To compare survival data it was necessary to construct a survival table. This also involved devising a calendar to show days and weeks on study for each housing group, taking into account the starting dates for each group. This also included tables showing the numbers of days and weeks animals were on study and a table comparing the survival data from various sources.

We constructed a chart showing diet calculations (gm./kg) and total amounts of DKP used (gm./batch).  This is attached as exhibit #30.

Three tables were constructed which summarize the FDA statistical analysis of body/feeder weight data.  They are attached as exhibits #39-41.

All of the charts, diagrams and tables that we constructed are attached to the report as exhibits and are referred to in various sections of the report.

EXHIBITS

#1.  G.D. Searle & Company Annual Report for l976.

#2.  Organizational Chart of Pharmaceutical/Consumer Products Group.

#3.  Organizational Chart of World Wide Pharmaceutical R&D Group.

#4.  Organizational Chart of Preclinical R&D Group.

#5.  Organizational Chart of Product Safety Assessment Group.

#6.  Copies of Computer-Generated Randomization Tables used by Searle to assign the Dose & Housing Groups.

#7.  Diagram showing Typical Housing Group of 30 animals, containing a random distribution of control and treated animals.

#8.  Diagram showing arrangement of food cups on cart, used in feeding the animals.

#9.  Copy of "Glossary of Terms for Aspartame and its Diketopiperazine" and "Analytical Data and Specifications of Food Grade Aspartame".

#10. Copy of shipping labels for rats received from [missing]

#11. Copy of protocol with amendments for Study P.T. 988S73 (E-77/78).

#12. Copies of CV's for principal persons involved in study E-77/78.

#13. Copies of Batch Records for the manufacture of DKP, lots 1R through 5R.

 #14. Copies of pages from SEarle chemist Jack Drogt's notebook, concerning the manufacture of DKP.

#15. Copies of Analytical Reports for DKP, lots 1R through 7R.

#16. Copy of Searle memorandum dated 12/4/69, concerning DKP Specifications.

 #17. Copy of DKP Specification Sheet (not dated) entitled "Tenative Specifications for SC-19192".

#18. Copy of DKP Specification Sheet entitled "Specifications for SC-19192, Specification #C40606C".

#19. Copies of pages 75-84 & 285 of lab notebook #AR-39, concerning assay of DKP, lots 1R, 2R & 3R.

#20. Copies of pages 60-63 of lab notebook VSH-I, and page 269 of lab notebook book #AR-23, pertaining to analysis of DKP lot 4R.

#21. Copies of pages 250, 251 and 257 of lab notebook #AR-57, and pages 44-49 of lab notebook #AR-68, pertaining to analysis of DKP lot 5R.

#22. Copies of pages 83-86 of lab notebook #AR-77, concerning analysis of DKP lot 6R.

#23. Copy of page 31 of lab notebook #AR-93, concerning analysis of DKP lot 7R.

#24. Copy of protocol for DKP stability study, dated 1/13/72.

#25. Copies of pages 51-56 of laboratory notebook #AR-49, assigned to C. Seul.  These pages describe a preliminary TLC Test for recovery of DKP from the diet mixture.

 #26. Copies of pages 53-59, 67-72, 88-89, 106-107, 144-145, 156-157, and 284-285 of laboratory notebook #AR-51, assigned to Barbara Bickford.  These pages refer to the assay procedure and methods for the DKP Stability Study.

#27. Copies of Analytical Reports for DKP Stability Study.

#28. Copies of DKP Compound Inventory Cards.

#29. Two photographs showing a non-homogeneous sample of DKP diet mixture.

#30. Chart showing diet calculations (gm.kg.) and total amounts of DKP  used (gm./batch).

#31. Two memos dated 7/14/77 from Thomas F.X. Collins concerning interview with Ray Schroeder.

#32. Memo dated 7/19/77 from Thomas F. X. Collins describing the 7/18/77 interview with Ray Schroeder.

#33. Memo of Telephone Conversation between Jerome Bressler and Attorney John H. Bickley Jr., dated July 25, l977.

#34. Copies of records concerning calculation of diet concentrations, food concentrations prediction records, dates of bath mixing, and calculation of mean food intake values.

#35. Charts organized by dose group, showing the identification and pathology history of each of the 360 animals on study.

#36. Memo dated April 5, l976, from Dr. John H. Rust to Dr. R. McConnell.

#37. Searle memo dated September 30, l974, by Dr. McConnell.

#38. Memo dated August 29, l974 from Dr. G. L. Schoenhard to Dr. K.S. Rao.

#39. Table 1 - Summary of Average Body Weights and Weight gain (%change/week) from the FDA Statistical Analysis.

#40. Table 2 - Summary of food intake (g/day and g/kg./day and dosage (mg./kg./day) from the FDA STatistical Analysis

#41. Table 3 - Summary of Food Efficiency (g. gained/100g. actual food consumed) calculated in the FDA STatistical Analysis.

#42. Computer printout of FDA Statistical Analysis of food intake and body weight data.

#43. Pathology report from Division of Pathology, Bureau of Foods, concerning uterine polyps, along with correspondence, and memo from Janet Springer.

#44. Pathology report from Armed Forces Institute of Pathology, concerning uterine polyps.

 #45. Pathology report from Massachusetts Institute of Technology, concerning uterine polyps.

 #46. Written account of interviews with Dr. Jean Taylor on 6/2/77, 6/3/77,and 6/7/77.

#47. Written account of interview with Judy Beauchamp on 6/2/77.

#48. Written account of interview with Barbara Bickford on 6/1/77.

#49. Written account of interview with Clifford J. Seul on 6/2/77.

#50. Written account of interview with Bartolome R. Tangonan on 6/1/77.

#51. Written account of interviews with Tony Martinez on 5/19/77,6/3/77, 7/7/77, and 8/2/77.

#52. Written account of interview with Ted Reichert on 5/24/77.

#53. Written account of interview with Barbara Bickford and Clif Seul on 6/2/77.

#54. Written account of interview with Judith Schmal on 6/2/77 and 6/7/77.

#55. List of animals bled at 104 and 114 weeks.

#56. Written account of interview with Alan Mitchell on 7/20/77.

#57. Written account of interview with Raymond G. Schroeder on 7/18/77.

#58. Injection records showing administration of penicillin, dates of administration, rat numbers, and units injected.

#59. Methodology for "Phenistix" determination of phenylketones in urine.

#60. Dr. Frith's report of examination of slides for DKP study (E-77/78).

#61. Key for animal identification card numbers used on the body/feeder weight teletype sheets.

#62. Chart correlating animal cage numbers with pathology numbers, arranged by dose group.

#63. Chronological list of pathology numbers and corresponding animal cage numbers.

 #64. Organizational charts showing responsibility during the time that study E-77/78 was conducted.

#65. Volume entitled "tissue masses & deaths".  Chronological list of all animals that died, during study, and dates that masses were first observed.

#66. Charts of days on study for each animal.

#67. Calendar for duration of study showing starting dates, days and weeks for each group.

#68. Survival table.

#69. Charts of Housing/Dosage Groups.

#70. "Observations for Drug Effects" records for housing groups A through F.

#71. "Observations for Drug Effects" records for housing groups G through M.

#72. Ophthalmoscopic records and copies of pathology sheets that have ophthalmoscopic findings.

#73. Life table analysis and statistics on body weight and food consumption data by Dennis Wilson, Div. of Mathematics, Bureau of Foods.

#74. Evaluation of feeding study on DKP, a conversion product of Aspartame, by Janet Springer/Ann Ducca, FDA Division on Mathematics.

#75. Volume A - teletype sheets for body and feeder weight data, housing groups.

      Volume B -           "

      Volume C -           "

#76. Copy of Searle Computer Program.

#77. Volume of protocols, organ weights, dosage, hematology, urinalysis, blood chemistry, and protein electrophoresis.

#78. Complete gross pathology sheets, males.

#79. Complete gross pathology sheets, females.

#80. Key to slide tissue identification numbers and abbreviations.

#81. Key to stain abbreviations.

#82. Copies of submission appendix tables relating to hematology,  clinical chemistry, urinalysis, and electrophoresis, along with check marks showing errors, and attached copies of raw data sheets documenting the errors.

#83. Copies of submission appendix tables for organ weights, with errors indicated, and copies of pathology sheets documenting the errors.

#84. Data sheets showing the phenylketones test erroneously labeled "phenylalanine".

Signed by:

John S. Arnold

Investigator

David M. Eerspamer

Investigator

Dr. Jean Taylor

Toxicologist

Dr. Leonard Friedman

Biochemist

Addendum:

Exhibit #85   - Copy of Volume 1 of the submission to FDA.

Exhibit #86   - Copy of Volume 2 of the submission to FDA, consisting of the individual pathology summaries, both gross and  microscopic.

Exhibit #87   - Statistical analysis of Blood and Clinical Chemistry Data by Dennis Wilson, Division of Mathematics, HFF-110.

Exhibit #88   - Copies of pages from Histology accession book #770C,  and Histology inventory sheets.

Exhibit #89   - Documents from Searle's Math-Stat. Dept. concerning statistical analysis of study 988S73.

Signed

Jerome Bressler