- Email: [email protected]
Ethics committees
Ethics committees
money, that
S:R—Robbins (March 11, p 653) makes a plea on behalf of hard-pressed clinicians who wish to participate in trials. As chairman, I reply on behalf of our local research ethics committee. We are well aware of the difficulties faced by investigators who require approval from committees up and down the country. If a trial has been passed elsewhere, we have to assess whether it is suitable to be carried out in our area, which it
might
not
be if the
resources
of
our
National
Health Service trust are inadequate, usually because we do not have suitably qualified staff to ensure that the patients are
managed adequately.
A second issue is whether the investigators have provided information that enables patients to understand the nature of the trial, and this may need an interpreter and for questionnaires to be written in ethnic minority languages. I suggest that the requirements for the Bradford area, with its high proportion of residents of Asian origin, are rather different from those of Guildford, with its mainly European
population. We receive vast amounts of information with respect to the statistical analysis of studies, especially from drug companies, but we do not particularly need to see this provided it has been passed elsewhere. My plea in this regard has fallen on deaf ears. We would be happy to adopt a system in which a study is approved by a lead local committee and we merely confine ourselves to considering local factors. I do not find it bizarre that a trial should be accepted in one district but not in another; this merely reflects local differences of opinion, resources, and social and medical issues.
means about C1400 per event prevented, if bendrofluazide is used. The temptation is to extend the results of the trial to other agents; with ACE inhibitors, if the efficacy is similar, the cost will now be 100000 per event saved. In the 35 days after myocardial infarction, aspirin 160 milligrams daily prevented death in 1 patient out of every 42 patients treated.3We estimate that each life was saved at a cost of [185 (and with non-proprietary aspirin the cost would be 7.50). From the results of the 4S study, ’ it would cost L60 500 per life saved to use simvastatin in patients who have sustained myocardial infarction or suffered from angina; the survival difference between groups was 36% over 70 months, equivalent to treating 162 patients for a year to prevent one death. Many doctors argue privately that cost should not determine whether treatments are used, provided that the treatment is proven to work. Others assume that if a strategy for treatment works in a group at high risk, it will also work effectively in a group at low risk. Neither view should pass without debate, because huge differences in cost can be masked by apparently similar trial results. Unless there is an increase in overall health expenditure, choice of an expensive treatment will inevitably mean that high spending in one domain will limit spending in another.
*R E
NHS Trust, Birmingham B18 7QH, UK; and University Department of Public Health and Primary Care, Radcliffe Infirmary, Oxford
1
Anonymous. Streptokinase plus aspirin does the trick: ISIS 3. Lancet
2
MRC Working Party. MRC trial of mild hypertension. BMJ 1985; 291: 97-104. ISIS-2 Collaborative Study Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction. Lancet 1988; ii: 349-60. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-89.
1992; 339: 780-81.
P G R Godwin Airedale General
Hospital, Steeton, Keighley, West Yorkshire BD20 6TD, UK
SiR-Robbins proposes that multicentre trials should be assessed by one national ethics committee rather than many local ones. As chairman of a busy regional ethics committee I would subscribe to his view, were there not EC guidelines for good clinical practice. These guidelines require not only that the responsible committee checks if staffing and patient supply at the centre are appropriate for the study but also that the local investigators’ qualifications and equipment are adequate to fulfil the requirements of the study; this cannot be done from a long distance. If we were only required to check all ethical aspects of the protocol and the local authorities local feasibility, a single committee vote would be sufficient. Karl H Kimbel North-Rhine Chamber of
Physicians, Tersteegenstrasse 31,
Dusseldorf 40474,
Germany
A suitable
case
for treatment
decisions are made easier by good trial data that show a treatment to be effective for the primary condition, and easier still if the trial measures overall health benefit. The ISIS and GISSI studies in myocardial infarction have amply demonstrated how large trials can help us decide how to treat patients, even if they leave some questions unresolved.’ They do not, however, tell us directly whether we should be committing resources to one form of treatment rather than another. Simple calculations show the enormous differences in cost among treatment strategies. The Medical Research Council’s trial of primary preventive treatment in mild hypertension showed that 800 patients would have to be treated for 1 year to prevent one event.2 Translated into
SiR-Therapeutic
Ferner, H A W Neil
*City Hospital
3
4
HIV-1
subtype C in China
SIR-The presence of several subtypes of HIV-1 with small variation within each subtype in several areas of Asia suggests recent multiple introductions of different HIV subtypes. Until 1994, all characterised HIV-1 isolates from Yunnan province, China, were classified as subtype B.’ In late 1994, serum samples from 5 women who had returned from commercial sex work in Thailand were reported as serologically relative to a subtype E peptide.2 We report identification and characterisation of subtype C HIV in China. 31 serum samples were randomly selected from male intravenous drug users who were HIV-1 seropositive in a general survey during 1992-93 in Longchuan and Ruili counties of Yunnan province. Viral RNA was extracted, reverse-transcribed into HIV-1 cDNA, and subjected to nested PCR. Amplified DNA was obtained from 11 of the 31 serum samples and sequenced directly. Based on the phylogenetic tree constructed by the neighbour-joining method, the 11 HIV-1 sequences clustered into two distinct subtypes (figure). 4 isolates grouped with the Thailand variant (Thai-B), which is genetically distinct from subtype B strains commonly found in America and Europe.3 The remaining 7 were subtype C strains and were only 4-5% divergent from subtype C strains found in India (D747, D757, and D760).’ All 31 serum samples were also tested by peptide-binding enzyme immunoassay based on subtype-specific peptides. After exclusion of those that could not be typed, the 1051
money, that
S:R—Robbins (March 11, p 653) makes a plea on behalf of hard-pressed clinicians who wish to participate in trials. As chairman, I reply on behalf of our local research ethics committee. We are well aware of the difficulties faced by investigators who require approval from committees up and down the country. If a trial has been passed elsewhere, we have to assess whether it is suitable to be carried out in our area, which it
might
not
be if the
resources
of
our
National
Health Service trust are inadequate, usually because we do not have suitably qualified staff to ensure that the patients are
managed adequately.
A second issue is whether the investigators have provided information that enables patients to understand the nature of the trial, and this may need an interpreter and for questionnaires to be written in ethnic minority languages. I suggest that the requirements for the Bradford area, with its high proportion of residents of Asian origin, are rather different from those of Guildford, with its mainly European
population. We receive vast amounts of information with respect to the statistical analysis of studies, especially from drug companies, but we do not particularly need to see this provided it has been passed elsewhere. My plea in this regard has fallen on deaf ears. We would be happy to adopt a system in which a study is approved by a lead local committee and we merely confine ourselves to considering local factors. I do not find it bizarre that a trial should be accepted in one district but not in another; this merely reflects local differences of opinion, resources, and social and medical issues.
means about C1400 per event prevented, if bendrofluazide is used. The temptation is to extend the results of the trial to other agents; with ACE inhibitors, if the efficacy is similar, the cost will now be 100000 per event saved. In the 35 days after myocardial infarction, aspirin 160 milligrams daily prevented death in 1 patient out of every 42 patients treated.3We estimate that each life was saved at a cost of [185 (and with non-proprietary aspirin the cost would be 7.50). From the results of the 4S study, ’ it would cost L60 500 per life saved to use simvastatin in patients who have sustained myocardial infarction or suffered from angina; the survival difference between groups was 36% over 70 months, equivalent to treating 162 patients for a year to prevent one death. Many doctors argue privately that cost should not determine whether treatments are used, provided that the treatment is proven to work. Others assume that if a strategy for treatment works in a group at high risk, it will also work effectively in a group at low risk. Neither view should pass without debate, because huge differences in cost can be masked by apparently similar trial results. Unless there is an increase in overall health expenditure, choice of an expensive treatment will inevitably mean that high spending in one domain will limit spending in another.
*R E
NHS Trust, Birmingham B18 7QH, UK; and University Department of Public Health and Primary Care, Radcliffe Infirmary, Oxford
1
Anonymous. Streptokinase plus aspirin does the trick: ISIS 3. Lancet
2
MRC Working Party. MRC trial of mild hypertension. BMJ 1985; 291: 97-104. ISIS-2 Collaborative Study Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction. Lancet 1988; ii: 349-60. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-89.
1992; 339: 780-81.
P G R Godwin Airedale General
Hospital, Steeton, Keighley, West Yorkshire BD20 6TD, UK
SiR-Robbins proposes that multicentre trials should be assessed by one national ethics committee rather than many local ones. As chairman of a busy regional ethics committee I would subscribe to his view, were there not EC guidelines for good clinical practice. These guidelines require not only that the responsible committee checks if staffing and patient supply at the centre are appropriate for the study but also that the local investigators’ qualifications and equipment are adequate to fulfil the requirements of the study; this cannot be done from a long distance. If we were only required to check all ethical aspects of the protocol and the local authorities local feasibility, a single committee vote would be sufficient. Karl H Kimbel North-Rhine Chamber of
Physicians, Tersteegenstrasse 31,
Dusseldorf 40474,
Germany
A suitable
case
for treatment
decisions are made easier by good trial data that show a treatment to be effective for the primary condition, and easier still if the trial measures overall health benefit. The ISIS and GISSI studies in myocardial infarction have amply demonstrated how large trials can help us decide how to treat patients, even if they leave some questions unresolved.’ They do not, however, tell us directly whether we should be committing resources to one form of treatment rather than another. Simple calculations show the enormous differences in cost among treatment strategies. The Medical Research Council’s trial of primary preventive treatment in mild hypertension showed that 800 patients would have to be treated for 1 year to prevent one event.2 Translated into
SiR-Therapeutic
Ferner, H A W Neil
*City Hospital
3
4
HIV-1
subtype C in China
SIR-The presence of several subtypes of HIV-1 with small variation within each subtype in several areas of Asia suggests recent multiple introductions of different HIV subtypes. Until 1994, all characterised HIV-1 isolates from Yunnan province, China, were classified as subtype B.’ In late 1994, serum samples from 5 women who had returned from commercial sex work in Thailand were reported as serologically relative to a subtype E peptide.2 We report identification and characterisation of subtype C HIV in China. 31 serum samples were randomly selected from male intravenous drug users who were HIV-1 seropositive in a general survey during 1992-93 in Longchuan and Ruili counties of Yunnan province. Viral RNA was extracted, reverse-transcribed into HIV-1 cDNA, and subjected to nested PCR. Amplified DNA was obtained from 11 of the 31 serum samples and sequenced directly. Based on the phylogenetic tree constructed by the neighbour-joining method, the 11 HIV-1 sequences clustered into two distinct subtypes (figure). 4 isolates grouped with the Thailand variant (Thai-B), which is genetically distinct from subtype B strains commonly found in America and Europe.3 The remaining 7 were subtype C strains and were only 4-5% divergent from subtype C strains found in India (D747, D757, and D760).’ All 31 serum samples were also tested by peptide-binding enzyme immunoassay based on subtype-specific peptides. After exclusion of those that could not be typed, the 1051