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425 STATEMENT OF JEAN D. GIBBONS My name is Jean Dickinson Gibbons. My current position is Professor of Statistics and Chairman of the Applied Statistics Program at the Graduate School of the University of Alabama. I am currently a Fellow of both the American Statistical Association and the International Statistical Institute and a member of the Committee on National Statistics of the National Academy of Sciences. I received the bachelor's and master's degrees in mathematics from Duke University and the Ph.D. degree in statistics from Virginia Polytechnic Institute and State University. My previous faculty appointments were at the University of Pennsylvania and the University of Cincinnati. I was a senior Fulbright-Hays scholar at the Indian Statistical Institute in 1973. I was Associate Editor of The American Statistician for eight years, currently act as editorial collaborator on many statistical journals, includ- ing The Journal of the American Statistical Association, Biometrics, and Technometrics, and serve as a reviewer for grant proposals to the National Science Foundation. I am a member of several professional societies and have served two terms on the Board of Directors of the American Statistical Association. My publications include four scholarly books on statistics and over 30 articles in refereed professional and learned journals in my field. I was named Outstanding Scholar in 1981 and Board of Visitors Research Professor in 1974 at the University of Alabama. My current curriculum vita is attached to this statement.

42' In February of 1978, 1 was asked to review the reported statistical studies that formed the basis for the Food and Drug Administration's (FDA) decision to include a boxed warning in the patient and physician labeling on oral contraceptive (OC) products which states that cigarette smoking increases the risk of serious cardiovascular side effects for OC users. In October of 1978, at the request of Representative L. H. Fountain, I testified as an expert witness at a House Subcommittee Hearing on the "Quality of Scientific Evidence in FDA Regulatory Decisions (The Adoption of an Antismoking Warning in Oral Contraceptive Pill Labeling)." My conclusion at that time was that the statistical evidence published in the literature about the interactive effects of smoking and oral contraceptives on risk of cardiovascular disease is quite weak because the sample sizes in'most studies are extremely small, the results may be subject to significant sampling errors, and the results in some studies are based on convenient but unfounded assumptions. The authors of these papers in many cases pointed out these limitations of their data and deficiencies in their analyses. At that time I suggested that the FDA should run a controlled experiment to obtain sufficient and relevant data on factors such as length of time of OC use; number of years and amount of smoking; genetic, environmental, and psychological characteristics; among others. My prepared testimony and the discussion following at that hearing are a part of the written record. Bill H.R. 4957 contains a finding that states "(5) women who take birth control pills and smoke are more likely to suffer a heart attack or stroke than women who don't smoke". This finding is similar to the wording on the patient insert warning on boxes of OC which was at issue in my previous -2- testimony. Therefore, when Representati• February of this year on this matter, I studies that have been published on this current study included over 20 papers, i: for the previous testimony and the 3 add and were mentioned during the questionin references for the papers appearing sinc to this statement. This statement includes a brie studies published since 1978. I have lo data, findings, and conclusions of the a pendent calculations to measure the stat and OC use in their data and to check th analyzed those papers in which the auth:, tncreased risk of heart attack or stroke well as those papers where the authors c increased risk of heart attack or stroke have not included in this written analys relevant to the finding stated in H.R. 4 9ignificance, or do not help clarify the My primary overall conclusion 3i11 H.R. 4957 is at present groundless vhich it is based is limited, weak, conc criticism by impartial experts. There that, while also subject to criticism, I 95-077

427 al )n ~ A ic ag .t ise 1, 9 in or. and .ould :tors MY rt of testimony. Therefore, when Representative Fountain again contacted me in February of this year on this matter, I examined and reviewed the statistical studies that have been published on this topic since my previous analysis. My current study included over 20 papers, in addition to the 13 papers examined for the previous testimony and the 3 additional papers that appeared in 1978 and were mentioned during the questioning at that hearing. A complete list of references for the papers appearing since 1978 that I have studied is attached to this statement. This statement includes a brief analysis of each of the relevant studies published since 1978. I have looked carefully and objectively at the data, findings, and conclusions of the authors, and also performed some inde- pendent calculations to measure the statistical relationship between smoking and OC use in their data and to check their conclusions. I have critically analyzed those papers in which the authors claimed there is no (or a slight) increased risk of heart attack or stroke for women who smoke and use OC, as well as those papers where the authors claimed that there is a definite and increased risk of heart attack or stroke. The papers which I reviewed but have not included in this written analysis are, in my opinion, either not relevant to the finding stated in B.R. 4957, or do not add any new results of significance, or do not help clarify the situation. My primary overall conclusion is that Congressional Finding (5) in Bill H.R. 4957 is at present groundless because the statistical evidence on which it is based is limited, weak, controversial, and subject to severe criticism by impartial experts. There are current studies in the literature that, while also subject to criticism, have come to the opposite conclusion 95-077 0-82-28

428 429 and indeed claim that there is no interactive effect of OC use and smoking on the occurrence of heart attack or stroke in women. The evidence for either conclusion is limited and weak and subject to serious scientific criticism. In my professional judgment, I believe that the Congress should not in good conscience find that "women who take birth control pills and smoke are more likely to suffer a heart attack or stroke than women who don't smoke" because the scientific evidence is inadequate. Most of the women who will be affected and influenced personally by this finding will not have the scientific back- ground to form their own conclusions and will interpret the finding as truth, when, in fact, it is at best a questionable opinion that has been neither confirmed nor denied by the data in the reported studies. I again strongly urge the Congress to recommend that a controlled study be carried out with a good data base so that the issue can be addressed properly. More research is urgently needed before Congress can make a finding of such public importance. In support of these.general conclusions, I have attached a brief eummary of my analyses of (I.) the group of reported studies that claim no increased significant risk of heart attack and/or stroke, and (II.) the group of reported studies that do claim an increased risk for women who smoke and use oral contraceptives. A complete list of references is attached. Addi- tional details are given in the Appendices. Analysis of Reported St, I. Studies which purport to find no (or sligh attack and/or stroke for women who smoke a A. Krueger et al. (1980) report a c of death from myocardial infarct for the period January 1974-June the five largest metropolitan ar on smoking habits and OC use wer died of MI and 326 control women sizes on which to base a conclus reasonably reliable. - _ A primary stated conclusion of t effect of OC use and smoking on recent studies in the U.S. of nc (p. 672). My independent stati: conclusion of no interactive ef: based simply on the reported nur among the cases. My three conc analysis are as follows: 1. In the population of from MI, the factors no statistical associ

® 429 Analysis of Reported Studies I. Studies which purport to find no (or slight) increased risk of heart attack and/or stroke for women who smoke and use OC. A. Krueger et al. (1980) report a collaborative case-control study of death from myocardial infarction (MI) in women aged 15-44 for the period January 1974-June 1975 in regions representing the five largest metropolitan areas in the United States. Data on smoking habits and OC use were reported for 163 women who died of MI and 326 control women; these are reasonable sample sizes on which to base a conclusion and these data appear reasonably reliable. A primary stated conclusion of the authors is "An interactive effect of OC use and smoking on risk of MI, as reported in recent studies in the U.S. of nonfatal MI, was not found . . ." (p. 672). My independent statistical analysis to verify their conclusion of no interactive effect, shown in Appendix A, is based simply on the reported numbers of smokers and OC users among the cases. My three conclusions from this independent analysis are as follows: 1. In the population of 163 women aged 15-44 who died from MI, the factors of cigarette use and OC use show no statistical association.

430 2. In the population of 44 women aged 15-44 who died from MI and had no predisposing conditions, the factors of cigarette use and OC use show no statis- tical association. 3. In the population of 119 women aged 15-44 who died from MI and had predisposing conditions, the factors of cigarette use and OC use show no statistical association. Another primary stated conclusion of the authors is "Smoking and OC use together appeared to be no more of a risk factor for fatal MI than either smoking or OC use separately, compared to a reference group of nonsmokers and non-OC users" (p. 667). The authors based this conclusion on the odds ratios reported in Table 13, p. 666, and I have verified these odds ratios in Appendix A by independent calculations. The odds ratios and 95% confidence limits (from Table 13, p. 666) are as follows: Nonsmokers, OC users 2.19 (0.60, 7.33) Smokers, non-OC users 2.15 (1.38, 3.39) Smokers, OC users 1.84 (0.81, 4.06) The fact that the confidence interval for smokers and OC users includes 1.0 is statistical evidence that there is not neces- sarily any increased risk of MI for women who smoke and use QC over those who do neither; the same conclusion applies to women who do not smoke and do use OC of these statements is .95. 1 smokers and OC users is smalle of the. groups (Nonsmokers, OC users) in fact implies the opp It is unfortunate that the pap the joint characteristics of c ceased controls so that the re who died from MI and women who also unfortunate that the data have no breakdown according tc use, and age category within t duration of OC use, duration c smoked, and age are important ing whether a relationship ex` B. Slone et al. (1981) report on of nonfatal MI with respect tc of current and past OC use, t: within 25-44 years, and four only data on rate-ratios prov smoking status snd OC use are p. 423):

431 who do not smoke and do use OC. The confidence level for each of these statements is .95. The fact that the odds ratio for smokers and OC users is smaller than the odds ratios for each of the. groups (Nonsmokers, OC users) and (Smokers, Non-OC users) in fact implies the opposite of a synergistic effect. It is unfortunate that the paper does not give information on the joint characteristics of cigarette and OC use among the de- ceased controls so that the results could be compared for women who died from MI and women who died from other causes. It is also unfortunate that the data given on both cases and controls have no breakdown according to amount of smoking, years of OC use, and age category within the 15-44 years. Surely the duration of OC use, duration of smoking, amount of cigarettes smoked, and age are important factors to consider in determin- ing whether a relationship exists. B. Slone et al. (1981) report on a case-control study of the rate of nonfatal MI with respect to the characteristics of duration of current and past OC use, three subcategories of age group within 25-44 years, and four categories of smoking status. The only data on rate-ratios provided in the paper that concern smoking status and OC use are as follows (from Table 7, p. 423):

432 Never Smoked 2.5 Ex-smokers 2.9 1-24 cigarettes/day 1.5 > 25 cigarettes/day 1.4 The authors conclude from these findings that "The rate-ratio estimates declined with increasing cigarette smoking, and the trend was statistically significant. This finding is at vari- ance with previously published observations on current use of oral contraceptives" (p. 423). HoweveY, the authors warn of possible bias in this study and recommend that the data be interpreted with caution. C. Maguire et al. (1979) extend the analysis of some previously reported data on a case-control study of four diagnostic cate- gories of thrombosis (including MI). The primary conclusion relevant here is that their analysis indicates "no strong evidence of modification in the relative risk associated with oral contraceptive use by age or smoking for any of the throm- bosis diagnoses considered. It is of interest, however, that in all groups except predisposed venous thrombosis the effect modifier coefficients were negative, suggesting a consistent pattern of decreasing estimated relative risk associated with pill use with both smoking and older age" (p. 193). 432 s.is.y et al. (1979) use vital :crt.lity from cardiovascular ,~%V pre-pill period as control :sers. (This is a re-examinat :)r a 1976 publication in Lanc eare included.) These author creasing mortality from cardio increased levels of pill use u 7~teir analyses fail to show a ;.ercent of women smoking and c: authors do point out, however, statistics as opposed to a cas, .I:ck et al. (1978c) report on c stroke in premenopausal women. 1a the report by the CGSS [Col'_ 3troke in Young Women], cigaret associated with stroke in healt independent analysis of their d that cigarette smoking is not a group of women. These authors indicate that oral contraceptiv stroke in healthy young women" of their data, also given In Ap indeed a positive association b

D. Belsey et al. (1979) use vital statistics from 21 countries on mortality from cardiovascular disease (CVD) for 1962-74, taking the pre-pill period as controls and post-pill period as OC users. (This is a re-examination of some data used by Beral for a 1976 publication in Lancet, but with an additional two years included.) These authors "find the conclusion of in- creasing mortality from cardiovascular disease associated with increased levels of pill use unsupported by the data" (p. 85). Their analyses fail to show a significant correlation between percent of women smoking and changes in CVD mortality. The authors do point out, however, the inadequacy of using vital statistics as opposed to a case-control study data base. E. Jick et al. (1978c) report on a case-control study of nonfatal stroke in premenopausal women. They conclude "In our study, as in the report by the CGSS [Collaborative Group for the Study of Stroke in Young Women], cigarette smoking was only weakly associated with stroke in healthy young women" (p. 59). My independent analysis of their data, given in Appendix B, shows that cigarette smoking is not associated with stroke in this group of women. These authors also state that their •"results indicate that oral contraceptives markedly increase the risk of stroke in healthy young women" (p. 59). My independent analysis of their data, also given in Appendix B, shows that there is indeed a positive association between OC use and incidence of

434 stroke at the .001 level of significance. It should be pointed out that the sample sizes for this study are quite small, a total of 56 control and 14 case subjects. F. Petitti et al. (1978b) use the Walnut Creek Data to study OC use, smoking, and other risk factors for venous thromboembolism and conclude "that OCa and smoking have independent effects in increasing the risk of the idiopathic form of the disease" (p. 484). Their conclusions are based on 17 cases without predisposing conditions grouped as follows: - Table: Number of Smokers and OC Users Among the 17 Cases (from Table 4, p. 483). Non-OC Users OC Users Totals Nonsmokers 2 4 6 Smokers 6 5 11 Totals 8 9 17 X . 0.7 .30<P<.50 Z • 1 Statistical Conclusion: Among women who have the disease and no predisposing conditions, the factors of cigarette use and OC use show no association. The authors also give relative risk estimates for cases versus controls, and the estimates for smokers and OC users are smaller than the estimates for women with only one of these factors. . 435 Table: Relative Risk Esti: Controls (from Tab Rc Among Smokers, OC users Among Nonsmokers, OC users Among OC Users, Smokers Among Non-OC Users, Smokers Because the sample sizes for cas confidence intervals are so wide able reliability. Studies which do purport to find a definit, attack and/or stroke for women who smoke aT A. Studies criticized in my previou; (i) Jain (1977) uses the di consisting of 63 women an MI and a control grc were three nonsmokers a OC at the onset of the too unbalanced and too conclusions about the i and OC use on MI. Jain these mortality data ar may be subject to signi-

. 435 Table: Relative Risk Estimates for Cases vs. Controls (from Table 4, p. 483) Relative Risk 90% Confidence Limits Among Smokers, OC users 4.7 (1.3-17.6) Among Nonsmokers, OC users 12.8 (1.8-90.2) Among OC Users, Smokers 2.3 (0.8- 7.1) Among Non-OC Users, Smokers 7.6 (1.6-36.2) Because the sample sizes for cases are so very small and the confidence intervals are so wide, these results are of question- able reliability. I:. Studies which do purport to find a definite and increased risk of heart attack and/or stroke for women who smoke and use OC. A. Studies criticized in my previous testimony: (i) Jain (1977) uses the data in Mann et al. (1975) consisting of 63 women under age 45 who had survived an MI and a control group. Among the cases, there were three nonsmokers and 13 smokers who were using OC at the onset of the MI episode. These numbers are too unbalanced and too small to justify any reliable conclusions about the interrelationship of smoking and OC use on MI. Jain concedes in his paper that these mortality data are based on small numbers and may be subject to significant sampling errors; this 0 -a h ~ i

caveat should not be ignored. Further, his analysis is based on two unwarranted but convenient assump- tions which he justifies making ". . . because the relevant data . . . are not available" (p. 51). This is a non sequitur, and highly unscientific reasoning. (ii) Beral (1977) uses the Royal College of General Practi- tioners (RCGP) data but the numbers are still very _-sma11, especially the deaths for nonsmokers. She concedes that "These estimates are based on small numbers and are necessarily approximate. Without more data it is not possible to examine the inter- relationships of age, smoking, and duration of oral contraceptive use . . ." (p. 730). (iii) Jick et al. (1978b) report data on 26 women with acute but nonfatal MI and 59 controls and give rela- tive risk estimates for OC users. However, no MI subjects were nonsmokers who did not take oral contra- ceptives so relative risk estimates for OC users who smoke could not be obtained. (iv) Petitti and Wingerd (1978) give relative risk factors for subarachnoid hemorrhage (SAEi) for women who smoke and use OC. flowever, this analysis is based on extremely small numbers, a total of U women, which includes none who were nonsmokers and non-OC users, and only six who were smokers and OC users. Certainly .-I this is insufficient data ing an interrelationship. 8. Shapiro et al. (1979) report a stud- with MI and 1742 control premenopau< the following age-adjusted rate rati dence intervals of MI for recent OC P. 745): Nonsmokers 4.5 (1. Smoke 1-24/day 1.2 (0. Smoke > 25/day : 4.3 (2. The estimated rate ratio for heavy sm, for non-smokers and the confidence in~ completely includes the confidence lir Further, the rate ratio estimate for ¢ siderably smaller than either of those smokers, and the confidence interval fc includes the value 1.0, which ehows no risk. The age-adjusted rate-ratio estimates g (p. 746), on the other hand, give a vern estimate for women who are heavy smokers that the Table VI results were derived f Table V, but the results in Tables V and that I do not see how they could have be,

this is insufficient data to use as a base for claim- ing an interrelationship. !, Shapira et al. (1979) report a study of 234 premenopausal women with MI and 1742 control premenopausal women. The authors give the following age-adjusted rate ratio estimates and 952 confi- dence intervals of MI for recent OC users (from Table V, - p. 745): Nonsmokers 4.5 (1.4-14.1) Smoke 1-24/day 1.2 (0.3- 4.4) Smoke > 25/day, ,- 4.3 (2.2- 8.2) The estimated rate ratio for heavy smokers is about the same as for non-smokers and the confidence interval for nonsmokers completely includes the confidence limits for heavy smokers. Further, the rate ratio estimate for moderate smokers is con- siderably smaller than either of those for nonsmokers and heavy smokers, and the confidence interval for moderate smokers includes the value 1.0, which shows no significantly greater risk. The age-adjusted rate-ratio estimates given in Table VI (p. 746), on the other hand, give a very large rate-ratio estimate for women who are heavy smokers. The authors state that the Table VI results were derived from the data shown in Table V, but the results in Tables V and VI are so inconsistent that I do not see how they could have been obtained from the

438 same data base. Further, the confidence intervals in Table VI are extremely wide for all categories of OC use and similarly for non-OC users who are heavy smokers. The confidence limits for moderate smokers who use OC include the value 1.0, a result that is consistent with the Table V results, but this again implies no risk. My independent calculations of rate ratios from the data in Table V without adjusting for age, as shown in Appendix C, are more consistent with Table V ratios than are those given by the authors in Table VI. Perhaps more important here is the small frequency of women in each group. See Appendix C. These limited sample sizes alone could justify an argument that the results given by Shapiro et al. are not reliable. C. Jick et al. (1978a) extend an earlier case-control study of nonfatal MI and its relation to OC use and smoking to include a total of 83 case and 154 control subjects. The authors claim a strong positive association between MI and OC use, and between MI and smoking. My independent analyses of their data, shown in'6ppendix D, confirm these conclusions. However, these authors also state "In both groups there is an extremely strong correlation between smoking and MI. Of the 83 case patients Interviewed, 74 (89%) were current smokers. The corresponding figure for the 153 controls is 67 (44Z)" (p. 2,549). As this D. 439 statement shows, it is certain smokers is larger in the case but this fact has nothing to d percentages have no relevance and smoking because the data b. cases and controls. This pape: frequences of women wit respec! acteristics. The NIH Report (1981) states "t firm that OC users who smoke or at somewhat [emphasis added] gr effects, particularly circulato However, no specific data or re the degree of greater risk real E. Petitti et al. (1979) also use - (p. 1,152) shows the relative r- smoke and 2.8 for women who smok risk is lower), and the lower 9C who smoke and use OC is 0.8, les MI cases are based on a total of Other relevant results in this t of 5.7 for smokers and 21.9 for based on a•total of Il observati

439 statement shows, it is certainly true that the percentage of smokers is larger in the case group than in the control group, but this fact has nothing to do with correlation; in fact, the percentages have no relevance for the relationship between MI and smoking because the data bases were not random samples of cases and controls. This paper gives no data on the joint frequences of women wit respect to MI, OC use or smoking char- acteristics. D. The NIH Report (1981) states "the Walnut Creek data also con- firm that OC users who smoke or who are older than 30 years are at somewhat [emphasis added]'greater risk of serious side effects, particularly circulatory disorders" (p. 1,071). However, no specific data or results are given to clarify what the degree of greater risk really is estimated to be. E. petitti et al. (1979) also use the Walnut Creek data. Table 1 (p. 1,152) shows the relative risks for MI as 2.9 for women who smoke and 2.8 for women who smoke and use OC (note this relative risk is lower), and the lower 90% confidence limit for women who smoke and use OC is 0.8, less than 1.0; these results for MI cases are based on a total of 26 observations, however. Other relevant results in this table are relevant risks for SAH of 5.7 for smokers and 21.9 for women who smoke and use OC, based on a-total of 11 observations, and relative risks for

440 other stroke as 4.8 for smokers and 2.0 for women who smoke and use OC (note this relative risk is lower than the relative risk for smokers), based on a total of 23 observations. Table 3 (p. 1,152) gives incidence rates for the combined types of cardio- vascular disease for 3 women under age 45 who neither smoke nor use OC, and 8 women under age 45 who both smoke and use OC. All of the aforementioned results or relative risks are highly questionable because of the extremely small numbers of cases in each subgroup (especially that of women under age 45). In spite of this severe limitation on reliability, the authors' conclusion is that "smoking and OC use appear to act syner- gistically to increase the risk of subarachnoid hemorrhage, hemorrhagic stroke, and @fI" (p. 1,154). In my opinion, their data do not justify this conclusion at all. . g. Layde, Beral, and Ray (1981) use the RCGP data to study the re- lationship between smoking and OC use in regard to mortality from SAH and from various circulatory diseases. An independent analysis of their data in Tables IV and V (p. 543), shown in Appendix E, implies that the following statistical conclusions are appropriate: In the population of women aged 35-44, there is no association between OC use and smoking for those who died from SAH, nor for those who died from circulatory disease. 441 The sample sizes here are small (20 deaths from circulatory disease). T deaths from circulatory disease to c and excess risk estimates for Ever-u Table V (p. 543), separately for eac smoking. The individual numbers of subgroups are extremely small (see A authors do not use these actual numb risks and excess risks; rather they 100,000 women-years and this leads t, larger sample sizes. Moreover, the ; risk [of circulatory disease] for ev, smokers than among non-smokers for e: The authors fail to point out that t! of relative risk for nonsmokers is cc for smokers for women aged 35-44, anc over; and in fact the interval for nc interval for smokers in each case, wt difference between relative risks foc G. Rosenberg et al. (1980) study the ef: MI in the presence and absence of ott factors including cigarette smoking. estimates and 95% confidence interval other predisposing conditions are as p. 63):

441 The sample sizes here are small (20 deaths from SAH and 65 deaths from circulatory disease). The authors use the 65 deaths from circulatory disease to compute the relative risk and excess risk estimates for Ever-users vs. Controls in Table V (p. 543), separately for each subgroup of age and smoking. The individual numbers of cases for each of these subgroups are extremely small (see Appendix E, Table 14). The authors do not use these actual numbers to compute relative risks and excess risks; rather they use mortality rates per 100,000 women-years and this leads to an impression of much larger sample sizes. Moreover, the authors state "The relative risk [of circulatory disease] for ever-users was greater among smokers than among non-smokers for each age group" (pp. 543-544). The authors fail to point out that the 95% confidence interval of relative risk for nonsmokers is considerably wider than that for smokers for women aged 35-44, and also for women 45 and over; and in fact the interval for nonsmokers includes the interval for smokers in each case, which implies no significant difference between relative risks for smokers and for nonsmokers. G. Rosenberg et al. (1980) study the effect of 0C use on nonfatal MI in the presence and absence of other predisposing risk factors including cigarette smoking. Their relative risk estimates and 95% confidence intervals for KI for women without other predisposing conditions are as follows (From Table 4, p. 63):

443 Normotensive nonsmokers 2.8 (1.0-7.8) Normotensive smokers 1.1 (0.5-2.6) These risk estimates are for current OC users relative to women who had never used OC. The relative risk for normotensive smokers is smaller than that for normotensive nonsmokers, and the lower confidence limit is 0.5, which implies that the additional risk for smokers using OC is probably nonexistent. And yet the authors claim "The increase in risk attributable to the combined effect of current OC use, cigarette smoking and hypertension was considerably greater than what would be predicted from the sum of the sepa- rate effects of these factors" (p. 59). Each of the risk estimates given in Table 4(p. 63) is based on a very small number of cases, however. Only 7 cases were OC users and smokers without other predisposing conditions, and only 12 cases were neither smokers nor OC users. Further, the data base is married U.S. female registered nurses, which is hardly representative of all U.S. females. Appendix A Analysis of Date from Krueger et Table 1. Number of Smokers and OC Users Amor (from Table 13, p. 666) Non OC Users Nonsmokers 42 Smokers 101 Totals 143 ~ . - .0033, .90 < P < .95 :?e appropriate statistical conclusion from Table Jomen aged 15-44 who died from MI, the factors of ao association. Table 2. Number of Smokers and OC Users Amor Predisposing Conditions (from Table Non OC Users Nonsmokers 6 Smokers 31 Totals 37 2 ( - .016, P - .90 1 Table 3. Number of Smokers and OC Users Amor disposing Conditions (from Table 1z Non OC Users Nonsmokers 36 Smokers 70 Totals 106 2 X - .1038, .70 < P < .80 1 -19- 95-077 95-077 0-82--29

disposing Conditions (from Table 14, p. 666) Non OC Users OC Users I Totals Nonsmokers 42 6 Smokers 101 14 Totals 143 20 2 ~ ~ .0033, .90 < P < .95 1 443 Appendix A Analysis of Date from xrueger et al. (1980) Table 1. Number of Smokers and OC Users Among the 163 Cases (from Table 13, p. 666) Non OC Users OC Users I Totals 48 115 163 The appropriate statistical conclusion from Table 1 is that in the population of women aged 15-44 vho died from MI, the factors of Cigarette Use and OC Use show so association. Table 2. Number of Smokers and OC Users Among the 44 Cases Without Predisposing Conditions (from Table 14, p. 666) Non OC Users OC Users Nonsmokers 6 1 Smokers 31 6 Totals 37 2 X " .016, P - .90 1 Nonsmokers 36 5 Smokers 70 8 Totals 106 13 2 X - .1038, .70 < P < .80 1 Totals 7 37 44 Table 3. Number of Smokers and OC Users Among the 119 Cases with Pre- 9SA77 0-82--29 -19- 41- 78 119

The appropriate statistical conclusions from Tables 2 and 3 are that in the population of women aged 15-44 who died from M2, the factors of Cigarette Use and OC Use show no association, irrespective of whether there are predisposing medical conditions. The odds ratios associated with OC use and smoking as given in Table 13, p. 666, are simple proportions of cases versus controls in each smoking cate- gory relative to the same proportion for nonsmokers, non-OC users, calculated as follows: Nonsmokers, non-OC users Reference Category - 1.0 Nonsmokers, OC users 6/9 * 42/138 - 2.19 Smokers, non-OC users 101/154 t 42/138 - 2.15 Smokers, OC users 14/25 • 42/138 ~ 1.84 -20- 445 Appendix B ' Analysis of Data from Jick et al Table 4. Number of Cases and Controls Who Sm Control Strok Nonsmoker 33 7 Smoker 23 Totals 56 14 2 1 - . 36, .50 < P < .70 r. L Statistical Conclusion: There is no association bE stroke and smoking in these women. Table 5. Number of Cases and Controls Who Use Control Stroke Non-OC User 49 3 OC User 7 11 Totals 56 14 2 ~ 25.60, p 1 < .001 Statistical Conclusion: There is a significant ass of nonfatal stroke and OC use in these women. -21-

e i 445 Appendix B Analysis of Data from Jick et al. (1978c) Table 4. Number of Cases and Controls Who Smoke or Not Control Stroke f _ Nonsmoker 33 7 Smoker 23 7 Totals 56 14 2 X ~ .36, .50 < P < .70 1 Totals 40 30 70 Statistical Conclusion: There is no association between incidence of nonfatal stroke and smoking in these women. ~ Table 5. Number of Cases and Controls Who Use OC or Not Control Stroke Non-OC User _ 49 _ . 3 OC User 7 11 Totals 56 14 2 X - 25.60, P < .001 1 Totals 52 18 70 Statistical Conclusion: There is a significant association between incidence of nonfatal stroke and OC use in these women. -21- 0

Table 6. Number of Smokers and Recent OC Users Among the 234 Cases and 1,742 Controls without Regard for Age (from Table V, p. 745) OC Use Smoking Status Yes No (MI 4 34 None (Control 52 754 (MI 3 79 1-24 (Control 51 566 (MI 22 92 > 25 (Control 32 287 The rate-ratio estimates unadjusted for age are computed as follows: Cigarette Smoking OC Use No Yes 447 Table 7. Separate and Combined Effects of in Relation to MI: Age-Adjusted Rate-Ratio Est (from Table VI, p. 746) Cigarette Smoking No None 1.0 (Reference Categor 1-24 3.4 (2.2 - 5.1) > 25 7.0 (5.2 - 11.5) . The authors state that Table VI results are "de, in Table V," but this derivation is by no means :ence limits are extremely wide for all OC use c for moderate smokers) and,for non-OC users who z tion, the numbers of OC users among the case (M: ,:s the following table shows (derived'from Tablc None 1.0 (Reference Category) 4/52 + 34/754 4/754 - 1.71 30 - 1 Cigarette Smoking 1-24 79/566 t 34/754 - 3.10 3/51 r 3 . > 25 92/287 + 34/754 - 7.11 22/32 + 34/754 - 15.25 None Without the age adjustment, the rate-rati o estimates for non-OC users are 1-24/day > 25/day similar to those given in Table VI, p. 746 (see Table 7, below). However, the estimates for OC users are mnch lower than those given by the authors. The rate-ratio for moderate smokers who use OC when unadjusted for age is smaller than the corresponding estimate for nonsmokers, which is also true in Table VI, p. 746. However, the rate-ratio estimate for heavy smokers who use OC is 15.25 when unadjusted for age and.Table.Vl, p. 746, gives the figure as 39 (see Table 7 below); the authors' confidence limits do not include my figure of 15. -22- 25-29 30-34 0 0 1 1 3 --- 8 "hese factors imply that the results presented i statistically reliable or valid. -23-

447 Table 7. Separate and Combined Effects of OC Use and Cigarette Smoking in Relation to MI: Age-Adjusted Rate-Ratio Estimates (95Z Confidence Limits) (from Table VI, p. 746) None 1-24 > 25 OC Use No Yes 1.0 (Reference Category) 4.5 (1.4-14.1) 3.4 (2.2 - 5.1) 3.7 (1.0-13.2) 7.0 (5.2 - 11.5) . 39.0 (22-70) The authors state that Table VI results are "derived from the date displayed in Table V," but this derivation is by no means clear. Further, the confi- dence limits are extremely wide for all OC use estimates (and even include 1.0 for moderate smokers) and,for non-OC users who are heavy smokers. In addi- tion, the numbers of OC users among the case (MI) women are extremely small, as the following table shows (derived'from Table V, p. 745) : OC Users Cigarette Smoking 1 25-29 30-34 35-39 40-44 45-49 None 1-24/day ? 25/day 0 0 0 1 3 1 1 1 0 0 3 8 3 5 3 These factors imply that the results presented in Table VI are probably not statistically reliable or valid. -23- Cigarette Smoking

448 Appendix D Analysis of Data from Jick et al. (1978a) Table 8. Number of Cases and Controls with No Predisposing Conditions According to OC Use (from p. 2,549) Control 'fI Non-OC User 49 7 OC User 14 23 449 Table 10. Number of Cases and Controls with According to Cigarette Use (from Table 2, p. 2,54 Control Nonsmoking Now 72 Smoking 54 Totals 126 Totals 56 37 ,. ` • I Totals 63 30 I 93 2 X - 25.14, P < .001 1 . - . . Statistical Conclusion: There is a significant association between incidence of MI and 0C use in women with no predisposing conditions. " Table 9. Number of Cases and Controls With Predisposing Conditions According to OC Use (from p. 2,549) Control MI Totals Non OC User 14 19 33 OC User 0 3 3 Totals - 14 22 36 2 X - 2.08 .10 < P < .20 1 Statistical Conclusion: There is a possible association between incidence of MI and OC use in women with predisposing conditions. -24- 2 ~ - 34.45, P < .001 1 Statistical Conclusion: . There is a significant a of MI and smoking in women with no predisposing c Table 11. Number of Cases and Controls with According to Cigarette Use (from Table 2, p. 2,54 Control "' Nonsmoking Now 14 Smoking 13 Totals 27 2 - 9.68, .001 < P < .01 1 . .J Statistical Conclusion: There is a significant a of MI and smoking in women with no predisposing c

According to Cigarette Use (from Table 2, p. 2,549) Nonsmoking Now Control 72 MI 4 Totals 76 Smoking 54 45 99 Totals 126 49 175 2 X ~ 34.45, P < .001 1 Statistical Conclusion: There is a significant association between incidence of MI and smoking in women with no predisposing conditions. Table According 11. Number of Cases and Controls with Predisposing Conditions to Cigarette Use (from Table 2, p. 2,549) Control MI Totals Nonsmoking Now 14 5 19 Smoking 13 29 42 Totals 27 61 2 x - 9.68, .001 <P<.01 1 Statistical Conclusion: There is a significant association between incidence of MI and smoking in women with no predisposing conditions. -25- 449 Table 10. Number of Cases and Controls with No Predisposing Conditions

450 Appendix E Analysis of Data from Layde et al. (1981) Table 12. Number of Smokers and OC Users Among the Deaths from SAH (from Table IV, p. 543) Deaths from SAH Nonsmokers Smokers Controls (Non-OC Users) 1 5 Ever OC Users 2 12 Totals - . 3 17 2 X - .0187, .90<P< .95 1 Statistical Conclusion: In the population of women aged 35-44 who SAN, there is no association between OC use and smoking. Table 13. Number of Smokers and OC Users Among the tory Disease (from Table V, p. 543) Totals 6 14 20 died from Deaths from Circula- Deaths from Circulatory Disease Nonsmokers Smokers I _ Totals Controls (Non-(C Users) 4 6 Ever OC Users 13 42 Totals 17 48 2 X - 1.17, .20 < P< .30 55 10 65 1 Statistical Conclusion: In the population of women aged 35-44 who died from circulatory disease, there is no association between OC use and smoking. Age Cber-User: 15-25 (4) Nonsmokers Smokers 25-34 Nonsmokers Smokers 7 18 4 17 -26- -27- 2 6 451 Table 14. Number of Cases for Each Sub , -* ! (from Table V, p. 543)

Table 14. Number of Cases for Each Subgroup of (from Table V, p. 543) Age Ever-Users Non-OC Users 15-25(4) Nonsmokers 0 0 Smokers 1 0 25-34 Nonsmokers 2 1 Smokers 6 1 35-44 . Nonsmokers 7 2 Smokers 18 3 45- Nonsmokers 4 1 Smokers 17 2 -27-

452 References Belsey, Mark A. et al (1979). Cardiovascular Disease and Oral Contra- ceptives: A Reappraisal of Vital Statistics Data. Family Planning Perspectives, Vol. 11, No. 2, March/April, 84-89. - Beral, Valerie (1977). Mortality Among Oral Contraceptive Users. The Lancet, October 8, 727-731. Beral, Valerie (1979). The Pill and Circulatory Disease. American Heart Journal, Vol. 97, No. 2, February, 263-264. , Inman, William H. W. (1979). Oral Contraceptives and Fatal Subarachnoid Haemorrhage. British Medical Journal, December 8, 1468-1470. Jain, Anrudh K. (1977). Mortality Risk Associated with the Use of Oral Contraceptives. Studies in Family Planning, The Population Council, Inc., 49-54. Jick, Hershel et al (1978a). Myocardial Infarction and Other Vascular Diseases in Young Women: Role of Estrogens and Other Factors, Journal of the American Medical Association, Vol. 240, No. 23, December 1, 2548-2552. Jick, Hershel et al (1978b). Oral Contraceptives and Nonfatal Myocardial Infarction. Journal of the American Medical Association, Vol. 239, No. 14, April 3, 1403-1406. Jick, Hershel et al (1978c). Oral Contraceptives and Nonfatal Stroke in Healthy Young Women. Annals of Internal Medicine, Vol, 89, July, 58-60. Jick, Hershel et al (1978d). Noncontraceptive Estrogens and Nonfatal Myocardial Infarction. Journal of the American Medical Association, Vol. 239, No. 14, April 3, 1407-1408. Jick, Hershel (1979a). Risk of Myocardial Infarction in Oral Contra- ceptive Users, The Lancet, June 2, 1187. Jick, Hershel (1979b). Risk of Myocardial Infarction in Oral Contra- ceptive Users. The Lancet, October 13, 800. Krueger, Dean E. et al (1980).- Fatal Myocardial Infarction and the Role of Oral Contraceptives. American Journal of Epidemiology, Vol. 111, No. 6, June, 655-674. Hrueger, Dean E. et al (1981). Risk Factors for Fatal Heart Attack in Young Women. American Journal of Epidemiology, Vol. 113, No. 4, April, 356-370. Layde, Peter M. et al (1981). Further Analyses of Mortality in Oral Contraceptive Users. The Lancet, March 7, 541-546. 453 Maguire, Maureen G. et al (1979). Increased Ri Oral Contraceptives: A Further Report. American Jo Vol. 110, No. 2, 188-195. NIH, From the (1981). The 'Pill' Receives Mixe of Walnut Creek Study, Journal of the American Medic No. 10, September 4, 1071-1072. Petitti, Diana B. et al (1978a). Use of Oral C, Smoking, and Risk of Subarachnoid Haemorrhage. The : Petitti, Diana B. et al (1978b). Oral ContraceF Factors in Relation to Risk of Venous Thromboembolic of Epidemiology, Vol. 108, No. 6, 480-485. . .. . , :0 1._ . Petitti, Diana B. et al (1979). Risk of Vasculz Journal of the American Medical Association, Vol. 24: 1150-1154. Rosenberg, Lynn et al (1980). Oral Contraceptiv Nonfatal Myocardial Infarction. American Journal of No. 1, 59-65. Shapiro, Samuel at al (1979). Oral-Contraceptiv cardial Infarction. The Lancet, April 7, 743-747. Slone, Dennis et al (1981). Risk of Myocardial Current and Discontinued Use of Oral Contraceptives. Medicine, Vol. 305, No. 8, August 20, 420-424. Lette ing this paper, Ibid., Vol. 305, No. 25, December 17, Thorogood, M. et al (1981). Fatal Subarachnoid : Women: Role of Oral Contraceptives. British Medical September 19, 762. Tietze, Christopher (1979). The Pill and Mortal. Disease: Another Look. Family Planning Perspectives April, 80-84. Vessey, M. P. et al (1981). Mortality in Oral Cc Lancet, March 7, 549-550. r

453 Maguire, Maureen G. et al (1979). Increased Risk of Thrombosis Due to Oral Contraceptives: A Further Report. American Journal of Epidemiology, Vol. 110, No. 2, 188-195. NIH, From the (1981). The 'Pill' Receives Mixed Reviews in Latest Report of Walnut Creek Study, Journal of the American Medical Association, Vol. 246, No. 10, September 4, 1071-1072. Petitti, Diana B. et al (1978a). Use of Oral Contraceptives, Cigarette Smoking, and Risk of Subarachnoid Haemorrhage. The Lancet, July 29, 234-236. Petitti, Diana B. et al (1978b). Oral Contraceptives, Smoking, and Other Factors in Relation "to Riak of Venous Thromboembolic Disease. American Journal of Epidemiology, Vol. 108, No. 6, 480-485. Petitti, Diana B. et al (1979). Risk of Vascular Disease in Women. Journal of the American Medical Association, Vol. 242, No. 11, September 14, 1150-1154. Rosenberg, Lynn et al (1980). Oral Contraceptive Use in Relation to Nonfatal Myocardial Infarction. American Journal of Epidemiology, Vol. 111, No. 1, 59-65. Shapiro, Samuel et al (1979). Oral-Contraceptive Use in Relation to Myo- cardial Infarction. The Lancet, April 7, 743-747. Slone, Dennis et al (1981). Risk of Myocardial Infarction in Relation to Current and Discontinued Use of Oral Contraceptives. New England Journal of Medicine, Vol. 305, No. 8, August 20, 420-424. Letters to the Editor concern- ing this paper, Ibid., Vol. 305, No. 25, December 17, 1530-1531. Thorogood, M. et al (1981). Fatal Subarachnoid Haemorrhage in Young Women: Role of Oral Contraceptives. British Medical Journal, Vol. 283, September 19, 762. Tietze, Christopher (1979). The Pill and Mortality from Cardiovascular Disease: Another Look. Family Planning Perspectives, Vol. 11, No. 2, March/ April, 80-84. - Vessey, M. P. et al (1981). Mortality in Oral Contraceptive Users. The Lancet, March 7, 549-550. -2-

455 SUpq4Ry OF INFORMATION CONCERNING .1EAN DICKINSON GIBBONS Present Position: (1974- Board of Visitors Research Professor of Statistics (d Statistics Chairman of Faculty Committee for the Program in App1ie (1975- ) and Professor of Mathematics (1976- ), Graduate School, University of Alabama Personal Data: Age 43; Female; Excellent health; Married to John S. Fielden Address: Box J, University of Alabama, University, Alabama 35486 Telephone: 205-348-6085 or 205-345-3750 Positions Held: 1971-1974: Chairman, Department of Statistics and Quantitative Methods, College of Commerce and Graduate School of Business Administration, University of Alabama 1970-Present: Professor of Statistics, University of Alabama 1973 Summer: Research Associate, Stanford University 1968-1970: Associate Professor, Department of Statistics and Operations Research, University of Pennsylvania 1963-1968: Assistant Professor, University of Pennsylvania 1961-1963: Assistant Professor of Mathematics, University of Cincinnati 1962-1963: Consultant in Biostatistics, College of Medicine, University of Cincinnati 1958-1960: Instructor in Mathematics, Mercer University Professional Recognition: Fellow of American Statistical Association, Elected 1972 International Statistical Institute, Elected 1980 Outstanding Scholar of the University of Alabama, Elected 1980 Education: A.B. magna cum laude, 1958, Duke University, Mathematics M.A., 1959, Duke University, Mathematics 'Ph.D., 1963, Virginia Polytechnic Institute, Statistics Attended Columbia University full time, 1960-1961 Academic Honors: Phi Beta Kappa (Junior year), A.B. mapina cum laude Phi Kappa Phi (graduate scholastic honorary) Pi Mu Epsilon (mathematics honorary) Chi Alpha Phi Chapter of Mu Sigma Rho (statistics honorary) Beta Gamma Sigma (business honorary) Biographical sketches in: American Men and Women of Science Dictionary of International Biography Outstanding Educators of America Personalities of the South The World Who's Who of Women Who's Who of American Women Who's Who in the South and Southwest Professional Society Memberships: American Statistical Association (A:B. International Statistical Institute (I Alabama Chapter of A.S.A. Current National Professional Activities: Committee on National Statistics of th( the National Academy of Sciences, 15 Executive Committee of the A.S.A. Secti 1982-84 (nationally elected office) A.S.A. Advisory Committee on Continuing Southern Regional Education Board Commi tative of The University of Alabama, Treasurer, 1978-80 Director at Large of Mu Sigma Rho, 1979 Committee on Affirmative Action of the t ematical Sciences, 1977- Reviewer of grant proposals submitted tc dation, 1976- Editorial Collaborator for various stati various times ) Jouraal of the Americ munications in Statistics, The Americ Biometrics, The Annals of Statistics, Technolo8y, Journal of Educational Re Statistics International Professional Activities: Member of the International Statistical Co-Editor of the Proceedings of the Inte: 1978-80; Participant in meetings, 1971 Senior Fulbright-Hays Scholar, Indian Ste Delegate to NATO Statistical Conference, Delegate to VI International Biometrics C Selected Past Professional Activities: Associate Editor, The American Statiscici Executive 6ommittee of the A.S.A. Section 1977-80 (nationally elected office) A.S.A. Advisory Committee to the U.S. Off 1976-80 Chairman of the Editorial Search Committe Board of Directors of A.S.A., 1975-77 (na: Chairman, A.S.A. Committee on Meetings, 1S Program Chairman for the 1976 annual meet- Advisory Board of the National Cancer Inst President, Alabama Chapter of the A.S.A., 1972-74 Chairman, National Committee on Women in S Lecturer for Visiting Lecturer Program of Representative-at-Large to the Council of • elected office) Constitution Committee of A.S.A., 1972-74 Committee on Elections of A.S.A., 1974 Recent Publications Editor of The American Co-Director, CBMS and NSF Conference on Mu. Summer 1973 President, Phi Beta &appa Chapter, Univers:

455 Professional Society Memberships: American Statistical Association (A.S.A.) International Statistical Institute (I.S.I.) Alabama Chapter of A.S.A. Current National Professional Activities: Committee on National Statistics of the National Research Council of the National Academy of Sciences, 1980-83 Executive Committee of the A.S.A. Section on Statistical Education, 1982-84 (nationally elected office) A.S.A. Advisory Committee on Continuing Education, 1981-83 Southern Regional Education Board Conmittee on Statistics, Represen- tative of The University of Alabama, 1972-; Chairman, 1980-82; Treasurer, 1978-80 Director at Large of Mu Sigma Rho, 1979-82 Committee on Affirmative Action of the Conference Board of the Math- ematical Sciences, 1977- Reviewer of grant proposals submitted to the National Science Foun- dation, 1976- Editorial Collaborator for various statistics journals, including (at various times ) Journal of the American Statistical Association, Com- munications in Statistics, The American Statistician, Technometrlcs, Biometrics, The Annals of Statistics, Sankhya, Journal of Quality . Technology, Journal of Educational Research, Journal of Educational Statistics International Professional Activities: Member of the International Statistical Institute, Elected 1980 Co-Editor of the Proceedings of the International Insurance Seminar, 1978-80; Participant in meetings, 1978-80 Senior Fulbright-Hays Scholar, Indian Statistical Institute, 1973 Delegate to NATO Statistical Conference, Greece, 1972 Delegate to VI International Biometrics Congress, Australia, 1967 Selected Past Professional Activities: Associate Editor, The American Statistician, 1972-80 Executive 6ommittee of the A.S.A. Section an Statistical Education, 1977-80 (nationally elected office) A.S.A. Advisory Committee to the U.S. Office of Management and Budget, 1976-80 Chairman of the Editorial Search Committee of A.S.A., 1979 Board of Directors of A.S.A., 1975-77 (nationally elected office) Chairman, A.S.A. Committee on Meetings, 1975-77 Program Chairman for the 1976 annual meeting of the A.S.A. Advisory Board of the National Cancer Institute, DREW, 1974-76 President, Alabama Chapter of the A.S.A., 1974-76; Vice-President, 1972-74 Chairman, National Committee on Women in Statistics of A.S.A., 1972-a6 Lecturer for Visiting Lecturer Program of A.S.A. and I.M.S., 1973-75 Representative-at-Large to the Council of A.S.A., 1972-74 (nationally elected office) Constitution Committee of A.S.A., 1972-74 Committee on Elections of A.S.A., 1974 Recent Publications Editor of The American Statistician, 1970-73. Co-Director, CBMS and NSF Conference on Multivariate Statistical Analysis, Sumer 1973 President, Phi Beta Eappa Chapter, University of Pennsylvania, 1967-69 i

457 Nonparametric Statistical Inference, McCraw-Hill Book Co., New York, 1971, pp. 306. This graduate level reference and textbook is included in the McCraw-Hill Series in Probability and Statistics and also in the International Student Edition Program. Nonparametric Methods for Quantitative Analysis, Holt, Rinehart and Winston, Inc., New York, 1976, pp. 463. This graduate level textbook, reference or handbook is included in the International Series in Decision Processes, edited by Ingram 01kin. Selecting and Orderin Populations: A New Statistical Methodology, co-authored with Professor Ingram 01kin, Stanford University, and Professor Milton Sobel, University of California, Santa Barbara, John Wiley & Sons, New York, 1977, pp. 569. This is the very first book on this topic; it is a volume in the Wiley Series in Probability and Mathematical Statistics. Concepts of Nonparametric Theory, co-authored with Professor John H. Pratt, Harvard University, Springer-Verlag, New York, 1981, pp. 462. This graduate and research level book is included in the Springer Series in Statistics. "On the Equiprobability of Two Rank Orders," Abstract with H. A. David, Annals of Mathematical Statistics, 1963, Vol. 34, 357. "Effect of Non-Normality on the Power of the Sign Test," Journal of the American Statistical Association, 1964, Vol. 59, 142-148. "On the Power of Two-Sample Rank Tests on the Equality of Two Distri- bution Functions," Journal of the Royal Statistical Society, B, 1964, -Vol. 26, 293-304. "A Proposed Two-Sample Rank Test: The Psi Test and its Properties," Journal of the Royal Statistical Society, B, 1964, Vol. 26, 305-312. "A Correlation Measure for Nominal Data," The American Statistician, December 1967, Vol. 21, 16, with Kenneth H. Ives as first author. "Correlation Coefficients between Nonparametric Tests for Location and Scale," Annals of the Institute of Statistical Mathematics, 1967, Vol. 19, 519-526. "Mutually Exclusive Events, Independence and Zero Correlation," The American Statistician, December 1968, Vol. 22, 31-32. "Estimation of the Number of Critical Sites in Expression During Viral Infection of Bacteria," Vol. 25, 537-544, with Samuel Litwia as second "Properties of the Percentile Modified Rank Tes Institute of Statistical Mathematics Supplement 95-114, with Joseph L. Gastwirth as second auth "A Unified Approach to Hypothesis Testing," Est "A Distribution-Free Two-Sample Goodness-of-Fit Alternatives," British Journal of Mathematical + 1972, Vol. 25, 95-106. • "On the Design of a Random Alarm," Journal of P1 Instruments, 1972, Vol. 5, 634-637, with Samuel "Comparisons of Asympototic and Exact Power for Rank Tests," Sankhya, B, 1973, Vol. 35, 15-24. "A Question of Ethics," The American Statisticiz Vol. 27, 72-76. "Estimation of the Unknown Upper Limit of a Unif Sankhva, B, 1974, Vol. 36, 29-40. "Reporting P-values as an Aid to Decision Making in Proceedings of Southwest Conference Meeting c for Decision Sciences, 1974, Cincinnati, Ohio, 1 "The Visiting Lecturer Program," Letter in The A 1974, Vol. 28, 35. "Simultaneous Estimation of the Unknown Upper an Two-Parameter Uniform Distribution," Sankhya, B, 41-54, with Samuel Litwin as second author. "P-values: Interpretation and Methodology," The 1975, Vol. 29, 20-25, with John W. Pratt as ecoi "The Status of Statistics in the Seventies," Let: Statistician, 1976, Vol. 30, 150. "Comparing the Mean and the Median as Measures o: International Statistical Review, 1977, Vol. 45, R. Stavig as first author. "Baseball Competitions-Do They Play Enough GameE Statistician, 1978, Vol. 32, 89-95, with Ingram C "Parameter Measures of Skewness," Communications Vol. 8, 161-167, with William G. Nichols as first "An Introduction to Ranking and Selection," The P 1979, Vol. 33, 186-195, with Ingram 01kin and Mil

457 "Estimation of the Number of Critical Sites in Limited Genome Expression During Viral Infection of Bacteria," Biometrics, 1969, Vol. 25, 537-544, with Samuel Litwin as second author. "Properties of the Percentile Modified Rank Tests," Annals of the Institute of Statistical Mathematics Supplement, 1970, Vol. 6, 95-114, with Joseph L. Gastvirth as second author. "A Unified Approach to Hypothesis Testing," Estadistica, 1970, Vol. 28. "A Distribution-Free Two-Sample Goodness-of-Fit Test for General Alternatives," British Journal of Mathematical and Statistical Psychology, 1972, Vol. 25, 95-106. "on the Design of a Random Alarm," Journal of Physics - E: Scientific Instruments, 1972, Vol. 5, 634-637, with Samuel Litwin as second author. "Comparisons of Asympototic and Exact Power for Percentile Modified Rank Tests," Sankhya, B, 1973, Vol. 35, 15-24. "A Question of Ethics," The American Statistician, April, 1973, Vol. 27, 72-76. "Estimation of the Dnknovn Upper Limit of a Uniform Distribution," Sankhya, B, 1974, Vol. 36, 29-40. "Reporting P-values as an Aid to Decision Making," competitive paper in Proceedings of Southwest Conference Meeting of American Institute for Decision Sciences, 1974, Cincinnati, Ohio, 18-20. "The Visiting Lecturer Program," Letter in The American Statistician, 1974, Vol. 28, 35. "Simultaneous Estimation of the Unknown Upper and Lower Limits in a. Two-Parameter Uniform Distribution," Sankhya, B, 1974, Vol. 36, 41-54, with Samuel Litwin as second author. "P-values: Interpretation and Methodology," The American Statistician, 1975, Vol. 29, 20-25, with John W. Pratt as second author. "The Status of Statistics in the Seventies," Letter in The American Statistician, 1976, Vol. 30, 150. "Comparing the Mean and the Median as Measures of Centrality," International Statistical Review, 1977, Vol. 45, 63-70, with Gordon R. Stavig as first author. "Baseball Competitions-Do They Play Enough Games?," The American Statistician, 1978, Vol. 32, 89-95, with Ingram 01kin and Milton Sobel: "Parameter Measures of Skewness," Communications in Statistics, B, 1979, Vol. 8, 161-167, with Williaa G. Nichols as first author. "An Introduction to Ranking and Selection," The American Statistician, 1979, Vol. 33, 186-195, with Ingram 01kin and Milton Sobel.

458 "Quantitative Coefficients for Selecting a Measure of Central Location," with Gordon R. Stavig. Chapter 18 in Sociological Methodology 1980 (K. P. Schuessler, Ed.), Jossey-Bass, San Francisco, pp. 545-558, 1980. "A Subset Selection Technique for Scoring Items on a Multiple Choice Test," Psychometrika, 1979, Vol. 44, 259-270, with Ingram 01kin and Milton Sobel. "organizations for Statistical Consulting at Colleges and Universities," The American Statistician, 1980, Vol. 34, 140-145, with R. J. Freund. "Selection Procedures: A New Statistical Methodology and its Applications for Marketing Research," Journal of Marketing Research, 1981, Vol. 18, 449-455, with Oded Gur-Arie. 459 Statement of Katherine McDermott Herrold, :4y name is Katherine McDermott Herrold. pathologist and am presently retired from position as medical director of the Unitec Health Service. "Brovn-Mood Median Test." An entry in the Encyclopedia of Statistical !*x Sciences, Volume 1(Norman L. Johnson and Samuel Kotz, Eds.), John Wiley & Sons, New York, 1982. - "Methods for Selecting the Best Process," Journal of Quality Technologq, 1982, Vol. 14, No. 2. Other Publications: Author of statistics section, pp. 106-108, of Nontraditional Careers for . Women by Sarah Splaver, Julian Messna , New York, 1973. ? Editor, Roster of Women in Statistics, The American Statistical Association, 3~ Washington, D.C., July 1974. "Nonparametric Statistical Methods," by Myles Hollander and D. A. Wolfe, John Wiley, New York, 1973, Review in Technometrics, 1974, Vol. 16, 477- 478. Quality of Scientific Evidence in FDA Regulatory Decisions, Hearing before a Subcommittee of the Committee on Government Operations, House of Repre- - sentatives, Ninety-Fifth Congress, U.S. Government Printing Office, Wash- ington, D.C., 1978. Technical Reports published by Johns Hopkins*IIniversity, University of of Michigan. °' it i d II vers y n Gaosgla, aa Selected Colloquia Pr.esentations: Virginia Polytechnic Institute, February 1976 SREB Susmer Research Conference, June 1977 1977 North Carolina State IIniversity, October University of South Carolina,. February 1978 Winter Simulation Conference, December 1978, Miami Monterey June 1979 hool S t d , , c ua a Naval Postgra A.S.A. Short Course, August 1979, Washington, D.C., with Robert E. Bacbhofer, Shanti S. Gupta, and Ingram 01kia, available on videotape from the A.S.A. A.S.A.-A.S.Q.C. Pall Technical Conference, October 1979, Minneapolis I received my medical degree from Women' Pennsylvania in Philadelphia in 1948. Frc I interned at George Washington Universit} D.C. Between 1952 and 1955 I was the chie the Federal Reformatory for Women in Alder 1955 and 1957 I was a resident in clinical tween 1957 and 1959 I was a resident in pe both of these positions being at the Natic Health in Bethesda. Between 1959 and 1971 pathologist at the National Cancer InstitL I am a member of numerous professional sc :+.:.erican Society of Clinical Pathologists, Pathologists, the International Academy of a.-erican Association for Cancer Research. :onorary medical society of Alpha Omega Al I have published papers in the scientifi -+ith pathology and cancer research. 95-077 0-82--30