Cancer clinical trials in Australia

The data collected by clinical trial registries have many applications. Clinicians and patients can search for trial options for specific conditions when standard treatments have been exhausted, or where no effective treatment exists. Comparisons between trials registered and those subsequently reported can suggest publication bias. Researchers planning new trials can avoid duplication by identifying gaps in the targeting of cancer types in current trials.

In this issue of the Journal (→ Landscape of cancer clinical trials in Australia: using trial registries to guide future research), Dear and colleagues have analysed data from the Australian New Zealand Clinical Trials Registry and an international registry based in the United States, ClinicalTrials.gov, to describe the landscape and funding sources of cancer trials in Australia, to aid the planning of future cancer trials.1 They found that the Australian situation reflects the international situation, where investment in trials for specific cancer types does not correlate with the disease burden caused by those cancers. For example, breast cancer accounted for 17% of trials, with high levels of patient recruitment, while lung cancer represented only 7% of trials despite its higher disease burden.

The authors concede that this observation from the registry data may be inaccurate because registration of trials is not mandatory in Australia, and there is no way of recording the nature of unregistered trials. Also, the registries more comprehensively list Phase III trials than early phase trials, so overrepresentation of some tumour types could partly reflect more success in identifying potentially effective new drugs to treat them, which then progress to Phase III trials. If such disparities in research do exist, one remedy is targeted funding to attract research on different tumour types.

Similarly, some types of tumour receive more popular exposure in the media than is warranted by their burden of disease, which allows speculation about the impact of consumers on the research agenda.2 This was postulated from the high number of non-drug intervention, non-industry-sponsored trials for breast cancer compared with other tumour types.1 It is also clear from the trial registries that non-drug trials, such as psychosocial trials, are generally underrepresented. These will rarely be funded by industry and require investment from government and community research funds.

The importance of pharmaceutical industry sponsorship to the cancer clinical trial effort in Australia is underpinned by the finding that 64% of drug trials are funded by industry. It is not unexpected that industry was found to predominantly sponsor drug trials involving metastatic disease, where therapeutic gains can be more promptly translated into commercial success. Adjuvant trials are often multinational and, because survival is often the endpoint, take many years to achieve a result, unless an earlier surrogate endpoint can be identified.

It is surprising that tumour type was not found to correlate with pharmaceutical industry sponsorship, as more trials involving higher-incidence tumours would have been anticipated. But the finding that systemic therapies attracted more industry sponsorship than local therapies was expected, as most sponsored studies would have new drug development as their goal. With the increasing development of targeted therapies, the histological type of cancer will become less important, but it remains a potential concern that financial incentives favour drug development for high-incidence tumours and that progress in treating rarer cancers is delayed. The registry data can provide a guide as to where future trial funding should be directed.

An additional issue of great concern that may be reflected by clinical trial registries is a decrease in clinical drug trials being conducted in Australia.3,4 Clinical trials are essential to developing the evidence base for improving cancer treatments, and traditionally Australia has had a high trial recruitment rate relative to its population.4

A robust clinical trial program fosters and retains local expertise in scientific and medical research and clinical care. It also ensures the opportunity of early access to new treatments and improved quality of care and monitoring for patients participating in clinical trials, which enables translation into improved routine care and outcomes.5,6 There are also economic benefits of clinical trials: the average dollar invested in health research and development returns $2.17 in health benefits, and sponsored trials of new drugs serve to reduce a hospital’s drug expenditure.5

What is required to enhance clinical trial activity in Australia is to both support independent cooperative trial groups and encourage increased pharmaceutical industry investment. Infrastructure funding for trial groups, such as that provided by Cancer Australia, is vital, but hospitals must also see support of clinical research as a core part of their business rather than a source of additional revenue through facilities fees, which increasingly make trials more expensive to perform. E-health platforms will also enhance trial capabilities by centralising data for easier access and sharing, and making verification of source data easier.7 Clinical trial registries that are more consumer-friendly should play a role in enhancing patient recruitment by making it easier for them to find suitable trials.

Centralising ethical review of multicentre trials, as is encouraged by the Australian Government’s Harmonisation of Multi-centre Ethical Review (HoMER) initiative, will streamline the ethics approval process, particularly for Phase III trials, without compromising the rigour of the review.8 Similarly, as part of the HoMER intiative, setting standards for the quality and timeliness of governance review of trials, which still must be done by individual health units, will also help facilitate the approval process.

Data from clinical trial registries should be used to monitor the progress of such efforts to ensure Australia has a robust clinical trial capability.