FDA piloting safety studies of NMEs, revamping AERS, based on IOM recommendations.At a March 12 meeting of the Institute of Medicine--designed to follow up on FDA's implementation of the September 2006 landmark report, "The Future of Drug Safety: Promoting and Protecting the Health of the Public"--Center for Drugs officials said the agency is embarking on a pilot study of safety profiles of new molecular entities and is trying to revamp re·vamp
tr.v. re·vamped, re·vamp·ing, re·vamps
1. To patch up or restore; renovate.
2. To revise or reconstruct (a manuscript, for example).
3. To vamp (a shoe) anew.
n. its Adverse Event Reporting System (AERS AERS Adverse Event Reporting System (database of drug adverse reactions)
AERS Association of Educators in Radiological Sciences
AERS Army Educational Requirements System
AERS Acute Equine Respiratory Syndrome
AERS Access/Egress Roadway System II).
One step the IOM IOM
See: Index and Option Market recommended in the report was for FDA FDA
Food and Drug Administration
n.pr See Food and Drug Administration.
n.pr the abbreviation for the Food and Drug Administration. to bring in post-marketing safety experts during the approval process for new drugs--specifically to "assign joint authority to the Office of New Drugs and Office of Surveillance and Epidemiology for post-approval regulatory actions related to safety."
Ellis Unger, M.D., Acting Deputy Director for Science in the Office of Surveillance and Epidemiology, told the meeting at IOM headquarters in Washington that CDER CDER Center for Drug Evaluation and Research (US FDA)
CDER Centre de Développement des Energies Renouvelables (French)
CDER Client Development and Evaluation Report is "evaluating the feasibility of involving OSE OSE - Open Systems Environment staff earlier in reviews." Such staff members are already included in trade name reviews and risk minimization plans, he noted. "CDER is evaluating models for more significant involvement of OSE in post-marketing decision making."
However, he noted problems with IOM's recommendation that CDER review teams should not only "regularly and systematically" analyze post-market study results but also "make public their assessment of the significance of the results with regard to the integration of risk and benefit information." Much of that information, Unger said, is "predecisional" and its release "could have adverse public health impacts." Decisions about disclosure of postmarketing safety assessments "have to be made on a case-by-case basis."
CDER Director Steven Galson, M.D., told the meeting that the Center has initiated a pilot program to assess safety profiles of newly approved products. The program involves review of adverse events, data mining analyses, epidemiological data, postmarketing clinical trial data and periodic safety update reports to identify safety concerns for selected new molecular entities 18 months after approval. The purpose of the pilot is to "evaluate whether such a look back can identify potential safety concerns early in the product lifecycle Product lifecycle or product life cycle is the course of a product's sales and profits over time. The five stages of each product lifecycle are product development, introduction, growth, maturity and decline. ," he explained.
The need to better understand the factors that put some patients at higher risk of adverse events than others was emphasized by both Galson and FDA Deputy Commissioner Janet Woodcock woodcock: see snipe.
Any of five species (family Scolopacidae) of plump, sharp-billed migratory birds of damp, dense woodlands in North America, Europe, and Asia. . In discussing urgent research needs to help improve drug safety, Woodcock stated that many adverse events "result from individual sensitivity based on drug target status," and also noted "slow metabolizers are at risk for serious AEs." She noted that genetic tests becoming available to help identify patients at greater risk for adverse events, but that FDA needs outcome studies in populations and is exploring the creation of consortia to study drug metabolizing enzymes.
Galson reported that FDA is now collaborating on development of "a pharmacogenetic algorithm to help personalize dosing of warfarin warfarin (wôr`fərĭn), anticoagulant used to treat blood clots. In large doses it causes bleeding. Warfarin, mixed with bait, is used in rodent control.
Anticoagulant drug, marketed as Coumadin. ," and also working on a project to determine "how such factors as age, gender and weight might influence patient response to warfarin."
But the need for new research goes beyond efforts to individualize in·di·vid·u·al·ize
tr.v. in·di·vid·u·al·ized, in·di·vid·u·al·iz·ing, in·di·vid·u·al·iz·es
1. To give individuality to.
2. To consider or treat individually; particularize.
3. therapy, Woodcock said. Other critical research areas include toxicological studies in such areas as nano-scale products and drugs used in pregnancy; predictive safety biomarkers and additional research on common drug toxicities such as hepatotoxicity hepatotoxicity (hepˑ··tō·t ; the abuse potential of drugs; and the root causes of medication error medication error Malpractice An error in the type of medication administered or dosage. See Adverse effect, Error. , from drug names that look and sound alike to confusion about various drug strengths.
Among IOM's key recommendations was that CDER conduct a systematic, scientific review of the existing AERS system to "improve the generation of new safety signals and hypotheses," noted Gerald Dal Pan, M.D., Director of CDER's Office of Surveillance and Epidemiology.
To that end, FDA is working to update AERS II to improve and expand its functionalities and allow more efficient use of the database. FDA recently sponsored a two-day workshop on the creation of a Sentinel Network, at which ideas for integrating public and private sector post-market safety monitoring Safety Monitoring of a clinical trial is conducted by an independent physician with relevant expertise. This is accomplished by review of adverse event, immediately after they occur, with timely follow-up through resolution. systems were discussed. Also in response to IOM recommendations, CDER is working to expand its intramural intramural /in·tra·mu·ral/ (-mu´r'l) within the wall of an organ.
Occurring or situated within the walls of a cavity or organ. and extramural extramural /ex·tra·mu·ral/ (-mur´il) situated or occurring outside the wall of an organ or structure.
situated or occurring outside the wall of an organ or structure. programs by accessing additional databases, such as that of the Center for Medicare and Medicaid Medicare and Medicaid
U.S. government programs in effect since 1966. Medicare covers most people 65 or older and those with long-term disabilities. Part A, a hospital insurance plan, also pays for home health visits and hospice care. Services; hire additional epidemiologists and increase partnerships with other federal agencies.
The acquisition of more and better data from public and private sources is critical to the development of a 21st-century system for post-marketing drug safety, said Mark McClellan Mark Barr McClellan (born June 26, 1963) was sworn in as Administrator for the Centers for Medicare and Medicaid Services in the United States Department of Health and Human Services on March 25, 2004. of the Brookings-AEI Joint Center for Regulatory Studies at Stanford University Stanford University, at Stanford, Calif.; coeducational; chartered 1885, opened 1891 as Leland Stanford Junior Univ. (still the legal name). The original campus was designed by Frederick Law Olmsted. David Starr Jordan was its first president. and former FDA Commissioner.
McClellan noted the present AERS system "is improving, but most adverse events are missed or not captured in a timely, consistent manner." To create a more effective safety system, he said, FDA needs "a better mechanism for pooling relevant data from private and public electronic databases on prescription use and outcome," such as those that exist in private health plans, Medicare and the Veteran's Administration health system. Public-private collaboration in analyzing data would further strengthen the system, he said, adding that "methods and results should be made available for public comment."
Galson agreed that "transparency in decision-making is critical" for the future of a credible postmarket safety monitoring system. He noted that FDA is "improving our use of advisory committees" and issuing new guidance documents to "improve Advisory Committee operations by making them more consistent, transparent and predictable."
In addition, risk communication was a key issue in the IOM report and at the conference. Galson reported that FDA is establishing "a new advisory committee on communication to obtain input to improve the agency's communication policies and practices." That committee will include "patients and consumers as well as experts in risk and crisis communication." Further, FDA this year will begin to regularly publish a web-based newsletter containing summaries of the results of FDA post-marketing reviews, information on emergency safety issues and on recently approved products "to inform providers and encourage reporting of adverse events to FDA."
Woodcock noted that research is also needed in the area of risk communication, including "effective ways to convey risks in drug ads and prescriber communications." It is critical, she said, to learn "how to communicate effectively to change prescriber behaviors."
In any efforts to improve post-market drug monitoring and drug safety, an overriding issue is "resources, resources, resources," McClellan said. "More resources and greater technical capabilities at FDA are essential to carry out IOM recommendations successfully," he said. "Additional regulatory authorities, organizational change and better information are not sufficient, and in fact, require more resources." FDA must provide more clarity about its resource needs, he added, noting that FDA "is spending a lot now on safety in the health care system--and will be spending more."
By Rebecca Mashaw