To compare groups of effective drugs, you need information on efficacy, safety, suitability and cost (Tables 3 and 4). Such tables can also be used when you study other diagnoses, or when looking for alternative P-drugs. For example, beta-blockers are used in hypertension, angina pectoris, migraine, glaucoma and arrhythmia. Benzodiazepines are used as hypnotic, anxiolytic and antiepileptic drugs.
Although there are many different settings in which drugs are selected, the criteria for selection are more or less universal. The WHO criteria for the selection of essential drugs are summarized in Box 2.
This column in Table 3 (Chapter 3) shows data on pharmacodynamics and pharmacokinetics. In order to be effective, the drug has to reach a minimum plasma concentration and the kinetic profile of the drug must allow for this with an easy dosage schedule. Kinetic data on the drug group as a whole may not be available as they are related to dosage form and product formulation, but in most cases general features can be listed. Kinetics should be compared on the grounds of Absorption, Distribution, Metabolism and Excretion (ADME factors, see Annex 1).
Box 2: Criteria for the selection of essential drugs (WHO)
Priority should be given to drugs of proven efficacy and safety, in order to meet the needs of the majority of the people. Unnecessary duplication of drugs and dosage forms should be avoided.
Only those drugs for which adequate scientific data are available from controlled clinical trials and/or epidemiological studies and for which evidence of performance in general use in a variety of settings has been obtained, should be selected. Newly released products should only be included if they have distinct advantages over products currently in use.
Each drug must meet adequate standards of quality, including when necessary bioavailability, and stability under the anticipated conditions of storage and use.
The international nonproprietary name (INN, generic name) of the drug should be used. This is the shortened scientific name based on the active ingredient. WHO has the responsibility for assigning and publishing INNs in English, French, Latin, Russian and Spanish.
The cost of treatment, and especially the cost/benefit ratio of a drug or a dosage form, is a major selection criterion.
Where two or more drugs appear to be similar, preference should be given to (1) drugs which have been most thoroughly investigated; (2) drugs with the most favourable pharmacokinetic properties; and (3) drugs for which reliable local manufacturing facilities exist.
Most essential drugs should be formulated as single compounds. Fixed-ratio combination products are only acceptable when the dosage of each ingredient meets the requirements of a defined population group and when the combination has a proven advantage over single compounds administered separately in therapeutic effect, safety, compliance or cost.
This column summarizes possible side effects and toxic effects. If possible, the incidence of frequent side effects and the safety margins should be listed. Almost all side effects are directly linked to the working mechanism of the drug, with the exception of allergic reactions.
Although the final check will only be made with the individual patient, some general aspects of suitability can be considered when selecting your P-drugs. Contraindications are related to patient conditions, such as other illnesses which make it impossible to use a P-drug that is otherwise effective and safe. A change in the physiology of your patient may influence the dynamics or kinetics of your P-drug: the required plasma levels may not be reached, or toxic side effects may occur at normal plasma concentrations. In pregnancy or lactation, the well-being of the child has to be considered. Interactions with food or other drugs can also strengthen or diminish the effect of a drug. A convenient dosage form or dosage schedule can have a strong impact on patient adherence to the treatment.
All these aspects should be taken into account when choosing a P-drug. For example, in the elderly and children drugs should be in convenient dosage forms, such as tablets or liquid formulations that are easy to handle. For urinary tract infections, some of your patients will be pregnant women in whom sulfonamides - a possible P-drug - are contraindicated in the third trimester. Anticipate this by choosing a second P-drug for urinary tract infections in this group of patients.
Cost of treatment
The cost of the treatment is always an important criterion, in both developed and developing countries, and whether it is covered by the state, an insurance company or directly by the patient. Cost is sometimes difficult to determine for a group of drugs, but you should always keep it in mind. Certain groups are definitely more expensive than others. Always look at the total cost of treatment rather than the cost per unit. The cost arguments really start counting when you choose between individual drugs.
The final choice between drug groups is your own. It needs practice, but making this choice on the basis of efficacy, safety, suitability and cost of treatment makes it easier. Sometimes you will not be able to select only one group, and will have to take two or three groups on to the next step.
Box 3: Efficacy, safety and cost
Efficacy: Most prescribers choose drugs on the grounds of efficacy, while side effects are only taken into consideration after they have been encountered. This means that too many patients are treated with a drug that is stronger or more sophisticated than necessary (e.g. the use of wide spectrum antibiotics for simple infections). Another problem is that your P-drug may score favourably on an aspect that is of little clinical relevance. Sometimes kinetic characteristics which are clinically of little importance are stressed to promote an expensive drug while many cheaper alternatives are available.
Safety: Each drug has side effects, even your P-drugs. Side effects are a major hazard in the industrialized world. It is estimated that up to 10% of hospital admissions are due to adverse drug reactions. Not all drug induced injury can be prevented, but much of it is caused by inappropriate selection or dosage of drugs, and you can prevent that. For many side effects, high risk groups can be distinguished. Often these are exactly the groups of patients you should always be very careful with: the elderly, children, pregnant women and those with kidney or liver disease.
Cost: Your ideal choice in terms of efficacy and safety may also be the most expensive drug, and in case of limited resources this may not be possible. Sometimes you will have to choose between treating a small number of patients with a very expensive drug, and treating a much larger number of patients with a drug which is less ideal but still acceptable. This is not an easy choice to make, but it is one which most prescribers will face. The conditions of health insurance and reimbursement schemes may also have to be considered. The best drug in terms of efficacy and safety may not (or only partially) be reimbursed; patients may request you to prescribe the reimbursed drug, rather than the best one. Where free distribution or reimbursement schemes do not exist, the patient will have to purchase the drug in a private pharmacy. When too many drugs are prescribed the patient may only buy some of them, or insufficient quantities. In these circumstances you should make sure that you only prescribe drugs that are really necessary, available and affordable. You, the prescriber, should decide which drugs are the most important, not the patient or the pharmacist.