and associated costs per head of population. Preliminary estimates of medication penetrance were between 36-90% between 2018-2019. This study also provided some initial data which suggest that there is scope for research into prescribing practices to provide deeper insights into reasons for jurisdictional variations in antifibrotic drug choices in Australia. This study was published in the Australian Health Review in October 2021.
Chapter 8 presents the first cost of illness analysis for IPF in Australia. This study included 162 participants and data sources included cost diary data from a completed survey and linked data from administrative databases from the Commonwealth Department of Health (MBS, PBS) and from Tasmania, Victoria, and New South Wales (hospital admissions and emergency department visits). We calculated both medical and non-medical service utilisation related to IPF. Direct medical costs, direct non-medical costs and total costs were estimated as annual costs per person, and then extrapolated to a population estimate using a prevalence-based approach. Antifibrotic medication, hospital attendances and medications for comorbidities accounted for the highest costs, while transportation, medication for comorbidities and diagnostic tests were the most used healthcare resources. Disease severity, having comorbidities and being on antifibrotic medication were influential factors on costs and resource utilisation. This study will be submitted to the European Journal of Health Economics in January 2022.
Chapter 9 presents the conclusions of this research and the most promising directions for future research.