Recent CDSCO order mandates that the ethics committee (EC) should decide how many trials an investigator can undertake. What steps EC should take to fulfil this responsibility?
Dr Maya Sitharaman

The ethics committee has to review and assess how much time the investigator spends to fulfil his/her regulatory and GCP responsibilities for each clinical trial project – sponsored and academic.

As per US FDA 2009 guidance on investigator responsibilities, the investigator should have sufficient time to properly conduct and supervise the clinical trial. The level of supervision should be appropriate to the staff, the nature of the trial, and the subject population. Many factors can affect the ability of an investigator to provide adequate supervision of the conduct of an ongoing clinical trial. These include: Staff - experience, workload; Nature of trial - complex clinical trials e.g., many observations, large amounts of data collected; Subject population - number of subjects enrolled and seriously ill.

FDA recommends that the investigator should have a plan for the supervision and oversight of the clinical trial. This should include time and procedures for (a) routine meetings with staff and sponsor’s monitors; (b) timely correction and documentation of problems identified; (c) documenting or reviewing the performance of delegated tasks; (d) consent process; (e) CRF and source data completion; (e) dealing with data queries and discrepancies; (f) ensuring compliance with the protocol and adverse event assessment and reporting, and compensation requirements; (g) addressing medical and ethical issues.

The EC will need to develop a SOP and checklist to obtain information from the investigator about how s/he manages time requirements for ongoing clinical trial projects. The EC should review this information considering the prime responsibility of the investigator to protect rights, safety, and welfare of study subjects and the investigator’s responsibility as a physician for his/her patients, and decide whether the investigator can undertake additional trials.

How long we need to keep records of subjects withdrawn from trial?
Amrit Pandey

Any data collected during the time the subject was actively enrolled, before withdrawal from the trial, should not be destroyed. The sponsor must retain records/data that were collected during the trial, prior to subject’s withdrawal.

As per ICH GCP, the essential documents should be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period however if required by the applicable regulatory requirements or by an agreement with the sponsor.

The retention period for records is dependent on whether the data will be used to support a marketing application with the regulatory authorities. As the sponsor is knowledgeable about the status of its investigational product, it is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained.

In an EDC trial, the CRA entered the protocol deviations into e-CRFs. It is acceptable?
Dr Shahi Wagle

No. The CRA should not enter or change data in the e-CRFs. There should be a data quality check system in the e-CRF programme that the CRA can use to highlight data entry errors.

US FDA guidance stipulates: Only clinical investigator(s) or delegated clinical study staff should perform modifications or corrections to eCRF data. Modified and/or corrected data elements must have data element identifiers that reflect the date, time, originator and reason for the change, and must not obscure previous entries.

A field should be provided allowing originators to describe the reason for the change (e.g., transcription error). Automatic transmissions should have traceability and controls via the audit trail to reflect the reason for the change.

Can we use date stamps with signatures in clinical research?
Suresh Nadkarni

From a regulatory standpoint, since the date stamps can be used by anyone who has access to them, the use of stamps would not be acceptable as regulations require verification of who accomplished a task and/or when it was accomplished. The regulatory authorities also need documentation, which can be verified as unique to the individual who has signed the document. Also, the rationale for a written date with the signature is to match handwriting with signature. A date stamp can be misused and defeat the objective for the signature - to testify that the person signing has reviewed or witnessed the information and when this was accomplished.