Allan Wilson, MD, Ph.D.

The problem of clinical trials involving patient-determined dosing is widely recognized. If data obtained in clinical trials where patients take medication once or twice a day are known to be inaccurate, it follows that data from patients taking medication intermittently over longer intervals will be even less accurate.

The researcher studying such medications is generally reliant upon the patient recording the date and time of self-medication.

One commonly used procedure for such clinical trials is unit dose packaged medication with a place to record the date and time of dosing beside each blister.

The package might be 6 inches by 9 inches in size and does not come with a pen attached. Is it likely that a patient will carry around a blister package and pen for several months when only the occasional tablet will be required? It is more likely the patient will take one or two tablets out of the package and put them away in a purse or pocket.

The problem of clinical trials involving patient-determined dosing is widely recognized. If data obt Are patients likely to remember to record the date and time they took the tablet? Probably not.

It should come as no surprise that very little is known about how patients self-administer such medications, and that at least two such medication categories - opiate analgesics and hypnotic sedatives - are widely abused by patients.

Unfortunately the methodology for obtaining accurate medication compliance data has fallen behind clinical research methodologies, research ethics, and the ability of pharmaceutical companies to develop new drugs. Compliance data is currently the weakest link in the process.

One area within clinical pharmaceutical trials where patient compliance data are especially problematic is in studies of medications designed to be titrated by the patient against signs or symptoms of disorders, such as:

Chronic pain syndrome

Angina pectoris

Asthma - COPD

Environmental allergies

GERD/dyspepsia

Gout

Migraine headache

Other medication side effects

It should come as no surprise that very little is known about how patients self-administer such medications.

In clinical pharmacy applications, the situation is complicated by the fact that two categories of medication that are widely prescribed (in many cases inappropriately) in this way are also the largest sources of prescription drug abuse and dependence. Hypnotic sedatives, especially benzodiazepines, are often prescribed to be taken as required (prn) for the management of anxious symptomatology or to induce sleep.

It is well known that a significant number of such patients abuse their medication by taking more than is prescribed, taking it more often than is recommended, using it to cope with interpersonal stresses, or combining it with alcohol to augment its effects. Abusers who are genetically predisposed are at high risk to progress to benzodiazepine dependence.

At the abuse stage the problem can be corrected in many patients without difficulty. Unfortunately, abusive patterns of benzodiazepine taking are often impossible to detect.

Monitoring the compliance of patients prescribed hypnotic sedatives on a prn basis would reduce the likelihood of dependence by indicating to their prescribing physician or pharmacist that a problem is developing before the patient reaches the dependence stage.

The same dynamics also apply to the development of dependence on prescribed opiate analgesics.

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