Viewpoint Compliance in clinical trials

SUMMARY Compliance with treatment can be an important determinant of the outcome of clinical trials. To date there is no completely satisfactory method of measuring compliance and some of the most widely used methods are inadequate. The various methods of measuring compliance and how they have been applied to clinical trials are described, and improvements in the standard of the measurement and reporting of compliance in clinical trials are suggested. Poor compliance is a major problem in medical practice. 1-3 In the broadest sense it can refer to any deviation in the patient's behaviour from that recommended by the doctor, including such areas as dietary advice, advice on smoking, or even advice about attendance for further investigation or follow up. The term 'poor compliance ' can imply failure of the patient to follow the doctor's advice because of communication problems, 'forgetfulness', or a volitional act of the patient. In common usage the term compliance usually refers to the patient's adherence to prescribed drugs and in this sense the end result of poor or inadequate compliance for whatever reason is the patient's failure to ingest prescribed drugs. Poor compliance with prescribed drugs can also jeopardise the outcome of clinical trials by reducing their power. It has been calculated that if 30 % of patients in a clinical trial had inadequate compliance then double the number of patients would need to be studied to produce a study with the same a and, values.4 The situation is further complicated by the fact that in a comparative study the clinical effect of the same level of incomplete compliance may vary with different drugs. For instance, for two drugs normally prescribed to be taken once daily the omission of one dose of a sustained release prepara-tion of a short half life drug may result in ineffective circulating concentrations of that drug for most of the day, whereas omission of a single dose of a long half life drug will have relatively little effect o