Spontaneous reports pharmacovigilance

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. 

Spontaneous reports received by the Netherlands Pharmacovigilance Foundation between 1985 and 1999 have been analysed in a case-control study (15). Relative to other antidepressants, SSRIs were about twice as likely to be implicated in spontaneous reports of extrapyramidal reactions (OR = 2.2 95% Cl = 1.2, 3.9). The risk was greater in patients who were also taking neuroleptic drugs. This result suggests that SSRIs have a modestly increased risk of producing extrapyramidal reactions compared with other antidepressants. However, increased reporting can be influenced by increased awareness. In addition, no account was apparently taken in this study of relative prescription rates of different antidepressants. 

The cumulative incidence of hepatic adverse reactions associated with antidepressant treatment has been estimated through spontaneous reports to the Spanish Pharmacovigilance System (12). For classical tricyclic antidepressants and SSRIs the estimated rate of adverse hepatic reactions was 1.28-4.00 per 100 000 patient years. However, the rate with nefazodone was much higher (29 per 100 000 patient years). This report supports concerns that nefazodone may be more hepatotoxic than other antidepressants. Significant hepatic reactions to nefazodone are relatively rare but can be serious. 

The cumulative incidence of hepatic adverse reactions associated with antidepressant treatment has been estimated through spontaneous reports to the Spanish Pharmacovigilance System (12). For classical tricyclic... 

Example In follow-up of the receipt of 7 reports acute interstitial nephritis (AIN) by the Netherlands Pharmacovigilance Centre Lareb, the databank of World Health Organisation Collaborating Centre for International Drug Monitoring in Uppsala, Sweden (containing about 3.7 million spontaneous reports from more than 80 countries worldwide) was searched for cases of AIN. A total of 150 AIN cases with recorded proton-pump inhibitors (PPI) use was found. The proportionality of PPI use within the AIN cases was compared to the same in the rest of all 3.7 million reports, resulting in a ROR of 9.4 for omeprazole. 

In pharmacovigilance terms, the true frequency in a treated population in a specified period, if it was known, of an AE observed in a marketed product, would be considered an incidence. All too often, the frequency of reported AEs (definitely not the complete or even estimated numerator), perhaps weighed against known sales (scarcely a true denominator), is mistakenly used to calculate a rate and called an incidence . At best, such spontaneous reports data should be termed reports rates . 

Spontaneous reports have been the cornerstone of pharmacovigilance the central goal of these efforts is to develop scientifically strong indicators of ADR and accurately identify rare, serious, unusual, or unexpected ADRs as soon as possible after marketing launch. The basic principles of this activity include ... 

Post-marketing surveillance (PMS) Safety-related activity after a product is marketed. This process includes but is not limited to spontaneous ADR reports. Pharmacovigilance activities start before a product is marketed after marketing this term may be regarded as synonymous with pharmacovigilance and, nowadays, it is less frequently used (see p. 33). 

Pharmacovigilance in complementary and alternative medicine Pharmacovigilance in complementary and alternative medicine has attracted much attention worldwide. The awareness of the need for surveillance of adverse reactions to natural health products has stimulated the implementation of a reporting system for suspected adverse reaction in Italy From April 2002 to March 2007, 233 spontaneous reports of suspected adverse reactions to natural health products were collected. A large proportion of the suspected adverse reactions were serious hospitalization was reported in 35% of cases 6% reported life-threatening clinical events, and there were two fatal events. Most of the reported cases involved herbal products (66%) 21 reports were associated with 27 homeopathic preparations, most of which contained a mixture of substances 14 reports attributed the suspected reactions to products containing propolis. 

Veterinary Products Committee (VPC), Appraisal Panel for Human Suspected Adverse Reactions to Veterinary Medicines. Report of Human Suspected Adverse Reactions Received by the Veterinary Medicines Directorate from 1985 2001 and Findings of the Appraisal Panel from Meetings in 2001, Veterinary Medicines Directorate, Addlestone, 2002. K. N. Woodward, Veterinary Pharmacovigilance. Part 2. Veterinary pharmacovigilance in practice - the operation of a spontaneous reporting scheme in a European Union country - the UK, and schemes in other countries, J. Vet. Pharmacol. Ther., 2005, 28, 149-170. 

The ramifications of the thalidomide tragedy were many-fold but the key lesson for the development of pharmacovigilance was that active systems for detecting hazards are needed. Within a few years this had been taken forward with the introduction of voluntary (or spontaneous ) schemes for reporting of suspected adverse drug reactions (ADRs). These have stood the test of time as an alerting mechanism or early warning system and wiU be covered in more detail in Chapter 3. 

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