Document bz9mrRQaJJpkgQqJpqNm1eb3

I CMA INTEROFFICE MEMO TO: Carol Stack, Ph.D, FROM: Patrick C. Joyce DATE: January 25, 1982 RE: Vinyl Chloride Contract with University of Louisville Enclosed correspondence from Dr. Musacchia appears responsive to my request of December 29, 1981 regarding our contractual difficulties. Please review the matter with the Panel and advise whether further services are desired. I will not acknowledge receipt of the letter until I hear from you. CMA 01-4236 Gndnatc School University of Louisville Belknap Campus January 20, 1981 Lootivilk, K; 40292 (502) 588-6495 Mr. Patrick C. Joyce Attorney Chemical Manufacturers Association 2501 M Street NW Washington, D.C. 20037 Dear Mr. Joyce: This is the follow-up of our telephone discussion and your letter of December 29, 1981 concerning the contract between the Chemical Manufacturers Association and the University of Louisville with Dr. Carlo Tamburro as principle investigator. I was pleased to have had the op portunity to discuss the proposal and some of the difficulties that we had experienced in the conduct of this particular research. I have had two meetings with Dr. Tamburro in order to learn about the problem that he had experienced within the University and which led to delays in providing final reports. I learned that there had been some internal problems with obtaining adequate computer time in order to meet commitments on a timely basis. Dr. Tamburro agreed that an outline of his plans for the completion of this project was necessary. He has been very cooperative in providing me the details of plans for the final report. I have taken the liberty of Xeroxing his communication with me since it presents the details in a succinct and professional manner. In our discussions, I assured Dr. Tamburro that necessary computer services would be made available in order that he be able to complete the project as initially defined. We estimated that it would take about three months for completion of the data analysis, writing the final report and preparing adequate numbers of copies for the Chemical Manufacturers Association, tty estimate is that this project should be completed and the final report in your hands on or about May 1, 1982. I appreciated the opportunity to outline our efforts to cooperate and your understanding of the fact that, from time to time, unpredicted impediments tend to slow down the proper progress of research. CMA 014237 Mr. Patrick C. Joyce Page two January 20, 1982 I look forward to an opportunity to meet with you peraonally when I am in Washington and, if you have an opportunity to visit Louisville, please give me a call and perhaps we can have lunch together. XJM:dc Enc. cc: Mr. Norbert Elbert, Vice President for Administration Dr. Herbert Garfinkel, Vice President for Academic Affairs Dr. Don Kmetz, Dean of the Medical School Dr. Carlo Tamburro, Professor of Medicine and Community Health Dr. John Brown, Office of Sponsored Programs CMA 014238 Sthnnl of Medicine IKpjrtmcnr of Medicine Dimimi of Diyesnve Diseases and Nutrition University of Louisville Health Sciences Center January 21, 1982 Louisville, Ky 40292 X. J. Musacchia, Ph.D. Professor, Physiology & Biophysics Dean, Graduate School - Administration University of Louisville Louisville, Kentucky 40292 Dear Joseph: The following describes what has been planned for the final report to the Chemists Manufacturing Association's agreement with the School titled "Research, Techniques, and Methods for Detection and Prevention of Carcinogenisis in Industrial Workers". The program began in 1976 and has undergone a number of changes from the original proposal. The final report, therefore, will have the following format: I. INTRODUCTION: A very short sumnary of the initial proposal, changes, modi fications and additions made to the original proposal will be summarized^ II. BACKGROUND: In short paragraph form, the background for each of the original seven and final additional two technical research proposals shall be described. III. RESEARCH PROGRAMS AND RESULTS: This will be the main body of the final report. It will be divided into nine parts, each related to one of the nine technical proposals. Each research proposal's final report will be presented in the following format: A. Objectives B. Background C. Research study, protocol, and performance D. Results E. Significance or relevance to chemical industry F. Reference to publications IV. SUMMARY: A concise sumnary of the entire program and its research results of no more than three pages will be included. V. APPENDICES: A copy of every publication, abstract, and preprint produced from the research work done will be Included. - CMA 014239 X.O. Musacchia, Ph.O. 1/21/82 Page 2 VI. ONGOING RESEARCH: An outline of all present ongoing research whose base was developed during the MCA proposal, but is not yet complete, will be presented in one-page summaries indicating: A. Objectives B. Present status of the work C. Approximate time estimate as to its completion Please feel free to submit this outline of the final report based on our under standing, with your letter to the Chemists Manufacturing Association's legal representatives. Sincerely yours CHT/vs Carlo H. Tamburro, M.D. Professor of Medicine and Conmunity Health Director, Liver Research Center Division of Digestive Diseases and Nutrition Chief, Division of Occupational Health CHA 0142-40 t Panel; \ZiAPjt C M A ATTENDANCE SHEET (please print) __ Date:--'Tartrti'-y. 2-?t /f/f:----- Location: ^Wy &Q*~ Secretary; S. PLEASE COMPLETE NAME /?*. Stock COMPANY CM# S .p 'T3fl i (St**'* P 0 U r N /J. KlTTtLSrA7? d /zr/l/ h r /) }/ L K t ft Str er l- <_ /f *>y Co^cc o /c /V //y//e*t ^//V/ o*t/ C** * dfJ TITLE /a f <s*+v-- < AiTtr+oU-*^ ADDRESS & PHONE 2-54/ 4i 5+rc*Jt MAJ. UJft^htn i tont 0-d.. z++ 3 ? zx-z/ r/7 - //fi ~>.o Sikh'S . y>/< > /a r* 7 7 oo/ C&n_p 0i+vcTQ*/J /i c T/A g t> /> a fi r *q 7-0*, r.o caotsr 77*' p. O /J c k * VAAt-iL'') ^os^-G-A. 7'A *9vrZ P O *3ofc Y31<0 tfoA>%ro*> )7ao 7/2-^ Hf-oo / !1 t /J u 1 7 a 73\>* X J(~ / 7c<sr,* 7 i * if ^ >t/ 7 y P'4 * >J*~J 3uY J*/ ? J.7C f CMA 0 1 4 2 4 1  NAME It & At Ji Lynch T. ^S- I3E MyA BcrH C^UtuIacL C M A ATTENDANCE SHEET (please print) COMPANY tfjoeDiFA) PLEASE COMPLETE TITLE (*6&P~7*<JCDfe ~ ADDRESS & PHONE t /YS-y Ct/W^cc/s ExX(5 N G-/ F W, Co & ^ dooc/prc. l) ^Trt ]5cn 3 13 H ^ee^r^/HJ{ os9 ?$ /e x/ / ^y. . "ZfKkD 1 1 f ' S'o & fa Y3t <1 A'^o+ry )CJ/t 39^-2* H-S( "Fi-oV1 * &>f -La >v#o/ UtCt'TlC<J TTU. irA-^ -Y^ pY f p**/ B/irvu ** & | ^4, Xa r`-T*s< &*** TYsj-f&liAj Y/t /y*p- sf* *-'*- B CMA Notice of Meeting of the Vinyl Chloride Program Panel PeQembeg 16/--1081 Time: 9:00 A.M. Place: CMA Offices 2501 M Street, N.W. Washington, D.C. 20037 I will attend the meeting. I will not be able to attend the meeting. (Name) M Nil (fr/U- (Company) retus* this' form to Dr. Carol Stack at itae v shown above. CMA 014243 4 i9d1 Axibjcam Journal of EptttMXOLOGY Copyright 1981 by Th* John* Hopkiai Uniwvtty School of Hygiene and Public Health Aii nghce reserved ' K' VoJ. 114, No, 5 Pnntod tn CT-S^4 POWER CONSIDERATIONS IN EPIDEMIOLOGIC STUDIES OF VINYL CHLORIDE WORKERS JAMES J. BEAUMONT' amd NORMAN E. BRESLOW* Beaumont, J. J. (NIOSH, Cincinnati, OH 45226) and N. E. Braalow. Power considaratlona In epidemiologic studlaa of vinyl chlorfda workers. Am J Epldamtoi 1981 ;114:725-34. Nina ratroapactlva mortality studlaa of workers exposed to vinyl chloride were reviewed to determine whether differences in their hypothesis testing results might be due to differences in statistical power. Where possible, the power of each study was calculated for cancer of the lung, brain and liver. When power was taken into consideration, the results for liver and brain cancer were found to be consistent with an etiologic role for vinyl chloride. For lung cancer, the data were not consistent with an etiologic role. In that two studies with very high power yielded negative results. epidemiologic methods; respiratory tract neoplasms; brain neoplasms; liver neoplasms; vinyl chloride The nine mortality studies of workers sites of cancer--liver, brain and lung-- exposed to vinyl chloride that have been was calculated, and their hypothesis test completed to date disagree in their hy ing results, positive or negative, were pothesis testing results for some causes of considered in the context of power. death, and for those causes it is difficult to draw conclusions about excess risk Methods (1-12). The studies that are negative for Power calculations a cause of death are especially difficult to interpret, since they may or may not have had the statistical power to detect an ex cess risk if, in fact, one existed. To aid in the interpretation of the studies, their statistical power with respect to three Statistical power is the probability of not overlooking an excess risk, i.e., of not making a Type II statistical error. To aid in the interpretation of this frequently confusing subject, a brief review of Type I and Type II errors follows. Investigators are most familiar with Received for publication November 14,1980, and in Seal form April 13,1981. < Industrywide Studies Branch P-8, National In stitute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, OH 45228 (address for reprint requests). * Dept, of Bioctatistics, School of Public Health and Community Medicine, U. of Washington, Seat tle. WA 98195. The author* thank Jay Lubin, Richard Waxweiler, Thomas Fischbach, Nod Weiss and William Halperin for their valuable advice. Their special thanks go to Philip Landrigan for encouraging this approach. This paper was prasanted at the Conference to Re evaluate the Toxicity of Vinyl Chloride, Polyvinyl Chloride end Structural Analogues, Rockville, MD, March 20-21,1980. Type I errors. If the true state of nature is the null hypothesis (no increase in risk), then a Type I error is wrongly rejecting the null hypothesis and declaring that there is an increase in risk. The probabil ity of a Type I error is known as alpha, or more commonly, the "level of signifi cance." For example, when an inves tigator finds an excess and declares it "significant at the 0.05 level," in a sense what he or she is saying is that there is less than a 5 per cent chance of having made a Type I error. Type II errors are less familiar but. CMA 725 For Distribution by CMA SPECIAL PS0C3AM3 DIVISION 014244 Ref. No. l/C - Pa 12 lib l 726 BEAUMONT AND BRESLOW nevertheless, very important (13). Under lying this concept is the fact that when the true state of nature is the alternative hypothesis (increased risk), the research goal is to detect it (i.e., reject the null hy pothesis). Suppose one has specified an alpha level (0.05, for example) for testing a null hypothesis of no increased risk for a particular exposure. If an exposure is harmful with a relative risk ofH, then not rejecting the null hypothesis (i.e., wrongly accepting the exposure as harm less) is called a Type II error. The proba bility of a Type II error is usually denoted beta ($). Conversely, the probability of correctly rejecting the null hypothesis and therefore of detecting the excess risk, is called the power and is equal to 1 - $. Thus, power quantifies the ability of a particular study to detect an excess risk that truly exists. It is intuitively clear that with a fixed amount of data there is a greater likelihood of detecting a large ex cess risk. Similarly, an increase in the amount of data increases the chance of observing a given risk, i.e., increases the power. The approximate power 1 - of the vinyl chloride studies to detect a relative risk R at the alpha level of significance was calculated from the following for mula, which uses the fact that the square root transformation stabilizes the vari ance of the Poisson distribution (see the statistical appendix): Z,_, - Z. - xVr - 1XVE) Here Z. denotes the upper 100. per centile of the standard normal distribu tion and E the expected number of cancer deaths based on general population rates. This approximation agrees well with exact power calculations based on Poisson probabilities made by Cutler et al. (14, 15). When the discreteness of the exact test based upon Poisson probabilities is accounted for, the approximate and exact power curves are virtually identical. A family of power curves based upon the approximation is shown in figure 1, where each curve is for a different rela tive risk. It can be seen that as the as sumed relative risk increases for a given number of expected deaths, the power also increases. Similarly, as the expected number of deaths increases for a given relative risk, the power also increases. Application to vinyl chloride literature The assumed relative risks for the power calculations were the median (ap proximate) standardized mortality ratios reported for each cancer site in the vinyl chloride literature. Power calculations are usually performed with a somewhat arbitrarily chosen relative risk, but since relative risk information was available from the vinyl chloride studies, it was thought best to make use of these data. Separate assumptions were made for analyses considering all person-years at risk and for analyses considering only person-years after a minimum latency (time since first exposure), because in the former case the risk was diluted by the 10 to 20 years that are often required for cancer to develop after exposure to a car cinogen. The median reported mortality ratio was not used in one instance: for overall lung cancer, where the median was 1.03, essentially no excess risk. Since some risk needs to be assumed to calcu late power, the arithmetic mean (approx imately 1.5) was used. The statistical powers of mortality studies of workers exposed to vinyl chloride were calculated with respect to three sites of cancer: liver, brain and lung. These three sites were chosen be cause they have been the subject of most of the discussion of causality in the vinyl chloride literature. The powers of the studies were subsequently plotted on power curves for two purposes: to show the variability in powers, and to relate positive and negative findings to power. For the purposes of this review, a positive finding was defined as an excess risk for a .1 S LU 3oa. particula canee at Poisson t It was was care should bt power sh the stud general, exposure of R acre assumpt cause, as differed The h vinyl ch. in table tions va: study by 1S, * T\ 1 _ Vw `A --* m CMA 014245 POWER CONSIDERATIONS IN VINYL CHLORIDE STUDIES 727 EXPECTED DEATHS Ficunc. 1. Approximate power curve* for varioui aMumed relative risk* in standardized mortality ratio studies .(for one-sided comparisons with alpha - 0.05). particular cancer with statistical signifi* cance at the 0.05 level, using a one-sided Poisson test. It was expected that if vinyl chloride was carcinogenic for an organ site, there should be a pattern: the studies with high power should, in general, be positive, and the studies with low power should, in general, be negative. TTus assumed that exposure would result in a constant value of R. across the various populations. The assumption was somewhat tenuous be cause, as discussed below, the populations differed in a number of respects. Results The historical prospective studies of vinyl chloride exposed workers are listed in table 1. The sizes of the study popula tions varied considerably, from 255 in the study by Nicholson et al. (3) to 9677 in the Equitable Environmental Health study (6, 7). The reports were not entirely in dependent; for example, many of the workers in the study by Ott et al. (10) were included in the Equitable Environ mental Health study, and there was an overlap of about 800 workers in the studies by Waxweiler et al. (4) and Wax- weiler (5). It should be noted that the studies were dissimilar in many other ways. As can be seen in table 1, a minimum exposure of 1-5 years was required in some studies, while others required only one day. Some studies reported findings based upon all person-years at risk, some included person-years at risk only after a mini mum time since first exposure, and some reported both types of analysis. The con trol (standard) populations used were dif ferent four of the five American studies BttriiflBijaiMMMMiairii< iwrai*i * X X 728 BEAUMONT AND BRESLOW X XX X XX XX X IX XX X xXX XX XXXX XXX X x XXXXXX Q V) Ifl C AA --o e AAA AA c* us ^ < IS Cl s r* N m 5 t* -- ^ tfd a r* N (C n ic n A 9VA * P* c* r* ttf W9 <8 Q) A A A sso V 4B Q A ^ t ^ fi c & aa a 1IcS- ! ez& 35 ed used United States rates, the fifth used Texas rates; and the British, Swedish and German studies used their respective na tional rates. There were also minor differ ences in the International Classification of Diseases codes included for the specific cancers. Finally, there were probably dif ferences in age composition which could be important if an effect were dependent upon age. While it was felt that none of these dissimilarities was important enough to prevent comparison of statistical powers, it should be noted that factors other than power could have had a bearing on the ability ofthe studies to detect excess risk. Liver cancer was reported in the four studies listed in table 2 and graphically presented in figure 2. When the results were tested for statistical significance with a one-sided Poisson test, it was found that three of the four studies showed sig nificant excesses (4, 5, 8, 11). The powers were all very high, despite the fact that the expected numbers of deaths were in all instances small. The small expected numbers would normally have led to low statistical powers, but the high estimated relative risks had a large effect on the cal culations. The powers of the studies are shown in two columns in table 2 and on two lines in figure 2 because the calcula tions assumed different relative risks for analyses considering all person-years at risk and for analyses considering only person-years after a minimum latency (relative risks of 5 and 10, respectively, were assumed for liver cancer). The results for brain cancer (table 3) were more variable, in that three of five studies had statistically significant find ings (5-7, 11), and that the powers ranged from 12 per cent to a maximum of approximately 80 per cent. In figure 3, the range of powers is presented graphically. It can be seen that, in general, the studies with high power had positive findings and those with low power had negative find ings. Of the eight studies of lung cancer, only Fox and C< Waxweiiar (10+ la Waxaiailar (IS* la expoaui Byran at a (10* la Rainl at a Ftcui ralau+a BYREN v-,-.-". . > x-'v. ;. N . .. . . .; ; V-., * .'V CMA 014247 TOWER CONSIDERATIONS IN VINYL CHLORIDE STUDIES 729 Tasli 2 Liver cancer: result* and powers of epidemiologic studies of vinyl chloride Author Obaorvad Expoetad Mortality death* daatha ratio Exceee p < 0.0S7 Power!*) URR - 5.0 IfRR - 10.0 Fox and Collier (1, 2) 4 1.6 2.44 - 93 Waxweiler (5) (10+ latency) 10 2.3 4.27 8 0.5 15.09 + + 98 92 Waxweiler et al. (4) (15+ latency, 5 + expoiurt; Byren et al. (11) (10+ latency) 7 0.4 16.08 + 86 4 1.0 4.13 + 80 4 0.7 5.89 98 Rainl et al. (8) 12 0.9 15.23 + 76 EXPECTED DEATHS Ficuix 2. Approximate power* ofvinyl chloride studios reporting results for liver cancer. 10.0 - aatumed relative risk after a niTMTM latency, 5.0 " wanted relative risk ovarmll. REINL Rainl at aL (8); BYREN - Byren at aL (11); FOX " Fox and Colliar (1,2); WAX m Waxwailar at at (4) and Waxwailar (5). two yielded statistically significant re* suits (4,5, 9) (table 4 and figure 4). Again, there was a wide range of powers, from 14 per cent to almost 100 per cent, but here the studies with very high power, were negative, an unlikely occurrence if vinyl chloride is indeed a human lung carcin ogen. Discussion The data regarding liver cancer in vinyl chloride exposed workers suggested CMA 014248 730 BEAUMONT AND BRESLOW sS i 3 3(C i! 6 p< n WA n it 'S : 1 i* rM* p^j C-l P5 -- N( n 6 kfi -- 7. mac il n i3 11 5 11 --J&*!*? S L -- -- | I|j| 15 ^ 15=*3. SUlSs-- wn* -- a*I, i1u strongly that the chemical is carcinogenic for the liver. Three of the four studies re ported statistically significant excess risks (4, 5, 3, 11), and the nonsignificant study (1, 2) reported a small excess (4 ob served, l.'S expected). The statistical pow ers of the studies were high tall above 75 per cent) due to the high observed relative risk. Even without knowledge of the animal studies, and without knowledge that angiosarcoma of the liver is ex tremely rare, one might conclude from these data that vinyl chloride is car cinogenic for the liver. The powers of the studies that reported brain cancer ranged from 12 per cent to SO per cent. The expected trend for a causa tive association was seen, in that the studies with high power were statistically significant and the studies with low power were, with one exception, nonsig nificant. The most reasonable interpreta tion, therefore, is that the data are consis tent with an etiologic hypothesis for vinyl chloride and cancer of the brain. Only two of eight studies reporting lung cancer results showed significant excesses (4, 5, 9). While some of the negative re sults could be explained by low statistical power, two studies that were negative had very high power (1, 2, 6, 7). The lack of trend is evidence that vinyl chloride may not be a lung carcinogen, or that the ac tual relative risks were much lower than the assumed values of 1.5 and 2.0, in which case the powers were also much lower. It should be noted that one of the two negative studies with high power (by Fox and Collier (1, 2)) was also negative for liver cancer. Since it is generally ac cepted that vinyl chloride is a liver car cinogen, it may be that the exposures in that study were minimal. The other nega tive study with high power (Equitable) did not report liver cancer results, but did find a significant excess of brain cancer, which may constitute evidence of sub stantive exposure. Examination of "positive" and "nega- c 80 -a1 so ce ui 3o 40 0. 20 0 Fit ( .it -f -I tive" hy light of several i dence of For exai relative bining t bers froi help of which s combine for the 1 the pres relative also a : homoge Reinl ( bined i cancer i CMA 014249 POWER CONSIDERATIONS IN VINYL CHLORIDE STUDIES 731 EXPECTED DEATHS Figuxi 3. ApproximsU powers of vinyl chloride studies reporting result# for brain cancer 3.0 assumed relative risk after a minimum latency, 2.0 assumed relative risk overall. BYREN Byren et al. (II); REINL - Reinl et al. (8); FOX - Fox and Collier (1, 2); WAX - Waxweiler et al. (4) and Waxweiler (5); EQUIT Equitable Environmental Health (8, 7). tive" hypothesis testing results in the light of statistical power is only one of several approaches to reviewing the evi dence of carcinogenicity for a substance. For example, one can compute a combined relative risk for each cancer site (by com bining the observed and expected num bers from the studies), and then, with the help of homogeneity testing, determine which studies are compatible with the combined risk estimate (see the Appendix for the homogeneity test). Liver cancer in the present review has a combined overall relative risk of 5.17 (p < 0.00001), and also a significant (p 0.002) result in homogeneity testing, largely due to the Reinl (8) relative risk of 15.23. The com bined relative risk for overall brain cancer is 1.74 ip < 0.01); here the results are more homogeneous ip " 0.10), al though Byren (11) is somewhat of an out lier with a relative risk of 6.12. Finally, the combined relative risk for overall lung cancer is 1.06 (nonsignificant), with some evidence (homogeneity p - 0.06) that the results from Waxweiler (4,5) and Buffler (9) are out of step with the others (relative risks of 1.49 and 2.89, respec tively). Close examination of the individual studies can also be helpful in searching for reasons for differing results. For example, the expected number of deaths from liver cancer in the Byren study (11) is unusually large relative to the expected numbers for brain and lung. Detailed examination of this anomaly might be informative. There are other consid- CMA 014250 a*M +1 fi1 > lu --lh Tau 4 Lung tumttr: ituijli nnW jautwrj of tiiiilnniolagic ntudtea of otnyt chiort*ie amir Otwerval death* KitivrlrJ death* Mortal ily ralM Eicrn p < 0067 Fewer () ir 88 - 16 If Hit - ; Kok and Collier U. 21 (16+ latency) Wnaweiler (6) OO t latency) 48 61 2 090 ,- 94 28 28 0 1.08 - 100 42 28.2 1.49 + 77 39 24.9 1.68 i 99 Waaweiler el at. (4) (16+ latency, 6+ exposure) II 67 1.94 * Equitable Enviranmenial Health (i, 71(1+ eaitoatira) 46 44.3 1 02 - 91 (16+ latency, 1 + eipoeure) 41 39.2 l 05 100 Bufller et al. (91 6 1.7 289 -* 14 (6+ latency, 2.29+ eapoaurel 4 1 0 3 81 + 21 Byren et al. (II) ,3 1.8 1 88 16 Duck el al. 02) Id 16.6 1 03 - 6 iteinl el al. (8) 22 248 0.95 - 76 Oil el el. (10) 4 6.2 0 77 27 BEAUMONT AND BRESLOW CMA 0 1 4 2 5 1 . POWER CONSIDERATIONS IN VINYL CHLORIDE STUDIES 733 Figuri 4. Approximate powers of vinyl chloride studies reporting result* for lung cancer 2.0 _ assumed relative risk after a minimum latency, 1.3 " assumed relative risk overall. BUFF - Buffler et al. (9); BYREN - Byren et al. (11); OTT - Ott et al. (10); DUCK - Duck et al. (12); REINL - Reinl et al. (8); WAX * Waxweiler et al. (4. 5); EQUTT Equitable Environmental Health (6, 7); FOX * Fox and Collier (1, 2). erations, such as dose-response, degree of exposure, concomitant exposures, and confidence limits for risk ratios, that also need to be kept in mind. While consid eration of statistical power cannot pro vide a complete answer, it is one more useful way of looking at epidemiologic evidence. Rxrxxxwcxs 1. Fox AJ, Collier PF. Low mortality rates in in dustrial cohort studies due to selection for work and survival in the industry. Br J Frev Soc Msd 1976;30:225-30. 2. Fox AJ. Collior PF. Mortality oxporionce of workars axposod to vinyl chloride monomer in the manufacture of polyvinyl chloride in Grsat Britain. Br J Ind Med 1977;34:1-10. 3. Nicholson WJ, Hammond EC, Ssidmen H, ct al. Mortality experience of a cohort of vinyl chloridt-polyvinyi chloride workars. Ann NY Acad Sri 1975;246:225-30. 4. Waxweilsr RJ, Stringer W, Wagoner JK, et al. Neoplastic risk among workers exposed to vinyl chloride. Ann NY Acad Sri 1976;271:40-8. 5. Waxweiler RJ. An epidemiologic investigation of lung cancer in a multixenobiotie environ ment. Ph.D. Dissertation. Chapel Hill, NC: University of North Caroline. 1978. 6. Taberahaw IR, Gaffey WR. Mortality study of workers in the manufseture of vinyl chloride and its polymers. J Occup Med 1974:16:509-18. 7. Equitable Environmental Health, Inc. Epidemi ologic study of vinyl chloride workers. Fine! re port submitted to Manufacturing Chemists As sociation, 1978. 8. Reinl W, Weber H, Greiser E. Diseeaee caused by vinyl chloride. Special report of tho State In dustrial Physician, Dusseldorf, West Germany, 1978. 9. Buffler PA, Wood S, Clayton E, et aL Mortality experience of workers in s vinyl chloride monomer production plant. J Occup Med 1979;21:196-203. 10. Ott MG, Langner RR, Holder BB. Vinyl chloride exposure in a controlled industrial environ ment Arch Environ Health 1975;30:333-9. 11. Byren D. Engholm G, Englund A, et al. Mortal ity and cancer morbidity in a group of Swadish 734 BEAUMONT AND 3RISLOW VCM nd PVC production workor*. Environ Health Peropoet 1976:17.167.70. 12. Duck BW, Carter JT, Coobo* EJ. Mortality study of worker* in a polyvinylchloride produc tion plant. Lancat 1975,2.1197-9. 13. r reiman JA. Chalmers TC, Smith H. et al. The importance of beta, the Type II error, and sam ple size in the design and interpretation of the randomized control trial. N Engl J Med 1973;299:690-94. 14. Cutler SJ, Schneiderman MA, Greenhouse SW. Some statistical considerations m the study of cancer in industry. Am J Public Health 1954:44:1159-66. 15. Molina EC. Poisson's exponential binomial limit. Huntington, NY: Robert E. Kneger Pub lishing Company. 1973. IS. Arautage P. Statistical methods in medical re search. Oxford: Blackwell Scientific Public*- tiona, 1971. Appendix The approximate power formula assumes that the observed number of deaths from the cause of interest follows a Poisson distribution with mean RE, where E is the ex pected number based on standard population rates and R is the ratio of rates (relative risk) for the study as opposed to the standard population. It follows that for large values of RE, the square root of the observed deaths is approximately normally distributed with mean \'RE and variance V* (16). Now, if a random quantity has a normal distri bution with mean m and variance oJ, its power 1 - 0 to reject the null hypothesis n m* at the a level of significance is given by Z.-s Z,, - Substitution of n \/RE, m V, and cr V4 into this expression yields the re quired result. The homogeneity test for the combined relative risk uses the chi-square distribu tion with n - 1 degrees of freedom.' The equation is x.*.-,, - fiml $Ej the number of studies, the observed deaths from the tth study, the expected deaths from the ith study, Z Otl the combined relative risk estimate. Aw*Hi THE d. , tc to affect, commun ing and The illnability, ment an Little schizopr Reeeiro in final fc 1 Dept. t of Medicic School of Dope. School of * Dept.of Medici Addrni 1006, Jol Baltiaort Thii w grout* fit CMA 014253 CHEMICAL MANUFACTURERS ASSOCIATION December 16, 1981 MEMORANDUM TO: Vinyl Chloride Program Panel FROM: Carol R. Stack Please note that the December Program Panel meeting has beer, rescheduled for January 27, 1982 at 9:00 A.M. in the Lobby Confer ence Room. Environmental Health Assoicates (EHA) is preparing an alter-', native proposal for the epidemiology study update. EHA expects to submit the proposal to CMA by the end of the year. Copies will be distributed to Panel members for review prior to the January 27- meeting. i. If you are unable to attend this meeting, please let me know as soon as possible. Tentative Agenda 1.0 Reassessment of epidemiology study update; status of contract negotiation 2.0 Review of alternative proposal from Environmental Health Associ ates 3.0 Status Report - University of Louisville study CRS/seh CMA 0142SA Formerly Manufacturing Chemists Association--Serving the Chemical Industry Since 1872, 2501 M Street. NW Washington. DC 20037 Telephone 202/887-1100 Telex 89617 (CMA WSH) kI - L> ? Air Products and Chemicais.^A^! ^ ^ 1^85? 8ox 538 Allentown PA 1 a105 (215)481-491 i j 18 January 1982 Dr. Carol Stack Chemical Manufacturers Association 2501 M Street, N.W. Washington, D.C. 20037 Dear Dr. Stack: As I have told your office, I will not be able to attend the meeting of the Vinyl Chloride Panel on 27 January because of a prior commitment. However, we have reviewed the revised proposal distributed with your letter of 5 January and wish to record our vote in favor of this proposal, providing that an agreement staisfactory to CMA can be reached on the items discussed in the 31 December letter from T. H. Mil by regarding the minor wording changes. We are sorry to lose the dose response data, but agree that the earlydefinitions of dose are not. satisfactory, and we can offer no other sug gestion. Searching and estimating by job description will give a partial substitute for dose. We have the death certificates for all employees who died while employed or on pension. It may expedite the study and lower the cost if each company is asked to return those certificates which are available when task 7 is performed. Please advise me of the outcome of this meeting. I am sorry that I cannot attend. If there Is anything else which I can do to assist this program, please let me know. Very^truly "yours, John T. Barr Manager, Regulatory Response JTB/sjw cc: Dr. T. Torkelson - Dow Chemical Co. Dr. A. R. Adams - APCI CMA 014255 Diamond Shamrock January 19, 1982 JAN 2 1 |gQ3 Carol R. Stack, Ph. D. Administrator Vinyl Chloride Program Chemical Manufacturers Association 2501 M Street, N. W. Washington, D. C. 20037 Dear Dr. Stack: Excuse my delay in informing you that no one from Diamond Shamrock Corporation will be attending the January 27th Vinyl Chloride Program Panel Meeting. Recent developments have caused us to modify our approach to participation in this program. Early in January it was announced that Diamond Shamrock Corporation had completed sale of parts of its Plastics Operations to B. F. Goodrich. This has led to a reallignment of responsibilities within the Diamond organization. Future monitoring and participation in the program will be handled by Mr. Edward J. Baier, Director of Industrial Hygiene. Correspondence should be directed to his attention at the following address: Diamond Shamrock Corporation World Headquarters 717 North Harwood Street Dallas, Texas 75201 His phone number is (214) 745-2738. Should you have any questions please do not hesitate calling me at (216) 357-3544. Very truly yours, J. R. Semancik Manager Technology Development /ss CMA 01425A Diamond Shamrock Corporation P O Box 348, Painesville. Ohio 44077 Phone 216 357-3000