Describing Clinical Data

I.THE "VARIABLE" -when reduced to lowest terms, all medical research is simply the study of relationships among variables -most often, medical investigators are interested in studying either associations or differences among variables -a variable is any: -quality -characteristic -constituent of a person or thing that can be measured -by definition a variable is subkect to change A.Scales used to measure variables -the four basic types of measurement scales listed below represent an increasing refinement of the measurement process. 1.Nominal Scale a.Definition a nominal scale uses: names, numbers or other symbols to assign each measurement to one of a limited number of categories that cannot be ordered one above the other -the categories of a nominal scale must be exhaustive and mutually exclusive -each measurement must fall into only one category -within any category, the members are assumed to be equivalent with respect to the characteristic being scaled -the names or symbols designating the categories can be interchanged without altering the essential information conveyed by the scale b.Examples -measurement of the variable blood type results in classification of a person's blood as type A, type B, type O, or type AB -for the variable psychiatric diagnosis, the measurement assigned to each patient is a number that corresponds to a specific diagnosis listed in DSM IV -other examples of variables measured on a nominal scale are: sex, race, and eye color 2.Ordinal Scale a.Definition an ordinal scale assigns each measurement to one of a limited number of categories that are ranked in terms of a graded order -differences among categories are not necessarily equal and often are not even measurable for example, the amount of the variable represented by a change from category 1 to category 2 is not necessarily the same as the amount represented by a change from category 3 to category 4 -the symbols assigned to represent the categories are not important as long as the ranking system is preserved

b.Examples -patients status or condition may be classified as: unimproved, stable, or improved -note that, although it is known that a patient classified as unimproved is more ill than a patient classified stable, it is not known how much more ill the first patient is -also, the difference in illness status from unimproved to stable is not necessarily the same as the difference in status from stable to improved -cancer staging typically uses an ordinal scale to classify disease according to the degree and nature of involvement of body tissues -for example, the staging of Hodgkin's disease is based on the degree of lymph node involvement, with stage I limited to a single lymph node region or single extralymphatic site and stage IV characterized by diffuse or disseminated involvement in extralymphatic tissues. 3.Interval Scale a.Definition an interval scale assigns each measurement to one of an unlimited number of categories that are equally spaced -the scale has NO true zero point (i.e., the zero point on the scale does not represent the true or theoretical absence of the variable being measured) -with an interval scale, it is possible to determine exactly how much more (or how much less) of the variable being measured is represented by each category b.Examples -temperature expressed in degrees Fahrenheit or Celsius is a variable measured on an interval scale -note that 00C is the point at which water freezes it does not representabsence of temperature 4.Ratio Scale a.Definition on a ratio scale, measurement begins at a true zero point and the scale has equal intervals -so ratio scale is equivalent to interval scale except the zero points including the unlimited number of categories (both have unlimited number of categories b.Examples -variables measured on a ratio scale are: length, time, mass, volume and temperature in degrees Kelvin B.Types of variables -variables can be broadly classified as: -qualitative -quantitative 1.Qualitative variables a.Definition are variables that are measured at a nominal level b.Examples a diagnostic test for pregnancy gives a result of either "positive" or

"negative" -the diagnostic test variable is a qualitative variable 2.Quantitative variables a.Definition are variables that are measured on an ordinal or interval/ratio scale b.Examples -a measurement of serum sodium concentration (e.g., 140 mEq/l) expresses the exact amount of sodium in the serum -serum cholesterol level, systolic blood pressure, and blood ureea nitrogen (BUN) level are other quantitative clinical variables C.Basis for variation -fluctuation among clinical measurements reflects the combined effects of several phenomena -the interpretation of clinical observations depends on the physician's ability to recognize these sources of variation and to account for them in the diagnostic and therapeutic processes 1.True biologic variation a.Definition -true biologic variation in clinical measurements is the sum of many unknown factors, each of which contributes a small random effect -random effects, based on the laws of probability are as likely to be positive (causing the measurement to exceed the true value) as they are to be negative (causing the measurement ot be less than the true value) -random effect is governed by the laws of probability = laws of chance b.Examples -a series of consecutive systolic blood pressure measurements on the same patient under theoretically identical conditions will not be exactly equal because of true biologic (random) variability inherent in these measurements within a given patient 2.Variation associated with making observations under different conditions = Systematic variation a.Definition -variation in clinical measurements occurs when the conditions under which the measurements are made are known to affect the values obtained -this type of variation is rather systematic rather than random, because its effect is predictable and not based on the laws of chance b.Examples -a patient's systolic blood pressure varies according to the time of day (temporal variation) and the position of the person (postural variation) when the measurement is taken -the pattern associated with these fluctuations is somewhat regular and predictable within a given person

3.Measurement variation a.Definition measurement variation (sometimes called measurement error) is variation among clinical observations that is attributed to the measurement process -measurement error may have both a: -random component -systematic component -random measurement error -is governed by the laws of chance and -results in a measurement that is either above or below the true value with equal probability -a series of measurements affected only by random variation will center on the true value of variable being measured -systematic measurement error -occurs when, as a result of a flaw in the measurement process, the measurements no longer center around the true value but around a value that is systematically higher or lower than the true value b.Examples -for a given sample of urine, a series of measurements of pH made with the same meter by the same analyst under theoretically identical conditions will not be exactly equal -random variations in these measurements is the sum of many components, including instrument precision systematic variation results if the instrument is out of calibration D.Withinpatient variation 1.Variation in the value of a clinical variable within a given patient may result from: -biologic variations that result from: -true biologic (random) variation -systematic variation ("bias") -varying conditions under which the measurement is made (systematic variation) -measurement error -a pathologic change in the biologic state of the patient 2.The physician is concerned with identifying the sources of variation within a given patient, because intervention should occur only if there is a true pathologic change E.Variation among patients 1.Variation from patient to patient in the value of a clinical variable is attributable to: -inherent biologic differences among patients these biologic differences (variations) can be: -"true" due to random changes -"bias" due to sampling error (a systematic change or variation) -systematic differences in conditions of measurement -measurement error -a pathologic change

2.The physician is concerned with variation among patients, because most answers to clinical questions for an individual patient are derived from information obtained from groups of patients with similar conditions for example, a physician would study variation among patients to answer questions such as: -"how unusual is Mr.Smith's creatinine kinase (CK) value relative to a group of persons known to be free of myocardial infarction?" -"do groups of patients who receive antihypertensive agent A have lower diastolic blood pressure measurements, on the average, than those who receive agent B?"

Types of variations: -Biologic variation can be: -"true" due to random changes -"bias" due to sampling error (a systematic change or variation) -Temporary systematic variations (changes) this can be ONLY systematic, unlike the other 2 variations -due to observations made under different conditions -Measurement variations = error -can be: -random (true) -systematic = bias

II. DESCRIBING VARIATION IN CLINICAL DATA -statisticians and clinicians have developed concepts to characterize variation in clinical meaasurements, including: -bias -accuracy -precision -validity A.Bias -here the discussion of "bias" is limited to cases in which multiple measurements are obtained from one patient -other types of bias (e.g., selection bias, confounding bias) arise when comparisons are made among groups of patients (e.g., to determine the most effective treatment of a disease) 1.Definition bias is a systematic component of both biologic variation and measurement variation -unlike random variation, bias results in measurements that are systematically higher or lower than the true underlying value of a diagnostic variable -bias may result from: -a flaw in the measurement process or -from sampling error that is why bias is a systematic component of the biologic variation (although the true biologic variation is random!)