WO1996041199A1 - Method for determining alcohol consumption rates - Google Patents
Method for determining alcohol consumption rates Download PDFInfo
- Publication number
- WO1996041199A1 WO1996041199A1 PCT/US1996/009898 US9609898W WO9641199A1 WO 1996041199 A1 WO1996041199 A1 WO 1996041199A1 US 9609898 W US9609898 W US 9609898W WO 9641199 A1 WO9641199 A1 WO 9641199A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- panel
- alcohol
- consumption
- constituent
- subject
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H10/00—ICT specially adapted for the handling or processing of patient-related medical or healthcare data
- G16H10/40—ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2496/00—Reference solutions for assays of biological material
- G01N2496/80—Multi-analyte reference solutions containing cholesterol, glucose and the like
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H10/00—ICT specially adapted for the handling or processing of patient-related medical or healthcare data
- G16H10/20—ICT specially adapted for the handling or processing of patient-related medical or healthcare data for electronic clinical trials or questionnaires
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
- Y10T436/143333—Saccharide [e.g., DNA, etc.]
- Y10T436/144444—Glucose
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
- Y10T436/146666—Bile pigment
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
- Y10T436/147777—Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
- Y10T436/147777—Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
- Y10T436/148888—Uric acid
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/17—Nitrogen containing
- Y10T436/171538—Urea or blood urea nitrogen
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/20—Oxygen containing
- Y10T436/203332—Hydroxyl containing
- Y10T436/204165—Ethanol
Definitions
- This invention is related generally to methods for evaluating individuals in terms of their rates of alcohol consumption and, more particularly, a method for identifying and/or screening those individuals of a larger population whose consumption rates indicate problematic behavior and/or alcoholic tendencies.
- Alcoholism is a serious human health issue and it has been predicted that it will affect about 16% of the population. Mortality rates among alcoholics are two to three times the rate for the general population and it has been suggested that it is one of the leading preventable causes of death, injury, illness and impaired functioning. In 1994, the National Institute on Alcoholism and Alcohol Abuse cited reports estimating the total societal costs for alcoholism in 1993 of about $140 billion dollars. Considerable effort has been directed toward the development of techniques for diagnosing alcoholism or excessive consumption rates. One technique involves the examination of blood serum variables, while the remaining three are psychological assessments.
- HDL cholesterol increased with increasing alcohol consumption up to about 450 mL of ethanol consumption per day, then decreased or appeared to decrease.
- the authors primarily examined the relationship between alcohol consumption and the level of HDL subclasses HDL2 and HDL3.
- McAndrew scale of the Minnesota Multiphasic Personality Inventory is representative of other similar approaches and generally accepted as a reliable method of alcohol assessment. It has been demonstrated to correctly classify about 84% of alcoholics when a cutoff score of 24 raw points is used. There are about 10 false negatives and 14 false positives using such cutoff point.
- the McAndrew test is composed of those items from the MMPI to which alcoholics respond differently than does the general
- the Khavari Alcohol Test is an example of such an approach.
- the Khavari test considers the drinking patterns of individuals (as provided by such individuals) and compares such patterns with established statistical drinking norms. These comparisons are then used for making diagnostic decisions.
- the Smith-Lewis et al. patent describes a method for determining magnesium ions in, among other things, blood serum and plasma. While the patent says the determination of such ion can be used for diagnosing and treating various ailments, alcohol consumption/abuse is neither mentioned nor suggested.
- Another object of this invention is to provide a non-subjective method for determining the rate of consumption of alcohol such that any evaluation or assessment is objective.
- Yet another object of this invention is to provide an improved method for identifying categories of alcohol consumption which can serve as a singular, or at least predominant, tool in diagnosing problematic alcohol-related behavior.
- Another object of this invention is to provide an improved method for determining rates of alcohol consumption rate which is efficient, economical and easily used in combination with standard blood work.
- Another object of this invention is to provide a method for identifying categories of alcohol consumption which can be used with equal effect in conjunction with, and without limitation, pre-employment screening, post- accident assessment, chemical drug trials to, inter alia, indicate alternative treatment approaches or concurrent drag abuse and pre-prescription diagnosis of potential drug interaction.
- Another object of this invention is provide a method for identifying and/or assessing alcohol consumption levels with or without correlation to daily ingestion volumes, notwithstanding periods of abstinence.
- Another object of this invention is to provide a method which can be used in conjunction with standard and/or widely-used alcohol markers, such that they are used selectively and more effectively as part of a reflex test to confirm a given consumption categoiy and/or minimize false positive results.
- Another object of the present invention is to provide a method for identifying alcohol consumption categories which utilize a previously-compiled base of blood panels and/or blood work up results, notwithstanding the circumstances under which the blood samples, panels, and/or results were obtained.
- Another object of the invention is to provide a method for use in conjunction with one of several statistical techniques which permits
- Another object of this invention is to provide a method for use in conjunction with one of several statistical techniques to predict a categorical outcome.
- Another object of this invention is to provide a mettiod for use in conjunction with one of several statistical techniques, such that panel constituents are not analyzed and/or compared merely on the basis of abnormalities, but also by consideration intra-panel constituent relationships.
- Another object of the invention is to provide a method for use in conjunction with one of several statistical techniques, such that accuracy is increased by incorporation of non-constituent factors into the analysis and/or comparison.
- Another object of the invention is to provide a method which permits adjustment of prior probabilities such that the analysis can be tailored to preferentially identify a particular consumption categoiy.
- Another object of the invention is to provide a method which permits adjustment of prior probabilities such that the analysis is tailored to
- Another object of the invention is to provide a method for determining a category of alcohol consumption rate which accounts for inter-laboratory differences, equipment variations, and related analytic anomalies.
- Another object of the invention is to provide a method for determining a category of alcohol consumption rate which involves, in part, correlation of subject and reference blood constituent panels with consumption rate categories derived from one of a variety of alcohol assessment standard instruments.
- FIGURE 1 illustrates the performance of the EDED of this invention, with respect to the validation data set.
- This invention is an improved method for the assessment of alcohol consumption, which provides a means to evaluate and determine an individual's rate of alcohol intake, in a manner which minimizes false positive results without a necessarily concomitant loss in sensitivity.
- the method can be varied through modification of a statistical model used therewith to preferentially weigh the analysis and identify one consumption category over another. Multi- variate and similar such statistical techniques correlate comparisons of individual/subject blood and reference panel constituents with recognized consumption rate categories.
- a method for assessing alcohol consumption rates includes (1) using a blood specimen from a human subject to develop an individual blood constituent panel, which has about at least ten constituents; (2) comparing the individual panel with a reference blood constituent panel to provide categories corresponding to rates of alcohol consumption; and (3) identifying the category of consumption rate for the subject indicated by the comparison.
- the reference blood constituent panel includes value ranges for the level of each constituent, whereby the relationship of one constituent to another can be determined.
- the reference panel is developed using a pool of human subjects and priority probability values corresponding to the likelihood that the subject would be classified in a particular category of alcohol consumption. A plurality of alcohol consumption categories are available for correlation to the reference panel, the number of categories depending upon the alcohol assessment standard instrument employed.
- a probability value of about 0.7-0.9 represents the lowest consumption rate; a probability value of about 0.08-0.20 represents the intermediate consumption rate; and a probability value of about 0.01-0.10 represents the highest consumption rate.
- the highest consumption rate is associated with the ratio of direct bilirubin concentration to total bilirubin concentration, a constituent used with one or both panels.
- consumption rate categories are derived from alcohol assessment standard instruments.
- Instruments useful with the present invention include psychological tests such as the Khavari Alcohol Test, the McAndrew scale, and MODCRIT.
- the standard instruments are volume frequency alcoholism assessment tests.
- the method of this invention can further include use of a statistical analysis which is modifiable to preferentially identified to one category of consumption rate over another.
- the analysis is a multi-variate statistical technique.
- the technique is selected from the group consisting of logistic regression, discriminant analysis, cluster analysis, factor analysis, and neuronetworking.
- the preferred technique includes standardization of individual/subject constituent panels through conversion of detected constituent levels to standard scores, to account for inter-facility/laboratory differences.
- the accuracy of the method is further increased where the individual and reference panels and statistical analysis incorporate such factors as age, gender, race, nationality, diet, geography, socioeconomic status, and drug interaction.
- the method of this invention can include a second comparison of an individual panel with a reference panel having ⁇ -hexacosanamine (Betahex) such that the category of consumption rate can be identified without false positive results.
- Additional reference panel constituents includes selenium, carbohydrate deficient transferrin, and hemoglobin associated acetaldehyde, among others.
- the present invention also includes a method for determining the approximate rate of alcohol consumption by a human test subject, having the steps (1) using a blood specimen from a subject to develop a subject blood constituent panel having at least 12 constituents, two of which are selected from the group consisting of high density lipoprotein, magnesium and the ratio of direct bilirubin to total bilirubin; (2) comparing the subject panel with a first reference constituent panel to provide categories corresponding to rates of alcohol consumption, the reference panel including two of high density lipoprotein, and magnesium, and the bilirubin ratio as constituents;
- the reference blood constituent panel includes value ranges corresponding to the level of each constituents, whereby the relationship of one constituent to another can be determined.
- the reference panel is developed using a pool of human subjects and prior probability values corresponding to the likelihood that the subject would be classified in a particular category of alcohol consumption. A plurality of alcohol consumption categories can be employed. In preferred embodiments, three categories of alcohol consumption, corresponding to increase
- consumption rates of alcohol per unit time are used and associated with prior probability values of about 0.70-0.90 for that category reflecting the lowest consumption rate, about 0.08-0.20 for that category reflecting the intermediate consumption rate, and about 0.01-0.10 for that category reflecting the highest consumption rate.
- Increased consumption and the highest consumption rate is associated with the ratio of direct bilirubin to total bilirubin, a constituent useful in conjunction with one or both panels.
- the categories of alcohol consumption are derived from alcohol assessment standard instruments.
- the instruments are volume frequency alcoholism assessment tests.
- the assessment tests are selected from the group consisting of the Khavari Alcohol Test, the McAndrew Scale, and MODCRIT.
- the method of the invention can further include use of a statistical analysis modifiable to preferentially identify one category of consumption rate over another.
- the analysis is a multi-variate statistical technique.
- the technique is a statistical model such as logistic regression, discriminant analysis, cluster analysis, factor analysis, and neuronetworking.
- the accuracy of the method is enhanced by incorporating into the panels and statistical analysis factors such as age, gender, race, nationality, diet, geography, socioeconomic status and drug interaction.
- the persons used to develop the reference panel of the present invention are preliminarily grouped into one of two classification variables related to alcohol consumption, i.e., abusive and non-abusive categories. Groups are derived through use of a psychological test, preferably selected from a group of such tests including the Khavari Alcohol Test, the McAndrew scale and MODCRIT. Of these, the Khavari Alcohol Test is a preferred assessment instrument.
- the accuracy of the invention is improved where the reference panel is developed using a relatively large number of subjects—typically, at least several hundred subjects and preferably about 1200 or more subjects.
- the resulting reference blood serum panel may include any of the widely-recognized SMA 6, SMA 12 and Hematological constituents although other similar, common tests and their corresponding constituents may also be used to develop such a reference panel.
- Still other embodiments of the present method involve development of reference and individual/subject panels, ranges of age, individual/subject gender and like factors to further enhance accuracy.
- the present invention includes a method for determining an individual's alcohol consumption level based upon certain blood constituents (or variables as they are sometimes called) and upon the levels of such constituents compared to a reference.
- the constituents are collectively known as a panel i.e., a listing of constituents such as glucose, albumin, red blood count and the like which are present (as detected by lab laboratory analysis) in blood serum.
- each constituent is accompanied by an indication of the level of such constituent (usually per unit of volume) present in the sample.
- each constituent can--and does—vary from person to person and from time to time for a particular person.
- so-called normal ranges recognize the possibility of such variations.
- the reference panel includes not only the normal range of values for each serum constituent but also includes at least two other ranges for each constituent. These additional ranges relate to "heavy" and "very heavy" consumption rates of alcohol.
- the reference and individual/subject panels include, alternatively, at least ten or at least twelve constituents, wherein two of the twelve are HDL and magnesium. But for the inclusion of HDL and magnesium with respect to the second alternative, the precise constituent makeup of either panel is not especially critical.
- many laboratories offer blood serum analysis services and provide their own panel construction.
- a variety of blood serum constituents can comprise either panel, the identity and number of which are limited only by their response, and accuracy thereof to the general level of alcohol consumption, their relationship one to another, and the analytic capabilities of an individual laboratory.
- the constituent response to either alcohol consumption or to another constituent is not necessarily linear and, in most instances, is distinctly non-linear.
- Constituents useful with the method of the present invention include but are not limited to neurophils-platelet type (BASO), calcium (Ca), chlorine (Cl), direct bilirubin (DBIL), lactose dehydrogenase (LDH), monophils-platelet type (MONO), sodium (Na), phosphorus (P), white blood count (WBC), copper (Cu), and zinc (Zn), among others.
- Blood constituents useful with the methods of this invention are generally alcohol-specific; that is, they are less affected by other events occurring in the body than they are by the level and/or rate of alcohol consumption.
- One embodiment of the invention includes high density lipoprotein and magnesium as constituents.
- the blood serum level of HDL increases with heavy drinking while that of magnesium decreases.
- Selenium, copper and/or zinc are additional constituents. In general, the levels of selenium and zinc decline with heavy alcohol consumption, while the level of copper increases.
- Selenium is also useful as a constituent for the purpose of a second comparison of an individual panel with a reference panel to eliminate false positive results.
- Other constituents used with the same effect include ⁇ -hexacosanamine, carbohydrate deficient transferrin, and hemoglobin associated acetaldehyde.
- the reference panel used with a method of the invention is derived from persons, taken from populations having, by percent distribution, known drinking habits, grouped preliminarily into one of two classification variables, i.e., abusive, consumer and non-abusive consumer categories, using one of several available alcohol assessment standard instruments. Notwithstanding accepted test methodology, a formerly-abusive consumer is grouped into the non-abusive consumer category only if s/he had been abstinent for at least 8 weeks rather than the customary 2-3 weeks.
- Preferred assessment instruments include psychological tests such as the Khavari Alcohol Test, the McAndrew scale and MODCRIT. Of this group, the Khavari test is most preferred.
- a feature of the Khavari test is that it elicits information from the subject which enables annual consumption rates of alcohol to be closely estimated. Annual consumption of ethanol is organized according to three groupings, one of which becomes the second classification variable described above.
- the Khavari test also includes check questions which aid greatly in assessing respondent veracity.
- ethanol annually comprises Group 3, light-to-moderate; consumption of 591- 1180 oz. annually comprises Group 2, moderate-to-heavy; consumption of more than 1180 oz. annually comprises Group 1, very heavy.
- the consumption rates represent one, two and more than two standard deviations above the mean, respectively.
- prior probability values can be assigned from categorization in Group 3, 2 or 1, and preferred values are between about 0.7 and 0.9, between about 0.08 and 0.20 and between about 0.01 and 0.10 for groups 3, 2 and 1, respectively. Within those ranges, prior probability values of about 0.86, 0.1 and 0.04, respectively, are highly significant. Such values correspond to the chances that a person belongs in a particular group, and are consistent with the level of alcohol consumption in the general population. Such values are useful in broad application of the present invention as a diagnostic tool by business, institutions and care providers.
- the member panels comprising the reference blood serum panel can be treated with a multi-variate statistical technique to provide weighted values for each constituent of the reference panel.
- discriminant analysis is a preferred statistical technique, although others can be used with comparable results without deviating from the scope of this invention.
- Discriminant analysis can be performed through use and with the aid of the DISCRIM computer program, from the Statistical Package For Social Science (SPSS) PC+ statistical package available from SPSS, Inc. of Chicago, Illinois.
- SPSS Statistical Package For Social Science
- Discriminant analysis is a technique commonly used in the social sciences and less frequently in medicine. It is similar to logistic regression in that it can be used to predict a nominal or categorical outcome. Discriminant analysis differs from logistic regression in several ways; most importantly: it assumes that the independent variables follow a multi-variate normal
- the procedure involves determining several discriminant functions, which are nothing more than linear combinations of the independent variables, that separate or discriminate among the groups to the extent possible.
- the number of discriminant functions needed can be determined by a multi-variate test statistic referred to as Wilks' Lambda.
- the discriminant functions' coefficients can be standardized, then interpreted in the same manner as with multiple regression to draw conclusions about which variables are important in discriminating among the groups.
- a method consistent with the invention may further include gender, age and the like categories as additional variables to further enhance accuracy of the method. Typical age categories are 18-35, 36-64 and over 64 years of age.
- Sources of light drinkers included three primarily white, middle-class churches, an inner-city African- American church, three support groups of recovering alcoholics and drug abusers, a college campus, a golf outing, and a work setting. Some heavy drinkers were also recruited from these settings but most were recraited from detoxification centers and from an inner city area that is impoverished and has a high rate of alcoholism. The volunteers recraited from the inner city had responded to advertising on bulletin boards in a church with an active program for alcoholism and in several blood banks in the same area.
- the data were divided into two groups for analysis: (1) a training data set that was used to derive an equation for identifying heavy drinkers and (2) a validation data set that was used to evaluate the performance of this equation.
- the validation data set included all of the 171 men who had the results of the three alcohol specific laboratory tests: HAA, CDT, and ⁇ -hexosamine.
- the validation data set permitted the performance of the three tests to be compared to the performance of the equation derived in the fraining data set.
- the validation data set also included all 32 subjects recraited after March 30, 1994 through December 17, 1994. All other subjects were included in the training data set.
- p 1/(1 + e -(a + x 1 b 1 + x 2 b 2 + . . .) )
- p is the probability that a subject is a heavy drinker
- x 1 is the value of the laboratory test and by is the coefficient for the values of that laboratory test.
- the statistical program estimates where p is the probability that a subject is a heavy drinker, x i is the value of the i-th laboratory test and b i is the coefficient of that laboratory test.
- the statistical program estimates the values of the coefficients to give probabilities that best fit the data.
- the strength of association of each variable in the EDED with heavy drinking is presented as the relative odds associated with an increase in the variable of one quarter of the normal range for that variable as determined by Roche Biomedical Laboratories.
- Roche Laboratories defined the normal range as the mean plus or minus 1.96 standard deviations for all of the laboratory variables that had a normal distribution in an apparently well ambulatory population. If the variable did not have an approximately normal distribution, the normal range was determined by Roche Laboratories using nonparametric methods to estimate the 95% confidence interval.
- the EDED was evaluated in the validation data. For this evaluation the sensitivity, specificity, and overlap index were used to measure how well the EDED score (i.e., the probability that a person was a heavy drinker based on the EDED) discriminated between heavy and light drinkers in the validation data set.
- the sensitivity of EDED was defined as the proportion of all heavy drinkers who had an EDED score of greater than 50%, and specificity was defined as the proportion of all light drinkers who had an EDED score of less than 50%.
- the overlap index is mathematically equivalent to several other statistics that can be used to measure the performance of a prediction equation including the area under the Receiver Operator Characteristic (ROC) curve, the C statistic and the Somers' D. The overlap index was used because it is intuitively easy to understand.
- ROC Receiver Operator Characteristic
- the overlap index would be 0.0 if the EDED score is greater for each heavy drinker than for all light drinkers. It would be 1.0 if the average rank of the EDED scores are the same for the heavy and light drinkers.
- the demographic characteristics of the study population are shown in Table B.
- heavy drinkers are younger than light drinkers and more likely to be African Americans.
- An equation derived in a sample more similar to the validation data set should perform better in the validation data than the equation derived in this training set.
- the association of the results of the individual laboratory tests with heavy drinking is shown in Table C. For most tests the association was statistically significant, and for many tests the association was significant at the p ⁇ .0001 level.
- the t-values for the most statistically significant tests were 9.08 for the percentage of white blood cells that were monocytes, -6.85 for sodium, 6.80 for gamma glutamyl transferase (GGT), and 5.01 for chloride levels. All of these t-values are statistically significant at the p ⁇ .0001 level. The t-value was much lower for the mean corpuscular volume which is often considered to be an important diagnostic tool for alcoholism.
- the variables included in the best logistic regression equation are shown in Table D. All of the variables in the EDED, except the platelet count, were associated with heavy drinking at the p ⁇ .0001 level in the univariate analysis presented in Table C. There were an additional 16 laboratory tests that were also associated with heavy drinking at the p ⁇ .0001 level in univariate tests but after adjusting for other variables were not significant and therefore were not included in the EDED. The equation was not improved using any of the variable transformations discussed in the methods section. No interaction terms were statistically significant at the p ⁇ .01 level. Even though race was highly associated with heavy drinking in a univariate analysis (p ⁇ ,0005 using a chi-squared contingency table test), it was not a statistically significant variable after adjusting for the other laboratory values.
- the value of the overlap index for the EDED is almost zero (0.017) indicating that in the training data almost all heavy drinkers have a higher EDED score (probability of being a heavy drinker) than almost all of the light drinkers.
- the logistic regression equation was derived to fit the data, the performance of the equation in this data set is better than it will be in other data sets.
- FIGURE 1 The performance of the EDED in the validation data set is shown in FIGURE 1.
- the EDED scores are shown for the light drinkers and for the heavy drinkers. The scores were greater than .95 for 88% (142) of the 161 heavy drinkers and less than .05 for 84% (36) of the 42 light drinkers. Only one of the 145 subjects with the highest scores (>.90) was a light drinker, and only one of the 39 subjects with the lowest scores ( ⁇ .10) was a heavy diinker. Because there was little overlap in the EDED scores between the heavy and light drinkers, the overlap index was .022. If 50% was used as a cut off score to identify heavy drinkers, the sensitivity of EDED was 95%, the specificity was 95%, and only 10 of the 203 subjects in the validation data were misclassified.
- Table E The ability of an abnormal value of each individual test in the EDED to identify heavy drinkers is shown in Table E. Although some of the tests are much more likely to be abnormal for heavy than for light drinkers, only the ratio of direct to total bilirubin had a moderately high sensitivity. As described above, Table A shows that age and race are confounded with heavy drinking. In Table F the possible effect of this confounding was examined. The table included both subjects in the training and validation data sets so that the sample size would be larger in the subgroups evaluated. When all subjects were considered, the mean EDED score for heavy drinkers, .95, is much larger than for the light drinkers, .09. Compared to African American subjects, white subjects have a lower mean EDED score, a lower sensitivity, and a higher specificity. However, the sensitivity and the specificity are high for both Whites and African Americans. Age did not affect the results for either race.
- the demographic factor with the strongest influence on the EDED score was insurance status, a marker for socioeconomic status. Heavy drinkers who were insured had a lower EDED score than uninsured subjects. The EDED score for White and African American heavy drinkers are similar if the insurance status is the same. Therefore, it is likely that socioeconomic status rather than race is the reason for differences in EDED scores between Whites and African Americans.
- the association between the probabilities of heavy diinking and the source of the subjects as listed in Table A for all subjects combined was also examined.
- the mean value for light drinkers ranged from .04 for the various middle class groups to .10 for the church group.
- For heavy drinkers the means ranged from .71 for the middle class groups to .99 for the inner city group.
- the specificity was 94%.
- the clustered array of group 1 centroids about 0.46860 and group 2 centroids about -1.96610 denotes a high degree of accuracy.
- One hundred percent of the non-abusive consumers and 79.1% of the abusive consumers were correctly identified, as a result of this analysis and subsequent comparison.
- Overall, 82.7% of the group cases were correctly identified, with zero false positive identifications.
- the discriminant functions were again determined with the coefficients standardized and assigned weighted values.
- a 10-constituent panel was again employed, with prior probabilities of 0.5 and 0.5 such tiiat the analysis was weighted or slanted toward a population having a higher number of problem consumers, and away from sociological norm.
- the data sets of the same 292 males under age 36 were again chosen, of which 240 comprised the reference panel and 52 were randomly selected, with the result being that random selection produced a different group of 52 than that used for validation purposes in Example 1. Again, a significance of 0.0000 showed the analysis liighly unlikely to be the result of chance. Subsequent comparison correctly identified 100% of the non- abusive consumers and 90.7% of the abusive consumers, with 92.3% overall correct identification and zero false positives.
- Example 1 Prior probabilities of 0.3 and 0.7
- Example 2 Prior probabilities of 0.5 for each group
- a statistical analysis used in conjunction with a method of this invention can be modified to preferentially identify one category of consumption rate over another. While false positives were eliminated in each, the former was somewhat less sensitive. For certain uses and/or applications, such a decrease in sensitivity is acceptable where the prime consideration is the elimination of false positive results. As such, where identification of only those having alcoholic tendencies is required (for instance, prior probabilities of about 0.1 and 0.9) a slight decrease in sensitivity is acceptable so long as false positive indications are eliminated.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU62692/96A AU698362B2 (en) | 1995-06-07 | 1996-06-07 | Method for determining alcohol consumption rates |
DE69629381T DE69629381T2 (en) | 1995-06-07 | 1996-06-07 | METHOD FOR DETERMINING THE ALCOHOL CONSUMPTION RATE |
CA002223760A CA2223760C (en) | 1995-06-07 | 1996-06-07 | Method for determining alcohol consumption rates |
AT96921475T ATE246809T1 (en) | 1995-06-07 | 1996-06-07 | METHOD FOR DETERMINING ALCOHOL CONSUMPTION RATE |
EP96921475A EP0852013B1 (en) | 1995-06-07 | 1996-06-07 | Method for determining alcohol consumption rates |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/481,656 | 1995-06-07 | ||
US08/481,656 US5798267A (en) | 1994-07-14 | 1995-06-07 | Method for determining alcohol consumption rates |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996041199A1 true WO1996041199A1 (en) | 1996-12-19 |
Family
ID=23912857
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1996/009898 WO1996041199A1 (en) | 1995-06-07 | 1996-06-07 | Method for determining alcohol consumption rates |
Country Status (6)
Country | Link |
---|---|
US (1) | US5798267A (en) |
EP (1) | EP0852013B1 (en) |
AT (1) | ATE246809T1 (en) |
AU (1) | AU698362B2 (en) |
DE (1) | DE69629381T2 (en) |
WO (1) | WO1996041199A1 (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6061657A (en) * | 1998-02-18 | 2000-05-09 | Iameter, Incorporated | Techniques for estimating charges of delivering healthcare services that take complicating factors into account |
BE1012448A3 (en) * | 1998-12-07 | 2000-11-07 | S C R L Dept Central De Fracti | Standard used in diagnostic and / or quantification. |
US6255047B1 (en) | 2000-02-28 | 2001-07-03 | Bio-Rad Laboratories, Inc. | Biosynthetic carbohydrate-deficient transferrin references |
US6549876B1 (en) * | 2000-07-25 | 2003-04-15 | Xyletech Systems, Inc. | Method of evaluating performance of a hematology analyzer |
JP2004185547A (en) * | 2002-12-06 | 2004-07-02 | Hitachi Ltd | Medical data analysis system and medical data analyzing method |
US20110161108A1 (en) * | 2009-12-30 | 2011-06-30 | Mckesson Automation Inc. | Systems and methods for detecting diversion in drug dispensing |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5126271A (en) * | 1991-07-16 | 1992-06-30 | James W Harasymiw | Method for determining the consumption rate of alcohol by a human subject |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4463098A (en) * | 1980-10-14 | 1984-07-31 | Albert Einstein College Of Medicine Of Yeshiva University A Division Of Yeshiva University | Hemoglobin marker of alcoholism |
SE440699B (en) * | 1984-02-06 | 1985-08-12 | Pharmacia Ab | ASSUME MEDIUM ISOTRANSFERRIN DETERMINATION ESTIMATE AN INDIVIDUAL ALCOHOL CONSUMPTION |
US4770996A (en) * | 1986-06-12 | 1988-09-13 | Boris Tabakoff | Identification of individuals predisposed toward alcohol abuse |
US4814280A (en) * | 1987-08-07 | 1989-03-21 | Peterson Charles M | Plasma and hemoglobin-associated acetaldehyde as a marker of alcohol use |
US5066583A (en) * | 1988-12-21 | 1991-11-19 | Wisconsin Alumni Research Foundation | Method for distinguishing alcoholics from non-alcoholics |
US5081011A (en) * | 1990-01-26 | 1992-01-14 | Board Of Trustees Operating Michigan State University | Method and test kit for detecting inherited substance abuse dependency |
-
1995
- 1995-06-07 US US08/481,656 patent/US5798267A/en not_active Expired - Lifetime
-
1996
- 1996-06-07 AU AU62692/96A patent/AU698362B2/en not_active Ceased
- 1996-06-07 AT AT96921475T patent/ATE246809T1/en not_active IP Right Cessation
- 1996-06-07 DE DE69629381T patent/DE69629381T2/en not_active Expired - Lifetime
- 1996-06-07 EP EP96921475A patent/EP0852013B1/en not_active Expired - Lifetime
- 1996-06-07 WO PCT/US1996/009898 patent/WO1996041199A1/en active IP Right Grant
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5126271A (en) * | 1991-07-16 | 1992-06-30 | James W Harasymiw | Method for determining the consumption rate of alcohol by a human subject |
Non-Patent Citations (1)
Title |
---|
HILLERS V N, ALLDREDGE J R, MASSEY L K: "DETERMINATION OF HABITUAL ALCOHOL INTAKE FROM A PANEL OF BLOOD CHEMISTRIES", ALCOHOL AND ALCOHOLISM, PERGAMON, OXFORD, GB, vol. 21, no. 02, 1 January 1986 (1986-01-01), GB, pages 199 - 205, XP002948934, ISSN: 0735-0414 * |
Also Published As
Publication number | Publication date |
---|---|
AU6269296A (en) | 1996-12-30 |
EP0852013A4 (en) | 2001-08-08 |
DE69629381D1 (en) | 2003-09-11 |
EP0852013A1 (en) | 1998-07-08 |
EP0852013B1 (en) | 2003-08-06 |
US5798267A (en) | 1998-08-25 |
ATE246809T1 (en) | 2003-08-15 |
AU698362B2 (en) | 1998-10-29 |
DE69629381T2 (en) | 2004-06-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6059724A (en) | System for predicting future health | |
Saunders et al. | Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption‐II | |
Boyer et al. | The development of an instrument for assessing the quality of life of people with diabetes: Diabetes-39 | |
Peralta et al. | Screening for intimate partner violence in a primary care setting: the validity of “feeling safe at home” and prevalence results | |
Batty et al. | Pre-morbid intelligence, the metabolic syndrome and mortality: the Vietnam Experience Study | |
MX2008013978A (en) | Methods and apparatus for identifying disease status using biomarkers. | |
Boardman et al. | Gene–environment interactions related to body mass: School policies and social context as environmental moderators | |
Ivandić et al. | Development and evaluation of a urine protein expert system | |
Hjemboe et al. | Empirical Assessment of Marital Distress: The Marital Distress Scale for the MMPI–2 | |
Harasymiw et al. | Identification of heavy drinkers by using the early detection of alcohol consumption score | |
De Beurs et al. | Optimizing the assessment of suicidal behavior: the application of curtailment techniques | |
Kahler et al. | An item response analysis of the Alcohol Dependence Scale in treatment-seeking alcoholics. | |
Kahler et al. | Item functioning of the alcohol dependence scale in a high-risk sample | |
Andrade et al. | White problem gamblers discount delayed rewards less steeply than their African American and Hispanic counterparts. | |
Hildebrand et al. | Predicting probation supervision violations. | |
O'Toole et al. | Suicide risk factors among Australian Vietnam era draftees | |
Joe et al. | The role of physical and psychological health problems in the drug use treatment process | |
Borgatta et al. | Alcohol use and abuse, life crisis events, and the elderly | |
AU698362B2 (en) | Method for determining alcohol consumption rates | |
Harasymiw et al. | The combined use of the early detection of alcohol consumption (EDAC) test and carbohydrate-deficient transferrin to identify heavy drinking behaviour in males | |
True et al. | Genetic and environmental contributions to healthcare need and utilization: a twin analysis. | |
Sorensen et al. | Race & ethnicity data | |
US5126271A (en) | Method for determining the consumption rate of alcohol by a human subject | |
US5823196A (en) | Method for detecting alcohol consumption rates | |
Harasymiw et al. | The early detection of alcohol consumption (EDAC) score in the identification of heavy and at-risk drinkers from routine blood tests |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA JP |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
ENP | Entry into the national phase |
Ref document number: 2223760 Country of ref document: CA Ref country code: CA Ref document number: 2223760 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1996921475 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1996921475 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 1996921475 Country of ref document: EP |