Risk Assessment of Observational Data: Risk Assessment of Observational Data: Good Pharmacovigilance Practices Good Pharmacovigilance Practices

andand Pharmacoepidemiologic AssessmentPharmacoepidemiologic Assessment

CDER / CBER Pharmacovigilance CDER / CBER Pharmacovigilance Working GroupWorking Group

2

Working Group MembersWorking Group Members

Group Leads:Group Leads:• Julie BeitzJulie Beitz• Mark GoldbergerMark Goldberger• Miles BraunMiles Braun

Project Manager:Project Manager:• Patrick GuinnPatrick Guinn

• Kathy MiraccoKathy Miracco

• Yi TsongYi Tsong

• Edward CoxEdward Cox

• Dan ShamesDan Shames

• Susan LuSusan Lu

• Joyce WeaverJoyce Weaver

• Marianne MannMarianne Mann

• Judy StaffaJudy Staffa

• Carol HolquistCarol Holquist

• Min ChenMin Chen

• Melodi McNeilMelodi McNeil

• Ralph SchmidRalph Schmid

• Jeff Siegel

• Bette Goldman

• Jerry Davis

• Roselie Bright

• Mary Beth Jacobs

Support:

• Aileen Ciampa

• Jane Axelrad

• Virginia Beakes

• Nichelle Cherry

• Jane McCarthy

3

Workshop AgendaWorkshop Agenda

• MorningMorning– OverviewOverview– Good Pharmacovigilance Practices Good Pharmacovigilance Practices – Presentations, Qs and AsPresentations, Qs and As

• AfternoonAfternoon– Pharmacoepidemiologic AssessmentPharmacoepidemiologic Assessment– Presentations, Qs and AsPresentations, Qs and As– Closing RemarksClosing Remarks

4

Scope of Concept PaperScope of Concept Paper

• Present FDA’s preliminary thoughts on:Present FDA’s preliminary thoughts on:– Important pharmacovigilance conceptsImportant pharmacovigilance concepts– Safety signal identificationSafety signal identification– Pharmacoepidemiologic assessment and Pharmacoepidemiologic assessment and

interpretation of safety signalsinterpretation of safety signals– The development of pharmacovigilance The development of pharmacovigilance

plansplans

5

Scope of Concept PaperScope of Concept Paper

• Focus on risk assessment based on Focus on risk assessment based on observational data sourcesobservational data sources– Case Reports, Case SeriesCase Reports, Case Series– Pharmacoepidemiologic StudiesPharmacoepidemiologic Studies• RegistriesRegistries• SurveysSurveys

6

What is Pharmacovigilance?What is Pharmacovigilance?

All post-approval scientific and data All post-approval scientific and data gathering activities relating to the detection, gathering activities relating to the detection, assessment, understanding, and prevention assessment, understanding, and prevention of adverse effects or any other product- of adverse effects or any other product- related problems related problems

This includes the use of This includes the use of pharmacoepidemiologic studiespharmacoepidemiologic studies

7

Pharmacovigilance: Why?Pharmacovigilance: Why?

• At the time of approval, clinical trial data are At the time of approval, clinical trial data are available on limited numbers of patients available on limited numbers of patients treated for relatively short periodstreated for relatively short periods

• Once a product is marketed, large numbers Once a product is marketed, large numbers of patients may be exposed, including:of patients may be exposed, including:– Patients with co-morbid illnessesPatients with co-morbid illnesses– Patients using concomitant medicationsPatients using concomitant medications– Patients with chronic exposurePatients with chronic exposure

8

Pharmacovigilance: Why?Pharmacovigilance: Why?

• After marketing, new safety information After marketing, new safety information may become available:may become available:– Through use of the product domestically or in Through use of the product domestically or in

other countriesother countries– Through use of other drugs in the same classThrough use of other drugs in the same class– From preclinical studiesFrom preclinical studies– From pharmacologic studiesFrom pharmacologic studies– From controlled clinical trialsFrom controlled clinical trials

9

What is a Safety Signal?What is a Safety Signal?

• An apparent excess of adverse events An apparent excess of adverse events associated with use of a productassociated with use of a product– Even a single well-documented case report Even a single well-documented case report

may be viewed as a signalmay be viewed as a signal

10

What is a Safety Signal?What is a Safety Signal?

• Preclinical findings or experience with Preclinical findings or experience with other products in the class may be other products in the class may be sufficient to generate a signal, even in the sufficient to generate a signal, even in the absence of case reports in patientsabsence of case reports in patients

• A product’s risk profile may be A product’s risk profile may be characterized by several safety signalscharacterized by several safety signals

11

Safety SignalsSafety Signals

• Are Are identifiedidentified– From case reports, other sourcesFrom case reports, other sources

• Are Are evaluatedevaluated– In pharmacoepidemiologic studies, registries, In pharmacoepidemiologic studies, registries,

surveyssurveys

• Are Are interpretedinterpreted– In the context of all available safety informationIn the context of all available safety information

• Are Are monitoredmonitored– Through enhanced pharmacovigilance effortsThrough enhanced pharmacovigilance efforts

12

What is a Pharmacovigilance Plan?What is a Pharmacovigilance Plan?

• A plan proposed by a sponsor A plan proposed by a sponsor – for the ongoing evaluation of safety signals for the ongoing evaluation of safety signals

identified with the use of a productidentified with the use of a product– to monitor at-risk populations which have not to monitor at-risk populations which have not

been adequately studiedbeen adequately studied

• Plan may be developed at the time of product Plan may be developed at the time of product launch or after a signal is identifiedlaunch or after a signal is identified

13

What is a Pharmacovigilance Plan?What is a Pharmacovigilance Plan?

• A sponsor’s plan may involve:A sponsor’s plan may involve:– Expedited reporting of serious adverse events of Expedited reporting of serious adverse events of

interestinterest– Submission of adverse event report summaries at Submission of adverse event report summaries at

more frequent, pre-specified intervalsmore frequent, pre-specified intervals– Conduct of additional observational studies or Conduct of additional observational studies or

clinical trialsclinical trials– Implementation of active surveillance activities to Implementation of active surveillance activities to

identify as yet unreported adverse eventsidentify as yet unreported adverse events

14

Active Surveillance May Involve...Active Surveillance May Involve...

• Product-based activitiesProduct-based activities– Follow cohorts of patients exposed to specific Follow cohorts of patients exposed to specific

productsproducts• Setting-based activitiesSetting-based activities– Surveillance of healthcare settings (e.g., EDs) Surveillance of healthcare settings (e.g., EDs)

for events likely to present therefor events likely to present there• Event-based activitiesEvent-based activities– Monitor registries for events that are often Monitor registries for events that are often

drug-related (e.g., liver transplant registries)drug-related (e.g., liver transplant registries)

15

Emerging new safety data may result Emerging new safety data may result in ongoing revisions to the sponsor’s in ongoing revisions to the sponsor’s pharmacovigilance plan for a productpharmacovigilance plan for a product

16

While additional safety information is While additional safety information is being developed, FDA will work with being developed, FDA will work with sponsors to: sponsors to: – communicate information about safety communicate information about safety

signals andsignals and– minimize events occurring in users of a minimize events occurring in users of a

product through risk management product through risk management programsprograms11

1Concept Paper: Risk Management Programs

17

Workshop AgendaWorkshop Agenda

• MorningMorning– OverviewOverview– Good Pharmacovigilance PracticesGood Pharmacovigilance Practices – Presentations, Qs and AsPresentations, Qs and As

• AfternoonAfternoon– Pharmacoepidemiologic AssessmentPharmacoepidemiologic Assessment– Presentations, Qs and AsPresentations, Qs and As– Closing RemarksClosing Remarks