As clinical trials surge into Australia, HHS targets US bottlenecks

CREATE Medicines, a biotech company based in Cambridge, Massachusetts, is developing three cancer medicines that have progressed to Phase 1 clinical trials, typically the first time people receive an experimental drug.

Despite the robust biotech and medical ecosystem in the Boston area and elsewhere in the US, CREATE did something that’s become increasingly popular among US biopharma companies: it conducted the Phase 1 trials for all three drugs over 16,000 km away, in Australia.

The country boasts first-rate universities and research institutes, but with a population of about 28 million, it has not yielded the kinds of pharma powerhouses that have sprung up in places like the US, Europe, and China. Only one of the world’s largest 100 pharmaceutical companies, as measured by 2023 sales, calls Australia home.

In the past 2 decades, however, the number of Phase 1 trials hosted in Australia has skyrocketed.

According to C&EN’s analysis of data from Clinicaltrials.gov, which is maintained by the US National Institutes of Health (NIH), and the Australian New Zealand Clinical Trials Registry, the number of Phase 1 clinical trials held in the US each year still significantly exceeds that of Australia. But on a per capita basis, Australia has surpassed the US every year since 2012 and continues to extend its wide lead.

Australia attracts companies looking to conduct Phase 1 trials largely because trials get off the ground quickly there. Phase 1 trials that might take more than a year to launch in the US can start up in Australia in just a few weeks.

US policymakers have recently started taking note—of both the inefficiencies in the US system and the potential solutions offered Down Under.

In June, the US Department of Health and Human Services (HHS) launched Operation TrialBlazer, a multiagency effort to accelerate domestic Phase 1 trials. Australia, according to the 22-page report, has “found success in early stage trials, being widely regarded as a top-tier country for Phase 1 clinical trials.”

By working to accelerate these trials in the US, the Donald J. Trump administration is aiming to encourage biopharma companies to conduct their trials in the country. Such an outcome would not only have economic benefits. The administration believes that Phase 1 trials are also a key front in its rivalry over biopharma innovation with China, which, for several years now, has conducted more clinical trials than the US, including Phase 1. There are national security risks, the thinking goes, if China continues to control a greater share of early-stage clinical research and the drugs that could result from it.

The US is hoping it can reassert its leadership in an area the TrialBlazer report calls a “competitive challenge with real consequences for American patients, industry, and national security.” And it’s looking to replicate Australia’s success, where, unlike in China, trials are run quickly and have a sterling reputation for data reliability and patient safety.

Some of the reforms proposed in Operation TrialBlazer even seem to be modeled after the Australian system. But a range of drug development experts are skeptical that the initiative will be enough to stem the tide of US companies flocking to Australia in ever-increasing numbers.

The Australian advantage for Phase 1 clinical trials

Speed is paramount for companies sponsoring clinical trials. The faster a company can launch and run a clinical trial, and generate data on whether a drug is safe and effective, the better its odds of getting the drug to market before competitors and securing lucrative patent protections. But for smaller companies like CREATE, moving quickly in the early stages of drug development can be crucial for simply staying in business, because investors often want to see encouraging Phase 1 results before providing more funding.

“How fast can we get to knowing whether a new drug works or not? That is the key,” CREATE CEO Daniel Getts tells C&EN. Australia “allows us to move super quickly . . . and that means that we leverage less investor capital.”

Gain Therapeutics, a small biotech company based in Maryland, chose Australia for its Phase 1 study of GT-02287, a drug to treat Parkinson’s disease. Many of the patients who received the drug in the Phase 1b portion of the trial saw a decrease in Parkinson’s biomarkers; the company is now planning to begin a larger, Phase 2 trial later this year.

“Australia is a wonderful place to do early clinical trial work, especially for companies that are heavily reliant on outside capital,” says Gain CEO Gene Mack. “It’s been a huge assistance to us.”

The financial benefits extend beyond start-up speed, according to Mack. The Australian government offers certain clinical trial sponsors a 43.5% tax rebate on research and development expenses incurred in the country, and the exchange rate means that US companies can get more for their dollar in Australia.

Furthermore, like the US, Australia is home to an ethnically and genetically diverse population, which means that trial sponsors can test their drugs in a variety of patient cohorts. And because the trials are considered trustworthy, sponsors can use Australian Phase 1 data to support later-stage trials in other countries, including the US. (Given Australia’s smaller population size, it can be difficult to assemble the larger cohorts needed for Phase 2 and 3 trials, which is why the country isn’t as favored for those studies.)

There are logistical challenges for US companies going to Australia, not to mention an extreme time zone difference. But all the benefits, which together are often called the “Australian advantage,” have spurred CREATE, Gain, and a growing number of other US companies to move their Phase 1 trials to Australia.

The boom has been overwhelmingly fueled by US companies. By far, the largest share of Phase 1 trials launched in Australia since 2020 have been sponsored by companies based in the US or their subsidiaries. US companies have led Australian companies in this regard since 2014. And US companies aren’t alone in seeking out the Australian advantage. At the start of the century, not a single trial in Australia was sponsored by a Chinese company, whereas they now consistently sponsor a few dozen trials there each year.

For Australian Phase 1 trials, but also those taking place in the US and elsewhere, the active treatment period typically lasts only a few months. Delays usually arise in the preceding study start-up period, when sponsors develop a detailed protocol, get approval from a regulator and an ethics committee, determine a budget, and recruit patients.

While data on the average start-up time for a Phase 1 clinical trial in Australia are sparse, those who work in the space say trials can launch in a matter of weeks.

Philip Ryan is the medical director at Nucleus Network, one of Australia’s largest contract research organizations (CROs) focused on early-phase clinical trials. He says clients typically need to wait only 8–10 weeks in between the submission of a study protocol and the first patient receiving the drug.

For MT-303, a chimeric antigen receptor (CAR) therapy that CREATE is developing for hepatocellular carcinoma, the first dose was administered in the clinical trial a mere 8 months after the company first “drew on the whiteboard what we wanted the molecule to look like,” according to Getts. (The MT-303 trial is being conducted in several Asian countries in addition to sites in Australia.)

There’s also been minimal study of the issue in the US context, but the data that do exist paint a picture of a much slower system. A 2018 survey of over 400 unique biopharma companies and CROs—75% of which were based in the US—found that the average length of time for selecting treatment sites and preparing them for patient enrollment in clinical trials was 25.7 weeks, and 35.6 weeks if the sites were new. And a separate survey of 61 US cancer centers found that the median time for activating a clinical trial site was 167 days.

The FDA as the primary bottleneck? “The data don’t support that”

The US and Australia have fundamentally different approaches for approving clinical trials. In the US, sponsors seeking to initiate a trial submit an investigational new drug (IND) application to the Food and Drug Administration, which reviews the preclinical data and the Phase 1 study protocol. Separately, an institutional review board (IRB), which includes physicians, scientists, and nonscientists like an ethicist or a lawyer, determines whether the trial is ethical and if the benefits of the intervention outweigh the risks.

For most trials conducted in Australia, in contrast, sponsors only have to notify the Therapeutic Goods Administration, the country’s FDA equivalent, of the intent to do the clinical study. Only the IRBs—which are called human research ethics committees (HRECs) in Australia—review and approve the protocol.

Operation TrialBlazer lays much of the blame for slow approval of US Phase 1 trials at the feet of the FDA’s IND system, noting that FDA reviewers are burdened with “substantial and growing portfolios of INDs, marketing applications, and adverse event reports” and that the agency historically “has not clearly communicated its requirements for starting first-in-human trials.”

But according to Molly Klote, a medical consultant and former director of the HHS Office for Human Research Protections, “the data don’t support that” the FDA is the primary bottleneck. (Klote was laid off from the role in April 2025 amid sweeping reductions in force across the HHS.)

By law, once the FDA receives an IND application, it has 30 days to either approve the study or place it on clinical hold to request more information, and the agency “actually has a pretty good track record of hitting that,” she says. Less than 10% of INDs for new cancer drugs, for instance, get put on clinical hold, according to FDA figures.

“I think everybody has to be honest about where the time is really going and then aim the reforms there,” Klote says. “The IND and the science review—it’s already fast, and it’s already pretty predictable.”

“My experience has been less about FDA being a bottleneck. . . . I’ve had a number of INDs, a number of interactions with [the FDA, and] the communication has always been great,” Getts says.

The real delays, Klote says, begin after a sponsor gets the IND approval. Even for small Phase 1 trials, there’s a wide range of stakeholders—the sponsoring company, doctors, hospitals and universities, drug manufacturers, ethicists, and patient advocates, to name a few—that need to get on the same page before patients start receiving the drug. It can take several months for the various parties to negotiate a budget, as well as propose and discuss protocol amendments, Klote says.

According to a 2016 survey from WCG CenterWatch, a clinical trial information service, and the Association of Clinical Research Professionals, more than half of trial sponsors said they experienced delays in trial start-up due to contract and budget negotiations, whereas only about a quarter said that regulatory compliance or IRB approval slowed them down.

TrialBlazer addresses some of these issues. It notes that protocol amendments often delay trial start-up and proposes that the FDA advise on how to minimize the chances of needing amendments. It also suggests the possibility of a single IRB overseeing all clinical sites in a trial; typically, each site requires its own IRB. But according to Klote, the document doesn’t prioritize fixing the trial contracting issues, even while acknowledging that IRB approval and contract negotiation can add up to 13 months before patients are enrolled.

Contracting “is the number 1 delay. We should have standardized master clinical trial agreements and budget templates that institutions either accept or don’t accept, with almost no renegotiation available to them,” she says.

An FDA spokesperson tells C&EN that “the agency is eliminating unnecessary regulatory burden, clarifying phase-appropriate requirements, while maintaining regulatory standards and building partnerships with government, academic medical centers, and the private sector,” but did not comment on the role of contracting in clinical trial delays.

Operation TrialBlazer faces implementation hurdles

These alignment issues are far less likely to cause delays in Australia, according to Michael Phelan, a regulatory consultant based in Melbourne, Australia. Not only are multisite trials commonly overseen by a single HREC, but the CROs in Australia are also well connected with sponsors, HRECs, clinicians, and the other stakeholders, enabling them to exchange information and resolve potential issues much earlier and more quickly than their US counterparts.

“Australia has a really robust clinical CRO system,” Phelan says. For instance, “you’ve got CROs indicating to sponsors which HREC [they] should go to” and which clinical sites they should use, to maximize speed. The HRECs, in turn, are “well staffed and well educated” on both the scientific and ethical fronts, so they’re able to advise sponsors before their official review on questions like whether the preclinical data support the Phase 1 design and on ensuring that patients are properly selected, Phelan notes.

According to Phelan, Operation TrialBlazer aims to mimic this integrated ecosystem through the launch of a pilot that will establish a network of what it calls qualified research institutions. These QRIs, according to the document, will include academic medical centers, health-care networks, CROs, and regulatory advisers who will review certain components of the IND and advise sponsors on IND submissions.

The HHS did not respond to a request for comment on whether Australia’s system inspired the QRIs or other aspects of TrialBlazer.

The idea of such a network is “very reasonable,” Phelan says, because when these groups talk to each other earlier in the process, they’ll be able to strike agreements more efficiently. “If you get the IRBs, and you get the CROs, and you get everybody to agree to the trial while the IND [is reviewed], then instead of doing everything sequentially, [they] can just do it all at the same time.”

But if the initiative is reasonable, it’s also largely hypothetical at this point, along with the rest of the proposals set forth in TrialBlazer, he says. The FDA and the other HHS agencies called upon in the document—which include the NIH, the Advanced Research Projects Agency for Health, and the Office of the National Coordinator for Health Information Technology—will need financial incentives, and practical guidance and training, to successfully implement TrialBlazer, according to Phelan.

Furthermore, Mack of Gain Therapeutics points to workforce reductions at the FDA and other federal agencies over the past year and a half as a possible obstacle to the HHS instituting major clinical trial reforms. And Getts of CREATE Medicines further notes that navigating which private insurers will cover which treatments for which patients adds significant cost and complexity to the Phase 1 trial start-up process in the US. These hurdles are bypassed in Australia, which has a single-payer health-care system.

“I’m very worried about the US ecosystem,” Getts says. “We’ve got to figure it out quickly.”

Until then, US companies may continue going across the world for their clinical trials. In late July, CREATE announced that it got approval to start a combined Phase 1/2 clinical trial for CRT-402, a CAR T-cell therapy for autoimmune disease. The trial will take place in Australia.