SAE Reporting Judy Breed, BA, RN June, 2011 CONFIDENTIAL

© 2011 Synta Pharmaceuticals Corp. 2 Why Drug Safety? Patient protection Safe drug development Corporate protection

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 3 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 4 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 5 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 6 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……

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 7 Serious Adverse Event Definition  Fatal  Life-threatening  Disabling or incapacitating  Hospitalization, new or prolonged  Congenital anomaly  Other medically important events

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 8 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 9 SAE Definition cont’d  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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 10 SAE Definition cont’d  Complication during Hospitalization? –Is an adverse event (AE) unless –Complication prolongs hospitalization = SAE

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 11 SAE Definition cont’d  Congenital Anomaly or Birth Defect –Occurring in the offspring of a female or male subject who received study drug

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 12 SAE Definition cont’d  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)

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 13  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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 14 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 15 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!

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 16 Expedited SAE Reports  Serious  Unexpected  Related

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 17 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 18 SAE Reporting to Regulators  15-Day Report –Serious –Unexpected –Not life-threatening or fatal

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 19 SAE Reporting to Regulators  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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 20 SAE Reporting Tools of the Trade  SAE Report Form  Pregnancy Report Forms  SAE Completion Guidelines

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 21 SAE Form Drug Safety Documents

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 22 SAE Completion Guidelines

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 23 Do Report Pregnancy Form

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 24 Drug Safety Contact Information Synta Fax for Reporting Drug Safety Phone (hot line) Judy Breed, Direct Ergomed Fax for Reporting Drug Safety Phone

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 25 Overview of SAE Report Form Sections

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp /F irst M iddle L ast Weight required for dosing Height required for dosing DOB must be a full date

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 27 SAE Report Forms The Trouble Spots

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 28 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp mg/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!

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 30 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 31 Submit printout of Medical History eCRF! Chronic, controlled conditions are Continuing Partial dates are OK: e.g., ??-???-1999

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 32 Helpful Not so helpful Both of these submitted pages are part of the permanent safety record!

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 33 Diagnosis If no Dx, major symptoms /F irst M iddle L ast Ever? Death As a result of this event Death = Outcome?, then Severity = Death/Grade 5 and Serious = Death Use Other if SAE predates study drug administration

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 34 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.

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 35 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®

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 36 Treatment meds used, but don’t want to write in here? Check [X] See CRF or source documents attached and submit them instead!

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 37 Submit printout of labs with reference ranges Write legibly please address- ALWAYS provide Always important and even more so if 7 or 15 day report!

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 38 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 39 SAE Follow-up from Synta or Ergomed Drug Safety  Format of Safety Request for Information – –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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 40 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

CONFIDENTIAL © 2011 Synta Pharmaceuticals Corp. 41  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?