Parents have consented to donate the eyes of deceased patients for corneal transplantation. The researcher now wants to use 1) Cadaveric retinal samples from the eye bank, 2) Samples from discarded eyes, 3) Surplus samples obtained (blood, CSF, bone marrow) for routine clinical care, 4) Samples from the removed eyeball for the study to identify biomarkers and to correlate eye tumours with genetic profile. What are the ethical issues arise in this situation for using these samples?

Research use of biological specimens collected for clinical use raises several ethical issues – consent of patient for research use, identity of patients, anonymization of samples, researcher’s commercial interest etc. Some excerpts from CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects are given below:

Use of medical records and biological specimens
Medical records and biological specimens taken in the course of clinical care may be used for research without the consent of the patients/subjects only if an ethical review committee has determined that the research poses minimal risk, that the rights or interests of the patients will not be violated, that their privacy and confidentiality or anonymity are assured, and that the research is designed to answer an important question and would be impracticable if the requirement for informed consent were to be imposed.

Patients have a right to know that their records or specimens may be used for research. Refusal or reluctance of individuals to agree to participate would not be evidence of impracticability sufficient to warrant waiving informed consent. Records and specimens of individuals who have specifically rejected such uses in the past may be used only in the case of public health emergencies

Secondary use of research records or biological specimens
Investigators may want to use records or biological specimens that another investigator has used or collected for use, in another institution in the same or another country. This raises the issue of whether the records or specimens contain personal identifiers, or can be linked to such identifiers, and by whom. If informed consent or permission was required to authorize the original collection or use of such records or specimens for research purposes, secondary uses are generally constrained by the conditions specified in the original consent. Consequently, it is essential that the original consent process anticipate, to the extent that this is feasible, any foreseeable plans for future use of the records or specimens for research. Thus, in the original process of seeking informed consent a member of the research team should discuss with, and, when indicated, request the permission of, prospective subjects as to: i) whether there will or could be any secondary use and, if so, whether such secondary use will be limited with regard to the type of study that may be performed on such materials; ii) the conditions under which investigators will be required to contact the research subjects for additional authorization for secondary use; iii) the investigators' plans, if any, to destroy or to strip of personal identifiers the records or specimens; and iv) the rights of subjects to request destruction or anonymization of biological specimens or of records or parts of records that they might consider particularly sensitive, such as photographs, videotapes or audiotapes.

What is the difference between PMS and phase IV study? It is necessary to notify both type of study to DCGI?
All studies done after the marketing of a drug are phase IV trials. PMS (post-marketing surveillance) is one type of phase IV study. Post marketing trials (phase IV) are studies (other than routine surveillance) performed after drug approval and related to the approved indication(s).  These trials go beyond the prior demonstration of the drug’s safety, efficacy and dose definition.  These trials may not be considered necessary at the time of new drug approval but may be required by the Licensing Authority for optimizing the drug's use. They may be of any type but should have valid scientific objectives. Phase IV trials include additional drug-drug interaction(s), dose-response or safety studies and trials designed to support use under the approved indication(s), e.g. mortality/morbidity studies, epidemiological studies etc. As per current norms, all phase IV studies require permission from DCGI office.

As per new rule, in case of injury, medical care will be provided free to the subject till required. How will this be ensured - subject 1st spends the money on it and it will be reimbursed by sponsor latter?
The spirit of the guideline is that a subject undergoing clinical trial should not suffer as a consequence of participation in trial. Hence, the subject should not be asked to pay for the treatment expenses. These have to be covered by the sponsor. The sponsor can provide the money as part of the trial budget to the investigator or can reimburse the investigator/institute.

Is it necessary to obtain EC permission for a prospective observation clinical study for age related conditions in which non-contact, non-invasive tests are used? There are no foreseeable adverse events and all procedures are safe for the patient.

As per ICMR guidelines, it is desirable that EC reviews such projects to assess the risk: benefit to participants and consent process.