Patient compliance measurement

The reported incidence of resistance to these drugs varies greatly, from less than 5% to 75%. In part this tremendous variation in incidence reflects the definition of resistance (recurrent thrombosis while on antiplatelet therapy vs in vitro testing), methods by which drug response is measured, and patient compliance. Several methods for testing aspirin and clopidogrel resistance in vitro are now FDA-approved however, their utility outside of clinical trials remains controversial. 

Let us consider each issue in turn the definition and measurement of patient compliance, and the value of information about patient compliance and its correlates in a changing health care environment. 

Advances in measurement have freed the estimation of patient compliance from its long-standing dependence on methods easily manipulated by patients, whose reluctance to acknowledge poor compliance contributes to self-reporting bias, documented in many ways. The years 1986-1987 saw the introduction of chemical marker and electronic monitoring methods, which provide different but complementary estimates of the time history of dosing by ambulatory patients. These advances have been extensively reviewed (Feinstein, 1990 Pullar and Feely, 1990 Urquhart, 1990 Cramer and Spilker, 1991 Bond and Hussar, 1991 Vander Stichele, 1991 Kruse, 1992). The gist of both methods is as follows. 

Ideally, biomarkers should be measurable in a versatile and easily accessible body fluid, such as serum or urine, to maximize clinical use in terms of patient compliance and readiness to interface with the diagnostic... 

Another contribution of gene cloning is the expression in transfected CHO cells of the N-terminal and C-terminal part of ACE (206). It has also allowed a more in-depth characterization of ACE inhibitors at its two active sites in the presence of different substrates, including N-acetyl (SDKP), whose hemoregulatory properties and physiological role are now being defined and which may become a target for future therapeutic research (207-210). In the meantime, the measurement of N-acetyl SDKP in plasma and urines may be a tool for the follow-up evaluation of patients compliance with ACE inhibitors (211). 

The high correlation we found between urine FSH and serial sampling serum FSH shows that the assay used is suitable for measuring FSH reliably. The fact that the best correlation is found with random void urine adds to patient comfort. Also, the excellent storage conditions make the assay practical for use in large studies. As urine samples provide a practical method for monitoring the endocrine function of patients and volunteers, we believe the assay we presented will be able to improve volunteer availability and patient compliance in studies regarding ovarian function. 

Evaluation of patient compliance. Merely asking patients whether they have taken the drug as directed is not likely to provide reliable evidence and it can be assumed that anything that can happen to impair compliance, will happen sometimes. Estimations of compliance are based on studies using a variety of measures. 

Patient compliance with prescribed nebulization regimes is primarily determined by the duration of the therapy. Nebulizer fluids may be atomized for a set period, or more usually, a measured volume of therapeutic liquid is nebulized to dryness. The time taken to achieve this is directly related to the volume to be delivered. However, not all the fluid in the nebulizer can be atomized, and some fluid remains associated with the baffles, internal structures, and walls of the nebulizer as the dead or residual volume. The proportion of fluid remaining as the residual volume and thus unavailable to patients is higher for smaller fill volumes. 

Another facet, obviously, is to deal with the patient whose compliance has been substandard and take effective action to make as much improvement as possible in drug intake, and to switch, if necessary, to the agent whose therapeutic actions are least influenced by lapses in dosing. These are, of course, new issues that have previously not been considered in drug evaluation, for the simple reason that reliable measures of patient compliance have not previously been available. The potential roles of pharmacists, nurses and other health professionals remain to be defined as this new information and its implications become available and integrated into clinical thinking. 

There are two ways to classify the types of data collected—subjective and objective. Subjective data refer to all information provided by the patient that cannot be confirmed independently. The weakness of subjective data is that it cannot be confirmed, observed, or measured by the interviewer. However, it can be validated by other means. For example, patient compliance with a medication regimen can be supported by talking with a family caregiver however, this is also subjective. 

Noncompliance with prescribed medication regimens is a major problem in pharmacotherapy and results in 300,000 deaths in the United States annually. There are three distinguishing phases to noncompliance (a) acclimatization period, (b) compliance with the decision, and (c) discontinuation. Several methods are used to measure patient compliance to drug therapy. They range from direct questioning and the use of interview instruments, to patient diaries, pill counts, MEMS, drug... 

Several indices are used to quantify compliance. These range from fraction of doses taken in the monitoring period (i.e., a pill count) to the fraction of days during which the patient adhered to the prescribed dosing. Dose timing has been measured as the fraction of doses taken at the prescribed dosing intervals. Other indices of compliance measurement are therapeutic coverage and time at risk. ... 

L. Gordis, Conceptual and methodologic problems in measuring patient compliance, in Compliance in Plealth Care, R. B. Haynes, D. W. Taylor, and D. L. Sackett (Eds.). Johns Hopkins University Press, Baltimore, 1979, pp. 23 5. 

Sequential biochemical measurements could complement such clinical trials. Demonstration of an increasing concentration of plasma zinc is evidence of effective zinc absorption and patient compliance. A rise in the activity of plasma alkaline phosphatase is... 

Cramer J (1991) Overview of methods to measure and enhance patient compliance. In Cramer JA, Spilker B (eds). Compliance in Medical Practice and Clinical Trials. Raven New York 3-10. 

Van der Stichele R (1991) Measurement of patient compliance and the interpretation of randomized clinical trials. Eur J Clin Pharmacol 41 27-35. 

Hyland ME, Kenyon CAP, Allen R, Howarth P. Diary keeping in asthma comparison of written and electronic methods. Br Med J 1993 306 487 89 Kelloway JS, Wyatt RA, Adlis SA. Comparison of patients compliance with prescribed oral and inhaled asthma medications. Arch Intern Med 1994 154 1349-1352. Steiner JF, Fihn SD, Blair B, Inut TS. Appropriate reductions in compliance among well-controlled hypertensive patients. J Clin Epidemiol 1991 44 1361-1371. Chmelik F Doughty A. Objective measurements of compliance in asthma treatment. Ann Allergy 1994 73 527-532. 

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