SP01-H Preparation of Trial Protocol
Version:
V02 F
Replaces Version: VO” D13
Author:
Urs Harnischmacher
Valid from: of:
02 August 2005
_________________ Date
Release: FG-QM
_________________ Date
Approved: Board KKS Network
_________________ Date
___________________ Author signature
___________________ FG-QM spokesperson
___________________ Board spokesperson
Target group: All Coordination Centres for Clinical Trials
Appendices:
SP01-H-A1 Sample Checklist for Trial Protocols
Contents Page Objective ......................................................................................................................... 2 Background ..................................................................................................................... 2 Processes ....................................................................................................................... 2 3.1 Preparation of a new trial protocol.............................................................................. 2 3.2 Revision of an existing trial protocol ........................................................................... 3 3.3 Format of the trial protocol ......................................................................................... 3 3.4 Registration of clinical trials ........................................................................................ 4 4. References...................................................................................................................... 5 5. Changes from last version .............................................................................................. 5 1. 2. 3.
SP01-H
Preparation of Trial Protocol
V02 F
1. Objective The objective of this SOP is to establish a quality standard for the KKS for the writing and preparation of clinical trial protocols.
2. Background The trial protocol forms the basis for the proper conduct of a clinical trial according to the legal requirements, the ICH Guidelines (ICH GCP E6, Section 6), and the Declaration of Helsinki. The trial protocol describes the rationale, objectives, design, population, trial conduct (planned interventions, data capture, and documentation), and evaluation (data management and biostatistical and scientific evaluation) of the clinical trial (see also definition in the GCP Directive: GCP-V, Article 3, Paragraph 2) for clinical trials conducted according to the German Dug Law (Arzneimittelgesetz; AMG). The trial protocol also determines the responsibilities of persons involved in the conduct of clinical trials. The trial protocol is intended for the investigators, all other persons involved in trial conduct, bodies convened for trial conduct (e.g. a Data Monitoring and Safety Board; DMSB) and other institutions or persons (such as hospitals, pharmacists, central laboratories). It also forms the basis for approval and assessments made by the ethics committee and the authorities. The KKS can be contracted to develop a trial protocol or revise an existing protocol. The following process description and the checklist in the appendix focus on clinical trials conducted with drugs pursuant to the AMG, but can also be used for other trials (with modifications, if necessary).
3. Processes The KKS can assume responsibilities on behalf of the sponsor for clinical trial activities provided this is agreed in advance (e.g. by contract or power of attorney).
Director KKS
In such cases, a study coordinator is responsible for the trial activities assumed.
Study coordinator
3.1 Preparation of a new trial protocol • Review of regulatory requirements.
Study coordinator
• Review of applicable SOPs. • Literature searches, if required. • Involvement of further experts, if required (such as toxicologists, preclinical experts, health economists). • Drafting of a trial protocol or part of a trial protocol based on the checklist in the appendix and the format requirements given in Section 3.3.
Study coordinator, biostatistician
• Production and revision of the trial protocol in close collaboration with the coordinating investigator of the clinical trial or principal investigator, the experts, the biostatistician, the sponsor or contractor and all other relevant persons and institutions involved (such as hospitals, pharmacists, central laboratories). • Review of the trial protocol developed with all persons involved. Page 2 of 5
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SP01-H
Preparation of Trial Protocol
• Production of the final version of the trial protocol. • Quality control of the trial protocol by an independent colleague. • Coordination of the signing of the trial protocol by the coordinating investigator of the clinical trial or the principal investigator, the biostatistician, the sponsor or contractor, and, if necessary, other persons involved in production.
V02 F
Study coordinator Person qualified Study coordinator
• Ensuring that the final version and all versions assessed by the ethics committee are stored in the TMF. 3.2 Revision of an existing trial protocol • Review of regulatory requirements.
Study coordinator
• Review of applicable SOPs. • Review of the content of the existing trial protocol based on the checklist in the appendix. • Revision of the trial protocol or part of the protocol, incorporation of missing sections.
Study coordinator, biostatistician
• All relevant persons (coordinating investigator of the clinical trial or principal investigator, the experts, the biostatistician, sponsor or contractor, and all other relevant persons and institutions [such as hospitals, pharmacists, central laboratories]) must be involved in the revision as far as appropriate. • Review of the trial protocol with all persons involved. • Production of the final version of the trial protocol. • Quality control of the trial protocol by an independent colleague. • Coordination of the signing of the trial protocol by the coordinating investigator of the clinical trial or the principal investigator, the biostatistician, the sponsor or contractor, and, if necessary, other persons involved in production.
Study coordinator Peron qualified Study coordinator
• Ensuring that the final version and all versions assessed by the ethics committee are stored in the TMF. 3.3 Format of the trial protocol • The cover page of the trial protocol includes the complete title, the trial numbers (sponsor’s or contractor’s trial number and EudraCT number [for details of obtaining this number, see the SOP “Official notification and approval pursuant to AMG”], or if applicable the International Standard Randomised Controlled Trial Number [ISRCTN]), the name and address of the sponsor or contractor and of the coordinating investigator of the clinical trial or principal investigator, the version number with the date, and a Page 3 of 5
Study coordinator
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SP01-H
Preparation of Trial Protocol
V02 F
confidentiality statement, if required. • The table of contents must cover the entire content of the trial protocol. Each appendix does not need to be listed separately in the table of contents, but there must be a complete list of all appendices in the text of the section ‘Appendices’. • A list of abbreviations is prepared, if required. This list gives a brief explanation of all abbreviations used in the trial protocol. • The section on organisational structure must list the sponsor or contractor, the coordinating investigator of the clinical trial or principal investigator and all other persons with a significant contribution, and at least one person responsible at each institution. Reference can be made to an attached list for individual investigators. • The summary (outline) lists all significant information on trial conduct (e.g. in tabular form). • The flowchart shows all trial visits (e.g. in tabular form), and includes all examinations at each visit and all information to be documented. • On a signature page, the persons responsible agree to the content of the version being signed and agree to abide by the provisions of the trial protocol. • On the same or a separate signature page, each investigator agrees to the content of the version of the trial protocol being signed. • All pages of the trial protocol carry standardised headers and footers. These must contain the trial title, the trial number and/or brief trial ID, version number, date, page number, and total number of pages. • A master English version of the trial protocol may be prepared for multinational trials. The trial protocol may be translated into local language versions; these, however, serve only as working versions. The English version approved by the authorities and ethics committee is always binding. Depending on the trial design, individual sections of the trial protocol may apply only to selected investigational sites or countries (e.g. details of subgroup analyses at individual investigational sites or sections dealing with country-specific approval procedures). These sections may be prepared on separate addendum pages for the individual investigational sites or countries, or may be included in a investigational site-specific section of all trial protocols designated as such. How they are included is decided upon by the sponsor or contractor depending on the scientific and ethical relevance of these sections to the project as a whole. 3.4 Registration of clinical trials The results of clinical trials may be published in relevant international journals only if they have been registered in a public free-of-charge trial registers before or when recruitment starts. Details of registration and a list of journals can be found on the homepage of the International Committee of Medicinal Journal Editors (ICMJE); http://www.icmje.org; Query: 24 Nov 2005). Page 4 of 5
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SP01-H
Preparation of Trial Protocol
The procedure for registration of clinical trials is given the SOP “Official notification and approval pursuant to AMG”.
V02 F
Study coordinator
4. References See the reference list of the Quality Management Group of the KKS Network.
5. Changes from last version Completely revised and adapted to the requirements of the 12th Amendment to the German Drug Law.
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