FDA Drug Safety Initiative
Fact Sheet
Background
In November 2004 the Food and Drug Administration (FDA) announced a series of steps designed to strengthen and improve the management of drug safety issues. Over the last two years the Agency has led an aggressive effort to improve the management of important drug safety issues. Safety has been, and continues to be, a central focus of our regulatory work. This effort is of vital importance to the health of the Unites States public and to the mission of FDA.
Physician & Patient Information
Each year, approximately 300,000 preventable adverse events occur in hospitals in this country, many as a result of confusing medical information. FDA has made significant strides in reducing the complexity of prescription drug information, making it more useful for physicians and their patients.
- A major revision to the format of prescription drug information, commonly called the package insert, to give healthcare professionals clear and concise prescribing information. In an effort to manage the risks of medication use and reduce medical errors, the newly designed package insert provides the most up-to-date information in an easy-to-read format that draws physician and patient attention to the most important pieces of drug information before a product is prescribed.
- The development of a new standardized electronic drug label will allow physicians and patients access to the most up to date information about a prescription drug through the DailyMed website, developed in collaboration with the National Library of Medicine. The DailyMed is making up-to-date information about FDA-regulated products widely available on the Internet at no cost (http://dailymed.nlm.nih.gov). To date the agency has provided NLM with more than 1,000 labels in this format.
- Issuing Public Health Notices to physicians in order to inform them of important changes to safety information on high-profile drug products.
Restructuring the Center for Drug Evaluation & Research (CDER)
Currently, more than 50 percent of CDER's resources are dedicated to drug safety. Over the past year, CDER has reorganized to create a more efficient and effective environment to further a cross-Center approach to drug safety.
- Dr. Gerald Dal Pan was selected from a strong field of candidates as part of a nationwide search to lead the agency's post-marketing drug safety program. As the Director of the Office of Surveillance and Epidemiology (OSE), formerly the Office of Drug Safety, Dal Pan reports directly to the Center Director.Dr. Dal Pan's team works closely with the Office of New Drugs (OND) in the ongoing post-marketing risk assessment of all drug products. (October 2005)
- Dr. Paul Seligman was appointed Associate Center Director for Safety Policy and Communication – a newly created position to provide a cross-Center focus for drug-safety related communications to the health care community and the public. Some consolidation of risk communication efforts will ensure efficiency and consistency of FDA's important public health messages. (April 2006)
- Since 2004, the agency has increased the staffing dedicated to the post-marketing safety program by almost 25 percent (94 to 132 FTE's) to ensure the OSE has equal representation in regulatory decisions related to post-marketing safety.
Enhancing the Culture of Safety in CDER
In 2003, CDER developed and administered the “CDER Culture Survey,” an in-depth, multi-dimensional assessment of employees' diverse perceptions, opinions, and work place productivity and satisfaction. While there were areas of the survey that indicated opportunities for broad improvements across the Center, overall the culture of CDER rated consistently higher than benchmarks in other government organizations and consistently equal to or higher than private industry. (69% favorable overall satisfaction compared to a 46% for other government organizations and 57% private-sector.)
CDER management has been addressing the issues raised by the survey. The various efforts begun include:
- The organization of a Process Improvement Team (PIT) located in the Office of New Drugs (OND) devoted to the topic of post-marketing safety. This team, in consultation with experts in OSE, has been working for more than a year to improve the review of post-marketing safety information by and communication between OND and OSE. As a result of this team's approach there is strengthened communication with regular meetings between the drug review divisions and OSE. In addition, the group has identified expert medical and regulatory staff in each review division responsible for post-marketing safety coordination.
- FDA implemented a pilot program for adjudicating differences of professional opinion. This new Manual of Policies and Procedures (MaPP) entitled, Documenting Differing Professional Opinions and Dispute Resolution – Pilot Program,” provides procedures for CDER staff to express their differing professional opinions concerning regulatory actions or policy decisions with significant public health impacts in instances when the normal procedures for resolving disputes are not sufficient.
Creation of the Drug Safety Board
To further enhance the management of drug safety issues, FDA established a Drug Safety Oversight Board (DSB). The primary objectives for the DSB are to provide oversight and advice to CDER leadership on the management of important drug safety issues and to manage the flow of emerging safety information to healthcare professionals and patients. Over the past two years, the Board has conducted timely and comprehensive evaluations of drug safety concerns and assisted FDA in ensuring that safe and effective drugs are available for patients by:
- Conducting nine meetings (5 in 2005, 4 in 2006) to discuss various drug safety issues including actions on the Fentanyl Transdermal Patch and Palladone, as well as discussion of issues related to the safe use of opioids in complex drug delivery systems such as extended release products.
- Provided advice concerning early communication about emerging drug safety issues. See Enhanced Risk Communication Efforts below.
- Improving Communication about Emerging Drug Safety Issues.
- Published 81 Healthcare Professional Sheets (44 in 2005, 37 in 2006)
- Published 79 Patient Information Sheets (41 in 2005, 38 in 2006)
- Published 47 Public Health Advisories (16 in 2005, 31 in 2006)
- A formal physician survey will be conducted in the fall of 2006.
Enhancing Risk Communication Efforts
In conjunction with the DSB, the FDA has launched an effort to establish an ongoing evaluation program for risk communication efforts. The agency is in the process of soliciting feedback from physicians, pharmacists and consumers to help define a clear approach moving forward.
- Several DSB meetings have focused on a discussion of the factors
when deciding whether to notify the public about an important emerging drug
safety concern. To assist the discussion, FDA staff briefed the Board on
recent actions taken on emerging drug safety issues and the Board members
then discussed and commented on general criteria to guide decisions on communicating
future emerging safety concerns.
- FDA held a public hearing on the current risk communication strategies for human drugs. The purpose of the hearing was to solicit input form the public about communications on drug safety issues.
- Since the announcement of the drug safety initiative, FDA has held 31 advisory committee meetings (14 focused on risk or safety and 17 focused on the safety and efficacy of new drug applications) to discuss complex drug safety and risk management issues.
- In March 2005, FDA issued three final guidance documents to help develop ways and improve methods to assess and monitor the risks associated with drugs and biological products in clinical development and general use.
Partnerships through the Critical Path Initiative
The Critical Path Initiative is the FDA's premier initiative to modernize the drug development process. Modernizing the medical product development sciences will create new opportunities to improve product safety by strengthening our postmarketing surveillance of adverse events and employing new fields of science (genomics, proteomics, and related disciplines, as well as bioinformatics) to improve scientific understanding and prevention of safety problems. The agency has entered into a number of partnerships to develop tools that will enhance our efforts in improving drug safety.
- Cardiovascular Drug Safety and Biomarker Research Program -- Through collaboration with the Critical Path Institute (C-Path) and the University of Utah, the FDA is working to establish an evidence-based framework for determining the clinical utility of cardiovascular biomarkers, including genetic variants that determine the anticoagulation response to warfarin —a drug with a wide range of efficacy in individuals that could drug that may lead to severe consequences of under- or over-dosing.
- Genetic Basis of Adverse Events -- The FDA is in discussion with several NIH institutes and other entities about the applied research that is needed to explain the genetic basis of adverse events to improve safety profiles of compounds in pre-clinical and clinical development and drugs in the marketplace. Ultimately, the goal will be to establish a network to share information among key stakeholders. Five NIH institutes, (NIGMS, NHGRI, NHLBI, NIDDK, and NIH) along with FDA representatives are developing an agenda for a workshop on the Genetic Basis of Adverse Drug Reactions to be held on December 11-12, 2006. In collaboration with the Pharmaceutical Biomedical Research Consortium (PBRC).
- Predictive Safety Testing Consortium -- FDA is providing scientific and strategic input to this collaboration between the C-Path Institute and 14 pharmaceutical company partners to validate preclinical (genomic) biomarkers of toxicity to use as experimental systems to test for the possibility of toxicity in humans. A particularly innovative aspect of this consortium will be the sharing of biomarkers for cross evaluation by other members of the consortium. These companies have agreed to share data assays about preclinical and clinical genomic, proteomic and metabolomic biomarkers of drug-induced nephrotoxicity, hepatotoxicity, vascular injury and genotoxic and non-genotoxic carcinogenicity.
- Severe Adverse Events Consortium -- FDA is acting in a scientific advisory role, providing guidance on the establishment of a Severe Adverse Events (SAEs) Consortium. It is hoped that this consortium, made up of representatives from public, private, non-profit entities, and patient advocates, will help (1) identify and qualify biomarkers for adverse events, including pharmacogenetic markers and identifiers; (2) leverage/establish appropriate databases and repositories; (3) coordinate the development of common research platforms, nomenclature, and standards; and (4) establish effective intellectual property and data-pooling strategies.
- Identify Indicators of Cardiac Toxicity: ECG Warehouse -- FDA has partnered with Mortara Instruments Inc., to design and build a virtual ECG Warehouse to hold the more than 180,000 ECGs submitted to the Agency obtained from clinical trials. It is envisioned that such a database will facilitate additional review and research and aid in the development of evaluative tools that can be used in drug development and clinical decision making. In a second phase to this effort, FDA and the Duke Clinical Research Institute (DCRI) are developing a collaborative consortium with members of academia, patient advocacy, other government and non-profits and industry partners to coordinate and support a variety of research projects involving ECGs obtained in clinical trials.
Development of Electronic Health Information Architecture
FDA is working to develop data standards and processes that will lead to more efficient and timely sharing of important drug safety information.
- Recently revised regulations require drug makers to submit to FDA prescribing and product information (i.e., the package insert or label) in a structured product labeling (SPL) format. Using embedded computer tags, the prescribing and product information in the SPL format can be electronically managed, allowing a user to search for specific information on a drug label including product names, indications, dosage and administration, warnings, description of drug product, active and inactive ingredients. With this information, physicians will be able to quickly search and access specific information they need before prescribing a treatment, resulting in fewer prescribing errors and better informed decision making.
- FDA is improving the Adverse Event Reporting System (AERS); a computerized information database that supports the Agency's post-marketing safety surveillance.
- FDA has developed plans for a replacement web-accessible computer system that will include the addition of signal detection and tracking tools, to allow safety reviewers to more efficiently and effectively identify and track safety signals from the increasing number of adverse event reports in the system. AERS II will also be web-based, which will decrease maintenance costs, allow more efficient updates, and will permit its use from remote locations as needed.
- FDA is developing a standard adverse event reporting form to be used across all centers that can be submitted online. Web-based submission of adverse event reports permits more timely receipt and evaluation at considerable cost savings for us and industry. Our initiative to encourage electronic reports continues to make progress and remains a high priority.
- FDA has proposed a new regulation that would require drug companies to electronically submit detailed information about the drugs they make and about where the drugs are made. If finalized, this rule will lead to an electronic searchable database for all drugs which will improve the quality and completeness of the drug product information that FDA receives and manages. An accurate, up-to-date inventory of drugs on the market make it easier for us to respond to drug emergencies such as recalls and drug shortages.
