Clinical trials Australia

In Australia, approval of clinical trials involves both the regulatory authority and an ethics committee. Under the Clinical Trial Exemption (CTX) scheme, a clinical trial proposal must first be evaluated by the TGA, and then approved by an ethics committee on-site. Under the Clinical Trial Notification (CTN) scheme, a trial is evaluated and approved by the local ethics committee, and then notified to the TGA. 

Differences in the systems used to regulate clinical trials in Australia and the Netherlands illustrate how the delegation of authority affects the ability of the central agency to monitor the working of the entire system. In Australia, all approved clinical trials must be notified to the TGA. There is no such reporting requirement for the MEB in the Netherlands. Information about the number and details of clinical trials conducted in the Netherlands is therefore not readily available to the MEB. 

Quantitative data indicate a general increase in the number of clinical trial applications in Australia, Cuba, Estonia, Malaysia and Venezuela for the period 1994-97. Figure 8.11 shows the four-year average number of clinical trial applications received by the relevant authorities in these countries. During this period, the number of clinical trial applications in Australia far exceeded those received in all the other countries combined. The same is also true when the number of applications is computed against the number of new drug applications (Figure 8.12). 

Section 8.7 explains the clinical trial and drug approval processes in Australia. 

Figure 8.15 Clinical trial applications in Australia. TABLE 8.4 TGA Fees, 2007...

The decision to approve a new drug is made by a national regulatory body (Food Drug Administration in the U.S.A., the Health Protection Branch Drugs Directorate in Canada, UK Europe, Australia) to which manufacturers are required to submit their appUca-tions. AppUcants must document by means of appropriate test data (from predinical and clinical trials) that the criteria of efficacy and safety have been met and that product forms (tablet, capsule, etc.) satisfy general standards of quality control. 

A Clinical Trial Exemption (CTX) Scheme was introduced in Australia in 1987, with the intention of encouraging clinical trial activity. However, in addition to the aforementioned TGA restrictions, which required all clinical trials of an active substance underway in Australia to be completed before the review of a general marketing application relating to that substance, the specified data package included requirements unique to Australia, and the 60 working day review period compared with a 35 calendar day review imder the UK CTX Scheme. 

Eees apply to almost all evaluation activities undertaken by TGA - not only to the review of general marketing applications but also to minor marketing-related matters, clinical trial applications and notifications, and GMP evaluations and inspections in Australia or overseas, but not to ADR assessments. 

The type of submission considered by DSEB to be appropriate for a PI update depends on the regulatory and clinical history of the drug in Australia and overseas, with special reference to the United Kingdom, United States, Sweden, Canada and the Netherlands. Submissions based on company sponsored clinical trials are usually required for drugs marketed for less than 5 years, whereas any of the three types of submission can be used for drugs marketed for more than 10 years. Drugs marketed between 5 and 10 years will be considered on a case by case basis, but it is generally expected that either a conventional or hybrid submission will be submitted. 

There are two schemes under which clinical trials involving therapeutic goods maybe conducted in Australia - the Clinical Trial Notification (CTN) Scheme and the Clinical Trial Exemption (CTX) Scheme. These schemes are used for clinical trials involving any product not entered on the ARTG, or use of a registered or listed product in a clinical trial beyond the conditions of its marketing approval. 

Furthermore, Australia has a strong framework in place to support the ethical conduct of clinical trials, provided by the NHMRC, its principal committees and HRECs. In June 2003, there were 226 registered HRECs in Australia - 125 hospital (public and private), 53 imiversity, 23 government and 25 associated with professional and other bodies. 

Compliance with the national statement is a requirement for all clinical trials conducted in Australia under the CTX and CTN schemes. The chairman of the HREC certifies that the HREC is constituted in accordance with guidelines issued by the NHMRC, has registered with the AHEC, and has approved the clinical trial in accordance... 

Currently, AHEC is working with HRECs around Australia to develop a nationally accepted clinical trial application format that will be acceptable to all HRECs. This will significantly benefit sponsors of clinical trials who currently have to prepare applications in different formats to meet individual HREC requirements, which delays submission of applications in Australia and adds to the workload. 

In order to promote a uniform approach to offering compensation to subjects and indemnity to investigators and institutions conducting clinical trials, Medicines Australia has published a Form of Indemnity for Clinical Trials and Guidelines for Compensation for Injury Resulting from Participation in a Company-Sponsored Chnical Trial. These documents are based on those published by the Association of the British Pharmaceutical Industry and are available from www.medicinesaustralia.com.au (the Medicines Australia website). 

The clinical trial guidelines published by the TGA specify that all clinical trials must be conducted in accordance with the Declaration of Helsinki, October 1996. The World Medical Association updated the Declaration of Helsinki in October 2000 but these changes were not adopted in Australia due to concerns in relation to the interpretation of two new clauses. 

The beanlike seeds of the trees and shrubs of the genus Erythrina, a member of the legume family, contain substances that possess curare-like activity. The plants are widely distributed in the tropical and subtropical areas of the American continent, Asia, Africa, and Australia, but apparently they are not used by the natives in the preparation of arrow poisons. Of 105 known species, the seeds from more than 50 have been tested, and all were found to contain alkaloids with curariform properties. Erythroidine, from E. americana, was the first crystalline alkaloid of the group to be isolated. It consists of at least two isomeric alkaloids, a and P-erythroidine both are dextrorotatory. Most experimental and clinical study has centered on the b form because it is more readily obtainable in pure state. P-Erythroidine is a tertiary nitrogenous base. Several hydrogenated derivatives of p-erythroidine have been prepared of these, dihydro-P-erythroidine has been studied most carefully and subjected to clinical trial. Conversion of P-erythroidine into the quaternary metho salt (p-erythroidine methiodide) does not enhance, but rather almost entirely, abolishes its curariform activity this constitutes a notable exception to the rule that conversion of many alkaloids into quaternary metho salts results in the appearance of curare-like action. 

Healy et al. (2006) described nine cases in England, Scotland, Australia, and the United States as illustrations of antidepressant-induced violence. Two paroxetine, three sertraline, and one fluoxetine case resulted in homicide. One paroxetine case resulted in assault, one venlafaxine case resulted in attempted murder, and one fluoxetine case resulted in assault and robbery. Some were associated with maniclike symptoms. They also evaluated clinical trial data (see subsequent discussion). 

There is no requirement for clinical trials to be performed in Australia before new or modified products are approved for registration. Also, since 1991, there have been no restrictions to applying for clinical trials in conjunction with applications for registration of a drug. This means that applications for registration of a drug... 

Unapproved (unregistered) products may be supplied in clinical tricds under special provisions in the Therapeutic Goods Act, 1989 which exempt these products from the need for prior registration. There are two mechanisms by which clinical trials may be initiated in Australia a Clinical Trial Exemption (CTX) where the goods require approval prior to their use in a trial, and a Clinical Trial Notification (CTN) where only a notification is required to the TGA. 

General Clinical trials of products approved for registration are not covered by the above categories and are considered to be subject to the Therapeutic Goods Administration s Guidelines for Good Clinical Research Practice (GCRP) in Australia.55... 

If this EU Directive on the protection of personal data were to be taken literally, most clinical trials would cease, particularly where clinical data were transferred outside the EU. Of the non-EU countries, only Switzerland and Hungary apparently meet the requirements of the Directive at the present time Other countries such as the US, Ganada, Australia and New Zealand apparently fail to meet the requirements of the Directive when handling personal data and therefore, in theory, European data cannot be processed in these countries. Fortunately, the so-called Safe Harbor scheme allows clinical data to be sent to defined organisations in the US that comply with the Directive s principles. It is anticipated that similar agreements will be set up to overcome these legislative hurdles so that global studies driven by European pharmaceutical companies and institutions can be undertaken without problems. 

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