Aes saes and eaes an overview
This presentation is the property of its rightful owner.
Sponsored Links
1 / 32

AEs, SAEs, and EAEs – An Overview PowerPoint PPT Presentation


  • 121 Views
  • Uploaded on
  • Presentation posted in: General

AEs, SAEs, and EAEs – An Overview. MTN 020 Training. Layers of Safety. Study participants Study site staff team Clinical affairs staff at SCHARP MTN-020 P rotocol Safety Review Team (PSRT) NIAID Vaccine and Prevention Data and Safety Monitoring Board (DSMB) site .

Download Presentation

AEs, SAEs, and EAEs – An Overview

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Aes saes and eaes an overview

AEs, SAEs, and EAEs – An Overview

MTN 020 Training


Layers of safety

Layers of Safety

  • Study participants

  • Study site staff team

  • Clinical affairs staff at SCHARP

  • MTN-020 Protocol Safety Review Team (PSRT)

  • NIAID Vaccine and Prevention Data and Safety Monitoring Board (DSMB) site


Definition adverse event

Definition: Adverse Event

Any untoward medical occurrence in a clinical research participant administered an investigational product that does not necessarily have a causal relationship with the investigational product.

An AE can therefore be an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product.

ICH E6, Glossary 1.2


Definition pre existing condition

Definition: Pre-Existing Condition

Any medical condition, problem, sign, symptom, or finding identified as ongoing in a study participant at the time of enrollment (prior to randomization).

Pre-existing conditions are not AEs.

However, if a pre-existing condition worsens in severity and/or frequency after randomization, the worsened condition is an AE.


Case 1

Case 1

  • A participant reports that she has hypertension during her baseline medical history

  • Has an AE occurred?

    • No

    • Yes

    • Not enough information to determine


Case 2

Case 2

  • A participant reports a migraine headache occurring two weeks before her Month 4 visit.

  • Has an AE occurred?

    • No

    • Yes

    • Not enough information to determine


Case 3

Case 3

  • A participant has a positive pregnancy test result at her Month 7 visit.

  • Has an AE occurred?

    • Yes

    • No

    • Not enough information


Case 4

Case 4

  • A participant reports new vulvar erythema at her Month 10 visit. You note erythema on pelvic exam that covers approximately 30% of her vulva.

  • Is this an AE?

    • Yes

    • No

    • Not enough information

  • What if the vulvar erythema had not been seen on exam – does this change your answer?


Definition reportable adverse event

Definition: Reportable Adverse Event

An AE that meets study protocol criteria for reporting on adverse event case report forms

For MTN 020, this means reportable on an Adverse Experience (AE) Log CRF

AEs that do not meet the protocol criteria for reporting on adverse event forms will be recorded on the Grade 1 AE Log CRF (GAE Log)


Reportable adverse events

Reportable Adverse Events

There are six types of AEs

that are reportable in MTN 020.

Can you name them?


Reportable aes

Reportable AEs

  • All genital, genitourinary, and reproductive system AEs except

    • Fetal losses

  • All AEs of severity Grade 2 or higher

  • All serious AEs

  • All AEs that results in permanent discontinuation of study product use

  • All lab test abnormalities

  • AEs that meet expedited reporting requirement

  • Any AE not covered above will go on a Grade 1 AE Log form


Ae log or grade 1 ae log crf

AE Log or Grade 1 AE Log CRF?

  • Grade 1 vaginal itching

  • Grade 3 headache

  • Grade 1 nausea

  • Grade 1 urinary tract infection

  • Grade 1 weakness prompting hospital admission to rule out stroke

  • Grade 1 allergic reaction to the vaginal ring


Describing aes

Describing AEs

Pelvic Exam Finding AEs

  • Report any and all new abnormal findings as AEs

    • Specify anatomical location (e.g., vulvar, vaginal, cervical)

    • Use finding term as it appears in FGGT or Pelvic Exam CRF, whichever is more specific

    • For example, do not report “genital sore.” Instead, report “vaginal ulcer.”


Describing aes1

Genital Bleeding AEs

Report only bleeding that is different from baseline

May be expected (due to menses or contraceptive use) or unexpected

Use appropriate term from FGGT/SSP

Use separate terms for pregnancy-related bleeding – SSP Section 10.6

If bleeding associated with pelvic exam finding, report finding as the AE

The bleeding is a sign of the finding, - comment on in Comments field

Describing AEs


Antepartum bleeding

Antepartum Bleeding

Bleeding during pregnancy prior to the onset of labor (regardless of trimester) will be graded per the table below:


Ae severity

AE Severity

  • The severity of all AEs must be graded as

    • Grade 1 = Mild

    • Grade 2 = Moderate

    • Grade 3 = Severe

    • Grade 4 = Potentially Life-Threatening

    • Grade 5 = Death

  • Assign grades based on the DAIDS Female Genital Grading Table (FGGT) and DAIDS Table for Grading Adult and Pediatric Adverse Events (Toxicity Table)

  • See SSP Section 11.3 for tips and guidance


Severity grading of vaginal candidiasis

Severity Grading of Vaginal Candidiasis

  • Normal = absence of symptoms regardless of candida test results

  • Grade 1 = positive wet mount or other laboratory test for yeast, with mild symptoms

  • Grade 2 = positive wet mount or other laboratory test for yeast, with moderate to severe symptoms

  • Grade 3: Not applicable

  • Grade 4: Not applicable


Relationship to study product

Relationship to Study Product

  • The relationship of each AE to study product must be assessed as:

    • Related

    • Not Related


Aes saes and eaes an overview

Factors to Consider

Pre-clinical and clinical profile of the study products: protocol, package inserts, investigators brochures, other published information

Timing of product use relative to onset, resolution, and/or recurrence of the AE

Likelihood of observing the AE in the study population in the absence of product use

Presence of other conditions or exposures that could have caused the AE

Clinical judgment, including judgment of biologic plausibility


Ae outcome

AE Outcome

  • All AEs – reportable and not reportable – must be followed clinically until the AE resolves or stabilizes

  • Resolution = return to baseline severity grade

  • Stabilization = persistence at a severity grade above baseline for 3 consecutive monthly evaluations


Ae outcome1

AE Outcome

  • At each visit, an authorized study clinician should review all previously reported ongoing AEs to evaluate their current status

  • Oftentimes the outcome of an AE will not be available when the AE is first documented

  • In such cases, documentation should be updated when the final outcome becomes available


Ae outcome2

AE Outcome

  • If an AE increases in severity or frequency, the higher grade AE must be documented (and reported) as a new AE

  • If an AE completely resolves and then recurs at a later date, the second occurrence must be documented (and reported) as a new AE


Definition serious adverse event

Definition: Serious Adverse Event

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

  • Is a congenital anomaly/birth defect

Important medical events that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of the above-listed outcomes, also may be considered serious.


Seriousness of adverse events

Seriousness of Adverse Events

  • Seriousness ≠ severity

  • SAEs are a subset of all AEs

  • All SAEs are reportable on AE Log forms

  • All AEs must be assessed by authorized study staff to determine whether they meet the definition of serious  source document and record on AE Log form


Expedited adverse event

Expedited Adverse Event

AE that meets criteria in the study protocol for additional reporting for rapid review and assessment by DAIDS

Reporting period begins once the participant is randomized and continues through the final study visit (Study Exit/Termination Visit)

Only suspected, unexpected serious adverse reactions (SUSARs) as defined in Version 2.0 of the EAE Manual will be reported to DAIDS NEED TO CHECK ABOVE


Let s discuss more adverse events

Let’s Discuss More Adverse Events

Suppose a participant has a grade 3 decreased hemoglobin at her semi-annual visit

Is this an adverse event?

  • Yes

  • No

  • Not enough information to determine


Let s discuss more adverse events1

Let’s Discuss More Adverse Events

Suppose a participant has a grade 4decreased hemoglobin at her semi-annual visit

Is this serious?

  • Yes

  • No

  • Not enough information to determine


Let s discuss adverse events

Let’s Discuss Adverse Events

Suppose a participant has an argument with her partner related to her participation in the study. She was late meeting him because a study visit took longer than expected. He thinks the study is taking up too much of her time and he does not want to hear any more from her about safe sex and using condoms. The argument escalates and he pushes her to the floor, resulting in a laceration on her forehead and a broken collarbone. She is treated in the emergency department and then admitted to the hospital for observation related to her head injury.

How many AEs have occurred?

  • One

  • Two

  • None


Let s discuss adverse events1

Let’s Discuss Adverse Events

Suppose a participant has an argument with her partner related to her participation in the study. She was late meeting him because a study visit took longer than expected. He thinks the study is taking up too much of her time and he does not want to hear any more from her about safe sex and using condoms. The argument escalates and he pushes her to the floor, resulting in a laceration on her forehead and a broken collarbone. She is treated in the emergency department and then admitted to the hospital for observation related to her head injury.

How many AEs are EAEs?

  • One

  • Two

  • None


Let s discuss adverse events2

Let’s Discuss Adverse Events

Suppose a participant has a positive pregnancy test at her Month 6visit. At her Month 7visit, her pregnancy test is negative. She reports having no symptoms between visits and is surprised that she is no longer pregnant.

Is this an adverse event?

  • Yes

  • No

  • Not enough information to determine


A few extra reporting tips

A Few Extra Reporting Tips

  • Only symptomatic BV confirmed by wet mount should be reported as an AE

  • Only report symptomatic candida infections confirmed by wet mount should be reported as an AE

  • Chlamydia should be “genitourinary chlamydia infection”

  • Gonorrhea should be “genitourinary gonorrhea infection”

  • Suspected herpes lesions should be captured as “ulcers”


Aes saes and eaes an overview

Questions?


  • Login