Reactions 1015 - 21 Aug 2004

Update on the Office of Drug Safety at the US FDA– Rosie Stather –

The Drug Information Association Annual Meeting [Washington, DC, USA, Jun 13-17, 2004] hosted an interactivepanel discussion on the structure and function of the new Office of Drug Safety (ODS) and some of the activitiesin which this office has recently been engaged in. Delegates heard about safety signal detection/data-mininginitiatives, drug-induced liver-injury, developments in assessing risk management plans and medication-errorissues.

literature. A safety signal work-up involves developmentOrganisation of the ODSof case series, calculation of adverse event reportingThe panel chairman, Dr Paul Seligman, started with anrates and implementation of observational studies suchintroduction to the organisation of the ODS. The ODSas pharmacoepidemiological safety studies, registrieswas created in 2002 from the former Office of Post-and surveys. Whether postmarketing study ismarketing Drug Risk Assessment. The ODS is locatedundertaken depends on the risk of the event, its severity,under a new "super" office, the Office ofthe population at risk and whether it involves medicalPharmacoepidemiology and Statistical Science headederrors and drug-drug interactions.by Dr Seligman. This office is part of the Center for Drug

Evaluation and Research (CDER), which in turn is part of Specific DDRE Initiativesthe US FDA. According to Dr Avigan, the DDRE is undertaking a

The ODS is now responsible for the MedWatch data-mining initiative in order to enhance signalprogramme, which was formerly with the Office of detection in the AERS database. DDRE has a cooperativeTraining and Communications, and for the patient research and development agreement with Lincolnlabelling and risk communication functions, formerly Technologies to develop "Web Visual Data Miningwith the Division of Drug Marketing, Advertising and Environment" (Web VDME). The goals are to create aCommunications. web-based desktop software tool for safety evaluators

The ODS consists of three divisions: and epidemiologists to enhance efficiency of signal• Division of Drug Risk Evaluation (DDRE) detection/evaluation, to determine appropriate• Division of Surveillance, Research and applications of the system and to optimise the system’s

Communication Support (DSRCS) user friendliness and critical data-links. Web VDME is• Division of Medication Errors and Technical Support currently being piloted by DDRE safety evaluators and

(DMETS) epidemiologists as a part of safety surveillance andevaluation activities. Another area of specific interest toActivities at DDREthe DDRE is drug-induced liver injury. Specific goalsDr Mark Avigan, who has been director of DDRE for ainclude: improving the postmarketing surveillance andlittle less than a year, presented an overview of thecharacterisation of drug-induced liver injury; anddivision’s activities.development of consistent approaches to evaluate thePostmarketing, DDRE is involved with safety signalhepatotoxic risk of drugs both pre- and postmarketing.detection and risk evaluation, epidemiological risk

In summing up, Dr Avigan said that the mostassessments and phase IV study design. Pre- and peri-important challenges for the DDRE were to recognizeapproval DDRE staff assess proposed risk managementnew drug-related safety issues in a timely manner and toplans and they have safety conferences with OND staffevaluate risks that are of a public health concernto discuss product labelling and plans for postmarketingthroughout the lifecycle of a product.monitoring/evaluation. According to Dr Avigan, in 2003,

the DDRE undertook 670 consults including consults to Current Functions of the DSCRSthe CDER’s new Office of Therapeutic Biologics. In the The Director of the DSRCS, Dr Gerald Dal Pan,same year, DDRE also undertook safety reviews for outlined the current functions of his division as theagents granted paediatric exclusivity, co-authored the acquisition, analysis, maintenance of relevant data toproposed risk management plan reviews with other support ODS and CDER functions, risk communicationODS divisions and made presentations at a number of to both patients and healthcare professionals andODS and OND-sponsored FDA Advisory Committees. involvement in risk management programmes. On the

Safety signal detection for all marketed drug products data front, the DSCRS provides support andis the primary role of the safety evaluators. They work management for the AERS database. It also maintainsclosely with medical reviewers at the OND so that contracts with drug utilization databases used by thepotential safety signals are placed in the context of ODS.existing knowledge about the drugs in question from the

MedWatch and Consumer Informationpreclinical and clinical development phases. TheThe DSCRS actively promotes MedWatch byepidemiologists review phase IV study protocols and

educating healthcare professionals about the need toevaluate various postmarketing surveillance tools thatreport adverse events. The DSCRS uses MedWatch tomay be incorporated into risk management strategies,disseminate risk information both directly on thesuch as patient registries and restricted distributionwebsite and by using listserv e-mail alerts. MedWatchsystems. They estimate the public health impact ofwebsite postings by the DSCRS include: safety alertssafety signals by evaluating data from the Adverse Event(Dear Doctor/Healthcare Provider Letters describingReporting System (AERS) Database, which contains overimportant safety labelling changes; class I recalls; public3 million adverse event reports, and data fromhealth advisories; drug withdrawals); and monthlyinternational sources such as the WHO database, thesummaries of safety labelling changes.EMEA, clinical study databases and the published

The DSCRS oversees consumer information activities

1

Reactions 21 Aug 2004 No. 10150114-9954/10/1015-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

Single Article

Update on the Office of Drug Safety at the US FDA – continuedsuch as medication guides and patient package inserts. • Disseminates important medication-error safetySocial scientists working in the DSCRS review studies information to the public, with collaboration of theon, for example, label comprehension by users and reviewing divisionspatient surveys to assess patient comprehension of drug • Develop new methodologies and tools in detectinginformation and drug use behaviour. signals for error prevention

Postmarketing surveillance involves surveillance of allReview of Risk Management Programmesmedication-error reports through MedWatch, USReview of risk management programmes is a Pharmacopeia and the Institute For Safe Medicationcollaborative process involving all parts of the ODS and Practices (~ 300 reports per month). A root causethe OND review divisions. DSRCS involvement in the analysis is conducted and then a recommendation onreview of such programmes includes: intervention strategies is forwarded to the review• Drug utilization analyses division within CDER. Premarketing surveillance begins• Pharmacoepidemiological analyses for each drug at the end of phase II studies and the• Patient package insert/medication guide review lodging of a new drug application. Staff at DMETs• Review of educational plans conduct a name analysis – which is a multi factorial• Review of surveys process that includes computer-assisted analysis.• Review of comprehension studies. Labelling and packaging are analysed, an overall risk

Role of DMETS evaluation is made and a written recommendation isprovided to the review division. DMETS looks for namesCommander Carol Holquist, director of DMETS, gavethat sound like/look like:an overview of this ODS division. The division is made• currently marketed drug namesup of three teams: the information technology team, the• drug names pending approvalmedication-error team and the project management• other medicinal productsteam. The information technology team provides• commonly used medical abbreviations, medicalvarious support and maintenance functions for the ODS.

procedures, and/or laboratory tests.The medication-error team:About one-third of names are rejected due to sound• Performs postmarketing surveillance and analysis of

alike/look alike issues or because the names areall medication errorsassociated with misleading promotional claims.• Performs premarketing safety analysis of all

Concluding her talk with what’s ahead for DMETS,proprietary names in CDERCommander Holquist summarised the challenges as• Conducts safety analyses of labelling for CDERissuing a guidance this year on proprietary names and(container, carton, prescribing information, patientpreparing a guidance on labelling and packaging andpackage inserts)another on medication-error prevention analysis.• Provides consultation to CDER on medication-error

800967276safety questions

2

0114-9954/10/1015-0002/$14.95 Adis © 2010 Springer International Publishing AG. All rights reservedReactions 21 Aug 2004 No. 1015