Medicinal Products

Good Documentation Practice

Expectations of clinical trial documentation

Based on deviations identified during GCP supervision, the Agency wishes to specify expectations regarding documentation generated in clinical trials.

Local regulation and ICH GCP guidelines define the documents that must be available in the trial master file as well as in the investigator’s file/file at the trial site.

Good documentation is an important part of the quality management system and is necessary to confirm that the clinical trial is planned, completed, analyzed and reported in accordance with good clinical practice.

According to the local regulations of the Serbia, the sponsor is responsible for the conduct and quality of the clinical drug trial, that it must ensure that the trial is planned and conducted in accordance with good clinical practice and that the data is registered and reported according to procedures that ensure the quality of every aspect of the trial.

Also, it is stated that the investigator should ensure the accuracy, completeness, readability and timeliness of the data reported to the sponsor through the systems and in all necessary reports. A record of where the original data can be found must also be available.

In addition, all changes to registered data must be visible and dated and signed by the person who made the changes. If the reason for the changes is not obvious, an explanation must be given.

The investigator must have his own autonomy in managing/creating documentation in the Subject Files. It is considered bad practice for a Contract Research Organization (CRO),  who cooperates with sites in Serbia on behalf of the sponsor, to forward ready-made templates related to visit reports – and act as „co-creator“ (especially for screening and randomization visits). The visit report should contain those information related to the visit that cannot be found in the SD behind (conversation with the study participant, data on adverse events, medication compliance, advice and use of contraception, etc., and is not related to data that is already in the papers/documents that are an integral part of the same visit). If we observe similarity or identicality of investigator reports in two or more sites for the same protocol – it will be considered a significant finding where responsibility is shared by both – the sponsor and the investigator.

In order to reduce the efforts of the study team due to the work in clinical studies and standard practice, it is not necessary to copy the data from the invested SD, which is an integral part of the visit. The visit report should have the date and time when it was printed at the bottom of the document, in the footer. Investigator should not create a visit report when filling in data in eCRF (retrograde).

If investigator uses his own forms/templates, i.e. prepares his own documents (form for inclusion criteria, physical exam, study nurses’ forms for measuring vital parameters…), then he/she should ensure that a version number is added to each document.

The approval of the material by the investigator should be documented, and it should also be documented to whom the material was distributed and when.

Traceability

It is a requirement that documents, forms and other documentation are prepared, checked and distributed with traceability in accordance with the approved trial protocol and other documents relevant to the trial itself. Therefore, it must be documented to whom the material was distributed and when.

In general, both sponsors and investigators are expected to ensure that all trial-related data/documentation is recorded, handled and stored in a manner that allows for accurate reporting, interpretation and verification. This is the basic principle of the ICH GCP guideline.

Changes in documents and registered data that are not obvious must be explained. In GCP regulatory supervision, we often find that changes are made but not explained; it is not obvious why the changes were made.

Documents, forms and other documentation must be dated and signed.

It is regularly noted that investigators did not sign and date letters or notices they received from sponsors. Each letter from the sponsor to the investigator is a direct communication with the „owner“ of the clinical trial, the sponsor, and the investigators have the obligation to mark with their signature and date when they received the information and from when they should apply it. The same applies to security information (whether it is a paper document or portal access).

Worksheets, and sometimes questionnaires, are examples of other documents that are often not signed and dated. Since both documents often contain source data, it is important to see who collected/populated the data and when (participant or investigator).

Sometimes, we also find that the principal investigator did not sign the ID Log. This is a key clinical trial document and we expect that the principal investigator to sign it at the end of the trial at the latest (preferably signing the completed pages) to indicate that it is a complete list of included trial subjects.

In general, documents must be approved, signed and dated by relevant/authorized persons.

Initials and/or signatures placed on documents must be accompanied by a date. Dates added later or in advance are not acceptable.

Regarding electronic documents and data, see the document Guideline on computerized systems and electronic data in clinical trials – During the regulatory supervision, the systems and documents relevant to this section will be reviewed in accordance with this guideline.

Instructions that are additional to the instructions described in the protocol must, as a rule, be written down. In daily, clinical practice, verbal agreements/instructions are sometimes followed.

However, the documentation requirements related to clinical trials are more stringent. Any activity performed by team members that is part of standard practice (such as a study nurse performing procedures that a physician is expected to perform and is standard practice at the institution) must have written instructions for documentation in clinical trials.

Furthermore, it is expected from the sponsor or investigator to implement quality control to ensure the above, e.g. through monitoring, auditing, on-site checks, etc., and that supervisionhas to be documented.