Clinical trial authorization

Clinical trials and clinical trial authorizations in the European Union are controlled under the Clinical Trial Directive, 2001/20/EC [9], and all member states are bound by its requirements. Under the provisions of the Directive, a clinical trial is an investigation in human subjects that is intended to discover or verify the clinical, pharmacological, and/or other pharmacodynamic effects of one or more medicinal products, identify any adverse reactions or study the absorption, distribution, metabolism, and excretion, with the object of ascertaining the safety and/or efficacy of those products. This definition includes pharmacokinetic studies. 

Before starting clinical trials in humans, an authorization should be obtained from the FDA. This is known as a clinical trial authorization request for a new medication (AEM), on which it is necessary to establish the following ... 

Clinical trial authorization (CTA) by national competent authorities... 

The regulatory procedure involved is a so-called Clinical Trial Authorization appH-cation (CTA) and consists, in addition to a Clinical Trial Protocol (CTP) and Investigator s Brochure (IB), of an Investigational Medicinal Product Dossier (IMPD) in CTD format. The IMPD consists of quality data, nonclinical pharmacology and toxicology data, clinical trial and previous human experience data, and an overall risk-benefit assessment. A copy of the CTA is sent to each EU Member State where the study is conducted, as well as to the Ethics Committees for approval. These also have to be notified in case of any amendments, study termination and adverse reactions. The contents of the IMPD are case specific and may be simplified or even replaced by the... 

Clinical trial assay (CRA) 133 Clinical trial authorization application (CTA) 1697... 

CTA. Clinical Trial Authorization. In the UK this is the MHRA document for authorizing clinical trials of medicinal products, replacing the older system of clinical trial certificates (CTCs) and exemptions (CTXs) on 1 May 2004. 

Before a clinical trial can commence, it is necessary to submit a Clinical Trial Application (CTA) to the Competent Authority of each Member State, where it is... 

During the course of its conduct, the sponsor may need to amend a clinical trial, as a consequence of the emergence of new information. If the amendments are deemed to be substantial, in that they may impact on the safety of trial subjects, or change the interpretation of the scientific documents in support of the conduct of the trial, or are otherwise significant, the sponsor shall notify the Competent Authority and the Ethics Committee, using a Trial Amendment Form. The Ethics Committee are permitted 35 days to approve the amendment. 

In addition to the expedited reporting described above, sponsors shall submit, once a year throughout the clinical trial, or on request, a safety report to the Competent Authority and the Ethics Committee. This should cover SUSARs, other serious adverse reactions, and an analysis of the subjects safety during the course of the trial. 

The Competent Authorities are obliged to appoint Inspectors for checking that all activities associated with clinical trials are conducted in compliance with the regulations. The inspectors can inspect any sites concerned with the clinical trial, particularly the trial site (GCP), the manufacturing site of the investigational medicinal product (GMP), any laboratory used for analyses in the clinical trial (GLP), and/or the sponsor s premises. 

It is worthwhile to note that, in the US, where the applicant will just be dealing with a single authority, there is no need to re-submit data that was previously submitted as part of an IN D application to conduct clinical trials. Instead, the applicant can cross-reference the IND file. This does not apply in Europe, because clinical trial applications will have been submitted to individual Competent Authorities, whereas marketing authorisation applications are usually submitted either centrally to the European Medicines Agency (EMEA) or collectively to a number of Competent Authorities. Thus, the files need to be self-supporting. 

Caution. Contains a new animal drug for use only in investigational animals in clinical trials. Not for use in humans. Edible products of investigational animals are not to be used for food unless authorization has been granted by the U.S. Pood and Drug Administration or by the U.S. Department of Agriculture. 

Before initiating a clinical investigation, the manufacturer (or his/her authorised representative) must prepare a statement containing the information outlined in Figure 10.2, and notify the relevant Competent Authorities of the proposed study. The manufacturer must also keep available for inspection by the Competent Authorities the information outlined in Figure 10.3. Unlike for clinical trials, a standard application form has not been developed. Instead, appropriate application forms are... 

The regulatory authorities must be informed of any planned recall actions (see Chapter 12). Procedures are also required for emergency un-blinding of materials undergoing clinical trial. The responsibility for complaints and the initiation of product recalls should be assigned to designated individuals. 

A recent meta-analysis of total abstinence as an outcome in clinical trials of acamprosate (Mann et al. 2004) included 17 studies and a total of more than 4,000 patients. The authors found a significant advantage for acampro-... 

Errors and Inconsistencies in Formatting Dates. It is also necessary to use standardized formats to record dates. For example, Oracle stores a date as the number of seconds since January 1, 4712 BC, and then uses various functions to display the dates in more human-friendly formats. There are many different and personal ways for recording dates one of the authors (AS) has noted at least 25 different ways in a single clinical trial submitted for FDA review Should February 1,2007 be recorded as 1 February 2007,1 Feb 2007, 1 Feb 07, or 02/01/07 This problem still exists when data for numerical dates are extracted into software programs such as Excel that do not force the user to select a unique format for dates. 

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). 

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