Drug Safety 5 (Suppl. I): 137-140, 1990 0114-5916/90/0001-0137/$2.00/0 © ADIS Press Limited All rights reserved. DSSUP1784
Pharmacovigilance
The French System Rene Jean Royer
French National Committee for Pharmacovigilance, Centre Hospitalier Regional et Universitaire de Nancy, Nancy, France
Summary
The French system of drug surveillance (pharmacovigilance) is a combination of mandatory reporting and intensive hospital surveillance. The Regional Centres are decentralised but coordinated through a national network. An algorithm index is used to assess the relationship between drugs and adverse effects. The adverse reactions alert system is produced by the compilation and analysis of the cases entered in a data bank (8062 in 1988) and by the analysis of queries from general practitioners (20000 in 1988). The duties of the centres are also to provide information, analyse data and to improve the safe use of drugs.
Postmarketing surveillance of drugs is a major concern for the national regulatory authorities and pharmaceutical companies. Adverse effects of drugs are mostly unpredictable and of low frequency. Nowadays, because most of the national systems are essentially based on voluntary reporting, risk frequencies are underestimated. Epidemiological methods are proposed but their advantages are not clearly defined. The French system of drug surveillance (pharmacovigilance) is a combination of mandatory notification by practitioners and intensive hospital surveillance (Moore et al. 1985; Royer & Lagier 1986). The causal relationship between drugs and adverse effects is established by means of an algorithm index accepted by both public and private sectors of the system (Begaud et al. 1985; Dangoumau et al. 1978).
1. Pharmacovigilance in France
1.1 Regional Centres of Pharmacovigilance
France is divided into regions, each of which is supervised by at least one Regional Centre ofPhar-
macovigilance situated in a clinical pharmacology department or a Poison Control Centre. There are 30 regional centres, each with 3 to 6 physicians or pharmacists. On average, they cover 1.9 million inhabitants and 5520 doctors, of whom 1520 are private practitioners. The duty of each centre is as follows: • to collect and record adverse reaction reports and assess them in order to establish causal relationships • to provide information to doctors regarding the risks of various drugs, and to help set up a diagnosis of drug adverse effects • to conduct national inquiries on drug safety • to teach and to initiate research into pharmacovigilance. The continuous exchange of information with practitioners has increased the number of reponed cases and the number of queries, and helped to improve the safe use of drugs.
138
1.2 The Technical Committee of Pharmacovigilance The regional centres are not totally independent; they are linked in a national network coordinated by the Technical Committee, which includes all the regional centre directors and civil servants from the Ministry of Health and other concerned authorities. Every 2 months, an entire day is devoted to the analysis of data, producing the adverse reaction alerts, following up specific inquiries on a product and preparing reports for the National Committee. 1.3 The National Committee of Pharmacovigilance This consists of representatives of general practitioners, pharmacists, research centres and regional centre directors. The Committee's mandate is to analyse the reports and to give advice to the Ministry of Health for any decision to be made on drugs that could represent a danger to public health. The meetings are held at regular intervals, but can be convened at short notice for emergency cases.
2. Methods 2.1 Information and Internal Communication The adverse effects assessed by regional centres are entered into a national computerised data bank accessible to each centre and the Ministry of Health. In addition, all the centres and the ministry are linked together with an electronic mail or 'Minitel'. 2.2 Compulsory Notification by the Pharmaceutical Industry The decree of May 1984 obliges drug manufacturers to report any adverse effects to the National Committee at regular intervals. They also have to assess the adverse effects by following a prescribed method, since these cases are not routinely entered into the data bank.
Drug Safety 5 (Suppl. 1) 1990
2.3 Imputability (Causal Assessment) In France, both private and public sectors use the same method of imputability chosen for maximum sensitivity, at some cost to specificity (Begaud et al. 1985; Dangoumau et al. 1978). This method is used for the alert system, which independently considers each drug taken by a patient together with any data on record. When an alert is established, the data are reviewed in the context of the national data bank. The main advantage of this unique method is the use ofa common adverse drug reaction assessment system by all those involved in the pharmacovigilance programme. 2.4 National Inquiries A coordinating regional centre is chosen by the Technical Committee and, in conjunction with the marketing authority of the drug under scrutiny, studies all the reports held by the manufacturer and the regional centres. A risk frequency is evaluated in terms of the volume of sales or prescriptions, and a consensus is reached during a meeting held by the Ministry of Health with the various authorities. The file is submitted to the National Committee, which reaches a decision after consultation with the pharmaceutical company. 2.5 Queries to the Regional Centres The queries to the regional centres come mostly from general practitioners. Most of them (59%) concern patients for whom prescribing advice is needed (Castot et al. 1986). They deal with pregnancy (65%), drug interactions (12%), breastfeeding (8%), pharmacogenetics (2%) and paediatrics (1 %). Other contact with regional centres is with regard to notifications in which the adverse effects have not been adequately described or with regard to accidents which evidently are not drug related. An experimental study recorded questions on-line and searched for an alert signal by matching queries with recorded information (Begaud et al. 1987; Dangoumau et al. 1986). The results suggest that it is possible to detect new alert signals which do not appear in the analysis of the notifications or from the data bank.
139
Pharmacovigilance
20000 18000 16000 14000 12000 r-
r-
10000
.
en III en
8000
"
6000
~
4000
'0
r-
E ::>
z
2000 0 1973
74
•
75
• J 76
77
~~ 78
'-
79
80
81
'-
82
83
84
-
85
'-
86
87
88
Year Fig. 1. Annual number of notifications coming from regional centres and the pharmaceutical industry in France (_) compared with those in the UK (1lJj]).
3. Results The number of adverse effects reported in France continues to increase. All in all, the cases reported to authorities were 4093 in 1981 and 17500 in 1987, with 4093 and 7552 cases, respectively, coming from regional centres, i.e. 100% to 39.7% of the total (figs I and 2). Generally, notifications from the centres concern more serious effects than do those coming from industry. The number of queries from practitioners was 13774 in 1985 and had increased to 19000 in 1988. Each year the centres give about 200 graduate courses, write 100 technical articles and publish about 200 scientific studies. They have an annual congress and a 2-day workshop, with pharmaceutical industry personnel in charge of pharmacovigilance (table I). Between 1985 and 1987, the National Committee issued recommendations which have led to 24 modifications of data sheet information, 40 modifications to prescription regulations and 11 withdrawals from the market (table II). All the committee recommendations have been implemented by the Ministry of Health.
The cost of the system is not very high and is shared between the Ministry of Health, covering the national charges, i.e. the inquiries, computer costs, travelling expenses and documentation, and the university hospitals in which the centres are located and which pay for heating, mail, and tele10000 8000
. "
Pharmacovigilance
The French System Rene Jean Royer
French National Committee for Pharmacovigilance, Centre Hospitalier Regional et Universitaire de Nancy, Nancy, France
Summary
The French system of drug surveillance (pharmacovigilance) is a combination of mandatory reporting and intensive hospital surveillance. The Regional Centres are decentralised but coordinated through a national network. An algorithm index is used to assess the relationship between drugs and adverse effects. The adverse reactions alert system is produced by the compilation and analysis of the cases entered in a data bank (8062 in 1988) and by the analysis of queries from general practitioners (20000 in 1988). The duties of the centres are also to provide information, analyse data and to improve the safe use of drugs.
Postmarketing surveillance of drugs is a major concern for the national regulatory authorities and pharmaceutical companies. Adverse effects of drugs are mostly unpredictable and of low frequency. Nowadays, because most of the national systems are essentially based on voluntary reporting, risk frequencies are underestimated. Epidemiological methods are proposed but their advantages are not clearly defined. The French system of drug surveillance (pharmacovigilance) is a combination of mandatory notification by practitioners and intensive hospital surveillance (Moore et al. 1985; Royer & Lagier 1986). The causal relationship between drugs and adverse effects is established by means of an algorithm index accepted by both public and private sectors of the system (Begaud et al. 1985; Dangoumau et al. 1978).
1. Pharmacovigilance in France
1.1 Regional Centres of Pharmacovigilance
France is divided into regions, each of which is supervised by at least one Regional Centre ofPhar-
macovigilance situated in a clinical pharmacology department or a Poison Control Centre. There are 30 regional centres, each with 3 to 6 physicians or pharmacists. On average, they cover 1.9 million inhabitants and 5520 doctors, of whom 1520 are private practitioners. The duty of each centre is as follows: • to collect and record adverse reaction reports and assess them in order to establish causal relationships • to provide information to doctors regarding the risks of various drugs, and to help set up a diagnosis of drug adverse effects • to conduct national inquiries on drug safety • to teach and to initiate research into pharmacovigilance. The continuous exchange of information with practitioners has increased the number of reponed cases and the number of queries, and helped to improve the safe use of drugs.
138
1.2 The Technical Committee of Pharmacovigilance The regional centres are not totally independent; they are linked in a national network coordinated by the Technical Committee, which includes all the regional centre directors and civil servants from the Ministry of Health and other concerned authorities. Every 2 months, an entire day is devoted to the analysis of data, producing the adverse reaction alerts, following up specific inquiries on a product and preparing reports for the National Committee. 1.3 The National Committee of Pharmacovigilance This consists of representatives of general practitioners, pharmacists, research centres and regional centre directors. The Committee's mandate is to analyse the reports and to give advice to the Ministry of Health for any decision to be made on drugs that could represent a danger to public health. The meetings are held at regular intervals, but can be convened at short notice for emergency cases.
2. Methods 2.1 Information and Internal Communication The adverse effects assessed by regional centres are entered into a national computerised data bank accessible to each centre and the Ministry of Health. In addition, all the centres and the ministry are linked together with an electronic mail or 'Minitel'. 2.2 Compulsory Notification by the Pharmaceutical Industry The decree of May 1984 obliges drug manufacturers to report any adverse effects to the National Committee at regular intervals. They also have to assess the adverse effects by following a prescribed method, since these cases are not routinely entered into the data bank.
Drug Safety 5 (Suppl. 1) 1990
2.3 Imputability (Causal Assessment) In France, both private and public sectors use the same method of imputability chosen for maximum sensitivity, at some cost to specificity (Begaud et al. 1985; Dangoumau et al. 1978). This method is used for the alert system, which independently considers each drug taken by a patient together with any data on record. When an alert is established, the data are reviewed in the context of the national data bank. The main advantage of this unique method is the use ofa common adverse drug reaction assessment system by all those involved in the pharmacovigilance programme. 2.4 National Inquiries A coordinating regional centre is chosen by the Technical Committee and, in conjunction with the marketing authority of the drug under scrutiny, studies all the reports held by the manufacturer and the regional centres. A risk frequency is evaluated in terms of the volume of sales or prescriptions, and a consensus is reached during a meeting held by the Ministry of Health with the various authorities. The file is submitted to the National Committee, which reaches a decision after consultation with the pharmaceutical company. 2.5 Queries to the Regional Centres The queries to the regional centres come mostly from general practitioners. Most of them (59%) concern patients for whom prescribing advice is needed (Castot et al. 1986). They deal with pregnancy (65%), drug interactions (12%), breastfeeding (8%), pharmacogenetics (2%) and paediatrics (1 %). Other contact with regional centres is with regard to notifications in which the adverse effects have not been adequately described or with regard to accidents which evidently are not drug related. An experimental study recorded questions on-line and searched for an alert signal by matching queries with recorded information (Begaud et al. 1987; Dangoumau et al. 1986). The results suggest that it is possible to detect new alert signals which do not appear in the analysis of the notifications or from the data bank.
139
Pharmacovigilance
20000 18000 16000 14000 12000 r-
r-
10000
.
en III en
8000
"
6000
~
4000
'0
r-
E ::>
z
2000 0 1973
74
•
75
• J 76
77
~~ 78
'-
79
80
81
'-
82
83
84
-
85
'-
86
87
88
Year Fig. 1. Annual number of notifications coming from regional centres and the pharmaceutical industry in France (_) compared with those in the UK (1lJj]).
3. Results The number of adverse effects reported in France continues to increase. All in all, the cases reported to authorities were 4093 in 1981 and 17500 in 1987, with 4093 and 7552 cases, respectively, coming from regional centres, i.e. 100% to 39.7% of the total (figs I and 2). Generally, notifications from the centres concern more serious effects than do those coming from industry. The number of queries from practitioners was 13774 in 1985 and had increased to 19000 in 1988. Each year the centres give about 200 graduate courses, write 100 technical articles and publish about 200 scientific studies. They have an annual congress and a 2-day workshop, with pharmaceutical industry personnel in charge of pharmacovigilance (table I). Between 1985 and 1987, the National Committee issued recommendations which have led to 24 modifications of data sheet information, 40 modifications to prescription regulations and 11 withdrawals from the market (table II). All the committee recommendations have been implemented by the Ministry of Health.
The cost of the system is not very high and is shared between the Ministry of Health, covering the national charges, i.e. the inquiries, computer costs, travelling expenses and documentation, and the university hospitals in which the centres are located and which pay for heating, mail, and tele10000 8000
. "
