FAQ : Clinical Trials – Safety Reporting

SAE reporting is NOT required but SUSAR reporting to NPRA is mandatory.

In case of SAE reporting, the report should be submitted to the respective Ethics Committee depending on their requirements. We encourage you to check with the individual Ethics Committee to find out their reporting requirements.

In the pre-approval clinical experience with a new medicinal product or its new usages, all noxious and unintended responses to a medicinal product related to any dose should be considered as ADR. The phrase responses to a medicinal product means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e. the relationship cannot be ruled out.

Regarding marketed medicinal products, ADR is a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function.

It is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, or is a congenital anomaly / birth defect.

Other important medical events that may not be immediately life-threatening or result in death or hospitalization, but when based on appropriate medical judgement, may jeopardise the subject or may require intervention to prevent of the outcomes in the definition of “Serious” ADR above should also be considered Serious ADR.

It is an adverse reaction where the nature or severity of which is not consistent with the applicable product information (e.g. Investigator’s Brochure for an unapproved investigational product or package insert / summary of product characteristics for an approved product).

The event must fulfil all the following criteria before reporting to NPRA:-
(a) The event is an adverse drug reaction (ADR). Please read FAQ # 2.
(b) The suspected drug is the investigational product, which requires CTIL/CTX, not the comparator or placebo.
(c) The ADR is serious. Please read FAQ # 3.
(d) The ADR is unexpected. Please read FAQ # 4.
(e) The source of report should be occurred at trial site in Malaysia.
(f) The report must contain the minimum information for expedited reporting. Please read FAQ # 9.

Local SUSAR (Malaysia trial sites): Individual SUSAR report in the format of CIOMS must be notified to NPRA.

SUSAR outside of Malaysia trial site:  Only six-monthly SUSAR line listing report must be notified to NPRA. Individual SUSAR reports is not required. 

The report with an accompanying cover letter can be submitted via email to mysusar@npra.gov.my.

Acknowledgement of Receipt (AoR) will be generated for the reports submitted.

Reporting to NPRA is optional.

The reporting of local SUSAR commence on the date a notification of CTIL/CTX approval is received from NPRA. This activity must continue until the CTIL/CTX involved has expired or the End of Study Summary Reports have been submitted for all trial sites in Malaysia, whichever is later.

It is acceptable to report six-monthly SUSAR Line Listing (SLL) according to global reporting timeline. However, SLL must be reported based on protocol specific in which Malaysia participates in. Individual SUSARs arising from trials which are not conducted in Malaysia is not required to report to NPRA.

The expedited report must include the following information, but not limited to:-
(a) An identifiable patient
(b) The name of a suspected medicinal product
(c) An identifiable reporting source
(d) An event or outcome that can be identified as serious and unexpected
(e) There is a reasonable suspected causal relationship

You can verify the receipt of SUSAR, SUSAR Line Listing and DSUR reports by sending the following details of your submission as a query to mysusar@npra.gov.my. Phone call follow-ups on this matter will generally not be entertained.

(a) The subject of the email or SUSAR, SUSAR Line Listing and DSUR reports reference number

(b) Date of submission

There are two (2) reporting timelines depending on the nature of report as following:-

(a) For SUSAR with death and/or life-threatening events, initial report should be submitted within 7 CALENDAR days and followed by full report as complete as possible within 8 additional CALENDAR days.

(b) For SUSAR with non-fatal or non-life-threatening events, initial report should be submitted within 15 CALENDAR days and followed by full report as it becomes available.

The timeline starts from neither “Date Received by Manufacturer” nor “Date of SUSAR Report”. It starts after first knowledge by the sponsor that a case qualifies as a SUSAR for expedited reporting. This date should be written in the report.

When a serious adverse reaction is judged reportable on an expedited basis, it is recommended that the blind be broken for that specific patient by the sponsor even if the investigator has not broken the blind. This is to prevent the placebo and comparator (usually a marketed product) cases to be filed unnecessarily.

When a fatal or other "serious" outcome is the primary efficacy endpoint in a clinical investigation, the integrity of the clinical investigation may be compromised if the blind is broken. Under these and similar circumstances, you should request from NPRA in advance to submit the blinded SUSAR reports or exempt from expedited reporting concerning serious events that would be treated as disease-related and not subjected to routine expedited reporting. When the blind is eventually opened, which may be many weeks or months after reporting to NPRA, an update in the CIOMS-I format as a follow up report will be sufficient.

NO.

NO. NPRA does not have any specific requirement on SUSAR reporting to Investigator. However, you should update the investigator adequately when the safety finding(s) could affect the safety of subjects, impact the conduct of the trial or alter the IRB/IEC's approval/favourable opinion to continue the trial.

The party responsible for safety reporting should be clearly stated in the Clinical Trial Agreement (CTA). In most of the cases, Company A is responsible for safety reporting for Trial A whereas Company B for Trial B. Thus, in the above scenario, only Company A should expedite the SUSAR report to NPRA.

(a) SUSAR Reports Line Listing
(b) Development Safety Update Report (DSUR)
(c) Annual Safety Report (ASR)

(a) Six-monthly SUSAR Reports Line Listing is compulsory for SUSAR outside of Malaysia trial site
(b) Development Safety Update Report (DSUR) is compulsory
(c) Annual Safety Report (ASR) is currently not mandatory, but will be generally accepted.

For inquiries regarding the safety reporting of investigational products in clinical trials, please contact the Head of Section of Investigational Product Evaluation & Safety Section, Dr. Zaril Harza Zakaria at zaril@npra.gov.my.