Adverse Events and Serious Adverse Events - Katalyst HLS

Adverse Events &

Serious Adverse Events

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05/02/23Katalyst Healthcares & Life Sciences

Objectives:

Recognize Adverse Events and Serious Adverse Events Review FDA inspection findings related to Adverse

Events Review regulations related to Adverse Events Discuss recording and reporting of Adverse Events Discuss auditing of Adverse Events Demonstrate audit of Adverse Events

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05/02/23

Katalyst Healthcares & Life Sciences

FDA Inspection:

“Failure to prepare and submit complete and accurate and timely reports of unanticipated adverse device effects”

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Recognizing:4


Adverse Events:

Any adverse event associated with the use of a drug in humans, whether or not considered related. 21CFR 314.80

Any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment ICH E6

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Adverse Event:

NCI An unexpected medical problem that occurs during

treatment with a drug or other therapy. Adverse events do not have to be a caused by the

drug or therapy

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Serious Adverse Event:

Fred Doesn’t Have Any Money Left

FatalDisabilityHospitalizationAnomalyMedically SignificantLife Threatening

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Expected Vs. Unexpected

Expected Known to Occur and

is Listed in the Investigational Brochure, Informed Consent, or General Investigational Plan

Unexpected Not listed in

Investigational Brochure, Informed Consent, or General Investigational Plan

Also not listed in a drug package insert

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Recording:

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Recording:

Know which adverse events the protocol requires to be captured

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Source Documentation:

Source Documentation of adverse events include documentation in the medical records of: Event Date it occurred Grade as determined by CTCAE Expected or Unexpected Attribution as assigned by PI Date resolved Treatment patient received specifically related to event

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Sample Adverse Event Recording Form

See template behind this presentation

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Attribution (Causality) The attribution (relationship or causality or drug

related assessment) must be determined

A determination made by a clinical investigator that describes the relationship or association of the study product with an adverse experience

This determination must be recorded both in the medical record as well as in the case report form.

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Attribution

What should the investigator consider prior to assigning attribution? Individual medical history Known effects of concomitant medications

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Attribution:

Definite – Clearly related to study agent Probable – Likely related to study agent Possible – May be related to study agent Unlikely – Doubtfully related to study agent Unrelated – Clearly not related to study

agent

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How to Capture Adverse Events?

Split or Lumped Fever, Diarrhea, and Vomiting (Viral

Gastroenteritis) Cough, Sniffles, Sore throat (Flu)

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How to Capture Adverse Events?

Problems with similar terms Rash or Dermatitis Wheezing, reactive airway disease,

congestion, cold, , asthma

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Documenting Resolution Dates:

Challenge Does the patient remember when their adverse

event resolved? Do you call the patient? Or wait till the next visit?

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Patient Toxicity Diary:

Diaries where patients capture toxicities between their follow up appointments

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Patient Toxicity Diaries:

Patient writes down constipation because he did not have a bowel movement one day Research nurse captures constipation without assessing

further Physician copies the research nurse’s note and also dictates

constipation Did anyone ask about the constipation?

According to CTC V3, constipation is grade 1 only if there is occasional or intermittent symptoms; occasional use of stool softeners, laxatives, dietary modification, or enema

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Patient Adverse Event Diaries:

Advantages Allows capturing

information on a daily basis while patient is away from clinic

A communication tool for patient returns to clinic

Useful in capturing onset and resolution dates of adverse events

Disadvantages Time consuming Patient non-compliance Patient self diagnosis or

interpretation Complicated Instructions

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Question to Ask:

When should site staff begin collecting adverse event information?

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Question to Ask:

How long should one collect adverse events after the subject completes study treatment?

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Reporting:25


Reporting Serious Events

An investigator must promptly report to the sponsor any adverse effect that may reasonably be regarded as caused by or probably caused by the drug. If the adverse effect is alarming, the investigator shall report the adverse effect immediately. 21CFR312.64

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Reporting Criteria:

Routine Reporting Know which events can be reported at

interim analysis or annual reviews Expedited Reporting

Know which events require immediate reporting

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Reporting Criteria

Know which type of expedited reports each regulatory body requires FDA Sponsor Co-Sponsor MD Anderson NCI Collaborative Groups

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Issues in Reporting:

Primary events Example

Patient admitted with Congestive Heart Failure Subsequently develops: Pulmonary Edema and

Cardiogenic Shock

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Consequences of Improper Reporting

Protocol Violations IRB will close protocol FDA Hold Sponsor Hold Research Privileges Revoked Patient Safety

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Auditing:

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Auditing Check Points

Was the event a dose limiting toxicity? Should the dose have been reduced? If so, did the research team realize it as such and

identify it correctly?

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How are AEs being recorded in the medical record?

Does documentation include grade, onset, resolution, and attribution?

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Were all toxicities included? Was the proper CTCAE version used for

the protocol? Were the toxicities graded

appropriately?

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Auditing

Are adverse events appropriately reported within the time periods required by regulations, sponsor, and IRB policies?

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We have reviewed……….

Recognizing adverse events and serious adverse events Inspections and findings related to adverse events Regulations related to adverse events Recording and reporting of adverse events Auditing of adverse events

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Thank YouThank You&&

QuestionsQuestions

05/02/23

Contact:Katalyst Healthcare’s & Life SciencesSouth Plainfield, NJ, USA 07080.E-Mail: [email protected]

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Adverse Events and Serious Adverse Events - Katalyst HLS