The informed consent document (ICD) is the most important document in a clinical trial. Prospective participants sign the ICD after they have been informed of all the aspects of the trial relevant to their decision, thus allowing them to make an express choice to voluntarily participate in the trial. The principle underlying informed consent is the right to self-determination of every adult of sound mind.
Informed consent is not just a signature on a form but an ongoing process of exchange of information between the investigator and the participant. For a legally effective informed consent by the participant or their legally authorized representative (LAR), the consent should be freely given and not obtained by coercion, undue influence, fraud, mistake or misrepresentation.
In trials conducted in India, the ICD is set out in the Drugs and Cosmetics Rules, 1945, in Appendix V of Schedule Y, with an ethics committee (EC) or institutional review board (IRB) having the final authority for ensuring the adequacy of the information in the ICD. In clinical trial studies that are subject to US Food and Drug Administration regulations, the ICDs should meet the requirements of title 21 of the Code of Federal Regulations (CFR) 50.20 and contain the information required by each of the basic elements of 21 CFR 50.20(a) and each of the six elements of 21 CFR 50.20(b) that is appropriate to the study.
The ICD must be signed by the investigator, witness and prospective participant or their LAR after giving the latter a sufficient opportunity to consider whether to participate in the trial. The ICD should be in a language known to them, avoiding any scientific jargon, and should explicitly mention that the trial involves research, the purpose of the trial, treatment options in trial randomization, number of subjects in the study, trial procedures, participants’ responsibilities, known risks, expected benefits, alternative treatment options available and expected duration of the trial.
The trial participant or LAR must also be given information on the procedures to be followed, including invasive procedures, and a description of any reasonably foreseeable risks or discomforts and any specific appropriate alternative procedures or therapies available to the participant.
The ICD should describe the extent to which confidentiality of records identifying the participant will be maintained and who will have access to participants’ medical records. It should not contain any exculpatory language through which the participant or LAR is made to waive or appear to waive any rights, or release or appear to release the investigator, the sponsor, the institution, or its agents from the liability for negligence. Responsibility for ensuring that the informed consent process is adequate lies with the EC or IRB, clinical investigator and research sponsor.
Stating that participation is voluntary, that the participant can withdraw from the study at any time and that refusal to participate will not involve any penalty or loss of benefit to which the participant is otherwise entitled is also an important aspect of the ICD. When withdrawal from a research study may have deleterious effects on the participant’s health or welfare, the ICD should explain any withdrawal procedures that are necessary for the participant’s safety and specifically state why they are important to the participant’s welfare.
In exceptional circumstances, however, participation in the study may be terminated by the investigator without regard to the participant’s consent. This may occur in the event that the participant does not follow the investigator’s instructions. If any significant new finding is made during the course of the research which may affect the participant’s willingness to continue participation, the participant or LAR must be notified in a timely manner. The EC or IRB should ensure that a system or a reasonable plan exists to make such notification.
Under recent amendments on injury compensation in the Drugs and Cosmetic Rules, 1945, it is now mandatory to incorporate into the ICD trial injury compensation and name of the beneficiary for compensation in the event of death of the trial participant.
During clinical trials changes may be made in the research protocol depending on the direction of the ongoing trial, which may necessitate informing the trial participant and taking a fresh consent. This may lead to multiplicity of ICDs.
Ensuring that an ICD truly represents the informed consent of illiterate subjects is still a challenge. The future is likely to witness video recording of the informed consent process to ensure that the consent is truly informed, affording more transparency to clinical trials. The ICD is a legally binding contract and any breach could lead to legal proceedings.
Dr Rachna Bharadwaj is an associate at Krishna & Saurastri Associates and an advocate registered with the Bar Council of India.
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