Quantitative and qualitative chemical analyses are indispensable components of health care. In pharmacy, two major areas rely on chemical analysis. One is the quality control of pharmaceuticals, which gives the assurance that the product dispensed to the patient contains and provides the active ingredient as stated and expected. The second is the measurement of endogenous and exogenous substances and organisms in body fluids to provide information for diagnosis of health status and to monitor therapeutic regimens.

In this course, the major objective is to present the fundamental basis of chemical analyses in diagnostics and therapeutics and to review the current methodologies. By mastering the fundamentals of clinical chemical analyses, methodology and terminology, you will be prepared to successfully evaluate and apply future developments in methodology to interpretation of patient data. Although the meaning of the data generated is presented, the association of "numbers" with disease state and therapeutic regimen will be gained mainly by experience in reviewing patient charts or profiles in the context of the total patient history. Correct interpretation of results requires some understanding both of the acceptable analytical reproducibility and of physiological variations in the patient population.

A second objective is to present related and logistical topics, e.g., sample handling, toxicological analyses, drug abuse screening, automation, and analyses done outside of the clinical laboratories.

The primary texts are "Textbook of Clinical Chemistry" edited by Tietz, "Principles of Clinical Chemistry" by Blick and Liles and "Clinical Laboratory Medicine" 5th Ed., by Ravel (see Appendix A page AI for discussion of style and relative merits of texts). Margin notes will be coded as T301 for Tietz (1st Edition) page 301, B101 for Blick and Liles page 101, or R24 for Ravel page 24. Margin notes in parentheses refer to page number in 2nd Edition of Tietz. The following written material presumes a background in chemistry including quantitative analytical chemistry and biochemistry in particular. The margin notes and bibliography should allow you to review these background areas when necessary.

Material in the chapters appearing in small print is for reference only and will not be on examinations.

Requesting Tests: Rationale for Selection

Billions of analyses and tests are done every year costing many billions of dollars. Physicians order tests for different reasons: (1) to monitor critically ill patients; (2) to detect and diagnose diseases; (3) and, unfortunately, because the test is available. Contributing to the situation is the automated system which provides a battery of tests on a single patient sample. Not all tests may be necessary for a given patient. Totally unnecessary testing probably accounts for less than 10%, but it represents an area of potential health care cost reduction.

Physicians' perceptions as to what constitutes "good" data varies both in general and for specific laboratory tests. Also, individual physicians vary in deciding what is a significant change in a test result when repeated, and how much of a change justifies a change in therapy.

Specific examples of this variation include glucose in a well-controlled diabetic hospitalized patient with myocardial infarction, and cholesterol in a routine physical exam.

In the case of glucose, if the reported value is 110 mg/dL (+ 7 mg/dL, analytical variation), 42% of 125 internists felt a second day result of 145 mg/dL was clinically significant, 22% thought 140 mg/dL was clinically significant and 17% thought 130 mg/dL was clinically significant.

In the case of cholesterol with a reported value of 240 mg/dl (+ 19 mg/dL, analytical variation), 22% felt that 260 mg/dL on a second office visit was clinically significant, 20%, 290 mg/dL, and 15%, 280 mg/dL.

These physician responses would seem to lessen the desire for the laboratory to improve their accuracy and precision. However, increased accuracy and precision allows interlaboratory performance to improve and to focus on the predictive value of the analytical result, which ultimately provides the physician with the probability of positive diagnostic information.

The predictive value of the analytical result is based on the specificity and sensitivity of the analytical method and the incidence of the disease in the tested population. (More precisely, the frequency of the disease during a specified time period.)

The predictive value for any given test can be calculated from population data (i.e., number of patients with and without the disease), the result of true positive and false negative results and the prevalence of the disease during the time period in which the tests were done.

To give you a feeling for this, let's look at some hypothetical results. A test with 95% sensitivity and 95% specificity will have the following predictive values with the corresponding disease prevalence:

---

¹ Percent sensitivity of a test is the number of true positive results divided by the sum of the true positive results and the false negative results times 100.

Percent specificity of a test is the number of true negative results divided by the sum of the true negative results and the false positive results times 100.

% Prevalence	% Predictive value
1 5 10 25 50	16.1 50.0 67.9 86.4 95.0

Low predictive value would appear to argue against the utility of tests for diseases of low incidence, which otherwise appear to be quite good. However, when the tested population is modified by other tests or clinical judgements so that the prevalence in the tested population is increased, then the predictive value is enhanced.

The ordering of laboratory tests should be done with as much care and understanding as any other part of the diagnostic process.

(See Chapter 2C of Tietz, for extensive discussion of these topics.)

The course materials have been divided into four categories: t

1. Main study guide of more than 400 pages
2. Appendices A and B
3. Clinical cases paginated "Clin. 1" through "Clin. 39"

Prior to beginning the course you should have purchased the "Study Guide" and the "Clinical Cases."

III. RECOMMENDED TEXTBOOKS:

1. Burtis, Carl A. and Ashwood, Edward R., Tietz Textbook of Clinical Chemistry. 2nd ed., W.B. Saunders Co., 1994. The Tietz Textbook of Clinical Chemistry is highly recommended for additional and sipplemental reading to accompany the Course Manual. Direct references to this book are made throughout the Course Manual. This text is not required but it is a valuable reference.
2. Ravel, R. Clinical Laboratory Medicine: Clinical Application of Laboratory Data. 5th ed. Chicago: Year Book Medical Publishers, 1989.

COURSE ACKNOWLEDGEMENTS.

The College of Pharmacy
The University of Illinois at Chicago

UICPHARM@uic.edu
Last modified: January 9, 2000