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Prescriptive Screening
LEADING ARTICLES
THE LANCET LONDON
16
NOVEMBER
1968
Prescriptive Screening EARLY detection of chronic non-communicable disease greatly interests countries where the prevention and
control of communicable diseases have been largely achieved. It is, however, easier to define the principles underlying the screening of populations or selected groups for presymptomatic chronic non-communicable disease than to evolve satisfactory programmes whereby these diseases can be sought in the community and effective treatment thereafter made available to the people who truly merit it. The chief medical officer of the Ministry of Health referred to some of these problems in his report1 for 1965, and in the following year2 he announced the setting up of a laboratory automation trials group, which was to be particularly concerned
1065
whether screening would result in the better use of limited resources than the available alternatives. They restrict their review of screening procedures to " prescriptive screening ", a new term which they define as investigations whose primary aim is a direct contribution to the health of individuals (specifically excluded are screening programmes in which the primary aims were either research or the protection of public health). The contributors seek to validate prescriptive screening in relation to ten different conditions which have each been the subject of screening: bacteriuria in pregnancy, breast cancer, cervical cancer, deafness in childhood, diabetes
mellitus, glaucoma, iron-deficiency anaemia, phenylketonuria, pulmonary tuberculosis, and rhesus hxmolytic disease of the newborn. These conditions were selected because each
was within the range of interest of members of the group, and because each brought out particular aspects of the problems associated one or more
with screening. The views of McKEOWN and the working group are authoritative. Each attempts to define the problem and to review the position as it was before screening was introduced, and they then consider the effectiveness of the proposed screening methods as well as the benefits with the development of screening techniques in experiof the treatment to be offered. In each of the ten mental laboratories. Symposia on presymptomatic examples the advantages and disadvantages of screening diagnosis and on laboratory screening procedures have are assessed against alternative methods of diagnosis and since been held by the Royal Society of Medicine 34 and these laudable attempts at cost-benefit and the Royal College of General PractitionerS5 ; and treatment, are reviewed and extended by J. D. POLE in a analysis a subcommittee of the U.S. Senate has published on economic aspects of screening. The authors the advice it received from many quarters.6 The most chapter of acquiring further evidence for the valiauthoritative recent review on screening is the work of suggest ways dation of screening methods (where this evidence still WILSON and JUNGNER,7 but even this could not hope to seems necessary) and they discuss how best to apply be comprehensive, and already several other publicaeach screening programme once a decision has been taken tions 8-11 have appeared which, in various ways, complethat screening is in fact justifiable. Emphasis is rement and extend this W.H.O. text. The latest is a colleclaid on the need for more research, even into tion of essays 11 prepared by a group working under the peatedly such conditions as phenylketonuria, for which screening chairmanship of Prof. THOMAS McKEOwN. has become a legal requirement in many of the United Last year we adopted a cautious attitude towards States. McKEOWN suggests some of the needs for screening,12 13 and McKEOWN and his colleagues 11 are organising and financing research programmes. also guarded. They follow a common pattern, laid down Notes of caution overenthusiastic screening by McKEOwN in his discussion of the validation of are often sounded onagainst medical grounds, and a careful screening procedures, in which he considers the obligaof the conditions listed by WILSON and tions in screening programmes, both biological and analysis 7 as having greater " relative worth " in caseeconomic. In the later essays the authors have constantly JUNGNER in mind the need to ensure that each screening procedure finding might reveal other areas where reappraisal of has as its aim the early identification of treatable disease, screening programmes is needed. Another conclusion and they present data on which to base an assessment of that emerges very clearly is that no evidence has so far been produced to justify the view that screening offers a 1. On the State of the Public Health 1965. H.M. Stationery Office, London. 2. On the State of the Public Health 1966. H.M. Stationery Office, London. means of important financial savings to the N.H.S., and 3. Proc. R. Soc. Med. 1966, 59, 1169. the central economic problem of prescriptive screening 4. ibid. 1968, 61, 763. 5. Early Detection of Imported and Endemic Disease. J. R. Coll. gen. must still be to compare its effects with the effects of Practnrs, 1968, 16, suppl. no. 2. different types of medical expenditure. We adhere to our 6. Detection and Prevention of Chronic Disease Utilizing Multiphasic Health Screening Techniques. U.S. Government Printing Office, earlier conclusion, therefore, that it is premature to advoWashington, 1966. 7. Wilson, J. M. G., Jungner, G. Principles and Practice of Screening for cate nation-wide attempts at the presymptomatic recogDisease. Public Health Papers no. 34. W.H.O. Geneva, 1968. See nition of disease either on medical or economic grounds. Lancet, 1967, ii, 83. 8. Butterfield, W. J. H. Priorities in Medicine. London, 1968. If we are right to be cautious about screening, what 9. Ferrer, H. P. Screening for Health. London, 1968. 10. Whitby, L. G. Br. J. Hosp. Med. 1968, 1, 79. should be said about " admission profiles " of bio11. Screening in Medical Care: Reviewing the Evidence. London: Oxford chemical investigations for all patients entering hospital ? University Press for the Nuffield Provincial Hospitals Trust. 1968. Pp. 173. 35s. Developments in automated laboratory equipment, and 12. Lancet, 1967, ii, 83. the imminent introduction of computers into hospital 13. ibid. p. 706.
1066
biochemistry laboratories, should mean that these departments will greatly augment their capacity for repetitive work. Already some laboratories have rearranged their work so as to standardise and simplify organisation ’14 15 and as a dividend " they report the results of unsolicited investigations as well as the results of requested examinations. These biochemical profiles have been carefully assessed, particularly in so far as they help individual patients.16 17 A surprising outcome is how rarely these unsolicited biochemical investigations have revealed a new diagnosis, or caused a significant change in a diagnosis, as a result of which the patient can be said to have greatly benefited. Perhaps the present range of biochemical investigations in hospital laboratories, carried out mostly on patients with symptoms and signs of disease, do not represent the best combination of tests for detecting diseases at earlier stages in their natural history. Certainly it would be premature to say that biochemists have developed their methods of investigation to a stage where they hold the key to the better understanding of disease "
processes. For the future, carefully designed research studies must evaluate programmes of prescriptive screening. These plans might also with advantage be combined with long-term biochemical inquiries, since multiphasic screening is cheaper to perform and more acceptable to the public than the repeated calling together of people for the equivalent number of more limited screening tests. If the biochemical investigations can be conducted with satisfactory and maintained standards of quality,4 results could be analysed retrospectively to seek early patterns of abnormality linked to the later development of specifically identified diseases.10 The value of biochemical profiles will depend essentially on the establishment of a normal range " for each individual,18 and hospital records will have to be linked satisfactorily with the results of earlier screening assessments. The prospect is challenging, since a mass of data may accumulate on individuals studied over several years or decades. Careful thought will be needed on how best to handle the great increase in information which could be generated by multichannel biochemical analysis carried out on instruments with capacities for work as high as the Autochemist or the Vickers 300. The number of figures a doctor can assimilate and interpret for each patient is limited, and important facts could be overlooked if too much information flows from the laboratories. A workable solution might be for reports to carry only those results for requested investigations, plus those which differ significantly from normal (as judged by comparison with the appropriate range of normal) and those where an analytically significant change has appeared since the previous examination; the unreported data could be assumed to be normal, but would be stored and remain "
Thiers, R. E., Bryan, J., Oglesby, K. Clin. Chem. 1966, 12, 120. Gaddie, R., Northam, B. E., Roberts, L. B. in Automation in Analytical Chemistry 2 (edited by E. Kawerau); p. 63. New York, 1968. 16. Bryan, D. J., Wearne, J. L., Viau, A., Musser, A. W., Schoonmaker, F. W., Thiers, R. E. Clin. Chem. 1966, 12, 137. 17. Whitehead, T. P. Bio-Med. Eng. 1968, 3, 467. 18. Files, J. B., van Peenen, H. J., Lindberg, D. A. B. J. Am. med. Ass. 1968, 205, 94. 14. 15.
available for
retrospective
multivariate
analysis
if
required. Research is again needed to determine the best pattern of biochemical profiles, and the work of WHITEHEAD 17 and his colleagues is of fundamental importance. We need to know the sectors of the population from which profiles could most profitably be taken and the frequency with which each set of observations should be repeated. The economic justification for performing biochemical profiles must be established before they become a regular feature of 20th-century medicine. A conflict of interest could arise if the smooth operation of laboratories or the niceties of equipment and instruments are allowed to weigh too heavily in planning decisions.
An Extra X Chromosome A PERSON with an extra X chromosome runs twice the usual risk of being admitted to hospital with some form of mental illness. Loss of an X, on the other hand, has no association with mental illness: for an XO female the chance of mental hospital admission is not raised; and YO individuals are not born. These interesting probabilities are suggested by the results of a very large survey of patients in Scottish mental hospitals.l The buccal smears of 30 out of 6000 males were chromatin positive: 20 of them were thought to be XXY, and 10 mosaics (the expected number of chromatin positive males, from a large series of Scottish live births, was 12). 17 of 7202 female patients had the XXX constitution (including mosaics), compared with an expected 7. None of the female patients was chromatin negative (XO constitution), compared with an expectation of 2. These findings confirm the results of smaller surveys in Scandinavia 23 and the U.S.A.4-6 A somewhat higher proportion of XXY males was found in an English survey7 (6 out of 529), but here the criterion of selection-chronicity of psychosis-was to some extent subjective, so that selection bias cannot be ruled out. Interpretation of the Scottish data is complicated by the fact that an extra X chromosome also predisposes to mental subnormality. 9 of the chromatin-positive males and 4 of the XXX females had diagnoses of subnormality. However, if these are excluded, the observed prevalence of extra X chromosome in patients in mental hospitals is still, for both sexes, nearly twice the expected figure. Part of the increase may be due to impairment of intelligence not amounting to mental deficiency. It is well known that chronic schizophrenia causes a patient to slide down the occupational scale, and any factor which lowers his starting position will increase his chances of sliding off the bottom of the scale into hospital. But this cannot be the whole story, for the prevalence of psychosis among 1. Maclean, N., Court Brown, W. M., Jacobs, P. A., Mantle, D. J., Strong, J. A. J. med. Genet. 1968, 5, 165. 2. Nielsen, J. Lancet, 1964, i, 1109. 3. Olanders, S. Br. J. Psychiat. 1967, 113, 1097. 4. Tedeschi, L., Freeman, H. Arch gen. Psychiat. 1962, 6, 109. 5. Raphael, T., Shaw, M. W. J. Am. med. Ass. 1963, 183, 1022. 6. Kaplan, A. R. in Recent Advances in Biological Psychiatry (edited by Joseph Wortis); p. 21. New York, 1967. 7. Anders, J. M., Jagiello, G., Polani, P. E., Gianelli, F., Hamerton, J. L., Lieberman, D. M. Br. J. Psychiat. 1968, 114, 1167.
THE LANCET LONDON
16
NOVEMBER
1968
Prescriptive Screening EARLY detection of chronic non-communicable disease greatly interests countries where the prevention and
control of communicable diseases have been largely achieved. It is, however, easier to define the principles underlying the screening of populations or selected groups for presymptomatic chronic non-communicable disease than to evolve satisfactory programmes whereby these diseases can be sought in the community and effective treatment thereafter made available to the people who truly merit it. The chief medical officer of the Ministry of Health referred to some of these problems in his report1 for 1965, and in the following year2 he announced the setting up of a laboratory automation trials group, which was to be particularly concerned
1065
whether screening would result in the better use of limited resources than the available alternatives. They restrict their review of screening procedures to " prescriptive screening ", a new term which they define as investigations whose primary aim is a direct contribution to the health of individuals (specifically excluded are screening programmes in which the primary aims were either research or the protection of public health). The contributors seek to validate prescriptive screening in relation to ten different conditions which have each been the subject of screening: bacteriuria in pregnancy, breast cancer, cervical cancer, deafness in childhood, diabetes
mellitus, glaucoma, iron-deficiency anaemia, phenylketonuria, pulmonary tuberculosis, and rhesus hxmolytic disease of the newborn. These conditions were selected because each
was within the range of interest of members of the group, and because each brought out particular aspects of the problems associated one or more
with screening. The views of McKEOWN and the working group are authoritative. Each attempts to define the problem and to review the position as it was before screening was introduced, and they then consider the effectiveness of the proposed screening methods as well as the benefits with the development of screening techniques in experiof the treatment to be offered. In each of the ten mental laboratories. Symposia on presymptomatic examples the advantages and disadvantages of screening diagnosis and on laboratory screening procedures have are assessed against alternative methods of diagnosis and since been held by the Royal Society of Medicine 34 and these laudable attempts at cost-benefit and the Royal College of General PractitionerS5 ; and treatment, are reviewed and extended by J. D. POLE in a analysis a subcommittee of the U.S. Senate has published on economic aspects of screening. The authors the advice it received from many quarters.6 The most chapter of acquiring further evidence for the valiauthoritative recent review on screening is the work of suggest ways dation of screening methods (where this evidence still WILSON and JUNGNER,7 but even this could not hope to seems necessary) and they discuss how best to apply be comprehensive, and already several other publicaeach screening programme once a decision has been taken tions 8-11 have appeared which, in various ways, complethat screening is in fact justifiable. Emphasis is rement and extend this W.H.O. text. The latest is a colleclaid on the need for more research, even into tion of essays 11 prepared by a group working under the peatedly such conditions as phenylketonuria, for which screening chairmanship of Prof. THOMAS McKEOwN. has become a legal requirement in many of the United Last year we adopted a cautious attitude towards States. McKEOWN suggests some of the needs for screening,12 13 and McKEOWN and his colleagues 11 are organising and financing research programmes. also guarded. They follow a common pattern, laid down Notes of caution overenthusiastic screening by McKEOwN in his discussion of the validation of are often sounded onagainst medical grounds, and a careful screening procedures, in which he considers the obligaof the conditions listed by WILSON and tions in screening programmes, both biological and analysis 7 as having greater " relative worth " in caseeconomic. In the later essays the authors have constantly JUNGNER in mind the need to ensure that each screening procedure finding might reveal other areas where reappraisal of has as its aim the early identification of treatable disease, screening programmes is needed. Another conclusion and they present data on which to base an assessment of that emerges very clearly is that no evidence has so far been produced to justify the view that screening offers a 1. On the State of the Public Health 1965. H.M. Stationery Office, London. 2. On the State of the Public Health 1966. H.M. Stationery Office, London. means of important financial savings to the N.H.S., and 3. Proc. R. Soc. Med. 1966, 59, 1169. the central economic problem of prescriptive screening 4. ibid. 1968, 61, 763. 5. Early Detection of Imported and Endemic Disease. J. R. Coll. gen. must still be to compare its effects with the effects of Practnrs, 1968, 16, suppl. no. 2. different types of medical expenditure. We adhere to our 6. Detection and Prevention of Chronic Disease Utilizing Multiphasic Health Screening Techniques. U.S. Government Printing Office, earlier conclusion, therefore, that it is premature to advoWashington, 1966. 7. Wilson, J. M. G., Jungner, G. Principles and Practice of Screening for cate nation-wide attempts at the presymptomatic recogDisease. Public Health Papers no. 34. W.H.O. Geneva, 1968. See nition of disease either on medical or economic grounds. Lancet, 1967, ii, 83. 8. Butterfield, W. J. H. Priorities in Medicine. London, 1968. If we are right to be cautious about screening, what 9. Ferrer, H. P. Screening for Health. London, 1968. 10. Whitby, L. G. Br. J. Hosp. Med. 1968, 1, 79. should be said about " admission profiles " of bio11. Screening in Medical Care: Reviewing the Evidence. London: Oxford chemical investigations for all patients entering hospital ? University Press for the Nuffield Provincial Hospitals Trust. 1968. Pp. 173. 35s. Developments in automated laboratory equipment, and 12. Lancet, 1967, ii, 83. the imminent introduction of computers into hospital 13. ibid. p. 706.
1066
biochemistry laboratories, should mean that these departments will greatly augment their capacity for repetitive work. Already some laboratories have rearranged their work so as to standardise and simplify organisation ’14 15 and as a dividend " they report the results of unsolicited investigations as well as the results of requested examinations. These biochemical profiles have been carefully assessed, particularly in so far as they help individual patients.16 17 A surprising outcome is how rarely these unsolicited biochemical investigations have revealed a new diagnosis, or caused a significant change in a diagnosis, as a result of which the patient can be said to have greatly benefited. Perhaps the present range of biochemical investigations in hospital laboratories, carried out mostly on patients with symptoms and signs of disease, do not represent the best combination of tests for detecting diseases at earlier stages in their natural history. Certainly it would be premature to say that biochemists have developed their methods of investigation to a stage where they hold the key to the better understanding of disease "
processes. For the future, carefully designed research studies must evaluate programmes of prescriptive screening. These plans might also with advantage be combined with long-term biochemical inquiries, since multiphasic screening is cheaper to perform and more acceptable to the public than the repeated calling together of people for the equivalent number of more limited screening tests. If the biochemical investigations can be conducted with satisfactory and maintained standards of quality,4 results could be analysed retrospectively to seek early patterns of abnormality linked to the later development of specifically identified diseases.10 The value of biochemical profiles will depend essentially on the establishment of a normal range " for each individual,18 and hospital records will have to be linked satisfactorily with the results of earlier screening assessments. The prospect is challenging, since a mass of data may accumulate on individuals studied over several years or decades. Careful thought will be needed on how best to handle the great increase in information which could be generated by multichannel biochemical analysis carried out on instruments with capacities for work as high as the Autochemist or the Vickers 300. The number of figures a doctor can assimilate and interpret for each patient is limited, and important facts could be overlooked if too much information flows from the laboratories. A workable solution might be for reports to carry only those results for requested investigations, plus those which differ significantly from normal (as judged by comparison with the appropriate range of normal) and those where an analytically significant change has appeared since the previous examination; the unreported data could be assumed to be normal, but would be stored and remain "
Thiers, R. E., Bryan, J., Oglesby, K. Clin. Chem. 1966, 12, 120. Gaddie, R., Northam, B. E., Roberts, L. B. in Automation in Analytical Chemistry 2 (edited by E. Kawerau); p. 63. New York, 1968. 16. Bryan, D. J., Wearne, J. L., Viau, A., Musser, A. W., Schoonmaker, F. W., Thiers, R. E. Clin. Chem. 1966, 12, 137. 17. Whitehead, T. P. Bio-Med. Eng. 1968, 3, 467. 18. Files, J. B., van Peenen, H. J., Lindberg, D. A. B. J. Am. med. Ass. 1968, 205, 94. 14. 15.
available for
retrospective
multivariate
analysis
if
required. Research is again needed to determine the best pattern of biochemical profiles, and the work of WHITEHEAD 17 and his colleagues is of fundamental importance. We need to know the sectors of the population from which profiles could most profitably be taken and the frequency with which each set of observations should be repeated. The economic justification for performing biochemical profiles must be established before they become a regular feature of 20th-century medicine. A conflict of interest could arise if the smooth operation of laboratories or the niceties of equipment and instruments are allowed to weigh too heavily in planning decisions.
An Extra X Chromosome A PERSON with an extra X chromosome runs twice the usual risk of being admitted to hospital with some form of mental illness. Loss of an X, on the other hand, has no association with mental illness: for an XO female the chance of mental hospital admission is not raised; and YO individuals are not born. These interesting probabilities are suggested by the results of a very large survey of patients in Scottish mental hospitals.l The buccal smears of 30 out of 6000 males were chromatin positive: 20 of them were thought to be XXY, and 10 mosaics (the expected number of chromatin positive males, from a large series of Scottish live births, was 12). 17 of 7202 female patients had the XXX constitution (including mosaics), compared with an expected 7. None of the female patients was chromatin negative (XO constitution), compared with an expectation of 2. These findings confirm the results of smaller surveys in Scandinavia 23 and the U.S.A.4-6 A somewhat higher proportion of XXY males was found in an English survey7 (6 out of 529), but here the criterion of selection-chronicity of psychosis-was to some extent subjective, so that selection bias cannot be ruled out. Interpretation of the Scottish data is complicated by the fact that an extra X chromosome also predisposes to mental subnormality. 9 of the chromatin-positive males and 4 of the XXX females had diagnoses of subnormality. However, if these are excluded, the observed prevalence of extra X chromosome in patients in mental hospitals is still, for both sexes, nearly twice the expected figure. Part of the increase may be due to impairment of intelligence not amounting to mental deficiency. It is well known that chronic schizophrenia causes a patient to slide down the occupational scale, and any factor which lowers his starting position will increase his chances of sliding off the bottom of the scale into hospital. But this cannot be the whole story, for the prevalence of psychosis among 1. Maclean, N., Court Brown, W. M., Jacobs, P. A., Mantle, D. J., Strong, J. A. J. med. Genet. 1968, 5, 165. 2. Nielsen, J. Lancet, 1964, i, 1109. 3. Olanders, S. Br. J. Psychiat. 1967, 113, 1097. 4. Tedeschi, L., Freeman, H. Arch gen. Psychiat. 1962, 6, 109. 5. Raphael, T., Shaw, M. W. J. Am. med. Ass. 1963, 183, 1022. 6. Kaplan, A. R. in Recent Advances in Biological Psychiatry (edited by Joseph Wortis); p. 21. New York, 1967. 7. Anders, J. M., Jagiello, G., Polani, P. E., Gianelli, F., Hamerton, J. L., Lieberman, D. M. Br. J. Psychiat. 1968, 114, 1167.