Measures of efficacy

In the previous posts we had considered the optimization of warfarin dosages. The genotyping offers an added dimension to the optimization process, but may not be really cost effective. The warfarin problem is probably not a good example for predictive genotyping. This is because it already has a very good biomarker of clinical response - the INR (International Normalized Ratio). Most other drugs do not have good measures of clinical response. The absence of such measures of efficacy makes the optimization much more challenging.

Some drugs like warfarin allow direct measurement of the therapeutic efficacy. So for warfarin, it is the INR. For antihypertensive drugs, it could be the blood pressure response. For an antiasthmatic bronchodilator, it could be the airway relaxation, FEV1 for example. For an antidiabetic drug, it could easily be the blood glucose response. There are many other examples.

But for many therapeutic areas, the clinical response is much less directly quantifiable. For example, in the use of an antiepileptic drug, without a good surrogate measure of response, one is never really sure whether appropriate amounts of drug have been used. Likewise, for an antibiotic or a chemotherapeutic agent, the inappropriateness of the dosing regiment may not be recognized until it is too late.

For such situations, the availability of a 'surrogate' measure of response may be critical in patient care. One such surrogate measure is the measurement of circulating drug concentrations. Crude though it may be, getting the patient into a 'therapeutic range' may provide some guidance as to whether or not appropriate dosages have been used. Such an approach is sometimes referred to as the 'target concentration strategy'. There are however limitations to this method and it is not always applicable.

For the target concentration strategy to work, there must be evidence that circulating concentrations bear a good relationship to therapeutic outcome.