Clinical trial, application

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... 

Figure 5.4 A checklist of documentation to be provided with a Clinical Trial Application.

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. 

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). 

Shork NJ et al. The use of genetic information in large-scale clinical trials applications to Alzheimer research. Alzheimer Dis Ass Disord 1996 10(Suppl 1] 22—26. 

Clinical trial applications are not centralized. Submissions are made through individual member states. Refer to Section 8.3 for details of clinical trial application in Europe. 

Similar to the US requirements, there are two regulatory steps to go through before a drug is approved to be marketed in the European Union. These two steps are clinical trial application and marketing authorization application. There are 27 member states in the European Union (as of August 2007) clinical trial applications are approved at the member state level, whereas marketing authorization applications are approved at both the member state or centralized levels. 

A Sponsor submits a clinical trial application to the Competent Authority in each member state where the trials are to be conducted. The Competent Authority has 60 days to review and approve or reject the application. Application is in prescribed forms and covers the proposed clinical trial protocol, manufacturing, and quality controls on the drug, and supporting data, such as (1) chemical, pharmaceutical, and biological data, (2) nonclinical pharmacological and toxicological data, and (3) clinical data and previous human experience. The supporting data are submitted in the Common Technical Document (CTD) format (see Section 7.11). 

In the United Kingdom, clinical trial applications are submitted to the Medicines and Healthcare Products Regulatory Agency (MHRA). There are several schemes for clinical trial application the major two are the Clinical Trial Certificate (CTC) and Clinical Trial Exemption (CTX) schemes. 

Clinical Trial Application (CTA) has to be submitted to Health Canada seeking permission to conduct clinical trials. The submission should include information regarding drug characteristics, test data, animal studies, and clinical protocol. A clinical trial may be stopped when either it is shown to be unsafe or dramatic benefits are obtained. The approval process may be fast-tracked if a drug is shown to have substantial benefits, such as for treatment of life-threatening or severely debilitating conditions. 

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

Information in regulatory files (e.g., clinical trial applications). Existing literature and current compliance guidelines and procedures. Feedback on early phase methods. 

A revised clinical trial application evaluation scheme introduced in 1983 aimed for a response time of 45 working days for Phase 1 and early Phase 11 trials, and 80 working days for Phase 11 and Phase 111 trials, but in practice it took... 

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. 

Under the CTN scheme the sponsor of the clinical trial provides detailed information about the proposed trial to the principal investigator who submits an application to conduct the clinical trial to the HREC at the institution or other site at which the trial is proposed to be conducted. The clinical trial application generally includes the protocol, the investigator s brochure, related patient information, supporting data and the CTN form. HRECs usually have their own standard format for applications to conduct a CTN trial at their institution. The HREC evaluates the scientific and ethical validity of the proposed clinical trial and the safety and efficacy of the medicine in the context of its stage of development. The TGA does not evaluate any information about the clinical trial. 

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. 

The risk-benefit assessment is of paramount importance in clinical trial applications, largely because of the uncertainty of the potential benefits. The points covered in the Subheading 4.1 and the Subheading 4.2 analysis should be borne in mind for this section of the IB. 

Clinical investigations are clearly the most critical and demanding stage in the new dmg development phase. When a dmg company believes it has sufficient preclinical testing data to show that a new dmg candidate is adequately safe for initial small-scale clinical studies, the company assembles and submits an investigational new dmg (IND) application in the United States or a clinical trial application (CTA) in the European Union. The IND or CTA is the prerequisite for a company to obtain... 

If the answer is "yes" to both questions the development team is ready to prepare an IND or a CTA (Clinical Trial Application) application the European equivalent of an IND to request permission to begin a clinical trial program. 

In the preclinical development stage, data are collected in order to enable the filing of an investigational new drag (in the US) or a clinical trial application (in Europe). These data are comprised of details on the composition of the drag and the... 

The Board reviews 200-250 clinical trial applications each year of which Category 3 predominate, forming 70-80 percent of the total. Refusal of permission is unusual, running at two to five instances per year. Inappropriate use of placebo, leading to patients being denied a standard treatment, and inappropriate (underqualified) investigators tend to be the most common cause of refusal. Modifications of protocols are requested in about 10 percent of applications. 

Clinical trial applications Biotechnology Group New Chemical Licensing Abridged License applications European Centralised applications Europecin Mutual Recognition applications CSM Secretariat. 

The Clinical Trials Directive now requires the filing of a clinical trial application for bioequivalence studies in normal volunteers or patients. In the United States, an IND is always needed if the generic drug is without an approved innovator in the United States, is radioactive or is a cytotoxic. However, when single- or multiple-dose studies in normal volunteers do not exceed the approved clinical dose sizes and there will be retention samples available for inspection, then there can be exemption from the need to file an IND. An IND is needed for a multiple-dose bioequivalence study, when it is not preceded by a singledose study. The usual protections for human subjects are required, and, of course, these include an approval from the Institutional Review Board. 

Within 30 days of approval of a clinical trial application, the medical institution in charge must submit a detailed clinical trial protocol to the Bureau of Drug Policy and Administration, with copies to the central Committee of Drug... 

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