Overview
9.1
Clinical trials are essential for evaluating the effectiveness and safety of medicines, devices, services and interventions to help prevent, detect or treat illness and disease. It is through the research done in clinical trials that people gain access to better treatments. Clinical trials also boost the economy and support a highly skilled workforce.
9.2
Australia has an excellent reputation in relation to the safety and quality of its clinical trials. Over the last decade there has been work done at the national, state and territory levels together with industry and stakeholders to improve the clinical trial environment and to attract more clinical trials to Australia. It is in Australia’s best interest to hold onto its reputation as a tier one clinical trials country to reap the benefits from a public health and economic perspective.
9.3
Many countries compete internationally for clinical trials as they provide early access to novel medicines and therapies for patients. They advance medical knowledge including increasing clinician experience with new innovations and enhance the translation of evidence into local practice. In addition, clinical trials forge links between local and international researchers and drive investment in Australia’s economy.
9.4
In Australia, a number of national policy initiatives and investments have underpinned recent improvements in the clinical trials sector. The Australian Government’s Clinical Trials Project Reference Group oversaw the implementation of the $7 million Federal Budget measure in 2016 to encourage more clinical trials in Australia, with a further $6 million committed in the recent 2021-22 Federal budget to enhance Australia’s status as a leading option to conduct clinical trials.
9.5
Industry investment in active clinical trials was estimated to be worth over $1 billion to the Australian economy in 2015. This investment helped support 6,900 jobs with a potential for up to 6,000 new highly skilled jobs to be created by 2025.
9.6
The environment in which clinical trials are conducted is complex, often occurring across multiple jurisdictions and with every trial needing ethics and governance approvals before it can commence.
9.7
In Australia, clinical trials are delivered by teams of clinical trial investigators and clinical and non-clinical staff working in partnership with trial sponsors, regulators, trial participants, consumers, patients their families and carers. Clinical trials are delivered in public and private health service organisations and in trial sites ranging from sole proprietorships to large statutory corporations and public companies.
9.8
This chapter outlines the Government’s current clinical trial regulations and outlines Australia’s current competitive advantage for attracting clinical trials. It discusses what changes are needed and why, in areas of regulation, infrastructure, funding, clinical trial registries, data collection and reporting requirements. These changes will ensure Australia maintains its excellent reputation as a tier one clinical trial country now and into the future.
Regulations for clinical trials in Australia
Clinical Practice Guidelines in Australia
9.9
Australia has adopted the European Union version of Good Clinical Practice (GCP) guidelines. These guidelines detail the requirements for trial documentation, protocol amendments, requirements such as indemnity, reporting lines for adverse events and provision of medical care for trial participants.
9.10
Although the methods for implementing and enforcing the principles of Good Clinical Practice vary, the main objective is a global environment in which trials collect high quality, credible data that contribute to the answering of specific scientific and clinical questions, while most importantly protecting the rights, safety and well-being of clinical trial participants.
9.11
Complementing these guidance documents is Australia’s National Statement on Ethical Conduct in Human Research (National Statement), published by the National Health and Medical Research Centre (NHMRC). The National Statement provides guidance on a wide range of ethical issues in human research. It describes the overarching principles of ethical conduct in research, but provides guidance for specific types of research, specific instructions for the formation and operation of human research ethics committees, advice regarding consideration of multi-centre research and specific issues for Human Research Ethics Committees (HREC) to consider when reviewing a clinical trial proposal.
9.12
The National Statement requires that, before granting approval to a clinical trial, a HREC must be satisfied that the protocol conforms to:
the World Medical Association Declaration of Helsinki
where relevant, the CPMP/ICH Note for Guidance on Good Clinical Practice (CPMP/ICH-135/95), the ISO 14155 Clinical Investigation of Medical Devices and the requirements of the TGA, and
any requirements of relevant Commonwealth or state/territory laws.
Therapeutic Goods Administration regulates access only
9.13
In Australia, the Therapeutic Goods Administration (TGA) must be notified of clinical trials involving unregistered therapeutic goods and the intention to start a new trial under the Clinical Trial Notification (CTN) Scheme or the Clinical Trial Authorisation (CTA) Scheme. The TGA also ensures compliance with International Organization for Standardization Guidelines for Therapeutics and Medical Devices.
Regulatory pathway for clinical trials
9.14
The TGA operates the CTN and a Clinical Trial Exemption (CTX) schemes.
9.15
Clinical trials of unapproved medicines in Australia are conducted by a trial sponsor with oversight by a HREC. For the vast majority of trials that are notified through a CTN, the TGA does not (re‐) evaluate the trial.
9.16
Clinical trials that do not involve the use of ‘unapproved’ therapeutic goods (including placebos) are not subject to CTN or CTX requirements. However, all clinical trials require HREC approval before the clinical trial can commence.
9.17
The Department of Health (the Department) provided the following table of information on the number of notifications for new clinical trials involving unapproved therapeutic goods received for the past few years:
Table 9.1: Notifications for new clinical trials for unapproved therapeutics
|
Year
|
2017–18
|
2018–19
|
2019–20
|
|
Number of new clinical trial notifications (CTN)
|
920
|
1059
|
984
|
Source: Department of Health, Submission 15, p. 21.
9.18
The CTX route is generally designed for high‐risk or novel treatments where there is no or limited knowledge of safety. For medical device trials, the CTX scheme may be more appropriate where the experimental device introduces new technology, new material or a new treatment concept, which has not been evaluated previously in clinical trials in any country. The CTX scheme should be considered for medical devices that pose a risk of serious patient harm.
9.19
In many cases, a HREC recommends that the CTX scheme is used and this will depend on whether the committee has access to appropriate scientific and technical expertise in order the safety of the product. However, certain Class 4 biologicals must be submitted under the CTX scheme.
Clinical trials involving Genetically Modified Organisms
9.20
The Department informed the Committee of the mandatory processes when dealing with Genetically Modified Organisms (GMOs).
Before a clinical trial involving GMOs can proceed, it must be appropriately authorised under both the Gene Technology Act and the Therapeutic Goods Act 1989. Each approval process is independent and typically occurs in parallel.
As risks to trial participants are addressed through oversight by TGA and HRECs, the Gene Technology Regulator’s focus is on assessing risks posed to people other than those participating in the clinical trial, and to the environment. This includes risks to people preparing and administering the GMO therapeutic, and risks associated with import, transport and disposal of the GMO. Clinical trials with CAR‐T cells are Exempt Dealings (no licensing required under the Gene Technology Act).
Australian Government initiatives and funding
9.21
In late 2020, the Department outlined the Australian Government’s multi-pronged approach to encourage clinical trials in Australia, taking into consideration the current environment and the impacts of the COVID-19 pandemic. This included: international promotion; funding to attract international clinical trials and research, investigators and investment; and streamlining the operating environment and improving processes to make it easier to undertake trials in Australia.
9.22
The Department informed the Committee that virtual roadshows promoting Australia as an ideal destination for clinical trials to potential sponsors in Greater China, Korea and the United States were delivered in partnership with industry stakeholders, with 300 industry delegates attending the sessions from these regions. Austrade led a strong Team Australia delegation (hybrid) to Bio Korea 2021 with all major states and MTPConnect, and involving both physical pavilion and virtual Australia capability promotion activities.
9.23
The Australian Government has been focused on providing direct investment in the clinical trials sector to encourage companies to undertake clinical trials in Australia. Two examples include:
… the Biomedical Translation Fund (BTF) which invests in promising biomedical discoveries with the aim to address various costs constraints, which may include support for clinical trials in Australia. The Modern Manufacturing Initiative (MMI) Translation grant stream for medical products in part aims to help overcome barriers to commercialisation costs including costs associated with clinical trials.
Government funding for clinical trials
9.24
The Australian Government announced a $5 billion, 10 year investment plan for the Medical Research Future Fund (MRFF) in the 2019-20 Federal Budget. This plan continues to support lifesaving research and gives researchers and industry some longer term certainty and direction. Under the MRFF 10 Year Plan, $614 million has been committed to the Clinical Trials Activity Initiative.
9.25
Programs funded under MRFF Clinical Trials Activity Initiative include Rare Cancers, Rare Diseases and Unmet Need (RCRDUN) and International Clinical Trial Collaborations (ICTC).
9.26
RCRDUN supports clinical trials research that investigate new drugs, devices or treatments for rare cancers/diseases or for areas of unmet medical need. Examples of funded grants include studies on larotrectinib (a new drug) for children with newly diagnosed high‐grade glioma; treating mitochondrial dysfunction with a novel form of anaplerosis; and clinical trial combining azactidine and defactinib for high‐risk myelodysplastic syndrome patients who fail to respond to azacitidine alone.
9.27
The Department commented that in 2020-21 ‘there will be two grant opportunities under the Clinical Trials Activity Initiative including $25 million for Rare Cancers, Rare Diseases and Unmet Need for COVID‐19 and $25 million for Rare Cancers, Rare Diseases and Unmet Need.
9.28
The Australian Government has invested a total of $614.2 million over 10 years in the Clinical Trials Activity Initiative to increase clinical trial activity in Australia.
9.29
The ICTC, which has been consolidated into the Clinical Trial Activity Initiative under the MRFF 10-year plan, supports Australian research teams to lead or participate in international investigator-initiated clinical trials through the establishment and co-ordination of clinical trial sites in Australia. Researchers, not pharmaceutical companies, run this type of trial.
Australia’s competitive advantage
9.30
Throughout the inquiry many stakeholders reiterated that Australia has a competitive advantage of running high quality clinical trials on an international scale. More specifically, witnesses commented that Australia is well respected and has a well-qualified workforce that included nurses, research centres and hospitals. However these stakeholders went on to suggest that there were critical areas of clinical trials that needed immediate reform to future proof Australia’s standing as a tier one nation for clinical trials.
9.31
Medicines Australia set the scene and informed the Committee that:
In 2019, there were 1,820 ongoing trials in Australia: a 22% increase on 2015. This contributes an estimated $1.1 billion a year to the economy.
9.32
Medicines Australia suggested that:
…sustaining this reputation is increasingly challenging, as international competition for the placement of clinical trials has already begun to erode Australia’s advantage. Rather than relying on historical recognition as a reliable destination for quality clinical research, Australia needs to actively demonstrate superiority against other international benchmarks in clinical trials, to secure status as a preferred destination of choice.
9.33
Dr Anna Lavelle, Chair, Medicines Australia, commented that Australia is seen as being attractive for clinical trials for two reasons:
One is that Australia has ethnic diversity, which is very attractive to companies. Also, we have quality data, so our data is considered highly reliable, which is extremely important for them.
9.34
Dr Kaustuv Bhattacharya, Scientific Adviser, Rare Voices Australia (RVA) stated that Australia does deliver high quality clinical trials however it needs to improve its efficiency of delivering trials:
We definitely have high-quality clinical trials delivered by this country. That's what we have to be able to market as a country: we deliver and we deliver a good product. But we have to do it more efficiently and effectively than we have done so far.
9.35
Roche highlighted that there are enormous growth opportunities for clinical trials in Australia.
Compared to most other nations Australia has managed the COVID-19 pandemic relatively well, and this provides a stable environment to undertake clinical trials. Combined with other key population advantages and a strong medical research sector there is room for expansion.
However, expansion within some hospital and healthcare settings will need encouragement. Most large hospitals are already inundated with clinical trials and are not able to take up all opportunities because of space and capacity constraints. Work will need to be undertaken to grow the clinician researcher workforce, find funding solutions for sponsor monitoring, data management and research nurse costs, and crucially, provide space within hospitals.
9.36
AusBioTech highlighted the importance of maintaining Australia’s competitive advantage to attract local clinical trials. It stated:
Global competition for clinical trial investment is intense and hinges on factors such as start-up times, researcher capabilities, tax incentives and quality assurance. Investment capital is mobile and will move to the country best able to meet the research needs in the time available.
Early access to new medicines
9.37
Clinical trials not only assists in increasing access to research and potential new medicines in the health care system, they provide one avenue for patients to receive early access to new medicines.
9.38
AusBioTech suggested that early access to new medicines through clinical trials is an important part of the health ecosystem. It discussed the benefits of providing access to patients for new treatments, and other benefits for researchers and the health sector education and training experience and economic gains.
This access has been estimated to save Australian taxpayers around $100 million annually in healthcare costs, as well as providing patients with significant benefits from timely treatments. This healthcare saving includes reduced Government expenditure on the PBS due to patients’ access to innovative treatments. Other benefits include: enhanced translation of evidence into local practice; enhanced local clinical trial expertise; enhanced global profile and linkages for Australian researchers; and retention of researchers in the Australian public health system.
9.39
Whitecoats Foundation illustrated:
Clinical Trials can also provide patients with access to potentially life-saving options in the management of their health particularly in circumstances where choices are limited or there are none.
Rare Disease
9.40
For many people living with a rare disease, participation in a clinical trial may be the only way to access treatment.
9.41
A 2016 Australian study found that almost 90 per cent of respondents living with a rare disease were interested in joining a patient registry, in recognition of the key role that registries play in linking people living with a rare disease with clinical trials for new health technologies (drug treatments and therapies). The translation of rare diseases research into clinical settings, while currently hampered, is vital. This two-way relationship benefits from active participation by patients, their families and carers, and patient advocacy groups to ensure the best outcomes for people living with a rare disease.
The challenges for clinical trials in Australia
9.42
The Committee received numerous suggestions from stakeholders in relation to improvements that could be made to make Australia a more attractive location for clinical trials.
9.43
The harmonisation of regulations and reducing red tape was clearly at the top of the list requiring immediate attention. Other barriers discussed included the non-existence of a national clinical trial register, lack of data and reporting, infrastructure deficits, rising costs, and cell and gene technology limitations.
Regulation – ethics and governance
9.44
Many submitters stressed that the harmonisation of regulations between jurisdictions had received a lot of attention recently however they commented there was still more to do if sponsors were going to view Australia as a favourable country to undertake clinical trials here in the future.
9.45
Research Australia commented that the road to reform had been long and slow and that a better ‘single system’ technological platform was required:
The reform of the Australian clinical trials environment has been ongoing for over a decade. While progress has been made in many areas there is still more work to be done. When it comes to ethics approval, the current National Mutual Acceptance scheme has been an improvement, but more work needs to be done to achieve a truly national and all-inclusive scheme.
More can also be done to create a ‘single system’ post the ethics approval, with the adoption of common technology platforms, processes and reporting requirements by all parties, including state regulators.
9.46
Myositis highlighted disincentives for sponsors bringing clinical trials to Australia and described the delays incurred from individual ethics and governance regulations:
The diverse ethics approval processes between Australian research sites is a disincentive for clinical trial set-up and results in recruitment delays and cost burdens.
Australia's decentralised Ethics Committee process is a discouraging aspect of the conduct of clinical trials in this country.
Under the Australian system, the ethics review process for clinical trials requires human research protocols to be reviewed by institutional level ethics committees. That is, the Ethics Committee at each hospital/institution site for the trial, both public and private, undertakes its own review of the ethics protocols. In addition to delays, this can lead to inconsistencies, lack of transparency and lack of public accountability.
9.47
Medicines Australia also emphasised the time delays as problematic and called for one ethics approval that is acceptable to all institutions.
…the start-up of a clinical trial involves a range of activities, the most significant of which is the ethical review and approval of the trial by a Human Research Ethics Committee (HREC) and the Research Governance Review and approval via a Site-Specific Assessment (SSA). These processes are almost always managed consecutively at present, despite local evidence that parallel review significantly increases start-up times.
9.48
Ms de Somer, CEO, Medicines Australia, continued:
The second barrier is that each individual institution then implements their own governance processes, which obviously are relevant to that institution but differ from institution to institution. Therefore, trying to get through all of the governance at each institution wastes time. We believe there could also be agreement across public and private institutions on the level of governance that's required so that one standard of governance would be suitable for all institutions.
9.49
Medicines Australia outlined difficulties in streamlining the Ethics Review for clinical trials:
Success has been limited as public health policies do not allow the use of all ethics committees that have been nationally certified by the [National Health and Medical Research Council] NHMRC for multi-centre research (e.g. private ethics committees).
In addition, public health policies do not routinely allow private research centres to be covered by public hospital ethics committees without a range of varying written agreements in place. As it is very common for a mix of public and private trial centres to be included in trials, at least two ethics committees are required and possibly three if university centres are also involved. This leads to a duplication of effort, increased costs and inefficiency for the initial submission and delays in approval of a clinical trial, resulting in unnecessary delays in patient access to medical treatment.
9.50
Medicines Australia suggested several ways to improve the current system:
To improve the efficiency of regulatory processes the review and approval times for Human Research Ethics Committees (HRECs) and Research Governance Offices (RGOs) should be prescribed to an acceptable timeframe. For multi-centre trials conducted across sites residing in different jurisdictions, it is usual to require the services of more than one HREC and each trial site conducts its own Research Governance Review. The timelines for review and approval of the trial by both HRECs and Research Governance offices (RGOs) are variable and unpredictable.
9.51
Numerous stakeholders including AAMRI echoed the following sentiments and all agreed that despite the efforts that have already taken place to streamline the ethics and governance processes, more was need to be done in a timely manner:
The ethics and governance approval processes can take too long, delaying clinical trials and making Australia a less appealing destination for investment. The COVID-19 pandemic has shown that when needed the approval process can be sped up safely.
For Australia to be more competitive in a global market a streamlined approval process is needed. Significant work has been undertaken to find ways to streamline processes, such as the accreditation framework for clinical trial sites, but more effort is needed. The processes currently differ by state, by institution, by setting, and whether the recruiting site is public or private. Action is needed to both speed up processes, and for one single approval process to cover clinical trials across the whole of Australia.
9.52
Roche Australia stated:
If Australia is to remain competitive on this global stage, we need to continue to advance the environmental conditions for clinical trials. An important first step in this regard would be to reduce red-tape around how clinical trials are structured and administered.
9.53
QIMR Berghofer submitted the following:
Mutual acceptance of ethical review should be implemented nationally (where research has been reviewed and approved by an NHMRC-certified Human Research Ethics Committee)
Standardised governance processes (site-specific assessment) should be implemented across public health hospitals and health services.
9.54
AusBioTech highlighted many of the red tape difficulties that industry must navigate to bring clinical trials to Australia:
There are over 200 Human Research Ethics Committees (HRECs) in Australia, each with similar concerns, but different requirements. The National Mutual Acceptance (NMA) Scheme only supports the acceptance of a single scientific and ethical review for multi-centre research conducted in publicly funded clinical sites. Given that clinical trials are commonly conducted across public and private hospitals, ethical approvals for trial start-up must be separately granted by different HRECs, leading to multiple submissions and unnecessary duplication of effort.
9.55
Mrs Nettie Bourke from Cystic Fibrosis Australia called for a national office of ethics:
We really believe that there should be an office of ethics which would oversee ethics across Australia. That would be about ethics for clinical trials and also for registries. After COVID, the big companies overseas want to come to Australia to do clinical trials because we have a clean environment, but the ethics get in our way every time. That's where the expertise comes in.
9.56
Mr Lance Dale, Policy Officer, Save or Sons Duchenne Foundation, highlighted a serious barrier that Australia has in terms of ethics approval processes. He stated:
We have a problem with protracted ethics and research government approval processes, which lag way behind the rest of the world. We take 100 to 160 days to get approval, compared to the UK's 90 days. Something can be done in that space.
9.57
Mr Ali, Chief Executive Officer (CEO), MND Australia concurred with the calls to streamline the ethics approval process for clinical trials. He stated:
One of the other recommendations is the need to implement a streamlined single-point ethics approval process rather than the very convoluted, time-intensive ethics approval process. We need to be concerned about how quickly people die with MND and why we need the processes to change.
National clinical trials governance framework
9.58
The Australian Commission on Safety and Quality in Health Care was engaged by the Department to develop a National Clinical Trials Governance Framework (the Governance Framework) on behalf of all Australian jurisdictions. The draft Governance Framework was endorsed for implementation by Health Ministers in 2019. Its implementation will streamline clinical trial approval processes and improve time to trial start-up, workforce capacity, and engagement with sponsors.
9.59
The Governance Framework requires health service organisations to do the following:
Monitor compliance with national regulation, legislation and policies and requires health services conducting clinical trials to monitor compliance with legislation, regulation and state or territory requirements
Keep information about instances of noncompliance with the organisation’s policies, procedures and protocols. Where appropriate, incorporate the information into the organisation’s risk register and quality improvement planning processes.
Maintain well-designed legislative compliance processes. Incorporate a compliance register to ensure that the organisation’s policies are regularly updated, enabling the organisation to respond to regulatory changes, compliance issues and case law.
9.60
The Department commented that:
The pilot and finalisation of the National Clinical Trials Governance Framework is an important element of the clinical trials reform agenda to ensure nationally consistent accreditation of health services undertaking trials. In November 2019, all Health Ministers endorsed the Governance Framework and the national pilot commenced on 1 September 2020 following a COVID‐19 suspension. Pilot outcomes will be evaluated in early‐mid 2021.
9.61
In August 2021, the Department provided the Committee with the following update on the Governance Framework:
A priority is to continue to build on recent work to develop and pilot the National Clinical Trials Governance Framework, currently being finalised and widely recognised as a significant and positive reform for the sector. Implementation, anticipated from 2022, will streamline trial approval processes, improve time to trial start-up, improve workforce capacity, reduce administered efficiencies and better engage sponsors. The outcome will be the integration of clinical trials into health service corporate and clinical governance systems and nationally consistent accreditation of clinical trial services under the National Safety and Quality Health Service Standards.
National mutual acceptance scheme
9.62
The Committee received evidence from the Australian Commission on Safety and Quality in Health Care (ACSQHC) discussing its current work scoping the expansion of the National Mutual Acceptance Scheme across public health services in all states and territories. The objective of this scheme will:
… enable mutual recognition of non-public, accredited Human Research Ethics Committees (HRECs) approvals by the public, private and not-for-profit sectors, will streamline the acceptance of the HREC approvals across jurisdictions and the public and private health care sectors.
9.63
The ACSQHC continued:
Consultation is also underway on the requirements for a national platform for all health and medical human research, with jurisdictional and industry support. It represents an opportunity for transformative change for the sector, providing a national ethics authorisation and research management system, which incorporates of the Clinical Trial Notification (CTN) and Clinical Trial Authorisation (CTA) schemes. This platform will reduce duplication, expedite approvals and trial commencement and enable the first real-time national picture of health and medical human research activity.
Training as an investment
9.64
In addition to providing the incentives to encourage industry to bring more clinical trials to Australia, Australia should ensure it has the best infrastructure and training in place to facilitate clinical trials.
9.65
Continuous educating and training of staff involved with clinical trials was an important issue raised by Medicines Australia:
… we are already falling behind the eight ball on creating the infrastructure for clinical trials because we don't have training of clinical trial nurses, assistants and people who monitor clinical trials, and that's for the number clinical trials we've got right now. We are also in this unique position of being relatively COVID free with a First World health infrastructure. Clinical trials are as much of an export as education. We should be exporting our knowledge, our capacity and our ability to do clinical trials to encourage that direct foreign investment into more clinical research, so there is absolutely an opportunity.
9.66
Johnson and Johnson discussed the importance of training in areas including the potential benefits of standard training processes for ‘staff involved in governance activities and standard processes for centres involved in clinical research.’
National One-Stop-Shop
9.67
The ACSHC is currently conducting national consultations on behalf of all jurisdictions to scope the requirements for a National One-Stop-Shop. This proposed national online portal will make it easier for researchers, industry representatives and sponsors to find, conduct, participate and invest in research in Australia.
9.68
The concept for the National One-Stop-Shop was developed by the Clinical Trials Project Reference group and presents a significant opportunity to achieve a national, interconnected, rapid and streamlined approvals platform that will:
include a cross-jurisdictional ethics and governance approvals platform that incorporates key application, notification and approval systems
incorporate the Clinical Trials Notification and Clinical Trials Approval schemes administered by the Therapeutic Goods Administration (TGA)
include an embedded and automated next-generation national clinical trials registry
provide sophisticated monitoring and reporting functionality for different users.
9.69
Options for improving patient recruitment through a related National Clinical Trials Front Door will be considered. Consultations start in July 2021 to gather the requirements for the National One-Stop-Shop and the National Clinical Trials Front Door. A project advisory group, chaired by Professor Ian Chubb, former Chief Scientist and clinical trial participant, will be established to guide the consultation process.
9.70
In August 2021, the Department provided the Committee with an update of the One Stop Shop for Clinical Trials and Human Research Approvals and commented:
The announcement to establish the one stop shop has been applauded by the sector and presents a significant opportunity to achieve a national, interconnected, rapid and streamlined approvals platform and will make it considerably easier to undertake and participate in research in Australia.
9.71
The Department continued:
It builds on international evidence that nationalised platforms are critical to building a stronger and more competitive research sector, and that jurisdictional collaboration is critical to success in federated systems.
The National One Stop Shop will facilitate rapid and streamlined approvals and address long-standing challenges with duplication, delays and fragmentation that are unlikely to be otherwise overcome. It will underpin the new nationally consistent approach to accreditation for trials sites in public and private hospitals, and provide reporting functionality that will serve to maintain Australia’s reputation for safety and quality in research, and drive quality improvement and strategic positioning.
Through ongoing and effective collaboration with jurisdictions, the Commonwealth Government considers that a harmonised national approach is achievable through the Governance Framework, to incorporate clinical trials into routine health service provision, and the single national platform for approvals – the One Stop Shop.
National clinical trials registry
9.72
Many witnesses called for a national clinical trials registry. There were discussions around the challenges that exist between Commonwealth and States that precluded a streamlined system from being in place in Australia. This was seen as a difficulty to navigate for not only industry but for patients and clinicians as well.
9.73
Whitecoats Foundation described the benefits that would accrue if Australia developed a national clinical trials registry.
Improving awareness and participation rates to clinical trials in Australia not only delivers potential health benefits to patients but it can also improve Australia’s profile as a more desirable destination to conduct more clinical trials.
Protracted recruitment timelines delay time to market for sponsors and can lead to increased research and development costs. The lost revenue opportunity is estimated at $600k/day for niche market drugs and up to $8million/day for blockbuster drugs.
Timely recruitment and sites/countries with demonstrated success are favoured by sponsors. There are many factors that can affect recruitment, however, one of the key reasons associated with poor participation and engagement is low awareness. The awareness issues extend to both health care professionals and the general public.
9.74
Many of the peak bodies for disease informed the Committee that they already have patient registries. Dr Gethin Thomas, Executive Director, Motor Neurone Disease (MND) Australia, made the following salient comment about clinical registries:
We have a national patient registry for MND that is funded through an NHMRC partnership grant plus contributions by ourselves and Fight MND. That has been very effective. ... The biggest problem for these is funding… It's very easy to establish these; it's very difficult to maintain them.
9.75
Medicines Australia emphasised that this area of patient recruitment needs a digital innovation solution that will secure patient recruitment and consent and deliver cost effective data from the trials.
Australia will need to improve patient identification, patient recruitment, retention and completion rates for existing trials.
As many as 86% of clinical trials do not reach participant recruitment targets and as such, the ability of sites within a country to recruit to their contracted participant target is a key factor in study placement in the country.
9.76
HealthMatch suggested that the Australian Government needed to support truly patient-centric tools and technologies that promote equal and direct access to discovery, education and participation in clinical trials.
9.77
AstraZeneca recommended the following measures could make Australia a more attractive location for clinical trials:
Recommend the implementation of a National Health Registry (NHR). This disease-agnostic registry will utilise a “general” OPT-IN consent for future participation in a wide variety of health conditions. Similar model to the Scottish Health Research Registry (SHARE).
9.78
AstraZeneca continued and said it agreed with the recommendations made by Medicines Australia in its submission to the Senate Select Committee on COVID-19 in May 2020. Those recommendations suggested that Federal and State Governments work together with industry, through Medicines Australia and the Research and Development Taskforce (RDTF), to:
Promote domestically and internationally that Australia is open for business to conduct clinical trials
Embed clinical trials as part of the standard treatment of care in the national health infrastructure, including regionally through clinical tele-trials
Harmonise ethics, governance and regulatory processes nationally for consistently faster and more efficient establishment of clinical trials across Australia, building on the proposed Front Door initiative and work underway through the Australian Commission on Safety and Quality in Health Care
Strengthen the capacity to conduct clinical tele-trials in rural, remote and regional areas
Develop nationally agreed clinical trials standards and guidance on:
remote monitoring (including delivery and management of Investigational Medicinal Product)
the utilisation of digital technology, such as access to electronic Medical Records (eMR),
e-signatures and e-consent
Retain for the future, the more efficient changes to ethics, governance and regulatory measures implemented under COVID-19
Linkage of existing Health care data, possibly via eHealth, forming an up-to-date National Health Registry. This would help to cement research as part of routine healthcare
Introduction of a National Framework for Australian Trials: Inclusive of contractual negotiations and governance, reporting etc
Introduction of a National Trials Centre with the purpose of supporting researchers with trial design and execution. A large part of the centre should be dedicated to participant recruitment.
9.79
Roche suggested that it would be helpful if the Australian Government would assist with identifying where clinical trials are located, provide a valet style service to connect sponsors of trials with research organisations, and connect potential partners that can access harmonised patient registries. Further, Roche suggested the Australian Government should move quickly to:
adopt and invest in technologies and associated practices to ensure all clinical trial centres (public hospitals) have Electronic Medical Records
allow for remote monitoring of clinical trial participant records by sponsors
establish national standards for the use of e-Consent in clinical trials
adopt technologies for e-signatures on clinical trial documents.
This harmonisation should be coordinated through a new Clinical Trials Front Door agency that provides these services, collects metrics on clinical trials and assists with navigating with startups and patient transitions at the conclusion of the trial.
9.80
The Committee heard evidence from The George Institute for Global Health, an independent global medical research institute, based in Sydney with major centres in China, India and the United Kingdom (UK). The George Institute along with George Health have developed a national research register called ‘Join Us’.
9.81
Professor Bruce Neal, Executive Director, The George Institute for Global Health explained that the two key purposes of the Join Us register were to get people efficiently into clinical trials and to enable the efficient use of the collected health data. Professor Neal commented:
The Join Us proposal is seeking a million Australians—any adult Australian over the age of 18—to go to the website and click the sign-up button and read an explanation of the project. They then provide basic contact details and agree to be contacted about studies that might be relevant to them. To make sure we send appropriate invitations, we also collect some basic checkbox data about medical conditions they might or might not have.
In the second part of the sign-up, participants agree to allow Join Us to gather their routinely collected health data and store it for research purposes. At that point, any researcher anywhere in the country and at any institution seeking to answer any question can come to the Join Us register and ask for our assistance. We can identify participants who may be eligible for their study and, on behalf of the researchers, extend an invitation. This hugely simplifies the recruitment process because you've basically got a one-stop shop that is directly connected to hopefully a million people who might be interested in joining the research.
9.82
In August 2021, the Department updated the Committee with the following information regarding the National Clinical Trials Front Door initiative.
The Australian Commission on Safety and Quality in Health Care (ACSQHC) has been engaged to undertake national consultations on these initiatives. A project advisory group, chaired by Professor Ian Chubb, former Chief Scientist and clinical trial participant, will guide the consultation process.
Australia New Zealand Clinical Trials Registry
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The Australia New Zealand Clinical trials Registry (ANZCTR) was established in 2005 with $1.5 million in funding from the Australian Government, through a National Health & Medical Research Council Enabling Grant. The ANZCTR is overseen by an Advisory Committee with wide representation from a variety of stakeholders including government, clinicians, the research community, journal editors, the pharmaceutical industry and regulator, and consumers.
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The ANZCTR receives funding from the Department, Therapeutic Innovation Australia, National Collaborative Research Infrastructure Strategy, and the Health Research Council of New Zealand.
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The ANZCTR is an online public registry of clinical trials, held at the NHMRC Clinical Trials Centre, University of Sydney. It is a Primary Registry in the World Health Organization (WHO) Registry Network, which means that it fulfils certain criteria for content, quality and validity, accessibility, unique identification, technical capacity and administration. Trials from all ICTRP Primary Registries can be searched at: www.who.int/trialsearch
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The ANZCTR accepts both interventional and observational studies for registration from all countries and from the full spectrum of therapeutic areas including trials of pharmaceuticals, surgical procedures, preventive measures, lifestyle, devices, treatment and rehabilitation strategies and complementary therapies.
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Key points about the ANZCTR included that:
It is publicly owned and managed by a not-for-profit organisation
All details of trials registered on the ANZCTR are made publicly available
Registration is voluntary, but if a registrant chooses to register a trial, certain fields are mandatory
Registration is free of charge
Responsibility for registration lies with the sponsor.
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The ANZCTR is part of the worldwide initiative to make public all clinical trials being conducted for the following reasons:
To improve research transparency: Making details of all trials publicly available improves research transparency and helps to overcome publication bias and selective reporting, thereby enabling clinicians and consumers to make more informed decisions.
To facilitate trial participation: People interested in participating in a clinical trial and doctors investigating relevant trials for their patients have access to a reputable and comprehensive on-line register showing what trials are occurring across all areas of health, which may facilitate recruitment.
To avoid duplication: Improving awareness of similar or identical trials will make it possible for researchers and funding agencies to avoid unnecessary duplication.
To identify potential research areas: Describing clinical trials in progress can make it easier to identify gaps in clinical trials research.
To promote research collaboration: Enabling researchers and health care practitioners to identify trials in which they may have an interest could result in more effective collaboration among researchers.
To improve trial quality: Registries checking data as part of the registration process may lead to improvements in the quality of clinical trials by making it possible to identify potential problems (such as problematic randomisation methods) early in the research process.
The clinicaltrialsNSW project
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The Committee received evidence from the NSW Department of Health’s Office for Health and Medical Research, that discussed the clinicaltrialsNSW project. The project acts as the front door for sponsors and researchers seeking to undertake clinical trials in NSW:
clinicaltrialsNSW works across the sector to enable clinical trial capacity, capability and collaboration, and embed clinical trials in core hospital service delivery and clinical care. It has designed a continuous improvement agenda for clinical trials that develops the ecosystem across trial quality, operations, workforce and equity of access.
Multi-centre trials
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Multi-centre trials – those that are held over multiple sites and/or in multiple jurisdictions – are becoming more common as technologies improve. This is bringing more flexibility to conducting clinical trials and huge benefits to both patients and sponsors.
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Medicines Australia discussed the importance of establishing clinical trials in regional areas in Australia. The benefits were discussed as being good for patients, good for research data and good for the regions in terms of upskilling the workforce in regional and remote areas:
Decentralisation of clinical trials can increase patient diversity in clinical trials, allow faster recruitment to target and ultimately accelerate the development of new treatments. Importantly, it also strengthens the healthcare service in regional areas of the country by exposing doctors and other healthcare professionals to innovations in clinical practice and treatments. Through clinical tele-trials, smaller regional hospitals and clinics can be involved in clinical trials by partnering with larger health service organisations via a hub and spoke model.
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Dr Kaustuv Bhattacharya, Scientific Adviser, RVA, suggested that rare disease would really benefit from multi-centre clinical trials set up all over Australia.
Ideally, you would set up that kind of trial as a multicentre. You would recruit from all of Australia. In that sense, I agree with you that we should set up across the whole country in order to attract the numbers from across the whole country. We're automatically discriminated against by our population relative to, say, India or Brazil or other more populous countries.
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Noxopharm supported the need for more funding to enable the collaboration of multi-centre trials. This would involve allowing Australian hospitals and research networks to capitalise on overseas networks using a multi- centre trial for clinical trials conducted in Australia:
One of the key challenges in conducting clinical trials in Australia is simply the low population. Recruiting sufficient trial participants, in a timely manner, to create a statistically meaningful study is challenging, especially for less common health conditions. There are a number of Australian hospitals that have clinical research networks outside of Australia, however smaller organisations do not have the resources and networks to readily tap into these groups.
Government relationships and incentives to encourage these hospitals to leverage their networks to initiate multi-centre trials for Australian health technology innovations will enable the establishment of meaningful clinical trials that include an Australian population.
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Roche alerted the Committee to the following problem for multi-centre trials:
Currently multiple ethics approvals are required for a clinical trial that is undertaken in more than one state or territory. A number of initiatives designed to implement the recommendations from the McKeon Review (2013) to harmonise and streamline the start-up of clinical trials are still continuing. Despite these initiatives, a range of public health policies do not allow national certification by the National Health and Medical Research Council for multi-site trials.
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Novartis commented that Australia needs to better incentivise locally hosted clinical trials:
There should be better incentives for companies to invest in conducting R&D in Australia and/or enrol Australian patients in multinational trials. Conducting multinational trials in Australia is an important way for Australian clinicians and patients to gain early access and experience with new therapies.
Teletrials
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The Department outlined progress has been made for teletrials across different jurisdictions.
A National Teletrials Compendium was developed through effective cross-jurisdictional collaboration and funding from the Encouraging More Clinical Trials in Australia measure. The Compendium aligns with the minimum standards of the International Council for Harmonisation (ICH) Guideline for Good Clinical Practice (GCP) and the National Clinical Trials Governance Framework, and will support a consistent national approach. It is expected to contribute to growth in the number of teletrials in Australia, and pave the way more international teletrials and clinical trials in future.
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Research Australia noted the following issues could improve efficiencies in the recruitment and administration of clinical trials in Australia.
The early lockdown in Australia disrupted research but also led to new innovations, including more ‘remote’ recruitment of participants for clinical trials. This innovation is complemented by a current initiative in Australia to normalise the use of electronic consent for participation in clinical trials, currently being led by CT:IQ.
The COVID-19 pandemic has also accelerated the introduction of telehealth, ‘normalising’ remote engagement for patients and clinicians. This also provides an opportunity for clinical trials to expand the use of remote engagement with patients, potentially enabling more people, particularly in rural and remote Australia, to participate in clinical trials.
Technology
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Many submitters recommended that industry invests in technologies to utilise Electronic Medical records wherever possible and establish standards for the use of e-Consent and e-signatures.
Data collection and reporting
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Stakeholders sent a clear message to the Committee that modern health technology platforms to be used for data collection and reporting were critical to the success of attracting clinical trials to Australia.
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Johnson and Johnson commented that health data is a critical element in delivering better health outcomes. It is vital in:
determining the real value of new treatments and the terms and conditions upon which access to those treatments is secured
driving the research and development of new treatments
providing the most useful tools to help secure clinical trial investment in Australia
to drive significant system efficiencies.
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The Monash Institute for Medical Engineering (MIME) made the following suggestion to make Australia a more attractive location for clinical trials:
A critical gap for our clinical trials industry is the software platforms required for clinical trial management or recruitment cohort identification and efficient data study extraction from electronic health records.
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MIME continued and stated:
The main gap in our national strategy to increase clinical trial activity is the application of digital innovations to:
maximise identification of patients and their recruitment, with suitable consent;
ensure cost efficient recruitment to trials;
efficiently capture date[data]; and
project manage and maximise retention in trials.
Monash Partners Academic Health Science Centre, of whom MIME partners, is developing a digital, whole-of-country model to achieve these goals. It is being undertaken in partnership with the university, public health and patient advocacy communities and at a federal and state government level.
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Sydney Children’s Hospital highlighted the need for improved health technology platforms:
Enhanced support for information and health technology platform-development to increase diagnostic capacity and improve recruitment and triaging of patients to enable rapid access to emerging therapies via clinical trials or special access schemes. Emerging capabilities for data linkage, ‘omics and organoids present an opportunity to transform the way we identify, diagnose and select patients that are likely to benefit from novel or repurposed therapeutic approaches.
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In a 2016 report released by the Department it said that limited research and data is available on clinical trial participation nationally, with the exception of oncology trials, and there is currently no central coordination point for the collection of clinical trials data, including recruitment and retention rates:
In 2011, the Clinical Trials Action Group (CTAG) reported that 18,600 people were enrolled in 1,265 trials conducted in 2009. A 2014 survey conducted by Clinical Trials Connect (CTC) assessed the recruitment success for a range of clinical trials in Australia. The survey identified that 20% of trials met their recruitment deadline and the majority of respondents met their targets 50-79% of the time. Research and consultation also revealed limitations on data in relation to retention, with exact rates generally unpredictable.’
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Medicines Australia commented that whilst a national office for clinical trials had been considered frequently by government and industry, it was ‘not sure that introducing another layer of regulatory process is necessarily the answer.’
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The Whitecoats Foundation was supportive of mandatory reporting requirements.
Mandatory reporting related to clinical trial outcomes on a publically accessible register is essential to building and securing public trust and engagement with research. This will also help reduce research duplication and waste.
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Research Australia commented:
At a Commonwealth Government level, Research Australia notes with approval the recent funding provided to the Therapeutic Goods Administration (TGA) to modernise its IT systems. This provides an opportunity to improve the provision of clinical trials data to the TGA and also the reporting of adverse events.
There are currently multiple systems, specifications and standards used across Australia and internationally for the collection and reporting of health information, including for clinical trials reporting. While a single system might be unattainable, better harmonisation of systems and improvements in interoperability within Australia could provide significant efficiency benefits for Australian clinical trials as well as the health system more broadly. This could help make Australia a more attractive location for international clinical trials.
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Professor Bruce Neal from The George Institute for Global Health at UNSW commented that recruitment, particularly to clinical trials, is a major problem in Australia.
… the processes for accessing routinely collected health data introduce major inefficiencies and waste in the research process, and also recognise that widespread implementation of Join Us has the potential to immediately provide an actionable solution to these problems.
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HealthMatch suggested that the Australian Government should leverage innovation in patient recruitment technologies in the private sector to support public good and explore partnerships to lessen the burden on taxpayer funded projects.
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In line with the McKell report released in 2016, the Committee was reminded of Recommendation 7 that stated:
The Federal Government must design legislation, administrative processes and policies that will simplify the access to health data collections for medical research. The policies must maintain privacy and security.
Marketing – education and awareness
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The Western Australia (WA) Department of Health suggested Australia needs to invest in marketing itself better as a trial destination of choice.
In WA, Linear Clinical Research has grown significantly over the last several years and currently attracts global studies to WA. Lessons learnt from companies such as Linear can contribute to the design of marketing approaches for other companies involved in the research and development of new drugs and novel technologies.
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PSA suggests greater investment in raising awareness about clinical trials with patients, families and the public is essential. This is not only to encourage patient participation in clinical trials but to generate conversations and improve understanding about the potential value of clinical trials more generally.
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It is acknowledged that pharmacists are:
‘a very accessible and trusted source of health information for the community’ and therefore uniquely placed to support patients with clinical trials information.
Infrastructure
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Medical research and the development of new medicines, therapies and devices have expanded rapidly in recent years and countries are becoming competitive in terms of offering incentives to run clinical trials. The Australian Government has been investing in this area however infrastructure is an area of clinical trials that requires further consideration.
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AAMRI commented that there are enormous growth opportunities for clinical trials in Australia:
Combined with other key population advantages and a strong medical research sector there is room for expansion. However, expansion within some hospital and healthcare settings will need encouragement. Most large hospitals are already inundated with clinical trials and are not able to take up all opportunities because of space and capacity constraints.
Work will need to be undertaken to grow the clinician researcher workforce, find funding solutions for sponsor monitoring, data management and research nurse costs, and crucially, provide space within hospitals.
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AusBioTech suggested examining opportunities to better leverage public hospital facilities and public health networks to better support clinical trials in areas of unmet need or priority need.
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The WA Department of Health proposed the following:
To enable Australian companies to expand and attract clinical trials and global investment there needs to be suitable access to infrastructure such as manufacturing facilities and wet laboratories.
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Ms Nicole Millis, Chief Executive Officer, RVA suggested a lot more can be done to make Australia a more attractive and sustainable location for clinical trials:
Australia needs … investment in clinical trial infrastructure, including registries, and also building up workforce and staffing capacity through the development of centres of excellence. We need the adoption of unique and more appropriate trial designs and to have these prioritised and recognised in HTA [Health Technology Assessment] processes. We also need to reduce the regulatory and bureaucratic burden of running clinical trials.
Clinical trial networks
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The Committee received evidence from the Australian Clinical Trials Alliance (ACTA), a national peak body representing Clinical Trial Networks (CTNs), Clinical Quality Registries (CQR) and Coordinating Centres (CCs). The CTNs represent groups of clinicians and researchers spanning a wide range of disease areas comprising over 10 000 clinical researchers. All of these trials are referred to as investigator-initiated trials (IITs).
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ACTA highlighted the important role CTNs have in Australia’s clinical trial sector:
CTNs play a significant role in increasing clinical trial recruitment to address unanswered clinical questions. CTNs help to ensure that national, consumer and community priorities are met. Clinical trials require specialised skill sets. CTNs, and the coordinating centres that support them, strengthen the collaborative development of research proposals through extensive consultation processes involving internal peer review of study proposals to ensure scientific merit and rigour.
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ACTA discussed the important shared intellectual and virtual infrastructure that CTNs bring to clinical trials.
Considerable efficiencies are created through the recruitment of specialists in trial design that build and share intellectual and virtual infrastructure across a longitudinal series of trials conducted within a network, making trial initiation easier, quicker and more cost-effective. Peer input and experienced coordinators generate a higher-quality trial design with a greater impact on patient outcomes and gross value generation.
Established CTNs possess critical trial infrastructure including access to a greater sample size through the collaboration of more sites, CTNs are ideally placed to conduct trials for orphan, personalised and off-patent drugs that could be repurposed and used to treat new conditions.
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ACTA works with the Department to increase the effectiveness of CTNs in Australia. It pointed out that more seed funding was required to get more CTNs started, such as an Indigenous Health CTN and it was emphasised that funding needs to be sustainable:
Greater funding is needed for CTNs to support large-scale, investigator-led clinical research in Australia to generate evidence of comparative effectiveness and test innovative approaches. Networks need core infrastructure support. Infrastructure support will enable networks to be more efficient and sustainable in order to liaise with industry and facilitate further trials.
Costs of clinical trials for sponsors
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Several industry representatives commented that the different set up costs in Australia had increased over recent years. This has created a disincentive to bring clinical trials to this country.
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Novartis Australia indicated that Australia had missed out on at least two studies, in part, due to high institutional and per-patient costs compared to similar top-tiered countries (such as the USA and Western Europe).
Growing variation in Institutional costs of conducting clinical trials in Australia (including the addition of significant ‘overheads’ to already high study visit costs) may be contributing to Australia becoming less attractive as a destination for global clinical trials. Although Australia (understandably) sits in the top tiers of countries in terms of trial costs, Australian Institutions have been gradually increasing costs over recent years. This is pushing our trial costs well above comparable countries. Due to the resulting high per-patient costs, Novartis is seeing global decision makers capping enrolment from Australian sites.
There have been two national initiatives in recent years to seek to standardise Institutional trial costs utilising the Independent Hospital Pricing Authority. Unfortunately these initiatives have not proved effective in reaching agreement on trial costs that are mutually accepted by Institution or sponsors. Sponsors should rightfully pay the cost of conducting global clinical studies in the Australian health system, however there should also be recognition of the significant benefits that global clinical trials accrue to patients, medical staff and the health system when institutions formulate clinical trials costings.
Costs to conduct trials have similarities across institutions, although they must currently be separately negotiated with each institution. The IHPA developed a standardised framework for costing services in 20158F9, although this has not been widely adopted. The requirement to agree costs delays contracting and, ultimately, trial start up.
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A study completed by the Department found that ‘one of the key barriers to both Australian and international pharmaceutical companies looking to conduct trials in Australia was cost, noting that this country was more expensive than South-East Asia and Latin American sites.’
Free drugs for lifetime
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BioMarin discussed two barriers they believe exist when consideration is given to holding clinical trials in Australia. The first concern was about Australia not having a timely reimbursement process. The second concern was to do with sponsors being required to provide a continuation of free drugs to participants after the trial has finished:
The challenge in obtaining timely reimbursement for new drugs and novel technologies is one of the greatest barriers to bringing clinical trials to Australia, because sponsors may be ethically required to provide free drug to participants for many years up to a lifetime if a viable pathway to funding does not exist.
The consequences of challenging reimbursement conditions can be seen in the PHARMAC system, where significant delays and/or indefinite deferrals of medicine reimbursement have resulted in sponsors becoming extremely wary of investing in clinical trials in New Zealand.
Cell and gene technology
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The Committee heard evidence throughout the inquiry that cell and gene therapies were becoming an important and increasingly more common treatment for precision medicine. As a result, this has led to complex regulations to try to fit cell and gene therapies into Australia’s current regulatory systems. This has created an untidy system of regulation that is time consuming to navigate and creates a barrier to investments in the clinical trials sector.
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The Sydney Children’s Hospital supported the need to streamline the processes for cell and gene technology:
Streamlining gene technology licencing processes for investigators and industry. For many advanced therapeutics, clinical trial readiness relies on having adequate facilities (PC2 lab) and navigating complex regulatory processes. Some clinical trials of gene and cell therapies require a licence from the Office of the Gene Technology Regulator under the Gene Technology Act 2000, and most licences require sponsor accreditation. This process can take in excess of 4 months which is currently a deterrent for Sponsors to bring gene therapy clinical trials to Australia.
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Pfizer highlighted the barriers that currently exist with clinical trials and cell and gene therapies, noting there are significant challenges in navigating the regulatory processes to set up a clinical trial for a gene therapy.
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The complex regulatory environment acts as a hindrance to bringing clinical trials to Australia and providing patients early access to novel therapies. Pfizer's recent experience establishing clinical trials for fidanacogene elaparvovec is a prime example of this.
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The Office of the Gene Technology Regulator (OGTR) is responsible for administering the Gene Technology Act 2000 (Cth). Specifically, it regulates dealings with genetically modified organisms (GMOs) including dealings conducted in human clinical trials involving therapies that contain a GMO.
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Before commencing a clinical trial in Australia involving a GMO, an organisation must complete/obtain the following permissions:
Accreditation (90 business days): The process of accreditation assists the Regulator in assessing if the organisation has the resources and the internal processes in place to enable it to effectively oversee work with GMOs. Once an organisation is accredited, in order to maintain the accreditation status, it must comply with a range of conditions on an ongoing basis. Note, the organisation is not required to apply/renew accreditation for each new clinical trial.
Access to and partnership with an Institutional Biosafety Committee (IBC): Before an organisation can be accredited, it must have established, or have access to, an IBC. IBCs provide a quality assurance mechanism, providing advice to assist organisations with the identification and management of the risks associated with GMO dealings, including containment of GMOs. They also review an organisation's GMO licence application prior to submission to the Regulator to confirm that the information included is complete.
Licence application for each individual GMO therapy: The DNIR licence application preparation is extensive involving 16 parts with more than 70 questions and a significant amount of work to complete. There is limited opportunity to leverage existing work completed for trials run conducted in equivalent overseas markets so additional work is required to make information relevant for the Australian experience.
Endorsement of the application by the IBC: Prior to submitting to the OGTR, the draft application must be reviewed and supported by an Institutional Biosafety Committee (IBC) for the purpose of ensuring that all of the necessary information is complete. In Pfizer's experience, the involvement of the IBC involves a significant amount of collaboration, with the process taking approximately 6 weeks to complete before the application form is finalised.
OGTR evaluation timeline: Once the licence application has been submitted, the OGTR has a minimum legislated timeline of 90 business days to evaluate the application.
Following approval of the DNIR licence the organisation must complete a Clinical Trial Notification to inform the Therapeutic Goods Administration (TGA). This process takes approximately 5 to 10 days to approve.
An application must also be made to Human Research Ethics Committee (HREC), part of the National Health and Medical Research Council. This process takes approximately 30 business days.
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Pfizer Australia currently holds a DNIR licence for the purpose of running a trial for fidanacogene elaparvovec.
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This entire process involves close to nine months' work across at least three different national agencies. While we acknowledge that regulatory governance is critical to ensuring the maintenance of appropriate standards of quality, safety and efficacy, Pfizer commented that Australia can do more to expedite regulatory efficiency and support timely access to innovative and transformational therapies in the gene therapy space.
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Pfizer Australia suggested there were opportunities for streamlining the regulatory pathway for a clinical trial approval in this space. These include:
clarifying and streamlining the partnership and governance responsibilities of the IBC and OGTR, particularly in the licence application processes and seeking approval for commercial supply, as well as creating opportunities to expedite regulatory review in Australia by leveraging overseas clinical trial applications and equivalent biosafety approvals delivered by equivalent regulatory markets overseas.
Injury from clinical trials
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Dr Diane Sheehan provided a submission that highlighted issues with the clinical trials system in Australia when Adverse Events (AE’s) affect patients involved in clinical trials.
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Dr Sheehan commented that there needs to be investigation into how AE’s are dealt with including:
more support for trial participants, improved clarity around where trial participants can get information and advocacy support, to be provided before, during the trial and increased to an appropriate level following any (AE).
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Further, Dr Sheehan proposed the following changes to clinical trials:
It would be useful to have a systematic approach to sharing information with trial participants and giving them a voice and input when the trial is being set up. Plus a full discussion about the information shared with trial participants and a framework of protection and management set up around those involved in trials, this needs to be a practical extension of the “National Statement on Ethical Conduct in Human Research”.
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Dr Sheehan pointed out that Australia’s National Clinical Trials Governance Framework does not address any issues that patients may encounter such as Adverse Events and possible compensation. Dr Sheehan commented that it would be beneficial to wrap protection around clinical trial participants by including a framework that:
Protects trial participants by setting up a regulatory environment
Expands an Information and Communication strategy
The use of advocates to manage participants and liaise with trial co-ordinators
Support participants throughout the trial.
The future
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Australia’s clinical trial sector has the potential for significant growth in the near future. The Committee heard evidence that Australia needed to make some changes to be ready for a surge in demand for novel medicines and devices in the clinical trial sector.
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Medicines Australia alerted the Committee to this and encouraged the Australian Government to make some significant reforms to capitalise on the future demand for tier one countries carrying out clinical trials.
Australia currently holds a strong international reputation as a location for high quality clinical trials. However, sustaining this reputation is increasingly challenging, as international competition for the placement of clinical trials has already begun to erode Australia’s advantage. Rather than relying on historical recognition as a reliable destination for quality clinical research, Australia needs to actively demonstrate superiority against other international benchmarks in clinical trials, to secure status as a preferred destination of choice.
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Medicines Australia suggested clinical trials in Australia could ‘expand clinical trial access to regional areas, [as this] would generate economic activity and support economic and health recovery.
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The Department acknowledged that they needed to improve the clinical trials system in relation to gene technology. Adjunct Professor John Skerritt, Deputy Secretary, Health Products Regulation, Department of Health commented:
The final area where people felt that we needed to have clearer guidance, especially around clinical trial requirements and manufacturing standards, was medicines made through gene technology. We've commenced a targeted stakeholder consultation to identify those issues and to see if there's a need for regulatory changes or explaining the current system better.
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Professor Adam Jaffe, Member of Scientific and Medical Advisory Committee, RVA, discussed a gap in Australia’s current clinical trials. Professor Jaffe is a specialist in rare diseases who deals with precision medicine and sees the landscape changing rapidly in this field of medicine. He described the ‘need to understand novel clinical trial design, such as basket clinical trials or adaptive clinical trials, which are a relatively new concept, and understanding the use of technology and embedding them in precision medicine.’ Professor Jaffe went on to state:
For example, in cystic fibrosis, there is the use of tissue organoids as precision medicine to project clinical responses. It's about ensuring that there's equity of access for patients with rare and ultra-rare mutations. …
These are bits of tissues that we take from children. We can have them in a test tube and we can test them against new treatments. For example, we have a child with a rare mutation who would respond to this drug, but we'll never get access through the current process.
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Professor Jaffe argued against using this new approach for some clinical trials as he stated it is unethical to take a child off a medication:
In fact, some trial designs have shown that, if you take them off a medication for a washout period to start on a new drug, their lung function starts declining. We need to look at new paradigms of how we do clinical trials. Hence my point earlier that we should be looking at adaptive trials. We should be using precision medicine. In our case, we use organoids.
If we can develop a companion diagnostic that gives regulators, physicians and patients confidence—'We have tested your child in a test tube and we can predict that your child should not take this medication,' because they won't respond to, say, Orkambi, but they will respond to Trikafta. That saves the taxpayer $300,000, it saves the child from any potential side effects, but it also gives you the opportunity to make sure that the child gets on a better drug, because 'We have evidence in our test tube that a drug not available in Australia is better than a currently available drug in Australia. It's probably available in Europe.' We need to embrace new technologies.
You need a body that could actually understand the change and could advise the TGA, the PBAC and MSAC. That's the gap that's missing, and a precision medicine advisory committee or group would fill that gap.
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Medicines Australia advised that to remain a world leader in the delivery of clinical trials, and to attract more clinical trials to Australia, we must be able to:
Commence trials quickly and in a consistent, harmonised, and efficient manner across multiple centres around Australia
Increase the ability for patients to participate in clinical trials. In particular, ensure there is wide recognition and equitable access to clinical trials for patients located in regional areas, through building tele-trials capabilities. This will ensure that clinical trials recruitment is similar to, or greater than that seen in other countries
Adopt modern and future-ready technologies to enable clinical trial processes to be conducted efficiently, cost-effectively, and where possible, remotely.
Committee Comment
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An important challenge for the Australian Government is the continuation and enhancement of Australia’s excellent reputation as a tier one country for clinical trials. The way forward needs to be considered carefully to maximise the advantages that clinical trials bring to the Australian healthcare sector and the economy.
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Australia’s regional neighbours are becoming more competitive on an international scale and could potentially be chosen over Australia to conduct clinical trials now and in the future. The Committee believes Australia needs to strengthen its position by streamlining regulations in ethics and governance as a matter of urgency to ensure Australia remains a tier one nation for clinical trials.
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The Committee understands that a lot of good work has been done over the past few years to make changes to ethics committees harmonisation between different jurisdictions. However it is imperative that the Australian Government act now to implement a seamless ethics and governance system. This important change will facilitate a regulatory process for sponsors that is easy to navigate and guarantee timeframes that are competitive with overseas countries.
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The current work being undertaken by the Australian Commission on Safety and Quality in Health Care (ACSQHC) must finalise an agreement between all jurisdictions for the National Mutual Acceptance Scheme to harmonise ethics approvals within all jurisdictions. Governance requirements must be streamlined into a simplified national system.
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Equally, the Committee believes the infrastructure needs to keep pace with advances in medicines and technologies to ensure the clinical trials can be run successfully in Australia. This includes ensuring there is sufficient space within hospitals to conduct clinical trials, along with highly trained staff and optimal technology.
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The Committee believes an Australian national clinical trial register is critical for Australia to attract sponsors to conduct clinical trials here. Sponsors currently find Australia attractive for clinical trials due to our diverse population and a highly skilled workforce. Australia will become even more attractive to sponsors if it has a well-maintained database of patients registered for different diseases, which will have a beneficial effect on medical research. A national registry should use state-of-the-art technology so that relevant data can be sourced from the My Health e-records of individual patients.
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The Australian Government should consider doing more to encourage the participation of Aboriginal and Torres Strait Islander populations in clinical trials. This should be taken into consideration when developing the national clinical trial register. The Australian Government should provide seed funding for Indigenous Health Clinical Trial Networks. In addition, the Committee sees benefit in providing Clinical Trial Networks with medium to long term funding to strengthen research findings, improve data management systems and connect with industry to facilitate further trials.
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Multi-centre trials are becoming more common in Australia. To further support them, it is imperative that there is more investment by the Australian Government in technological platforms, infrastructure, and education and training. Encouraging and supporting multi-centre trials is critical given Australia’s widely dispersed population and sometimes large distances between hospitals. Australia must ensure it has the infrastructure to support multi-centre trials. Further investment will not only attract foreign sponsors but will benefit rural, regional and remote patients wanting to participate in clinical trials.
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The Committee is of the view that the collection of data and the reporting of clinical trials should be improved. The Australia Government should investigate the costs that are currently being charged for clinical trials and benchmark them against other countries. The Committee believes that Australia needs to make itself as internationally competitive as possible and this includes keeping costs of running clinical trials at a reasonable level. The Committee sees merit in standardising the costs for clinical trials throughout Australia.
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Cell and gene therapy is a new field of medicine that is expected to increase significantly with new innovation and discoveries for medical therapies and devices. The clinical trials sector in Australia needs to be examined closely to streamline processes that will facilitate cell and gene therapy trials. The Committee believes this is a high priority and that it needs further examination to better integrate the clinical trials system with the Health Technology Assessment (HTA) process.
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The Committee believes Australia’s HTA systems need to become more flexible in terms of relying on evidence by way of head-to-head clinical trials for new medicines, therapies and medical devices. With the benefit of horizon scanning, Australia can adapt our approval systems early on to maximise the benefits of new medical technologies.