50937 Cologne Germany Data Monitoring Committee Definition and description of the tasks and working methods of the Data Monitoring Committee (DMC): checking of trial progress, safety data, checking of efficacy variables, for example as part of a blinded interim analysis, advising the sponsor on the continuation, modification or termination of the clinical trial based on interim results or safety results (see also Guideline EMEA/CHMP/EWP/5872/03 Corr). This paragraph should include the description of information and data pathways. In case the DMC is involved in the reporting procedure (unblinding) for adverse events, this has to be taken into account (detailed description in Section 7.3.6). Be aware that a DMC is independent and therefore can have its own charter which determines its working procedures. (see also EMA “Guidline on Data Monitoring Committees”, EMEA/CHMP/EWP/5872/03). If appropriate, the reasons why a DMC is not considered necessary should be given here. A Data Monitoring Committee made up of independent experts will be set up. It consists of two physicians and a statistician who are not involved in the conduct of the trial and independent from the sponsor (see Section 11.4). The task of the DMC is to monitor the safety of the trial subjects in the clinical trial by periodically assessing the safety and efficacy of the trial therapy, and to monitor the integrity and validity of the data collected and the conduct of the clinical trial. Throughout this process of surveillance, the DMC provides the sponsor with recommendations with regard to continuing the trial (e.g. termination or modification) based on the data collected. The data necessary for the DMC to fulfill this function are provided by the sponsor as determined by the DMC. Amongst other datasets, these must include listings providing information on serious adverse events and further variables that the DMC considers necessary at least every 6 months and when formal interim analyses are conducted. Further committees This chapter and its subchapters are optional.
Known Potential Benefits Include a discussion of known potential benefits based on both clinical and nonclinical studies/data. Note that payment to participants is not considered a “benefit.” Provision of “intensified care” is also not to be considered a benefit. Assessment of Potential Risks and Benefits Include an assessment of potential risks and benefits, addressing each of the following: rationale for the necessity of exposing participants to risks and a summary of the measures to minimize the risks to participants, justification of the risks in relation to potential benefits. Selection of trial population The characteristics of the trial population should be described in medical terms. If necessary, the reasons for including, for example, children or subjects who are unable to give informed consent must be given and the measures taken to ensure the welfare of such groups must be described. Reasons for gender distribution The expected gender distribution must be given, as well as the reasons why this distribution in the population affected appears adequate to detect any gender-specific differences in efficacy or safety of the pharmaceutical preparation under testing. If appropriate, a cross reference to Section 6.1.5 should be added. Inclusion criteria Trial indication A general rule is that inclusion and exclusion criteria should be described as unequivocally as possible. The inclusion criteria should also include the methods used to verify the indication (e.g. “findings demonstrated by coronary angiography that must be available in the trial subject’s records, not conducted earlier than 2 months before” or “at the discretion of the principal investigator/subinvestigator based on the trial subject’s medical history”). It must be kept in mind that inclusion and exclusion criteria may sometimes require trial-related (e.g.
Ethical and regulatory aspects Ethics committee The clinical trial will not be started before favourable opinion of the competent ethics committee. At each trial site the clinical trial will not be initiated unless favourable opinion has been given concerning the suitability of the trial site and the qualification of the principal investigator and his/her deputy. Ethical considerations The present trial protocol and any amendments were and will be prepared in accordance with the principles of the Declaration of Helsinki. If necessary, critical ethical aspects of the clinical trial should be discussed again here. Legislation and guidelines The present clinical trial will be conducted in accordance with the principles of the guidelines for Good Clinical Practice (ICH-GCP) and applicable legislation. principles cover, amongst other aspects, ethics committee procedures, the obtaining of informed consent from trial subjects, adherence to the trial protocol, administrative documentation, documentation regarding the IMP, data collection, trial subjects’ medical records (source documents), documentation and reporting of adverse events (AEs), preparation for inspections and audits, and the archiving of trial documentation. All principal investigators and other staff involved in the trial will be informed that local and national competent authorities as well as competent authorities from foreign countries and authorised representatives of the sponsor have the right to review trial documentation and the trial subjects’ medical records at any time. Notification of the authorities, approval and registration Before the start of the clinical trial, all necessary documentation will be submitted to the competent authority for approval (Federal Institute for Drugs and Medical Products,