9090-08 SAE Reporting Judy Breed, BA, RN June, 2011 CONFIDENTIAL.

9090-08 SAE Reporting

Judy Breed, BA, RNJune, 2011

CONFIDENTIAL

CONFIDENTIAL© 2011 Synta Pharmaceuticals Corp. 2

Why Drug Safety?

• Patient protection

• Safe drug development

• Corporate protection


What?

Adverse events

Any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product


AEs What ?

Examples

• Exacerbation of a pre-existing illness

• Increase in the frequency or intensity of a pre-existing or intermittent event

• New illness or condition

• Pregnancy


When to Report Adverse Events

Immediately following Informed Consent signing until 30 days after the last dose of study drug

.…unless a new anti-cancer treatment is initiated after study termination


AEs and Serious AEs

Severe vs Serious

Severity = Intensity of an event

Pain 9 on a 0-10 scale really hurts, but is not Serious unless……


Serious Adverse Event Definition

Fatal

Life-threatening

Disabling or incapacitating

Hospitalization, new or prolonged

Congenital anomaly

Other medically important events


SAE Definition cont’d

Fatal Event– The event results in death

– Death is not the event, it is the outcome of the event

Disabling or incapacitating– Substantially disrupts ADLs



Hospitalization

Admission to hospital for diagnosis and/or treatment of an event or condition

Event term = Diagnosis or major symptom(s)

Event term ≠ a Procedure



Complication during Hospitalization?– Is an adverse event (AE) unless

– Complication prolongs hospitalization = SAE



Congenital Anomaly or Birth Defect

– Occurring in the offspring of a female or male subject who received study drug



Medically Important Event

– Event does not meet any other criterion for Serious, but

– May jeopardize the subject, may require intervention to prevent the one of the other outcomes (death, life-threatening, hospitalization or congenital anomaly or birth defect)


Hospitalizations for the sole purpose of study drug administration

Hospitalization for elective procedure planned/scheduled prior to study

Hospitalizations for the verbatim term Disease Progression

Death as the event (Death = an outcome)

What’s NOT an SAE


What NOT to Report

Disease Progression – it is a study endpoint and is captured elsewhere

Unless- E.g., initially hospitalized for Severe Abdominal Pain for pain management and hydration and discovered to have disease progression that is clearly resulting in the abdominal pain


SAEs: When to Submit

Within 24 hours of learning of the event

– If a specific subject and event that meets the definition of serious is discussed with any Synta or Ergomed employee, the reporting clock has been started!


Expedited SAE Reports

Serious

Unexpected

Related


SAE Reporting to Regulators

7- Day Report– Serious

– Unexpected

– Life-threatening or fatal

– Date Synta learns of the event = Day 0

– Regulatory Clock is in calendar, not business, days



15-Day Report– Serious

– Unexpected

– Not life-threatening or fatal



Expedited Reports (7 and 15-Day reports) may be downgraded to just Serious

Serious Adverse Events may be upgraded to 7 or 15-Day Reports


SAE Reporting

Tools of the Trade

SAE Report FormPregnancy Report FormsSAE Completion Guidelines


SAE Form

Drug Safety Documents


SAE Completion Guidelines


Do Report

Pregnancy Form


Drug Safety Contact Information

Synta Fax for Reporting + 1 866 558 2230Drug Safety Phone (hot line) + 1 866 255 0025

Judy Breed, Direct + 1 781 541 7201

Ergomed Fax for Reporting +48 12 622 44 60Drug Safety Phone +48 12 622 44 69

email [email protected]


Overview of SAE Report Form Sections


0123 8012/FirstMiddleLast

Weight required for dosing

Height required for dosing

DOB must be a full date


SAE Report Forms

The Trouble Spots


Trouble….the Hotspots

Relationship to ganetespib and docetaxl

Medical History- Chronic, controlled conditions

Submission of blank pages

Prior history of the event

Ongoing vs Resolved at time of death


150mg/m2, IV weekly X 3/cycle

Dose reduced to 125mg/m2 12DEC2010, 300mg IV weekly X 3/cycle

Hypersensitivity reaction? Complete Dechallenge & Rechallenge questions for sure!!

ganetespib

Stop date is date of final dose. If dosing continues, leave blank

Date of last dose prior to SAE is the most recent dose

Relationship- must be included on the Initial report!


docetaxel

Lot #: Capture in real time! Include in source docs

Hypersensitivity reaction? Complete Dechallenge & Rechallenge questions for sure!!

75mg/m2 IV on Day 1 of 3 week cycle

125mg IV on Day 1 of 3 week cycle

Complete in same way as Section E for ganetespib


Submit printout of Medical History eCRF!

Chronic, controlled conditions are Continuing

Partial dates are OK: e.g., ??-???-1999


Helpful

Not so helpful

Both of these submitted pages are part of the permanent safety record!


Diagnosis If no Dx, major symptoms

01238012/FirstMiddleLast

9090-08

Ever?

Death As a result of this event

Death = Outcome?, thenSeverity = Death/Grade 5 and Serious = Death

Use Other if SAE predates study drug administration


Admission note, consultation notes, discharge notes etc may be attached.Discharge notes- please read before sending! Not always informative

Death certificate and autopsy not required by protocol. Send if available.


Indication should correspond to Medical History Information

Medications within preceding 30 days

No SAE treatment meds here!

Trade or generic name unless combination drug, e.g., Tylenol PM®


Treatment meds used, but don’t want to write in here? Check [X] See CRF or source documents attached and submit them instead!


Submit printout of labs with reference ranges

Write legibly please

Email address- ALWAYS provide

Always important and even more so if 7 or 15 day report!


SAE Follow-up from Study Sites

Follow-up SAE Reports

Must be submitted when:– Event term changes

– Relationship to study drug changes

– Another concomitant event meeting SAE criteria occurs

– Event resolves or stabilizes

– Any new information or reports are received


SAE Follow-up from Synta or Ergomed Drug Safety

Format of Safety Request for Information– Email

– Will identify if event meets 7 or 15 Day Reporting Requirements and due date for additional key information and Regulatory Reporting

Requests for– Missing data

– Clarification of existing data or terms

– Additional information


SAE Follow-up from Study Sites to Drug Safety Queries

Format of Site Response– Amended SAE Report Form

– Source documents e.g., Discharge summary

– Autopsy report, if available

RDC Requirement– Update RDC with new or revised SAE data

Data Management may also have queries on AS/SAE data that will require amendment of a previously Reported SAE


Well documented, accurate reports

The complete picture

Translations of relevant non-English source documents

No abbreviations or acronyms

No missing data or inconsistencies

Prompt reply to all Follow-up questions

An SAE report which seems insignificant at the time of reporting, could result in identification of an important safety signal!

What do we really want?

9090-08 SAE Reporting Judy Breed, BA, RN June, 2011 CONFIDENTIAL.

Documents

synta pharmaceuticals

definition of serious

event pain

event death

study hospitalizations

dose of study drug

study termination

definition contdcomplication