GCP Questions

Understanding the overall issues in GCP and adopting procedural norms as per national and international guidelines becomes imperative in present times, especially for India which is turning out to be the hub of clinical research activities. There are many imponderables, both for the sponsors and investigators. Doubts and queries, even in the simplest of procedures which could have been taken for granted in the past, can arise.

To enlighten readers on such issues, we at Express Healthcare Management bring to you this monthly column which will appear in the first issue of the month wherein all your queries will be answered by Dr Arun D Bhatt, well known clinical pharmacologist from Mumbai.

1. I am conducting a clinical trial in paediatric population. Does the informed consent form (ICF) require assent by children? Is it necessary to obtain the signature of children on ICF?

Dr Sunita Nadkarni, Mumbai

Many investigators and independent ethics committees (IEC) consider it a standard practice to obtain the agreement of older children who can understand the circumstances before enrolling them in research. However, as children are a vulnerable population it is essential to obtain informed consent of the child’s legally authorized representative before enrolment. Parents, legal guardians and/or others may be able to give permission to enrol children in research. IECs generally require investigators to obtain the permission of one or both of the parents or guardian (as appropriate). Some IECs may insist on the assent of children who possess the intellectual and emotional ability to comprehend the concepts involved. Older children may be well acquainted with signing documents through prior experience with testing, and/or other procedures normally encountered in their lives. It would be reasonable to request them to sign a form to give their assent for research. Younger children, however, may never have had the experience of signing a document. For these children, requiring a signature may not be appropriate, and some other technique to verify assent could be used. For example, a third party may verify, by signature, that the assent of the child was obtained. The relevant guideline from ICH-GCP is cited below: ICH GCP 4.8.12 “When a clinical trial (therapeutic or non-therapeutic) includes subjects who can only be enrolled in the trial with the consent of the subject’s legally acceptable representative (e.g., minors, or patients with severe dementia), the subject should be informed about the trial to the extent compatible with the subject’s understanding and, if capable, the subject should sign and personally date the written informed consent.”

2. I am conducting a trial in hypertensive patients. In my outpatient clinic, I see many patients who could be potential subjects for the trial. The protocol requires several screening tests to decide eligibility. Can I advise the potential subjects to undergo the screening test without obtaining the subject’s informed consent?

Dr Surendra Gupta, Delhi

Most clinical study protocols require screening procedures to assess whether prospective subjects are appropriate candidates for inclusion in trial. The subject’s participation in the study begins when he/she is screened for deciding eligibility for the study. The investigator can discuss availability of studies and the possibility of entry into a study with a prospective subject without first obtaining consent. Any procedures that are conducted for diagnosis or treatment of a disease (as part of the practice of medicine) and which would be done whether or not study entry was contemplated, can be performed and the results subsequently used for deciding study eligibility without first obtaining consent. However, informed consent must be obtained before initiation of any screening procedures that are performed solely with the objective of deciding whether the subject is eligible for the clinical trial The relevant guideline from ICH-GCP is cited below: ICH-GCP 4.8.8 “Prior to a subject’s participation in the trial, the written informed consent form should be signed and personally dated by the subject or by the subject’s legally acceptable representative, and by the person who conducted the informed consent discussion.”

3. I am the principal investigator for a clinical trial. Do I have to personally obtain informed consent from each subject? Do I have to sign each informed consent form?

Dr Vidhya Subrahmanyam, Chennai

The clinical investigator is responsible for ensuring that informed consent is obtained from each research subject before the subject participates in the research study. The person who conducts the consent interview should be knowledgeable about the study and able to answer questions. ICH-GCP guidelines do not specify who this person should be. The investigator can designate any competent member of her team to conduct the process of obtaining consent. . However, if someone other than the clinical investigator conducts the interview and obtains consent, the clinical investigator should formally delegate this responsibility and the person so delegated should have received appropriate training to perform this activity It is not essential for the investigator to sign each form, if the consent is dated and signed by the person designated by her. However, some sponsors and some IRBs/IECs require the clinical investigator to personally conduct the consent interview. Hence, it is a desirable practice for the investigator to review and sign each consent form. The investigator remains ultimately responsible, even when delegating the task of obtaining informed consent to another individual knowledgeable about the research. The relevant guideline from ICH-GCP is cited below: ICH-GCP 4.8.5 “ The investigator, or a person designated by the investigator, should fully inform the subject or, if the subject is unable to provide informed consent, the subject’s legally acceptable representative, of all pertinent aspects of the trial including the written information and the approval/ favourable opinion by the IRB/IEC.” ICH-GCP 4.8.8 “ Prior to a subject’s participation in the trial, the written informed consent form should be signed and personally dated by the subject or by the subject’s legally acceptable representative, and by the person who conducted the informed consent discussion.”

4. I am a member of ethics committee of our institution. Recently, we reviewed the informed consent form for a study and found that the sponsor’s name was not included in the form. Can an ethics committee insist that the sponsor of the study be identified on the study’s consent document?

Dr Alok Bhattacharya, Kolkata

Yes. Ethics committee can insist on such information from the sponsor in the informed consent form. The ICH-GCP requirements for informed consent (ICH-GCP 4.8.10) are the minimum basic elements of informed consent that must be presented to a research subject. However, an IEC may require inclusion of any additional information that it considers important to a subject’s decision to participate in a research study. The relevant guideline from ICH-GCP is cited below: ICH-GCP 3.1.5 “ The IRB/IEC may request more information than is outlined in paragraph 4.8.10 be given to subjects when, in the judgement of the IRB/IEC, the additional information would add meaningfully to the protection of the rights, safety ad/or well-being of the subjects.”