PAN AMERICAN HEALTH SECOND MEETING ORGANIZATION 17-21 June 1963 Washington, D.C. ADVISORY COMMITTEE ON MEDICAL RESEARCH

INTER-AMERICAN INVESTIGATION OF MORTALITY

Ref: RES 2/8 2 May 1963

PAN AMERICAN HEALTH ORGANIZATION Pan American Sanitary Bureau, Regional Office of the WORLD HEALTH ORGANIZATION

WASHINGTON, D.C. RES 2/P

REGIONAL DEVELOPMJiLNT CF LPIDJ4ICILOGICAL STUDIES

INTER-AIMERICAN INVESTIGATICN UF IVOCTALITY *

The Inter-American Investigation of Mortality, a co- operative research program made possible by a grant from the

National Institutes of Health, United States Public Health

Service, was initiated early in 1962. The research plan, outlined in a report (RES 1/8) to the First Meeting of the

PAHG Advisory Committee on Medical Research, provides for the submission of clinical and other information in a standard form from collaborating centers in 12 cities with the object of establishing reliable and comparable estimates of mortality for different causes of death for the populations cDncerned. The present report gives information about the progress of the investigation and an indication of some of the preliminary results obtained.

Progress of the Investigation

Of the 12 research centers which are now cooperating in the project, four are established in schools of publie health, two in schools of medicine and two in existing research institutes. The remaining four centers are located in the

*Prepared for the Second Meeting of the PAHO Advisory Committee on Medical Research, 17-21 June 1963, by the Medical Officer, Health Statistics Branch, PASB. - 2 - RES-- 2/8

central offices of national or local health administrations and in three of them the principal collaborator is also actively associated with a school of medicine or public health. In each center a principal collaborator is in charge of a small staff, consisting of medical interviewers, social workers and a secretary, whose task it is to complete approximately 2,000 questionnaires each year, for two vears, concerning deceased residents of the city aged from 15 to 74 years. The following table sets out for each city the period to be covered by the field of investigations and the number of completed questionnaires received in Washington up to the end of April 1963.

Inter-American Investigation of DMIortality, Study Period to be Covered in 12 Cities and Numbers of Completed Questionnaires April 30, 1963

City Study Period Completed Questionnaires

Bogota, Colombia Jan. 1962-Dec. 1963 1,413 Bristol, England Oct. 1962-Sept. 1964 496 Cali¡ Colombia May. 1962-April 1964 1,609 Caracas, Venezuela Jan. 1962-Dec. 1963 1,644 Guatemala City, Guatemala Mar. 1962-Feb. 1964 1,100 La Plata, Argentina Jan. 1962-Dec. 1963 1,543 Lima, Peru Jan. 1962-Dec. 1963 1,454 Mexico City, Mexico Mar. 1962-Feb. 1964 1,070 Ribeirao Pr^to, Brazil Jan. 1962-Dec. 1963 575 Sao Paulo, Brazil Jan. 1962-Dec. 1963 1,756 San Francisco, California Oct. 1962-Sept. 1964 51 Santiago, Chile Jul. 1962-June 1964 907 - 3 - RES 2/f

Some changes had to be made in the original plan. Delays were encountered in establishing centers in English-speaking cities and the field work in Bristol, England, did not start until October 1962 and in San Francisco, California, until January 1963. Ribeiráo Preto was initially regarded as part of the project in Sao Paulo but is now operating as a separate center. The names and positions of the principal collaborators are set out in the Appendix A. The progress of the field work has varied from city to city depending on the nature of the local problems that had to be overcome and on the availability of suitable staff. The processing of the data, centrally, has been delayed because Dr. Percy Stocks, one of the two medical referees, who had planned to work as medical referee for three periods during 1962, was able to work only for one period but will devote June and July, September and October, 1963 to this project. Dr. Dario Curiel, the other medical referee, has meanwhile been able to review a large part of the material. The t ocessing of the data for machine tabulation can, of course, be completed only after the referees have reviewed that part of the material which is to be referred to them in accordance with the study design. In four of the cities (Cali, Guatemala City, La Plata and Ribeirao Preto) all the deaths of residents aged 15-74 years are investigated. In the other cities the total of deaths in this age range would be too large to be manegeable and a systematic sample is therefore drawn for study using an appropriate sampling - 4 - RE1S 2/1 factor. In these cities tests have been made periodically to see that the sample selected for investigation was properly representative. The results have indicated that the selection procedures being followed yielded satisfactory samples in all cities except one. In this latter city the procedures had to be changed in order that the deaths included in the investigation were truly representative of the mortality experience of the population concerned.

Some Preliminary Results

In June-July 1962 a limited analysis was undertaken of 1,561 questionnaires from 7 cities with the object of evaluating the progress of the project and assessing the suitability of the data being obtained from the point of view of the objectives of

the investigation. Comparison of the cause of death as stated on the death certificate with the final assignment made by the medical referees after reviewing the additional information

in the ouestionnaire indicated that in every city we can expect

the resulting pattern of mortality to differ in certain significant

respects from that which appears in the customary statistics.

For example, the number of deaths assigned to ill-defined causes will be reduced, the nurmber of maternal deaths increased, and the body site involved in deaths from cancer will be designated with more precision in many irstances. Though based on relatively

small numbers from any one city, this preliminary analysis suggested also that significant differences between cities in the

relative frequency of different cancers and of the tyw s of -5- PES 2/8 cardiovascular diseases would emerge. In January 1963 an analysis was made of 1,239 deaths from cancer in five cities and the results were reported to a Conference on Epidemiological Research on Cancer held in Lima, Peru, in February 1963.* Two tables are appended to this present report which indicate the nature and quality of the data on cancer. These tables are similar to tables presented to the Lima conference but have been brought up-to-date and now deal with 1,525 cancer deaths. The first table (Appendix B) shows for each of the five cities, the number of deaths attributed to the main sites of cancer and the number that would have been expected if, in each of five age-groups, the deaths from cancer in the city had been distributed by body site in the same way as cancer deaths in the same age group in the white population of U.S.A. in 1959. From this table it is clear that, when compared with the United States, gastric cancer accounts for an unusually high proportion of cancer deaths in all five cities. Cervical cancer is unusually common in Cali and in Lima and, to a lesser extent, in Caracas. Iung cancer is unusually frequent in La Plata and reb tively infrequent in Cali and Lima. Oesophageal cancer is more common in La Plata and Sao Paulo but not markedly so in the other cities. Cancer of the intestine is relatively uncommon in Cali and Caracas, and to a lesser extent in Sao Paulo. Another finding, not shown in this table, is that cancer of the urinary bledder in La Plata is apparently unusually frequent among males, there being 21 deaths while F'expected"' deaths were 8.4. This form of cancer does not

*See RES 2/ 7 - 6 - R.ES 2/8 occur more frequently than expected in the other four cities, nor is it urnduly frequent among females in La Plata. It is encouraging to note from the table in Appendix C that the diagnosis as regards body site was well established in a high proportion of cancer deaths. In these cities it will be seen that in 90 per cent of deaths from malignant diseases there was additional evidence in the form of histological reports, gross findings at surgical operation or autopsy, radiological or cytological findings to support the clinical diagnosis. The proportion of deaths where such supporting evidence was obtained was even higher than this in cancer of the biliary tract (93 per cent), the bladder (95 per cent), cervix uteri (96 per cent), the lung (99 per cent), and in leukemia (94 per cent). A study of the first yearts material from Ribeirao Preto has indicated very clearly the importance of "cardiopathy" as a cause of death in that city, particularly at younger ages. If deaths from violent causes are excluded, nearly one death in three in the age range 15 to 44 years would seem to be due to this condition. The clinicai features presented by these fatal cases resembly closely the classical picture of chronic Chagas' disease. There is, however, need for more general agreement.:on the criteria, both clinical and pathological, vrhich should determine whether a death is properly to be attributed to this condition. All aquestionnaires from Ribeirao Preto -- as well as a few from

Sao Paulo and Caracas -- where Chagas' disease was thought to have been concerned as the sole, the main or a contributory cause -7- RES 2/8 of death have been identified and it is hoped to arrange for these questionnaires to be reviewed by a panel of specialists with a view to defining what the criteria should be for assigning a death to Chagas? cardiopathy.

It is not possible at this stage to indicate with any certainty what other findings vrill eventually emerge in the field of cardiovascular mortality. It is, however, obvious that the association of chronic conditions (such as hypertension, diabetes, atherosclerosis) in the same patient often poses pro- blems of great difficulty for the classification of causes of death.

It will be evident that in this research project a wealth of material is being collected in a systematic way from very diverse populations. Some of the data could well prove of value to other investigators with special interests. As an example, deaths from violence and in particular perhaps from suicide as reflected in the material collected routinely in this investigation might be mentioned as subjects worthy of study.

Future Plans

It is clear that the original intention, namely that the field work should be complete by April 1964, will have to be modi- fied for two reasons. In the first place, the u2nderlying assumption that the time-lag between the date of death and the submission of the completed questionnaire should not exceed three months has proved in practice to be unrealistic, partly - 8 - R S 2/g because of the dealy often experience in obtaining detailed reports from pathologists on deaths where full hospital autopsies have been performed. It now seems likely that to complete the study satisfactorily in a city an interval of six months must be added to the study period. In the second place, the study period has varied, for unavoidable reasons, from city to city so that the períod runs for the two calendar years 1962-1963 in some cities and from October 1962 to September 1964 in others. The effect of these modifications will be that, while the bulk of naterial from all cities (and all the material from some) should have been received by mid-1964, the last of the data will not be available until well into 1965. The work of the medical referees cannot, therefore, be completed before late 1965 and the final report cannot be expected before the summer of 1966 at the earliest. Meanwhile, of course, detailed studies will be prepared of such parts of the material as are both numerically adequate and sufficiently representative for analysis to be profitable. In one respect the delays that have been encountered, though regrettable, will not apparently result in any avoidable deferment of the final results because census data are also likely to be late in appearing. The minimum census information required for any detailed analysis (age-sex composition of the population of each city) is currently available for only two of the twelve cities. Recent censuses have been held in seven other cities and results will be appearing in due course but at the time of writing the date of the census are not definitely scheduled in three cities. -9- RIS 2/1

Other Matters

A report on the progress of the investigation was presented to the XVI Pan American Sanitary Conference held in Minneapolis in August 1962. The representatives at the Conference from Argentina, Brazil, Chile, Peru and the United States expressed the satisfaction of their delegations at the initiation of the investigation and their confidence that important results in the field of mortality statistics would flow from this research. The Conference passed Resolution XIV which included the following recommendations: '1. To recommend that as the Organization makes progress in the investigation of mortality appropriate extensions be made for understanding patters of mortality in the Region, and a similar investigation be undertaken of mortality of chil- dren in the age-period 1-14 years for study of the underlying and multiple causes responsible for mortality. 2. To recommend to the Director of the Pan American Sanitary Bureau that the Organization proceed with the planning of epidemiological research on cancer and cardiovascular diseases, so that studies can be undertaken taking advantage of wide differences in customs and living conditions. 30 To recommend that the Governrnents of the Organization promote the development of post- graduate training programs in medical schools for the preparation of pathologists for hospital and medico-legal services." In some of the participating cities it is already evident that the conduct of the investigation is having a very be.neficial effect in stimulating the interest of the medical profession in the whole question of certification of the cause of death and mortality statistics. In Venezuela, a report on the project was well received by a national conference of - 10 - Rt..S 2/8

cardiologists. In Brazil, as a direct consequence of the

investigation applications are being made to have staff admitted

to the training courses in the use of the International

Classification of Diseases which are held periodically at the Latin American Center for the Classification of Diseases in

Caracas and also to have a course given in Sao Paulo. In one city it is reported that the system of medical record keeping

at a main hospital has been reorganized because serious short- comings in the existing system were brought to light as a result

of the investigation. In another city a marked improvement has been noted,since the investigation started,in the quality of the

records kept by private physicians. Finally, the following

comment made by Dr. I.M. Moriyama who, as consultant for PAHO and at the request of the Government undertook in 1962 a survey

of the Biostatistical Department of the Ministry of Health and

Welfare of the Republic of Mexico, is quoted:

"The participation of the Republic of Mexico in the Inter-American Investigation of Mortality is extremely timely. Aside from the significance of the study in terms of cardiovascular diseases and cancer, the by-products will prove to be extremely valuable in pointing up the major problems in mortality statistics for the Federal District. More studies of an evaluative nature are needed both in the Federal District and in the States." - 11 - R1ES 2/8

APPENvDIX A PRINCIPA3 COLLABORATORS

Bogota, Colombia: Dr. luis E. Giraldo, Assistant Professor Department of Epidemiology, School of Public Health, National University, Bogota, Colorlbia. Bristol, England: Professor R.C. Wofinden, lJedical C;fficer of Health, City and County of Bristol, and Professor of Public Health, University of Bristol School of Medicine, England. Cali, Colcmbia: Dr. Pelayo Correa, Professor of Pathology and Chief, Department of Pathology, Faculty of U-edicine, University of Valle, Cali, Colombia. Dr. Bernardo Aguilera (Co-principal Collaborator) Sub-Chief of the Department of Preventive Medicine and Public HealUh, Faculty of Medicine, University of Valle, Cali, Colombia. Caracas, Venezuela: Dr. Carlos Luis Gonzalez, Technical Adviser, Director of Public Health, Ministry of Health and Social Welfare, Caracas, Venezuela, and Professor of Preventive Medicine, Jose Maria Vargas School of Medicine, Caracas, Venezuela. Guatemala City; Guatemala: Dr. J. Romeo de Leon, Jr., Medical C;fficer, Epidemiiology Branch, Division of Public Health, Institute of Nutrition of Central America and Panama (INCAP), Guatemala City, Guatemala. La Plata, Argentina: Dr. Carlos Ferrero, Professor of Biostatisti< School of Public Health, University of Buenos Aires, Buenos Aires, Argentina. Lima, Peru: Dr. Abelardo Temoche, Chief, Division of Vital Statistics, Ministry of' Public Health and Professor of Medical Statistics, San Marcos Medical School, Lima, Peru. Mexico City, Mexico: Dr. Miguel Angel Bravo Becherelle, Scientific Investigator, Laboratory of Epidemiology and Biostatistics, Institute of Health and Tropical Diseases, Mexico City, Mexico. - 12 - RES 2/8

Ribeirao Préto, Brazil: Dr. Geraldo Duarte, Associate Professor of Hygiene of the Faculty of Medicine of Ribeirao Preto, Ribeiráo Pr0to, Brazil. San Francisco, California, U.S.A.: Dr. Ellis D. Sox, Director of Public Health, City and County of San Francisco, California, U.S.A. Santiago, Chile: Dr. Adela Legarreta, Professor of Biostatistics, School of Public Health, University of Chile, Santiago, Chile. Sao Paulo, Brazil: Dr. Elza Berquo, Professor of Biostatistics, Department of Statistics, Faculty of Hygiene and Public Health, University of Sao Paulo, Brazil. APPENDIX B

Observed Deaths by Cancer Site, Five Cities of Latin America, 1962, and Expected Numbers on Basis of Distribution by Site of all Cancer Deaths, by Age, in the United States, White Population, 1959 ___ _ Cali Caracas La Plata Lima Sao Paulo . . Site Ob- Ex- Ob - EX- Ob-E x-- UD- Ex- Ob- Ex- served pected served pected served pected served pected served pected i 1 4 i a i m i 1I · MALES ¡ 15-74 years All cancer 74 74.0 154 154.O 264 264,0 133 133.0 125 125.0

Buccal cavity and pharynx (140-148) 4 2.6 5 5.5 4 9.8 5 4.6 3 4.5 Oesophagus (150) 4 1.8 3 3.6 15 6.8 5 3.0 10 2.9 Stomach (151) 29 5.9 37 12.0 36 21.8 32 10.0 34 9.3 Intestine, except rectum (152,153) 1 6.5 1 13,2 13 23.5 9 11.1 3 10.3 Rectum (154) 3.1 6.3 11 11.3 3 5.3 5 5.0 Larynx (161) 2 1.2 5 2.3 9 4.4 1 1.9 6 1.9 Lung and bronchus, etc. (162-163) 7 18.6 36 37.8 92 69.9 13 31.6 19 31.5 Prostate (177) 1 4.0 12 7.4 9 14.2 4 6.1 3 4.9 Skin (190,191) 1.4 2 3.3 2 4.7 1 3.0 3 2.8 Bone and connective tissue (196,197) 1.1 2.3 1 3.0 4 2.4 2 2.0 Leukaemia (204) 1 3.9 8 8.6 5 12,1 14 8.1 3 7.2 Lymphosarcoma and other lymphatic 1 (200-203,205) 5 5.1 12 11.6 9 16.0 5 10.9 8 9.9 *tAll other sites 17 18.8 33 40.1 58 66.5 37 35.0 26 32.8 i · r · r i 1 ~ ~~~1 1 FEMALES: 15-74 yeara All cancer 132 132.0 175 174.9 152 152.0 180 179.9 136 136.1

Buccal cavity and pharynx (140-148) 1 1.3 7 1.7 2 1.5 1.8 1 1.4 Oesophagus (150) 0.8 4 1.1 5 1.1 1 1.2 5 0.9 Stomach (151) 15 5.8 21 8.0 19 7.7 37 8.7 23 6.4 Intestine, except rectum (152,153) 3 13.5 4 18.5 17 17.4 6 19.6 6 14.6 Rectum (154) 4.2 4 5.7 3 5.3 8 6.0 3 4.5 Larynx (161) 0.2 0.3 1 0.3 0.3 0.3 Lung and bronchus, etc. (162-163) 3 5.5 6 7.2 2 6.4 6 7.4 5 5.6 ' Breast (170) 11 31.3 20 41.3 27 33.4 26 40.9 21 30.9 Cervix uteri (171) 51 12.5 35 16.6 12 12.2 44 16.0 16 12.2 Other uterus (172-174) 3 6.3 4 8.6 11 7.7 3 8.9 5 6.7 Skin (190,191) 2 2.2 4 2.7 2.1 1 2.8 2.2 Bone and connective tissue (196,197) 4 1.5 3 1.9 1 1.5 3 2.0 4 1.6 Leukaemia (204) 2 5.7 8 7.0 6 5.9 4 7.4 3 5.9 Lymphosarcoma and other lymphatic * (_200-203,205)i 5 7.3 5 9.1 4 7.6 5 9.5 7 7.5 1l other sites 32 33.9 50 45.2 42 41.9 36 47.4 37 35.4 ¡ A. L 1 6 6 - APPENDIX C

Methods of Confirming the Diagnosis, Deaths and Percentages, by Site, in Five Cities of Latin America from the Inter-American Investigation of Mortality - 1962

Liver Biliary Lung and Cervix Leu- All Stomach tract, Bronchus ast Uter kaemia other Evidence CAnlcrCancer Primar etc. (151) (155.0) (155.1) Q62-163) (170) (171) (181.0) (204) 1.y______1 ______a __ DEATHS Total 1,525 283 37 41 189 105 158 39 54 619

A. Histology 893 116 19 27 61 88 141 27 26 388 B. Gross findings 226 63 6 10 32 6 10 8 1 90 at surgical operation or autopsy C. Radiology 188 64 - 1 69 - - 1 - 53 D. Cytology 58 2 - - 25 - 1 1 24* 5 E. Clinical only 160 38 12 3 2 11 6 2 3 83

*Autopsies (include (131) (24) (5) (3) (12) (2) (11) (6) (7) (61) in A or B above)

PER CENT

Total 100 100 99 99 100 100 100 101 100 101

A. Histology 59 41 51 66 32 84 89 69 48 63 B. Gross findings 15 22 16 24 17 6 6 21 2 15 at surgical operation or autopsy C. Radiology 12 23 - 2 37 - - 3 - 9 D. Cytology 4 1 - - 13 - 1 3 44* 1 E. Clinical only 10 13 32 7 1 10 4 5 6 13

Autopsies (included (9) (8) (14) (7) (6) (2) (7) (15) (13) (10) in A or B above) 1 ¡ 1 1

* Deaths from leukaemia diagnosed on peripheral blood picture.