‘An impartial witness is required only if the subject is illiterate’
What are the guidelines for conducting clinical trials of cosmetic products?
There are no special/separate guidelines for clinical trials of cosmetic products. General principles for any drug trial are applicable.
I have the following queries on amended Schedule Y:
a) Which permission is required to be taken first by the sponsors: the Ethics Committee (EC) or regulatory authorities?
b) In the list of references to be attached with the clinical trial report, two of the references are patient data listings. What exactly does this mean? Case Report Forms (CRFs) of cases involving death and life threatening adverse event cases. Does this mean original CRFs?
c) In case of a Serious Adverse Event (SAE), till what point can an investigator and a sponsor follow up?
a) The sponsors can apply for permission from EC and regulatory authorities concurrently.
b) ICH E 3 guidelines on preparing report cover the details.
c) SAE is followed till resolution or till there is a steady state eg. stable values of abnormal liver function or as specified in the protocol eg. one month after completion of treatment and follow-up.
Can a sponsor (for single centre trials) consult an independent EC to approve the study when a local EC is present?
It is the responsibility of an EC to safeguard the rights, safety and well-being of all trial subjects. The Institutional Ethics Committee (IEC) also has to conduct a continuing review of the approved trial and assess reports of AEs. In case of any major issues, for example death of a subject, there could be medico-legal issues for the sponsor/investigator/institute. In such a situation, the regulatory authorities approach the IEC to investigate the matter.
If the trial is not approved by an IEC and if there is an inquiry into the conduct of clinical trial, the sponsor and investigator will find it difficult to satisfy the enquiry committee. Besides, during regulatory inspection, the inspectors usually wish to meet the EC and audit their processes. In view of all these considerations, the best option for ethical, legal and practical reasons is to seek approval for the IEC.
I am conducting a multi-centric trial and one of the criteria for inclusion is 18-70 years old male/female. But one investigator recruited patients aged 15 years. Is this a protocol deviation or GCP violation? If we become aware of such a deviation during the trial, what is the course of action?
As per ICH GCP 4.5.1 the investigator should conduct the trial in compliance with the protocol. Hence, this is a GCP violation. If you become aware of an inclusion of any patient who is 15 years of age at any stage during the trial, the patient should be withdrawn from the trial. The reason for withdrawal should be documented in the CRF and reported in the final report for regulatory submission.
a) In a situation where the symptoms of the disease reappear during the study period after not being present for sometime before during the study; what do we call these-adverse event or exacerbation of the disease. Is it necessary to mention its reappearance?
b) Should the contact information of the site and investigator be in vernacular language if the Informed Consent Document is given in vernacular language or can it be in English?
Dr Manisha Maganji
a) It would depend on the judgment of the investigator. If the symptoms appear to be an exacerbation of underlying disease, it has to be recorded as per the follow-up visit re-cord requirements. However, if the investigator feels that these symptoms cannot be explained as an exacerbation and possibly have a link with the investigational drug, they have to be recorded as AEs.
b) The objective of the contact information is to facilitate the patient in case of any issues about the trial. Hence, the contact information should be in vernacular language.
a) Is it necessary to have an impartial witness sign the Informed Consent form in BA/BE trials?
b) Can the witness be another study subject in the same BA/BE trial?
a) No. An impartial witness is required only if the subject is illiterate and his legal representative is illiterate.
b) As per ICH-GCP definition an impartial witness is a person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial.
As the other study subject is involved in the study, he can be influenced by the study team. Hence, he can not become an impartial witness.
Dr Arun D Bhatt, well-known clinical pharmacologist from Mumbai, and currently president, ClinInvent Research India Pvt Ltd, answers your questions on Good Clinical Practices. Please send in your questions at: email@example.com All queries should ideally reach him by the 15th of each month