EUGENE GARFIELD INSTITUTE FO!I SCIENTIFIC 1NFO!lk4AT10tde 3501 MAR KETST W++LADELWIA PA 79104

Mapping the World of Epidemiology. Part 2. ‘he Techniques of I Tracking Down Disenae 1 Number 36 Ser)temberr-- ..––.5.1988_, ____

Part 2 focuses on epidemiological methods and techniques, including statistical arudysis. The essay describes some of the technological advances that have broadened the scope of this discipline. LIsrs of journals, institutions, and organizations involved in epidemiologicat researchare provided. We sdsopoint out that epidemiologydeserves better recognition.

fn the past century or so, epidemiology, Among the factors that must be considered once only the study of the causes of infec- by epidemiologists h demographic char- tious disease, has broadened its scope con- acteristics, such as age, sex, and race; bio- siderably. Modem epidemiology encom- logical characteristics, such as blood levels passes all diseases, whether infectious or of antibodies, enzymes, and chemicals; so- noninfectious, and is rdso concerned with ciaf and economic factors, includiig educa- controlling and preventing iflness. Part 1 of tional background and occupation; perscm- this essay outlined the history of the field al habits, such as the use of tobacco or and highlighted some of its leading research- drugs; and such genetic characteristics as ers and major breakthroughs. 1This part fo- blood type. The generaf purposes of epide- cuses on the methods of the epidemiologist rniological studies are to describe the causes and lists institutes and organizations around or origins of a disease (its etiology), to for- the world that are involved with epidesniol- mulate hypotheses and test them either clisl- ogy, as well as the journals that publish ep- icafly (at the bedside) or experimentally (in iderniologicaf research. the laboratory), and, finafly, to develop and As noted in Part 1, epidemiologists are evaluate procedures that will control or pre- concerned with patterns of disease in the hu- vent the illness (or to recommend public- man population and the factors that influence heafth practices).2 those patterns. 1According to Abraham M. Lilienfeld (1920-1984), Department of Ep- idemiology, The “Epidemiolo@d Method” School of Hygiene and Public Health, Bal- timore, and David E. Lilienfeld, Division In Part 1 we discussed the fact that the of Environmental and Occupational Medi- field of epidemiology has expanded from its cine, Mt. Sinai School of Medicine, New traditional interest in infectious diseases to York, epidemiologists are primarify inter- encompass noninfectious diseases as well. I ested in the occurrence of disease by time, There is still considerable debate, however, place, and persons; they try to determine regarding the definition and limits of the whether a specti~c dkease has increased or field. decreased over time, whether one geograph- According to Milton Terns, formerly ical area is experiencing a higher frequency (1960- 1964) head of the Chronic Disease of a disease than another, and whether the Unit, Division of Epidemiology, Public characteristics of those afflicted with a par- Health Research J.rtstituteof the City of New ticukwdisease@ them apatt from those& York, and now editor, Journal of Public of it.z Health Policy, “some epidemiologists have

290 tended to broaden the definition of epide- methods that we will be using in epidemi- miology to the point where it becomes al- ology in a few decades will be different from most meaningless.”~ Terns wrote in 1962 what they are today.”s that to claim the existence of an’ ‘epidemi- ologicrd method” applicable to a wide va- riety of problems outside the scope of epi- Biostatiatica and Computer Modeling demiology is tantamount to reducing epide- miology to’ ‘a method rather than a field of As the scope of epidemiology broadened, study. ”3 He claims that a wide variety of new methods had to be developed to deal methods have been found useful in the with new or different types of disease. As course of the epidemiologist’s work; some noted by Samuel W. Greenhouse, Depart- were developed by epidemiologists, while mentof Statistics, George Washington Uni- others have been borrowed from other sci- versity, Washington, DC, among others, ences, including statistics, microbiology, tvhenepidemiology expanded from the study biochemistry, clinical medicine, geogra- of infectious diseases to include noninfec- phy, demography, and sociology, among tious diseases as well, certain difficulties, others. 3 both theoretical and methodological, were The standard measure of sickness in pop- encountered 7 ulation groups, for example, is statistics; at- However, thanks to advances in computer tributes of popukttiorts, such as height and and biostatistics, epidemiologists weight, can be expressed as means (or aver- may now investigate causal and risk factors ages) and distribution curves. Mathemati- in chronic disease by participating in large- cal models of population groups are con- scale intervention trials to decrease risk fac- structed from observations and measure- tors, surveying entire populations, and con- ments of samples drawn from that popula- ducting longitudinal studies of thousands of tion; the reliability of the sample is evaluated people over a period of several years. using further statistical procedures. And Case-control techniques also have been cru- since it is often impossible to precisely mea- cial in the investigation of such factors. In- sure the intluence of one factor upon another deed, Roger I. Glass, Center for Infectious on the basis of a single investigation, epi- Diseases, Centers for Disease Control demiologists often use a battery of data sets (CDC), Athmta, feels that modem technol- and analytical techniques in combination to ogy “is making epidemiology more inter- draw conclusions about the occurrence of esting and versatile, by providing tools to diseased refine population-based studies of risk fac- In response to ‘Terris’sclaims, Edward H. tors, disease associations, and causality. Kass, Charming Laboratory, Harvard Med- l%is new methodology is already having an ical School, and Brigham and Women’s impact on the prevention and control of Hospital, Boston, Massachusetts, among disease.’ ‘g others, contends that “it is impossible to In the realm of biostatistics, two major separate the methods of a field from the in- contributions were made by Jerome Cor- tellectual content of the field.... There is no nfield,National Cancer Institute (NCl), NIX-I. such thing as the epidemiological method, In 1951 Cornfield demonstrated a relative- but there certainly is a general body of ly simple method for accurately estimating knowledge and a speciai mind-set that char- the relative risk of contracting a dkease;g acterizes most peopie Who cdl themselves about 10 years later Cornfield introduced a epidemiologists.”~ Haroutune K. Armenia- method of analyzing tabular material that n, Department of Epidemiology, Johns was more sensitive and accurate than those Hopkins Schooi of Hygiene and Public in use at the time. 10According to the Lil- Health, responds by saying that 4‘epidemi- ienfelds, Cornfield’s work “ushered in the ology is a purposive discipline and applies modem era of case-control studies.”11 a variety of methods to elucidate etiology However, Greenhouse claims that’ ‘the es- and prevent disease. The dynamism of the timate of relative risk is now so common- discipline is in its constantly changing and place that most application papers no longer immovin~ methodological base. The reference the Corrdield source.”7 And in

291 fact, data from the Science Citation Indexm Table 1: selected&t& or@rlzatkms and researctt show that Cornfield’s classic 1951 paper has fnstitrrtes providing information on and cmxlucting research in the field of epidemiology, been cited “only” 185 times since 1955; I have discussed the Mertonian “obliteration American Cancer Seciety phenomenon” so often that references to it Department of Epidemiology and Statistics seem superfluous-the ultimate compliment. 4 West 35th .%ee: Another major statistical advance came in New York, NY 10016 1959, when Nathan Mantel and William Anwrican Epi&miologiczd Seciety Haenszel, Biometry Branch, NCI, published Emory University their landmark paper, “Statistical aspects of Schwl of Medicine 735 Gatewomi Road, NE the analysis of data from retrospective stud- Atlanta, GA 30322 ies of disease. *~12 In the article the authors American Health Framdation discuss the relationship of the retrospective Mahoney Institute for Health Mairrtemmce study to the prospective study in the inves- Division of Epidemiology tigation and occurrence of disease. They 320 East 43rd Street provide a chi-square test for the statistical New York, NY 10017 significance of an observed association be- Centers for Diaezw Control tween a disease and a spectlc factor under 1600 Clilbn Reed, NE AUanta, GA 30333 study. TMS classic work, published in the Journal of the Nm”onal Cuncer Institute, has Chairrr Sheta Medical Center Tel Aviv University received nearly 2,100 citations. (The MH Sackler Scheel of MaJicine is one of a number of organizations around Department of Clinical Epidemiology the world that are involved in epidemiolog- Tel Haahomer icaf research; a selext list of these institutes Israel appears in Table 1.) Interestingly, in his Ci- International Epidemiological Association tation Clussic@ commentary on the work, UniversiV of Pennsylvania School of Medicine Mantel writes, “In a way, our work was an Reom 229 L NEBIS2 extension of still earlier work by Jerome , PA 19104 Cornfield, who had suggested the effective National Crmcer Center utilization of retrospective studies. ” 13 Research Institute The publication of some of the first re- D&iaion of Epidemiology sults of what is now commonly referred to 1-1, Tsukiji 5+home, Chuo-Jm, Tokyo 104 as “The Framingham Study” in 1971 rep- Japan resented another advance in the statistical National Center for Health Statistics methodology of epidemiology. 14Published Office of Amdysis and Epidemiology Progmm by William B. Karmel and colleagues, Heart 3700 East-West Highway Disease Epidemiology Study, Framingham, Hyattsville, MD 20782 Massachusetts, and the Nationaf Heart and Natiomd Health & Medical Research CmmciJ Lung Institute, MH, it has been cited in af- Unit of Epidemiology & Preventive Medicine most 850 publications. The study, started in University of Western Australia Ncdlanda V1C2 185 1949 and still ongoing, is an investigation WA 61X19 of the effects of a large number of variables Austrrdia on the risk of developing coronary heart dis- Society for Epidemiologic Research ease, the number-one killer in the US. In c/o American Journaf of Epidemiology his C’itarion Ckz.rsic commentary, Kannel 624 North Broadway, Suite 225 states that the 1971 study “was one of the 8altimore, MD 21205 largest bodies of data showing the impact WHO (World Health Organirzetion) of cholesterols and lipoproteins on risk us- Epidemiology and Statiaeica Department Avenue Appia ing prospective data. ‘‘15The techniques of 2H-1211 Geneva 27 multifactorial analysis developed for this Switr.crlmd study have revolutionized the analysis of ep idemiological data. We identified this study Among the first to recognize the need for in an analysis of highly cited papers from he mechanized management of data were the Annals of Internal Medicine. lb ;ir Richard Doll, then of the Statistical Re-

292 search Unit, Medical Research Council, family studies could provide the best means London, and A. Bradford Hill, London of studying the interaction of genetics with School of Hygiene and Tropical Me&cine, environment, he tried to incorporate funda- UK, who in the early 1950s began an ob- mental epidemiological principles into the servational study of the relationship between methodology of genetics.zl tobacco use and iung cancer in England. IT According to Muin J. Khoury and col- They surveyed 34,440 British male physi- leagues, Department of Epidemiology, cians, aged 35 and over, on their smoking Johns Hopkins School of Hygiene and Pub- habits and followed them over the course of lic Health, the central theme of genetic epi- decades to determine the cause of death demiology is the study of genetic factors in when it occurred, paying particular atten- disease and their interaction with environ- tion to deaths from lung cancer. Initially they mental factors. In this discipline, genetics reported that smokers had 10 times the mor- also brings its own tools for counting and tality rate from lung cancer than nonsmok- analysis, and epidemiology brings method- ers. 18In 1976 Doll and Richard Pete, Rti- ological principles from widespread medical cliffe Infii, University of Oxford, UK, research. The result is a field that cart ad- reported the results of a 20-year follow-up dress medical and public-health issues from of these doctors. 19They found that between a broad perspective.~ In recognition of this one-half and one-third of the deaths of cig- growing field, the journal Genetic E@&mi- arette smokers were linked to smoking-re- ology was launched in 1984. It appears on lated diseases, such as heart disease, lung our selected list of key epidemiology jour- cancer, and various other cardiac and pul- nals, shown in Table 2. monary disorders. Without the aid of ma- chines, analysis of the vast amount of data by age, smoking history, snd cause of death Where Epidemiobgical I&arch Is would have been impossible. We are still Published and Where It Is Used awaiting a commentary on thk Citation Table 2 is by no means exhaustive, but Ckzssic. it does represent a fair slice of the journals publishing research related to epidemiology. It is perhaps not surprising that the oldest Breakthroughs in Moleeular and journal on the list, dating back to 1904, is Genetic Biology the Journal of Infectious Diseases, since it harks back to epidemiology’s roots. The New techniques that are revolutionizing newest journal on the list is Epia%mz”ology molecular biology are also being put to use and Infection, founded in 1987. in epidemiology, especially in the study of Table 2 not only allows us to see where infectious disease. Kaye Wachsmuth, Divi- epidemiologicrd research is being published, sion of Bacterial Disease, CDC, points out but also gives us a clue as to who is using that genetic probes, DNA hybridization, and it. In an attempt to qoanti& the research spe- DNA-sequence analyses have been used for cirdties using epidemiological results, An- the rapid identification and characterization drew L. Dannenberg, Department of Epi- of microorganisms causing infectious dis- demiology, Johns Hopkins School of Hy- ease, as well as for genes involved in ge- giene and Public Health, analyzed citations netically caused illness and cancer. Genetic- to and from the American Journal of Epi- sequence studies have also been used to demiology from 1974 thrOU@ 1982.23Dan- identify the organisms involved in Eschen”- nenberg believes that epidemiological meth- chia coli infections, cholera, and Polio.zo cxlshave been applied unevexdyamong med- Such advances have helped bring about icrd specialties and that identifying current the emergence of the discipline’ ‘genetic ep uses and areas of potential research would iderniology. ” Among the many researchers help clarify and define the field. In 1985 he whose work helped marry genetics with ep- reported that internal-medicine and public- idemiology was Abraham Lilienfeld, who heakh/epidemiology journals accounted for made both substantive and methodological most of the citations. On the other hand, al- contributions to the field. Recognizing that lergy, anesthesiology, and dermatology —

293 journals are among the publications that ac- Table 2: Selected I&tof@r@s repnrtfngon epkk counted for few of the citations either to or srdofogy.Tbe flrat year of publication is included in from the American Journal of Epidemiob- parentheses. gy. Dannenberg concluded that the inter- American Journal of Epidemiology (192 I) change between clinicians and epidemiolo- M. .%klo, cd. gists is adequate and that citation anrdysis Johns Hopkins University Schnnl of Hygiene and is a useful tool in eXamininginteractions and Public Health Baltimore, MD trends within a field.zs Bulletin nf the World Health Organization (1947) WHO world Heaftb Organization) Is Epidemiology an Unsung Hero? Geneva, SwirzerJand Epidemiologic Reviews (1979) We have seen in both parts of this essay H.K. Armeoian, ed. the key role that epidemiology has played Johns Hnpkins University School of Hygiene and in the eradication of a number of diseases, Public Hcaftfr in identifying new agents in epidemics be- Baltimore, MD fore their causes were known, and in the Epi&miology and Jrrfection ( 19g7) control and prevention of others. Yet the JR. Patdamr, ed, Cambridge University Press field has been neglected by the recognition New York, NY system of science. There is no Nobel Prize Genetic Epidemiology (1984) speciilcally for epidemiology, nor anything D.C, Rae, ed. even comparable. The John Scott Award, Atari R. ~lSS given to makers of usefid inventions,zq has, New York, NY on occasion, recognized contributions that International Journalof Epidemiology(1972) have had epidemiological applications. in C. du Ve Florey, cd. Oxford University Press 1981 the award was given to Benjamin A. Oxford, United Ki@om Rubin, the inventor of the bifurcated nee- Journal of Clinicat Epidemiology (1955) dle that was used by WHO in its worldwide W.0, Spitr.er & A.R. Feinatein, eds. campaign against smallpox; while working Pergamon Press on ways to administer the sxnallpoxvaccine, Oxford, United Kingdom Rubin designed a needle that made the vac- Journal of EpidemiologyandCommunityHealth cination process quicker and easier.~ How- (1947) ever, this is not a spezific recognition of the J.R.T.Coney,ed. field of epidemiology. In Part 1 we men- BritishMedical Association London, United Kingdom tioned that more recently the award was pre- sented to David W. Fraser, now president, Joumaf of Jnfsainus Diseaaea (1904) M.D. YOW, d Swarthmore College, Pennsylvania, for his University of Cbicagn Prtiss part in solving the Legionnaires’ disease ri- Chicago, IL ddle.1 Jo.rnaJ of Public HcaJtb Poficy (19S0) Terris claims that epidemiology has been M. Terns,ed. ignored largely because of an’ ‘almost com- JournaJ of PublicHealthPolky pletely therapeutic orientation of the medical SouthBurlington,VT and allied health professions, whose attitudes MMWR–MorbidityandMortaJityWeekty Refmn range, with relatively rare exceptions, from (1950) M.B.Gregg,ed. sheer indifference to outright hostility to- Centers for Disease Control ward epidemiology, preventive medicine, Atlanta. GA and public health .... The public’s heroes ... Revue d’Epidemiologic et de Sarrte Publique (1953) are the surgeons and other clinicians who D. Schwartz & R. Snbier, da. work miraculous cures in hospital set- Masann tings. ~$26 But at ~~t part of the problem of Paris, France the lack of acceptance with which epidemio- logy has been met lies in the of its vestigators to accept.zs Many biological evidence. Many epidemiological findings scientists are uncomfortable with essentird- are based on statistical analysis, which is ly mathematical concepts, which accounts hard for many clinicians and laboratory in- for much of this reluctartce.s

294 However, with the recent contributions duced in the titles of some of the journals that epidemiologists have made in uncover- in the field. The Amen”can Journal of Hy- ing the etiologies of many infectious and giene became the American Journal ofEpi- noninfectious diseases, it is hard to believe demiology in 1965; the British Journal of that epidemiology will not soon earn more Preventive and Social Medicine became the explicit recognition of its centrrd role in Journal of Epidemiology and Community modem medical and environmental re- Health in 1977; and the Journal of Chronic search. Some indkators would include the Diseases became the Journal of Clinical Ep- memberships of leading epidemiologists in ia%-ziology in 1988.6 groups such as the NationrdAcademy of Sci- Etymologists will note that such changes ences and the US Institute of Medicine were long overdue, and merely confirm, a (IOM). This year, Doll, who, incidentally, postenori, what had happened long ago. received an honorary PhD from Harvard this One wonders where this exciting field will past June, became a foreign member of the go in the years to come. IOM. I’ve also been told that Alexander D. Langmuir, Department of Preventive add ***** Sccial Me&cine, Harvard Medical School, mentioned in Part 1, and Kass are also senior My thanks to Stephen A. Bonaduce and physicians in the IOM.5 Marianne Zajdel for their help in the prep- That epidemiology is receiving an increas- aration of this essay. ing level of recognition over the past few decades is evidenced by the changes intro- 0,9s$ ml

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