Trial protocol

The sponsor with input from the investigator must prepare a trial protocol. This document should describe the objective(s), design, methodology (including subject... 

Figure 5.3 A typical clinical trial protocol template (in this case as required by the Irish Medicines Board www.imb.ie Irish Medicines Board).

Unlike human trials. Institutional Review Boards/Independent Ethics Committees are not involved, while informed consent is only required from the owner of the trial animals. In addition to the standard items associated with human trials, aspects such as management and housing of animals, diet and disposal of trial animals and their produce should be included in the trial protocol. Studies may be blinded from the investigators in order to avoid bias in the reporting of animal observations. 

Predict outcome for alternate designs (molecular, clinical trial) allowing optimization of portfolios, experiments, and trial protocols... 

The clinical trial protocol is a detailed written plan that outlines how the study procedures are to be carried out and how the data are to be collected and analyzed. It insures the quality and integrity of the trial, particularly when multiple research sites are participating in data collection (Chow and Liu, 1998). The purposes of the protocol are to outline ... 

Further information and advice related to the use of the clinical trial design can be found in a variety of sources including textbooks, manuscripts, organizations and Internet sites. In addition to the chapter reference list which cites helpful sources of information related to clinical trial protocol development, design and analysis, the following sources are also recommended. 

There has been a large number of field trials of transgenic crops that accumulate recombinant proteins, but the results of only a few have been reported so far. Of particular interest for the future are reports of detailed trial protocols that address confinement concerns multi-location, multi-year performance and stability data environmental impact and non-target impact studies and GLP production. The impact of production conditions on extraction efficiency and product quality are also significant issues that should be addressed through field-testing. 

Proper and comprehensive planning of a clinical trial is essential to the successful development of any drug. The first issue to be considered when developing a trial protocol is to define precisely what questions the trial results should be capable of answering. As discussed previously, the terms safety and efficacy are difficult to define in a therapeutic context. An acceptable meaning of these concepts, however, should be committed to paper prior to planning of the trial. 

Uses of Specific Laboratory Tests to Discover, Confirm, and/or Exclude a Disease. Some tests can confirm the diagnosis of a disease (e.g., tissue histology from a broncho scopic biopsy to confirm lung cancer), but cannot be used to exclude the disease or discover the disease in routine screening. Other tests can be used both to confirm and to exclude the diagnosis of a disease (e.g., glucose tolerance test for diabetes mellitus), but are too inconvenient to be used to discover the disease in routine screening. The uses of each laboratory test to discover, confirm, or exclude a disease should be considered before a test is simply added to a clinical trial protocol. This ensures that the test is appropriate in the context of the planned clinical trial. 

A normal course of event in initiating a clinical trial is for the Sponsor (see below) to prepare an Investigator s Brochure and select an Investigator to conduct the trial. The Sponsor and Investigator then prepare the trial protocol. 

Clinical Trial Protocol and Protocol Amendments Investigator s Brochure... 

Name and description of the clinical trial protocol Summary of results from nonclinical studies Potential risks and benefits to human subjects Description and justification for route of administration, dosage, and treatment plan Compliance to GCP... 

Based on the design of the trial protocol, statistics are used to calculate the number of people to be recruited for the trial, how the trial should be randomized (Exhibit 6.12), and finally analysis of the data. Statistics provide a nonbiased means to evaluate the trial results. 

Clinical trials are conducted according to GCP. There should be a protocol that states the reason for the clinical trial, how it is to be conducted, the number of people to be included, eligibility criteria, medical tests and observations to be made, and information to be collected. Clinical trial protocol must be approved by the IRB/IEC before commencement. 

Statistics analysis is an integral part of a clinical trial. A clinical trial protocol includes information on statistical parameters that the trial is expected to be based on and methods for the analysis of data. 

An Investigator, not an employee of the Sponsor, is appointed to be responsible for the conduct of a trial. An appropriate quality system is followed and deviations from trial protocols are reported. Serious adverse events have to be reported to regulatory authorities within a specified time. 

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 view of the regulatory delay that was caused by the need to apply for a CTC, a Statutory Order (SI 1974/498) was made during 1974, to provide an exemption from the need to hold a CTC in such cases, subject to certain conditions. This order applied to trials conducted by doctors and dentists on their own responsibility (DDX). The basis of the clinical trial exemption (CTX) scheme, introduced in 1981, to include studies initiated by the pharmaceutical industry, was that together with a detailed clinical trial protocol and summaries of chemical, pharmaceutical, pharmacological, pharmacokinetic, toxicological and human volunteer studies, a clinical trial in patients may proceed without the need for the additional details normally required for a CTC or Product Licence application. This exemption scheme was based on the requirements that ... 

Where a clinical trial was proposed with a marketed product then the CTMP scheme could be used. This was a streamlined process based on the fact that there were no quality issues with a product that had already been granted a marketing authorisation. The applicant submitted a copy of the trial protocol, provided information on the investigators and, depending on whether or not the applicant was the MAH, information on the procedures for reporting adverse drug reactions. It was only possible to use this procedure for UK marketed products. It did not apply to unauthorised products manufactured specifically for trial or to products, which were licensed only in countries other than the United Kingdom. 

The government had required that the sponsors should have their own in-house study review board to review the ethical aspects of clinical trial protocols. Such a requirement was based on the former Japanese GCP, which stipulates that the company should organise an internal formal body or mechanism that reviews and authorises its planned studies before submitting to either study centres or the MHW for clinical trial plan notification. 

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