What would constitute conflict of interest for an EC member?

ICMR 2006 guidance defines conflict of interest as a set of conditions in which professional judgment concerning a primary interest like patient’s welfare or the validity of research tends to be or appears to be unduly influenced by a secondary interest like non-financial (personal, academic or political) or financial gain.

Some of the categories would be (Ref: University of Washington SOP)

Participation on the research team –

Investigator, co-investigator, or any member of research team on the same study

Co-investigator or member of research team on another study with the investigator  

Investigator under the professional supervision of the EC member e.g. professor/head is an EC member which reviews his/her re a PG student’s research project

Financial conflict of interest in the research

Personal relationship with the investigator:

An immediate family relationship or other close personal relationship with the investigator, or with co-investigators who have a significant role in the research

Competitive relationship with the investigator

If a sponsor would like to conduct a study at a small clinic or nursing home having no EC, can that site approach the institutional IRB for the approval, is it acceptable? If yes, for how many sites the EC can give approval?

Yes. As per CDSCO checklist and considering EC responsibility for 1) protecting rights, safety and well-being of subjects and 2) continuing oversight/monitoring of the site, it would be ethically recommended that the EC should be from the same city. There should be documentation as per Schedule Y that the approving ethics committee(s) is willing to accept their responsibilities for the study at such trial site(s) and the trial site(s) is/are willing to accept such an arrangement. Also the EC should comply with all requirements of 122DD especially continuing oversight /SAE reporting etc.

It would be difficult to decide how many sites EC can oversee in the current challenging regulatory environment. EC should consider how it will fulfill all the EC responsibilities for all sites as per current regulatory requirements/122 DD for all the sites under its oversight. As per Schedule Y, the EC should make, at appropriate intervals, an ongoing review of the trials for which they review the protocol(s). Such a review may be based on the periodic study progress reports furnished by the investigators and/or monitoring and internal audit reports furnished by the sponsor and/or by visiting the study sites. The EC needs to consider the risk and responsibly of overseeing/monitoring sites outside the institution, and then decide for how many sites outside the institution it can provide ethical oversight.

If we want to conduct a phase 4 study with an approved drug (less than 4 year old in Indian market) in the approved indication in India then:
(1) Does sponsor need to provide study drug to patients or can patient directly buy it from market?
(2) Is informed consent required for this phase 4 study?

Phase 4 studies include several different types of studies (ICMR 2006)
1) Post marketing surveillance study (PMS) to obtain additional information about the risks and benefits resulting from long term usage of drug. Such studies are usually non-interventional trial in which the medicinal product is prescribed in the usual manner in accordance with the terms of the marketing authorization. The assignment of the patient to a particular therapeutic strategy is not decided in advance by a trial protocol but falls within the current practice and the prescription of the medicine is clearly separated from the decision to include the patient in the study. No additional diagnostic or monitoring procedures shall be applied to the patients.

In this type of study drug samples are not provided by the sponsor. Informed consent is required for this study.

2) Studies designed to evaluate the marketed drug in specifically designed studies, which have inclusion/exclusion criteria, objectives and end points. The drug is used for the labeled indication in these studies.

3) Study to evaluate the drug for a new indication of a marketed drug,
For category 2 & 3, the sponsor has to provide drug samples and informed consent would be essential.

Is it ethical for the study doctor to send reminder through text messages in the form of SMS or email to the clinical trial subject regarding his date of visit to the clinic, study drug, drug intake or drug instillation? Do you think confidentiality of the patient could be compromised?

Sending reminder to patients in any form is not unethical. In fact, earlier the reminders were sent by letter/post card. Even the post cards/letters were misplaced or delivered to someone else. The issue of a third party accessing such info is true for all SMS/email communication. Even the cell phone companies are unable to prevent such unauthorized access. In such a scenario, a doctor's good intentions of ensuring compliance should not become a burden for the doctor.