ADROIT NOTES

COMMITTEE ON SAFETY	MEDICINES CONTROL
OF MEDICINES	AGENCY

ADVERSE DRUG REACTION INFORMATION SERVICE

GUIDANCE ON INTERPRETATION OF YELLOW CARD DATA

DRUG ANALYSIS PRINTS

Introduction
This sheet provides background information on the UK’s Yellow Card Adverse Drug Reaction (ADR) Reporting Scheme^{1 2}and gives advice on how to interpret information collected through the Scheme.

The Drug Analysis Print gives a complete list of all suspected adverse reactions reported through the Scheme to the Committee on Safety of Medicines (CSM)/Medicines Control Agency (MCA) in association with a named drug substance.

The Yellow Card Scheme
The Yellow Card Scheme was set up in 1964. It receives reports of suspected ADRs directly from doctors, dentists, coroners, pharmacists and indirectly through pharmaceutical companies¹. These are placed on a specialised computer system, Adverse Drug Reactions On-line Information Tracking (ADROIT)³ to facilitate rapid processing and analysis of reports.

Information collected through the Scheme is an important means of monitoring drug safety in normal clinical practice, by increasing knowledge about known adverse drug reactions and acting as an early warning system for the identification of previously unrecognised adverse reactions². Over the years many important early warnings of new adverse reactions have been identified through the Scheme. Information from ADA reports is used to assess causal relationships between drugs and reported reactions, and identify possible risk factors contributing to the occurrence of reactions such as age, underlying disease or drug interactions². Information from this and other sources provides evidence on whether changes need to be made in the use of a medicine to minimise risks and maximise benefits. Such changes may include restriction in use, reduction in dose, or special warnings and precautions. Rarely, a drug may need to be withdrawn from the market if risks outweigh benefits. The bulletin, ‘Current Problems in Pharmacovigilance’, which is distributed to all doctors, dentists. coroners and pharmacists three or four times a year, provides information on adverse drug reactions and gives advice on safe use of medicines. Previous issues of these bulletins are available upon request from the Medicines Control Agency, Pharmacovigilance Support Unit, Room 1001, Market Towers, 1 Nine Elms Lane, London SW8 5NQ.

Information provided on the Drug Analysis Print

The Drug Analysis Print:

lists all reactions reported to have occurred in association with the named suspect drug substance.

lists ALL reactions included on the original report. Because many reports contain more than one reaction, the total number of reactions usually exceeds the number of reports received for the drug. The total number of reactions and reports is shown at the end of the print. Each report relates to one patient.

lists all reactions reported for a particular drug substance irrespective of whether the reporter provided the approved drug substance name or a brand name of the substance. Brand names are shown on the print if they have been associated with at least one reported adverse reaction for the product.

includes data for reports where:

(a) the approved drug substance was given as a single constituent.
(b) the approved drug substance was used in combination (multi-constituent) products. It may not be possible to decide which (if any) of the drug substances in the combination products responsible for a particular reaction.

groups related adverse drug reaction terms in a hierarchical structure. The ‘preferred term’ (e.g. ventricular fibrillation) is grouped under the broader heading the "high level term" (e.g. ventricular arrhythmias). High level terms are contained within the "system organ class’ (e.g. cardiovascular disorders). The ‘preferred term’ is the most specific term on the Drug Analysis Print, while the ‘system organ class is the most general.

lists the number of deaths associated with each reaction when the reaction was considered to have contributed to the death.

shows the date on which the information was extracted from the computer and the date of the earliest reported reaction.

Guidance on interpretation of Drug Analysis Prints

Interpretation of the data in a Drug Analysis Print should take into account the following:

· The inclusion of a particular reaction on the print does not necessarily mean that it has been caused by the drug. Many factors have to be taken into account in assessing causal relationships including temporal association, the possible contribution of concomitant medication, and the underlying disease.

· Interpretation of reactions to medicines in cases where multiple other therapies are being used requires special care. This is particularly relevant for vaccines as many are administered in combination. In these circumstances it may be difficult to ascribe the cause of the reaction to an individual vaccine or drug.

· Certain reported reactions are conditions which often occur spontaneously. In these cases there may be a temporal relationship between the medicine and the reaction which is not necessarily causal. This applies particularly to vaccines.

· The number of reports received should not be used as a basis for determining the incidence of a reaction as neither the total number of reactions occurring, nor the number of patients using the drug is known.

· The number of prescriptions for a particular product can be used as a surrogate for drug use in order to calculate ADA reporting rates. However many factors influence the number of reports received and in most situations there is considerable ‘under-reporting’ of reactions. It has been estimated from various surveys that only 10-15% of serious ADRs are reported.

· ADR reporting rates are influenced by the seriousness of ADRs, their ease of recognition, the extent of use of a particular drug, and may be stimulated by promotion and publicity about a drug. Reporting tends to be highest for newly introduced medicines during the first one to two years on the market and then falls off over time.

· ~‘Numerical comparisons should not be made between reactions associated with different drugs on the basis of the data in these prints alone. Comparisons can be misleading unless they take account of variations in the level of reporting, the extent of use of the drugs, and a number of other confounding variables².

Publication
If you wish to copy or circulate either the print itself or information contained within it to others, please ensure that a copy of these notes for guidance are also provided. The CSM/MCA encourages the use of data from the Yellow Card Scheme in publications, but wishes to facilitate interpretation of the data. For this reason, we request that a copy of any proposed publication should be sent to the CSM/MCA for approval. We shall endeavour to respond to all requests quickly. Copies of the proposed manuscript and requests to quote data should be addressed to the Director, Post Licensing Division, Medicines Control Agency, Market Towers, 1 Nine Elms Lane, London SW8 5NQ.

Please support the Yellow Card Reporting Scheme by reporting suspected adverse drug reactions.

References
1. Rawlins M D Spontaneous reporting of adverse drug reactions I: The. data Br. J. Clin Pharmac. 1988:26:1-5.
2. Rawlins M D Spontaneous reporting of adverse drug reactions II: Uses Br. J. Clin Pharrnac. 1988; 26: 7-11.
3. Wood S M and Coulson R Adverse drug reactions on-line Information tracking (ADROIT) Pharmaceutical Medicine 1993; 7: 203-213.

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