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close this bookThe Use of Essential Drugs: Eight report of the WHO Expert Committee (WHO - OMS, 1998, 84 p.)
View the document(introduction...)
View the documentWHO Expert Committee on the Use of Essential Drugs - Geneva, 1-5 December 1997
View the document1. Introduction
View the document2. Guidelines for establishing a national programme for essential drugs
View the document3. Criteria for the selection of essential drugs
View the document4. Guidelines for the selection of pharmaceutical dosage forms
Open this folder and view contents5. Quality assurance
Open this folder and view contents6. Reserve anti-infective agents and monitoring of resistance
View the document7. Applications of the essential drugs concept
Open this folder and view contents8. Essential drugs and primary health care
View the document9. Drug donations
View the document10. Post-registration drug studies
Open this folder and view contents11. Research and development
View the document12. Nomenclature
View the document13. Drug information and educational activities
View the document14. Selection and updating of lists of essential drugs
View the document15. Model List of Essential Drugs (tenth list)
View the document16. Considerations and changes made in revising the model list
View the document17. Glossary of terms used in the report
View the documentAcknowledgement
View the documentReferences
View the documentAnnex 1. Application form for inclusion in the Model List of Essential Drugs1
View the documentSelected WHO publications of related interest
View the documentBack Cover

10. Post-registration drug studies

Clinical studies for the development of new drugs take place, for the most part, in major medical centres in developed countries, with extensive facilities and highly trained staff. The patients entering the clinical trials in these centres will usually have received full medical evaluations.

Certain groups of patients such as pregnant women, young children, old people and ethnic groups will usually have been excluded from the trials. For this reason, the patients receiving the new drug prior to registration will not represent the full range of patients who will receive the drug after registration. In addition, the genetic and environmental factors influencing populations in other parts of the world may differ from those that characterize the populations in which the drug was studied and may cause differences in population dose-response relationships.

Little is known about the clinical consequences of different prescribing patterns between countries or between regions within a country. There are few systematic and comprehensive data on the use of drugs after they have been marketed but it is recognized that they are often not used to their full potential or in accordance with generally accepted criteria. Moreover, data on overdose effects and uncommon or longer-term adverse effects are usually not available at the time of registration. It is important, whenever feasible, to quantify these risks in order to identify the safest available products and to remove from the market those that are unacceptably dangerous. Such information is essential for rational drug selection.

Other information that can be obtained when a drug is used in practice relates to unanticipated uses discovered when the drug is given to patients with both the accepted indication and another illness. Furthermore, when used in practice, a drug may fail to produce the benefit that was expected on the basis of the pre-registration studies. This may be because the results of the pre-registration clinical trials cannot be applied to the entire population of patients with the indication for the drug or because the dosage form being used contains less than the labelled amount of the drug or contains the labelled amount, but not in a bioavailable form. These latter factors could result from poor manufacturing practices or from counterfeiting of legitimate dosage forms.

In order to obtain all the information needed for rational use of essential drugs, post-registration drug surveillance or surveys are needed.

Depending on their purpose and the facilities available, drug surveys can be carried out at various levels. Their value is enhanced by using standard procedures (common drug classification systems and units of measurement) in different regions and countries. These procedures should be used to provide data on all relevant drugs in a particular therapeutic class, paying attention to both cost and quantities prescribed, and taking differences in therapeutic practice into consideration.

The main purpose of drug surveys is to quantify present usage and estimate future demands. Studies can be designed simply to quantify the drug inventory only or to evaluate drug use. Data can also be used: (a) to measure the effects of informational and regulatory measures, price policy, etc.; (b) to define areas for further investigation of the absolute and relative efficacy and safety of drug therapy; (c) to aid in the determination of benefit/risk ratios and cost-effectiveness; and (d) when properly interpreted, to indicate the overuse, underuse or misuse of individual drugs or therapeutic classes of drugs.

Many drug regulatory authorities have recognized the value of post-marketing surveillance and the need for sustained international surveillance schemes. For many years the WHO Collaborating Centre on International Drug Monitoring has collated the reports of national monitoring schemes based on spontaneous notification by health professionals. Originally the programme included only countries with highly evolved regulatory agencies, where its main use was for generating signals of possible adverse drug reactions and for confirming cases. Currently the Collaborating Centre is attracting many developing countries which are in the process of establishing national drug policies. WHO is collaborating closely with the Council for International Organizations of Medical Sciences to promote epidemiologically based methods of monitoring.

The ability of most developing countries to carry out studies using such methods is limited by cost and the need for skills in pharmacoepidemiology. Nevertheless, when concern arises over the safety of a drug used exclusively for a tropical disease, the need for post-marketing surveillance is as great as in any other situation. Such a matter is already being addressed by WHO in the instance of the use of ivermectin in community-based mass treatment programmes for onchocerciasis. Such surveillance may also require the establishment of special reporting facilities and small follow-up studies of people exposed to specific drugs may be necessary.

If the detection of longer-term adverse sequelae to drug use is to become more efficient, reliable methods of linking prescribing information to hospital records will need to be more widely introduced. This, in turn, will require a means of assuring the confidentiality of personal information. Until these methods are developed, the application of epidemiological principles to the assessment of drug-induced effects will remain difficult to explore. WHO possesses the appropriate consultative capacity to promote debate of the issues, to promote the most suitable methods, and to monitor the results of their application.

These principles apply not only to the detection and assessment of adverse drug effects but to all other indicators of drug performance. In particular, access to microbiological reference laboratories is essential for the rational use of the expensive reserve antimicrobials.

The opportunities to advance therapeutics through post-registration drug studies will be only partially utilized until all health care professionals accept their responsibility to report on the effects of drugs in actual use.