Pharmacoepidemology: An answer to drug safety

Pharmacoepidemology: An answer to drug safety

It is a new bridge of science drawn from the disciplines of pharmacology, therapeutic epidemiology and statistics, says K Satyanaryanan

Pharmaceuticals provide important benefits to the healthy and sick people. With the increasing life expectancy large number of people are exposed to multiple drugs for longer period of time. Drugs are also risky and have the potential to cause harm. The balance between benefits and risk of drugs is undoubtedly healthy. Pharmacoepidemiology offers a methodology and knowledge to increase the health benefit of drugs and to reduce their risks. The study and practice of pharmacoepidemiology is gaining momentum in North America and Europe and other developed countries in the world.

Aim and definition

Pharmacoepidemiology is the study of drugs as determinant of health and disease in the general unselected population. Incorporating the science of measuring drug mediated health events in large, unselected well-defined population it links exposure and the outcome in term of the therapeutic gain, length and quality of life or adverse events for any appropriate sub groups in any selected drug. Port and Hartzeema define the discipline as ‘The application of epidemiological knowledge, methods and reasoning to the effects (beneficial and adverse) and use drugs in human population.’ It is a new bridge of science drawn from the disciplines of pharmacology, therapeutic epidemiology and statistics. The questions that pharmacoepidemiology attempts answer or which it position to other disciplines can help us in defining the interest and boundaries of this field.

The examples of problems addressed by pharmacoepidemiology are: Are there difference in the number of hypertensive people diagnosed and treated among different population? What is the impact on cardiocerebrovacular morbidity of such differences? How much of the past years decline in coronary heart disease can be accounted for by the effects of cardiovascular drugs? What are the most common uses of beta-blockers? Why is that some of those uses do not agree with the academic recommendations and that conclusions can be drawn from these observations? With the treatment of hypertension be influenced by changes in the health care system in the next ten years?

The above example is cluster of questions relate to antihypertensive drugs. Similar questions can be developed for other therapeutic categories. Examples of some other questions addressed by pharmacoepidemiology are like: What is the cost effectiveness of hepatitis B vaccine, oral hypoglycemic agents, cardiovascular vasodilators, hypolipedemics for selected indications? What can be done by the pharmaceutical industry to alleviate the burden of disease in older populations? How does cancer chemotherapy interact with natural course of disease?

Pharmacoepidemiology applies the methods of epidemiology to the contents area clinical pharmacology. Therefore, in order to understand the approaches and methodological issues specificy to the field of the basic principles of epidemiology must be understood. An epidemiological study method involves three stages.

In the first stage, one studies a sample of subjects. Second, one generalises the information obtained from this sample study subject, and drawing and conclusion about a population in general. This conclusion is referred an association. Third, one generalisation again drawing a conclusion about scientific theory or causation. The above process can be represented as:

  • Study Samples
  • Conclusion about a population (association)
  • Conclusion about scientific theory (causation)

For example, one might perform a randomised clinical trails of the efficacy of methyldopa in lowering blood pressure by randomly allocating a total of 40 middle aged hypertensive men to receive either methyldopa or placebo and observing their blood pressure six weeks later. One with active drug decrease more than the blood pressure of 20 men treated with placebo. In this study, the 40 study subjects would represent study sample.

At the point one would tempted to make generalisation that methyldopa lowers blood pressure in middle aged hypertensive men. However, one trust explore whether this observation could have occurred simply by chance. In order to evaluate this possibility, one can per form statistical test. If the results of any study under consideration demonstrate a statistically significant difference, than one is said to have an association. If their is an association then one is tempted to generazile the results of the study even further.

For example in above, it is to state that methyldopa is an antihypertensive drug in general. This is referred to as scientific or biological inference and the result is a conclusion about causation, that is to say the drug methyldopa lowers the blood pressure in a population of treated patients. To draw this type of conclusion however, one requires to generalize to population other than included in the study, such as women, children and elderly.

Pharmacoepidemiology study designs

The different epidemiological study designs used by a pharmacoepidemiologist to draw a conclusion and association are:

-Randomized clinical trails (experimental study)

-Cohort study

-Case control study

-Analyses of secular trends

-Case series

-Case report

As one goes from the design at the bottom of (case report) to the (randomized clinical trails), the study is progressively harder to perform, but are progressively convincing. In other words, association shown by randomised clinical trails is more likely to be causal association than a case report study.

Case reports

Case reports are simple reports of single patients As used in pharmacoepidemiology, a case report describes a single patient, who was exposed to a drug and experiencing a particular outcome. For example on might see a published case report about young women, who was taking oral contraceptives and who suffers a pulmonary embolism.

Case reports are useful for raising hypotheses about drug effects to be tested with more vigorous study design. However, one cannot usually determine whether the adverse outcome was due to the drug exposure or would have happened anyway. As such it is very rare that a case report can be used to make statement about causation.

Case series

Case series are collection of patients, all of whom have a single, exposure, whose clinical outcomes are then evaluated and described. For example, one might observe 100 consecutive women under the age of 50, who suffer from a pulmonary embolism, and note that 30 of them had taken oral contraceptives.

After drug marketing, case series are most useful for two related purposes. First, they can be used for quantitating the incidence of an adverse reaction. Second, they can be used for being certain that any particular adverse effect of concern does not occur in a population, which is larger than studied prior to drug marketing.

The writer is with Divis Laboratories Ltd (R&D)