1 15 6 https://www.nal.usda.gov/exhibits/speccoll/files/original/b3c8d196bfeae2fd16cca439f997949b.pdf 0279bc68f76bccafff6b8ddf7b92337d PDF Text Text Item ID Number ("592 Author Corporate Author Roport/Artldo TltlO Executive Summary: Ranch Hand -MAS Marine Study Comparison Journal/Book Title Year 000 ° Month/Day Color n Number of Images 17 DOSCTlptOn NOtOS Paragraph summary accompanied by information in list, graphic, and table form. Wednesday, May 23, 2001 Page 1593 of 1608 �EXECUTIVE SUMMARY RANCH HAND - NAS MARINE STUDY COMPARISON The exposed Ranch Hand cohort consists of approximately 1,200 individuals and 6,000 controls, while the proposed NAS Marine Study consists of 5,900 individuals near the herbicide flight paths, on the same day of spraying and for which there are 212,100 controls. Despite the fact that the Ranch Hand study involves smaller sample sizes than the proposed Marine effort, the Ranch Hand Study is more powerful statistically. Specifically, lower exposure to herbicide and misclassification in Marine exposure groups renders the Marine Study less powerful than the Ranch Hand effort, as set out in the attached tables and graphs. In the attached materials, misclassification and decreased exposure are seen to be independent factors additively decrementing Marine Study statistical power. Even when all 21,900 Marines within the herbicide spray paths up to 28 days following the spray operations are considered exposed, the Ranch Hand Study is noted to be significantly superior. �KEY ITEMS OF CONSIDERATION MARINE STUDY RELATIVE TO RANCH HAND STUDY "EXPOSED " MARINES RECEIVED AN AVERAGE EXPOSURE 1/1000 THE AVERAGE DOSE RECEIVED BY RANCH HAND PERSONNEL MARINE EXPOSURE ALLOCATIONS BASED ON DISTANCE FROM SPRAY PATHS LEAD TO SERIOUS MISCLASSIFICATION OR BIAS MARINE EXPOSURE ALLOCATIONS BASED ON TIME IN A SPRAY AREA SUBSTANTIALLY ALTER THE SIZES OF THE STUDY AND CONTROL POPULATIONS AND LEAD TO SERIOUS MISCLASSIFICATION �1979 GAO REPORT COMPARED GROUND TROOP LOCATIONS WITH HERBICIDE ORANGE MISSION TIME - 1, 7, 14, 2B DAYS GEOGRAPHY PROXIMITY - 0,5, 1,5, 2, ASSUMED BATTALION TURNOVER RATE - 202/MONTH ALL TROOPS LOCATED AT BATTALION HQ DRIFT IN ALL DIRECTIONS �1979 GAO REPORT MARINE CORPS INFANTRY BATTALIONS CLOSEST TO HERBICIDE ORANGE SPRAYING MISSIONS ON DAY OF SPRAYING (CON THIEN VACINITY) BATTALION HEADQUARTERS FLIGHT PATH OF SPRAYING MISSION CLOSEST DISTANCE BETWEEN HEADQUARTERS AND FLIGHT PATH (IN KILOMETERS) A B 1st BATTALION 4th REGIMENT C 2nd BATTALION 9th REGIMENT D SCALE 1" = 2 Km. 1st BATTALION 3rd REGIMENT 3rd BATTALION 4th REGIMENT �CRITIQUE - 1979 GAO ATYPICAL SPRAYING IN D1Z INADEQUATE RECORDS-BELOW BATTALION LEVEL TEN-PERCENT OF TROOPS AT BATTALION HQ REMAINING TROOPS IN "ROVING UNITS" UNIT LOCATIONS ONLY FOR COMBAT ACTION HEAVY VEGETATION/mUNTAIM TERRAIN MINIMIZED GROUND LEVEL EXPOSURE SPRAY DRIFT LIMITED AND DIRECTIONAL ENVIRONFENTAL FATE DISREGARDED �FATE IN AIR (HERBICIDE) PARTICLE SIZE <100u 1,9% 10Q-500u76,2% >500y 21,9% 87% IMPACT WITHIN 1 MIN 13% DRIFT/VOLATILIZE (?) PHOTODEGRADATION �FATE ON VEGETATION (HERBICIDE) MULTI CANOPY FOREST INTERCEPTED * 94% GROUND - LEVEL DEPOSITION * 6% (0,17 GAL/A = 1,4 LB AI/A) CUTICULAR PENETRATION OCCURRED WITHIN 30 MIN �ENVIRONMENTAL FATE OF TCDD RAPID PHOTODEGRADATION IN AIR/PLANT SURFACE (CROSSBY, > 98% IN 6 HR) (NASH, 86% IN 32 HR) MIN TRANSLOCATION IN PLANTS NEG, PLANT UPTAKE SOIL: 20% PHOTODEGRADES IN 6 HR T 1/2 WITH HERBICIDE = 1 YEAR T 1/2 WITHOUT HERBICIDE = 3 YEARS BIOACCUMULATION IN ANIMALS (EGLIN AFB STUDY) �CONSIDERATION OF THE EXPOSURE ALLOCATION FOR THE MARINE POPULATION SUBJECTIVE MEANS: PERSONAL HISTORY OF THE MARINES PROBLEMS: BIAS FROM COMPENSATION CARROT MISIDENTIFICATION OF SPRAYING AIRCRAFT PROBABLE RESULTS: POSITIVE HISTORIES RESULTING EFFECT: SUBSTANTIAL POSITIVE BIAS �CONSIDERATION OF THE EXPOSURE ALLOCATION FOR THE MARINE POPULATION "OBJECTIVE" MEANS: HERB TAPES; GEOGRAPHIC PROXIMITY OF MARINE HQs TO SPRAY PATHS PROBLEMS: TAPE INACCURACIES; COMBAT MANEUVERS OF MARINES FROM HQs; SHORT ENVIRONMENTAL FATE OF TCDD; CONFOUNDING EXPOSURE TO CONTROL GROUP VIA PERIMETER GROUND SPRAYING PROBABLE RESULT: SUBSTANTIAL MISCLASSIFICATION OF "EXPOSED" GROUP PLUS MINOR MISCLASSIFICATION OF "UNEXPOSED" CONTROL GROUP RESULTING EFFECT: SUBSTANTIAL DILUTION OF HEATH EFFECTS, IF PRESENT SIGNIFICANT DILUTION OF EFFECTS IF MARINES ADDED TO RANCH HAND POPULATION FOR STUDY �MORTALITY ANALYSIS POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATION AND RELATIVE EXPOSURE POWER TABLE RANCH HAND POWER MISCLASSIFICATION 1-B .92 MARINE STUDY POWER EXPOSURE LEVELS RELATIVE TO RANCH HAND 1/10 1/20 1/100 1/1000 0 .19 .10 .06 .05 10 .17 .10 .06 .05 25 .14 .09 .06 .05 ASSUMPTIONS: RH STUDY POP. 1,200: 6,000 (1:5) MARINE STUDY POP. 5,900: 212,100 NORMAL INCIDENCE OF DISEASE = 0.01 DISEASE INCIDENCE IN RH = 0.02 LINEAR DOSE - RESPONSE MISCLASS. OF MARINE CONTROLS EXCLUDED �MORTALITY ANALYSIS POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATIQN AND RELATIVE EXPOSURE POWER* TABLE RANCH HAND POWER 1-B MARINE STUDY POWER EXPOSURE LEVELS RELATIVE TO RANCH HAND MISCLASSIFICATION 1/10 .87 0 10 25 ASSUMPTIONS: RH STUDY POP. 1,200: 6,000 (1:5) MARINE STUDY POP. 5,900: 212,100 NORMAL INCIDENCE OF DISEASE 0.001 DISEASE INCIDENCE IN RH 0.004 LINEAR DOSE - RESPONSE MISCLASS. OF MARINE CONTROLS EXCLUDED 1/20 1/100 .18 .18 .15 .10 .09 .09 .06 .06 .06 1/1000 .05 .05 .05 �POWER CURVES OF THE MARINE STUDY CONSIDERING RELATIVE EXPOSURE AND MISCLASSIFICATION OF THE STUDY POPULATION 1.0 r 0.8 NO MISCLASSIFICATION 0.6 5,900 EXPOSED 0.4 25 % MISCLASSIFICATION 212,100 CONTROL RH RR-4.0 p ^.001 0.2 p 2 =.004 j 0.0 .001 .01 i i l l i ii i i .1 MARINE EXPOSURE/RANCH HAND EXPOSURE i i i i i i ii 1.0 �MORTALITY ANALYSIS POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATION AND RELATIVE EXPOSURE * POWER TABLE RANCH HAND POWER 1-B MARINE STUDY POWER MISCLASSIFICATION 1/10 .92 EXPOSURE LEVELS RELATIVE TO RANCH HAND 1/20 1/100 1/1000 .41 .17 .07 .05 10 .36 .16 .07 .05 25 ASSUMPTIONS: 0 .28 .13 .06 .05 RH STUDY POP. 1,200; 6,000 (1:5) MARINE STUDY POP. 21,900: 196,100 NORMAL INCIDENCE OF DISEASE = 0.01 DISEASE INCIDENCE IN RH = 0.02 LINEAR DOSE - RESPONSE MISCLASS. OF MARINE CONTROLS EXCLUDED * INCORRECT POPULATION NUMERICS BASED ON ENVIRONMENTAL FATE OF TCDD �MORTALITY ANALYSIS POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATION AND RELATIVE EXPOSURE * POWER TABLE ANCH HAND POWER 1-B MARINE STUDY POWER % MISCLASSIFICATION EXPOSURE LEVELS RELATIVE TO RANCH HAND 1/10 1/20 1/100 .87 0 10 25 ASSUMPTIONS: RH STURY POP. 1,200; 6,000(1:5) MARINE STUDY POP. 21,900: 196,100 NORMAL INCIDENCE OF DISEASE =0.001 DISEASE INCIDENCE IN RH = 0.004 LINEAR DOSE - RESPONSE MISCLASa OF MARINE CONTROLS EXCLUDED .38 .33 .26 .17 .15 .13 .07 .06 .06 1/1000 .05 .05 .05 * INCORRECT POPULATION NUMERICS BASED ON ENVIRONMENTAL FATE OF TCDD �POWER CURVES OF THE MARINE STUDY CONSIDERING RELATIVE EXPOSURE AND MISCLASSIFICATION OF THE STUDY POPULATION 1.0 r .8 INCORRECT POPULATION NUMERICS BASED ON EVIRONMENTAL FATE OF >GO TCDD NO MISCLASSIFICATION .6 25% MISCLASSIFICATION .4 21,900 EXPOSED 196,100 CONTROL RH RR = 4.0 .2 p p 1 =.001 =-004 0.0 .001 J .01 I » I I I II .1 MARINE EXPOSURE/RANCH HAND EXPOSURE J I I I I I II 1.0 �CONCLUSIONS RANCH HAND VERSUS OR PLUS THE MARINE POPULATION • OVERWHELMING ALLOCATION PROBLEMS FOR"EXPOSURE-NONEXPOSURE" IN MARINES - MISCLASSIFICATION BY GAO CRITERIA = DILUTIONAL EFFECT - ALLOCATION BY PERSONAL HISTORY = BIAS • MARINE EXPOSURE 1/1000 OF RANCH HAND EXPOSURE • MARINE - RANCH HAND POPULATIONS DIFFER BY HOST FACTORS; AGE, RACE, EDUCATIONAL LEVEL, ETC •• BY CONSIDERATION OF EXPOSURE DIFFERENTIAL AND MISCLASSIFICATION, RANCH HAND STUDY FAR MORE POWERFUL THAN INDEPENDENT MARINE STUDY OR ADDITIVE STUDY TO INCLUDE MARINES •• ADDITION OF MARINE POPULATION TO RANCH HAND POPULATION = UNACCEPTABLE SCIENCE � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 059 Folder The folder containing the original item. 1592 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Executive Summary: Ranch Hand -NAS Marine Study Comparison Subject The topic of the resource Air Force Health Study mortality trends Marine Corps exposure ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/4db5f3af947565e11920ccd04710b45d.pdf e7910789115207f09a36d676ed50e28e PDF Text Text Item ID Number 01473 Author Corporate Author Report/Article Title Manuscript: Exposure Estimates for Herbicide Orange of Ranch Hand and ground troops in Vietnam Journal/Book Title Year 000 ° Month/Day Color '—' Number of Images 25 Descrlpton Notes Tuesday, May 15, 2001 Page 1478 of 1514 ���Z7 C triditdi C /tf ��/o * AtX Jju* tfJ^MAf^&<4 CktMlWAU"' �G> /f -j 700 ���' /// " �x 3 > ^ / Jerttt) �ft �f z, 2^ �7? �s-r a </,s-r o.uz /s 0-49 0,210 �0,03 16 /•¥/ �32, 3OO �/, a /c^ >f*# ym / 10 ty vnaw IDO% �O.0/S e TCib iff? £ 7t0 (9 V �/ d' f 7 T 9.27 *#y T - 0437*) 0.5V #4} MI �j / /) TlGM • 70 fy 7 Q 7~ �? iI Tti. ,| 10 / ' �7 I 7 5 uio �i . j fe 1227 _JL :.-__& 51<i,!C -w v fioGUML �/2 «*> jUfls f>- y • 7fa> ^^ » sOW& ^tv4s �� Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 055 Folder The folder containing the original item. 1478 Series The series number of the original item. Series III Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Manuscript: Exposure Estimates for Herbicide Orange of Ranch Hand and ground troops in Vietnam Subject The topic of the resource exposure assessment Marine Corps exposure dioxin ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/0e50613879a9fa29be27c2bba9af06d6.pdf 34189ec953d0ae8977d30a5d4d84d3a5 PDF Text Text Item ID Number °1598 Author Corporate Author Report/Article TltlB Notes: Ranch Hand Exposure Journal/Book Title Year 000 ° Month/Day Color Number of Images 9 DeSCrlptOU Notes Includes both handwritten notes by Alvin Young and typed notes. Wednesday, May 23, 2001 Page 1599 of 1608 �._3.Q /Wsp 0 / 90 A) 10 x J- •*" £ fr\ db '•H Ccis X- f *^v X WliSSe.t>/^ i �. I. .5" l/Ufc-^5 e.io/Ho ^^•>ijiiiULHHir -irr—r- ' _t x I �Ri 154 UTaVucfcSor 66-67 fAo4 £6-67 4 I.H5 f.fel I.HP .6.7- 6 SO ' 1 (05 Pvlo fct - 70 95 143 30(3 1. .5 1 �DIRECT APPLICATION TO MAN 1 SQUARE FOOT PLANAR SURFACE 110 LB HUMAN = 50 KG BODY WEIGHT MAN STANDING IN OPEN AND SPRAYED DIRECTLY IS ESTIMATED TO INTERCEPT SPRAY EQUIVALENT TO 1 SQUARE FOOT OF HORIZONTAL PLANAR SURFACE 2,4-D + 2A5-T 12,63 + 13,23 LB/A = 131,3 + 137,6 MG/SQ, FT,', = 131,3 + 137,6 MG/50 KG BODY WEIGHT £ 2,6 + 2,7 MG/KG OF BODY WEIGHT = 1/100 LD50 FOR'2,4-D + 2A5-T IN RATS TCDD 6 MG'/A = 0,14 JJG/SQ, FT, - 0 J4 JJG/50 KG BODY WEIGHT =? 0,003 JJG/KG OF BODY WEIGHT = 1/10,000 LD5Q IN RATS AS SINGLE TOPICAL APPLICATION ON HEAD AND SHOULDERS, PROTECTED BY HAI.R AND CLOTHING, CAN BE WASHED OFF, �•DIRECT CONTAMINATION-OF SOIL 1 ACRE OF SOIL \%^/ 3 INCHES THICK = 1 MILLION POUNDS BARE SOIL illlLil OF SOIL AGENT ORANGE SPRAYED ON BARE SOIL AND PENETRATING TO A DEPTH OF 3 INCHES WOULD GIVE MAXIMUM CONCENTRATION IN SOIL: 2,4-D = 12,63 LB/1 MILLION LB = 12,63 PPM 2A5-T = 13,23 LB/1 MILLION LB = 13,23 PPM IF 2>^5-T CONTAINED 1 PPM TCDD, SOIL WOULD CONTAIN 0,000013 PPM TCDD - 0,013 PARTS PER BILLION TCDD 53 13 PARTS PER TRILLION TCDD LEVELS IN SOIL WOULD GENERALLY BE CONSIDERABLY LOWER THAN THIS DUE TO INTERCEPTION OF SPRAY BY OVERSTORY FOLIAGE, UNDERSTORY FOLIAGE, BRUSH, GRASS AND GROUND LITTER �DIRECT CONTAMINATION OF POND WATER AVERAGE DEPTH 1 FT 1 SQ FT OF SURFACE 1 FT DEEP = 62,4 LB = 28,4 = 1 CU FT KG OF WATER AGENT ORANGE SPRAYED AT 3 GAL/A DIRECTLY ON POND SURFACE = 131,3 MG 2,4-D/28,4 KG = 5 PPM 2,4-D + 137,6 MG 2,4,5-T/28,4 KG = 5 PPM 2,4,5-T +0,14 UG TCDD/28,4 KG = 0,005 PPB TCDD IF 50 KG WOMAN DRANK 2 LITERS OF THIS POND WATER EACH DAY, SHE WOULD INGEST 0,2 MG 2,4-D + 0,2 MG 2,4,5-T + 0,002 UG TCDD PER KG OF BODY WEIGHT PER DAY, PROVIDED IT ALL REMAINED IN SOLUTION OR SUSPENSION AND DID NOT DEGRADE WITH TIME, NO-EFFECT LEVELS IN TERATOGENI.C STUDIES IN RATS; FOR 2,4-D = 25 MG/KG BODY WEIGHT PER DAY FOR 2,4,5-T = 24 MG/KG BODY WEIGHT PER DAY FOR TCDD = 0,03 JJG/KG BODY WEIGHT PER DAY �DIRECT CONTAMINATION OF DRINKING WATER HOUSE 20 x 50 FT, ESTIMATED TO INTERCEPT 1000 SQ, FT, OF SPRAY DIRECT SPRAYING OF 1000 SQ, FT, WILL DEPOSIT 131,3 GRAMS 2,4-D + 137,6 GRAMS 2 A 5-T +0,11 MG TCDD .IF ROOF IS WASHED OFF COMPLETELY BY 0,5 INCH OF R A I N AND ALL R U N O F F IS COLLECTED IN AN EMPTY CISTERN (0,5/12) x 1000 x 7,5 = 313 GALLONS OF WATER = 2600 LB OR 1180 KG OF WATER IN CISTERN THE WATER COULD THEORETICALLY CONTAIN A MAXIMUM OF 111 PPM 2,4-D + 116 PPM 2 A 5-T + 0,0001 PPM TCDD BUT AGENT ORANGE is NOT THIS SOLUBLE IN WATER, A SATURATED SOLUTION CONTAINS ONLY 20 PPM = 10 PPM 2AD BUTYL ESTER + 10 PPM 2A5-T BUTYL ESTER OR 8 PPM 2 AD A,E, + 8 PPM 2A5-T A,E, TCDD IS EXTREMELY INSOLUBLE IN WATER, SATURATED SOLUTION CONTAINS 0.2 PPB TCDD. IF A 50 KG WOMAN DRANK 2 LITERS OF SATURATED WATER EACH DAY-. SHE COULD INGEST 16 MG 2 AD + 16 MG 2,4,5-T + 0,4 JJG TCDD EQUIVALENT TO 0,3 MG/KG/DAY 2 AD +0,3 MG/KG/DAY 2 A5-T + 0,008 JJG/KG/DAY TCDD IF N O N E DECOMPOSED WITH TIME, HOWEVER, SATURATED SOLUTION OF AGENT ORANGE WOULD NOT LIKELY BE USED AS DRINKING WATER DUE TO UNPLEASANT ODOR AND DISAGREEABLE TASTE, �2,4-D AND 2,4,5-T ARE USED AS HERBICIDES TO CONTROL BROADLEAF hfEEDS IN TOLERANT CROPS SUCH AS RICE AND SUGARCANE, RECOMMENDED RATES FOR RICE ARE 1,25 ¥o 1,7 LB/A, DIRECT SPRAYING WITH AGENT ORANGE AT 3 GAL/A (25,86 LB PHENOXY ACID EQUIVALENT PER ACRE) WOULD CAUSE DAMAGE AND LITTLE OR NO CROP WOULD SURVIVE TO MATURITY, IF PART OF THE SPRAY IS INTERCEPTED BY OVERSTORY AMD UNDERSTORY FOLIAGE, CROPS COULD RECEIVE TOLERATED DOSES OF 2,*f-D OR 2A5-T, • * * IF THE RICE RECEIVED 1,25 LB 2,'hD + 2A5-T PER ACRE NO DETECTABLE RESIDUE (<0,01 PPM) 2,*M) OR 2A5-T WOULD BE PRESENT IN THE 2000 KG OF RICE GRAIN HARVESTED FROM THAT ACRE, IF THE 2A5-T CONTAINED 1 PPM TCDD AN£ ALL TH£ TCDD ENDED U£ I£ THE RJLC£ GRAIN, THE GRAIN WOULD CONTAIN ABOUT 0,00015 PPM TCDD = 0,15 PPB TCDD, IF A 50 KG WOMAN ATE 300 GRAMS OF THIS RICE EACH DAY, SHE WOULD INGEST LESS THAN 0,001 /JG OF TCDD PER KG OF BODY WEIGHT PER DAY. UNLIKELY AS THE ABOVE MAY BE, u is STILL 30 TIMES LESS THAN THE NO-EFFECT LEVEL FOUND IN TERATOGENIC STUDIES IN RATS, �AGENT ORANGE 50/S N-BUTYL ESTER OF 2,1-D 50% N-BUTYL ESTER OF 2,1,5-T 1,21 LB 2,1-D ACID EQUIVALENT (A,E.) PER GALLON 1,11 LB 2,1,5-T ACID EQUIVALENT PER GALLON APPLIED IN VIETNAM AT 3 GAL, PER ACRE = 12,63 LB 2,1-D A.E./A + 13,23 LB 2,1,5-T A,E,/A • TOTAL = 25,86 LB PHENOXY A.E./A 1 LB/A = 10,1 MILLIGRAMS PER SQUARE FOOT AGENT ORANGE AT 3 GALLONS PER ACRE = 131,3 MG 2,1-D A.E./SQ FT + 137,6 MG 2,1,5-T'A,E,/SQ FT IF THE 2,1,5-T BUTYL ESTER CONTAINS 1 PpM 2,3,7,8-TETRACHLORODIBENZO-p-DIOXIN (TCDD) USE OF AGENT ORANGE AT 3 GALLONS PER ACRE = 6 MILLIGRAMS TCDD PER ACRE (MG/A) 0R 0-1^ MICROGRAMS TCDD/SQ FT (jUG/SQ FT> AT 10 PPM TCDD IN 2,1,5-T BUTYL ESTER 3 GAL/A = 60 MG/A OR 1,1 pG/SQ, FT, � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 060 Folder The folder containing the original item. 1598 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Notes: Ranch Hand Exposure Subject The topic of the resource Air Force Health Study Ranch Hand crew contaminant distribution Marine Corps exposure ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/349d4743aac5166a5ed60c3b69335fab.pdf 37aa40a46cbd198251f8a518b4f5b1b4 PDF Text Text Item ID Number °1599 Author Corporate Author Roport/Artldo HUB Supporting Statement with Attachments Journal/Book Title Year 000 ° Month/Day Color '' Number of Images ^ DOSGriptOn NotOS 'tem includes: Supporting Statement which discusses aspects of the Ranch Hand II study, Letter from Thomas B. Bruton, Judge Advocate General dated 22 October 1984 regarding confidentiality issues with the Ranch Hand II study, Fact Sheet sent to Ranch Hand I participants, and pages 17-55 of unknown source discussing the Ranch Hand II study Wednesday, May 23, 2001 Page 1600 of 1608 �SUPPORTING STATEMENT A. Justification: 1. In 1981, the Assistant to the President for Domestic Affairs and Policy, directed the A1r Force to undertake the Ranch Hand epidemiology study, as recommended by the Interagency Work Group to Study the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants. The Initial portion of this ongoing study was begun 1n October 1981. The follow-up phase of this study will begin in 1985. This series of questionnaires will be used as a part of the follow-up phases of the Ranch Hand study. A contractor (National Opinion Research Center [NORC]) experienced 1n Interviewing techniques will conduct the questioning of study participants. The data derived from the questionnaire will be utilized by Science Applications International Corporation (SAIC) and the USAF School of Aerospace Medicine to statistically assess the existence and/or the development of various disease states 1n present and former A1r Force personnel who participated in herbicide spraying (Operation Ranch Hand) during the years 1962 to 1971. A control group of nonexposed individuals will be additionally questioned. No previous data exists which can be used to assess the current health status of these groups. 2. Four data collection instruments will be used, all nearly identical to previously approved questionnaires (OMB 10701-0033). They will be administered by personnel of NORC, Chicago, Illinois. Two hundred participants who are newly entered into this ongoing study will be given an in-home interview, lasting approximately 1.5 hours, and their current and former wives will be interviewed as well (approximately 200 wives for 45 minutes). A 30-minute self-administered interval fertility history questionnaire will be mailed to the 2400 wives who participated in the 1981/82 baseline interviews. Additionally, 7863 previously identified but uncontacted Air Force veterans will be contacted by telephone and asked six questions relating to current state of health and socioeconomic status. These data will permit proper matching for these key demographic variables. All collected data will be used to determine the presence or absence of health effects related to wartime exposure to Agent Orange. If these data are not collected, resolution of major scientific and social issues will not be achieved. 3. Improved data collection techniques and program modifications have resulted in a projected 1021.5 hour decrease in interviewing time. 4. Duplication has been avoided through the action of the Cabinet Council Agent Orange Working Group, its Science Panel and Advisory Committee. These groups have coordinated Agent Orange and related research throughout the federal sector to prevent unnecessary duplication and its associated information collection burden. Thestudy protocol and the members of the Agent Orange Working Group have set a requirement to conduct this study over a 20-year period. 5. Similar health information from an identified population with quantifiable exposure to Agent Orange is unavailable from any other source. �6. Information will be collected from Individual volunteers, and no small businesses or other entitles will be Involved. 7. Baseline data were collected 1n 1981-82 from this predominantly middle-aged population. Follow-up data are required 1n 1985 and 1987 so Increasing disease Incidence 1s detected promptly. The average age of this population places the members at a time when diseases associated with the aging process are most common. After 1987, data collection will only occur at 5-year Intervals. 8. This data collection effort 1s being conducted 1n full compliance with 5 CFR 1320.6. 9. The White House Office of Science and Technology Policy, the Cabinet Council Agent Orange Working Group, Its Science Panel, and Advisory Committee have maintained a continuing review of this project and approved the data collection methods, frequency of collection, Instructions and record keeping procedures, and report formats. Additionally, periodic contact (at least annually) is maintained with key members of the study population. a. Name Address Telephone Contact Mr Jack Spey Ranch Hand Association 850 Tarpon Drive Fort Walton Beach FL 32548 (904) 243-5696 1983,1984 Mr. Ralph Dresser 3410 Stonehaven Drive San Antonio TX 78230 (512) 699-0761 1983,1984 Mr. Charles Hubbs 6002 Summerhill Road Temple Hills MD 20748 (301) 899-6716 1983,1984 Mr. Delmar Spivey 2524 Jennifer Terrace Palm Harbor FL 33563 (813) 784-9681 1938,1984 b. There have been no unresolved problems during the consultations. c. Other public contacts have included briefings to House and Senate committees, press releases, press conferences, and speeches to public scientific and nonscientific audiences. 10. Confidentiality is granted in accordance with direction of the U.S. Air Force Judge Advocate General and will be strictly maintained. Since "the protective privilege ends where the public peril begins," appropriate civil agencies would be notified in the event serious medical problems which impact public health and safety are identified. The Fact Sheet sent to all potential participants and the Judge Advocate General's letter of 22 October 1984 are attached (attachments 1 and 2, respectively). �11. Sensitive Questions: a. The questionnaire contains questions on the following sensitive topic areas: Marital and nonmarltal relations Reproductive histories Birth defects Alcohol history Use of marijuana b. Responses relating to sexual activity and outcome are necessary for assessing the Incidence of birth defects and reproductive effects alleged by a number of Vietnam veterans. Additionally, since Vietnam was a complex environment, other factors which could bear upon -observed disease Incidences must be evaluated. It 1s essential to the study that these questions be Included. 12. There 1s no cost to the respondents. The data collection for this study will cost the A1r Force $670,000 In FY85, $218,000 1n FY86, $677,000 1n FY87, and $221,000 1n FY88. These costs are based on a firm, fixed-price contract between the A1r Force and SAIC, McLean VA. These are actual costs and the Air Force will Incur no additional costs for data collection using these questionnaires. 13. Each of the 7,863 previously uncontacted subjects will be contacted by telephone and given the 6-mlnute short questionnaire (pages 275-276 of the attached USAFSAM-TR 82-42 [attachment 3]). Two hundred of these Individuals will be selected as replacements for other noncompHant individuals and given the additional baseline questionnaire (pages 1-153 of USAFSAM-TR 82-42). Their wives will also receive the baseline spouse questionnaire (pages 159-193, USAFSAM-TR 82-42). The 2600 spouses of subjects who took part in the study in 1981-82 will be sent a self-administered fertility questionnaire, slightly modified from that given at baseline (pages 159-193, USAFSAM-TR 82-42). The instrument will be identical in format but will only collect interval data since the baseline collection effort in 1981-82. Except for the 200 replacement subjects, individuals will only be contacted once. Consultation with respondents has occurred (see paragraph 9a above). Specific time burdens for each of these questionnaire instruments are shown below. As noted, a decrease of more than 1,000 hours has been realized relative to the baseline effort in 1981-82. The time estimates are based on the mean time required for administration of the same instruments to the same or similar populations at baseline. Adequate time has been included in the Information Collection Budget for these tasks. �Table 1 BURDEN ESTIMATES FY85/86 Source (USAFSAMInstrument Number of Respondents Duration TR 82-42) 1981/82 1985 (Hours) Difference 1981/82 vs 1981/82 1985 1985 Total Study Subject (Baseline) pp 1-153 1532 200 1.5 2298 300 -1998 Spouse (Baseline) pp 159-193 1500 200 0.75 1125 150 -975 Spouse Pol low-Up Modified (Interval from pp 159History) 193 0 2600 0.5 0 1300 +1300 786 +779 Telephone Questionnaire Modified from pp 275276 69 7863 0.1 6.9 Next of Kin Not being used 85 0 1.5 127.5 Net Difference (in hours) 0 -127.5 -1021.5 14. The above decrease in burden is due to program modification from the requirements of the baseline data collection phase. 15. The results of the requested data collection will not be published as raw data; rather, they will be statistically analyzed by SAIC under contract to the U.S. Air Force prior to publication . All statistical methods and procedures are in accordance with the protocol of the study which underwent extensive peer review and was approved by the Agent Orange Working Group. After the data have been analyzed, a report will be prepared for public release in early 1987, just prior to the start of the next follow-up phase. These same questionnaires will be readmfnistered in 1987, and the results of the analysis of the new data released in 1989. Data collection using these instruments will begin as soon as they are approved and continue until the end of the first follow-up phase in February 1986. The second follow-up phase will begin in May 1987 and continue until March 1988. Additional follow-up data collection efforts will take place in 1992, 1997, and 2002, in accordance with the previously approved study plan. B. Collection of Information Employing Statistical Methods 1. All 1278 of the Air Force personnel who were directly involved in the aerial spraying of herbicides in South Vietnam from 1962-1971 have been identified and all 1256 who survived their tour of duty were included in the study. No subsampling was used in the "exposed" group. Approximately 20,00 personnel from C-130 equipped units in Southeast Asia were selected as potential comparison subjects. The "nearest-neighbor" matching technique of Kupper was used to �select an 8:1 matched set of comparisons for each "exposed" Individual (matched on age, sex, rank, and military occupational category). After the order of the matched set was randomized, the first willing comparison and the "exposed" Individual were Invited to participate 1n the study. Thus, all "exposed" Individuals and a random selection of the comparison group were Involved 1n the baseline and follow-up data collection phases of the study. Details are provided below: Table 2 Respondent Selection Exposed Population Selected for Potential Use Selected for Data Collection 1n 1981-82 Selected for Data Collection in 1985 1256 1256 1256 1202* Comparison 20000 10048 1256 1202 *54 have died Table 3 Response Rates Group 1981-82 Exposed Group 97% Comparison Group 93% 2. The statistical methods used for sample selection were described in paragraph Bl above and are more fully discussed in attachment 4 which is taken from the Study Protocol (USAFSAM-TR 82-44). After the comparison "universe" was selected, "nearest-neighbor" matching resulted in a selection of an eight-member set of comparisons for each exposed individual (matched for sex, race, age, and military occupational category). A single comparison was then randomly selected for participation in the data collection effort. No estimation was required and no stratification techniques were used. Accuracy of data collected in the baseline was achieved through reviews of medical records and birth/death certificates. Similar procedures will be used during the follow-up phases. No unusual problems requiring more specialized sampling procedures occurred. After the second follow-up phase (1987), further data collection efforts will only occur at 5-year intervals. 3. Response rates in the baseline collection phase were quite high and are expected to remain so throughout the follow-up phases of the effort. Ninetyfive percent of the individuals who participated in the baseline expressed a strong desire to remain in the study. Nonresponse in the exposed group can not �be corrected through the Inclusion of additional Individuals since the entire "universe" was Included 1n the study. Extensive statistical approaches to the assessment of bias arising from differential participation and other factors are Included 1n the requirements of the contract with SAIC. All of these Issues of cohort selection, sample size, statistical analysis, frequency of data collection and appropriateness of the study have been evaluated and approved by the Agent Orange Working Group. 4f Pretesting of the data collection Instruments for the follow-up phase of the study will not be necessary since they are Identical to the questionnaires used at baseline. The only modifications occur 1n changing dates ("1981" or "1982" to 1985) and the collection of Interval fertility data (1982-1985) rather than life-long data. Similar modifications of specific questions will be needed 1n the 1987 questionnaire to reflect 1985-1987 Interval data. 5. Consultants for Statistical Aspects of the Study Peer Review Groups Reviewing Agency 1. 2. 3. 4. University of Texas, School of Public Health A1r Force Scientific Advisory Board Armed Forces Epidem1olog1cal Board National Research Council, National Academy of Sciences Date Jun 1979 Aug 1979 Aug 1979 Dec 1979 Advisory Committee of the Agent Orange Working Group Robert Miller, M.D., Chairman Chief, Clinical Epidemiology Branch NCI, NIH (Room 8C41) 7910 Woodmont Avenue Bethesda MD 20814 Telephone: (301) 496-5785 Science Applications International Corporation (Contractor) James Striegel, Ph.D. 8400 Westpark Drive McLean VA 22102 Telephone: (703) 821-4600 National Opinion Research Center (Subcontractor) Mary C. Burich University of Chicago 6030 South Ellis Chicago IL 60637 Telephone: (312) 962-1033 �20324 JA Reevaluation of Assurance of Confidentiality, Project Ranch Hand II AF/SG 1. We have reviewed the issue of granting full confidentiality to the study pwrticipants in the Ranch Hand II study. There has been no significant change in the legal issues regarding the granting of full confidentiality since our initial recommendations to you in 1980 and 1981. We recommend that there be no change to the current grant of strict confidentiality with the two exceptions, 2. This recommendation is based upon a review of the current case law, statutory and regulatory law, and the public policy • issues governing the protection of the public health and safety. Even though there is no federal statute mandating the disclosure of information obtained during the course of the Ranch Hand II study* we still remain subject to complying with a valid court order for production as well as adhering to the court supported proposition that "the pro-. tective privilege ends where 'the public peril begins". (Tarasoff v. The .Regents of the University of California , 551 PZd 334 [~<5al 1976J). 3. The statutory authority relied upon by the CDC/VA in granting full confidentiality to their Agent Orange study participants is applicable only to CDC epidemiological and other specified research projects. It has no applicafMnn Tn fln Air Frvrr* «rnriy. Fiirfhermnra , if -I c our opinion that this statute does not grant any protection to the CDC in resisting a valid court order for production, nor does it grant immunity to the CDC in complying with the principles ennunciated in Tarasoff when the public health and safety are involved. The CDC determined that it was not necessary to state these possible, though remote, exceptions co the promise of full confidentiality. We believe that these exceptions should be stated in any notice of confidentiality. 4. If you desire further discussion on this matter, please let us know. THOMAS 3. ERUTCM Major Gsnsrd, US..'...? The Ju;i"'r> .'Iciv;^^ "snared �FACT SHEET INTRODUCTION The USAF School of Aerospace Medicine, Brooks AFB, Texas, is conducting the study. You are being invited to participate in this study because of your specific duties and period of assignment in Southeast Asia. PURPOSE To determine whether there is a causal relationship between your duty in Southeast Asia and adverse health experience. METHODS An in-depth health questionnaire will again be administered to you by a member of the health evaluation team from the National Opinion Research Center (NORC). A complete profile of your current health will be obtained by physical examination which will be conducted by the Scripps Clinic and Research Foundation in La Jolla, California. An additional questionnaire and physical examination will be given by these same organizations in 1987. Other examinations are planned for 1992, 1997 and 2002. Your travel expenses (including food and lodging) for the physical examination will be paid by the Air Force. Lodging will also be provided for accompanying family members, but their food and travel expenses are not covered by the Air Force. A stipend of $100 per day will be paid to participants who are not on active duty, Government employees, or otherwise precluded by law from receiving such a stipend. Confidentiality is to be strictly maintained. However, legal confidentiality of medical information is always based on the proposition that "the protective privilege ends where the public peril begins." Therefore, serious medical problems which impact public health and safety or a judicial order to release medical data will be the only circumstances in which information on a particular study participant would be released. The Air Force and the Justice Department were successful in preventing the release of health data from the first examination during a major court case in 1984. If for example, a participant were found to have typhoid fever or tuberculosis and his illness directly impacted the health and safety of others, a �committee composed of a physician (who is a specialist in the illness in question), a physician of the participant's choosing, a flight surgeon, an Air Force lawyer, and a representative from the participant's occupation win be formed to review the information. Before any information is disclosed, the committee must determine that the findings Jeopardize the public health and safety. These same confidentiality procedures were provided during the first examination in 1982, and no problems arose. No one was grounded or had his job adversely affected by his participation in the study. There is no reason to suspect that this examination phase of the study will be any different. BENEFITS TO YOU You will receive a comprehensive health review and physical examination of top level, executive caliber at no cost to yourself. You will be completely informed of all examination procedures, you can decline to take any specific portion of the examination that you wish, and you will be completely informed of all examination results. The information from this study will be provided to your personal physician if you so request. Questions concerning the study may be referred in writing to the USAF School of Aerospace Medicine, Epidemiology Division, Brooks AFB, Texas 782355000, or if more convenient, the information may be provided by phoning AUTOVON 240-2H14, or within the state of Texas call collect at (512) 536-3309, or from outside the state of Texas call toll-free 1-800-531-7231. Please complete the attached locator card and advise the USAF School of Aerospace Medicine, at the above address and phone number, of any address or phone number changes. �V. Epidem1olbg1c Study Design; Matched Cohort A. Design Considerations The goal of this study clearly mandates a comprehensive ep1dem1olog1c approach, Incorporating mortality, .and historical, current, and followup morbidity studies* Exposure to herbicides during the 1962-1971 time period may have Initiated, long-term health effects that may or may not be progressive. If such effects are detectable! by a review of the subject's past medical history, and can be verified*,',direct links to compensation Issues can be made.\ turhent health status, a:S mirrored by a large number of recent VA claims* and Inquiries, 1s of major Interest, because such claims and Inquiries may Indicate medical conditions that night be confirmed by a comprehensive physical examination. If analyses of both mortality and morbidity data yield only Indetermlnant or weakly suggestive findings, It may be that sufficient time has not yet passed for substantial emergence of longterm health effects. This dictates a requirement for a follow-up element to the study. Methodological shortcomings are Inherent In each element of this comprehensive study. To some extent, the classical deficiencies of each particular ep1dem1olog1c approach are compensated by the concurrent use of the other elements. For example, the low chance of identifying a relatively uncommon disease solely by the use of a mortality study is offset by the inclusion of a current morbidity study. The relatively quick feedback that can be attained from current morbidity and mortality studies will serve to better define the follow-up study, and will help to alleviate problems that arise as a result of changes 1n diagnostic criteria and methods over time. Nevertheless, problems that can affect ascertainment of disease In all phases of the study will remain. Inaccurate patient recall of antecedent events, the distortion of information by knowledge of anticipated symptomatology, and participant or observer knowledge of their exposure status can only be corrected to a limited extent by review of records for symptom validation and "blind" assessment protocols. In addition, fundamental problems dealing with adequate selection of . a control group and limiting loss to study can influence any comprehensive epidemiologlc investigation. These and other pitfalls in study design will be discussed in more detail in Section VIII. The management of this project will be conducted through standard Air Force Research and Development procedures, including program monitors at Air Force Headquarters and Air Force Systems Command, and a Program Management office at Brooks AFB, Texas. Contract monitors will insure that all contractual efforts are conducted according to strict quality assurance procedures, and an on-s1te monitor will insure that the physical examinations are conducted in strict accordance with the study protocol. Since the study has three elements and confronts a health issue with incompletely specified or uncertain endpoints, strong potential bias, and severe time contraints, the following design represents the best overall framework for achieving validity. The design process is complex and in itself Mine dependent. 17 �B. Selection and Ascertainment of the Populations for Study (1) The Exposed Military Groups (a) Operation RANCH HAND Personnel Operation RANCH HAND personnel flew C-123 aircraft in RVN during 1962-1971. Data from hand-compiled lists obtained through the RANCH HAND Association (a reunion organization), Air Force personnel records, unit historical records, and actual C-123 flight orders, place the herbicide exposed population at approximately 1264 Individuals. Of those personnel confirmed as RANCH HAND participants, 25% are still on active or reserve duty, with the remainder being composed of retired, separated, or deceased persons. To identify all RANCH HAND participants, an-indepth search was conducted of all organizational records stored at the Military Records Division, National Personnel Records Center (NPRC), St. Louis, Missouri. Introductory letters will be sent to the last known address of all Identified persons, and nonresponse will be pursued by cross-locator systems available within the government (e.g., Social Security Administration, VA, Internal Revenue Service). Significant efforts will be made to account for at least 99% of the total population (see Figure A-2, Section XV). Because of the limited number of RANCH HAND personnel, no subsampllng of the exposed group 1s planned in any phase of the study. All members will be strongly encouraged to participate In all phases of the Investigation. All RANCH HAND personnel are males currently ranging in age from 30-69 years (mean » 42.4 years). The normal C-123 crew composition was one pilot, one copilot/navigator (both officers), and one spray equipment console operator (enlisted) 1n the rear of the aircraft. The aircrew officerenlisted ratio is 2.2:1; however, the Inclusion of RANCH HAND support personnel (predominantly enlisted) 1n the stMdy will make the overall officerenlisted ratio 1:1.7. Approximately 98% of the officers and 92% of the enlisted men were Caucasian. Attempts have been made to Identify all maintenance personnel assigned to the RANCH HAND units. Maintenance of the RANCH HAND aircraft was performed within a step-wise organizational structure. Routine daily maintenance (primary) was conducted by flight line support personnel who were often dedicated exclusively to RANCH HAND operations. More extensive maintenance (secondary) was carried out by consolidated support units at the base level, which were also responsible for non-RANCH HAND C-123s as well. Major aircraft overhauls and modification were conducted by maintenance units at Clark Air Base, Philippines. The maintenance personnel In these centralized units were not directly assigned to RANCH HAND, and their exposures to RANCH HAND C-123 aircraft and herbicide cannot be 'validated. From 1962 through 1964, the primary flight line maintenance teams were dedicated to RANCH HAND aircraft, and these Individuals have been Identified by the mechanisms described above. In 1965, flight line maintenance was performed by personnel of the centralized maintenance organization (secondary), and It is not feasible to adequately Identify all of these Individuals from available records. After 1966, the RANCH HAND organization transferred their 18 �base of operations to a new location, and primary maintenance was once again performed by personnel assigned specifically to RANCH HAND. These individuals have been readily identified. Thus, maintenance personnel directly assigned to RANCH HAND will be included in the study. These complexities are summarized in Table 4. Table 4 FEASIBILITY OF IDENTIFYING AIRCRAFT MAINTENANCE PERSONNEL (TOTAL POPULATION) EXPOSED TO HERBICIDE ORANGE Primary Maint Personnel Secondary Maint Personnel2 Jan 1962-Jul 1964 Yes No Aug 1964-Dec 1966 Yes/No3 No Jan 1967-Oct 1971 Yes No Time Hndividual assigned to RH; total number (denominator) known individual not assigned specifically to RH, although may have serviced the aircraft; denominator not ascertainable 3 other documents permit ascertainment of a portion of this group Because of the significant combat hazard associated with low, slow flying missions, some early RANCH HAND crewmembers were elite volunteers (see RiskTaking Bias, Section VIII, C). In fact, RANCH HAND crewmembers comprised one of the most highly decorated units during the RVN Conflict. Anecdotal stories reveal that most crew members were, on occasion, heavily exposed to Herbicide Orange due to normal or combat induced equipment malfunctions within the aircraft. Many former RANCH HAND personnel are expected to be currently employed in the aerospace industry as commercial airline pilots, airline managers, and flight mechanics. RANCH HAND personnel still on active duty are expected to be found in senior management positions. (b) Alternate Exposed Populations (I) Introduction The principal investigators, members of all of the peer review committees, and independent consultants have clearly recognized that the statistical power of this RANCH HAND study 1s suboptimal for the detection of specific uncommon conditions or diseases* This limitation is inherent because the size of the RANCH HAND population is fixed at approximately 1200 individuals, and 1t cannot be Increased. 19 �A brief review of alternate military populations is in order to highlight the significant advantages of the RANCH HAND population. The desire to achieve more optimal statistical power by merely increasing the size of the population under study must be balanced with a careful analytic process which assesses the exposure level of alternate populations, and categorizes them as either additive or nonadditive to the RANCH HAND study population. (2) U.S. Army Ground Personnel Some U.S. Army personnel were undoubtedly exposed to herbicides during their duty in Vietnam; however, the objective ascertainment of exposed individuals is not possible. Any attempts to identify individuals assigned to combat units which may have been exposed would result in an unacceptable degree of misclassification since U.S. Army personnel records do not exist which would allow the accurate identification of soldiers below the battalion level. This lack of demoninator data, and the high degree of misclassification in determining the exposure status of Army troops makes this population unsuitable for inclusion in the framework of the RANCH HAND Study. (1) Ancillary Air Force Groups (Non-RANCH HAND Personnel) Air Force handlers of herbicide drums in RVN were exposed to herbicides because of drum leakage. As the drum handlers were ad lib participants, no personnel designator was assigned to these individuals, thus prohibiting computer tracking and identification. The size of this population is unknown, but it is expected to be small (less than 200), as the majority of drum handlers are known to have been Vietnamese. Additional groups such as U.S. Army helicopter crews, casual observers (both Army and Air Force), and experimental fighter-bomber personnel who may have occasionally conducted spray operations were also potentially exposed. However, population-at-risk determinations for all of these groups cannot be made, and any identification of individuals exposed in these situations must rely on self-selection or incomplete ascertainment. Also, the selection of suitable control groups for a study of these individuals is difficult If not impossible. (£) U.S. Marine Corps Troops On 16 November 1979, the GAO released a report which suggested that a herbicide-exposed population of nearly 22,000 U.S. Marine Corps troops could be Identified, and that this identified group would be appropriate to study. Records exist which locate Marine Corps battalion headquarters near the C-123 spray paths. The GAO. made several Improper assumptions to conclude that all of the identified marines were in fact exposed. Specifically, all battalion troops were assumed to be located at the battalion headquarters. Further, the effect of prevailing winds on the direction of spray drift, and the photodegradatlon of the chemicals were not considered by the GAO. The National Research Council panel considered the GAO analysis, and proposed a study of 5900 marines who were "near" spray paths on the same day 20 �as the spraying. The '"exposed" group was to be contrasted with the mortality experience of 212,000 presumably unexposed controls (also marines). The RANCH HAND study described in this protocol consists of approximately 1200 exposed individuals and 6000 controls for the mortality study phase. Despite the fact that the RANCH HAND Study involves a smaller sample size than the proposed Marine effort, the RANCH HAND Study is more powerful statistically. Specifically, lower exposure to herbicide by a conservative factor of from 1/10 to 1/1000 and misclassification in Marine exposure groups renders the Marine Study far less powerful than the RANCH HAND effort. As described in Section VI, misclassification and decreased exposure are seen to be independent factors additively decrementing Marine Study statistical power. Even when all 21,900 marines within the herbicide spray paths up to 28 days following the spray operations are considered exposed, the RA1O HAND Study is noted to be significantly superior. Conclusions The Operation RANCH HAND participants are the most suitable of the military populations to study in evaluating the longterm effects of herbiclde/dloxin exposures. The RANCH HAND group had a much higher level of exposure which was sustained over a prolonged period of time. This Increased level of exposure implies that RANCH HAND personnel would be more likely to develop more acute and chronic symptoms from the exposure, and would manifest them sooner than the other exposed military personnel. The addition of significantly less exposed and/or misclassified groups to the RANCH HAND population for the attractive purpose of Increasing statistical power would constitute an egregious dilutional error. (2) Control Group (Not exposed to Herbicide Orange) A review of all specialized flight units present in Southeast Asia during the RVN conflict, reveals clearly that there is no absolutely ideal control group for the RANCH HAND population. C-130 aircrew members and support personnel were selected because of sufficient population size, similar training profiles, and psychologic similarities to the RANCH HAND group. Total ascertainment of the C-130 population is being conducted by computer and hand selection for specific military flying organizations, and foreign country service, during the Interval from 1962 thru 1970. Over 2.3 million personnel records have been reviewed, and the approximate C-130 population size Is 23,978 Individuals. Aircrew members who flew C-130 aircraft in Southeast Asia during 1962-1970 were selected as controls for the RANCH HAND • aircrew population. The C-130 flight line maintenance population were ascertained from personnel records by similar mechanisms, and served as the spe'•: £lf1c control population for the RANCH HAND support personnel. The proporj; jtlons on active duty, and non-active duty status are expected to parallel the f patterns In the exposed group. *• Another possible control group, the non-RANCH HAND C-123 popula: tlon, is known to be too small (approximately 3000) to provide adequate sampling flexibility and replacement -under the proposed matched variable concept 21 �(see below and Section VI). Also, many of the RANCH HAND aircraft were reconfigured for transport and Insecticide missions and thus, the non-RANCH HAND C-123 crews responsible for these other missions may have been exposed to significant Herbicide Orange residue In these aircraft. Therefore, this group may not have been truly unexposed to herbicides, and was discarded as an appropriate control population. Crewmembers of C-7 transport aircraft were also considered as a potential control group; however, because of small sample size (1000-2000) and the fact that they served 1n RVN only during the post 1967 era, they were also dropped from consideration. ' The normal crew composition of a C-130 1s three officers and two enlisted personnel. The control group Is considered to- be "pure" from the standpoint of lack of occupational exposure to herbicide. The entire control group will be considered MnonvolunteerM-w1th respect to abnormally high combat risk. While 1n general they will possess lifestyle characteristics and socioeconomic backgrounds similar to the exposed group, their overall combat morbidity/mortality and the resultant stress influences upon general health may be slightly less than in the exposed group. For those separated and retired C-130 controls, similar proportions to the exposed group are expected to be employed in the aerospace industry. Known and estimated factors of the control and exposed populations are summarized in Table 5. (3) Matching Procedures and Rationale Each member of the exposed group has been computer matched to a set of C-130 controls comprised of approximately 10 individuals using three variables. Since the L,;O groups are highly selected and inherently similar with respect to many variables, very close matches are feasible. This epidemiologic design incorporates a matched concept because: (1) a matched cohort design will provide maximum test power throughout the entire study, and (2) statistical intergroup comparisons may be made without normalization by three key variables known to effect symptom frequencies of interest, thus providing greater power for complex statistical .testing. It is apparent that following the match, both exposed and control populations will be very nearly identical with respect to the three influencing variables so that a replacement concept is feasible (see F below). In the event that frequent match breaks occur, stratification techniques can be used. The selection of the control group produces an inherent match for equivalent SEA experience, and additional matching has been conducted for (1) age, by year of birth and closest month possible, (2) Air Force Speciality Code (AFSC) as an absolute match, and (3) race (Caucasian versus nonCaucasian) as an absolute match. Specific rationale for these variables is as follows: (1) the age match controls for the many clinical symptoms and signs associated with advancing age, (2) AFSC controls for officer-enlisted status (as well as crewmember-noncrewmember status), a variable strongly linked to educational background, current socio-economic status, and moderately linked to age (5 year median difference) and socio-economic background, and (3) race controls for differences in chronic disease development, socio-economic background, etc. 22 �• rv**"i* ••>• ••• •• -*: ="T w- ,-u:"-!-.- .•.: * '<*' ' s ---.---,"•:.. ;•. , ' •. ' . '> ^Tabl* 5 >ARISON OF THE STUDY GROUP TO POSSIBLE CONTROL GROUPS BY ' KNOWN AND ESTIMATED FACTORS KNOWN FACTORS POSSIBLE CONTROL GROUPS STUDY GROUP RANCH HAND C-123 Non-RANCH HAND C-123 C-7 C-130 POPULATION SIZE 1264 3000 1200 23,978 OFFICER/ENLISTED RATIO 1:1.7 1:2 1:2 1:2 AIRCRAFT FUEL (AV-GAS) fNJ YES (+JP-4)* YES (+JP-4)* YES NO (JP-4 only) OCCUPATIONAL HERBICIDE EXPOSURE YES YES/NO** NO NO OCCUPATIONAL INSECTICIDE EXPOSURE 2+ 0 0 0 COMBAT HAZARD 4+ 3+ 3+ 2+ RVN-IN COUNTRY ASSIGNMENT 4+ 4+ 4+ 2+ ESTIMATED FACTORS *In 1968, aircraft were modified with a JP-4 booster. "Contaminated aircraft reconfigured for transport may have resulted in exposure to non-RANCH HAND personnel �The Inherent match fop SEA experience controls for combat-Induced physiologic, psyehophys1o1og1c, and other related morbidity and mortality disorders. Additionally, this Inherent match may reflect the effects of alcohol consumption, the use of chemoprophylactic and/or Illicit drugs, and the acquisition of tropical diseases associated with life In SEA. The comparisons of the exposed (RANCH HAND) subjects and their selected sets of controls are detailed In Appendix Table A-4. Only 4 of the ten categorical AFSC/case strata had less than ten controls for each exposed subject. The group of Caucasian pilots had a mean of only 9.5 controls per exposed subject, due to the extreme ages of several Individuals, and the strata of Black pilots and other Black officers had means of 2.7 and 5.0 controls respectively. However, since there were only seven black officers 1n the exposed group and only thirty controls, high numbers of tight matches could not be achieved. Black enlisted aircrewmembers had a mean of 9.8 controls each. (4) Computer Science and Statistical Details of the Matching Process As described above, the matching for this project has been performed using three variables: occupational category, race and age. Five occupational categories (officer/pilot, officer/navigator, officer/other, enlisted/flight engineer, and enlisted/other) have been used to reflect socloeconomlc status and aeronautical rating. The variable of race has been dichotomized Into black and non-black. Ten matched controls have been selected for each exposed subject, regardless of current vital status. The computer method applied to select the control subjects Is an adaptation of a procedure studied by Raynor and Kupper (Nearest Neighbor Matching on a Continuous Variable, Technical Report, Department of Blostatlstlcs, University of North Carolina, 1979). As the first step, the RANci! HAND and control groups were partitioned Into ten strata using the categorical occupational and race variables. The Raynor and Kupper matching procedure was then applied Heratively within each of the strata to match for the continuous variable of age, given In months. The Raynor-Kupper procedure Involves the following steps: STEP #1. The RANCH HAND cohort in a given strata is randomly permuted. STEP #2. The first RANCH HAND subject in the permuted set is selected for matching. STEP #3. The closest available control is assigned to the selected RANCH HAND subject using the absolute value of the difference between the months of birth of the RANCH HAND and the control subjects. If the closest available control is further than 60 months from the selected RANCH HAND subject, a blank is assigned. Tied assignments are broken randomly. STEP #4. Step #3 is repeated for all RANCH HAND subjects in the strata proceeding down through the permuted set, until the entire RANCH HAND cohort is exhausted. STEP #5. Steps #1 through #4 are repeated ten times for each RANCH HAND subject to construct a 1:10 study set. At the completion of the matching activity, the RANCH HAND - Control study matrices for each of the ten occupation-race strata can be diagrammatically represented as in Figure #1. 24 �i • Figure 1. MORTALITY ANALYSIS COHORTS RANCH HAND COHORT 10 V,J Ci.i C Ci 3 l,2 V* 1 J 1 3 » p R2 p °2 , 1 °2,2 R3 C-i , 1 ^3 , ^3,2 r, ,3 ^2 r. ** 3 R, Ci» ! ^»f ,2 ••••• r<» 1200,1 C l,10 ^2,<t ^2, 10 ^3,^ 3,10 ^ , 10 l200,2 C 1200,i» 12QO,10 Figure 2. MORTALITY MATRIX RANCH HAND COHORT CONTROL COHORTS c i,2,m' c j,5,m' R i200 C120o,i,m' C120o,2,m' *** In each row of this matrix the controls are ordered from nearest to farthest in terms of age of the matched RANCH HAND person. The next operation defining the control group involved randomization of all of the controls in each row of each stratum matrix to negate the ordering by age. Then, the first five members of each control set for each RANCH HAND person are identified as being subjects in the mortality portion of the study. The resulting occupation-race strata matrices now have the form shown In Figure 2. In Figure 2, Cj^' or Cj^^1 may be equivalent to any to the randomization process. of Figure 1 due Table 6 summarizes the results of the matching process, and Appendix Table A-5 provides a more complete statistical description of the process. In these tables, the age difference between the month of birth of the control and the month of birth of the RANCH HAND person, (counting months from 1900) and the cumulative number of controls and the cumulative percentage with this difference are shown. 25 �Table 6. RESULTS OF THE MATCHING PROCESS (1:10) Age Difference (in Months) Cumulative Number of Controls Cumulative Percent 0 8612 70.6 1 10287 84.3 2 10749 88.1 3 10984 90.1 4 .11167 91.6 5 11322 92.8 6 11410 93.5 12 11688 95.8 24 11921 97.7 36 12028 98.6 48 12129 60 12197 ' 99.4 100.0 (5) Study Group Selection Procedures (a) Mortality Analysis A 50% random sample of each control set will be drawn and used to comprise a 1:5 mortality analysis, as described in section (4). The vital status of each subject In this sample and of all exposed subjects will be ascertained at a minimum frequency of every five years for the 20 year duration of the study. Those individuals dying of combat causes will be excluded from the mortality analysis as it is assumed that combat death is independent of herbicide effect. Further, the known differential combat death rate between the RANCH HAND and control groups can be attributed to the hazardous and unique nature of the RANCH HAND mission. Twenty-two RANCH HAND personnel (15 officers and 7 enlisted) died 1n combat. Medical record reviews will be accomplished to assess the illness experience of these individuals prior to combat mortality. (b) Historical Morbidity Study Retrospective or historical health data will be gathered on each exposed subject and from the first randomly selected mortality control from his set by questionnaire techniques. Living but noncompliant controls in 26 �the historical morbidity study will be replaced by a compliant control selected from the control set. In order to avoid an information gap for data on deceased individuals, surrogate interviews will be obtained from the first order next-of-kin of exposed and control subjects dying of noncombat related causes between the date of their assignment to Southeast Asia and the initiation of this study. Since the validity and accuracy of surrogate derived data may not be equivalent to data obtained directly from living study subjects and their spouses, these data will be subsetted for analysis. All available medical records, (military, VA, and civilian) will be reviewed for all subjects selected for this morbidity analysis. (c) Prospective Morbidity Study A baseline physical examination and review of systems will be conducted, and a prospective or followup approach will be used to assess the current state of health of study subjects using a series of questionnaires and physical examinations over the next 20 years. Each 1iving exposed subject and the randomly selected primary control will be included in the questionnaire and physical examination phases. In this prospective study of morbidity, primary controls who are deceased, unaccountable or unwilling to participate in the followup studies, will be replaced by a willing subject from the remainder of the control set (Figure 3). The selected control for a RANCH HANDER dying of a noncombat cause will be retained throughout the questionnaire, physical examination, and followup phases of the study. Since the control's vital status and volunteerism should be independent of the matching sequence, many primary controls should enter the study. The remaining members of the control set will be used as replacement candidates for possible use later in the study (see section F below). All replacement controls will be clearly identified for the purposes of subset analysis so that population differences, if any, between the first randomly assigned selectees (noncompliant) and the replacements (compliant) can be assessed. Specific rules and procedures for study entry are found in Table A-6 and Figure A-3 of the Appendix. (d) The Interrelatedness of the Comparison Groups It should be clear from the foregoing discussion that the study populations of the mortality, historical morbidity, and prospective followup phases are highly related but different. Once selected, the mortality control cohorts will remain unchanged throughout the 20 years of observation. The population under study in the historical morbidity phase will initially be a randomly selected subset of the mortality comparison group; however, some of these primary controls may be decreased or noncompliant for the voluntary aspects of this phase of the study. In this phase, noncompliant controls will be replaced, but deceased controls will not, as surrogate Interviews with the rrext-of-k1n will be used to reconstruct morbidity data. The subsetting and replacement procedures create the difference between the mortality and historical morbidity comparison groups. The population 1n the prospective morbidity phase is the comparison group from the retrospective phase plus additional replacements for the deceased controls. Thus, It 1s clear that the comparison groups are slightly different, but they would be identical if no deaths occurred since 1962 and all primary controls were compliant. 27 �Figure 3. SELECTION PROCEDURE FOR THE QUESTIONNAIRE, PHYSICAL EXAMINATION, AND FOLLOW-UP STUDY LIVING RANCH HAND INDIVIDUAL CONTROL INDIVIDUALS Randomly Selected Mortality Controls JL I ** 1:1 t t t * ** Deceased Unwilling Volunteer Replacement Candidates C. Overview of Statistical Methodology The design of the study 1s presented In schematic form In Figure 4. R' refers to RANCH HAND personnel and C" 1 refers to the collection of all possible control Individuals. As defined, r and C" will contain individuals who are deceased of noncombat causes. Combat deaths are excluded from R' and C". Since C" is approximately 20 times larger than R', a randomized subsample C 1 and C" will be obtained. C 1 will be constructed from C" by computer selection of the ten matched controls for each exposed study subject. As previously noted, close matches will be mide for the variables of age, AFSC, and race. The matched controls will form tin cohorts, Ci through C 10 , as shown in Figure 1. A 50% random sample from each of the matched control sets of 10 will be selected for inclusion in the mortality assessment so that a group, C' is obtained that consists of 5 matched controls for each exposed subject. These controls will be designated as initial replacement candidates for the morbidity and follow-up studies. The remaining individuals in the control set will be additional replacement candidates in the event that replacement must occur beyond the members of the mortality set (see Figure 3). C 1 w1H be constructed without regard to whether the individual is currently living or dead so that an assessment of noncombat mortality can be accomplished. 28 �FIGURE 4 DESIGN SCHEMATIC EXPOSED R ro vP MORTALITY ANALYSIS UNUSED QUESTIONNAIRE PHYSICAL EXAMINATION �Referring again to Figure 4, R and C indicate living RANCH HAND members and primary matched controls. If mR 1 Is the proportion of R 1 found to be deceased, then R - (1 - mR'jR1 The questionnaire will provide data concerning specific symptoms and other findings In the R and C groups. Thus, various questionnaire finding rates 1n R, SR, will be calculated and compared with the corresponding rates 1n C, so The questionnaire will allow allocation of RANCH HAND personnel Into those with symptoms on questionnaire, Indicated by RS, and those without, R?. Similarly, the control J/idlviduals will be placed Into symptomatic, Indicated CS, and asymptomatic, C*S~ groups. The physical examination performed on Individuals from R and C will allow estimation and comparison of rates of physical findings in these groups. Rates of abnormal physical findings can be symbolically Indicated as fR and fc for RANCH HAND and control groups respectively. Comparison of these rates is very Important and details will be discussed below. Let fRs be the rate of physical findings among RANCH HAND personnel with findings by questionnaire and let fR$ be the rate of physical findings among RANCH HAND people with no findings on their questionnaire. For most disease processes it would be expected that fR$ should be a larger rate than fRS*. If fRs 1s observed to be equal to or less than fRjf, an Interpretation of over-reporting may be warranted, although the possibility of subclinlcal disease is recognized. Rates fcs w-|1 fr,$" will also be estimated, and and comparisons between fR$, fc$» fRS and fcr 1 De accomplished. The eight rates IDR', me', SR, Sc, fRS, fR$, frs» and their refinements fully characterize chls study. As depicted in. Figure "vertical comparisons of these rates provide relative risks mR'/mr,'. SR/SC, fR/fc» fRS/^CS ancl ^RS/^CS" which are of central importance in defining herbicide effects. "Horizontal comparisons" relate fR to SR» fRS to f RS» fC to -C and fCS to fCS"' Specifically, the ratio fR/SR is the ratio of physical findings to reported symptoms in the RANCH HAND population. This ratio may be contrasted with the ratio fr/sc and if fR/SR is less than fc/$c over-reporting is suggested. Likewise, if fR$ is less to than fR$~, over-reporting is further suggested. A comparison of fR$/fR$ ^CS/^CS contrasts the odds of findings given symptoms in the RANCH HAND population with the odds of findings given symptoms in the control group. If these odds are lower in the RANCH HAND group, overreporting is again implied. Further discussion of these rates is presented in Section V.G. During the questionnaire and physical examination phases of this study, only one of the five randomly selected mortality study controls will be used for each RANCH HAND individual. If this control is unwilling to participate, another mortality study control will be used as indicated in Figures 3 30 �and 7. These replacements w i l l b e carefully labelled for purposes of statistical analysis. A detailed discussion of this replacement concept is found in Section VI. D. Mortality Study (1) Introduction The mortality, retrospective morbidity, and follow-up studies are components of a "non-concurrent" prospective study used in the observation of a specially exposed group or industrial population starting from some date in the past. The initial exposures occurred 11-19, years ago and varied in Intensity and duration from one RANCH HAND, member to another. Access to employment, medical, or other types of records is an obvious requisite for such a study. The classical "case-control", retrospective study is not operative 1n this protocol due to the lack of defined clinical endpolnts. The mortality study will be conducted in two phases; a review of past mortality, and a continuing assessment of the death rate in the exposed and control cohorts over the twenty year duration of the RANCH HAND II project. Based upon USA vital statistics, 8.6% of the study subjects are expected to have died between completion of their Vietnam tour and Initiation of this study. Of these deaths 1n the control group, approximately 30% should have been due to cardiac causes, 24% to neoplasia, 13% to accidents, 5% to cirrhosis, and 0.1% to leukemia. (2) Data Collection Methods The mortality status of the exposed cohort and the randomly selected controls will be ascertained using multiple techniques including: payments of Veterans Administration Death Benefits, Social Security Administration Records, Air Force Accounting and Finance Center wage and retirement payments, and interviews with subjects or thetr families. Death certificates, autopsy reports, and medical records will be obtained for each deceased subject. The International Classification of Disease, Ninth Revision, 1978, will be used for coding. At the time of the first followup examination, all participants will be asked to allow an autopsy to be performed at government expense at the time of their death, and have the tissues forwarded to the Armed Forces Institute of Pathology, and the results sent to USAFSAM. (3) Analysis of Mortality Data (a) Basic analyses Considering the basic groups R 1 and C 1 1n Figure 4, individuals will be classified into three categories: alive, dead, or unaccounted. If a large number of Individuals 1n each group are unaccounted for, the study can obviously be severely biased. Thus, significant effort will be expended to reduce the unaccounted category as much as possible. At most, 1 to 3 percent of both groups can be allowed to remain unaccounted, with a 1% rate 31 �being preferred. If for example, the mortality rate In C' Is 0.10, then an unaccountabmty rate of 0.01 could alter the mortality rate by as much as 10%. Whatever the unaccountablllty rates, the pattern of unaccountabmty must also be compared between groups R 1 and C1. For example, the possibility of age differences must be examined, particularly 1f the unaccountabmty rates are high. The following paragraphs discuss the analysis of mortality under the assumption that low unaccountablllty rates have rendered the mortality analysis meaningful. Multiple mortality assessments will be accomplished during the course of this study, one at the beginning of 1 study, using available the mortality data on the basic mortality cohorts In C and R 1 (5:1 ratio), and others using mortality data on R 1 and all controls used In the study (both C 1 and replacements) as controls accumulate prospect1vely. The procedures described here will be used In all of these assessments. Henceforth, within the protocol, the term "mortality data" does not distinguish between that data collected Initially and that data collected In the future. The mortality data will be analyzed using several different approaches. Crude age-specific death rates will first be calculated and tabulated. Age will be divided Into k strata, and person-years will be observed for each strata as will be the number of deaths 1n each strata. In this manner a tabular display will be developed as shown In Table 7. Table 7 STRATIFIED FORMAT OF AGE-SPECIFIC DEATH RATES Ranch Hand Person Years Deaths 1 PH mu 2 Pl2 m12 3 Controls Pl3 Death Rate Person Years m r 22 P ik 2k Death Rate 21 P P23 m Deaths m 22 23 r zk Since the death rates r^j and r2j are Poisson variables, they can be contrasted directly. If the relationship of r t j to r2j is found to be consistent between age strata (within statistical variability), a summary mortality index may be calculated. One summary index that will be calculated is the Standardized Mortality Ratio (SMR) which is (Armitage, 1971): 32 �SMR = M x 100 k P M = J-l "Classical" standardized mortality ratios using national mortality data as the reference will not be calculated for RANCH HAND II due to the effects of the healthy worker phenomenon. The term £ rn'ij is the total number of deaths observed in the RANCH HAND group while I Py r2j is the number of deaths that would be expected were the age-specific RANCH HAND death rates the same as the age-specific control death rates. Thus the concern is for an SMR greater than 100%. If a crude death rate for controls, dc, is calculated as d c k I P2j J-l then the standardized crude rate for the RANCH" HAND group dRu is d RH s MdC' An approximate statistical test would regard dgx as a Poisson random variable with mean dr,. An alternative approach to the provision of a proportionate mortality ratio is that of Breslow and Day (1975). In this treatment, a multiplicative model 1s Employed, for example: where Ajjfc is the mortality rate, e-j Is the contribution due to population differences (RANCH HAND versus Control), $j is the contribution due to age 33 �group, and ^ 1s the contribution due to length of time 1n RVN, etc. The statistical approach here 1s via maximum likelihood. Logistic models (Walker and Duncan, 1967) have been extensively studied at USAFSAM for application 1n cardiovascular disease analysis. These models, 1n the herbicide context would have the form where P A T R E = probability of death • age 1n years = length of time 1n RVN = Indicator variable for race = exposure variable and where o lf 61, 1»1,2,... are coefficients to be estimated from the data. Testing for a group difference can be accomplished by estimating Bi, and the Interaction coefficients such as 05. If all interaction coefficients involving the exposure variable E are zero and E is treated as a 0/1 variable, Cox (1958a, 1958b) has shown that tho most powerful test for non-zero ei,, in the setting of matched pairs, is McNemar's test. This latter test makes full use of the paired design of the study. For McNemar's test, the data are cast into a 2 x 2 table as shown in Table 8. In this table, "a" Is the number of pairs in which both members have died, "b" is the number of pairs in which only the RANCH HAND person has died, etc. Using McNemar's test, the test statistic X2 b +c is calculated and referred to the chi-square distribution with one degree of freedom. Cox (1966) and Meittinen (1969) provided extensions of McNemar's test for R controls per exposed (R-to-1 matching). Of course the above analyses will be accomplished considering all deaths, and deaths by specific cause. As previously discussed, RANCH HAND personnel may be characterized as risk takers. This risk taking behavior may be associated with increased mortality from a variety of causes. On the other hand, herbicide exposure has caused neuropathy in the RANCH HAND personnel, one could anticipate that this disability would increase the probability of accidental death. Therefore, 34 �Table 8 FORMAT OF McNEMAR'S TEST CONTROLS RANCH HAND PERSONNEL Dead Alive Total DEAD ALIVE TOTAL a c a+c b d a+b c+d n b+d accidental death rates among RANCH HAND participants will be corrected for risk taking. This can be accomplished by including assessment of risk taking behavior in the questionnaire, indepth interview, and psychological evaluation. Both control and RANCH HAND mortality could be corrected using these measures, with the resultant rates being less biased and, therefore, a better indicator of exposed versus control effect. (b) Morta1ity analysis without covariates. The first step in the statistical analysis of survival data is descriptive, i.e., the construction of summary measures which provide a basis for comparing different exposure groups without any allowance for the effects of possibly confounding variables (e.g., age) except perhaps for some limited stratification. Since one must expect many "losses to follow-up", only methods which take full cognizance of this complication will be considered. It should be pointed out that all the methods described below assume independence between censoring (e.g., loss to follow-up) and death or morbid event, although some techniques permit different patterns of censoring 1n different exposure groups. The life table method can be adapted to obtain a step-function approximation to survival distributions in the presence of censoring (Chiang, 1968, Gross and Clark, 1975). The failure time distribution is the function F°(t) which provides the probability of deajfh at or before time t in the study. The Kaplan-Meier estimator of F°(t) is F°(t) where - 1 - n [1 - i/R(Ti)] 1eD(t) In this equation, D(t) 1s the "death set" at time t, I.e., the set of all Indices i of Individuals who were observed to fail before time t. R(Tf) is the number of individuals who were at risk just before time Tj, the time of death (or morbid event) of the 1tn study individual in D(t). A nonparametric approach to testing the equality of survival distributions in a matched 35 �pair study has been developed by We1 (1980). His statistic Is a generalization of the Gehan (1965a) statistic. A second test for homogeneity of survival distributions for dlscretlzed failure data 1s the test for marginal homogeneity In a KxK table due to Stuart (1955). Thirdly, the McCullough Model and test may be used on the KxK array to test for marginal homogeneity and stochastic ordering. (c) Mortality analysis with covarlates. These methods allow adjustment of mortality rates or morbidity rates using covarlates such as age, race, length of time 1n RVN, AFSC, risk taking score, etc. For t.he purposes of this discussion 1t will be assumed that the covarlables are categorical, that there are only two such covaMables and the covarlables do not Interact In affecting the hazard of death or morbidity. These assumptions can all be relaxed using available methods. The hazard function h^(t) for the 1th Individual 1n the study is the function which provides the conditional probability of death or morbid event in the time interval (t, t+dt) given his survival up to time t. The function H,(t) where t Hl(t) = / »H(T)dT 0 is called the cumulative hazard for the ith individual. It 1s readily shown that the failure time distribution F?(t) is given by: F°(t) = 1 - exp(-Hi(t)) From this last equation it follows that hi and F° are transforms of each other, hence the dependence of F° on covariables may be modeled via h^. This may be accomplished as follows. Let X-j(t) and Y^(t) denote discrete valued stochastic processes pertaining to the ith individual and describing two covariates of interest (e.g., one may be an exposure variable and the other may be covariate such as age or crew position). A basic model for hazard is: hi(t) = exp [5Xi(t) + nYi(t)] where 5 and n are "log-relative risks". This model may t* extended to allow for any number of possibly interacting factors. Inference about log-relative risks may be drawn using either an approach derived fro* 0. R. Cox (1972) by E. Peritz and R. Ray (1978) or using an approach descrirvd by Frank (1977). Another model, termed the proportional hazards model, is c*ven by 36 �Mt) • * The proportional hazards model has been discussed, for the special case that Xi(t) does not change with time, by Cox (1972). A test for the equality of survival distributions in a matched pair study which incorporates the proportional hazard model has been given by Breslow (1975). A test of fit for the proportional hazards model is given by Schoenfeld (1980). E. Morbidity Study (1) Genera1 Cons i derat1ons A vigorous attempt to determine the morbidity experience of all exposed subjects and their primary controls will be undertaken using questionnaires, indepth personal interviews, and physical examinations. A waiver will be requested from the U.S. Attorney General so that medical information collected during the conduct of this study may be exempted from subpoena into Federal Court. Total confidentiality of medical information will be granted to subjects who are not on active duty, and partial confidentiality will be given to active duty subjects with release of information to the DOD only in instances where there is a public safety or national security risk. The schedule and method of contact with the study subjects is depicted in the Appendix Table A-7. (2) Questionnaire Methods All living exposed subjects and their primary controls will be offered a comprehensive personal and family health questionnaire administered in the subject's home by a civilian contractor. In addition to subject interviews, a face-to-face interview will be conducted with the current spouses of the subjects to obtain a more accurate and complete assessment of fertility and reproductive function. Reproductive information that will be collected includes but is not limited to the number of live births, the number of still births, the number of miscarriages, the number of children conceived, the number of abnormal offspring, and the total years of marriage. Previous spouses of divorced or remarried subjects will also be interviewed to obtain similar data. Interviews with the first order next-of-kin of deceased subjects will provide morbidity data on the subject prior to his death. Whenever subjects, their spouses or next-of-kin will not consent to participate in a face-to-face interview, attempts will be made to elicit the Information by telephone. The questionnaire 1s an important part of this study because noncompliance rates for the physical examination and its face-to-face medical interview are expected to be substantially greater than non-compliance with the initial questionnaire. The questionnaire serves a four-fold purpose: (1) to capture baseline personal and medical data on subjects who might be noncompliant for subsequent physical examinations, (2) to serve as a cross-reference 37 �source for objective data obtained at the time of physical examination, (3) to obtain a targeted medical Inventory, Independent of the physical examination process, and (4) to obtain health perception data to serve as a foundation for the replacement strategy. As depicted In the Appendix, Figure A-2, only an estimated 40% of the RANCH HAND population will participate In the examination, while at least 65% will respond to the questionnaire. The Information collected by questionnaire from these additional 309 Individuals and their controls will provide valuable morbidity data which would otherwise be lost. The questionnaire (see Section XI) will emphasize Identification data, RVN tour history, dermatologlc conditions, neuropsychlatrlc conditions^ fertility aberrations, genetic defects 1n offspring, sensory defects, and personality factors. A targeted medic?:i ^nv^ntory will be Included In the questionnaire, and will Inventory symptoms prior to, .during, and after duty In RVN as well as those currently manifested. It will take approximately six months to complete all Initial questionnaires on both groups. The questionnaire will be "fieldtested" by the contractor on former Air Force personnel with RVN experience. Specific questions on the questionnaire will be directed to verifiable Information, wherever possible. Questionnaire development and refinement, Including specific response verification procedures have been pursued through civilian contract. Questionnaire data will be cross-linked and Integrated with medical record Information and physical examination findings. Questionnaire data from Individuals not completing all phases of the study will not be discarded, but will be Incorporated within the entire data base where statistically appropriate. Each participant will be asked to sign release forms so that all civilian health records, including those of dependents, can be obtained and reviewed as necessary. Attempts will be made to obtain pathological reports and specimens following surgical procedures. Federal health records on all family members on file in the NPRC will be retrieved. For retired members, and separated members with VA privileges, all available VA medical records will be obtained. All retrieved medical records will be reviewed, scored, compared to questionnaire data for reliability, and then be entered into a repository system. I 'antified participants who are nonresponsive to questionnaire will be pursued to determine status, disinterest, moribund state or death, etc. These individuals will be cross-referenced in other federal record systems in an attempt to achieve total ascertainment. Death certificates and autopsy reports will be retrieved on all dead exposed and matched control subjects fo • the mortality analysis. Birth/death certificates will be sought for all offspring. (3) Physical Examination A voluntary comprehensive physical examination will be offered to all individuals in both the exposed and primary control groups within one year of questionnaire administration. The condition for entry into the examination phase of the study will be the completion of the baseline questionnaire. In the event that the primary control does not complete both the questionnaire and the physical examination, a replacement will be selected from the control set [See Figure 3 and Section F(3)J. Statistical testing will be conducted by a variety of techniques on both questionnaire and examination findings. At the time of physical examination, an extensive physical examination, medical 38 �history, and review of symptoms will be conducted. A standardized protocol will be used to insure comparability of data. This will provide crossreference data to the initial questionnaire and to medical record data, if retrievable. Specific response verification and bias indicator questions will be included in this interview as well. (a) Examination Parameters A comprehensive physical examination will be conducted on all willing participants. The examination will be structured as outlined below and 1n Section XII and will be performed at the earliest practical time following the completion of the questionnaire. The close sequencing of these study components will limit the development of major symptoms in the interval between the questionnaire and the examination. Examinations will be performed under contract at a single civilian medical center having dermatologic, neurologic and electromyogram/ nerve conduction capabilities. Informed consent forms will be obtained for all procedures. Physicians and technicians will handle all participants without a knowledge of exposed or control status, and will conduct the examinations by standardized protocols to minimize variability. Medical students, Interns, and residents will not be allowed to perform these examinations, and specialty trained neurologists and dermatologists will perform the appropriate portions of the examination. An onsite monitor will Insure that the examination protocol 1s followed. All laboratory tests will be subject to rigid quality control. Laboratory and physical examination data will be measured on a continuous scale whenever possible in order to improve statistical power 1n the analysis. Under special circumstances, additional testing will be accomplished. Karyotyping of the Individual and his family members will be considered if clinical history or physical examination findings are suggestive of this need. Most well conducted studies have shown that, when present, chromosomal abnormalities due to TCDD are transient. If on detailed analysis of the baseline examination and questionnaire, reproductive areas are heavily affected, routine karyotyplng may be included in the test battery for the followup phases of the study. TCDO analysis on blood and urine will be considered in the future provided that (1) strong cause and effect relationships can be ascribed to Herbicide Orange and (2) high resolution mass spectrometry technology achieves 10 femtogram sensitivity with high isomeric specificity. Serum, urine, and semen specimens will be obtained from all participants, aliquoted, and preserved at -70°C for possible analysis in the future. These serum and/or urine specimens will also be used for analysis of porphyrin metabolites If analytic techniques make this a feasible diagnositc procedure. Extensive Immunologlc function analyses will be conducted on a randomly selected group of subjects. Physical examination and laboratory data will be placed in the member's coded master file for detailed cross-analysis to questionnaire data. Information Identifiable to the subject will not be released without his consent in accordance with the Privacy Act. However, 1n accordance with Air Force regulations, active duty flying personnel and active duty air traffic controllers found to have conditions which are disqualifying for flying duty will be temporarily "grounded" pending resolution of the medical condition. 39 �Physical Examination Profile General Physical Examination FBS, 2 Hr Post Prandial Urinalysls BUN/Creat1n1ne Cholesterol/HDL Trlglycerides Serum Protein Electrophoresls Hemoglobin Hematocrlt White Blood Cell Count and Differential Platelet Count RBC Indices Sedimentation Rate Prothrombln Time CPK ECG Chest X-Ray VDRL/FTA Cortlsol Differential Thyroid Profile (RIA) Pulmonary Function Studies Blood Alcohol Dermatologlc Examination Urine Porphyrins Urine PorphoblUnogen Delta-aminolevulenlc Add Neuro-Psychiatric Examination General Neurologic Examination Psychological Battery: Nerve Conduction Velocities MMPI WAIS WRAT Halstead-Reitan Wechsler Memory Scale Subtests Cornell Index Reproductive Examination LH, FSH, Testosterone Semen Analysis Neoplastlc/Hepatlc Examination SGOT Alkaline Phosphatase SGPT LDH (Isoenzymes 1f elevated) GGTP Hepatitis B Antigens/Antibodies B1l1rub1n, Total and Direct Additional Studies (Individuals with abnormal history or examination) Karyotyping Immunoelectrophoresls Hepatitis A Antigens/ Bilateral profile and fullAntibodies face photographs Anti-Nuclear Antibody Skin Biopsy Quantitative Immunoglobulins Additional Consultations as Required Immunologic studies (conducted on a randomly selected group of subjects) Enumeration of B and T Cells B and T Cell Function Enumeration of Monocytes 40 �(4) Analysis of Questionnaire and Physical Examination Data The Questionnaire and Physical Examination will produce data of three types: (1) dichotomous, (2) polytomous and (3) continuous. Dichotomous (e.g., present/absent) rates will be evaluated using the tools described above for mortality analysis. For example, the questionnaire will provide data concerning the first occurrence of disease states by age, and standardized rates and relative risks may be calculated. The occurrence of such findings can be related to age, time spent in RVN, exposure, and other variables using logistic models followed by McNemar's test where appropriate. These tests will examine the presence or absence of group effect and allow assessment of the statistical significance on non-unity relative risks. Polytomous findings will occur in both questionnaire and physical examination responses. As an example consider retinal findings categorized into four grades, and studied as a function of age and exposure group as represented in Table 9. In this table the XJJK'S are counts of occurrence. In analyzing tables such as these, techniques as described by Bishop, Fienberg, and Holland (1975) will be used. Specifically, if m^ is the expected value of x-fj|<, general log-linear models of the form in mfjk = u + u^i) + u2(j) + u3(k) + ul3(1k) + u23(jk) + u123(ijk) will be used, where u^i) is the effect of RANCH HAND membership alone on cell frequency, u12(ij) is the effect of an interaction on RANCH HAND membership with retinal grade, etc. This model can work with dichotomous as well as polytomous data. Under appropriate conditions on expected values of entries 1n Table 9, the pairing in the study design can be used with the data being organized as shown in Table 10. In Table 10, N-JJ is the number of pairs such that the exposed person has retinal grade i, and the control person has retinal grade j. Appropriate tests for this setting are indicated by Fleiss (1973) and McCullough (1978). With regard to continuous variables, the intended method follows Carpenter (1977) who found substantial gains in analysis efficiency by matching cases, subsequently employing covar lance analysis to remove non-controlled effects. The conditional logistic regression model for relative risk, Holford, White and Kelsey (1978), Is also applicable and will be used. 41 �Table 9 FORMAT OF CATEGORICAL REPRESENTATION OF RETINAL CHANGES RANCH HAND PERSONNEL CONTROLS "^x^Age Category Retinal Category^Xs"x^ 1 2 3 1 *l'.l X 112 X 2 X 121 X 122 3 X 131 X 132 4 X X 1 2 3 4 1U X 211 X 212 X 213 X 21"+ X 123- X 12»» X 221 X 222 X 223 X 22«f X V 1 tl 1 4 133 113 V 1 li j? X 13>» V 1 ^4 3 1l4l4 v A 231 X 2t4l y A 232 V v A 233 V 9l4!? y A 23i* V 9^4^ 9l4t4 Table 10 FORMAT OF PAIRING FOR GRADES OF RETINAL FINDINGS .Control Grade RANCH HAND Grade" 1 1 N U ^ 1 2 "13 2 N21 3 N 31 N22 N23 N 32 N 33 4 (5) Analysis of Fertility/Reproduction^Data. The herbicides under consideration in this study have been alleged to effect fertility and/or reproductive functioning. An attempt will be made to address these allegations by analyzing at least three primary variables: the total number of conceptions since exposure in RVN, the number of miscarriages in spouses since exposure in RVN and, the number of abnormal offspring since exposure in RVN. The interview with current and former spouses will provide much more accurate information on fertility and reproductive functioning than if similar data were obtained from the male subjects themselves. The study questionnaire will provide the numbers of miscarriages, abnormal offspring and of live births. The sum of the number of miscarriages, still births, and live births will provide an estimate of the total number of conceptions. If differing divorce rates are found in the RANCH HAND and control groups, this may render the average number of years of marriage and the distribution of the years of marriage different in the two groups. This will be investigated and adjusted 42 �for if need be, either by analyzing total number of conceptions divided by (or normalized by) the number of years of marriage, or by using a more detailed covariance analysis. Further, the ratio of the number of miscarriages to adjusted total conceptions will be calculated and compared, as will be the ratio of the number of abnormal births and adjusted total conceptions. In summary, the following statistics relating to fertility will be calculated and analyzed at the very least: TOTAL CONCEPTIONS = Rive Births + IStill Births + #Miscarriages NORMALIZED FERTILITY INDEX MISCARRIAGE FRACTION ABNORMALITY FRACTION TOTAL CONCEPTIONS YEARS OF MARRIAGE # MISCARRIAGES TOTAL CONCEPTIONS # ABNORMAL OFFSPRING TOTAL CONCEPTIONS F. Follow-up Study (1) Study Adaptations Following complete data analysis of the initial mortality and morbidity studies, adaptive or restrictive health surveys will be developed and administered to all follow-up study subjects three, five, ten, fifteen and twenty years after the initial questionnaire. Similarly, a condensed physical examination profile that will achieve adequate sensitivity and specificity for prospective diagnosis will be developed. The adaptive physical examination will be offered to all follow-up participants, and will also be conducted in years three, five, ten, fifteen, and twenty (see Appendix, Table A-5). An interim examination in year three 1s essential in this study because the age group under study is approaching that portion of the mortality/Illness incidence curve with the steepest slope. A lapse of five years between the first two examinations could easily miss significant development of disease in the intervening years. Ample precedent for Interim examinations can be found in the Framlngham cardiovascular disease study, and In the follow-up evaluation of West Point graduates being conducted by the Air Force. 43 �(2) Entry Criteria All exposed or control Individuals completing the baseline questionnaire and physical examination will be entered Into the follow-up; further continuation will depend upon the member's willingness/ability to participate 1n additional health surveys and condensed examinations. Specific study entry rules are detailed In Table A-6 and Figure A-3 of the Appendix. (3) Loss to Study; Key Issues Loss of participants over time adversely affects any epidemiologic study In two ways. Ar the sizes of the study groups decrease, statistical power also declines, and bias 1s Injected Into the study If losses are not randomly distributed in the study populations. It 1s reasonable to assume that in this study, losses will be non-random with greater non-compliance among individuals who perceive their health as "well," since there is less incentive for this group to continue participation. As shown in Figure 5, such a differential pattern of loss will alter the population, and skew the frequency distribution curve. Most previous epidemiologic studies have approached the problem of declining statistical power by beginning the study with multiple controls per exposed subject, and passively allowing attrition to occur throughout the study period. However, this approach does not address the problem of bias. This study will take an active approach to both of these problems by using a replacement concept. As a control is lost to study, a replacement will be chosen from the original set of ten matched controls. The replacement will be selected from the control set, and will have a perception of health similar to that of the lost control (Figure 6). The replacement strategy will maintain statistical power and the integrity of the matched design despite loss to study in the control group, and will correct anticipated bias while minimizing the number of required physical examinat'ons. At the initiation of the follow-up study, loss of an exposed member will not be cause to cease surveillance of his primary matched control. In the event of a control loss (for reasons other than death), another control from the set will be brought to study (Figure 7), the comprehensive questionnaire will be administered, and a baseline physical examination performed. If a control is noncompliant for one portion of the study and is replaced by another control, the noncompliant individual will be approached at the time of subsequent questionnaires and examinations, and encouraged to reenter the study. If he reenters, both he and the replacement will be included in the evaluation. Similarly, noncompliant exposed subjects will also be aggressively recruited for all subsequent study phases. 44 �FIGURE 5 EFFECT OF NON-RANDOM LOSS TO STUDY IN THE CONTROL POPULATION en N WELL *~ HEALTH SPECTRUM IF CONTROL LOSSES ARE ILL, A SPURIOUS EFFECT !S ATTRIBUTED TO HERBICIDE EXPOSURE. IF CONTROL LOSSES ARE WELL, A TRUE/VALID HEALTH EFFECT IS DILUTED. ILL �THE REPLACEMENT STRATEGY EXPOSED PRIMARY CONTROLS LOSSES REPLACEMENTS MATCHED FOR HEALTH STATUS (DEAD CONTROLS NOT REPLACED �CONTROL REPLACEMENT FOR THE MORBIDITY AND FOLLOW UP STUDIES FIGURE 7 EXPOSED CONTROL 1000 YEAR 6 -1 • QUESTIONNAIRE DATA O RECONSTRUCTED DATA #• LOSS TO STUDY PHYSICAL EXAMINATION DATA �For exposed and control individuals who drop out of the study but subsequently re-enter, medical data for the intervening years will be reconstructed from questionnaire and interview responses. IN ALL CASES OF LOSSTO-STUDY, INTENSIVE EFFORTS WILL BE MADE TO DETERMINE THE SPECIFIC REASONS FOR NON-COMPLIANCE, AND DATA FROM REPLACEMENT CONTROLS WILL BE REVIEWED TO ASSESS COMPARABILITY WITH THE LOST INDIVIDUALS. Medical record reviews of new entrants will continue throughout the follow-up period. (4) Study Length The fpllow-up st-'dy is initially planned for 20 consecutive years. Procedures, progress, anJ interim results of the study will be monitored by an independent scientific review group, responsible to the Office of Science and Technology Policy in the White House. G. Determination of "Disease" (1) Introduction Since this study is dealing with an unknown clinical endpolnt with unknown latency, determination of a disease state by statistical methodology is a prime scientific thrust of the investigation. From the literature, chloracne is the only generally accepted chronic disease associated with high exposure to dioxin. The questions of primary interest are: (1) Does a history of chloracne invariably lead to future disease? and (2) In the absence of chloracne, is there emergence of other attributable diseases? Under a broad concept of "spectrum of illness", either or both of these conditions are" possible. The clarification of their respective contributions to the natural history of past or of subsequent "disease" is of significant interest. (2) Discussion Inferences about a disease state from this study can be derived from several logical approaches. Tho'-.e approaches can be grouped into two categories: (1) those dealing with symptoms which can be used to construct a symptom complex that may represent disease, and (2) those dealing with physical signs which in themselves rep -esent disease. In the former, one can form a subset of individuals that have symptoms (e.g., infertility) and study them during the morbidity and follow-up studies. Focusing on the overall patterns of alleged symptoms and categorizing them into a symptom complex may identify those individuals with a disease syndrome, or those at higher risk of developing disease (e.g., genetic disorders, cancer). In the latter approach, data on abnormal physical signs (e.g., genetic defects in offspring) and laboratory results can be compared between exposed and non-exposed groups in an attempt to again establish the presence or absence of disease. By putting this array of data into a logical decision-making scheme, specific relative risks can be calculated in the follow-up study, and specific response patterns can be inferred as shown in Figure 8. 48 �FIGUkE >'• INTERPRETATION OF HORIZONTAL COMPARISONS OVERT EFFECT SUBCLINICAL MR * Mc •i = «c S R * S C S F R - F C F — D •— n R * F R O * " Fpc no vo FD O^ nQ F F R S * FCs MORTALITY/SYMPTOM/ SIGN REGRESSION ON EXPOSURE Q O f* b F C R MR = MC C s 0D n " c FR = FC r •P C l/o r rD It = F S-FC S F RS f c FCS SIGN REGRESSION ON EXPOSURE F OVER-REPORTING S=FCS R NO REGRESSION ON EXPOSURE SEEN RS S R"*" F RS u-SR 1 �Again referring to Figure 8, at least three clinical patterns can defined. These patterns are delineated using relative risks (mr/mc, sr/sc, fr/fc etc., between group or "vertical" comparisons, referencing Figure 4) and using within group ("horizontal" study) comparisons such as regressing symtoms and findings rates against an Index of herbicide exposure, and other comparisons. Specifically, an overt clinical effect would be marked by: an Increased mortality rate 1n the RANCH HAND group (mr > me), an Increased rate of symptom formation In the RANCH HAND group (sr > sc), and an Increased rate of objective medical findings 1n the RANCH HAND group as compared to the control group (fr > fc). Further, the occurrence of physical or objective medical findings would consistently relate to symptoms 1n the overt case (that is, frs > fcs and frs > fcs^, anH finally, in the classic Instance, mortality, and symptom and sign formation would- be seen to be increased with increasing herbicide exposure. A subclinlcal pattern is indicated in the central column of Figure 8. In this setting, one expects no statistically significant differences in mortality or symptom reporting between the two groups, exposed versus control. However, one expects a consistent predominance of medical signs 1n the RANCH HAND group with regression of the signs on increasing herbicide exposure. A pattern strongly suggesting over-reporting 1s presented as the right column of Figure 8. In this setting, there is no difference between the groups as regards mortality or medical sign incidence; however, more symptoms are reported by the RANCH HAND group. While in this pattern the RANCH HAND subjects are reporting more symptoms, objective medical finding rates are not consistent with symptom reporting. When no regression of symptoms on exposure level is found, over-reporting is clearly and strongly suggested. This discussion of response patterns has used regression on an exposure index in a central way. Development of such an index Is discussed below. It is noted, however, that a direct index of exposure can be confounded by other factors such as cellular repair mechanisms or bioaccumulation in adipose tissue with release over time upon weight loss. Use of other factors, such as time since exposure, should help to overcome these confounders. The strength of any inferences made from these analyses is dependent upon the statistical power inherent in the study. In addition, due to the possibility of latency being a factor in this study, a negative analysis at any time within the study does not categorically imply lack of disease, since sufficient time for emergence may not have passed. H. Exposure Indices (1) Exposure Concepts A major concern in conducting this study is the lack of accurate exposure data. Although most personnel assigned to RANCH HAND squadrons were undoubtedly exposed to Herbicide Orange and TCDD, the exposures within the 50 �group must have varied widely. Exposure to herbicides and TCDO by RANCH HAND personnel occurred almost daily. Anecdotal information suggests that many had direct skin contact which was repetitive over a long period of time (one-year tour for most individuals). Further, it is also suggested that most RANCH HAND personnel felt that the herbicides employed in the operations were not toxic to animals and man, and hence, they did not exercise the caution in handling these chemicals that is recommended today. From a historical review of RANCH HAND operations, it appears most individuals can be classified into one of three groups based on their likely potential for exposure to the herbicides: (1) Pilots, Co-pilots and Navigators:low potential (2) Crew Chiefs, Aircraft Mechanic, and other Support Personnel: moderate potential (3) Console Operators and Flight Engineers: high potential The "pilot" group received most of their exposure during preflight checks as well as during the actual dissemination missions. The crew chief group experienced contact with herbicides during dedrumming and aircraft loading operations, as well as during on-site repair of the aircraft and spray equipment. The console operator group was exposed while supervising the loadIng of the aircraft, during ground testing of equipment, and by tank leakage during dissemination missions. The available historical records on Operation RANCH HAND indicate that personnel assigned to the project seldom had a "routine" work schedule or environment, thus complicating estimates of the level of herbicide and dioxin exposure. Since actual exposure data (e.g., mg of herbicide/kg body wt) are not available, an exposure index will be used. The exposure indices will be calculated for each RANCH HAND individual to obtain frequency distribution, and will be calculated by evaluating the known factors that would have influenced exposure. These will include such factors as: (1) Date of tour with RANCH HAND 1n Vietnam. (2) Number and lengths of tours in Vietnam with RANCH HAND. (3) Number of herbicide dissemination missions (as reflected by flying hours and air medals). (4) Herbicides employed (records are available that reflect the amount of each herbicide sprayed each month and year). (5) Crew position. (6) Routes of exposure (the major route of exposure for most RANCH HAND personnel was probably percutaneous, although exposure through .inhalation may have also been significant). 51 �A crude exposure Index which 1s applicable to the entire RANCH HAND cohort is expressed with the following formula: E, • qj X T, In this formula, Ej is the calculated exposure for the ilL RANCH HAND member, q\ is the quantity of TCDD-contain1ng herbicide sprayed from aircraft assigned to the iUl subject's base during his assignment, and T^ 1s the length of the illl subject's assignment (tour length). However, great care must be exercised when applying the above index. For example, the Index should be used as an independent regression variable aga'lnst clinical findings only within occupational strata, to.'avoid confounding occupational effects with exposure effects. Different degrees of regression between clinical findings and the exposure index can be expected 1n differing occupational groups since: (a) modes of exposure are likely to be different 1n different occupational categories, (b) sodoeconomic correlates within occupational category could confound an herbicide effect, and (c) other exposures which could synerglstically or antagonistically interact with TCDO-conta1n1ng herbicide may be correlated with occupational category. Another factor which must be considered when applying this crude exposure index is the problem on confounding a possible herbicide effect with an effect associated with tour length. Being in a comabt zone is a major psychophysiological stress, and time spent in such an area may be significantly associated with changes in long term morbidity and/or mortality. This crude exposure index, when used alone, could result in a positive regression with disease incidence or prevalence which is not due to the herbicide exposure. An approach that will correct for this potential confounding is to regress observed medical findings on both EJ and T^ to differentiate the independent effects of herbicide exposure and combat zone experience. The values of qi and Tj needed to calculate Ej are generally available from government records. Specifically, tour dates are available from military personnel records, and the quantity of herbicide sprayed is available for the period January 1965 through April 1970 from the "HERBS TAPES." These tapes are comprised of computerized data obtained from actual spray mission reports. This material provides the date, base of mission origin, amount and type of material sprayed (Herbicides Orange, Blue, or White) and location of the intended spray target. Estimates of the amount of herbicide sprayed prior to 1965 may be available from procurement records for Herbicides Purple, Pink, and Green, which were sprayed exclusively from Tan San Nhut Air Base from 1962 through 1964. Animal data imply that TCDD is the most toxic component in the herbicides used in RVN. By using qi, the amount of herbicide sprayed, one is using a variable that roughly correlates with TCDD exposure. However, it would be highly desirable to be able to analyze observed health effects in terms of specific TCDD exposure. The material sprayed from 1965-1970 had significantly lower 52 �TCDD contamination then did those herbicides manufactured and purchased prior to 1962 and used from 1962 through 1964, but due to data limitations from a scarcity of Herbicide Purple, Pink, and Green samples, TCDD concentration profiles for those chemicals cannot be quantitatively determined. However, it may be feasible to develop estimates of the degree of contamination based upon the TCDD concentration from military and manufacturers' data. As another approach to examining the effect of TCDD itself, one might consider stratifying the exposed cohort by date of assignment 1n Vietnam, expecting that those assigned earlier were more heavily exposed to TCDD. While it may well be true that earlier assignees were exposed to higher TCDD concentrations, it is unlikely that differences between "early" and "late" assignees, if they occur, can be reliably attributed to TCDD concentration changes, since several potentially confounding variables exist: '(a) volunteerism among early assignees, (b) differing assignment patterns between early and late RANCH HANDers (TOY vs long term pattern) and (c) different RVN living conditions. It is preferable to use an exposure index which 1s more closely tailored to the specific individual than the crude index discussed above. While T| is subject specific, qj is a value which refers to all individuals on the base during the period of time represented by 1\. A refined index for ground crew can be expressed as: E i = F. X q i X C X T1 • : 7 x where, f"'. ?v ". Fj = Average flights per day served by the iitL ground crew member. °,1 - Average quantity of herbicide dispensed by flights served by the ij-ll ground crew member. C = Estimated TCDD concentration of the herbicides in use during the iM subject's tour of duty. TI = Time spent in TVN in days for the ilil ground crew member. The variable F^ can be estimated by dividing the number of RANCH HAND flights per day by the number of crew chiefs during the time period T-j. All other variables are estimated as with the crude index. A refined index is also possible for aircrew members and is expressed as ;n fOl1OWS : E1 = M 1 X D 1 X q 1 X C X P 1 * total number of missions flown by the iJill air crew member. = average duration of missions flown by the ilP. air crew member. * average quantity of herbicide dispensed per flight served by the ilil air crew member. = estimated TCt)D concentration of the herbicides 1n use. = a cr-?w position weighting factor. 53 �As with the refined ground crew Index, this refined aircrew index cannot directly calculated in a strictly quantitative sense using available govern, ment records, since records to specifically link missions with particular individuals are not available to objectively determine MJ and Dj. He ever, reasonably accurate estimates of these parameters may be feasible uslni questionnaire data. Also air medal awards may allow an Indirect estimate, The crew position parameter PI must also rely upon estimations. While t| specific crew duties of each subject are known, the differential exposur associated with the crew positions within the C-123 aircraft were hot detq'/ mined during RVN spray missions. The 355th TAS/Spray Branch, Rickenbacher OH is presently using the C-123 aircraft, configured with the A/A 45 . ^ Internal Dispenser and attempts to as'sess Pj can be made. Air flow measure ment and herbicide simulant deposition studies conducted by Meek are perfor during the course of four C-123 flights. However, difficulties with tf measurement equipment limit the validity of the value of the data in an exposure index. Further work along these lines could yield a more quantitative, position weighting factor, Pf, for each individual. Refined ground crew and air crew exposure Indices can be used singly or combination with the crude exposure Index first presented; however, as wltj the crude index, confounding must be avoided when the refined indices are us'ej in statistical analyses. The exposure indices listed above are, of course, only applicable to the Ram Hand cohort. As mentioned, a positive regression of disease Incidence prevalence with increasing exposure index will strongly support herb1ci( causation. We do not wish to minimize however the role of RANCH HAND versus control group disease incidence/prevalence differences as Indicators of :) herbicide effect. A major component differentiating the RANCH HANDers fre the controls is the increased residence of RANCH HANDers in the RVN Itself^ If within country time does not correlate with disease incidence, RANCH HANpJ versus control disease incidence differences may be strongly related tc herbicide. If in-country time is significant as a disease correlate, this It itself will be valuable information with regard to assessment of the RVfl experience. 54 �VI. Special Statistical Considerations I 1 The previous discussion has outlined, the general statistical approach followed by this protocol, and has outlined planned analytical methods and inferential strategies for the mortality, questionnaire and physical examina; tion study phases. This section provides an indepth consideratior of some j . special statistical study aspects. $ A. Fa1se Report ing/Mis rep resentat i on | Since concern for compensation could unconsciously or consciousl | influence symptom reporting, and since press reporting itself can st * anxiety-based symptom formation, a discussion of false reporting is iridi| cated. A data pattern indicating overreporting has already been discussed f>" Section V. The goal here is to understand the effect of misrepresentation on I estimates of relative risk and the odds ratio. Let S stand for presence of a symptom, and T denote its absence. This false reporting may be represented as 1n Figure 9. Figure 9 FALSE REPORTING/MISREPRESENTATION TRUE STATUS s r Total A B A+B C D REPORTED STATUS C+D B+D A+C The proportion of correctly classified positives is defined by A/(A+C) and is lied the sensitivity of the classification scheme; the proportion of corly classified negatives D/(B+D) 1s called the specificity. When there 1s non-differential misrepresentation, that is, when the isitivity and the specificity are the same among the exposed and nonexposed, fehe bias Induced in the estimate of relative risk will be-toward the null talue. The situation is summarized by Figure 10. 55 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 060 Folder The folder containing the original item. 1599 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Supporting Statement with Attachments Subject The topic of the resource Air Force Health Study Ranch Hand crew Marine Corps exposure ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/13fbf0049313bcfb2a85c2e6d63bab19.pdf 906870d51324bec1e84cf13cccb50f40 PDF Text Text Item ID Number 01597 Author Corporate Author Roport/Alticlo TitlO Typescript: Mortality Analysis, Power Comparison of the Ranch Hand Study to the Marine Population Considering Misclassification and Relative Exposure Journal/Book Title Year 000 ° Month/Day Color n Number of Images 1 DOSCrlptOD NOtOS Includes a handwritten observation. Wednesday, May 23, 2001 Page 1598 of 1608 �MORTALITY ANALYSIS POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATION AND RELATIVE EXPOSURE^ POWER TABLE RANCH HAND POWER 1-B ,92 ASSUMPTIONS MARINE STUDY POWER % MISCLASSIFICATION EXPOSURE LEVELS RELATIVE TO RANCH HAND 1/10 1/20 1/100 1/1000 M ,17 0 ,36 ,16 10 ,28 ,13 25 RH STUHY Pnp. 1,200; 6,nrin (1-5) MARINE STUDY PHP, 21,900: 196,100 NORMAL INCIDENCE OF DISEASE = 0,01 DISEASE INCIDENCE IN RH = 0,02 LINEAR DOSE - RESPONSE MISCLASS, OF MARINE CONTROLS EXCLUDED ,07 ,07 ,06 ,05 ,05 ,05 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 060 Folder The folder containing the original item. 1597 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Typescript: Mortality Analysis, Power Comparison of the Ranch Hand Study to the Marine Population Considering Misclassification and Relative Exposure Subject The topic of the resource Air Force Health Study Marine Corps exposure ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/4cad9e104281ea21aa6d58077c25dc9a.pdf 6089c4098b1b8003a618435654fe0d69 PDF Text Text Item ID Number 01474 Author Corporate Author ROpOrt/ArtlOlO TltlO Typescript: Notes and diagrams regarding TCDD exposure Journal/Book Title °°00 Year Month/Day Color n OOSOrfptOD NOtOS Typescript and diagrams regarding TCDD exposure, Australian Senate Committee on Science and the Environment, Ranch Hand versus Marine exposure Tuesday, May 15, 2001 Page 1474 of 1514 �PARAMETERS OF TCDD EXPOSURE HERBS TAPE ACCURACY ENVIRONMENTAL FATE OF TCDD PERSONNEL PROXIMITY TO SPRAY VIA RECORDS REVIEW ECOLOGIC MODELING �ISSUE: CAN A VALID HERBICIDE ORANGE (TCDD) EXPOSURE ALLOCATION BE MADE FOR EACH INDIVIDUAL (GROUP) IN PREPARATION FOR A STUDY OF GROUND PERSONNEL? EXPOSURE ALLOCATION OUTCOMES STUDY OUTCOMES VALID TRUTH MISCLASSIFIED INDETERMINANT BIASED POSITIVE OR NEGATIVE NOT TRUTH �EXPOSURE ALLOCATION METHODS SUBJECTIVE MEANS: * QUESTIONNAIRE TECHNIQUES OPINION: INTENTIONAL MALATHION EXPOSURE BY SIMILAR AIRCRAFT IN RVN HAS CREATED A POSITIVE IRREVOCABLE BIAS ® SOLICITATION FOR "EXPOSED" VOLUNTEERS OPINION: UNCORRECTABLE SELECTION BIAS �EXPOSURE ALLOCATION METHODS OBJECTIVE MEANS: e RECORD REVIEWS IN SELECTED OCCUPATIONAL GROUPS OPINION: BIAS, MISCLASSIFICATION POSSIBLE, SMALL SAMPLE SIZE ASSURED ® PROBABILISTIC DETERMINATION VIA HERBS TAPES AND RECORD REVIEW FOR TIME/DISTANCE ESTIMATES OPINION: MISCLASSIFICATION ASSURED; SELECTION BIAS PROBABLE, TRUE ERROR RATES IMPOSSIBLE TO MEASURE; VALIDITY COMPROMISED �PROCESS OF EXPOSURE ALLOCATION INFLUENCES: > COHORTS (STUDY AND COMPARISON) TO BE SELECTED > METHOD(S) OF COHORT SELECTION > SAMPLE SIZE OF COHORTS » STATISTICAL POWER > OPERATION OF CONFOUNDERS (MALATHION, COMBAT STRESS, ETC.) \ SCIENTIFIC/LAY ACCEPTANCE OF STUDY �SOME STUDY OPTIONS BASED ON EXPOSURE DILEMMA 9 PERFORM A "RVN EXPERIENCE STUDY" ® DECLARE AGENT ORANGE STUDY NOT DOABLE ' © BOTH OPTIONS ABOVE » DETERMINE FEASIBILITY OF USING OCCUPATIONAL GROUPS • CONDUCT AGENT ORANGE STUDY BASED UPON PROBABILISTIC EXPOSURE • ABOVE OPTION, ADD COHORT(S) FOR "RVN EXPERIENCE STUDY" �OPINION BASED UPON $ WORLD LITERATURE: ZERO TO LOW INCIDENCE OF HEALTH CONSEQUENCES, RARE OR DIFFICULT TO MEASURE CLINICAL ENDPOINTS ® FACT OF UNESTIMATABLE ERROR "RATES FOR EXPOSURE ALLOCATION IN GROUND TROOPS BASED UPON HERBS TAPES @® YIELDS A STUDY OF UNKNOWN ABILITY (POWER) TO DETECT A EFFECT USE OF PROBABILISTIC MEANS TO DETERMINE EXPOSURE IS SCIENTIFIC HOKUM �AUSTRALIAN SENATE COMMITTEE ON SCIENCE AND THE ENVIRONMENT CONCLUSIONS LITTLE LIKELIHOOD AUSTRALIAN TROOPS WERE DIRECTLY OR INDIRECTLY EXPOSED TO HERBICIDES DIRECT EXPOSURE TO MALATHION WAS HIGHLY PROBABLE IN THE MAJORITY OF CASES EXPOSURE TO ANTIMALARIAL DRUGS WAS ROUTINE ANY ADDED CARCINOGENIC/TERATOGEN1C.BURDEN ON AUSTRALIAN TROOPS WAS RELATIVELY SMALL ' BASED ON CURRENT DATA, "THERE IS NO CONVINCING EVIDENCE THAT BIRTH ABNORMALITIES, PSYCHIATRIC DISORDERS AND MORTALITY ARE EXCESSIVE AMONG VIETNAM VETERANS." ALL FUTURE AUSTRALIAN GOVERNMENT STUDIES WILL ADDRESS THE ISSUE OF VIETNAM SERVICE, NOT SPECIFIC CHEMICAL EXPOSURE �KEY ITEMS OF CONSIDERATION MARINE STUDY RELATIVE TO RANCH HAND STUDY "EXPOSED " MARINES RECEIVED AN AVERAGE EXPOSURE 1/1000 THE AVERAGE DOSE RECEIVED BY RANCH HAND PERSONNEL MARINE EXPOSURE ALLOCATIONS BASED ON DISTANCE FROM SPRAY PATHS LEAD TO SERIOUS MISCLASSIFICATION OR BIAS MARINE EXPOSURE ALLOCATIONS BASED ON TIME IN A SPRAY AREA SUBSTANTIALLY ALTER THE SIZES OF THE STUDY AND CONTROL POPULATIONS AND LEAD TO SERIOUS MISCLASSIFICATION �CONCLUSIONS RANCH HAND VERSUS OR PLUS THE MARINE POPULATION • OVERWHELMING ALLOCATION PROBLEMS FOR "EXPOSURE-NONEXPOSURE" IN MARINES - MISCLASSIFICATION BY 6AO 8RITERIA = OILUTIONAL EFFECT - ALLOCATION BY PERSONAL HISTORY = BIAS • MARINE EXPOSURE 1/1000 OF RANCH HAND EXPOSURE « MARINE - RANCH HAND POPULATIONS DIFFER BY HOST FACTORS; AGE, RACE, EDUCATIONAL LEVEL, ETC •• BY CONSIDERATION OF EXPOSURE DIFFERENTIAL AND MISCLASSIFICATION, RANCH HAND STUDY FAR MORE POWERFUL THAN INDEPENDENT MARINE STUDY OR ADDITIVE STUDY TO INCLUDE MARINES •• ADDITION OF MARINE POPULATION TO RANCH HAND POPULATION = UNACCEPTABLE SCIENCE �MORTALITY ANALYSIS POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATION AND RELATIVE EXPOSURE * POWER TABLE MARINE STUDY POWER ANCK HAND POWER 1-B % MISCLASSIFiCATION EXPOSURE LEVELS RELATIVE TO RANCH HAND • 1/10 1/20 1/100 1/1000 .87 0 10 25 ASSUMPTIONS: RH STURY POP. 1,200; 6,000 (1:5) MARINE STUDY POP. 21,900: 196,100 NORMAL INCIDENCE OF DISEASE =0.001 DISEASE INCIDENCE IN RH - 0.004 LINEAR DOSE - RESPONSE MISCLASS OF MARINE CONTROLS EXCLUDED .38 .33 .26 .17 .15 .13 .07 .06 .06 .05 .05 .05 * INCORRECT POPULATION NUMERICS BASED ON ENVIRONMENTAL FATE OF TCDD � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 055 Folder The folder containing the original item. 1474 Series The series number of the original item. Series III Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Typescript: Notes and diagrams regarding TCDD exposure Subject The topic of the resource human exposure AVHS Ranch Hand Marine Corps exposure ao_seriesIII