Spontaneous reports

Szarfman A, Machado SG, O Neill RT. Use of screening algorithms and computer systems to efficiently signal higher-than-expected combinations of drugs and events in the U.S. FDA s spontaneous reports database. Drug Saf 2002 25 381-92... 

ADR reporting may be either voluntary or obligatory. Spontaneous reporting by health professionals is often favoured, since it is very difficult to make reporting compulsory. But in many countries, considerations of ethical responsibility and/or technical expediency have inclined governments to make reporting mandatory for the holders of marketing authorizations. 

The spontaneous report event is categorized as serious or nonserious, expected or unexpected ... 

Table 21.5 summarizes FDA reporting requirements for spontaneous reports in terms of how the case event is first submitted to the agency. The definitions of serious, unexpected, and so forth, are in 21 CFR 314.80(a) (CFR, 1994). 

Meaningful codes may or may not be needed for modem dictionaries. For example, the new Adverse Drag Reactions On-Line Information Tracking (ADROIT) dictionaries do not use meaningful codes, but rely on linkage of related terms and effective text processing. Where codes are considered necessary, they should be as short as possible (Westland, 1991). Whenever a system is used for AEs from the literature, spontaneous reports, clinical trials or a combination of these, the needs of the users of the system will influence the selection of the dictionary. 

The focus is on ADRs, which include all spontaneous reports and all drug-related clinical trial and literature reports. 

Fung, M., Thorton, A., Mazbeck, K., Wu, J.H., Hombuckle, K., and Muniz, E. (2001). Evaluation of the characteristics of safety withdrawal of premarketing prescription drugs from worldwide pharmaceutical markets—1960 to 1999. Drug Information J. 35 293-317. Goldman, S.A. (1998). Limitations and strengths of spontaneous reports data. Clin. Ther. 201 Supplement C, CAO-58. 

Because ARMS is a form of passive surveillance that is based on spontaneous reports, it has a number of limitations. Most importantly, it cannot establish a definitive, causal relationship between the ingestion of an incriminated substance and the occurrence of symptoms. Since people are exposed daily to a myriad of food ingredients, it is inherently difficult to attribute an adverse event to a specific food substance. Moreover, symptoms reported are often vague or general in nature. Other confounders, which were discussed by Bradstock et al. (1986), include ... 

Stem, R.S. and Bigby M., An expanded profile of cutaneous reactions to nonsteroidal antiinflammatory dmgs reports to a specialty-based system for spontaneous reporting of adverse reactions to drugs, JAMA, 252,1433-1437,1984. 

Strengthening the spontaneous reporting scheme via electronic reporting... 

Patients with bulimia are typically embarrassed by their binging and purging behaviors and therefore seldom spontaneously report them. In addition, their weight is usually within the normal to slightly obese range. As a result, BN does not command the immediate clinic attention of AN and is often a secret, hidden illness for many... 

The entire basis of medicine is, quite properly, moving from the art of medicine to the science of medicine, and the reporting of clinical events observed while a patient is receiving a drug should reflect this change of attitude. At the time of observation, apart possibly from a temporal relationship between the administration of a drug and the event, there may be no other evidence on which to base an attribution of causality. In these circumstances, it would be correct to term the observation an event and not a reaction, the latter term being strictly reserved for the situation in which a causal relationship has been reasonably established. The vast majority of spontaneous reports, apart from those... 

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. 

Table 15.6 Spontaneously reported adverse reactions in WHO database from EU countries...

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 absolute numbers of spontaneous reports relating to any particular clinical event are dependent on a number of fairly obvious factors. 

There are a number of situations in which spontaneous reporting is essentially inappropriate for the detection of ADEs. 

Much time and discussion has gone into this question over the past several years The c)mics would say that more is already being expected of spontaneous reporting than it can ever deliver, and that it has probably reached its limits. The more optimistic - or possibly the more naive - would say that improvements are possible and that we should set about achieving them. 

Anyone who has examined a few hundred spontaneous reports will know that there is great variability in both the quantity and the quality of their content. The reports range from the totally useless to excellent records of important clinical observations. In between, the great majority reflect the real dilemma faced by the reporting physician. Is the observation worth reporting or is it just an irrelevance Is this going to cause trouble for me for the company for the authorities for the patient How is it possible to judge potential causality ... 

Assuming that the quality of the input is maximal then improving the output will be dependent upon the analysis and evaluation of the data. Because the spontaneous report alone will seldom, if ever, contain sufficient information to determine causality satisfactorily, it is usually necessary to seek additional data which may be available from hospital records, laboratory investigations or post-mortem reports. It is highly desirable that comparable methods and formats of reporting should be used as widely as possible, particularly if international comparisons are to be made. A major benefit of formalised systems of causality assessment, which will be considered in greater detail later in this chapter, is the element of standardisation that is brought to the process of interpretation. 

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