Spontaneous reporting system

At the present time, several countries have well-organised and experienced spontaneous reporting systems which contribute the bulk of ADE reports. In particular the United States, the United Kingdom, France and the Scandinavian countries have records going back several decades, and can claim to have in their possession data of reasonable quality. The section on p. 438 considers the various methods of causality assessment that are available and the data that are required for their application. 

Since then there have been many publications and reviews of the UK yellow card system and spontaneous reporting systems internationally.A summary of the capabilities and limitations of the method is given in Table 15.6. Although these have been discussed in the greatest detail over the past three decades, the obligations that exist for pharmaceutical companies in the reporting of adverse events to the regulatory authorities at both national and international levels make it essential to review them in this chapter. 

The term pharmacovigilance has now been adopted by all Member States for the activities involved in the study and evaluation of drug safety. Although pharmacovigilance covers a broad range of data collection methods, it is the spontaneous reporting systems sponsored by all European governments to which the term usually refers. 

Hypersensitivity reactions Serious hypersensitivity reactions have been rarely reported. One case of a life-threatening hypersensitivity reaction has been observed in a patient who received a single dose of sodium ferric gluconate complex in a postmarketing study. Three serious hypersensitivity reactions have been reported from the spontaneous reporting system. 

Under-reporting, reports of known reactions, and false causality attribution are the common criticisms of spontaneous reporting systems. Several studies show that workload, doubt about causal relationship, and doubt about whether it is worth reporting, are the common reasons for under-reporting. It follows that the attribution of causality is at least as good as any other careful clinical diagnosis, often after the exclusion of other disease (because doctors are less likely to report where there is doubt over causality) if under-reporting is due to workload, then there must be a real motivation to send a report. 

Bixler EO, Kales A, Brubaker BH, et al. Adverse reactions to benzodiazepine hypnotics spontaneous reporting systems. Pharmacology 1987 35 286-300. 

Wysowski DK, Barash D. Adverse behavioral reactions attributed to triazolam in the Food and Drug Administration s Spontaneous Reporting System. Arch Intern Med 1991 151 2003-2008. 

Anello C. Adverse behavior reactions attributed to triazolam in the FDA s Spontaneous Reporting System. Presented at the Pharmacological Drugs Advisory Committee Meeting, Washington, DC, September 1989. 

Wysowski DK, Green L. Serious adverse events in Norplant users reported to the Food and Drug Administration s MedWatch Spontaneous Reporting System. Obstet Gynecol 1995 85(4) 538-42. 

Breggin, P.R. Review of Behavioral Effects of Benzodiazepines with an Appendix on Drawing Scientific Conclusions from the FDA s Spontaneous Reporting System (MedWatch). In Brain Disabling Treatments in Psychiatry Drugs, Electroshock and the Role of the FDA. New York Springer Publishing, 1997. 

Standard textbooks and reviews spanning more than two decades as well as a variety of clinical studies confirm widespread recognition of BZ-induced behavioral abnormalities (Arana et al., 1991 Ashton, 1995 DiMascio et al., 1970 Kochansky et al., 1975 Maxmen, 1991 Rosenbaum et al., 1984 Shader et al., 1977). My 1998(b) review titled Analysis of Adverse Behavioral Effects of Benzodiazepines With a Discussion of Drawing Scientific Conclusions From the FDA s Spontaneous Reporting System probably remains one of the most complete reviews in the scientific literature. 

Evidence From the Food and Drug Administration s Spontaneous Reporting System... 

In 1987, Bixler et al. reviewed adverse reactions to BZs recorded in the FDA s spontaneous reporting system (SRS). They compared triazolam with two other BZs commonly used to induce sleep temazepam (Restoril) and flurazepam (Dalmane). They controlled the reports for the number and size of prescriptions for each of the three drugs. In regard to psychiatric adverse reactions, they found ... 

In the past, the FDA (1995) itself has been vocal about the limits of premarketing testing and about the importance of the supposedly less scientific postmarketing spontaneous reporting system (SRS) in which... 

In describing the impact of the MedWatch spontaneous reporting system (SRS), the FDA s Kessler (1993) said ... 

In each of the above three cases, the FDA decision to withdraw the drug had nothing to do with data generated by controlled clinical trials. The decision was based on reports made to the FDA s spontaneous reporting system and clinical reports in the scientific literature. 

The reports were sent to the FDA through its postmarketing spontaneous reporting system (SRS). The FDA representative projected the data onto a screen, but the data were not included in the transcript of the meeting. Although this issue was of overriding, central importance to its deliberations, the FDA advisory panel made no response at all to it. It was as if the data, so critical to their conclusions, had been presented to an empty room. 

As emphasized in chapter 13, the data once again confirm the importance of the spontaneous reporting system compared to controlled clinical trials in revealing dangerous adverse drug reactions, in this case violence and aggression. 

Bixler, E., Kales, A., Brubaker, B., Kales, J. (1987). Adverse reactions to benzodiazepine hypnotics Spontaneous reporting system. Pharmacology, 35, 286-300. 

Breggin, P. (1998b). Analysis of adverse behavioral effects of benzodiazepines with a discussion of drawing scientific conclusions from the FDA s spontaneous reporting system. Journal of Mind and Behavior 19, 2150. 

Food and Drug Administration. (1993, January 23). Summary of post-marketing reports on Prozac from the Spontaneous Reporting System of the FDA. Rockville, MD Author. 

Spigset, O. (1999). Adverse reactions of selective serotonin reuptake inhibitors Reports from Spontaneous Reporting System. Drug Safety, 20, 277-287. 

Wysowski, D., Barash, D. (1992, July). Use of spontaneous reporting system data. Archives of Internal Medicine, 152, 1528-1529. 

Given the perceived failure of spontaneous reporting systems and the paucity of ADR reports/ some institutions have instituted more active methods of ADR detection to supplement spontaneous reports. Medication order screening has become a common practice in U.S. hospitals. Manual chart reviews and audits and computer programs are used for retrospective/ concurrent/ and prospective medication utilization evaluation. Certain events often prompt an evaluation of a suspected adverse reaction. These include abrupt discontinuation of a medication/ abrupt dosage reduction/ orders for antidotes and emergency medications/ orders for special tests or serum drug concentration measurements/ and abnormal results from laboratory tests and medical procedures. 

Additional advantages of spontaneous reporting systems include the detection of extremely rare ADRs and ability to identify at-risk subgroups. In order to enhance the spontaneous reporting system approach, the FDA developed the MedWatch form. This form can be faxed to the agency (1-800-FDA-1078) or called in (l-800-FDA-1088). ° The forms also can be... 

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