8.The standard operating procedures to be followed by the committee in general:

General principles and ethical issues that are applicable to all biomedical and health research involving human participants or research using their biological material or data must be kept in focus during the conduct of biomedical and health research involving human participants. It is the responsibility of Ethics Committee to ensure that the research is conducted in accordance with the basic principles and general ethics.

8A. Application Submission Procedure:

1. All proposals should be submitted in the prescribed application form (hard & soft copy) to the Office of IEC/Member Secretary for review in the prescribed format and required documents as per IEC SOP.
2. All relevant documents should be enclosed with the application.
3. The required number of copies of the proposal along with the application and documents in prescribed format duly signed by the Principal Investigator (PI) and Co-investigators/Collaborators should be forwarded by the Head of the Department.
4. The Office of the IEC/ Member Secretary will acknowledge the receipt and indicate any lacunae. Missing information should be supplied within one week.
5. The date of the meeting will be intimated to the Principal Investigator who should be available to offer clarifications, if necessary.
6. The decision of the IEC will be communicated to the Principal Investigator. If revision is to be made, the revised document in required number of copies should be submitted within a stipulated period of time as specified in the communication or before the next meeting.

8B. Documentation:For a thorough and complete review, all research proposals should be submitted with the following documents:

1. Title of the project
2. Names of the Principal Investigator and Co-investigators with designation.
3. Name of any other Institute/Hospital/Field area where research will be conducted.
4. Approval of the Head of the Department/ Institute (if applicable).
5. Protocol of the proposed research.
6. Proposal should be submitted with all relevant annexure like proforma, case report forms, questionnaires, follow–up cards, etc. to be used in the study.
7. Patient information sheet and informed consent form in English/Hindi/local language should be enclosed.
8. For any drug/device trial, all relevant pre-clinical animal data and clinical trial data from other centres within the country/other countries, if available.
9. Any regulatory clearances, if required (copy of clearances). This is necessary for new drug/device not approved for marketing in India, justification for sending of biological samples outside India and the use of radioactive pharmaceuticals in clinical studies.
10. Source of funding and budget along with the supporting documents.
11. Indemnity issues including insurance for the compensation to the participants etc.
12. An undertaking to immediately report Serious Adverse Events (SAE) to IEC & Clinical Trial Registry of India (CTRI).
13. Statement of conflicts of interest, if any.
14. A statement describing any compensation for the study participation (including expenses and access to medical care) to be given to research participants.
15. Agreement to submit/present progress report and final report/thesis at the end of study as per institutional and university guidelines.
16. Plans for publication of results–positive or negative–while maintaining the privacy and confidentiality of the study participants, and abiding with the publication ethics.
17. Any additional document(s) relevant to the study as required by IEC.

8C. Review Procedure:
The EC is responsible for scientific and ethical reviews of research proposals.
The EC secretariat should screen proposals for completeness before categorizing them as exempted from review, expedited review or full committee review.

1. The proposals should be sent to IEC Office/members at least 2 weeks before the notified date of the IEC meeting for review.
2. The protocol may be reviewed by the Scientific Committee/IEC members.
3. Meetings of IEC shall be held at scheduled intervals as prescribed (once in 3 months/as per the notification of the institution head). Additional meetings will be held as and when necessary.
4. Principal Investigator should be available during the meeting and may be invited to offer clarifications.
5. Decisions will be taken by broad consensus after discussions or majority votes.
6. Independent consultants/Experts may be invited to offer their opinion on specific research proposals.
7. The decisions of the meeting shall be recorded in the minutes’ book/printed format and shall be confirmed before/during the next meeting.
8. In case of any grievance, the researcher can approach the head of the institute who serves as an Appellate Authority.

The IEC will monitor the progress of ongoing proposals, and reviews serious adverse events (SAE), protocol deviations/ violations, new information and final reports.
EC documentation should be dated, filed and preserved. Records must be archived for at least 3 years (5 years for regulatory clinical trials) after completion/termination of the study.

8D. Element of Review:

1. Scientific design and conduct of the study.
2. Approval of scientific review committee and regulatory agencies, if any.
3. Assessment of predictable risks/harms and potential benefits.
4. Procedure for selection of subjects including inclusion/exclusion, withdrawal criteria and other issues like sample size and advertisement details.
5. Management of research-related injuries, adverse events and compensation provisions.
6. Justification for placebo in the control arm, if any.
7. Availability of products to the trial subjects after the study, if applicable.
8. Patient information sheet and informed consent form in English/Hindi and local language.
9. Protection of privacy and confidentiality of subjects.
10. Disclosure of conflict of interest
11. Involvement of the community, wherever necessary.
12. Protocol and proforma of the study including the consent form.
13. Plans for data analysis and reporting.
14. Adherence to all regulatory requirements and applicable guidelines.
15. Competence of investigators, research and supporting staff.
16. Facilities and infrastructure.

8E. Types of Review:

1. Exemption from review:Proposals with less than minimal risk where there are no linked identifiers.
2. Expedited Review:Proposals that pose no more than minimal risk may undergo expedited review and the proposals which are recommended for minor revisions will be reviewed by the IEC members for clearance and approval.
3. Full Committee Review:All research proposals presenting more than minimal risk that is not covered under exempt or expedited review should be subjected to full committee review.

8F. Decisions Making:

1. Only IEC members will make the decision to approve, reject or revise the proposals. Specific suggestions for modifications and reasons for rejection should be given.
2. Revised proposals may be subjected to an expedited review.
3. All approved proposals will be subject to the following standard conditions.

Additional conditions may be added by the IEC.

• i). PI should submit an annual report of the ongoing project to the IEC.
• ii). The final report of the completed study should be submitted by the Principal Investigator.
• iii). The PI should highlight the changes in the protocols/brochures/Informed consent form etc. being amended from the previous documents while submitting amended documents to IEC.

8G. Communicating the Decision:

1. Decision will be communicated to Principal Investigator by the Member Secretary in writing.
2. Suggestions for modifications and reasons for rejection shall be communicated to the Principal Investigator.

8H. Follow-up Procedures:

1. Protocol deviation, if any, should be informed with adequate justifications.
2. Any amendment to the protocol should be submitted for approval.
3. Any new information related to the study should be communicated to IEC.
4. Premature termination of study should be notified with reasons along with a summary of the data obtained so far.
5. Change of investigators should be done with the approval of IEC.

8I. Informed Consent Process:

Voluntary written informed consent should be obtained in an informed consent document (ICD) from each participant to protect each individual’s freedom of choice.
Informed consent is a continuous process involving three main components:

• Providing relevant information to potential participants
• Ensuring competence and comprehension of the information and
• Voluntariness of participation

Informed consent should be voluntary, in local languages and be signed by the participant after receiving information, understanding it and discussing it with family/friends (if required).
In the case of research involving children, in addition to parental consent, verbal (7-12 years) or simplified written (>12 – 18 years) assent should also be taken from the participant.
Electronic/online consent may be obtained for research involving sensitive topics while safeguarding information and data and also if required for regulatory clinical trials.
Individual consent is important and required, even if the community gives permission for participation in a research study.

Characteristics of an ICD:

Conditions for granting waiver of consent:

The EC may grant a consent waiver in the following situations:

• research cannot practically be carried out without the waiver and the waiver is scientifically justified;
• retrospective studies, where the participants are de-identified or cannot be contacted;
• research on anonymized biological samples/data;
• certain types of public health studies/surveillance programmes/programme evaluation studies;
• research on data available in the public domain; or
• research during humanitarian emergencies and disasters, when the participant may not be in a position to give consent. An attempt should be made to obtain the participant’s consent at the earliest.

8J. Serious Adverse Events (SAEs):

The IEC should review and address the SAE and unexpected events involving risk to the research participants.

• The researcher is responsible for reporting all SAEs to the EC within 24 hours of knowledge.
• A report on how the SAE was related to the research must also be submitted within 14 days.
• The EC is responsible for reviewing the relatedness of the SAE to the research, as reported by the researcher, and determining the quantum and type of assistance to be provided to the participants.
• For clinical trials under the purview of CDSCO, the timeline and procedures as notified from time to time may be followed.
• All research participants who suffer harm, whether related or not, should be offered appropriate medical care, psycho-social support, referrals, clinical facilities, etc.
• Medical management should be free if the harm is related to the research.
• Compensation should be given to any participant when the injury is related to the research. This is applicable to participants in any of the arms of research, such as intervention, control and standard of care.
• While deliberating on the quantum of compensation to be awarded to participants who have suffered a research-related injury, the EC should consider aspects including the type of research (interventional, observational, etc.), the extent of injury (temporary/permanent, short/long term), loss of wages, etc.
• For other sponsored research, it is the responsibility of the sponsor (whether a pharmaceutical company, government or non-governmental organization (NGO), national or international/bilateral/multilateral donor agency/institution) to include insurance coverage or provision for possible compensation for research-related injury or harm within the budget.
• The researcher should ensure free treatment for research-related injury (disability, chronic life-threatening disease and congenital anomaly or birth defect) and if required, payment of compensation over and above medical management by the investigator and/or institution and sponsor(s), as the case may be.

8K. Action on Serious Adverse Events:

Appropriate action will be taken by the IEC based on consensus decisions some of which may be as below:

• Termination of study
• Suspension of study till additional information is obtained.
• Suspension of study till the review is completed
• Suspension of the study for a fixed duration of time
• Recommendation to further stop enrolment of the research participants
• Recommendation to amend the protocol
• Amendment in informed consent including information on SAE and obtaining fresh consent to further continue the study, etc.

Details of documents to be included in the protocol
(As per the ICMR Guidelines, 2017 and Institutional policy):

1. Cover letter to the Member Secretary
2. Type of review requested
3. Application form for initial review
4. The correct version of the informed consent document (ICD) in English and the local language(s). Translation and back translation certificates (if applicable)
5. Case record form/questionnaire
6. Recruitment procedures: advertisement, notices (if applicable)
7. Patient instruction card, diary, etc. (if applicable)
8. Investigator’s brochure (as applicable for drug/biologicals/device trials)
9. Details of funding agency/sponsor and fund allocation (if applicable)
10. Brief curriculum vitae of all the study researchers
11. A statement on Conflict of Interest, if any
12. GCP training certificate (preferably within 5 years) of investigators (clinical trials)
13. Any other research ethics/other training evidence, if applicable as per EC SOP
14. List of ongoing research studies undertaken by the principal investigator (if applicable)
15. Undertaking with signatures of investigators
16. Regulatory permissions (as applicable)
17. Relevant administrative approvals [such as Health Ministry’s Screening Committee (HMSC) approval for international trials]
18. Institutional Committee for Stem Cell Research (IC-SCR) approval (if applicable)
19. Memorandum of understanding (MoU) in case of studies involving collaboration with other institutions (if applicable)
20. Clinical trial agreement between the sponsors, investigator and the head of the institution(s) (if applicable)
21. Documentation of clinical trial registration (preferable)
22. Insurance policy (it is preferable to have the policy and not only the insurance certificate) for study participants indicating conditions of coverage, date of commencement and date of expiry of coverage of risk (if applicable)
23. Indemnity policy, clearly indicating the conditions of coverage, date of commencement and date of expiry of coverage of risk (if applicable)
24. Any additional document(s), as required by EC (such as other EC clearances for multicentric studies)
25. Protocol of the research.

Details of documents to be included in the protocol
(As per the ICMR Guidelines, 2017 and Institutional policy):

The protocol should include the following:

1. The facing page carrying the title of the proposal with the signatures of the investigators;
2. Brief summary/ lay summary;
3. Background with the rationale of why a human study is needed to answer the research question;
4. Justification of inclusion/exclusion of vulnerable populations;
5. Clear research objectives and end points (if applicable);
6. Eligibility criteria and participant recruitment procedures;
7. Detailed description of the methodology of the proposed research, including sample size (with justification), type of study design (observational, experimental, pilot, randomized, blinded, etc.), types of data collection, intended intervention, dosages of drugs, route of administration, duration of treatment and details of invasive procedures, if any;
8. Duration of the study;
9. Justification for placebo, benefit-risk assessment, plans to withdraw. If standard therapies are to be withheld, justification for the same;
10. Procedure for seeking and obtaining informed consent with a sample of the patient/participant information sheet and informed consent forms in English and local languages. Audio-Visual (AV) recording if applicable; informed consent for stored samples;
11. Plan for statistical analysis of the study;
12. Plan to maintain the privacy and confidentiality of the study participants;
13. For research involving more than minimal risk, an account of the management of risk or injury;
14. Proposed compensation, reimbursement of incidental expenses and management of Research-related injury/illness during and after the research period;
15. Provision of ancillary care for unrelated illness during the duration of research;
16. An account of storage and maintenance of all data collected during the trial; and
17. Plans for publication of results – positive or negative – while maintaining confidentiality of personal information/ identity.
18. Ethical considerations and safeguards for protection of participants.

8L. Record Keeping and Archiving:

• All documentation and communication of an EC should be dated, filed and preserved according to written procedures.
• Confidentiality should be maintained during access and retrieval procedures by designated persons.
• All active and inactive (closed) files should be appropriately labelled and archived separately in designated areas.
• Records can be maintained in hard copies as well as soft copies.
• All records must be archived for a period of at least 3 years after the completion/ termination of the study.
• Documents related to regulatory clinical trials must be archived for 5 years after the completion/termination of the study or as per regulations.
• Records may be archived for a longer period if required by the sponsors/regulatory bodies.
• IEC records should be accessible for inspection by authorized representatives of regulatory agencies.

8M. Documents to be maintained by EC for record

Administrative documents:

• Constitution and composition of the EC
• Signed and dated copies of the most recent curriculum vitae of all EC members
• Signed confidentiality agreements
• Conflict of Interest (COI) declarations of members
• Training records of EC members
• Registration/accreditation documents, as required
• A copy of national and international guidelines and applicable regulations
• Regulatory notifications
• Meeting-related documents
• Agenda and minutes
• All communications received or made by the EC
• Standard operating procedure (SOP)

Proposal-related documents:

• One hard copy and a soft copy of the initial research proposal and all related documents
• Decision letters
• Any amendments submitted for review and approval
• Regulatory approvals (as applicable)
• Serious adverse events (SAE), Adverse events (AE) reports (as applicable)
• Protocol deviations/violations
• Progress reports, continuing review activities, site monitoring reports (as applicable)
• All correspondence between the EC and researchers
• Record of notification issued for premature termination of a study with a summary of the reasons
• Final report of the study and publications, if any

11.Policy to monitor or prevent the conflict of interest along with standard operating procedures:

Conflict of interest (COI) is a set of conditions where professional judgement concerning a primary interest such as participants’ welfare or the validity of research tends to be unduly influenced by a secondary interest, financial or non-financial (personal, academic or political). COI can be at the level of researchers, EC members, institutions or sponsors. If COI is inherent in the research, it is important to declare this at the outset and establish appropriate mechanisms to manage it.

• Researchers must ensure that the documents submitted to the EC include disclosure of interests that may affect the research.
• EC must evaluate each study in light of any disclosed interests and ensure that appropriate means of mitigation are taken.
• COI within the EC should be declared and managed in accordance with the standard operating procedures (SOP) of that EC.
• If a conflict of interest exists between researchers/members of the EC, then that has to be mentioned and that member should not participate in the meeting/review process.

Declaration and management of Conflict of Interest within EC Members:

• Any actual, potential or perceived conflict of interest in any research project that is submitted for consideration by IEC, these interests may include any personal involvement or participation in the research, any financial interest in the outcome of the research any involvement in competing research.
• The member shall immediately disclose to the Chairperson of the IEC any actual or potential conflict of interest that he/she may have in relation to any particular research project submitted for review by the committee, and abstain from any participation in discussion or recommendation or voting in respect to the final approval.
• Each member should declare conflict of interest before final approval of the project.