safety reporting to irb online handouts apr2020 · 2 days ago · kindly note that all information...

Safety Reporting to IRB_Online_Handouts_Apr2020 1

SAFETY REPORTING TO IRB

Online Learning ModuleUpdated as of April 2020

Developing Clinical Research Professionals for the Nation

Training Disclaimer

This training and training materials are for educational and

informational purposes only.

This training material should be read in conjunction with the applicable

latest research policy and regulations from the learner’s research

organisation and/or institution, Singapore Regulatory Authority and

Ministry of Health.

Kindly note that all information and opinions presented in this training

and training materials were written to the best knowledge available at

the time of writing.



Module Outline

1. Adverse event

2. Adverse drug reaction

3. Serious adverse event

4. Suspected Unexpected Serious Adverse Reaction

5. Reporting of serious adverse event to IRB


Why collate AEs/SAEs?

• Safety monitoring of Investigational Product

• In all phases of trials

• Protect subjects while in trial.

• Protect patients after drug marketed.



Any untoward medical occurrence in a patient or clinical

investigation subject administered a pharmaceutical product and

which does not necessarily have a causal relationship with the

treatment.

An AE can therefore be any unfavourable and unintended sign

(including an abnormal laboratory finding), symptom, or disease

temporally associated with the use of a medicinal product, whether or

not related to the medicinal product.

ICH-GCP E6 (R2) 1.2

Adverse Event (AE) Definition

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In the pre-approval clinical experience with a new medicinal product or

its new usages, particularly as the therapeutic dose(s) may not be

established: all noxious and unintended responses to a medicinal

product related to any dose should be considered adverse drug

reactions. 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: 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.

ICH-GCP E6 (R2) 1.1

Adverse Drug Reaction (ADR) Definition

Unexpected

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Safety Events Reporting Periods

Medical History

Start of AE Reporting: After ICF obtained

/start dosing?



Medical History


/start dosing?

Start of SAE

Reporting: After ICF obtained




Medical History


/start dosing?

Start of SAE


AE / SAE Reporting continues

during study period



Medical History


/start dosing?

Start of SAE



during study period

End of AE / SAE

Reporting: xx days after last IP dose

(Washout)

Refer to information

found in Protocol or

CRF Guidelines!




Medical History


/start dosing?

Start of SAE



during study period

End of AE / SAE

Reporting: xx days after last IP dose

(Washout)

Refer to information

found in Protocol or

CRF Guidelines!

SAE Reporting:

Only if deemed as related to IP


1. Directly observed events.

e.g. observable rash on skin during PE

2. Events elicited from subject.

e.g. non-directive questioning during study visit

3. Events spontaneously volunteered by study subjects.

4. Laboratory, ECG or other tests’ reports.

e.g. out of reference range lab data or abnormal ECG report

5. Diaries/Data collection instruments.

e.g. AE recorded in the patient’s diary.

Sources of AEs



AE Reporting

Investigator must review all

protocol-specified investigation

results

(e.g. blood results, CXR, ECG etc)

Investigator must document review

1. Sign & date

2. CS or NCS (for abnormal results)

CS

NCS

Clinically

Significant

Non-Clinically

Significant

Report as AE

1) Seriousness criteria

2) Severity grading

3) Expectedness

4) Causality


Serious Adverse Event (SAE) Definition

A Serious Adverse Event (SAE) is any untoward medical occurrence

that at any dose:

1. Results in death

2. Is life-threatening

3. Requires inpatient hospitalization or prolongation of existing

hospitalization

4. Results in persistent or significant disability/incapacity

• Substantial disruption to subject’s normal life and

activity.

5. Is a congenital anomaly/birth defect

6. Is a medically important event

• Not immediate life threatening

• May required intervention to prevent any of the above

outcomes.ICH-GCP 1.1.50



Serious Vs Severe

Severe

• Describe the intensity (severity) of a specific event (as in mild,

moderate, or severe myocardial infarction).

• The event itself, however, may be of relatively minor medical

significance (such as severe headache).

Serious

• Based on patient/event outcome or action criteria usually

associated with events that pose a threat to a patient’s life or

functioning.


Expectedness & Causality assessment(Extract from DSRB Investigator’s Manual Edition 3)

1) Unexpectedness – any AE which is not listed in the Investigator

Brochure (IB) / more severe than describe in IB will be considered

as unexpected.

2) Causality – assess based on the following conditions:

a. The event has a reasonable temporal relationship to the

intervention. E.g. event occur after dosing (diarrhoea vs cancer)

b. The event could not have been produced by the

underlying disease states. E.g. hyperthyroidism patient

having migraine

c. The event could not have been due to other non-study

interventions.

d. The event follows a known pattern of response to the

intervention. E.g. study drug cause rash stated in IB

e. The event disappears with cessation of intervention.



Who is responsible for

reporting SAE to IRB?

Site is responsible for the documentation, investigation,

follow-up and timely reporting of all SAE to IRB.

Animations inserted


How to Report SAE to IRB?

CRC identify a potential SAE

Inform PI immediately

PI to assess and determine the:

• Expectedness

• Causality of the SAE

PI report the SAE to:

• DSRB via Expected SAE Report Form or;

• CIRB via Local SAE Report Form

Animations inserted



What is a SUSAR?

Suspected Unexpected Serious Adverse Reaction

Sometimes during a clinical trial for a certain drug, there may be

serious adverse reactions in subjects given the drug, that may or

may not be dose-related, but are unexpected, as they are not

consistent with current information.

Animations inserted


What is the difference between

SAE and SUSAR?

An SAE that occurs during research with a medicinal

product is a SAR if there is a certain degree of

probability that the SAE is a harmful and undesired

reaction to the investigational medicinal product,

regardless of the administered dose.

If the SAR is unexpected it is called a SUSAR.

Animations inserted



Non-local SAE Reporting Periods

Start :

Upon IRB approval

End :

After submission of study closure report form


DSRB Safety Reporting(Extract from Investigator’s Manual Edition 3)

UPIRTSO: A problem that is

1) Unexpected

2) Related or possibly related

3) Suggests that the research places subjects or others at greater

risk of harm.



Always check with your institution for the

latest update on the safety reporting timeline.

DSRB CIRB


What happen if a reportable SAE is

discovered but there’s insufficient

information?

Report to sponsor and IRB ASAP with the minimum

information.

Provide more information when available promptly.

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What to do for

unresolved Adverse Events

when subject’s study participation ended?

Follow up until resolved/stabilized, or as stated in

protocol

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Key Takeaways

• Important to understand what are the differences

between adverse event and serious adverse

event

• Always refer to IRB guidelines for requirements

and timelines to report safety events



References

• DSRB Expected Serious Adverse Events (SAE) ROAM Guide (For Site). Available at:

https://www.research.nhg.com.sg/wps/wcm/connect/a056dc80450ae56e9a98de9080

d6b809/ROAM+Guide+to+Reporting+Expected+SAE+for+Site.pdf?MOD=AJPERES

• NHG Investigator Manual 3rd Edition, October 2017

• SingHealth CIRB Reporting Requirement and Timeline for SAE/AE, Version 9, 20

August 2018. Available at:

https://research.singhealth.com.sg/PDF/CentralisedInstitutionalReviewBoard/Timeline

%20and%20Procedures%20for%20Reporting%20of%20SAE%20v9%20-

%20%2020%20Aug%202018.pdf

Thank you for Completing the

Safety Reporting to IRB Online Learning!


Join us at the CRC Level 1 Programme

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Topics Covered

• Overview and Protocol

• Disease and Investigations

• Essentials in Clinical Practice

• Start-up Activities

• Ethics and Study Visits

• Informed Consent

• Site File and Monitoring

• CT Regulations and Safety

• Investigational Product

• Laboratory and Study Supplies

• Study Closure

https://www.research.nhg.com.sg/wps/wcm/connect/a056dc80450ae56e9a98de9080d6b809/ROAM+Guide+to+Reporting+Expected+SAE+for+Site.pdf?MOD=AJPERES

https://research.singhealth.com.sg/PDF/CentralisedInstitutionalReviewBoard/Timeline%20and%20Procedures%20for%20Reporting%20of%20SAE%20v9%20-%20%2020%20Aug%202018.pdf

https://www.scri.edu.sg/clinical-research-coordinator-level-1-programme/

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safety reporting to irb online handouts apr2020 · 2 days ago · kindly note that all information...

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