Introduction to Post-marketing Drug Safety Surveillance: Pharmacovigilance in FDA/CDER
Sara Camilli, PharmD, BCPS, Safety Evaluator Team Leader Selena Ready, PharmD, CGP, Safety Evaluator Division of Pharmacovigilance Office of Surveillance and Epidemiology Center of Drug Evaluation and Research May 30, 2015
PresenterPresentation NotesThank you, Kara. Welcome and Good afternoon to everyone joining us for todays webinar. My name is XYZ and Im excited to present an Introduction to Postmarketing Drug Safety Surveillance. In particular, I will discuss Pharmacovigilance in FDAs Center for Drug Evaluation & Research (CDER). Ill start with our objectives (slide change)
CDER Center for Drugs Evaluation & Research
CFR Code of Federal Regulations
DEPI I & II Division of Epidemiology I & II
DILIN Drug-Induced Liver Injury Network
DMEPA Division of Medication Error & Prevention Analysis
DPV I & II Division of Pharmacovigilance I & II
DRISK Division of Risk Management
DSC Drug Safety Communication
EMA European Medicines Agency
FDA Food & Drug Administration
FDAAA Food & Drug Administration Amendment Act
FAERS FDA Adverse Events Reporting System
HCP Health Care Provider
MO Medical Officer NDA New Drug
Application OND Office of New Drugs
PMC Postmarketing Commitment
PMR Postmarketing Requirement
REMS Risk Evaluation & Mitigation Strategy
SE Safety Evaluator WHO-UMC World Health
Organization Uppsala Monitoring Centre
Define Pharmacovigilance Describe the Division of Pharmacovigilances (DPVs) key
safety roles in FDAs Center for Drug Evaluation and Research (CDER).
Understand components of postmarketing drug safety surveillance.
Understand regulatory requirements and the role of MedWatch for reporting postmarketing safety information.
Describe how adverse event reports are collected and analyzed by FDA/CDER/DPV
PresenterPresentation NotesBy the end of this presentation, participants will be able to. READ objectives And hopefully, at the end of this presentation, youll realize how important YOU (as healthcare providers) are in Pharmacovigilance.
Outline Pharmacovigilance Background Postmarketing Surveillance Spontaneous Adverse Event Reports and the FDA Adverse
Event Reporting System (FAERS) Signal Detection Components of a Good Case Report Case Series Development and Evaluation
PresenterPresentation NotesTo fulfill these objectives I have organized the talk into the following sectionsFirst I will discuss the FDA and where PV fits into the big picture of drug regulationNext, I will cover Postmarketing Surveillance and Spontaneous Adverse Event Reports and the FDA Adverse Event Reporting System (FAERS)I will then cover Signal DetectionAnd finally I will detail Components of a Good Case Report and Case Series Development and Evaluation
Office of Regulatory Affairs (ORA)
Center for Food Safety & Applied Nutrition (CFSAN)
Center for Drug Evaluation & Research (CDER)
Center for Biologics Evaluation & Research (CBER)
Center for Devices & Radiological Health (CDRH)
Center for Veterinary Medicine (CVM)
Center for Tobacco Products (CTP)
PresenterPresentation NotesThis slide briefly reviews FDAs overall organizational structure and the 7 main centers that carry out the FDAs public heath mission, which are divided by product type. This includes the centers for food, veterinary medicine, medical devices, biologic products, drugs, tobacco, and regulatory affairs. We love acronyms at FDA, and I included the acronyms for each center. The talk today will focus on drug safety activities within the Center of Drug Evaluation and Research or CDER (animation).
Office of Surveillance & Epidemiology
Office of Surveillance
Pharmacovigilance & Epidemiology
Office of Medication Error Prevention & Risk
Medication Error Prevention &
Division of Risk
Pharmacovigilance I and II
(DPV I and II)
Epidemiology I and II
(DEPI I and II)
PresenterPresentation NotesLooking closer at CDER, the drug safety activities and surveillance discussed today take place in CDERs Office of Surveillance and Epidemiology or OSE. This slide displays the structure of OSE, and the main divisions and disciplines that work to fulfill our drug safety missions. In the bottom row, the Divisions of Pharmacovigilance is highlighted; Other divisions include epidemiology, medication error prevention and analysis, and risk management.
The science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems.
* The Importance of Pharmacovigilance, World Health Organization 2002
PresenterPresentation NotesWhat is Pharmacovigilance? Pharmacovigilance is defined by the World Health Organization as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems.Examples of other drug-related problems include:Wrong doseDrug interactionsRisk assessmentName confusion, labeling
Divisions of Pharmacovigilance Evaluate the safety of drug and therapeutic biologic
products Advance public health by detecting and analyzing safety
signals from all available data sources, utilizing evidence-based methods
Recommend appropriate regulatory actions, including labeling changes, Risk Evaluation and Mitigation Strategies (REMS), etc.
Communicate relevant safety information
PresenterPresentation NotesBased on the Pharmacovigilance definition and our placement in the Office of Surveillance and Epidemiology this slide details the major responsibilities of the Division of Pharmacovigilance, which are,-Evaluating the safety of drug and therapeutic biologic products-Advancing public health by detecting and analyzing safety signals, utilizing evidence-based methods-Recommending appropriate regulatory actions, including labeling changes, Risk Evaluation and Mitigation Strategies (REMS), or other necessary means.AND finally Communicating relevant safety information
we will go into detail on each of these aspects.
Safety Evaluators (SEs) 10 teams of SEs
Majority clinical pharmacists Provide critical analysis of sources of postmarketing data to
identify and evaluate safety signals
Team coverage aligned with the Office of New Drugs (OND) review divisions therapeutic areas
~ 4-7 SEs per team (including Team Leader) Each SE covers assigned product group(s) aligned with therapeutic
PresenterPresentation NotesThe Pharmacovigilance activities are carried out by safety evaluators (or SEs) divided into 10 teams. SEs are typically clinical pharmacists. They provide critical analyses of sources of postmarketing data to identify and evaluate safety signals. Team coverage is based on relevant clinical therapeutics area and is aligned with the Office of New Drugs in CDER, which is also divided by therapeutic area. There are approximately 4-7 SEs on each team, and each SE has particular product assignments in the respective clinical area. For example, my team covers metabolic and endocrine products and is aligned with the Division of Metabolic and Endocrine Products in the Office of New Drugs.
Medical Officers (MOs) Provide clinical expertise in various therapeutic areas such
as dermatology, oncology, rheumatology, etc. Collaborate with DPV teams on safety evaluation Collaborate with Office of New Drugs (OND) on safety
PresenterPresentation NotesIn addition to the Safety Evaluators, the Divisions of Pharmacovigilance have Medical officers who provide clinical expertise in various therapeutic areas such as dermatology, hematology, oncology, rheumatology, and geriatrics.These Medical Officers collaborate with Pharmacovigilance teams and the Office of New Drugs (OND) on safety evaluationBACKUPDermatologyEpidemiologyGastroenterologyGeriatricsHematology/OncologyInfection DiseaseInternal MedicinePathologyPediatricsPulmonaryRheumatology
PresenterPresentation NotesNow, I will discuss the science and principles of post marketing surveillance/
Challenge Question #1
True or False Safety data is only collected during the later phases of
the clinical development program for a medical product.
PresenterPresentation NotesThis brings us to our first challenge question.
True or False, Safety data is only collected during the later phases of the clinical development program for a medical product.
You can answer this question by selecting the appropriate radio button next to each answer choice.For those who answered False you are correct. Safety data collection is NOT limited to the later phases of the clinical development program. Answer: False
APP R OVA L
Strategies and Actions to Minimize Risk
Safety in the Lifecycle of FDA-regulated Products
PresenterPresentation NotesBefore we discuss postmarketing safety surveillance we need to discuss pre-marketing safety and safety in the overall life-cycle of FDA-regulated drug products. Many of you may have seen this graphic before. Not surprisingly, safety is addressed in all aspects of the product lifecycle. Prior to drug approval, safety is evaluated throughout the Phase 1 to Phase 3 clinical trials in conjunction with the dosage and efficacy evaluation. Following drug approval, safety surveillance continues in the postmarketing setting, with a variety of data sources that I will soon discuss. As the bottom region of this slide emphasizes, a critical part of the overall safety evaluation, whether prior to or following product approval, is the implementation of strategies and actions to minimize the risk of these identified safety concerns. In the next few slides, I will go over some of the differences between premarketing and postmarketing safety information.
Limitations of Premarketing Clinical Trials
Size of the patient population studied Narrow population - often not providing sufficient data on
special groups Narrow indications studied Short duration
PresenterPresentation NotesAlthough premarketing clinical trials are the gold standard to determine safety and efficacy at the time of drug approval, many limitations exist.First, the Size of the patient population studied is small and only fairly common adverse events will be captured. For example drug-induced liver injury is a very serious reaction, but typically rare, thus if an event occurs in every 10,000 patients, trials (with even a few thousand patients) are too small to identify this risk.Also, a narrow patient population is usually included, thus if certain drug interactions or adverse events are more common in the elderly, they will not be captured in clinical trials since often times this population is excluded. Also children and pregnant women are rarely included in these trials.Next, narrow indications are typically studied and trials will often exclude patients with many comorbid conditionsFinally trials typically have a short duration and thus are not reflective of a drugs chronic use and cannot identify safety concerns that may only occur after long-term use of the drug.
Benefits of Postmarketing Monitoring
The ability to study the following: Low frequency reactions (not identified in clinical trials) High risk groups Long-term effects Drug-drug/food interactions Increased severity and / or reporting frequency of known
PresenterPresentation NotesIn contrast, post marketing safety monitoring can address many of the limitations of premarketing studies because it can better detect:
- Low frequency reactions not identified in clinical trials, rare but serious adverse events. - Postmarketing monitoring can also address High risk groups (like the elderly and children) that arent typically included in clinical trials. - These data can also address long-term effects like lipodystrophy with protease inhibitors used for the treatment of HIV. - Drug-drug/food interactions may also be captured in postmarketing data - Finally increased severity or reporting frequency of known reactions can be monitored using postmarketing data, while clinical trials typically will only give a quick snapshot of the safety profile.
Types of Postmarketing Surveillance Spontaneous/voluntary reporting of cases
National (FDA MedWatch) Local or Regional (Joint Commission Requirement) Scientific literature publications
Postmarketing studies (voluntary or required) Observational studies (including automated healthcare databases) Randomized clinical trials
Active surveillance Drug-Induced Liver Injury Network (DILIN) Sentinel initiative
PresenterPresentation NotesKnowing the advantages of postmarketing monitoring, here are various types of postmarketing surveillance data sources:First, Spontaneous/voluntary reporting of adverse events: cases can be found in National sources (like FDA MedWatch), at Local or Regional institution levels, or in Scientific literature publications like case reports or meta analyses.Second, Postmarketing studies: these studies can be voluntary or required by FDA. Types of studies include Observational studies (including those that use automated healthcare databases) or even Randomized clinical trials.Finally, active surveillance sources: such as the Drug-Induced Liver Injury Network (DILIN) which actively enrolls cases of DILI as well as the FDAs Sentinel initiative which uses the information from health care claims databases to identify or strengthen drug-related safety concerns.
Postmarket Adverse Event Reporting and MedWatch
PresenterPresentation NotesThe remainder of the talk will focus on postmarket adverse event reporting, a key aspect of postmarketing safety surveillance and how important YOU (as healthcare providers) are in Pharmacovigilance
Challenge Question #2
Which of the following countries does not require practitioners to report adverse events to a national registry? A. France B. Norway C. Sweden D. US
PresenterPresentation NotesThis brings us to challenge question 2: Which of the following countries does not require practitioners to report adverse events to a national registry? A) France B) Norway C) Sweden or D) USParticipants can answer this question by selecting the appropriate radio button next to each answer choice.
The correct answer is D, the US. Here in the US there is no adverse event reporting requirement for practitioners.
How Postmarketing Reports Get to...