1、STD-APIIPETRO PUBL 4b48-ENGL L77b 81 0732270 05b3477 7T7 American Petroleum Institute sir.,*mf“ TJni HUMAN NEUROBEHAVIORAL STUDY METHODS: EFFECTS OF SUBJECT VARIABLES ON RESEARCH RESULTS Health and Environmental Sciences Department Publication Number 4648 Decem ber 1996 STD.API/PETRO PUBL 4L48-ENGL
2、177b M 07322911 05b3500 Zit7 nE4- Siraigzufor T documenting performance; and communicating with the public. API ENVIRONMENTAL MISSION AND GUIDING ENVIRONMENTAL PRINCIPLES The members of the American Petroleum Institute are dedicated to continuous efforts to improve the compatibility of our operation
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5、ond to community concerns about our raw materials, products and operations. *t. To operate our plants and facilities, and to handle our raw materials and products in a manner that protects the environment, and the safety and health of our employees and the public. e. To make safety, health and envir
6、onmental considerations a priority in our planning, and our development of new products and processes. 9 To advise promptly, appropriate officials, employees, customers and the public of information on significant industry-related safety, health and environmental hazards, and to recommend protective
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10、 handle, use, transport or dispose of similar raw materials, petroleum products and wastes. STD.API/PETRO PUBL 4b4-ENGL 179b Sl U73Z270 05b350L 185 Human Neurobehavioral Study Methods: Effects of Subject Variables on Research Results Health and Environmental Sciences Department API PUBLICATION NUMBE
11、R 4648 PREPARED UNDER CONTRACT BY: W. KENT ANGER, PHD*, O.J. SIZEMORE, SANDRA J. GROSSMANN, JULIE A. GLASSER, AND CRAIG A. KOVERA CENTER FOR RESEARCH ON OCCUPATIONAL AND ENVIRONMENTAL TOXICOLOGY OREGON HEALTH SCIENCES UNIVERSITY (L606) PORTLAND, OREGON 97201 DECEMBER 1996 *W. Kent Anger bears exclus
12、ive responsibility for study analysis, report write-up, and conclusions, with significant contributions from other OHSU authors; authors from other institutions contributed significantly to the testing. American Petroleum Institute STDSAPIIPETRO PUBL 4b98-ENGL 177b R 0732290 0563502 OLL FOREWORD API
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16、0 05b3503 T5A ACKNOWLEDGMENTS THE FOLLOWING PEOPLE ARE RECOGNIZED FOR THEIR CONTRIBUTIONS OF TIME AND EXPERTISE DURING THIS STUDY AND IN THE PREPARATION OF THIS REPORT API STAFF CONTACT David Mongillo, Health and Environmental Sciences Department MEMBERS OF THE NEUROTOXICOLOGY TASK FORCE Wayne Daugh
17、trey, Exxon Biomedical Sciences, Inc David Logan, Mobil Oil Corporation Charles Ross, Shell Oil Company Ceinwen Schreiner, Mobil Business Resources Corporation Christopher Skisak, Pennzoil Company CONTRACTORS ACKNOWLEDGMENTS Richard Letz, PhD, Crystal Barnwell, Zack Moore, and Deb Harris-Abbott Emor
18、y University School of Medicine Atlanta, GA Rosemarie Bowler, PhD, Francisco Cuadros, and Brigitte Johnson San Francisco State University (SFSU) San Francisco, CA iv ABSTRACT Behavioral tests are used to detect and characterize the effects of neurotoxic chemical exposures in human populations. These
19、 tests have been used extensively in worksite research, but little attention has been paid to the potentially large influence of subject variables on test performance. This project sought to evaluate the impact of two subject variables, education and cultural group, on widely used tests of neurotoxi
20、c insult. Subjects aged 26-45 were recruited through a range of advertising. Behavioral tests from the two consensus neurotoxicity test batteries (established by the World Health Organization and the US Agency for Toxic Substances and Disease Registry) were administered to 715 people with 0-18 years
21、 of education. The cultural groups studied were European-descent majority, Native American Indian, African-American, and Latin-American populations. Differences in educational level and locale (rural vs. urban) and gender were examined in the majority population. Education, cultural group, age and g
22、ender all affected the outcome of the behavioral tests studied as revealed by ANOVA, MANOVA and multiple regression techniques. Education followed by cultural group explained the most variance in the tests studied. More importantly, years of educational and cultural group had 13-25% shared variance
23、on the cognitive tests, suggesting that these factors should be controlled in the design of a study rather than in the statistical analysis. Failure to do so can lead to false conclusions about the presence or absence of neurotoxic effects. Four critical confounding factors which can mimic neurotoxi
24、c effects, or obscure them, in workplace epidemiological investigations are defined by this study for 34 measures drawn from 22 frequently used tests. Also established are key factors needed to plan and analyze a competent cross-sectional workplace study, statistical power analyses, and the distribu
25、tions for each test. STD.API/PETRO PUBL 4b4-ENGL L97b E 0732270 05b350Li 774 M STD.API/PETRO PUBL qb48-ENGL L77b 0732270 Cb3505 820 H TABLE OF CONTENTS Sect ion Paae EXECUTIVE SUMMARY . e5-1 1 . INTRODUCTION . 1-1 PROJECT GOALS 1-1 DEVELOPMENT OF STANDARDIZED BATERIES 1-2 FIELD ASSESSMENTS OF NES. N
26、CTB. AENTB 1-3 2 . METHODS 2.1 SUBJECTS . 2-1 BEHAVI ORAL TESTS . 2.2 PROCEDURES . 2.2 EXAMINERS . 2.4 DIVERGENCE FROM PROPOSAUCONTRACT 2.5 3 . RESULTS . 3-1 DISTRIBUTION OF EXAMINERS . 3-1 SUBJECT DEMOGRAPHICS 3-2 ANALYTIC STRATEGY 3-2 SENSORY TESTS 3-10 MOTOR TESTS 3-13 COGNITIVE TESTS 3-19 MEASUR
27、ES OF AFFECT . 3-24 MEASURES OF VOCABULARY . 3-26 4 . DISCUSSION . 4-1 DISTRIBUTIONS (NORMALITY) 4-1 THE MAJOR FACTORS (SUMMARY) 4-1 EDUCATION . 4-4 CULTURAL GROUP . 4-6 GENDER . 4-6 STD-API/PETRO PUBL 4bLI-ENGL L99b PI 0732290 05b350b 7b7 m TABLE OF CONTENTS Section Paae 4. DISCUSSION (Continued) A
28、GE . 4-7 VOCABULARY TESTS . 4-7 POWER ANALYSES . 4-8 CONCLUSIONSIRECOMMENDATIONS . . #. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-1 O REFERENCES R-1 APPENDICES APPENDIX A-1 APPENDIX B. B-1 APPENDIX C. C-1 APPENDIX D.,.,. D-1 APPENDIX E. E-1 Fiaure I. 2. 3. 4. 5. 6. 7.
29、 8. 9. -l O. 11. 12. 13. 14. 15. LIST OF FIGURES Paae Number of majority male and female subjects educated in urban and rural schools tested by the three Oregon Examiners 3-1 Distribution of years of education, by grade, in each cultural group 3-2 Male and female strength measurements in ages 26-35
30、and 36-45 across 3 educational ranges 3-7 Male and female vibration thresholds in ages 26-35 and 36-45, across 6-9, 10-1 2, and 13-16 years of education 3-1 3 Original distribution of Pegboard Both hands and same distribution after a square root transformation was applied 3-1 5 Number of taps by maj
31、ority, American Indian, Latin, and African American subjects across educational levels 0-5, 6-9, 10-1 2, and 13-1 6 . 3-1 7 Tapping by males and females in age ranges 26-35 and 36-45 across education ranges 6-9, 10-12, and 13-1 6 3-1 8 Original distribution of NES Symbol Digit latency and same distr
32、ibution after a log transformation was applied . 3-20 Number of spans recalled in the Digit Span test by Majority, Native American, Latin and African American subjects with 0-5, 6-9, 10-12, and 12-16 years of education 3-22 Digit spans recalled by majority males and females, ages 26-35 and 36-45 wit
33、h 6-9, 10-1 2, and 13-1 8 years of education . 3-23 NES Mood scores in male and female majority subjects 26-35 and 36-45 years of age, with 13-1 6 years of education 3-26 Distributions of scores on the WAIS, Peabody, and NES vocabulary tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
34、. . 3-27 Original distribution of NES Vocabulary and the same distribution after a log transformation was applied . 3-28 Simple regression plots of the NES, WAIS and Peabody vocabulary tests across years of education, for all subjects 3-29 Regression plots of years of education in majority subjects
35、and African American subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-30 LIST OF FIGURES (Continued) Fiaure Page 16. Scatterplot with regression line of Digit Symbol performance in Latin Ameri
36、can subjects against years of education . 3-32 17. Differences on vocabulary test performance across three education levels in majority females . 3-33 18. Urban/Rural WAIS vocabulary comparisons for majority females and males in educational and age groups . 3-34 19. Regression plots of population in
37、 the town in which subjects were educated against Raven Errors, mean Simple Reaction Time, and NES vocabulary test performance in majority subjects 4-5 STD.API/PETRO PUBL 4bYB-ENGL L77b 8 n732270 05b3507 47b LIST OF TABLES Table Paae 1. 2. Summary of Distribution and Subject Factors ES-3 Number of S
38、ubjects Required to Detect Effect Sizes of 5, IO, 15 or 20% Based on Power Analyses for Males and Females in the Majority Population . ES-5 Distribution of Tested Subjects by Years of Education and Cultural Group . 2-2 Behavioral Tests by Battery from Which the Tests Were Drawn 2-3 Order of Test Pre
39、sentation in Phases I (Minority) and II (Majority) . 2-4 3. 4. 5. 6. 7. 8. Subject Distribution Sought in Study 2-6 Distribution of Subjects Tested and Included in Analysis 2-6 Number of Subjects, Mean Age and Years of Education of Latin American, African American, Native American Indian, and Majori
40、ty (RuraWrban) Subject Groups, by Gender and Education MANOVA Table for Main Study Factors . 3-5 Number of Subjects and Percent Responses to Questions on Diseases, Abuse, Recent Drug/Alcohol Consumption, by Educational Mean, Median, Standard Deviation, Skew, Kurtosis, and the Best Transformation to
41、Approximate Normality in Sensory Measures for All Subjects . 3-1 1 Probability of Effects of Main Study Factors on Sensory Tests 3-1 1 Percent Variance Accounted for by Main Study Factors on Sensory Mean, Median, Standard Deviation, Skew, Kurtosis, and the Best Transformation to Approximate Normalit
42、y for Motor Measures for all Subjects, and Skew and Kurtosis of Transformed Data . 3-14 Subgroups 3-3 9. IO. Categories 3-9 I I. 12. 13. 14. Tests Using Hierarchical Multiple Regression . 3-1 2 15. 16. Probability of Effects of Main Study Factors on Motor Tests 3-15 Tests Using Hierarchical Multiple
43、 Regression 3-1 6 Percent Variance Accounted for by Main Study Factors on Motor LIST OF TABLES (Continued) Table Paae Mean, Median, Standard Deviation, Skew, Kurtosis, and the Best Transformation to Approximate Normality for Cognitive Measures in All Subjects . 3-19 17. 18. 19. 20. Probability of Ef
44、fects of Main Study Factors on Cognitive Tests 3-20 Percent Variance Accounted for by Main Study Factors on Cognitive Tests Using Hierarchical Multiple Regression 3-21 Mean, Median, Standard Deviation, Skew, and Kurtosis for Measures of Affect in NES Mood Test . 3-24 21. Probability of Effects of Ma
45、in Study Factors on Affective Measures in NES Mood Test 3-25 22. 23. Percent Variance Accounted for by Education and Cultural Groups on NES Mood Test of Affect Using Hierarchical Multiple Regression 3-25 Mean, Median, Standard Deviation, Skew, Kurtosis, and the Best Transformation to Approximate Nor
46、mality for the NES Vocabulary Test 3-27 Probability of Effects of Main Study Factors on Vocabulary Tests . 3-29 Percent Variance Explained by WAIS Vocabulary Test and Years of Education across Cultural Groups 3-31 Percent Variance Accounted for by Main Study Factors on Vocabulary Tests Using Hierarc
47、hical Multiple Regression . 3-32 Correlations between Reported Years of Education and WAIS, NES, and Peabody Vocabulary Tests in Majority Subjects 3-34 Summary of Distribution Characteristics of Tests . 4-2 Summary of Distribution and Subject Factors 4-3 Power Analyses for Female Majority Subjects .
48、 4-9 Power Analyses for Male Majority Subjects 4-1 O Number of Subjects and Percent Responses to Questions on Diseases, Abuse, Recent Drug/Alcohol Consumption, by Cultural Group . D-I 24. 25. 26. 27. 28. 29. 30. 31 . D-I. , STD.API/PETRO PUBL ibLiB-ENGL L77b W 0732Z70 05b35LL U24 W LIST OF TABLES (C
49、ontinued) Table eaae D-2. Probability of an Effect on Test Performance (ANOVA) of Reports of Numbness or Tingling, Institutionalization for Substance Abuse, Probability of Performance Differences among Cultural Groups Previously Institutionalized for Abuse vs. Never-Institutionalized Subjects 0-5 Alcohol Consumption in Last 48 Hours, and in All Subjects . D-4 D-3. - STD * AFI/P EXECUTIVE SUMMARY Behavioral tests are used to detect and characterize effects of neurotoxic chemical exposures in people. Three batteries (collections) of behavioral tests which dominate cross-sectional e
