4.1. Current NBS Policies and Processes
Within Australia, NBS is offered free of charge, and, although not compulsory, participation is high [43
]. Australian NBS programs began with screening for phenylketonuria (1967), followed by the addition of congenital hypothyroidism (1977), cystic fibrosis (1981 in New South Wales, 1999 in all other states) and galactosemia (early 1980s). In the late 1990s with advances in technology the list has expanded to include around 25 different disorders [44
]. There had been a long silence, with no new conditions added for over 17 years, until the recent initiation of two pilot studies in New South Wales, for primary immune deficiency and spinal muscular atrophy.
All NBS services are coordinated from five centralized screening laboratories (one each in New South Wales, Queensland, South Australia, Victoria, and Western Australia). However, prior to 2018, specific program policies and which conditions to include were individually decided by each state jurisdiction. This has now been replaced with a National Policy Framework, which is accessible via the internet (http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/newborn-bloodspot-screening
]. This framework unites these programs for the first time since their inception over 50 years ago. Importantly, it provides a nationally agreed vision and way of working and outlines what will be needed to ensure the ongoing success of the NBS program in Australia; noting that state and territory governments will have the final responsibility for adding the condition in their jurisdictions.
As part of this framework, there is now a national evidence-based process to evaluate proposals to include new conditions in the NBS program [45
]. This framework requires the provision of published evidence to support the condition proposed, the test that will be used and the availability and efficacy of treatment such that decisions to include new conditions can be made in line with agreed criteria. These criteria include consideration of (1) whether there is benefit to the baby from early diagnosis of conditions screened, (2) whether the benefit is reasonably balanced against any harms and costs, (3) the availability of a reliable test suitable for newborn bloodspot screening and (4) the availability of a satisfactory system in place to deal with diagnostic testing and follow-up care of babies with abnormal screening results.
The National Policy Framework sets out a step-wise decision-making pathway to carefully evaluate all applications [45
]. Following a request to include a new condition in the NBS program and assessment of the available evidence, the possible outcomes include a recommendation to screen, a recommendation to conduct a pilot study, a recommendation to review at a later point in time and a recommendation not to screen.
4.2. Application to Include PD in the NBS
On the basis of the criteria set out in the new NBS National Policy Framework, the Australian Pompe Association took the initiative to submit an application to add IOPD to the NBS program. An initial application was submitted in 2018 but was not reviewed; it was then resubmitted in November 2018 to meet the timelines for a 2019 meeting and decision.
As part of its submission, the Australian Pompe Association calculated that the cost of first-tier dry blood spot testing for PD would be $8.78, amounting to approximately AUD$2.7 million each year, assuming an estimated total birth rate of 310,000 per annum and testing via established tandem mass spectrometry methods. However, recognized additional cost considerations included the need for each State/Territory to purchase a new mass spectrometer because current facilities are believed to be at capacity, funding for additional staff to manage this workload, the establishment and provision of genetic counseling services and costs incurred in second-tier confirmatory testing.
A key consideration of the application was its focus on IOPD, given that this has the most benefit to be gained by minimizing the diagnostic delay. It was hoped that, at the very least, this application would have been seen as a positive step forward and enable a pilot program to be implemented. A pilot program to evaluate first-tier testing has been developed but not implemented due to lack of funding and clinical resources. Such a program would help to define the prevalence of PD in Australia, enable evaluation of the optimal methodology for measuring GAA activity, and better inform costs and resourcing needs for NBS. In addition, it would aid in establishing post-testing diagnostic and confirmatory protocols and procedures for managing JOPD, LOPD, and patients with pseudodeficiency alleles that can lead to false positives.
After consideration by the Standing Committee on Screening, the application has not progressed to a more detailed review. The primary reasons for this being limited longitudinal evidence of survival improvements in treated IOPD patients as a result of identification via NBS and concerns regarding the negative impact of identifying patients at risk of developing LOPD. To a large extent, as has been discussed in this paper, literature providing answers to these concerns is becoming more readily available.
The rapid pace at which new data are emerging, coupled with the increase in uptake of NBS in developed countries like the USA, underscores the drive of the clinical, research and patient communities to provide earlier diagnosis and better outcomes for PD patients and their families. The Australian Pompe Association is encouraged by this and will seek to resubmit its nomination for adding IOPD to the Australian NBS program in the future.
4.3. Access to Current Therapies in Australia
Australia has an established and advanced program for the treatment of rare diseases, the Life Saving Drugs program (LSDP) was established in the mid-1990s and provides people with rare and life-threatening disease with access to medicines that are not listed on the Pharmaceutical Benefits Scheme. Currently 10 conditions are supported by the program, and of the treatments available alglucosidase alfa (Myozyme®) is subsidized for the treatment of IOPD, JOPD, and LOPD.
The LSDP requires that patients meet specific conditions to obtain access to treatment; including initial and ongoing eligibility criteria, and that they undergo annual reviews. Clear protocols are in place for diagnosing the disease and for its ongoing management, including starting and stopping treatment.
The decision by the Australian government to fund treatment through the LSDP is an example to all countries for programs to establish treatment for minority patient groups who face the challenge of living with a rare disease. Treatment is expensive. The only currently approved treatment is ERT and a recent review of the economic costs of PD has established that while available data demonstrate a high cost to patients and healthcare systems, there are substantial gaps in the literature [46
]. It is hoped that as new treatment options became available, and competitive interest develops, production methodology will become more cost effective enabling the overall cost of ERT treatment to decline.
4.4. Potential Impact of Future Therapies
Prior to 2006, the only therapy available to patients with PD was palliative. ERT, the only currently available treatment for PD, has been very successful; it can extend the lifespan of babies born with IOPD and stabilize disease progression in patients with LOPD. However, it does not represent a cure. Research continues with many potential avenues including investigations into other therapies such as immune modulation, upregulation of receptor expression, second-generation recombinant ERT, chaperone therapy, substrate reduction therapy, and gene therapy [47
]. Recent reviews provide up-to-date information of the available data for these potential new therapies [48
Amongst these therapies, the prospect of gene therapy is of great interest. Currently several biotechnology companies are actively developing gene therapies for PD, while some therapies are still in preclinical development, other have entered early phase clinical trials [48
]. Gene therapy has the potential to enable sustained enzyme supply after a single medical intervention; by enabling the patient to produce his or her own enzyme it will vastly change the way in which PD is managed.
As we enter the 2020s, for the first time in 56 years we have an opportunity to significantly reduce the suffering, distress and despair that a diagnosis of PD brings. NBS combined with the potential for gene therapy provides hope that in the not too distant future such patients will be able to say ‘Yes I had PD as a baby, but I am fine now thanks to my early detection and treatment’.