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Influence of misleading publications on general practitioners and purchasers
THE LANCET
Figure: Axial T2-weighted magnetic resonance imaging scans show tethered spinal cord to upper margin of fourth lumbar vertebra (white arrow)
common causes such as myelitis, multiple sclerosis, and neoplasms. The importance of this rare condition is in the risk of iatrogenic damage of the spinal cord by lumbar puncture or myelography, which are frequently used as primary diagnostic tools in the management of these patients. Careful clinical inspection for cutaneous stigmata of spinal dysraphism (subcutaneous lipoma, midline hypertrichosis, sacral naevus) and plain radiographs of the spine (showing a spina bifida in more than 95% of patients with TCS1–3) should be used as screening methods. Stefan Kiechl, Martina F Kronenberg, Miklos Marosi, Günther G Birbamer, *Leopold Saltuari Departments of Neurology and Magnetic Resonance Imaging, University of Innsbruck, Innsbruck; and *Department of Neurology, District General Hospital Hochzirl, A-6170 Z irl, Austria
No attempt is made in this article to review the considerable number of publications on factor V Leiden, and only one report is referenced. It was particularly disappointing that this article, published in February, 1996, did not include the specific information on factor V Leiden and the new generation pills reported in The Lancet in December, 1995.3 Recent guidelines4 have suggested that activated protein C resistance is screened for in specific patients at high risk of recurrent venous thrombosis. The work of Bertina and colleagues5 has shown that this phenotype is associated with heterozygosity or homozygosity for the factor V Leiden mutation in more than 95% of cases. The detection of factor V Leiden therefore offers a direct way of looking for this commonest cause of thrombophilia rather than an indirect functional test, and in Exeter, where the test is available for £16.50, it is not much more expensive. There are advantages in looking for the point mutation—it can be done when a patient is already on warfarin or during the acute thrombotic episode. Detection of factor V Leiden mutation is important in thrombophilia to test for specific patients at risk at recurrent thrombosis; this does not mean that it needs to be advocated in widespread screening programmes but certainly we should not be advising clinicians not to request it in appropriate patients. Although there is a need for journals and other publications providing guidelines to evidence-based health care, there is a real responsibility to ensure that these guidelines are accurate. It is regrettable that Bandolier does not have a correspondence section allowing contrary views to be expressed. Andrew T Hattersley Molecular Genetics Laboratory, Royal Devon and Ex eter Hospital, Ex eter EX 2 5DW, UK
1 1 2 3
4 5
Pang D, Wilberger JE. Tethered cord syndrome in adults. J Neurosurg 1982; 57: 32–47. Kaplan JO, Quencer RM. The occult tethered conus syndrome in the adult. Radiology 1980; 137: 387–91. Zumkeller M, Seifert V, Stolke D. Spinale dysraphie und Ascensionsstörung des Rückenmarks bei Erwachsenen. Z Orthop 1989; 127: 336–42. Dale AJD. Diastematomyelia. Arch Neurol 1969; 20: 309–17. Yamada S, Zinke DE, Saunders D. Pathophysiology of ‘tethered cord syndrome’. J Neurosurg 1981; 54: 494–503.
Influence of misleading publications on general practitioners and purchasers SIR—With the increasing demand for evidence-based medicine, busy clinicians and purchasers increasingly rely on publications reviewing evidence-based practice. We have been made aware that decisions about the purchasing of factor V Leiden may be influenced by the front page story in Bandolier, an evidence-based health-care summary publication, which is produced in Oxford, UK.1 This publication is read by many general practitioners and purchasers and we are concerned that their recent coverage of factor V Leiden was not based on all the evidence. Under the unusual title of “Sex change priest in mercy dash to palace shock!” they highlight that the media response to Rees and colleagues’ publication in The Lancet2 was sensationalised to suggest that genetic tests could be used to predict which patients would be at highest risk when using a new generation pill. They conclude that the clinician or family planning doctor should not request testing for this genetic mutation until “well conducted studies” are done.
Vol 348 • August 3, 1996
2 3
4 5
Anon. Sex change priest in mercy dash to palace shock! Bandolier 1996; 3: 1. Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133–34. Bloemenkamp KWM, Rosendaal FR, Helmerhorst FM, Buller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995; 346: 1593–96. Anon. Management of patients with thrombophilia. Drug Ther Bull 1995; 33: 6–8. Bertina RM, Koeleman BPC. Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64–66.
Authors’ reply SIR—Bandolier does publish critical letters in the journal but we do not receive many. The aims of Bandolier include helping our readers become better critics, able to understand and use concepts such as the number needed to treat (NNT) and odds ratios, and better able to find and appraise articles on new tests and treatments. We are not against tests for thrombophilia. Indeed, we have already organised a workshop to explore their use.1 The conclusion was that, “we ought to be able to arrive at rational policies”. We do not, however, believe that a new test should enter clinical practice because an excellent observational study published in The Lancet2 is translated in a few weeks to a dramatic banner headline in a newspaper for general practitioners. The headline of the Bandolier article to which Hattersley objects pointed out this irony by the use of its headline. We agree that a strong association has been shown between a measurable biological factor and an increased risk of a disease. Rees and colleagues2 called specifically for prospective trials of screening. We cannot find a systematic review of intervention studies, the gold standard for
343
THE LANCET
appraising a new test.3 Nor do we believe that the criteria to understand the clinical role of a new diagnostic test have been satisfied.4 Another workshop will address these issues together with the benefits and costs of introducing a thrombophilia risk reduction programme. Readers should be aware that the cost provided by Hattersley is only the laboratory cost of the assay. In the meantime we stand by our article and our headline. Strength of association is not enough to justify the adoption of a new policy and introduction of a new programme. The widespread passage of prostate-specific antigen into clinical practice in a semi-screening mode is but the latest in a long list of new tests bypassing the rigorous appraisal process standard for new drugs. This screening double standard has already been spotlighted.5 The lesson of cervical screening, which is only now starting to have a greatly beneficial effect after 20 years, should not be forgotten. A headline in a GP newspaper will not produce the best policy. It could lead to 10 000 policies, one for each practice, or even 30 000 policies, one for each practitioner in the UK, each based on an individual’s interpretation of what might constitute a family history of thrombosis. We believe that a systematic approach to implementation is better for patients, and pays more respect to science, than leaving it to the process of diffusion, which too often allows inappropriate application of research.
proguanil, and 4% other preparations. Exposure to information on health issues related to their holiday on television (in most cases Watchdog), and discussing health issues with friends before the trip, were closely associated with reported concerns about health, especially about the effects of taking anti-malarials. During follow-up, more detailed information was gathered on the advice given to tourists by health professionals and the impact of Watchdog. Only one tourist interviewed had been dissuaded from taking Lariam by seeing the programme. Ten respondents whose concerns were raised by the programme re-consulted health professionals about side-effects, were reassured, and continued to take the drug. Four respondents reported that friends or relatives had seen the programme and expressed their concerns and that this influenced their decision to switch from Lariam to chloroquine plus proguanil. It also appeared that one general practitioner had refused to prescribe mefloquine after receiving information from Roche issued in response to Watchdog. The decline in sales of Lariam reported by Roche may thus reflect the extent and importance of lay and professional referral, rather than a direct and unmediated result of the coverage itself. It remains to be seen whether reduced usage of Lariam among travellers to malarious areas will persist, or whether usage will return to pre-Watchdog levels. *Stephen Clift, Peter Grabowski
Bandolier, Pain Relief Unit, The Churchill, Headington, Oxford OX3 7LJ, UK
Centre for Health Education and Research, Canterbury Christ Church College, Canterbury, Kent CT1 1QU, UK; and Faculty of Business, University of Luton
1
1
Andrew Moore, Henry McQuay, *Muir Gray
2 3
4
5
Sidebottom E. Commissioning new genetic services: report of a conference held on May 8, 1996. Available from Bandolier or on http://www.jr2.ox.ac.uk/Bandolier/bandopubs/bandopubs.html. Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133–34. Irwig L, Toteson ANA, Gastonis C, Lau J, Colditz TC, Mostellaer F. Guidelines for meta-analyses evaluating diagnostic tests. Ann Intern Med 1994; 120: 667–76. Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical epidemiology: a basic science for clinical medicine. 2nd ed. Boston: Little, Brown, 1991. Raffle A. Once bitten twice shy. Why evidence-based purchasers are right to be cautious about screening. Evidence-based purchasing. Bristol: NHSE South and West, 1996: May.
Malaria prophylaxis and the media SIR—In early November, 1995, the BBC television’s consumer programme Watchdog drew attention to possible adverse side-effects from mefloquine (Lariam) used for malaria prophylaxis. Medical concerns were raised that travellers’ anxieties about mefloquine might be heightened and result in an increase in the numbers of travellers deciding against taking it. Roche Products Ltd, manufacturers of Lariam, have reported a decline in sales since the programme. Some light is cast on the impact of the Watchdog coverage on British tourists by a survey we conducted among visitors to The Gambia, West Africa, in December, 1995. Travellers to this country are advised that mefloquine is the preferred prophylactic unless contraindicated on medical grounds or on account of severe or serious side-effects.1 A total of 113 tourists on holiday in The Gambia (45% male, 55% female, aged from late teens to 60 or more) were interviewed with a structured questionnaire. 87 tourists agreed to be followed up on their return home, and 78 were contacted, mainly by telephone in mid-January, 1996. Four tourists reported taking no prophylaxis. Among those (the majority) who did take drugs, 75% reported taking mefloquine, followed by 21% taking chloroquine plus
344
Bradley DJ, Warhurst DC, et al. Malaria prophylaxis: guidelines for travellers from Britain. BMJ 1995; 310: 709–14.
Impact of UK malaria prophylaxis policy on imported malaria SIR—Recent UK media interest on adverse events attributed to the use of mefloquine led us to evaluate the benefits of mefloquine as a chemoprophylactic agent. In May, 1993, the British malaria guidelines recommended1 for the first time the use of mefloquine as an alternative to chloroquine and proguanil chemoprophylaxis for travellers to Kenya and other regions with highly chloroquine-resistant falciparum malaria. Kenya is a favoured tourist destination for which patterns of imported malaria have been monitored.2 Using malaria surveillance reports from the Malaria Reference Laboratory (MRL) of UK residents returning from Kenya, and the total number of visits by UK residents to Kenya from the international passenger survey (IRN Ltd, personal communication), we calculated quarterly malaria attack rates in tourists (figure). As a proxy of transmission intensity on the Kenyan coast where two-thirds of all visitors to Kenya spend some of their visit,3 we also examined hospital admission of 1–119-month-old patients to Kilifi district hospital with the primary diagnosis of malaria.4 Malaria admissions in Kilifi remained stable with seasonal fluctuations until the third quarter of 1994 when a large increase in admission was noted. The trends of malaria in the local population and tourists were similar between the first quarter of 1991 and the first quarter of 1993. They nearly mirror the seasonal fluctuations, suggesting malaria acquired by travellers follows local transmission. However, imported malaria incidence fell from eight to four cases per 10 000 visits between 1992 and 1994, and in 1995 there was a further fall to two cases per 10 000 visits. The introduction of the drug was not associated with any other specific measures to improve prophylaxis compliance
Vol 348 • August 3, 1996
Figure: Axial T2-weighted magnetic resonance imaging scans show tethered spinal cord to upper margin of fourth lumbar vertebra (white arrow)
common causes such as myelitis, multiple sclerosis, and neoplasms. The importance of this rare condition is in the risk of iatrogenic damage of the spinal cord by lumbar puncture or myelography, which are frequently used as primary diagnostic tools in the management of these patients. Careful clinical inspection for cutaneous stigmata of spinal dysraphism (subcutaneous lipoma, midline hypertrichosis, sacral naevus) and plain radiographs of the spine (showing a spina bifida in more than 95% of patients with TCS1–3) should be used as screening methods. Stefan Kiechl, Martina F Kronenberg, Miklos Marosi, Günther G Birbamer, *Leopold Saltuari Departments of Neurology and Magnetic Resonance Imaging, University of Innsbruck, Innsbruck; and *Department of Neurology, District General Hospital Hochzirl, A-6170 Z irl, Austria
No attempt is made in this article to review the considerable number of publications on factor V Leiden, and only one report is referenced. It was particularly disappointing that this article, published in February, 1996, did not include the specific information on factor V Leiden and the new generation pills reported in The Lancet in December, 1995.3 Recent guidelines4 have suggested that activated protein C resistance is screened for in specific patients at high risk of recurrent venous thrombosis. The work of Bertina and colleagues5 has shown that this phenotype is associated with heterozygosity or homozygosity for the factor V Leiden mutation in more than 95% of cases. The detection of factor V Leiden therefore offers a direct way of looking for this commonest cause of thrombophilia rather than an indirect functional test, and in Exeter, where the test is available for £16.50, it is not much more expensive. There are advantages in looking for the point mutation—it can be done when a patient is already on warfarin or during the acute thrombotic episode. Detection of factor V Leiden mutation is important in thrombophilia to test for specific patients at risk at recurrent thrombosis; this does not mean that it needs to be advocated in widespread screening programmes but certainly we should not be advising clinicians not to request it in appropriate patients. Although there is a need for journals and other publications providing guidelines to evidence-based health care, there is a real responsibility to ensure that these guidelines are accurate. It is regrettable that Bandolier does not have a correspondence section allowing contrary views to be expressed. Andrew T Hattersley Molecular Genetics Laboratory, Royal Devon and Ex eter Hospital, Ex eter EX 2 5DW, UK
1 1 2 3
4 5
Pang D, Wilberger JE. Tethered cord syndrome in adults. J Neurosurg 1982; 57: 32–47. Kaplan JO, Quencer RM. The occult tethered conus syndrome in the adult. Radiology 1980; 137: 387–91. Zumkeller M, Seifert V, Stolke D. Spinale dysraphie und Ascensionsstörung des Rückenmarks bei Erwachsenen. Z Orthop 1989; 127: 336–42. Dale AJD. Diastematomyelia. Arch Neurol 1969; 20: 309–17. Yamada S, Zinke DE, Saunders D. Pathophysiology of ‘tethered cord syndrome’. J Neurosurg 1981; 54: 494–503.
Influence of misleading publications on general practitioners and purchasers SIR—With the increasing demand for evidence-based medicine, busy clinicians and purchasers increasingly rely on publications reviewing evidence-based practice. We have been made aware that decisions about the purchasing of factor V Leiden may be influenced by the front page story in Bandolier, an evidence-based health-care summary publication, which is produced in Oxford, UK.1 This publication is read by many general practitioners and purchasers and we are concerned that their recent coverage of factor V Leiden was not based on all the evidence. Under the unusual title of “Sex change priest in mercy dash to palace shock!” they highlight that the media response to Rees and colleagues’ publication in The Lancet2 was sensationalised to suggest that genetic tests could be used to predict which patients would be at highest risk when using a new generation pill. They conclude that the clinician or family planning doctor should not request testing for this genetic mutation until “well conducted studies” are done.
Vol 348 • August 3, 1996
2 3
4 5
Anon. Sex change priest in mercy dash to palace shock! Bandolier 1996; 3: 1. Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133–34. Bloemenkamp KWM, Rosendaal FR, Helmerhorst FM, Buller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995; 346: 1593–96. Anon. Management of patients with thrombophilia. Drug Ther Bull 1995; 33: 6–8. Bertina RM, Koeleman BPC. Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64–66.
Authors’ reply SIR—Bandolier does publish critical letters in the journal but we do not receive many. The aims of Bandolier include helping our readers become better critics, able to understand and use concepts such as the number needed to treat (NNT) and odds ratios, and better able to find and appraise articles on new tests and treatments. We are not against tests for thrombophilia. Indeed, we have already organised a workshop to explore their use.1 The conclusion was that, “we ought to be able to arrive at rational policies”. We do not, however, believe that a new test should enter clinical practice because an excellent observational study published in The Lancet2 is translated in a few weeks to a dramatic banner headline in a newspaper for general practitioners. The headline of the Bandolier article to which Hattersley objects pointed out this irony by the use of its headline. We agree that a strong association has been shown between a measurable biological factor and an increased risk of a disease. Rees and colleagues2 called specifically for prospective trials of screening. We cannot find a systematic review of intervention studies, the gold standard for
343
THE LANCET
appraising a new test.3 Nor do we believe that the criteria to understand the clinical role of a new diagnostic test have been satisfied.4 Another workshop will address these issues together with the benefits and costs of introducing a thrombophilia risk reduction programme. Readers should be aware that the cost provided by Hattersley is only the laboratory cost of the assay. In the meantime we stand by our article and our headline. Strength of association is not enough to justify the adoption of a new policy and introduction of a new programme. The widespread passage of prostate-specific antigen into clinical practice in a semi-screening mode is but the latest in a long list of new tests bypassing the rigorous appraisal process standard for new drugs. This screening double standard has already been spotlighted.5 The lesson of cervical screening, which is only now starting to have a greatly beneficial effect after 20 years, should not be forgotten. A headline in a GP newspaper will not produce the best policy. It could lead to 10 000 policies, one for each practice, or even 30 000 policies, one for each practitioner in the UK, each based on an individual’s interpretation of what might constitute a family history of thrombosis. We believe that a systematic approach to implementation is better for patients, and pays more respect to science, than leaving it to the process of diffusion, which too often allows inappropriate application of research.
proguanil, and 4% other preparations. Exposure to information on health issues related to their holiday on television (in most cases Watchdog), and discussing health issues with friends before the trip, were closely associated with reported concerns about health, especially about the effects of taking anti-malarials. During follow-up, more detailed information was gathered on the advice given to tourists by health professionals and the impact of Watchdog. Only one tourist interviewed had been dissuaded from taking Lariam by seeing the programme. Ten respondents whose concerns were raised by the programme re-consulted health professionals about side-effects, were reassured, and continued to take the drug. Four respondents reported that friends or relatives had seen the programme and expressed their concerns and that this influenced their decision to switch from Lariam to chloroquine plus proguanil. It also appeared that one general practitioner had refused to prescribe mefloquine after receiving information from Roche issued in response to Watchdog. The decline in sales of Lariam reported by Roche may thus reflect the extent and importance of lay and professional referral, rather than a direct and unmediated result of the coverage itself. It remains to be seen whether reduced usage of Lariam among travellers to malarious areas will persist, or whether usage will return to pre-Watchdog levels. *Stephen Clift, Peter Grabowski
Bandolier, Pain Relief Unit, The Churchill, Headington, Oxford OX3 7LJ, UK
Centre for Health Education and Research, Canterbury Christ Church College, Canterbury, Kent CT1 1QU, UK; and Faculty of Business, University of Luton
1
1
Andrew Moore, Henry McQuay, *Muir Gray
2 3
4
5
Sidebottom E. Commissioning new genetic services: report of a conference held on May 8, 1996. Available from Bandolier or on http://www.jr2.ox.ac.uk/Bandolier/bandopubs/bandopubs.html. Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133–34. Irwig L, Toteson ANA, Gastonis C, Lau J, Colditz TC, Mostellaer F. Guidelines for meta-analyses evaluating diagnostic tests. Ann Intern Med 1994; 120: 667–76. Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical epidemiology: a basic science for clinical medicine. 2nd ed. Boston: Little, Brown, 1991. Raffle A. Once bitten twice shy. Why evidence-based purchasers are right to be cautious about screening. Evidence-based purchasing. Bristol: NHSE South and West, 1996: May.
Malaria prophylaxis and the media SIR—In early November, 1995, the BBC television’s consumer programme Watchdog drew attention to possible adverse side-effects from mefloquine (Lariam) used for malaria prophylaxis. Medical concerns were raised that travellers’ anxieties about mefloquine might be heightened and result in an increase in the numbers of travellers deciding against taking it. Roche Products Ltd, manufacturers of Lariam, have reported a decline in sales since the programme. Some light is cast on the impact of the Watchdog coverage on British tourists by a survey we conducted among visitors to The Gambia, West Africa, in December, 1995. Travellers to this country are advised that mefloquine is the preferred prophylactic unless contraindicated on medical grounds or on account of severe or serious side-effects.1 A total of 113 tourists on holiday in The Gambia (45% male, 55% female, aged from late teens to 60 or more) were interviewed with a structured questionnaire. 87 tourists agreed to be followed up on their return home, and 78 were contacted, mainly by telephone in mid-January, 1996. Four tourists reported taking no prophylaxis. Among those (the majority) who did take drugs, 75% reported taking mefloquine, followed by 21% taking chloroquine plus
344
Bradley DJ, Warhurst DC, et al. Malaria prophylaxis: guidelines for travellers from Britain. BMJ 1995; 310: 709–14.
Impact of UK malaria prophylaxis policy on imported malaria SIR—Recent UK media interest on adverse events attributed to the use of mefloquine led us to evaluate the benefits of mefloquine as a chemoprophylactic agent. In May, 1993, the British malaria guidelines recommended1 for the first time the use of mefloquine as an alternative to chloroquine and proguanil chemoprophylaxis for travellers to Kenya and other regions with highly chloroquine-resistant falciparum malaria. Kenya is a favoured tourist destination for which patterns of imported malaria have been monitored.2 Using malaria surveillance reports from the Malaria Reference Laboratory (MRL) of UK residents returning from Kenya, and the total number of visits by UK residents to Kenya from the international passenger survey (IRN Ltd, personal communication), we calculated quarterly malaria attack rates in tourists (figure). As a proxy of transmission intensity on the Kenyan coast where two-thirds of all visitors to Kenya spend some of their visit,3 we also examined hospital admission of 1–119-month-old patients to Kilifi district hospital with the primary diagnosis of malaria.4 Malaria admissions in Kilifi remained stable with seasonal fluctuations until the third quarter of 1994 when a large increase in admission was noted. The trends of malaria in the local population and tourists were similar between the first quarter of 1991 and the first quarter of 1993. They nearly mirror the seasonal fluctuations, suggesting malaria acquired by travellers follows local transmission. However, imported malaria incidence fell from eight to four cases per 10 000 visits between 1992 and 1994, and in 1995 there was a further fall to two cases per 10 000 visits. The introduction of the drug was not associated with any other specific measures to improve prophylaxis compliance
Vol 348 • August 3, 1996