AV recording cannot be discontinued for vulnerable subject in clinical trials

Can we discontinue AV recording without revision of protocol as per new Gazette?

As per G.S.R. 611 (E), Dated 31st July 2015: Audio-Visual (AV) recording of Informed Consent Process (ICP) is mandatory for vulnerable subject in clinical trials of New Chemical Entity (NCE)/New Molecular Entity (NME). So, AV recording cannot be discontinued for vulnerable subject in clinical trials of New Chemical Entity (NCE)/New Molecular Entity (NME)

As per G.S.R. 826(E), dated 30th October 2015 “New Chemical Entity” means an active substance in developmental stage which may be specified as a drug under the Act, after undergoing any clinical trial.’.

As per ICH-GCP 1.61 Vulnerable Subjects are defined as

Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.

Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

You need to check whether your protocol meets above criteria or not before deciding to discontinue AV recording.

We have serious ADR in a bioequivalence study. How long should this event be followed?  

ICH E2 D guidance recommends:

For serious ADRs, it is important to continue follow-up and report new information until the outcome has been established or the condition is stabilized. How long to follow up such cases is a matter of judgment.

Do we need to revise Investigator undertaking, when the protocol version is changed?

There is no regulatory requirement for amending / revising Investigator Undertaking as the Checklist for Major Protocol Amendment does not require Investigator Undertaking. (see below)

• Covering letter
• Copy of CT permission letter
• Copy of previous protocol amendment approval letter, if any
• Copy of the amended protocol
• Changes made in comparison with earlier protocol to be presented with rationale and major changes should be highlighted
• Safety and efficacy data in support of proposed amendment
• Regulatory approval from participating key country/countries (in case of language other than English, English Translated version along with Translation Certificate)

Is a change in central pathology lab in between trial considered as an administrative change?

As per CDSCO checklist, following are considered major protocol amendments.

1. Amendment with respect to age limit of subject, dose, and treatment duration.
2. Increase in number of subjects
3. Amendment in study design
4. Amendment in inclusion or exclusion criteria
5. Amendment in safety or efficacy parameters
6. Any other changes which has impact on safety of the subject

If the change in lab due to any of these changes, it would be considered a major amendment. Otherwise it would be a minor amendment.