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TRUTH AND CONSEQUENCES IN MEDICAL RESEARCH
1300 tion in rubella among pregnant women can only be achieved by vaccinating more adult women; in our series all but 1 of the patients who contracted rubella had left school before rubella vaccines were licensed. However, we do not feel that the correct approach to this problem is to direct a campaign towards anxious women through the popular Press: this may well result in vaccine being given in the presence of contraindications, as well as in more terminations because of rubella vaccination during pregnancy. The D.H.S.S. must, through well-informed and responsible publicity, encourage family doctors to increase the vaccine uptake rate among adult women. This can succeed only if there are adequate resources for rubella screening. There is at present no information on the proportion of health authorities with facilities to do this-let alone on their ability to cope with an increased work load. Antenatal screening and postpartum rubella vaccination of susceptible women is also officially encouraged, 14 but there is no information on vaccination uptake among such susceptible women. Since we have only been screening patients attending antenatal clinics since October, 1976, it is not surprising that the rubella immune status of but a small proportion of patients who were rubella contacts was known. Radial haemolysis provides a simple and sensitive technique which is, in our opinion, a more reliable screening test than the widely used H.A.I. technique; perhaps it should be more widely used. Work in the U.S.A.16 suggests that the risks to the fetus of vaccination in early pregnancy are considerably less than was once feared, for all infants delivered of 65 women known to be susceptible and vaccinated in early pregnancy were clinically normal at birth, although 2 had serological evidence of intrauterine infection. The U.S. workers calculate that the maximum risk of malformation is of the order of 5.5%. We feel that it would be premature to relax precautions, for there is, as yet, insufficient long-term follow-up information on many of their infants. Furthermore, there is still little information on the risks associated with the RA27/3 vaccine. In contrast with other vaccines, the immune response induced by this vaccine is qualitatively similar to that induced by naturally acquired infection, 3 17 perhaps because this strain has been passaged less than other strains.18 Possibly, therefore, the risk to the fetus may be greater with RA27/3. Although widely used in the U.K., this vaccine has only recently been licensed in the U.S.A., and the results in the U.S. studies may not apply to the RA27/3 vaccine. Might this outbreak not have occurred if the U.K. had adopted the U.S. rubella-vaccination policy, in which vaccination is directed principally at prepubertal children,19 with the aim of reducing the risk of virus transmission from children to pregnant women? Although there has been a considerable reduction in the incidence of both postnatally and congenitally acquired rubella since rubella vaccination started in the U.S.A.,2o it would be premature to conclude that this is the result of the rubella vaccination campaign, since rubella does not exhibit any clearly defined epidemic periodicity. Furthermore, we have yet to see whether vaccinated preschool children will, without boosters, be still immune when exposed to rubella in, say, their fifth decade of life. We therefore favour continuation of the existing policy, but urge that much more emphasis should be placed on
vaccination of women. If resources are insufficient for screening all sera, an alternative might be to collect blood from all adults before vaccination but test only samples from women who (against all advice) become pregnant within two months of vaccination. Perhaps within a few years it will be firmly established that all the rubella vaccines are non-teratogenic. We
are
grateful
to
the Medical
Laboratory
Scientific Officers in the
Department of Virology for their technical assistance; the medical and nursing staff of the Department of Gynaecology at St. Thomas’ Hospital for their cooperation; and the National Fund for Research into
Crippling Diseases (Action
Research for the
Crippled Child) for
their
support.
Requests for reprints should be addressed to J.E.B. REFERENCES
1. Public Health Laboratory Service. Unpublished. 2. Banatvala, J. E., Best, J. M., Bertrand, J., Bowern, N. A., Hudson, S. M. Br. med. J., 1970, ii, 247. 3. Al-Nakib, W., Best, J. M., Banatvala, J. E. Lancet, 1975, i, 182. 4. Clarke, M., Boustred, J., Seagroatt, V., Schild, G. C. J. Hyg. Camb. 1977,
79, 355. 5.
Sugishita, C., O’Shea, S., Best, J. M., Banatvala, J.
E. Clin. exp. Immun.
1978, 31, 50. 6. Peckham, C. S. Archs Dis. Childh. 1972, 47, 571. 7. Menser, M. A., Forrest, J. M. Med. J. Aust., 1974, i, 123. 8. British Medical Journal, 1978, ii, 967. 9. Lundström, R., Svedmyr, A., Hagbard, L., Kaijser, K. Acta pœdiat scand.
1967, 56, 279. R., Dudgeon, J. A., Hayes, K., Peckham, C. S., Wybar, K. Br. med. J. 1965, ii, 1027. 11. Gumpel, S. M., Hayes, K., Dudgeon, J. A. ibid. 1971, ii, 300. 12. Department of Health and Social Security Circular 9/70, 1970. 13. Department of Health and Social Security Circular 17/72, 1972. 14. Department of Health and Social Security Circular 4/76, 1976. 15. Department of Health and Social Security Circular 78/15, 1978. 16. Preblud, S., Nieburg, P. I., Hinman, A. R. Br. med. J. 1978, ii, 960. 17. Plotkin, S. A., Farquhar, J. D., Ogra, P. L. J. Am. med. Ass. 1973, 225, 585. 18. Plotkin, S. A., Farquhar, J., Katz, M., Ingalls, T. H. Am. J. Epidem. 1967, 86, 468. 19. Morbid Mortal, 1972, 21, Suppl. p. 23. 20. Hayden, G. F., Modlin, J. F., Witte, J. J.J. infect. Dis. 1977, 135, 337. 10. Butler, N.
Point of View TRUTH AND
CONSEQUENCES IN MEDICAL RESEARCH* M.
J.
R. HEALY
Department of Medical Statistics and Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT
Sir Karl Popper,l scientific theories are generalisations derived inductively from individual facts; rather they are bold conjectures from which predictions can be made and which have withstood attempts at refutation. One theory supplants another if it survives not only the tests that the other has passed but also some of those that it has failed. Statisticians might be expected to welcome Popper’s views since they have in a sense anticipated them.2 The crucial moment in the life of a theory, according to Popper, is that in which its predictions are confronted by the facts; but the question "do the facts agree with a theoretical prediction ?" is precisely that which is answered by a statistical test of significance. However, many scientists have no ACCORDING
to
not
Based on a chairman’s address Statistical Society.
*
to
the medical section of the
Royal
1301 use for statistical analysis; equally, many statisticians have come to regard significance testing as by no means their most important activity. A large part of medical research does not fit the Popperian model at all well. This includes the whole area of research, especially important in surgery and pathology, aimed not at testing a theory but at improving a technique. Another example is the large current clinical trial on the treatment of mild-to-moderate hypertension. In view of the findings on severe hypertension there is little doubt that the treatment will have some real effect in reducing the incidence of strokes and other accidents; the trial is needed not to demonstrate the existence of the effect but rather to find whether its size is sufficient to counterbalance the "costs" of treatment in a generalised sense.
great
If a large class of the things that medical research workers actually do are not adequately described by a widely accepted theory of scientific method, we must ask whether these activities are rightly regarded as scientific in a strict sense of the term. My thesis is that they are not; they fall, I suggest, more appropriately within the province of technology.
The distinction between science and technology may be ascribed to the questions which they ask. According to Popper, the key question which defines a scientific inquiry is, "does my theory fit the facts?", and this (statistical niceties apart) requires the answer ’,’yes" or "no". Technological work rarely asks a question of this kind. Its questions almost always involve "how much?" and the answers need to be quantitative. Statistically speaking, the technologist is more interested in estimation than in testing significance.
relationship between science and technology is commonly misunderstood. It is often assumed that the whole task of technology ("applied science") is to work out the practical consequences of scientific discoveries, and this is held to be a much less prestigious task than that of making the discoveries in the first place the work,say, of "mere technicians". This view neglects the historical fact that technology is an older activity than science (the invention of the wheel and the domestication of animals took place in societies to which the very notion of science would have been incomprehensible). It also ignores the role played by technology in the process of scientific discovery itself, that of defining and refining the areas within which the key scientific question can be asked. To a large extent, the directions in which science moves most successfully are determined by the tools which technology places within its grasp. It can in fact be argued that science depends upon technology rather than the other way round. The critical phase of scienThe
tific advance consists in the confrontation of theoretical
predictions with reality, and as theories become more sophisticated and their predictions more minute, so technological advances are needed for the confrontation to be decisive. If it is common for scientists to despise technology, the opposite reaction is also easy to find. To the downto-earth engineer, the scientist (a "mere academic") is a man with no proper sense of the value of money, whose neglect of the practical implications of his findings falls somewhere between incompetence and irresponsibility. Nor is it difficult to find counter-reactions in both direc-
tions-the academic technologist anxious to prove that his discipline is as useless as the next don’s, the scientist assuring the Rothschild-oriented grant-givers that his research will have a practical outcome next year or, at latest, the year after. In England especially, the split is far nearer the root of our troubles than that between the Two Cultures a la C.P. Snow. I have discussed these notions more fully elsewhere.3
Science and technology differ in their attitudes to research. Research is the life of science and a scientist is by definition one engaged in research. To the contrary, there is no reason why a technologist should do research; he may not be an innovator at all, or he may be concerned with new applications of existing techniques. But there is equally no reason why he should not do research. Because no-one knows what he can do until he tries, the way to technological improvement will be through research and experiment, though the experiments will have quantitative results, not the yes/no result of the scientific experimentum crucis. The distinction between science and technology is important for statisticians like myself. If our efforts have been underappreciated by scientists, they have been wholeheartedly welcomed by technologists in many fields. One of these is medicine, where the problem of the science/technology balance has been solved more successfully than anywhere else. Medical science is prestigious, well supported, even reasonably well rewarded, but it is recognised to be at the service of medical practice. Medical practice (neither an art nor a science but the blend which I call technology) is expected both by doctors and the public to keep abreast of advances in medical science and is provided, through the weekly journals and elsewhere, with the means to do so. Even in medicine, the distinction between science and technology is sometimes blurred. Schwartz and Lellouch45 distinguish between an explanatory and a pragmatic approach to clinical trials, and have shown that the two approaches lead to quite distinct methodologies, to the extent that an attempt to mix them can lead to experiments from which no useful conclusions can be drawn. The fact that medical students will almost all become technologists, with a minority even of those "going into research" becoming scientists sensu stricto, has implications for their training and curriculum, including that corner of it devoted to medical statistics. If statistics constitutes the technology of research, the same sort of considerations hold for the training and assessment of statisticians. age dominated by technology the scientist can afford to neglect the possible outcomes of his acperhaps tivities, but the technologist knows that he must accept responsibility for the consequences of his actions. The future of our society will depend largely on the activities of the technologists, and it is important that both society and the technologists acknowledge the fact. In
an
REFERENCES K. R. The Logic of Scientific Discovery. London, 1959. Fisher, R. A. Statistical Methods for Research Workers. Edinburgh, 1970. Healy, M. J. R. J. R. statist. Soc. A, 1978, 141, 385. Schwartz, D., Lellouch, J. J. chron. Dis. 1977, 20, 637. 5. Schwartz, D., Flamand, R., Lellouch, J. L’essai thérapeutique chez l’homme. Paris, 1970.
1. 2. 3. 4.
Popper,
vaccination of women. If resources are insufficient for screening all sera, an alternative might be to collect blood from all adults before vaccination but test only samples from women who (against all advice) become pregnant within two months of vaccination. Perhaps within a few years it will be firmly established that all the rubella vaccines are non-teratogenic. We
are
grateful
to
the Medical
Laboratory
Scientific Officers in the
Department of Virology for their technical assistance; the medical and nursing staff of the Department of Gynaecology at St. Thomas’ Hospital for their cooperation; and the National Fund for Research into
Crippling Diseases (Action
Research for the
Crippled Child) for
their
support.
Requests for reprints should be addressed to J.E.B. REFERENCES
1. Public Health Laboratory Service. Unpublished. 2. Banatvala, J. E., Best, J. M., Bertrand, J., Bowern, N. A., Hudson, S. M. Br. med. J., 1970, ii, 247. 3. Al-Nakib, W., Best, J. M., Banatvala, J. E. Lancet, 1975, i, 182. 4. Clarke, M., Boustred, J., Seagroatt, V., Schild, G. C. J. Hyg. Camb. 1977,
79, 355. 5.
Sugishita, C., O’Shea, S., Best, J. M., Banatvala, J.
E. Clin. exp. Immun.
1978, 31, 50. 6. Peckham, C. S. Archs Dis. Childh. 1972, 47, 571. 7. Menser, M. A., Forrest, J. M. Med. J. Aust., 1974, i, 123. 8. British Medical Journal, 1978, ii, 967. 9. Lundström, R., Svedmyr, A., Hagbard, L., Kaijser, K. Acta pœdiat scand.
1967, 56, 279. R., Dudgeon, J. A., Hayes, K., Peckham, C. S., Wybar, K. Br. med. J. 1965, ii, 1027. 11. Gumpel, S. M., Hayes, K., Dudgeon, J. A. ibid. 1971, ii, 300. 12. Department of Health and Social Security Circular 9/70, 1970. 13. Department of Health and Social Security Circular 17/72, 1972. 14. Department of Health and Social Security Circular 4/76, 1976. 15. Department of Health and Social Security Circular 78/15, 1978. 16. Preblud, S., Nieburg, P. I., Hinman, A. R. Br. med. J. 1978, ii, 960. 17. Plotkin, S. A., Farquhar, J. D., Ogra, P. L. J. Am. med. Ass. 1973, 225, 585. 18. Plotkin, S. A., Farquhar, J., Katz, M., Ingalls, T. H. Am. J. Epidem. 1967, 86, 468. 19. Morbid Mortal, 1972, 21, Suppl. p. 23. 20. Hayden, G. F., Modlin, J. F., Witte, J. J.J. infect. Dis. 1977, 135, 337. 10. Butler, N.
Point of View TRUTH AND
CONSEQUENCES IN MEDICAL RESEARCH* M.
J.
R. HEALY
Department of Medical Statistics and Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT
Sir Karl Popper,l scientific theories are generalisations derived inductively from individual facts; rather they are bold conjectures from which predictions can be made and which have withstood attempts at refutation. One theory supplants another if it survives not only the tests that the other has passed but also some of those that it has failed. Statisticians might be expected to welcome Popper’s views since they have in a sense anticipated them.2 The crucial moment in the life of a theory, according to Popper, is that in which its predictions are confronted by the facts; but the question "do the facts agree with a theoretical prediction ?" is precisely that which is answered by a statistical test of significance. However, many scientists have no ACCORDING
to
not
Based on a chairman’s address Statistical Society.
*
to
the medical section of the
Royal
1301 use for statistical analysis; equally, many statisticians have come to regard significance testing as by no means their most important activity. A large part of medical research does not fit the Popperian model at all well. This includes the whole area of research, especially important in surgery and pathology, aimed not at testing a theory but at improving a technique. Another example is the large current clinical trial on the treatment of mild-to-moderate hypertension. In view of the findings on severe hypertension there is little doubt that the treatment will have some real effect in reducing the incidence of strokes and other accidents; the trial is needed not to demonstrate the existence of the effect but rather to find whether its size is sufficient to counterbalance the "costs" of treatment in a generalised sense.
great
If a large class of the things that medical research workers actually do are not adequately described by a widely accepted theory of scientific method, we must ask whether these activities are rightly regarded as scientific in a strict sense of the term. My thesis is that they are not; they fall, I suggest, more appropriately within the province of technology.
The distinction between science and technology may be ascribed to the questions which they ask. According to Popper, the key question which defines a scientific inquiry is, "does my theory fit the facts?", and this (statistical niceties apart) requires the answer ’,’yes" or "no". Technological work rarely asks a question of this kind. Its questions almost always involve "how much?" and the answers need to be quantitative. Statistically speaking, the technologist is more interested in estimation than in testing significance.
relationship between science and technology is commonly misunderstood. It is often assumed that the whole task of technology ("applied science") is to work out the practical consequences of scientific discoveries, and this is held to be a much less prestigious task than that of making the discoveries in the first place the work,say, of "mere technicians". This view neglects the historical fact that technology is an older activity than science (the invention of the wheel and the domestication of animals took place in societies to which the very notion of science would have been incomprehensible). It also ignores the role played by technology in the process of scientific discovery itself, that of defining and refining the areas within which the key scientific question can be asked. To a large extent, the directions in which science moves most successfully are determined by the tools which technology places within its grasp. It can in fact be argued that science depends upon technology rather than the other way round. The critical phase of scienThe
tific advance consists in the confrontation of theoretical
predictions with reality, and as theories become more sophisticated and their predictions more minute, so technological advances are needed for the confrontation to be decisive. If it is common for scientists to despise technology, the opposite reaction is also easy to find. To the downto-earth engineer, the scientist (a "mere academic") is a man with no proper sense of the value of money, whose neglect of the practical implications of his findings falls somewhere between incompetence and irresponsibility. Nor is it difficult to find counter-reactions in both direc-
tions-the academic technologist anxious to prove that his discipline is as useless as the next don’s, the scientist assuring the Rothschild-oriented grant-givers that his research will have a practical outcome next year or, at latest, the year after. In England especially, the split is far nearer the root of our troubles than that between the Two Cultures a la C.P. Snow. I have discussed these notions more fully elsewhere.3
Science and technology differ in their attitudes to research. Research is the life of science and a scientist is by definition one engaged in research. To the contrary, there is no reason why a technologist should do research; he may not be an innovator at all, or he may be concerned with new applications of existing techniques. But there is equally no reason why he should not do research. Because no-one knows what he can do until he tries, the way to technological improvement will be through research and experiment, though the experiments will have quantitative results, not the yes/no result of the scientific experimentum crucis. The distinction between science and technology is important for statisticians like myself. If our efforts have been underappreciated by scientists, they have been wholeheartedly welcomed by technologists in many fields. One of these is medicine, where the problem of the science/technology balance has been solved more successfully than anywhere else. Medical science is prestigious, well supported, even reasonably well rewarded, but it is recognised to be at the service of medical practice. Medical practice (neither an art nor a science but the blend which I call technology) is expected both by doctors and the public to keep abreast of advances in medical science and is provided, through the weekly journals and elsewhere, with the means to do so. Even in medicine, the distinction between science and technology is sometimes blurred. Schwartz and Lellouch45 distinguish between an explanatory and a pragmatic approach to clinical trials, and have shown that the two approaches lead to quite distinct methodologies, to the extent that an attempt to mix them can lead to experiments from which no useful conclusions can be drawn. The fact that medical students will almost all become technologists, with a minority even of those "going into research" becoming scientists sensu stricto, has implications for their training and curriculum, including that corner of it devoted to medical statistics. If statistics constitutes the technology of research, the same sort of considerations hold for the training and assessment of statisticians. age dominated by technology the scientist can afford to neglect the possible outcomes of his acperhaps tivities, but the technologist knows that he must accept responsibility for the consequences of his actions. The future of our society will depend largely on the activities of the technologists, and it is important that both society and the technologists acknowledge the fact. In
an
REFERENCES K. R. The Logic of Scientific Discovery. London, 1959. Fisher, R. A. Statistical Methods for Research Workers. Edinburgh, 1970. Healy, M. J. R. J. R. statist. Soc. A, 1978, 141, 385. Schwartz, D., Lellouch, J. J. chron. Dis. 1977, 20, 637. 5. Schwartz, D., Flamand, R., Lellouch, J. L’essai thérapeutique chez l’homme. Paris, 1970.
1. 2. 3. 4.
Popper,