Safety surveillance

The Vaccine Adverse Event Reporting System (VAERS) is a national vaccine safety surveillance program co-sponsored by the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). VAERS collects and analyzes information from reports of adverse reactions after immunization. Anyone can report to VAERS, and reports are sent in by vaccine manufacturers, health care providers, and vaccine recipients and their parents or guardians. An example of the VAERS and instructions for completing the form are found in Appendix F. Any clinically significant adverse event that occurs after the administration of any vaccine should be reported. Individuals are encouraged to provide the information on the form even if the individual is uncertain if the event was related to the... 

IV Post-marketing safety surveillance undertaken for some drugs that are administered over particularly long periods of time (number of patients varies) Several... 

A case is a basic unit of drug safety surveillance. It is used to assure, to the greatest extent possible, the safety of approved drug products that are still in use. The basic unit of all postmarketing safety submissions is the adverse drug experience case , which is an individual adverse drug experience. 

Drug safety surveillance relies heavily on the techniques of pharmacoepidemiology which include ... 

Wise RP, Salive ME, Braun MM, Mootrey GT, Seward JF, Rider LG, Krause PR. Postlicensure safety surveillance for Varicella vaccine. JAMA 2000 284(10) 1271-9. 

Newly licensed POMs would not be considered for reclassification until the safety profile had been established. Drugs under intensive safety surveillance are indicated by a black triangle in the British National Formulary, which generally continues for approximately two years, dependent on whether any issues related to safety are discovered. 

As discussed in the chapter on Drug Surveillance, the safety surveillance mission is to implement the systematic review of spontaneous post-marketing data for proactive risk identification and assessment. In general, signal generation is done using clinical trials data, the medical literature, knowledge of class effects and spontaneous reports. 

There are two key approaches to safety surveillance. First, the intraproduct signaling, which seeks to identify changes in the overall AE pattern for specific products over time. This monitors selected AEs for a specific product over time to determine changes in the frequency and severity of AE reports. The other type of approach is the interproduct signaling which compares a specific product with all products in the database. 

Thus, it is clear that the safety surveillance process is an iterative one. It looks at multiple data sources, whether screening large regulatory databases, looking at company databases or looking at manufacturing Lot related AEs for patential problems. The surveillance process screens the data using both the intraproduct and the interproduct methods. The object is to identify topics for further review to develop case definition, to compile a case series and then to characterize that case series. 

The FDA s Spontaneous Reporting System (SRS) was in operation from 1968 to October 1997. The reports were transitioned to the AERS, which has been used from October 1997 to the present. A publicly released version can be purchased on a quarterly basis. It is a passive surveillance system where direct volunteer reporting accounts for 10% of reports from healthcare professionals and consumers. Ninety percent of reports in the FDA s postmarketing safety surveillance databases come from pharmaceutical companies, as they are mandated by regulations to report AEs that they receive. The combined SRS + AERS database currently contains more than 2.7 million reports and is growing rapidly, at about 465, 000 reports on an annual basis. The number of reports has more than doubled in the last 10 years and because the FDA is interested in serious, unlabeled reports, that has grown as a percentage of the total number of reports submitted to the FDA. 

The data mining output is similar to the safety surveillance output in that hypotheses are generated and these may need to be evaluated with additional quantitative analyses as appropriate, using the company database, stimulated reporting, enhanced surveillance or they may require the conduct of epidemiological studies. 

FDA new regulatory authority to require that drugs be demonstrated to be safe prior to commercialization. Since then, the scope of regulations and guidelines applicable to safety surveillance in the Unite States has become ex-tensive. ... 

Curran, C.F. Engle, C. An index of United States Federal Regulations and Guidelines which cover safety surveillance of drugs. Drug Inf. J. 1997, 31, 833-841. 

POSTMARKETING SAFETY SURVEILLANCE PHARMACOVIGILANCE AND PRODUCT RECALL INFORMATION SOURCES... 

Another component in postmarketing safety surveillance programs is the establishment of enforcement mechanisms to correct product problems. Errors can occur in drug production, packaging, and shipping that lead to adulteration, loss of potency, mislabeling, and other hazardous situations. Prompted by user reports or by results of their own internal quality control procedures, drug manufacturers routinely initiate voluntary product recalls. These actions typically involve limited quantities, or batches, which are cited in public notices of recalls published by the FDA. Product problems that represent serious and widespread threats to public health evoke another form of official publication Public Safety Alerts (entitled Public Safety Reports in Europe). 

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