Electronic medical record is a source record

How does one handle accidental unblinding in a clinical trial?
Indira Kale

Usually the CRA does not need to be aware of study arm assignments to handle monitoring responsibilities. As the CRA will be interacting with the site coordinator, there is the potential risk that randomization information may unintentionally be revealed that could break the blind for study staff. Hence, individuals e.g. CRA whose roles do not require knowledge of study treatment assignments should be kept blinded.  If a CRA faces a situation where unblinding may be needed, he/she should contact the sponsor who would determine how to proceed with those findings while maintaining the study's integrity.

Accidental unblinding can compromise the integrity of the study. It is a good practice to discuss and document the circumstances and impact of such accidental unblinding with the sponsor and If required by applicable law or regulation, report the incident to regulatory authorities.


What are regulatory/ethical considerations, when a subject is withdrawn from a clinical trial, during long-term follow-up?
Dr Narendra Mehta

In a long-term trial e.g. oncology, the subject may be asked to follow-up after the protocol mandated intervention and follow-up phase is completed. However, the subject may not wish to continue during the intervention phase or after completing the intervention phase.

When a subject withdraws from a study, the regulators would expect that data collected on the subject to the point of withdrawal remains part of the study database and should not be removed.

The investigator has to consider following situations in relation to subject’s data and consent.
•    In long-term follow-up studies, an investigator should ask a subject who wants to withdraw from study, whether the subject wishes to provide continued follow-up and further data collection after his/her withdrawal from the interventional phase of the study. In this situation, the discussion with the subject would distinguish between trial-related interventions and continued follow-up of associated medical / clinical outcome information e.g. disease course or laboratory results available in hospital/clinic notes and address the maintenance of privacy and confidentiality of the subject's information.
•    If subject wishes to withdraw from the interventional portion of the trial but agrees to follow-up of associated medical/clinical outcome information as described above, the investigator should obtain the subject's informed consent for this limited participation in the study. In such a case, Ethics Committee approval of informed consent documents would be required.
•    If subject wishes to withdraw from the interventional portion of a trial but does not consent to continued follow-up of associated clinical outcome information, the investigator should not access the subject's medical record or other confidential records requiring the subject's consent, for the objectives related to the trial. However, an investigator can review trial data related to the subject collected prior to the subject's withdrawal from the study.


Is it necessary for a monitor to check electronic medical records (EMRs)?
Prateek Murthy
EMR is a source record, even if the site maintains paper copies in the study files. If the investigator site keeps certified copies of the medical records of study participants, monitors and auditors will require to verify the completeness of these paper records with the source - EMR.
As the EMR can be selectively copied, the certified copies may not be complete records. The monitor/auditor will try to confirm that study selection criteria are met, and that there are no other medical issues that would prevent the individual's participation in the study or confound the results.

The investigator can give the monitor limited access to the medical records for the purpose of source data verification.

What is the regulatory expectation if a woman becomes pregnant during the clinical trial?
Dr Rutuja Sharma
If a woman becomes pregnant during a clinical trial, and the protocol does not specify the process for handling such a pregnancy, unblinding should occur so that counselling can be offered based on whether the foetus has been exposed to the investigational drug, placebo, or control.
If, after the discussion of risk: benefit of continuing versus stopping investigational treatment, the pregnant woman chooses to continue in the clinical trial should, she should undergo a second informed consent process that reflects these additional risk-benefit considerations.
If the female subject wishes to continue the pregnancy, then regulatory agencies would expect that she be asked to allow the investigator to follow her pregnancy to term (or longer if possible for developmental sequelae), so that any important safety information could be obtained.