January 29, 2018
With uncertainly about the impact of Brexit, and concerns about quality in India and China, drug development companies are looking to other markets to conduct clinical trials.
Based on data from ClinicalTrials.gov, registered drug clinical trials in India declined from 2010 to 2015, although these numbers are predicted to increase, following changes toward a more supportive regulatory environment in the country.
In the past year, the agency has sent officials to the country to participate in workshops on emerging issues, including inspections of clinical investigators, clinical trial sites, ethics committees and bioanalytical study sites, as well as maintaining data integrity in clinical trials.
Meanwhile, following reports of falsified clinical trials data in recent years, the Chinese government has launched verification initiatives and other efforts to deter fraud, including instituting severe criminal penalties.
In Europe, should Brexit negotiators fail to come to an agreement on recognizing clinical trials research, the increased complexity, costs and risk could drive research away altogether, according to Mike Thompson, chief executive of the Association of the British Pharmaceutical Industry (ABPI).
“If you’re a company and you’re saying, ‘I need 8,000 patients in this trial, so I’m going to need 40 centers or whatever to recruit those patients’ — if you’re got to go through two systems of approval, it’s quite possible that you’re going to say: ‘I can’t be bothered to do that,’” Thompson told a House of Commons committee, during a hearing on Brexit’s effects on the life sciences industry.
“If there isn’t complete alignment, the EU could say we’re not going to accept the results from UK centers, because they’re not going to be governed by exactly the same legislation,” he said, describing what he called “the nightmare scenario.”
With these global issues, Australia is positioning itself as an attractive destination for clinical studies and early-phase research.
The country’s Trade and Investment Commission touted a streamlined regulatory pathway for launching new trials, as well as dedicated Phase I units and tax credits for research, in a report that aims to attract new business.
With 37 clinical trials networks and several biobanks in place, plus over 232,000 employed in the Australian life sciences sector, about AU$33 billion is being spent on total research and development in the country, or nearly $27 billion in U.S. dollars.
The report estimates about 6,900 staff dedicated to conducting clinical trials, with AU$1.1 billion in direct commercial expenditures, plus AU$3 billion in government spending on medical research projects at public hospitals, universities and independent research institutes.
The past decade has seen dramatic growth in the number of Australian Phase I and first-in-human trials, at a rate that is beginning to overtake Phase III trials in certain disease areas, such as pain treatment, non-small cell lung cancer and other solid tumors. From 2012 to 2015, Phase I activity increased 17.2 percent, outpacing the global average of 1.8 percent, according to Austrade.
This reflects the availability of faster study start-up times, which only require notifying the country’s Therapeutic Goods Administration (TGA), instead of a full protocol review and approval process, according to Lucas Litewka, director of the clinical trials center at the University of the Sunshine Coast in Queensland, Australia.
Following safety and efficacy assessments and protocol approval by an institutional review board and ethics committee, sponsors simply submit a Clinical Trial Notification to the TGA, Litewka said.
Private and public IRBs can approve trials in as little as three weeks, with private organizations usually being faster than the centralized boards, he said. Site governance processes and approvals can be completed in parallel, according to Austrade.
“At best it is one month to start a study in Australia,” but typically two-to-three months, Litewka said. The TGA still has the authority to audit the management of clinical trials, however.
“Fairly quick compared to other regions,” he added, with data being accepted for registration by the FDA, European regulators, Japan and Canada.
The TGA holds observer status in the International Council for Harmonisation, and has adopted the ICH E6 guideline on good clinical practice. In addition, ICH or ISO GCP standards have been mandatory for all Australian clinical trials since 1989, according to the country’s main research body, the National Health and Medical Research Council (NHMRC).
Additional benefits include the country’s ethnically diverse, English-speaking population for patient recruitment. Seasonal differences between the northern and southern hemisphere allow global flu vaccine, allergy or respiratory trials to be conducted year-round, the NHMRC said.
Plus, 43.5 percent of R&D costs can be reimbursed to smaller companies with under AU$20 million in annual revenue, or about $16 million U.S., Litewka said. A 38.5 percent tax offset is available to other companies. The Australian government has also produced a standardized table of clinical trials costs for sponsors, to assist in negotiating site contracts.
However, the country still has work to do in enhancing patient numbers per trial, and improving clinical trial awareness, recruitment and retention, according to MTPConnect, an Australian government-funded non-profit focused on the pharmaceutical and medical device industries.
The country needs to invest in deeper capabilities for innovative types of studies, including adaptive clinical trial designs and complex first-in-human trials, instead of larger, later-phase studies that may require larger, more expensive patient populations.
“In trials with lower complexity in design or that require features such as large patient pools, Australia is increasingly rivalled by competitors with better access to larger patient pools and lower cost bases from Asia Pacific, Eastern Europe or Latin America,” the group said.
While progress has been made in streamlining ethics approvals, Australia also needs to develop better transparency and tracking measures for gauging overall sector performance.
With additional government investments in clinical trials infrastructure, including AU$30 million over the next four years, MTPConnect estimates the number of skilled jobs in the field could nearly double over the coming decade, with direct spending on trials increasing from AU$1.1 billion to over AU$2 billion.
As industry-sponsored trials continue to expand worldwide, companies will have to examine the quality of local research capabilities, regional medical experts and staff and national infrastructure in choosing where to set up their trials.
“As international competition for clinical trials intensifies, it will be critical for Australia to address the impediments outlined above to ensure continued growth in the sector,” MTPConnect warned.
—by Conor Hale @conorhale