Introduction to Post-marketing Drug Safety wmshp.org/sg_current_event_content_new/Pharmacovigilance_2015_05.pdf1 Introduction to Post-marketing Drug Safety Surveillance: Pharmacovigilance in FDA/CDER. Sara Camilli, PharmD, BCPS, Safety Evaluator Team Leader

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    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)

  • Acronyms

    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

    2

  • Acronyms, contd

    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

    3

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    Objectives

    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.

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    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

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    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).

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    Office of Surveillance & Epidemiology

    Office of Surveillance

    & Epidemiology

    Office of

    Pharmacovigilance & Epidemiology

    Office of Medication Error Prevention & Risk

    Management

    Division of

    Medication Error Prevention &

    Analysis (DMEPA)

    Division of Risk

    Management (DRISK)

    Division of

    Pharmacovigilance I and II

    (DPV I and II)

    Division of

    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.

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    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

    Pharmacovigilance

    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

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    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.

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    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

    area

    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.

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    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

    evaluation

    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

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    Postmarketing Surveillance

    PresenterPresentation NotesNow, I will discuss the science and principles of post marketing surveillance/

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    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

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    Phase 1

    Safety &

    Dosage

    Phase 2

    Safety &

    Efficacy

    Phase 3

    Safety &

    Efficacy

    APP R OVA L

    Post- Marketing

    Safety

    Surveillance

    Pre-clinical

    Safety

    & Biological

    Activity

    Safety Concerns

    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.

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    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.

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    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

    reactions

    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.

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    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.

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    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

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    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.

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    How Postmarketing Reports Get to...

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