There's an old project management adage: "Good, fast, cheap: choose 2". The implication is that when developing your product, you have the following options:
1) You can develop a product that is of high quality and you can run your project quickly, but it won't be a cheap exercise.
2) You can run things quickly and cheaply, but you will compromise on the quality of the end product.
3) You can develop a high quality product and it can be done cheaply, but it will take a long time.
The challenge in translational radiopharmaceutical (or any pharmaceutical) development is also constrained by this "Iron Triangle", often driven by corporate or investor demands.
Maximising the value of an early-stage asset in a competitive space relies heavily on budget, speed and convincing data. Finding a realistic solution to this conundrum should be high on any company's list of priorities.
Fortunately, in the world of radiopharmaceuticals, such a solution is available: run your first-in-human or proof of concept studies in Australia. Why? Because Australia is uniquely positioned to help you break the Iron Triangle and secure all 3 aspects of the ideal project:
1. Good (ie high quality results)
When it comes to obtaining quality data in early stage trials, start with experienced investigators who have done it before. Australia has some of the brightest minds and most experienced hands on the planet when it comes to first-in-human studies - the kind of professionals that know the right questions to ask about your product to assess its feasibility and determine the clinical appropriateness of your approach.
The Australian Nuclear Medicine community is small but sophisticated. Ground-breaking prospective clinical trials (such as the ProPSMA study) have resulted in well organised trial networks with motivated investigators, qualified equipment, standardised processes and streamlined logistics.
Australians in general are among the earliest adopters of technology in the world, and the same is true in Nuclear Medicine. Bleeding-edge hardware is available at many tertiary hospitals and Australia has a number of Centres of Excellence for the world's leading equipment makers. In addition to technology, clinicians in Australia have rapidly seen and embraced novel radioisotopes for diagnostic and therapeutic products, often bringing treatments to patients more rapidly than in large markets like the US.
Finally, Australia has numerous manufacturing and radiolabelling service providers, as well as preclinical imaging/therapy and toxicology CROs to help gather supportive data for regulatory and ethics submissions.
The simplicity of the Australian regulations for clinical trials of unapproved products is one of the principal attractions for many pharma and biotech companies to conduct studies here, and is a major competitive advantage compared to the US and EU. No formal regulatory review by the Therapeutic Goods Administration (TGA) is required to conduct a clinical trial. The system relies on a process called the Clinical Trial Notification (CTN) scheme, which requires the sponsor to pay a small fee of several hundred dollars and complete a proforma informing the regulator that a trial is being conducted. The whole process typically takes no more than a week or two.
Under this scheme, institutional ethics committees (called Human Research Ethics Committees or HRECs) are the bodies that review the project in detail to determine if it is acceptable to be conducted within their hospital. Although most first-in-human or early phase studies are conducted at a single site, the ethics application process is relatively straight forward in Australia, with 90% of sites using a standardised template and accepting reviews from other sites around the country. For radiopharmaceutical studies involving ionising radiation, the HREC will also require an independent risk assessment (typically by their in-house Radiation Safety Officer) which will look at expected exposures for research participants.
In Australia, study governance is also streamlined with an agreed template Clinical Trials Research Agreement and Indemnity Form which takes the hassle out of negotiating with the site's legal department. Many trial costs have been standardised across sites to ensure that the sponsor has a good idea of the costs of conducting the study
Perhaps the most appealing aspect of the Australian clinical trials industry is the cost-competitiveness. According to a recent study, Australia was a whopping 60% cheaper that the USA for conducting the same clinical trial. What are the elements that contribute to such savings?
- Operational: Australia is cheaper than the US across the board for operational expenditures such as CRO costs, Investigator and site fees and patient visits. Some reports estimate that these are around 20% cheaper.
- Exchange rate: the Aussie dollar typically trades well below the US dollar or the Euro. In the last several years the AUD rate has been 60 to 80 US cents and between 0.7 and 0.6 Euros. This provides a substantial discount of between 20 to 40% for R&D programs for overseas companies.
- R&D cash rebate: Australia provides a cash rebate of 43.5% on eligible expenditure for Australian resident companies with a turnover of less than AU$20 million. There are also attractive incentives for companies who's aggregate turnover is greater than AU$20 million. To claim the 43.5% incentive on R&D clinical trial expenditure, the company will have to set up a permanent local subsidiary and meet a few other non-onerous rules for eligibility.
As an example of these cost savings with current exchange rates, an early stage clinical program which might be budgeted at US$2 million in the US could be discounted to under US$1 million just by shifting the trial to Australia. And that is without the added regulatory costs associated with obtaining FDA or EMEA approval to conduct the trial.
Conducting your early stage radiopharmaceutical clinical trials in Australia can break the Iron Triangle by finding a "good, fast AND cheap" solution. This is particularly relevant for first-in-human studies, where the development strategy should be to determine the proof of concept as quickly, efficiently and cheaply as possible. This allows a company to either kill/optimise the product or move it rapidly into subsequent development. It is also crucial for smaller companies with less capital to invest in value creation, and where using money wisely to generate interest for subsequent capital-raising activities can help bridge the funding "valley of death".