Allan Wilson, MD, Ph.D.

It is widely accepted that patients participating in clinical trials are less than perfectly compliant with their medication regimens. The extent to which non-compliance affects the results of clinical trials is unknown. Several factors mitigate against the assessment of this phenomenon, principal of which is the lack of a methodology to monitor patient compliance in a non-invasive way.

Compliance with prescribed medication is thought to decrease with duration of therapy, the number of times a day the medication must be taken, side effects, and break-through of clinical signs and symptoms.

Clinical research depends largely on pill counts and the use of medication diaries. Participating patients are interviewed at intervals and their remaining pills are counted. Strategies may involve giving patients extra pills to assess their compliance. Patients are known to not be forthcoming about non-compliance, generally from embarrassment or a desire to please the researcher. They are also known to fill out medication diaries retrospectively just before their interviews, often with less-than-perfect recollection.

Even patients who have interviews and correct pill counts may be non-compliant. With most medication trials the aim is to keep plasma levels within a therapeutic window. Not taking medication on time, taking extra medication, missing one dose and doubling up on the next call all result in plasma levels dropping below or exceeding the therapeutic window. The result may be ineffectiveness of the therapy due to inadequate plasma levels or side effects due to increased levels. Both have serious implications for the clinical trials decision-making process.

Although mechanical devices are sometimes used to address non-compliance, these are all flawed for various reasons. Currently available devices all interfere with the process of taking the medication by requiring the patient to behave differently when using them, and by their bulk and resultant inconvenience. They also affect the clinical trial methodology by their cost. For these reasons, they cannot be used to clarify the non-compliance issue.

Proving efficacy - the ultimate goal in clinical trials - should not be left to data of questionable accuracy. More accurate patient compliance data during clinical trials is the key to better decision-making regarding investigational new drugs.

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