How will we conclude that the subject is illiterate?
Dr Prakash Atlam
The guidelines don’t use the term illiterate. Their focus is subject’s ability to read and/or write.

Schedule Y treats anyone who is unable to read or write in the same way. See the excerpt below.

If the subject or his/her legally acceptable representative is unable to read/write - an impartial witness should be present during the entire informed consent process who must append his/her signatures to the consent form.

While designing a protocol we found that there are high likely chances of worsening of some of the symptoms. Do we have to wait for these to happen and report it as SAE or in case we define them in the protocol upfront then can we prevent from expediting reporting it as SAE?
Om
Please see suggested guidance from ICH. Exemption from reporting such events would require prior agreement with regulatory authorities.

ICH E3 12.2.2 Display of Adverse Events: All adverse events occurring after initiation of study treatments (including events likely to be related to the underlying disease or likely to represent concomitant illness, unless there is a prior agreement with the regulatory authority to consider specified events as disease related) should be displayed in summary tables (section 14.3.1). The tables should include changes in vital signs and any laboratory changes that were considered serious adverse events or other significant adverse events. In most cases, it will also be useful to identify in such tables "treatment emergent signs and symptoms" (TESS; those not seen at baseline and those that worsened even if present at baseline).

ICH E9 In situations when there is a substantial background noise of signs and symptoms. (e.g. in psychiatric trials) one should consider ways of accounting for this in the estimation of risk for different adverse events. One such method is to make use of the “treatment emergent' (see Glossary) concept in which adverse events are recorded only >if they emerge or worsen relative to pretreatment baseline.

Other methods to reduce the effect of the background noise may also be appropriate such as ignoring adverse events of mild severity or requiring that an event should have been observed at repeated visits to qualify for inclusion in the numerator. Such methods should be explained and justified in the protocol.

In a two period cross-over BA/BE study, if any AE occurs on the day of dosing of period-2 but before dosing of period-2 e.g. fever. Then obviously the subject will not be dosed for period-2. In this case, in which AE form we should record the AE i.e. AE form for period-1 or period-2. Because all the information like relationship to the study medication, last dosing date & time, treatment code and time elapsed since last dosing etc will be considered with respect to dosing time and date of period-1 only. Please suggest in which AE form we should record the pre-dose AEs of period-2 i.e. AE form for period-1 or Period-2.
Dr Muneesh Garg
Going by the logic and practice of clinical trials, as the subject was screened and was waiting to be enrolled for period 2, the AE would be recorded in period-2 form. On the other hand, in clinical trials adverse events are followed up-to 30 days after the last visit/completion of protocol. By this logic, one can consider the AE as occurring in post-period 1 drug follow-up.

As long as the details are captured in the form, it would not matter in which form you capture period 1 or 2. In clinical trials, we use only 1 AE page. The details filled on the page are adequate to relate the drug to the causality assessment.

Let me know whether pregnancy detected after completion of one period of a BE study is an SAE?
Nanda Kumari
Pregnancy is special medically significant condition SAE requiring reporting.

Internationally, pregnancy is reported separately. In India, there is no separate guidance on pregnancy reporting. Hence, it will be reported as an SAE.

Is there any difference between Independent EC and Institutional EC?
Dr Sreevatsa
The only difference is their location. Institutional ECs function in Institutions. (GCP Definition: Institution - any public or private medical facility where a clinical study is conducted). The ECs which are not attached to any institution are considered private ECs abroad and independent ECs in India. However, the major difference is in their scope of authority. If there is a trial in an institution, the investigator has to seek approval of the institutional EC.u

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