[Validation of a measurement scale: example of a French Adverse Drug Reactions Preventability Scale]. / Validation d'une échelle de mesure: exemple de l'échelle française d'évitabilité des effets indésirables médicamenteux.

Adverse drug reactions (ADRs) have been recognised as an important cause of hospital admission. Most of these drug-related admissions were expected ADRs and, thus, partly preventable. However, as far as we know, the assessment of the preventability of ADRs was addressed in only two studies performed in France. In contrast, several other studies have been performed, mainly in the USA, and using different methods of assessing preventability. None of these methods were clearly evaluated with regard to reproducibility, validity or relevance. The purpose of this study was to initiate the validation of a French preventability scale. Here, we propose the first two phases of validation: the content validity and reliability of the scale. A working group of pharmacovigilance experts has been specifically established for this purpose. The content validity was assessed by collecting items representative of preventability. The choice and the formulation of items and a proposal of a score (global and for each item) were adopted after the consensus of the experts. A definitive version of the ADR preventability scale was used for the assessment of reliability. During the second phase, experts independently tested the new scale from observations of ADRs (49 central nervous system haemorrhages with antivitamine K). The concordance of the experts' judgements was calculated using two statistical methods (Kappa statistic and correlation coefficient). The content validity phase was performed during several workshops where experts discussed the choice and formulation of the best items. We decided to construct a scale with a small number of items, allowing a rapid evaluation of the preventability of ADRs. On the basis of a global score, four categories of preventability of ADRs ("preventable", "potentially preventable", "unclassable", "not preventable" ADRs) were proposed. The agreement of experts regarding the global score was low, with a poor correlation coefficient value (coefficient interclass = 0.491). Classification of ADRs in the four categories by the experts showed discrepancies (Kappa = 0.1136). The preventability assessment using this scale was feasible, although poor concordance between the judges has raised some questions. Several experts found use of this scale difficult in terms of a clear understanding of the items, and found that two of them were redundant. We have oversimplified some items and revision of their formulation will be necessary. Moreover, most of ADR notifications were poorly documented, resulting in a frequent choice of an "unevaluable" item. This represented an important bias in the calculation of the global score. This experience suggests the need for further studies to improve this French ADR preventability scale and validate it in differing circumstances, in order to provide a useful tool to enhance the rational use of drugs.

Appraisal of the MedDRA conceptual structure for describing and grouping adverse drug reactions.

Computerised queries in spontaneous reporting systems for pharmacovigilance require reliable and reproducible coding of adverse drug reactions (ADRs). The aim of the Medical Dictionary for Regulatory Activities (MedDRA) terminology is to provide an internationally approved classification for efficient communication of ADR data between countries. Several studies have evaluated the domain completeness of MedDRA and whether encoded terms are coherent with physicians' original verbatim descriptions of the ADR. MedDRA terms are organised into five levels: system organ class (SOC), high level group terms (HLGTs), high level terms (HLTs), preferred terms (PTs) and low level terms (LLTs). Although terms may belong to different SOCs, no PT is related to more than one HLT within the same SOC. This hierarchical property ensures that terms cannot be counted twice in statistical studies, though it does not allow appropriate semantic grouping of PTs. For this purpose, special search categories (SSCs) [collections of PTs assembled from various SOCs] have been introduced in MedDRA to group terms with similar meanings. However, only a small number of categories are currently available and the criteria used to construct these categories have not been clarified. The objective of this work is to determine whether MedDRA contains the structural and terminological properties to group semantically linked adverse events in order to improve the performance of spontaneous reporting systems. Rossi Mori classifies terminological systems in three categories: first-generation systems, which represent terms as strings; second-generation systems, which dissect terminological phrases into a set of simpler terms; and third-generation systems, which provide advanced features to automatically retrieve the position of new terms in the classification and group sets of meaning-related terms. We applied Cimino's desiderata to show that MedDRA is not compatible with the properties of third-generation systems. Consequently, no tool can help for the automated positioning of new terms inside the hierarchy and SSCs have to be entered manually rather than automatically using the MedDRA files. One solution could be to link MedDRA to a third-generation system. This would allow the current MedDRA structure to be kept to ensure that end users have a common view on the same data and the addition of new computational properties to MedDRA.

Child overdose: the value of the French pharmacovigilance causality assessment method.

BACKGROUND: In France, the regional pharmacovigilance centres manage drug overdose as adverse drug reactions (ADRs) using the French ADR causality assessment method, and some poison control centres (e.g. in Paris) do likewise for the most serious cases. AIM: The aim of the study was to analyse and compare the chronological and semiological scores calculated with this method, in cases of drug overdose and ADRs in children recorded in the French pharmacovigilance ADR database. RESULTS: In total, 7963 cases were analysed. The distribution of semiological criteria in drug overdose and ADR cases differed significantly (G-test), with a similar result for chronological criteria (but to a lesser degree). CONCLUSION: The distinction of two types of criteria in the French ADR causality assessment method appears useful for analysing cases of drug overdose in children. This finding triggers a renewed interest in the use of this method of causality assessment of drug overdose in children, and possibly in adults.

[Pharmacologic criteria for medical substitution in opiate dependence]. / Critères pharmacologiques d'un médicament pour la substitution de la pharmacodépendance aux opiacés.

Our goal was to establish new pharmacological criteria for a drug to be used in the treatment of opioid dependence. We propose the following six pharmacodynamic and pharmacokinetic criteria: (i) the same pharmacodynamic properties as the drug being substituted; (ii) a long duration of action (minimum 24 hours, not requiring several daily doses) in order to prevent fluctuations in effect and especially withdrawal symptoms; (iii) few euphoric effects together with a minimal reinforcing effect for the drug itself and other drugs; (iv) oral or sublingual administration without any special affinity for other routes, especially the intravenous; (v) a New Drug Application (NDA) in this indication, after submission of a dossier including both clinical randomised comparative trials and security data; and (vi) compatibility with a socially satisfying quality of life. These criteria were applied to methadone, buprenorphine and other drugs that were proposed in the treatment of opioid dependence (such as morphine or codeine).