Is it necessary that only a research staff, mentioned on delegation log for collecting adverse event (AE), report and document?
Dr Seema Desai
There is no regulatory requirement that the research staff/person, who discovers or reports the adverse event be on the delegation log. The discovery of an AE can come from many sources - the subject, the subject family members, medical records, hospitalization records, other medical personal etc. Hence, if adverse event reporting is restricted to the person on delegation log, many AEs would be missed. The adverse event should be reported/recorded when the research staff first becomes aware of the event.
Is there any regulatory guidance regarding the acceptable and reasonable time frame for review safety assessments e.g. lab values, by an investigator?
Ramesh Vaze
The regulations/guidelines do not specify any time limit for AE reporting by the investigator. However, the investigator is expected to comply with reporting time lines for SAEs e.g. 24 hours after occurrence and 14 calendar days after occurrence in India. As SAEs are a subset of AEs and certain categories of SAEs which require medical judgement, it is desirable that the investigator should review safety information especially clinical symptoms and signs or lab reports in a timely manner, to be able to comply with regulatory timelines for SAE reporting and to ensure that the rights, safety and well being of subject are protected.
During clinical trial, we receive many safety reports from sponsor at our site. Is it necessary to review these reports?
Inder Nath
The investigator’s prime responsibility is to ensure that rights, safety and well being are protected. As the safety reports from the sponsor include AEs/SAEs reported with the investigator product in the current ongoing trial or other concurrent clinical trials, these could impact safety of the subjects under the investigator’s supervision. Hence, the regulatory authorities would expect that the investigator to review safety reports received from the sponsor and document his/her opinion/recommendation/action.
What are the regulatory requirements for making a copy of clinical trial source document?
Dr Kiran Deshpande
ICH E6 R2 defines certified copy as a copy (irrespective of the type of media used) of the original record that has been verified (i.e. by a dated signature or by generation through a validated process) to have the same information, including data that describe the context, content, and structure, as the original. When a copy is used to replace an original document (e.g., source documents, CRF), the copy should fulfil the requirements for certified copies. Sponsors/CROs/investigator site should have written procedures to ensure consistency in the certification process.
How do we ensure data integrity for source document prepared in electronic format by investigator?
Varsha Thakkar
When original observations are entered directly into a computerized system, the electronic record is the source document. The US FDA regulations mandate that the clinical investigator must retain records required to be maintained, for a period of time specified in these regulations. This requirement applies to the retention of the original source document, or a copy of the source document.
The use of certified copies usually applies to situations where original records are copied to a different media for archiving purposes and the originals are destroyed. If the site / sponsor has decided to keep a certified copy as a substitute for the original, it would be desirable to have an SOP describing how such copies would be made, verified, and documented.
The person who certifies the copy as an accurate and complete representation of the original, having all of the same attributes and information should be the same person who actually made the copy from the original. Certification should be accomplished by having the person who makes the copy, sign or initial and date the copy to indicate it meets the requirements of a certified copy. The process of certification should be described in the SOP. The process could be - initialling and dating each copy or initialling and dating a document certifying copies in bulk. The SOP should describe the procedure used and ensure that the integrity of the original records is preserved.
For detailed information, please refer to (1) US FDA Guidance for Industry – Computerized Systems Used in Clinical Investigations and (2) FDA's Guidance for Industry – 21 CFR Part 11, Electronic Records; Electronic Signatures - Scope and Application.
Dr Arun Bhatt is a Consultant - Clinical Research & Development,
Mumbai. Readers can send their queries at:arun_dbhatt@hotmail.com