Fulfilling the Promise of Medicine Together New FDA Safety Reporting Requirements 2010 John McLane,...
-
date post
19-Dec-2015 -
Category
Documents
-
view
216 -
download
0
Transcript of Fulfilling the Promise of Medicine Together New FDA Safety Reporting Requirements 2010 John McLane,...
Fulfilling the Promise of Medicine Together
New FDA Safety Reporting Requirements 2010
John McLane, Ph.D.COO & Vice President Clinical and Regulatory AffairsClinquest, Inc. [email protected]
Fulfilling the Promise of Medicine Together2
Safety Reporting Requirements Different requirements for
• Sponsors• Investigators• IRBs
Different requirements depending on type of study and funding• FDA
Drug IND vs Postmarketing
Device Food Supplements
• Federal• ICH
Fulfilling the Promise of Medicine Together3
FDA: Sept 2010
Guidance for Industry And Investigators:• Safety Reporting Requirements for INDs and
BA/BE Studies New Regulations
• 21 CFR 312 IND Safety Reporting
• 21 CFR 320 BA/BE Studies Refers to Drugs and Biologicals Closer alignment to ICH/EMA
requirements
Fulfilling the Promise of Medicine Together4
Why New Regs and Guidances?
Too many reports unfiltered SAE reports associated with
• Manifestations of the disease morbidity for stroke
• Common in study population Strokes in elderly population
• Study Endpoints Confusion with phrase: “associated with the use
of the drug” and “reasonable possibility” Refine definitions
Fulfilling the Promise of Medicine Together5
Define: Adverse Event (AE)
Same as adverse experience Untoward medical occurrence
associated with the use of a drug• Whether or not considered drug related
Note separation from causality
Unfavorable or unintended sign or symptom
Temporally associated with any use of the drug
Fulfilling the Promise of Medicine Together6
Define: Suspected Adverse Reaction (SAR)
Any AE reasonably possibility that drug caused AE
Decreased level of certainty then an adverse reaction
1st use of “reasonable possibility” The SAR & use of “reasonable
possibility” is consistent with concepts about causality defined in ICH E2A
Fulfilling the Promise of Medicine Together7
Define “reasonable possibility”
Single occurrence of an uncommon event• AE know to be associated with drug
exposure
• Ex. Stevens-John syndrome 1 or more events not commonly
associated with drug exposure• Not common in the study population
Aggregate analysis of events that occur more frequently in tx arm
Fulfilling the Promise of Medicine Together8
Define: Unexpected AE or SAR
Safety event:• Not described in IB or protocol
• Event is of greater severity/specificity than previously described
Hepato-necrosis is a Unexpected AE if IB has only hepatitus
• Event is described as seen in similar drugs (class effect) but not yet observed with this drug
First occurrence of this type of event is a UAE
Fulfilling the Promise of Medicine Together9
Define: Serious (SAE)
Similar to prior use:• Death
• Life-threatening Excludes AE or SAR that had it occurred in
more serious form might have caused death
• In-patient hospitalization
• Prolongation of hospitalization
• Congenital anomaly/birth defect Refines the use of medical judgments
by either investigator or sponsor
Fulfilling the Promise of Medicine Together10
Safety Monitoring
Sponsor Evaluate Safety of Drug for
subjects
Serious, Expectedness, Reasonable Possibility
Analysis with other events related to drug use
Fulfilling the Promise of Medicine Together11
Review of Safety Information
Get safety information from all sources• Domestic/foreign trials
Foreign data to US: Safe Harbor Requirements
• Clinical epidemiology studies
• Annual literature review for safety
• Animal or in vitro expts.
Report in safety reports • ID all IND safety reports similar in nature
previously reported
• Notify FDA and all “participating investigators” 15 day reports
Fulfilling the Promise of Medicine Together12
SUSARS
For the first time FDA recognizes SUSARs
Three criteria• Suspected adverse reaction
• Serious
• Unexpected Expedited IND safety report
Fulfilling the Promise of Medicine Together13
Conclusion
Move towards harmonization• FDA will accept CIOMS I forms
• Use of SUSAR Clear definition
• Replace “associated with the use of the drug” with “reasonable possibility”
Fulfilling the Promise of Medicine Together15
Relationship between AEs and UAPs
The diagram illustrates three key points: • The vast majority of adverse events occurring in human
subjects are not unanticipated problems (area A) and do not need to be reported to the IRB.
• A small proportion of adverse events are unanticipated problems (area B) and need to be reported to the IRB.
• Unanticipated problems include other incidents, experiences, and outcomes that are not adverse events (area C) and need to be reported to the IRB.