As per 122 DAB, the investigator is supposed to report serious adverse events within 24 hrs of occurrence of the event. However, if the patient does not visit the hospital within the time frame, what should the investigator do?
Dr Sneha Limaye

As per amendment in 122 DAB (GSR 292 E), in case the investigator fails to report any serious adverse event within the stipulated period, he shall have to furnish the reason for the delay to the satisfaction of the Licensing Authority along with the report of the serious adverse event.

What is the National Accreditation Board for Hospitals and healthcare providers process for accreditation of Ethics Committees?
Amar Pandit

NABH accreditation of Ethics Committee has 10 standards and 49 objective elements. The EC should apply to NABH in prescribed application form along with self-assessment toolkit, relevant documents and application fees. NABH Secretariat, on intimation from the EC about the preparedness to take up assessment, appoints an assessment team comprising principal assessor and assessor from the pool of empanelled assessors. To obtain evidence on compliance with respect to NABH standards and applicable rules and regulations, the assessors conduct on-site assessment visit, which will include facility inspection, document and records review and interview of staff and subjects.

In our oncology study, we recently realized that one patient’s original ICF is missing. The patient is deceased. What actions we should take in this situation?
Dr Yogini Maheshwari

You should make all efforts to locate the original ICF. If this is not available, check whether a copy is available. If not, you should document the whole problem with dates and supporting evidence of patient’s continuing in trial e.g. follow-up visits, signed amended ICF etc. Also check whether the original ICFs of other patients are available. This would be helpful in case of an audit or inspection.
If ICFs of several patients are missing, it would be difficult to satisfy the auditor or the regulatory inspector about compliance to consent requirements.

What’s the role of a monitor in unbinding the treatments in case of an adverse event?
Deepika Gupta

As per ICH GCP 4.7 Randomization Procedures and Unblinding, the investigator should follow the trial's randomization procedures, if any, and should ensure that the code is broken only in accordance with the protocol. If the trial is blinded, the investigator should promptly document and explain to the sponsor any premature unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the investigational product(s).

Usually, the study site monitor does not have any role in unblinding of the treatments. The monitor doesn’t. need to be aware of study arm assignments in order to fulfil monitoring responsibilities. As he/she will be interacting with the site staff during monitoring, there is the potential that information may unintentionally be revealed that could break the blind for study staff. To avoid such a possibility, individuals whose roles do not require knowledge of study arm assignments should be kept blinded. If a monitor discovers findings 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.

What are the recommendations for how many attempts should be made to contact subjects who do often comes for follow-up visits?
Samira Ajnkye

In general, the sponsor could provide direction in the protocol or study plan regarding how and how often/long to pursue a subject who fails to show up for follow-up visits. This would provide consistency across the study. If there is no guidance from the sponsor, a site should make several attempts to contact these subjects, including use of a certified letter. Documentation of phone calls, and copies of all correspondence should be maintained in the subject's study file. The regulatory inspectors would expect to find such documentation. If many subjects are lost to follow-up, this could indicate that potential study subjects were not adequately informed of study expectations and the need to commit to appropriate follow-up prior to their inclusion in the study. If such a trend is obvious from initial monitoring visits, proper training/retraining of study personnel conducting the ICF process should be conducted. If there are many drop outs study-wide, the sponsor may need to consider whether the protocol requirements are too onerous, and whether the protocol requires amendments.


Dr Arun Bhatt is a Consultant - Clinical Research & Development,
Mumbai. Readers can send their queries at:arun_dbhatt@hotmail.com