Impartial witness is a person who will not be influenced

Can an Indian investigator delegate consent process and audio-visual recording of consent?

ICH GCP 4.8.5 permits the investigator, or a person designated by the investigator, to conduct the informed consent process and sign the consent form.

In contrast, Indian GCP 2.4.3.1. Informed Consent of Subject: does not use the term “designated”. Indian GCP mandates that prior to the subject’s participation in the study the written informed consent form should be signed and personally dated by the investigator.

Indian GCP defines investigator as a person responsible for the conduct of the study at the trial site. Investigator is responsible for the rights, health and welfare of the study subjects.

Schedule Y mandates that the investigator must provide information about the study verbally as well as using a patient information sheet, in a language that is non-technical and understandable by the study subject. Appendix V Format of informed consent form includes space for the study investigator to sign and date.

CDSCO draft guidelines (9 Jan 2014) on audio-visual recording of informed consent process recommend: Before requesting an individual’s consent to participate in clinical trial the investigator must provide the individual with the following information in a language that is non-technical and understandable by the study subjects and the same shall be recorded through audio-visual means. The investigator has the duty to communicate to the subjects/LAR/IW, all the information necessary for informed consent.

Considering the above Indian regulations/guidelines, an Indian investigator cannot delegate the consent process and its recording/documentation to his staff.

We have conducted a clinical trial of herbal preparation. Because of budgetary constraints, we have used local labs at the sites. Can we combine the lab results from all sites for final analysis?

As the local labs differ in infrastructure, personnel, training, equipment, reagents, materials, methods, kits, SOPs, and documentation, the quality of results will differ. Hence, you cannot combine the lab data from different local labs for safety analysis. You can follow some of the approaches recommended by ICH E3 guidance structure and content of clinical study reports.

Number of patients with abnormal values, or with abnormal values that are of a certain size

Number of patients with clinically significant values

Use of toxicity grading scales e.g., WHO, NCI

Shift tables - These tables show the number of patients who are low, normal, or high at baseline and then at selected time intervals.

Tables showing the number or fraction of patients who had a change in parameter of a predetermined size at selected time intervals. For example, for BUN, it might be decided that a change of more than 10 mg/dL BUN should be noted. For this parameter, the number of patients having a change less than this or greater than this would be shown for one or more visits, usually grouping patients separately depending on baseline BUN (normal or elevated).  

During the screening period of a clinical trial, we collected blood samples of a subject. However, the subject does not meet the inclusion/exclusion criteria. Can the blood samples collected from that subject continue to be used and analyzed?

If a subject has signed the informed consent form, it indicates that the subject is enrolled in the clinical trial.  When eligibility procedures e.g. lab investigations are performed, the subject's participation in research has begun although whether the subject meets the selection criteria for the study has not been decided. For regulatory purposes, records would need to be maintained on subjects who signed a consent form, even if, following the screening procedures, the subject is determined not to meet the selection criteria for the study. However, blood samples cannot be analyzed for the purposes of the study as the subject was considered a screening failure.

Who can be considered an impartial witness?

Indian GCP defines impartial witness as a person who will not be influenced in any way by those who are involved in the clinical trial, who assists at the informed consent process and documents the freely given oral consent by signing and dating the written confirmation of this consent. If the witness is not a person from the study team and is not under direct supervision of the investigator or other members of the team, he/she could be acceptable as an impartial witness.