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Saturday 13 July 1963

MULTIPLE SCREENING

J. M. G. WILSONM.B. Cantab., M.R.C.P.

SENIOR MEDICAL OFFICER, MINISTRY OF HEALTH, LONDON, S.E. 1

ON the far side of the Atlantic much has been said andwritten about population screening as a public-healthmeasure; and multiple screening programmes abound.But in this country interest has been mostly confined toa few well-defined procedures.Last year I visited the United States, on a W.H.O.

travelling fellowship, to hear and see what is now beingthought and done about screening in the early detectionof disease. Fifteen cities were visited in the East, Mid-West, and West, and discussions were held with ninety-seven persons, variously employed in the U.S. PublicHealth Service, State and city health departments,university schools of public health, independent researchorganisations, and public and private hospitals. Thisarticle sets out some conclusions, and their possibleapplication in this country.

The Concept of Multiple ScreeningThe idea of screening is simple. Though more fully

defined by the Commission on Chronic Illness,l it con-

sists, briefly, in the use of quick and only approximatetests or examinations, to differentiate those who probablyhave some disorder (especially a latent one) from thosewho probably do not. In the U.S.A. the tests are oftencarried out by persons specially recruited and trained inone technique only, such as electrocardiography or blood-sugar estimation. A good screening test should be easy toperform, yet reasonably reproducible: it should be sensi-tive enough to miss few persons with the condition sought,yet specific enough to avoid creating a large band of falsepositives. Naturally, too, screening can only be worthwhile in disorders common enough to give a fair yield ofdiseased persons.Seen in this light, screening has been in use for a very

long time. Thus in countries where malaria, trypano-somiasis, and worm infestation are indigenous, routineblood and stool examination is an effective way of dis-

covering them. In this country, mass radiography forpulmonary tuberculosis has been accompanied by a

dramatic fall in the condition; and screening of blooddonors for ansemia, using the Phillips-Van Slyke copper-sulphate technique, is long-established. Mass serologyfor detecting latent syphilis is another good example ofscreening, and in some countries where the disease is

common, routine premarital testing has been introduced.More recently, the value of exfoliative cytology in detect-ing accessible cancers, especially of the cervix uteri, hasbeen demonstrated beyond cavil.2-l01. Commission on Chronic Illness: vol. I, Prevention of Chronic Illness;

p. 45. Cambridge, Mass. 1957.2. Canelo, C. K., et al. Calif. Med. 1949, 71, 409.3. Weinerman, E. R., et al. Amer. J. publ. Hlth, 1952, 42, 1552.4. Kurlander, A. B., et al. Publ. Hlth Rep. 1953, 68, 1035.

So far, the aims of screening are clear cut, and mostpeople would agree with them. These aims could be

expressed in idealised form as follows:A potentially serious condition is highly prevalent among the

population, and it exists at a latent or presymptomatic stage,the mass detection of which, if left to ordinary clinical methods,would require a high expenditure of medical manpower. Arelatively simple test exists which, without the need for

preliminary medical examination, will reveal those who prob-ably have the condition. Those who are " positive " on screen-ing are physically examined and further tests are carried out.Finally, those with a positive diagnosis are treated, since thedisease is curable.

Development of Multiple Screening in the U.S.A.From this relatively secure position, the logical step was

taken in 1948, at San Jose, California, of combining anumber of screening tests into a programme operated bythe public-health department.2 The United States PublicHealth Service became interested, and funds were pro-vided for local health departments to run experimentalschemes, many of which have been reported .3-10 Theobvious attractions of multiple screening programmes forpublic-health authorities are twofold: firstly, at any rate intheory, a set of tools is provided for detecting illnessbefore it can be discovered clinically; and secondly, thereare economic and social advantages in the saving of costlyprofessional time spent in medical examination (whichwould require follow-up with laboratory and other investi-gations), and also in the sheer provision of medical care insome form for a part of the community which wasmedically underprivileged.The nature of screening also changed. Though it was

originally developed to detect endemic infective diseases,public-health workers began to apply it to the problems ofthe highly developed Western countries, where the chronicdegenerative diseases are now replacing the infective onesin importance. The screening programmes evolved in the1950s have largely been directed towards detection of thediseases of an ageing population-diabetes, arterioscleroticheart and vascular disease, chronic glaucoma, and theaccessible cancers. This decade also saw in the U.S.A.some opposition to the direction in which multiplescreening was showing signs of developing. Thus,Dr. Joseph Mountin, then assistant surgeon-general,U.S.P.H.S., felt it needful to point out 11 that, unlessmultiple screening forms part of a programme providingfor diagnosis, follow-up, and treatment, it loses muchof its potential value. He also expressed doubt about thevalidity of certain tests, such as blood-pressure and

blood-sugar levels, as indicators of a condition requiring5. Carroll, B. E., et al. ibid. 1954, 69, 1180.6. Breslow, L., et al. J. chron. Dis. 1955, 2, 375.7. American Medical Association. A Study of Multiple Screening. A.M.A.

Council on Medical Services. Chicago, 1955.8. Roberts, D. W., et al. J. Amer. med. Ass. 1956, 161, 1442.9. Herbolsheimer, H., et al. ibid. 1958, 166, 444.

10. Tomson, F. I. Publ. Hlth Rep. 1958, 73, 533.11. Mountin, J. W. ibid. 1950, 42, 1359.

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treatment. Later, Smillie 12 wrote of the risk of regardingthe population with negative screening tests as necessarilyhealthy, and not in need of medical care. As an alternativehe advocated open access to health-department laboratories.

In fact, it was very difficult to know what effect screen-ing programmes were having on the public health. In

1955, the American Medical Association,’ publishing asummary report on 33 surveys, noted that:

" Probably the greatest obstacle in any evaluation of multiplescreening is the lack of data on diagnosis resulting from thefollow-up on persons with positive indications of disease. In

only 15 of the 33 surveys were such follow-up data available,and even in these instances there was no way of knowing howmany of the positive screenees actually went to their own

physicians for further examination."

Despite these rather disappointing results, there hasbeen continuing interest in the potentialities of multiplescreening. In 1960, the American Public Health

Association,13 said:" It would be difficult to imagine any health endeavour more

helpful in secondary prevention of chronic disability in a

community that a public health department could initiate ...than periodic multiple screening examinations with wide

coverage."The U.S. Public Health Service, too, is concerned in thepromotion of multiple screening programmes, and theChronic Diseases Division of the Bureau of State Servicesis empowered to make direct grants in their support.A case-finding screening programme is normally

carried out by a local public-health department, under theaegis of the State health department, in collaboration withthe county medical society, representing the generalpractitioners and hospital service. Local voluntaryorganisations play a leading part in the necessary publicityand preparation; they also form an invaluable labour andtransport corps. Often these organisations raise the

money for, and sponsor, one-disease short-term screening" drives ", such as " diabetes weeks " and " G days " (forglaucoma). Recruitment may include the ad-hoc trainingof technicians to perform a single test, and on the appointedday the public is invited to submit to a " conveyor belt

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organisation of tests. These examinations may be carriedout in a health-department clinic, in a local hall, or atstands set up specially at places where the public con-gregates. A popular way of detecting diabetes, for

example, is to place a stand at the entrance to a super-market at the peak shopping period. More recently therehas been a move away from the " drive " towards

continuing programmes-a move which should provide abetter return in the long run.But in these case-finding programmes the yield of

proved cases of disease has often been disappointing.Planned Surveys

Several elaborately planned surveys with follow-uphave been carried out.

Baltimore

In Baltimore,14 part of a population sample of 12,000 personswas screened for pulmonary and cardiovascular disease, dia-betes, and renal disease. In parallel with the screening, a

selected sample of 1000 was examined physically, and medical-care needs were assessed by interviewing the same originalsample of 12,000. In the event, in this survey, only 29% ofthose invited to attend for screenins underwent the tests.

12. Smillie, W. G. Amer. J. publ. Hlth, 1952, 42, 255.13. American Public Health Association. Chronic Disease and Rehabilita-

tion. New York, 1960.14. Commission on Chronic Illness: vol. IV, Chronic Illness in a Large City.

Cambridge, Mass. 1957.

In 63-3% of those examined, screening showed some

abnormality, classed as " major " in 32-2%. The commonestpreviously unknown abnormalities were electrocardiographicchanges and raised blood-pressure. The abnormality ofgreatest prognostic significance was albuminuria, although thiswas present (unknown to the patient) in only 0-8 per 1000examinations.

After five years 15 the age-adjusted mortality of those in

whom screening had revealed an abnormality was 18 times thatof those in whom it had not. In relation to five-year mortality,the order of significance of positive screening tests was: urinaryalbumin, electrocardiogram, self-administered questionary,chest X-ray, urine sugar, blood-pressure, blood-sugar, sero-

logical test for syphilis, height and weight, and, finally, hxmo-globin level. However, as a yardstick, mortality undervaluesthe success of some tests," like those for haemoglobin andintraocular pressure, which uncover conditions rarely fatal inthemselves.

San FranciscoA follow-up at ten years of the members of the Longshore-

men’s Union in the San Francisco Bay area yielded somefindings of interest.16 At re-screening of 3311 members in1961, 66-1% had one or more positive tests. Of 818 personsfurther examined, 265 (32-4%) had previously undiscoveredabnormalities, of which the most frequent were visual defect,high blood-pressure, urinary sugar, and raised blood-sugar,followed by an abnormal electrocardiogram and chest X-ray-in that order. In 1951 63-2% of the sample had had positivetests; of those who were further examined 35-4% were diag-nosed as having disease, and in 19-4% of these the disease wasnewly discovered. Of the patients with a diagnosis confirmedthrough screening, only 19% had been under the care of a doc-tor at the time, although members of the union take part in aprepaid medical-care scheme.

Basic Problems of ScreeningPerhaps the chief objection to screening is that tests

have often been employed without knowledge of theirscope and limitations. Diagnostic tests (and, even more,screening tests) should be related to the natural history ofthe condition being sought. Looking at the conditions forwhich the screening process is often applied (anaemia,diabetes, accessible cancers, hearing defects, cardio-vascular disease, obesity, chronic glaucoma, tuberculosis,and syphilis) it is clear that we know a good deal moreabout some than others-particularly about the course andthe effects of treatment. In the early days of screeningthe medical officer of health was on relatively safe groundin looking for tuberculosis or syphilis. There, the naturalhistory was thought to be well understood, and the linesof treatment were clear. Now interest has turned rathertowards the chronic diseases, and we find we know muchless. It is here that departments of epidemiology and socialmedicine need to complete their contributions before thestage of population case-finding is reached. The area ofuncertainty is greatest in chronic conditions which takemany years to develop, and in which there is no clear

boundary between the well and the diseased-for example,high blood-pressure, chronic glaucoma, arterioscleroticheart-disease, and obesity. Unless the ground is firstcleared by epidemiological studies, it is difficult to see

how harm by indiscriminate screening can be avoided.Thus there is some conflict of interest between those

who develop methods and those more interested in practicalapplications. Those responsible for medical care of thecommunity naturally wish to press on with all methods ofdetecting early disease; but those who have to provide the15. Wylie, C. M. Publ. Hlth Rep. 1961, 76, 596.16. Borhani, N. O. San Francisco Longshoremen, 1951-60. Mortality and

Morbidity and 1961 Multiphasic Screening Examination. Unpublisheddata.

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tools for diagnosis (including screening tests) are reluctantto give their blessing until they can see some distance ahead.The U.S. Public Health Service has recognised thisdilemma and is supporting long-term epidemiological pro-jects concerned with chronic illness. Examples are the con-tinuing survey of diabetes in the community at Oxford,Massachusetts 11 18 ; the well-known Framingham Surveyof ischaemic heart-disease 19 20; the Tecumseh Project,21which aims at the continuing surveillance of all deviationsfrom health in relation to social factors, in a self-containedcommunity near Ann Arbor, Michigan; and the screeningof a population at Memphis, Tennessee, for cancer of thecervix. 22

In Great Britain, proportionately to a greater extent, theemphasis has been on the need for validating methods; thework at the Pneumocoriiosis Research Unit on observervariation 23-25 is a good example of this approach.Without a sound knowledge of the natural history of the

conditions being screened, trouble can soon arise for boththe patient and his medical adviser. If a public-healthdepartment carries out a screening programme, it mayremain in ignorance of impending trouble until madeaware of this by the complaints of clinicians. Examinationof the blood-pressure, for instance, is a popular screeningtest; it is easy to do and a temporary helper can easily betaught the technique; the examination does not take longand is not painful; it is cheap. Many thousands of peoplehave their blood-pressure taken at screening sessions, andtheir own doctors are informed if the pressure is higherthan a chosen level-frequently 160 mm. Hg. systolic or90 mm. Hg diastolic. This kind of practice, though wellintentioned, is ill considered: the natural course of thecommonest cause of high blood-pressure-essentialhypertension-is usually benign, and specific treatment isseldom needed. In deciding whether it should be giventhe important factor is the prognosis of the condition withand without treatment. Unless treatment reduces illnessand death from high blood-pressure, only harm will bedone by bringing the condition to the patient’s attention.This is not to deny that taking the blood-pressure is use-ful ; screening a population in this way will undoubtedlybring to light a number of people with severe essentialhypertension in need of treatment and a number of youngpeople with hypertension which may have a remedi-able cause, such as a unilateral renal lesion or a

phaeochromocytoma.This, however, illustrates one of the fundamental

problems of screening used as a public-health procedure.Where a patient consults his own personal doctor, forwhatever reason, it is easy for the doctor to make an

investigation-e.g., take the blood-pressure-and keephis own counsel on what he finds. But if a " non-patient " is invited to attend for an examination which hehimself (not feeling ill) does not initiate, responsibility isincurred by the authority which has invited him andwhich finds something wrong. This responsibility may betransferred to the personal doctor in the form of a letter:the " non-patient " is asked to attend his doctor, and henow becomes a " patient ". The situation will remain in17. Wilkerson, H. L. C., et al. J. Amer. med. Ass. 1947, 135, 209.18. Wilkerson, H. L. C., et al. ibid. 1959, 169, 910.19. Dawber, T. R., et al. Amer. J. publ. Hlth, 1957, 47, 4.20. Kannel, W. B., et al. Factors of Risk in the Development of Coronary

Heart Disease: Six-year Follow-up Experience. Ann. intern. Med. 1961,55, 33.

21. Francis, T. Publ. Hlth Rep. 1961, 76, 963.22. Dunn, J. E., Jr. Amer. J. publ. Hlth, 1958, 48, 861.23. Fletcher, C. M., et al. Brit. J. indust. Med. 1949, 6, 168.24. Cochrane, A. L., et al. Lancet, 1951, i, 1007.25. Cochrane, A. L., et al. ibid. 1952, ii, 505.

hand so long as the doctor then knows what to tell his

patient; but this may be very difficult in the case of someof the chronic diseases, of which border-line hypertension,diabetes, chronic glaucoma, and ischaemic heart-diseasehave already been mentioned.

For diabetes and glaucoma we do not yet know whethertreatment at the presymptomatic stage is effective or not;while in the diagnosis of ischaemic heart-disease the pre-dictive value of the electrocardiogram and serum-lipidlevels in the individual is doubtful, as are the effects ofearly treatment. Before populations are screened to findnew patients, we ought to be clearer on what we can offerthose who are found. Inquiries to this end are being madeboth in the U.S.A. and in this country. From the surveysat Ibstock 26 Birmingham 21 and Bedford,28 now at thefollow-up stage, we should in due course learn muchabout what ought to be regarded as early diabetes in needof treatment; the problem of the identification and treat-ment of chronic simple glaucoma is being approached inmore than one project; and, also in this country, compar-able studies are also being made on ischasmic heart-disease,chronic respiratory disease, and chronic urinary infections.Unfortunately, although the National Health Service

provides an unrivalled milieu for this type of investigation,the social-medicine approach to disease is still low down inthe pecking order for available funds and progress istherefore slow.

Looking at the FutureThe search for facts on which to base the management

of the early stages of these chronic conditions takes a longtime. Meanwhile, what lessons can we learn from theAmerican experience of the past fifteen years ?

Sir Winston Churchill is credited with saying thatGreat Britain and the U.S.A. are two nations divided bya common tongue; and certainly the differences of medicalcare in the two countries are cloaked by the many resem-blances in medical research and clinical medicine. Aftera time, however, the traveller becomes increasingly awarethat, in the poorer sections of the American population,the high cost of medical care prevents the easy satisfactionof need. In addition, the framework of the medical ser-vices in the U.S.A. is structurally different from that inGreat Britain and becoming more different. The numberof doctors solely engaged in general practice is diminish-ing 29 and the role of the family doctor is contractingbecause patients tend more and more to seek advice directfrom specialists or near-specialists. Also evident in NorthAmerica is the experimental approach, combined withsufficient affluence to bear the cost of making false starts,which has led to the nation being well in the van in thesearch for new methods of diagnosis.American public-health authorities finance screening

programmes, with the threefold object of (1) bringingthose needing medical attention to the care of a doctor,(2) revealing disease at an early stage, and (3) testing andimproving screening methods themselves. But, thoughtheir reasons are good, it does not follow that screening onthe same pattern could usefully be introduced into theNational Health Service. In Britain medical facilities ofall kinds are available to the population without directpayment, and general practice shows no sign of being on26. Walker, J. B., et al. Diabetes in an English Community. Leicester

University Press, 1961.27. College of General Practitioners. Brit. med. J. 1962, i, 1497.28. Butterfield, W. J. H. Guy’s Hosp. Gaz. 1962, 76, 470.29. Department of Health, Education and Welfare: Health Manpower

Service Book. Section 9. Public Health Service publication no. 263.1959.

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the wane. In this country, therefore, it seems right thatthe early detection of disease should naturally develop asan extension of normal family doctoring. This is not to saythat the other branches of the N.H.S. should not play animportant part; on the contrary, the hospital laboratoryservice would be the natural organisation to develop actualscreening procedures, whilst the services of the localhealth authority provide means of gathering those sectionsof the population at greatest risk for certain conditions-e.g., early cancer of the cervix and diabetes among womenattending antenatal clinics; and diabetes and defects ofhearing and sight among old people at welfare clinics. In

addition, the local authority’s health visiting and nursingservices can aid in detection in the home, helping both thegeneral practitioner and the public-health authorities.Apart from differences in the setting in the two coun-

tries, there are several more intrinsic reasons why generalpractice is the most suitable branch of the N.H.S. for theinitiation of early disease detection. Firstly, there seemslittle doubt that periodic health examinations, whencombined with laboratory tests initiated by the examiningdoctor, are a better case-finding instrument than multiplescreening programmes. That everybody should have

periodic health examinations is impracticable becausethere are not enough doctors; but a reasonable compromisemight be to provide practitioners with a number of well-tested screening procedures. Secondly, a great objectionto screening is removed when the examination is initiatedby the personal doctor: as I have said already, there is abig difference between asking a person to come for screen-ing for a specific condition and the general practitionerusing screening tests to find presymptomatic disease in hisown patients. If borderline abnormalities are found, asthey often are, less harm is likely to result when the situa-tion is handled by the personal doctor than when it is

passed through a health department. Lastly, in GreatBritain as elsewhere, there has been a tendency towardsincreasing specialisation in medicine, with a shift of muchtechnical work from general practice to the hospital field.This has led to a feeling that general practice has lost agreat deal of its more interesting attributes. The need forbringing general practice into the main stream of develop-ment in medicine is being increasingly recognised: thePlatt Committee 30 made two recommendations whichcould influence the family doctor’s approach to his workand guide it in the direction of preventive medicine. Thecommittee favoured (1) group practice, and (2) part-timework by practitioners in hospitals. A move in this direc-tion could speed the development of screening for earlydisease by general practitioners-firstly, because doctorsworking in a group should have more time for thoughtand activity in preventive medicine, and secondlybecause the practitioner in more direct contact with thehospital service would make use of laboratory techniques.The diabetes survey in Birmingham by the College ofGeneral Practitioners 27 was greatly facilitated by general-practitioner appointments to the local district generalhospital diabetes clinic, where the laboratory work waschiefly done.

Whilst it is certainly wise to take a long and careful lookat multiple screening, and to lay down sure foundationsfor the future, it would be wrong to delay the developmentof screening where this can be for the patient’s immediatebenefit and there is much that could be set in train at the

present time. A guiding principle might be to limit screen-30. Report of the Joint Working Party on the Medical Staffing Structure in

the Hospital Service; para. 112. London H.M. Stationery Office. 1961.

ing to high-risk groups of the population-so-calledselective screening. The use of exfoliative cytology fordetecting early cancer of the cervix is already beingdeveloped along these lines as one of the services of thehospital pathology laboratory. Other conditions for whichscreening might profitably be used in selected populationsare diabetes mellitus, anaemias, renal disease (includingbacteriuria), hearing and visual defects (including earlyglaucoma), and early chronic respiratory disease. All theseconditions are not uncommon in a population and can, ingeneral, be effectively treated.

A SuggestionA practical trial of screening for a group of conditions in

general practice in this country could provide usefulinformation. A random sample from several practicesmight be screened, and the morbidity and mortality (asmeasured, for example, by the number and type of seriousincidents of disease over one, two, and three years) com-pared with a control sample. The existence of the N.H.S.makes this country particularly suited to a survey of thiskind, which should yield much useful data not only aboutscreening but also about the amount of hidden morbidityin the population.

This type of longitudinal investigation could well be amodel for collaborative research in which the threebranches of the N.H.S. took part, though clearly one ofthem would need to be in control. In the Birminghamdiabetes survey the College of General Practitioners tookthe initiative, whilst at Bedford the first move came fromthe medical officer of health, soon to be supported by theforces of the department of experimental medicine at

Guy’s Hospital. This type of investigation is becomingmore feasible now that more pathology laboratories allowopen access by general practitioners. One way of keepingcontact with the pathologist would be for general practi-tioners to work part-time in a hospital laboratory.

Conclusions

To the clinician the idea of screening appears, at firstsight, pedestrian enough. What was unexpected in thistour of the U.S.A. was the fascinating glimpse of thewhole field of community medical care which one gotthrough the window of multiple screening.On superficial acquaintance multiple screening appears

to embody much that is bad in medicine. Yet the issueswhich screening attempts to meet are with us now andcannot be avoided. If we try to avoid them we may wellfind events shaping policy rather than the other way round.Much of the future pattern of our medical services

could depend on a sensible solution of these problems; asLester Breslow, of the California Health Department,has said, " we need to push back the boundary of clinicalconcern for health ".31 The problem is simple and maybe stated in the form of the question: " How can this bedone in the best interests of the patient ? " But to me atleast the answers still seem to need much thought, effort,and experiment before they can be given unequivocally.

I would like to record here my gratitude to the World HealthOrganisation for making this study possible. Needless to say, theviews expressed here are my own and in no way necessarily representthose of the W.H.O.

I am also grateful to Dr. Nemat 0. Borhani, head of the HeartDisease Control Programme, Bureau of Chronic Diseases, State ofCalifornia Department of Public Health, for permission to quote theunpublished data on the re-screening follow-up of the San FranciscoBay Longshoremen.

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31. Breslow, L. Personal communication.