FAQ - Documentation (GCP)

Is the monitor allowed in Austria to make clarifying entries in the CRF?

According to the Austrian Medicines Act, the recording of data is the responsibility of the investigator: "§36 (8) AMG The investigator must correctly collect, record and report the data. §34 (3) AMG The Monitor shall compare the entries in the inspection forms with the original findings and inform the inspector of any errors or omissions."

However, the ICH E6 Guideline for Good Clinical Practice provides that representatives of the sponsor may make changes and corrections to CRFs. This must be specified in writing in advance and these changes must be documented, necessary and approved by the investigator.

ICH GCP "4.9.3 .......Sponsor´s should have written procedures to assure that changes or corrections in CRFs made by sponsor´s designated representatives are documented, are necessary, and are endorsed by the investigator".

"5.18.4 (n) "....The monitor should ensure that appropriate corrections, additions, or deletions are made, dated, explained (if necessary), and initialed by the investigator or by a member of the investigator´s trial staff who is authorized to initial CRF changes for the investigator."

Is the monitor allowed to enter the answer in place of the investigator in questionnaires from the data management, so that the investigator only has to date and sign?

Questionnaires correspond to the changes and corrections of test forms listed in FAQ 1. Thus a representative of the sponsor can fill in questionnaires, if necessary. In this case, too, it must be determined in advance in writing who can do this in which case. In addition, it must be documented who, when and what entered in the questionnaire, and the investigator must approve the entry documented.

Is it correct that the use of a black ballpoint pen for entries in Trial Master Files, CRFs and other documents leads to findings during an AGES inspection?

No, but when signing patient consent forms, the use of blue lettering / pens is recommended to clearly distinguish the original from the copy.

What rules and regulations must be observed when documenting pre-screening measures within the framework of clinical trials?

Keeping records of the selection of patients from the overall patient pool by the trial site as part of the trial conduct is a responsibility of the investigator.

It serves to prove the objective patient selection and the exclusion of a possible selection bias by the examiner.

The documentation must be available at the trial centre, but not necessarily in the trial master file. The investigator should be able to identify the screened patients (before signing the informed consent form, without any study-related measures) (8.3.20 ICH-GCP to document identification of subjects who entered pre-trial screening).

Personnel assigned to the sponsor and the sponsor (monitor, etc.) may only inspect anonymous records (without patient identification). The patient's medical record may not be inspected due to lack of patient consent.

Reproducibility of randomization lists for clinical trials

On the basis of which (legal) basis is it necessary to document the seed value or start value when randomization lists are created?

According to ICH E9 "Statistical principles for clinical trials", the randomisation requirement is: "The randomisation schedule should be reproducible (if the need arises)".

Since, according to ICH E9, the ability to reproduce the randomisation table is a legal requirement, suitable framework conditions must be created for this. It is up to the manufacturer how this is technically implemented. The use of a generator that excludes the reproduction of the randomization table from the outset would not be in the spirit of GCP.

Does this represent a major or minor finding during an inspection?

Failure to meet this requirement is at least a major finding, but can become a critical finding if it causes a situation in which the rights, safety or well-being of subjects and / or the quality and integrity of the data are adversely affected.

Can a number generator be used where reproduction is not possible?

In principle, computer-aided systems used in clinical trials are subject to validation. Software that cannot be validated in the sense of GCP due to technical specifications is generally not suitable for use in clinical trials.

May the subject's date of birth appear in documents such as CRF, documents sent to the central laboratory, data sent to the IVRS/IWRS, etc.?

The relevant Austrian legal materials do not indicate a direct prohibition of the use of these parameters.

Rather, it depends on the combination of initials and date of birth. If encryption no longer exists, this is the collection of directly personal data.

This means that the sponsor has to judge for himself whether the encryption is still present in the chosen constellation. This depends on the indication, the region, any other data sets collected, incidence and prevalence, etc. Date of birth PLUS Initials alone are not sufficient in most cases to deduce the exact patient. However, only those data should be collected in the context of a clinical trial that are relevant to the objectives defined in the protocol.


Further inquiry note