SIV can be conducted anytime before beginning of trial at site

What are the requirements for transfer of biological samples outside India?

ICMR International Health Division guidelines require the following documentation:

• Duly filled in application form for transfer of samples.  
• A copy of the duly signed Material Transfer Agreement (MTA).
• A copy of the Institutional/Independent Ethics Committee (IEC) clearance along with the composition of Ethics committee.
• A copy of the patient information sheet and informed consent form ( as approved by IEC) giving details on the utilization of samples of the patient for a particular research/R&D study and the kind of benefit (direct/indirect or no benefit - as applicable) for appropriate decision making by the patient.
• A copy of the Informed consent/undertaking of individual patient(s) agreeing to the utilization of his/her said biological samples for a particular study/purpose. The undertaking should also clearly state that the patient is willing /not willing (as agreeable to patient) to claim any commercial benefit on the product developed as a result of work carried out on his/her biological samples.
• A copy of the import certificate as issued by the relevant foreign regulatory authority to the foreign laboratory receiving the Indian biological samples.
• A copy of the Memorandum of Understanding signed between Indian laboratory and international agency defining the commercial benefits to each party.
• A copy of safety or operations manual being followed/adopted as safety procedures by your laboratory for the workers involved in activities involving possible exposure to pathogens through blood or other body fluids is to be submitted.
• A copy of the National Accreditation Board for Testing and Calibration Laboratories (NABL) certificate as issued by the Department of Science & Technology, Government of India/or equivalent is to be submitted.
• The disposal plan and necessary clearances for disposal of biohazardous, potentially infectious leftover samples is to be submitted. An Undertaking that Government guidelines on biomedical disposal will be followed to be submitted.
• A copy of the valid recognition letter as issued by office of DCGI for approval as Bioavailability/Bioequivalence study centre (for laboratories where biological samples are being received for BA/BE studies).

One of the subjects in a BE study had a single generalized tonic clonic seizure and was hospitalized for evaluation, which was reported as an SAE. He is now on oral anticonvulsants and he did not have recurrence in the last 2 months since the first seizure was reported. However, hospital has suggested follow ups and treatment for a minimum of one year before they think of tapering the dose. Can this event be considered resolved as he was seizure free for the last 2 months?

As per ICH E2B Outcome of reaction/event at the time of last observation is to be recorded. Hence, it is crucial to decide when the last observation occurred in this case. This would depend on - 1) protocol requirements for AE/SAE followup, 2) half life of the drug, 3) your SOPs.

As the last observation available is at 2 months, the outcome would be resolved with no sequelae.

If you decide to follow-up the patient for long term, you can always create a follow-up SAE report with outcome at the end of follow-up period and revise the outcome based on the status at that time.

What is the difference between “assent documents for minors” and “participants informed consent form” in clinical trials?

When one conducts a trial in pediatric population - children, one requires  consent from parents/guardian and assent from the child.

See the regulation (Sch Y) below:

Paediatrics
Paediatric subjects are legally unable to provide written informed consent, and are dependent on their parent(s)/legal guardian to assume responsibility for their participation in clinical studies. Written informed consent should be obtained from the parent/ legal guardian. However, all paediatric participants should be informed to the fullest extent possible about the study in a language and in terms that they are able to understand. Where appropriate, paediatric participants should additionally assent to enrol in the study. Mature minors and adolescents should personally sign and date a separately designed written assent form. Although a participant’s wish to withdraw from a study must be respected, there may be circumstances in therapeutic studies for serious or life-threatening diseases in which, in the opinion of the Investigator and parent(s)/legal guardian, the welfare of a pediatric patient would be jeopardized by his or her failing to participate in the study. In this situation, continued parental/legal guardian consent should be sufficient to allow participation in the study.

Can site initiation visit be performed after DCGI approval before EC review provided sponsor ensures patients recruitment after EC approval?

The purpose of site initiation visit (SIV) is to review trial procedures the investigator and the investigator’s trial staff. So, in practical terms SIV can be conducted any time before the beginning of trial at a site.

SIV procedures would include handling of IP.

However, ICH GCP recommends

5.14.2 The sponsor should not supply an investigator/institution with the investigational product(s) until the sponsor obtains all required documentation (e.g. approval/favourable opinion from IRB/IEC and regulatory authority(ies)).

In view of this, most sponsors conduct SIV after the DCGI and EC approval.

Can you please let us know in a double blinded trial, medical monitor should unblind or investigator should unblind the treatment in case of emergency.

The unblinding has to be done for emergency purpose e.g. in case of an SAE. Hence, this is to be done by the investigator at the site..

Can a pharmacologist act as a clinician during the review meeting of EC? Will it suffice the quorum requirement?

Pharmacologist is considered a basic medical scientist not a clinician.