The purpose of this SOP is to provide instructions on the review and follow-up reports of serious adverse events (SAEs), expected adverse events (AE) and unexpected events for any active study approved by the IRB. The SAE must be reported by the investigators to the IRB within 24 hours after the incident.
Unanticipated risks are sometimes discovered during the course of studies. Information that may impact on the risk/benefit ratio should be promptly reported to and reviewed by the IRB to ensure adequate protection of the welfare of the study participants. The unanticipated risks may as well include any event that in the investigator’s opinion, may adversely affect the rights, welfare or safety of subjects in the study.
This SOP applies to the review of SAE reports submitted by Investigators to IRB members.
The primary responsibility of the IRB is to review and address SAE and unexpected events involving risks to research participants. In addition, the committee is authorized to mediate with the participant and/or family under appropriate circumstances.
IRB should also make sure that researchers are made aware of the policies and procedures concerning reporting and continuing review requirements.
The IRB Secretariat is responsible for receiving the complete SAE / unexpected events reports. The member secretary to present the SAE report in the IRB meeting.
Adverse Event (AE) Any untoward medical occurrence in a patient or clinical investigation participant administered an investigational product and which does not necessarily have a causal relationship with this treatment. The adverse event can therefore be any unfavorable or unintended sign or experience associated with the use of the investigational product, whether or not related to the product.
Serious Adverse Event (SAE) The adverse event is SERIOUS and should be reported when the patient outcome is any one of these following listed:
- Death – Report if the patient’s death is suspected as being a direct outcome of the adverse event.
- Life-Threatening – Report if the patient was at substantial risk of dying at the time of the adverse event or it is suspected that the use or continued use of the product would result in the patient’s death. Examples: Pacemaker failure; gastrointestinal haemorrhage; bone marrow suppression; infusion pump failure which permits uncontrolled free flow resulting in excessive drug dosing.
- Hospitalization (initial or prolonged) – Report if admission to the hospital or prolongation of a hospital stay results because of the adverse event. Examples: Anaphylaxis; pseudomembranous colitis; or bleeding causing or prolonging hospitalization.
- Disability – Report if the adverse event resulted in a significant, persistent, or permanent change, impairment, damage or disruption in the patient’s body function/structure, physical activities or quality of life. Examples: Cerebrovascular accident due to drug-induced hypercoagulability; toxicity; peripheral neuropathy.
- Congenital Anomaly – Report if there are suspicions that exposure to a medical product prior to conception or during pregnancy resulted in an adverse outcome in the child. Examples: Vaginal cancer in female offspring from diethylstilbestrol during pregnancy; malformation in the offspring caused by thalidomide.
Requires Intervention to Prevent Permanent Impairment or Damage – Report if suspect that the use of a medical product may result in a condition which required medical or surgical intervention to preclude permanent impairment or damage to a patient. Examples: Acetaminophen overdose-induced hepatotoxicity requiring treatment with acetylcysteine to prevent permanent damage; burns from radiation equipment requiring drug therapy; breakage of a screw requiring replacement of hardware to prevent malunion of a fractured long bone.
10.4 Detailed Instructions
10.4.1 Before each IRB Meeting
10.4.1.1: SAE related activities before IRB meeting
- The IRB Secretariat will verify that the reports are complete, signed and dated by the In case the IRB Secretariat notes that the report is incomplete, it will be forwarded to Chairperson for decision and also revert back to PI.
- The IRB Secretariat or member review the reporter’s assessment to determine whether the report requires review by full Board or by the Chairperson or other qualified EC member(s).
10.4.1.2: Criteria for the review
The review criteria are as follows:
- Assessment of adverse experience is unknown or unlikely
- Report is forwarded to the Chairperson for review and determination if report should be reviewed at the convened meeting by full Board.
- Assessment of relatedness of the SAE as per the criteria of GSR 52 (E) with amendments of 12th June 201511.
- The report is added to the agenda for review at a convened meeting by full Board.
- An adverse experience been previously seen by full Board but being resubmitted by another investigator participating in the multi-study site (as part of a multi-centre/site study). This notification does not require full Board review.
- Reviewed by the Chairperson or other qualified EC members and secretariat
10.4.2 During the IRB meeting
10.4.2.1: Review and discuss
- After reading and reviewing the report, the Chairperson or designee entertains discussion on the study and similar adverse experiences or advisories.
- If appropriate to the discussions, the Chairperson or another IRB member may call for a consensus on whether to:
- Request an amendment to the protocol or the consent form.
- Request further information.
- Suspend or terminate the study.
10.4.2.2: Decide what action should be taken
- If any of the above actions are taken, the Member Secretary notifies the investigator of the action taken.
- If the EC takes no action, a notation is made in the minutes and the study is allowed to continue.
10.4.2.3: Inform investigator or Licensing Authority
- The IRB secretariat member drafts a formal letter to the investigators or the licensing authority to notify them of the action they should take according to the EC decision.
- Get the Chairperson to approve, sign and date the letter.
- Send the letter and record the delivery date.
10.4.2.3: Compensation for research-related harm
According to chapter VI of the New drug and Clinical Trial Rule, 2019, No. 43 titled ‘Medical management and compensation for injury or death relating to biomedical and health research overseen by an Ethics Committee for biomedical and health research’ are to follow the ‘National ethical guidelines for biomedical and health research involving human subjects, ICMR 2107, India2.
The following are the recommendations.
- Research participants who suffer direct physical, psychological, social, legal or economic harm as a result of their participation are entitled, after due assessment, to financial or other assistance to compensate them equitably for any temporary or permanent impairment or
- In case of death, participant’s dependents are entitled to financial compensation.