When conducting clinical trials in Australia, there are some specific Australian requirements that differ to those in other countries. This section outlines key factors that should be considered when conducting clinical trials in Australia, and how CNS can assist in that process.
Australia offers many benefits, including a favorable regulatory environment. It’s also cost-competitive to run studies in Australia – it’s the most inexpensive in comparison with 14 other major drug development countries (Ernst and Young, Benchmarking Report, January 2001).
Queensland and Australia has an aging population that is comparable to other developed countries which is useful for clinical trials as it indicates that Australia has a similar population and disease structures as those countries from where the majority of clinical trial drugs, treatments and therapies are generated. Queensland has the highest number of General Practitioners per individual than any other state in the country. The high number of health practitioners per individual, the ample medical facilities, solid infrastructure as well as a substantial and well dispersed population, indicates that Queensland is in a prime position to grow a reputable clinical trials industry. (QCTN Survey 2006 Report).
Australia can offer what you expect
The Clinical Trial Process in Australia
Find out about the Clinical Trial Process in New Zealand
The following topics summarise the processes involved in conducting clinical trials in Australia. For full details, see the appropriate regulatory guidelines related to each topic.
Australian legal entity
The sponsor of a clinical trial in Australia must be an Australian legal entity. CNS can make arrangements to act as the Australian sponsor of a clinical trial if the overseas sponsor does not have an Australian affiliate to fulfil this role.
In Australia there are two routes that may be taken to gain regulatory approval to conduct a trial - the Clinical Trial Exemption (CTX) and Clinical Trial Notification (CTN) schemes.
These schemes are used for clinical trials involving:
Clinical trials in which registered or listed medicines or medical devices are used within the conditions of their marketing approval are not subject to CTN or CTX requirements however, they still need to be approved by a Human Research Ethics Committee (HREC) before the trial may commence.
CTN
CTN is a notification scheme and over 95% of all trials are approved via this route. Via this route the onus is on the HREC to bear the responsibility for approving:
The TGA does not review any data relating to the clinical trial but acknowledges the trial in writing within 10 days of receipt of the signed CTN form and appropriate payment. It is increasing common for the TGA to request copies of the protocol and IB at some stage after issuing a Letter of Acknowledgement and on occasion may request some additional information. The TGA is empowered to place an ongoing study on “Clinical Hold” should their concerns be significant. This is extremely rare and likely to only affect phase I studies being conducted under a CTN.
A separate CTN form must be completed for each potential trial site. It is standard for all fees to be reimbursed to the CRO by the sponsor as part of the trial budget. CTN trials cannot commence until the trial has been notified to the TGA and the appropriate notification fee paid.
CTX
CTX is a modified approval process by which a sponsor submits an application to conduct a clinical trial to the TGA for evaluation and comment. A TGA delegate decides whether or not to object to the proposed usage guidelines for the product. If an objection is raised, trials may not proceed until the objection has been addressed to the delegate’s satisfaction.
If no objection is raised, the sponsor may conduct any number of clinical trials under the CTX application without further assessment by the TGA, provided that use of the product in the trials falls within the original approved usage guidelines. Each trial conducted must be notified to the TGA.
A sponsor cannot commence a CTX trial until written advice has been received from the TGA regarding the application and approval for the conduct of the trial has been obtained from a HREC at each institution where the trial will be conducted. Two forms, each reflecting these separate processes (Parts), must be submitted to the TGA by the sponsor:
There is no fee for notification of trials under the CTX scheme. The CTX approach is rarely used in Australia.
Clinical trials in which registered or listed medicines or medical devices are used within the conditions of their marketing approval are not subject to CTN or CTX requirements but still need to be approved by a HREC before the trial may commence.
Fees for the regulatory approval of clinical trials
As of August 2005, TGA fees for the CTN scheme are AUD$240 for each notification. A notification can be made for all sites participating in the trial simultaneously or several notifications can be made for subgroups of sites. A notification fee applies for each single notification.
The fee for a CTX 50 day review is AUD$15,300 (review of chemical, pharmaceutical and biological, pharmaco-toxicological and clinical data). The fee for a 30 day review is AUD$1,240.
Human Research Ethics Committees (HRECs)
Irrespective of which regulatory route is followed, all clinical trials must be submitted to the Australian equivalent of an Independent Ethics Committee (IEC) – a Human Research Ethics Committee (HREC).
In line with the National Health and Medical Research Council (NHMRC) standards, numerous public and private health HRECs operate in Queensland to review clinical trial protocol submissions.
Many HRECs work cooperatively with industry by utilising:
The requirements of the NHMRC for HRECs exceed those of ICH GCP. The NHMRC is a federal government committee that, amongst other duties, oversees HRECs in Australia. The NHMRC is independent of the TGA.
Ethics approval timelines
Most HRECs require submission to be made 2-6 weeks prior to a planned meeting date. The submission must be comprised of, but not limited to the:
If the CTN scheme is being used it is common for the submission to be first passed to a HREC Research Committee, who perform a review of the science of a proposed study and then pass their recommendation on to the HREC. The HREC will commonly meet 4-6 weeks later to perform a traditional IEC review. At any time the review and approval process may be suspended whilst the committee seeks answers to questions put to the submitting investigator. A standard timeframe from submission to final approval is 12-16 weeks, dependent on the scheme used, complexity of the study, requirements for advertising and other key factors relating to the proposed trial. However, these timelines are often reduced when working with specialist units such as phase I facilities, due to experience, expertise and support of such groups HRECs.
Informed consent
Sites are required to have their own informed consent forms that comply with their own specific institutional standards and formats, any HREC guidelines and of course ICH GCP. As such sites are likely to request changes to sample informed consent forms provided by overseas sponsors. Australian details on data protection, patient compensation, reimbursement and contact details for emergency safety issues, as well as independent advice, must be provided.
Insurance, indemnity and compensation
Insurance is required to be held by the Australian sponsor throughout the study. Some Australian states have specific requirements regarding the level of insurance cover and some sites require a copy of the sponsor’s certificate of insurance before commencing a trial.
Medicines Australia, an organisation representing the interests of the pharmaceutical industry, publishes Guidelines for Compensation for Injury Resulting from Participation in a Company-sponsored Clinical Trial and a Form of Indemnity for Clinical Trials. A standard Medicines Australia Form of Indemnity must be signed off by the Australian sponsor and the institution where the trial activities will be performed.
When considering a trial proposal, a HREC needs to be satisfied that trial participants will be adequately compensated for the costs of any injury suffered as a result of participation in the clinical trial. HRECs verify compensation arrangements to ensure that they satisfactorily protect the interests of participants and the trial site. Terms of the available compensation should be explained to all prospective trial participants.
Patient recruitment costs
It is typical for sponsor companies to reimburse patients for all out of pocket expenses associated with attending scheduled trial visits. This reimbursement must be clearly indicated in the patient information sheet.
Advertising and accelerated recruitment strategies are permitted if approved by the HREC. The costs of advertising are typically covered by the sponsor company.
All clinical trials involving Australian investigators or participants, in all areas of health and testing all forms of interventions should be registered in the Australian Clinical Trials Registry (ACTR). ACTR is a national on-line register of clinical trials being undertaken in Australia.
Studies that meet the International Committee of Medical Journal Editors (ICMJE) definition of a clinical trial should be registered. That is, any research project that prospectively assigns human subjects to intervention and comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome. Medical interventions include any intervention used to modify a health outcome and include drugs, surgical procedures, devices, behavioural treatments, etc. If in doubt about whether to register or not, registration is recommended.
Responsibility for registration lies with the Sponsor. A Sponsor is defined by the NHMRC and TGA as "an individual, company or institution or organization which takes responsibility for the initiation, management and/or financing of a clinical trial". It is the Sponsors responsibility to ensure that the information submitted is accurate and up-to-date. For full details see ACTR.
Shipping and storage of trial related materials
CNS can arrange the importation of clinical trial materials (trial medication, laboratory agents, sample material etc.) and delivery either directly to the research site, or to a third party storage and dispensing facility. Local temperatures can exceed 36ºC during summer months and safe storage of materials is very important.
The logistics of delivering trial materials to Queensland are easily managed due to Brisbane’s status as a major shipping port.
Drug or device labelling requirements
There are more requirements for the labelling of drugs and medical devices used in clinical trials than there are for standard labelling of registered therapeutics. Because the majority of clinical trials are blind or double blind studies, there is a great need to ensure that contents of clinical trials packs are easily and rapidly identifiable in the event of a serious safety issue. Traceable information is required to appear on the inner and outer packaging.
Key information that must be included on the packaging includes:
The outer packaging may include symbols or pictograms that clarify required information and a statement to ‘Return empty packaging and unused products’. Additional information, such as warnings and handling instructions, may also be displayed. A copy of each type of label needs to be kept in the batch record.
More detailed information regarding ADR and ADE classifications, reporting and other reporting requirements can be found in Access to Unapproved Therapeutic Goods – Clinical Trials in Australia – October 2004.
Central laboratories
Australia’s local and central laboratories are strongly preferred by Australian investigators in order to avoid loss of or damage to test samples and reduce wastage of time and sample tissue. All packaging of infectious and non-infectious samples for transit must be performed by properly trained and certified staff. Most laboratories have their own local courier services which ensures appropriate packaging and timely delivery of samples to the assessing laboratory.
ADRs and ADEs
Well established national procedures are in place for the reporting of adverse drug reactions (ADRs) and adverse device events (ADEs) related to pharmaceuticals and medical devices respectively, whether registered or unregistered.
Suspected ADRs must be reported in specified formats within specific time frames to the Drug Safety and Evaluation Branch of the TGA. Serious reactions must be reported immediately and reporting of less serious events must comply with less urgent timeframes.
Serious ADEs must also be reported immediately, unless the HREC accepted protocol specifically lists an exemption from immediate reporting of specific ADEs. ADE reporting needs to be directed to the Medical Officer, Office for Devices, Blood and Tissues in the TGA.
More detailed information regarding ADR and ADE classifications, reporting and other reporting requirements can be found in Access to Unapproved Therapeutic Goods – Clinical Trials in Australia – October 2004.
Study close-out archiving issues
Australian regulations stipulate that records need to be retained for 15 years following the completion of a clinical trial, thus adhering to GCP. Investigational sites will often request financial support from the sponsor for offsite archiving by a third party. Conducting Clinical trials in New Zealand
New Zealand has a population of four million, predominantly of European descent, but with sizeable Polynesian and Asian populations. Advantages include:
Medical Standards
Clinical trial standards are high and practices are similar to those in Western Europe and North America, but with less bureaucracy and lower costs. New Zealand's medical training encourages doctors to spend time overseas, so many investigators have international experience and are familiar with ICH-GCP and other guidelines.
Clinical trial sites are well organised, with motivated staff. Investigators tend to be hands-on involved in clinical trials, meaning a more personal service for patients, better recruitment and retention, and quality data as a result.
Regulatory Authority
The Ministry of Health's (Medsafe) Standing Committee On Therapeutic Trials (SCOTT) approval process takes a maximum of 45 days, usually less. This is required for non-registered drug formulations, but not for medical devices, nor new indications of NZ registered formulations. Ethics Committee (EC) applications can be submitted in parallel. SCOTT applications cost NZ$9500 with no charge for Ethics Committee applications. Currency Conversion
Ethics Committee (Institutional Review Board)
Only one Ethics Committee (EC) review is required per study in New Zealand. It takes 1-2 months from submission to full approval. EC’s meet monthly / twice monthly except January, and require notice and prepared documents two weeks prior to a meeting to consider the application. All EC's in New Zealand use the same application form, and one regional or national committee represents all study sites, saving much paperwork. For more information including agenda and meeting dates see www.newhealth.govt.nz/ethicscommittees. There is no cost for this.