What is a bridging study? Do we require DCGI approval for such a study?
V. Sridhar
There is no concept of bridging study in Indian regulations. All Indian trials require DCGI approval

As per ICH E 5

A bridging study is defined as a study performed in the new region to provide pharmacodynamic or clinical data on efficacy, safety, dosage and dose regimen in the new region that will allow extrapolation of the foreign clinical data to the population in the new region.

One of the criteria for the adverse event to be considered as SAE is hospitalization as per the guidelines. But if during the study, the subject is taken to hospital for some time in emergency unit assistance, expert consultation or short-term observation for management of an AE and the subject is discharged on the same day. In that case should we consider it as SAE or not?
Dr Muneesh Garg
US FDA in response a query has advised the following:
“Common usage of "inpatient hospitalization" generally would include being treated by a physician in a hospital for at least a 24-hour period.”

What is the importance of ‘note-to-file' and when it should be a document?
Dr Prakash Atlam
Please see some of the literature excerpts on 'note-to-file'. A Note-to-file is a way to explain any discrepancy in the conduct of a research study or to clarify a decision made in regards to some aspect of the study.

Note-to-file is helpful if it covers the following:
● Identification of a problem
● Identification of a procedural change for preventing recurrence
● Institution of the procedure

Note-to-file is written by site team in site files and in the company files by concerned CRA. It is not submitted to regulatory authorities. However, they can view it in the files.

If there is a regulatory inspection, the inspector may cite the initial problem. However, a note-to-file describing the change in procedure mitigates the citation and supports the site in responding to the finding. .

It is recommended that a 'note-to-file' does not become a device to allow a research investigator or coordinator to ignore protocol or to accept laxity in conduct of a study.

In a clinical trial, is it mandatory that laboratory investigation reports should be signed by MD (Path)?
Shruti Kulkarni
As per NABL, the qualifications required for authorization depends on the nature of lab test. The person could be MD/Phd/MSc/MBBS.

We have got BE NOC (Export) from DCGI - 60 human volunteers and the innovator product is from USA. If we want to conduct the same study with lesser number of volunteers (i.e. <60, say 24) and the innovator product from Europe (same innovator - mfg location is different), whether we need to obtain amendment approval for the approved NOC or to apply fresh NOC or to send an intimation to DCGI without waiting for the approval. Will this change be considered as major or minor?
Balaji K
For the change in number of volunteers, there is no need for amendment, as there is no addition in the number of volunteers.

For the change in manufacturing site, you will require amendment of the import license. If this information is part of protocol, this will be a logistic change which does not require notification / approval of the protocol amendment.



Dr Arun Bhatt is currently, president, ClinInvent, Research Pvt Ltd, Mumbai. Readers can send their queries at: arunbhatt@clininvent.com