Reactions 1015 - 21 Aug 2004
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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 interactive panel discussion on the structure and function of the new Office of Drug Safety (ODS) and some of the activities in which this office has recently been engaged in. Delegates heard about safety signal detection/data-mining initiatives, drug-induced liver-injury, developments in assessing risk management plans and medication-error issues.
Organisation of the ODS The panel chairman, Dr Paul Seligman, started with an introduction to the organisation of the ODS. The ODS was created in 2002 from the former Office of Postmarketing Drug Risk Assessment. The ODS is located under a new "super" office, the Office of Pharmacoepidemiology and Statistical Science headed by Dr Seligman. This office is part of the Center for Drug Evaluation and Research (CDER), which in turn is part of the US FDA. The ODS is now responsible for the MedWatch programme, which was formerly with the Office of Training and Communications, and for the patient labelling and risk communication functions, formerly with the Division of Drug Marketing, Advertising and Communications. The ODS consists of three divisions: • Division of Drug Risk Evaluation (DDRE) • Division of Surveillance, Research and Communication Support (DSRCS) • Division of Medication Errors and Technical Support (DMETS)
Activities at DDRE Dr Mark Avigan, who has been director of DDRE for a little less than a year, presented an overview of the division’s activities. Postmarketing, DDRE is involved with safety signal detection and risk evaluation, epidemiological risk assessments and phase IV study design. Pre- and periapproval DDRE staff assess proposed risk management plans and they have safety conferences with OND staff to discuss product labelling and plans for postmarketing monitoring/evaluation. According to Dr Avigan, in 2003, the DDRE undertook 670 consults including consults to the CDER’s new Office of Therapeutic Biologics. In the same year, DDRE also undertook safety reviews for agents granted paediatric exclusivity, co-authored the proposed risk management plan reviews with other ODS divisions and made presentations at a number of ODS and OND-sponsored FDA Advisory Committees. Safety signal detection for all marketed drug products is the primary role of the safety evaluators. They work closely with medical reviewers at the OND so that potential safety signals are placed in the context of existing knowledge about the drugs in question from the preclinical and clinical development phases. The epidemiologists review phase IV study protocols and evaluate various postmarketing surveillance tools that may be incorporated into risk management strategies, such as patient registries and restricted distribution systems. They estimate the public health impact of safety signals by evaluating data from the Adverse Event Reporting System (AERS) Database, which contains over 3 million adverse event reports, and data from international sources such as the WHO database, the EMEA, clinical study databases and the published
literature. A safety signal work-up involves development of case series, calculation of adverse event reporting rates and implementation of observational studies such as pharmacoepidemiological safety studies, registries and surveys. Whether postmarketing study is undertaken depends on the risk of the event, its severity, the population at risk and whether it involves medical errors and drug-drug interactions.
Specific DDRE Initiatives According to Dr Avigan, the DDRE is undertaking a data-mining initiative in order to enhance signal detection in the AERS database. DDRE has a cooperative research and development agreement with Lincoln Technologies to develop "Web Visual Data Mining Environment" (Web VDME). The goals are to create a web-based desktop software tool for safety evaluators and epidemiologists to enhance efficiency of signal detection/evaluation, to determine appropriate applications of the system and to optimise the system’s user friendliness and critical data-links. Web VDME is currently being piloted by DDRE safety evaluators and epidemiologists as a part of safety surveillance and evaluation activities. Another area of specific interest to the DDRE is drug-induced liver injury. Specific goals include: improving the postmarketing surveillance and characterisation of drug-induced liver injury; and development of consistent approaches to evaluate the hepatotoxic risk of drugs both pre- and postmarketing. In summing up, Dr Avigan said that the most important challenges for the DDRE were to recognize new drug-related safety issues in a timely manner and to evaluate risks that are of a public health concern throughout the lifecycle of a product.
Current Functions of the DSCRS The Director of the DSRCS, Dr Gerald Dal Pan, outlined the current functions of his division as the acquisition, analysis, maintenance of relevant data to support ODS and CDER functions, risk communication to both patients and healthcare professionals and involvement in risk management programmes. On the data front, the DSCRS provides support and management for the AERS database. It also maintains contracts with drug utilization databases used by the ODS.
MedWatch and Consumer Information The DSCRS actively promotes MedWatch by educating healthcare professionals about the need to report adverse events. The DSCRS uses MedWatch to disseminate risk information both directly on the website and by using listserv e-mail alerts. MedWatch website postings by the DSCRS include: safety alerts (Dear Doctor/Healthcare Provider Letters describing important safety labelling changes; class I recalls; public health advisories; drug withdrawals); and monthly summaries of safety labelling changes. The DSCRS oversees consumer information activities
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Reactions 21 Aug 2004 No. 1015
Single Article
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Update on the Office of Drug Safety at the US FDA – continued such as medication guides and patient package inserts. • Disseminates important medication-error Social scientists working in the DSCRS review studies on, for example, label comprehension by users and patient surveys to assess patient comprehension of drug information and drug use behaviour.
Review of Risk Management Programmes Review of risk management programmes is a collaborative process involving all parts of the ODS and the OND review divisions. DSRCS involvement in the review of such programmes includes: • Drug utilization analyses • Pharmacoepidemiological analyses • Patient package insert/medication guide review • Review of educational plans • Review of surveys • Review of comprehension studies.
Role of DMETS Commander Carol Holquist, director of DMETS, gave an overview of this ODS division. The division is made up of three teams: the information technology team, the medication-error team and the project management team. The information technology team provides various support and maintenance functions for the ODS. The medication-error team: • Performs postmarketing surveillance and analysis of all medication errors • Performs premarketing safety analysis of all proprietary names in CDER • Conducts safety analyses of labelling for CDER (container, carton, prescribing information, patient package inserts) • Provides consultation to CDER on medication-error safety questions
Reactions 21 Aug 2004 No. 1015
safety information to the public, with collaboration of the reviewing divisions • Develop new methodologies and tools in detecting signals for error prevention Postmarketing surveillance involves surveillance of all medication-error reports through MedWatch, US Pharmacopeia and the Institute For Safe Medication Practices (~ 300 reports per month). A root cause analysis is conducted and then a recommendation on intervention strategies is forwarded to the review division within CDER. Premarketing surveillance begins for each drug at the end of phase II studies and the lodging of a new drug application. Staff at DMETs conduct a name analysis – which is a multi factorial process that includes computer-assisted analysis. Labelling and packaging are analysed, an overall risk evaluation is made and a written recommendation is provided to the review division. DMETS looks for names that sound like/look like: • currently marketed drug names • drug names pending approval • other medicinal products • commonly used medical abbreviations, medical procedures, and/or laboratory tests. About one-third of names are rejected due to sound alike/look alike issues or because the names are associated with misleading promotional claims. Concluding her talk with what’s ahead for DMETS, Commander Holquist summarised the challenges as issuing a guidance this year on proprietary names and preparing a guidance on labelling and packaging and another on medication-error prevention analysis. 800967276
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