the title of the clinical trial;
the EU trial number;
the sponsor's protocol code number specific for all versions of it (if relevant);
the date and number of the version, to be updated when it is amended;
a short title or name assigned to the protocol; and
the name and address of the sponsor, as well as the name and function of the representative or representatives of the sponsor authorised to sign the protocol or any substantial modification to the protocol.
a statement that the clinical trial is to be conducted in compliance with the protocol, with this Regulation and with the principles of good clinical practice;
a comprehensive list of all investigational medicinal products and of all auxiliary medicinal products;
a summary of findings from non-clinical studies that potentially have clinical significance and from other clinical trials that are relevant to the clinical trial;
a summary of the known and potential risks and benefits including an evaluation of the anticipated benefits and risks to allow assessment in accordance with Article 6; for subjects in a clinical trial in an emergency situation, the scientific grounds for expecting that the participation of the subjects has the potential to produce a direct clinically relevant benefit shall be documented;
where patients were involved in the design of the clinical trial, a description of their involvement;
a description of, and justification for, the dosage, the dosage regime, the route and mode of administration, and the treatment period for all investigational medicinal products and auxiliary medicinal products;
a statement of whether the investigational medicinal products and auxiliary medicinal products used in the clinical trial are authorised; if authorised, whether they are to be used in the clinical trial in accordance with the terms of their marketing authorisations, and, if not authorised, a justification for the use of non-authorised auxiliary medicinal products in the clinical trial;
a description of the groups and subgroups of the subjects participating in the clinical trial, including, where relevant, groups of subjects with specific needs, for example. age, gender, participation of healthy volunteers, subjects with rare and ultra rare diseases;
references to literature and data that are relevant to the clinical trial, and that provide background for the clinical trial;
a discussion of the relevance of the clinical trial in order to allow assessment in accordance with Article 6;
a description of the type of clinical trial to be conducted and a discussion of the trial design (including a schematic diagram of trial design, procedures and stages, if relevant);
a specification of the primary end-points and the secondary end-points, if any, to be measured during the clinical trial;
a description of the measures taken to minimise bias, including, if applicable, randomisation and blinding;
a description of the expected duration of subject participation and a description of the sequence and duration of all clinical trial periods, including follow-up, if relevant;
a clear and unambiguous definition of the end of the clinical trial in question and, if it is not the date of the last visit of the last subject, a specification of the estimated end date and a justification thereof;
a description of the criteria for discontinuing parts of the clinical trial or the entire clinical trial;
arrangements for the maintenance of clinical trial treatment randomisation codes and procedures for breaking codes, if relevant;
a description of procedures for the identification of data to be recorded directly on the Case Report Forms considered as source data;
a description of the arrangements to comply with the applicable rules for the collection, storage and future use of biological samples from clinical trial subjects, where applicable, unless contained in a separate document;
a description of the arrangements for tracing, storing, destroying and returning the investigational medicinal product and unauthorised auxiliary medicinal product in accordance with Article 51;
a description of the statistical methods to be employed, including, if relevant:
timing of any planned interim analysis and the number of subjects planned to be enrolled;
reasons for choice of sample size;
calculations of the power of the clinical trial and clinical relevance;
the level of significance to be used;
criteria for the termination of the clinical trial;
procedures for accounting for missing, unused, and spurious data and for reporting any deviation from the original statistical plan; and
the selection of subjects to be included in the analyses;
a description of the subject inclusion and exclusion criteria, including criteria for withdrawing individual subjects from treatment or from the clinical trial;
a description of procedures relating to the withdrawal of subjects from treatment or from the clinical trial including procedures for the collection of data regarding withdrawn subjects, procedures for replacement of subjects and the follow-up of subjects that have withdrawn from treatment or from the clinical trial;
a justification for including subjects who are incapable of giving informed consent or other special populations, such as minors;
a justification for the gender and age allocation of subjects and, if a specific gender or age group is excluded from or underrepresented in the clinical trials, an explanation of the reasons and justification for these exclusion criteria;
a detailed description of the recruitment and informed consent procedure, especially when subjects are incapable of giving informed consent;
a description of the treatments, including medicinal products, which are permitted or not permitted, before or during the clinical trial;
a description of the accountability procedures for the supply and administration of medicinal products to subjects including the maintenance of blinding, if applicable;
a description of procedures for monitoring subject compliance, if applicable;
a description of arrangements for monitoring the conduct of the clinical trial;
a description of the arrangements for taking care of the subjects after their participation in the clinical trial has ended, where such additional care is necessary because of the subjects' participation in the clinical trial and where it differs from that normally expected for the medical condition in question;
a specification of the efficacy and safety parameters as well as the methods and timing for assessing, recording, and analysing these parameters;
a description of ethical considerations relating to the clinical trial if those have not been described elsewhere;
a statement from the sponsor (either in the protocol or in a separate document) confirming that the investigators and institutions involved in the clinical trial are to permit clinical trial-related monitoring, audits and regulatory inspections, including provision of direct access to source data and documents;
a description of the publication policy;
duly substantiated reasons for the submission of the summary of the results of the clinical trials after more than one year;
a description of the arrangements to comply with the applicable rules on the protection of personal data; in particular organisational and technical arrangements that will be implemented to avoid unauthorised access, disclosure, dissemination, alteration or loss of information and personal data processed;
a description of measures that will be implemented to ensure confidentiality of records and personal data of subjects;
a description of measures that will be implemented in case of data security breach in order to mitigate the possible adverse effects.
adverse events or laboratory anomalies that are critical to safety evaluations and must be reported by the investigator to the sponsor, and
serious adverse events which do not require immediate reporting by the investigator to the sponsor.
eliciting and recording adverse events by the investigator, and the reporting of relevant adverse events by the investigator to the sponsor;
reporting by the investigator to the sponsor of those serious adverse events which have been identified in the protocol as not requiring immediate reporting;
reporting of suspected unexpected serious adverse reactions by the sponsor to the Eudravigilance database; and
follow-up of subjects after adverse reactions including the type and duration of follow-up.