- Email: [email protected]
Low-dose interferon-α and HIV infection
1106
bias, as a potential weakness; it was not a prospectively randomised trial and the authors admit that "selection bias can confound inferences about treatment effects". Details of other risk factors for HIV infection are not given. Cases continue to be reported in which zidovudine might have accelerated progression to AIDS.3 Moreover, Lauritsen has pointed to possible errors in early FDA evaluations of zidovudine, which were based (knowingly) on irregularities in patient recruitment and reporting of adverse reactions.’ Despite existing uncertainty about zidovudine, the data from Graham et al are sure to be a central focus for discussion at the International AIDS Symposium ("A Different View") to be held in Amsterdam on May 14-16. 1.
Duesberg PH. The role of drugs in the origin of AIDS. Biomed Pharmacother 1992; 46:
3-15. 2. Graham NMH, Zeger SL, Park LP, et al. The effects on survival of early treatment of human immunodeficiency virus infection. N Engl J Med 1992; 326: 1037-42. 3. Roos MTL, Lange JMA, de Goede REY, et al. Viral phenotype and immune response in primary human immunodeficiency virus type 1 infection. J Infect Dis 1992; 165: 427-32. 4. Lauritsen J. FDA documents show fraud in AZT trials. New York Native 1992; March 30: 20-23.
Low-dose interferon-&agr; and HIV infection About 2 years ago publicity about a report that Kemron, a low-dose oral interferon-alpha (IFN-fx) preparation, was an effective treatment for human immunodeficiency virus (HIV) infection led the World Health Organisation to point out the uncertainties of the fmdings and to design a clinical study (see Lancet 1990; 336: 935), which is still in progress. Widespread use of Kemron and other low-dose oral IFN-cx preparations by HIVinfected patients has prompted another assessment, by the AIDS Research Advisory Committee (ARAC) of the US National Institute of Allergy and Infectious Diseases (NIAID), which concludes that it cannot recommend these agents for the treatment of HIV infection. The NIAID report’ commissioned by the ARAC was limited to establishing whether there is confirmation of earlier reports, by Koech and colleagues, of the Kenyan Medical Research Institute, that Kemron raises CD4 count substantially and produces loss of HIV seropositivity. The report contains summaries of 13 studies from around the world that have been completed or are in progress. Neither of the two effects has been noted again. In the USA, Kemron (Hashibara, Kenya,$50 for a month’s supply) and Immunex (Immunil in the USA, Medikem, Kenya, $1200 for 3 months) are available through buyers’ clubs, where mixed results have been noted. The popularity of Kemron has led to the appearance of counterfeit (placebo) preparations on the market. The ARAC recommends that NIAID should encourage the completion of current trials of low-dose oral IFN-(x and should revise its report within a year, for review by the ARAC. 1. Division of AIDS, NIAID. An interim report: low dose oral interferon alpha as a therapy for human immunodeficiency infection (HIV-1); completed and ongoing trials. Available from AIDS Clinical Trials Information Service, NIAID Maryland, Bethesda, USA.
a separate research methods committee for places where much technical and complex scientific work is conducted; for other places specialists can be co-opted when
says the report, would be to have
appropriate. The author’s main recommendation is that there should be legislation to strengthen the RECs’ function and to empower them to do their duties with the support and training they need. RECs have no powers to insist that all research proposals be cleared with them, and they are not the fmal arbiters of whether the research can proceed. General practitioner trials, for instance, rarely come before RECs even though many GPs take part in phase IV studies. The author believes that if RECs can have their hand strengthened by legislation it is likely that funds will be provided for the committees to monitor the research they approve. Members were generally poorly briefed about developments relevant to research ethics; the proposal is that they be offered training sessions and circulated with relevant publications or at least the contents pages. RECs had several worries about how to obtain valid consent, among them the difficulty that patients have in understanding the principle of randomisation and other aspects of the study, or in absorbing the information (even when understood) about an element of risk. One recommendation is that information sheets be given in advance of the consent form. The report addresses a range of other issues such as legal liability and indemnification, payments to participants, and the setting up of national committees to vet multicentre trials, and it makes several recommendations as to how RECs could act as effective public watchdog and encourage good quality research, and educate the
public. 1.
Neuberger J. Ethics and health care. The role of research ethics committees in the United Kingdom. London: King’s Fund Institute. 1992. Pp 48. £7.95. ISBN 1-870607-29-5.
Medical
opposition in Minnesota
Doctors, it is often said,
are
innate conservatives who
can
be
expected to oppose any health-care reform. So, what are they criticising about the Minnesota HealthRight package (see p 1101)? The Minnesota Medical Association’s (MMA’s) first point is that because health insurance is not mandatory, those unprepared to pay their part of the premiums and the other co-payments will still remain uninsured. Moreover, the expected rise in premiums (which will occur if people take out insurance only when ill) might discourage those already insured from seeking coverage. Next, the means of funding the scheme will fall heavily on the sick, says the MMA, which calls for a broad-based revenue source. And it believes that the way to cut costs without reducing medical services is to slash administration expenses, not to create more-layers of bureaucracy. The scheme provides for four new commissions, one of which has the responsibility of advising on how to reduce rate of growth in spending by 10% per year for the first 5 years. This commission (on which there will be only 2 doctors among the 25 members) will also have to approve purchase of new technologies.
Nigerian sting Question of research ethics committees "The trial was approved by the hospital ethics committee." This statement appears in many reports of clinical trials and is taken by most readers to indicate that the subjects’ interests have been safeguarded. For these readers the King’s Fund report on ethics and health care will be an eye opener. The report, by Julia Neuberger, is based on a postal survey of members of research ethics committees (RECs) in England and Wales and on visits to 25 RECs. Rabbi Neuberger concludes that the fundamental flaw in the workings of RECs is their vagueness about what their task should be. Is part of their function the vetting of the proposed research for its scientific quality? Some believe that bad research is unethical research, but have they got the skills for assessing scientific quality? 44% of RECs had neither a pharmacist nor a pharmacologist, even though much of the research being vetted was drug related and many of the chairmen interviewed found clinical pharmacologists to be among the most useful members of the committee. The solution,
Anyone who receives a letter from a medical student at the University of Medicine, Abia State, Nigeria, requesting money to complete his or her course should beware. Such messages, it seems, have been despatched far and wide. A Ms J. E. Maduabuchi describes how through family poverty she is unable to pay her final-year examination fees and so will be unable to graduate. Her miserable story is supported by a letter from the university bursar, demanding settlement of the outstanding debt, and by an official summary of her examination performance to date. Inquiries to the provost of the university, Prof Osborne Uzoma, MB (Leeds), FRCP (London), confirm the student’s plight. Ms Maduabuchi is surely a worthy recipient of the small sum required (193). So it might seem, if a dermatologist in Leeds had not received two letters signed as the same individual but in different handwriting, and alerted The Lancet. The Nigerian embassy in London declared that there is no medical school in Abia state, the University of Leeds has no listing for 0. Uzoma, and the Royal College of Physicians has no such Fellow.
bias, as a potential weakness; it was not a prospectively randomised trial and the authors admit that "selection bias can confound inferences about treatment effects". Details of other risk factors for HIV infection are not given. Cases continue to be reported in which zidovudine might have accelerated progression to AIDS.3 Moreover, Lauritsen has pointed to possible errors in early FDA evaluations of zidovudine, which were based (knowingly) on irregularities in patient recruitment and reporting of adverse reactions.’ Despite existing uncertainty about zidovudine, the data from Graham et al are sure to be a central focus for discussion at the International AIDS Symposium ("A Different View") to be held in Amsterdam on May 14-16. 1.
Duesberg PH. The role of drugs in the origin of AIDS. Biomed Pharmacother 1992; 46:
3-15. 2. Graham NMH, Zeger SL, Park LP, et al. The effects on survival of early treatment of human immunodeficiency virus infection. N Engl J Med 1992; 326: 1037-42. 3. Roos MTL, Lange JMA, de Goede REY, et al. Viral phenotype and immune response in primary human immunodeficiency virus type 1 infection. J Infect Dis 1992; 165: 427-32. 4. Lauritsen J. FDA documents show fraud in AZT trials. New York Native 1992; March 30: 20-23.
Low-dose interferon-&agr; and HIV infection About 2 years ago publicity about a report that Kemron, a low-dose oral interferon-alpha (IFN-fx) preparation, was an effective treatment for human immunodeficiency virus (HIV) infection led the World Health Organisation to point out the uncertainties of the fmdings and to design a clinical study (see Lancet 1990; 336: 935), which is still in progress. Widespread use of Kemron and other low-dose oral IFN-cx preparations by HIVinfected patients has prompted another assessment, by the AIDS Research Advisory Committee (ARAC) of the US National Institute of Allergy and Infectious Diseases (NIAID), which concludes that it cannot recommend these agents for the treatment of HIV infection. The NIAID report’ commissioned by the ARAC was limited to establishing whether there is confirmation of earlier reports, by Koech and colleagues, of the Kenyan Medical Research Institute, that Kemron raises CD4 count substantially and produces loss of HIV seropositivity. The report contains summaries of 13 studies from around the world that have been completed or are in progress. Neither of the two effects has been noted again. In the USA, Kemron (Hashibara, Kenya,$50 for a month’s supply) and Immunex (Immunil in the USA, Medikem, Kenya, $1200 for 3 months) are available through buyers’ clubs, where mixed results have been noted. The popularity of Kemron has led to the appearance of counterfeit (placebo) preparations on the market. The ARAC recommends that NIAID should encourage the completion of current trials of low-dose oral IFN-(x and should revise its report within a year, for review by the ARAC. 1. Division of AIDS, NIAID. An interim report: low dose oral interferon alpha as a therapy for human immunodeficiency infection (HIV-1); completed and ongoing trials. Available from AIDS Clinical Trials Information Service, NIAID Maryland, Bethesda, USA.
a separate research methods committee for places where much technical and complex scientific work is conducted; for other places specialists can be co-opted when
says the report, would be to have
appropriate. The author’s main recommendation is that there should be legislation to strengthen the RECs’ function and to empower them to do their duties with the support and training they need. RECs have no powers to insist that all research proposals be cleared with them, and they are not the fmal arbiters of whether the research can proceed. General practitioner trials, for instance, rarely come before RECs even though many GPs take part in phase IV studies. The author believes that if RECs can have their hand strengthened by legislation it is likely that funds will be provided for the committees to monitor the research they approve. Members were generally poorly briefed about developments relevant to research ethics; the proposal is that they be offered training sessions and circulated with relevant publications or at least the contents pages. RECs had several worries about how to obtain valid consent, among them the difficulty that patients have in understanding the principle of randomisation and other aspects of the study, or in absorbing the information (even when understood) about an element of risk. One recommendation is that information sheets be given in advance of the consent form. The report addresses a range of other issues such as legal liability and indemnification, payments to participants, and the setting up of national committees to vet multicentre trials, and it makes several recommendations as to how RECs could act as effective public watchdog and encourage good quality research, and educate the
public. 1.
Neuberger J. Ethics and health care. The role of research ethics committees in the United Kingdom. London: King’s Fund Institute. 1992. Pp 48. £7.95. ISBN 1-870607-29-5.
Medical
opposition in Minnesota
Doctors, it is often said,
are
innate conservatives who
can
be
expected to oppose any health-care reform. So, what are they criticising about the Minnesota HealthRight package (see p 1101)? The Minnesota Medical Association’s (MMA’s) first point is that because health insurance is not mandatory, those unprepared to pay their part of the premiums and the other co-payments will still remain uninsured. Moreover, the expected rise in premiums (which will occur if people take out insurance only when ill) might discourage those already insured from seeking coverage. Next, the means of funding the scheme will fall heavily on the sick, says the MMA, which calls for a broad-based revenue source. And it believes that the way to cut costs without reducing medical services is to slash administration expenses, not to create more-layers of bureaucracy. The scheme provides for four new commissions, one of which has the responsibility of advising on how to reduce rate of growth in spending by 10% per year for the first 5 years. This commission (on which there will be only 2 doctors among the 25 members) will also have to approve purchase of new technologies.
Nigerian sting Question of research ethics committees "The trial was approved by the hospital ethics committee." This statement appears in many reports of clinical trials and is taken by most readers to indicate that the subjects’ interests have been safeguarded. For these readers the King’s Fund report on ethics and health care will be an eye opener. The report, by Julia Neuberger, is based on a postal survey of members of research ethics committees (RECs) in England and Wales and on visits to 25 RECs. Rabbi Neuberger concludes that the fundamental flaw in the workings of RECs is their vagueness about what their task should be. Is part of their function the vetting of the proposed research for its scientific quality? Some believe that bad research is unethical research, but have they got the skills for assessing scientific quality? 44% of RECs had neither a pharmacist nor a pharmacologist, even though much of the research being vetted was drug related and many of the chairmen interviewed found clinical pharmacologists to be among the most useful members of the committee. The solution,
Anyone who receives a letter from a medical student at the University of Medicine, Abia State, Nigeria, requesting money to complete his or her course should beware. Such messages, it seems, have been despatched far and wide. A Ms J. E. Maduabuchi describes how through family poverty she is unable to pay her final-year examination fees and so will be unable to graduate. Her miserable story is supported by a letter from the university bursar, demanding settlement of the outstanding debt, and by an official summary of her examination performance to date. Inquiries to the provost of the university, Prof Osborne Uzoma, MB (Leeds), FRCP (London), confirm the student’s plight. Ms Maduabuchi is surely a worthy recipient of the small sum required (193). So it might seem, if a dermatologist in Leeds had not received two letters signed as the same individual but in different handwriting, and alerted The Lancet. The Nigerian embassy in London declared that there is no medical school in Abia state, the University of Leeds has no listing for 0. Uzoma, and the Royal College of Physicians has no such Fellow.