- Email: [email protected]
Australia: Rational prescribing in general practice
1448
There
was a
small window
on
the side of the truck and
we
peered out. The road was full of holes and patients cried and started bleeding. Soon we arrived in the Chetniks’ village of Negoslavei. The cars stopped, and we heard voices, shouting "Ustashas (Croatian fascists from World War II; Serbs used to call all Croatians that name), no one will leave the village alive!"They accused us of murdering Serbs in the hospital. I sat by the door to protect the patients. Somebody from outside opened the door and asked what we were doing with Ustashas. We said neither we nor our patients were Ustashas. "Good", said a man with a white eagle insignia. "We will not dirty our hands with your blood when we slaughter you." Our vehicles were stoned and individuals were Several had attacked. patients and the smell of Pseudomonas post amputation infections, aeruginosa was nauseating. Despite these adverse circumstances, the medical service and patient survival were highly satisfactory, even excellent. Up to the last moment, we received medical supplies from outside. It was not enough, but it came-we knew the difficulties of such transport. Civilians collected medicines from their houses and brought them to the hospital. The spirit of the wounded cannot be described.
Germany: The nomifensine affair Hoechst’s antidepressant drug nomifensine (’Merital’, ’Alival’) was introduced to the German market in 1976 and marketed for almost a decade, even though it was soon
observed that it could induce severe immune reactions such ’flu-like syndrome with hepatitis, alveolitis, haemolytic anaemia, and impaired renal function. The drug was withdrawn world wide in January, 1986, after analysis of risk data by the UK Committee on Safety of Medicines and subsequent communications between the British authorities and Hoechst. The drug bulletin Arznei- Telegramm (1991; 9: 93--97) has published an account of the events and the factors involved in the failure of the German health office (BGA) and Hoechst to react adequately to the risks. The account was based on the report of investigators from the Hessen state criminal office in Frankfurt, which had been known about and discussed in the media for some time. The investigators searched Hoechst by court order in December, 1986, and confiscated reports on 612 cases of adverse events. In their evaluation of the data the investigators stated that Hoechst had received the first report on drug fever in January, 1977 and two reports of fatal hepatitis in October and December, 1977. Haemolytic anaemia was reported from the UK (3 cases) and France (1 case) in May, 1978. Deaths from haemolytic anaemia were reported from Switzerland in 1979 and from Germany in 1980. Immune-allergic lung disease (pneumonitis, alveolitis) was reported in 1978. The investigators found that, up to 1984, Hoechst failed to include information on the severity of such adverse reactions in the data sheet and to satisfy the reporting requirements of the German health authorities. Of 556 adverse events 102 were reported to the BGA after a delay of more than a year and 65 after more than 2 years. 123 were not reported at all. Hoechst were also found to have made false statements. On Aug 24, 1984, Hoechst stated in a letter to the BGA that there was no case report on haemolytic anaemia with ’Psyton’, a combination of nomifensine and clobazam, as a
although it had already received the first report of such an in December, 1982. In a sworn statement of June 13, 1985, Hoechst officials denied any knowledge of nomifensine-induced Guillain-Barré syndrome, but such a case had been reported to the US Food and Drug Administration in May, 1984. In a public statement in June, 1986, Hoechst maintained that the first fatal events were reported in March, 1985, when they had in fact received the first report in October, 1977. The investigators also expressed concern at the failure of the BGA to respond adequately to the reports of adverse events and to the strategies used by the company. The head of the department responsible "clearly misjudged the situation". He neither intervened against the concealment of information nor imposed regulatory measures to ensure event
sufficient information in the data sheet. For years he took no notice of the apparent discrepancies in the number of adverse event reports between the BGA (395 cases) and the company (556 cases). Hoechst acted similarly in relation to other national drug regulatory agencies. The Committee on Government Operations of the US House of Representatives investigated the licensing of nomifensine by the FDA and recommended legal action against Hoechst. The company was prosecuted in the district court in New Jersey for withholding from the FDA essential information on the safety of nomifensine, including fatal events. Hoechst pleaded guilty and, in April 1991, was fined the maximum penalty (US$202 000). The court in Frankfurt has now to decide on an indictment against Hoechst, since pharmaceutical companies are obliged by law to report to the BGA. The reason for delay may be the fact that German drug law does not provide an efficient legal basis for the prosecution of a pharmaceutical company; but political influences cannot be excluded. However, it should be pointed out that the inactivity of the BGA made it possible for Hoechst to continue its strategy of concealment. This strategy collapsed as soon as the British authorities took a strong stand. This appears to be the main lesson from the nomifensine case. But there are doubts that this lesson has been learnt by European or EC administrators. After the British authorities suspended licences for triazolam two months ago the Committee for Proprietary Medicinal Products reacted with window dressing on drug safety, and postponed a decision until, reportedly, Dec 11. Drug safety in the EC would be seriously threatened if decisions were to be adjusted to the lowest standards of regulatory activity in the member states. There are indications that Hoechst has learnt from the nomifensine affair by changing its management, strengthening reporting procedures, and opening up to critical judgment-at least in Germany. Furthermore, in view of this and the pending court action, any patient who suffered adverse effects from nomifensine should have a good chance of recovering damages from the company. Peter S. Schönhöfer
Australia: Rational
prescribing
in
general
practice A medical educator within the Royal Australian College of General Practitioners (RACGP) has asserted that more attention needs to be paid in graduate and undergraduate education to the principles of prescribing in general practice.
1449
Dr Nicholas Zwar is a medical educator within the College’s Family Medicine Programme (FMP), which educates graduates in the theory and practical aspects of general practice. He expressed his views in an article in Australian Prescriber (1991; 14: 75-78). Chief among the points he makes is that up to 70% of GP consultations result in a prescription, yet "scant attention is paid to principles of prescribing in medical education". Dr Zwar contends that prescribing behaviour among doctors needs to be rationalised, because it varies widely and depends on non-medical as well as medical factors. He implies that better communication skills, improvement of compliance, and the critical appraisal of drug information could alter general prescribing habits for the better. Dr Zwar suggests several non-medical factors that need to be considered more carefully by medical educators. They include the age and sex of the doctor; the level of doctors’ communication skills; their knowledge of and confidence in
in full accord with Dr Kessler on new drug rules. approval That was made clear at a press conference on Nov 13 where Mr Quayle, Dr Kessler, and Health Secretary Louis Sullivan unanimously agreed that the new rules should halve approval time. Whatever else may be said about these rules, they constitute a drastic change from the often cumbersome and drawn-out procedures of past decades. As one example, drugs that are supposedly easily and routinely reviewed-anti-allergy drugs, analgesics, antiinflammatory drugs, and antibiotics-would henceforth be consigned for review and approval to private contractors. The logic is that this would free FDA reviewers to focus on drugs for serious illnesses such as cancer and AIDS. Gay rights groups, impatient with FDA delays, support these changes. Within the Weiss subcommittee, the belief is that the assignment of some drugs to perfunctory review contradicts the FDA doctrine that there is no such thing as a
non-drug therapies; their perception of patient expectations of a prescription; and the use of a prescription to end a
risk-free drug. Another Quayle report
consultation.
Drugs most often prescribed, according to Dr Zwar, antibiotics, antihypertensives, respiratory drugs, psychotropics, NSAIDS, and analgesics. He highlights the potential and relative danger for the elderly in "irrational" prescribing, citing compliance and altered pharmacokinetics and pharmacodynamics as factors that must attract more attention in education and in practice. The critical appraisal of efficacy claims made for drugs is crucial in Dr Zwar’s scheme of things. He bravely suggests that questions should be asked about the qualifications of the researchers who make the claims; and that the information itself should be up to date, referenced, and not based only on restricted clinical experience. Dr Zwar also makes the very practical observation that the outcomes and subjects of clinical trials, to be of real value, should be readily identifiable in the reader’s own empirical experience. Dr Zwar agrees that this rational approach to prescribing should be taught to undergraduates as early as practicable in their course. Furthermore, he does not disallow that general practitioners who act as tutors for FMP trainees may themselves need to be tutored in this process. To this end, are
the FMP has invited Prof David Sackett of McMaster University in Canada to address seminars on the critical appraisal of published and other drug information. Peter
himself
as
provision says that the US "will place high priority on achieving harmonization that will enable the US to recognize foreign approval of drugs". The idea of a drug being sold here as safe because a foreign government says it is has furrowed some brows at the Weiss subcommittee. "The corollary to this is: We don’t need FDA", a subcommittee source told me last week. Peter Barton Hutt, a former chief counsel at FDA, on the other hand, thought it could take as long as a decade to draw up reciprocal agreements to implement this provision. According to Sidney Wolfe, director of the activist Public Citizen Health Research Group, the new plan also cuts FDA out of the loop in testing dangerous drugs. Currently, the FDA reviews animal studies for safety before the drugs are tested in man. Now, he says, this authority is to be given to a private reviewing board financed by a drug company. The consequences, he says, could be "devastating". The FDA can put most of the new drug procedure changes into effect without legislation, but Congress probably won’t leave it at that. Relations between the Weiss subcommittee and the FDA have become so strained that Mr Weiss’s staff have had to threaten the agency with a subpoena to obtain the documents used in the negotiations with Mr Quayle’s council.
J. B. Sibbison
Harrigan
Medicine and the Law USA: Short cuts to drug approval Congressional investigators are seeking to determine whether Vice President Dan Quayle improperly interfered with the decision-making process at the Food and Drug Administration. A subcommittee headed by Representative Ted Weiss of New York believes Mr Quayle may have required FDA Commissioner David A. Kessler to make his new plan to accelerate the prescription drug approval process more acceptable to the pharmaceutical industry. As chairman of the President’s Council on Competitiveness, Mr Quayle readily acknowledges that he asks for rule changes on industry’s behalf at the FDA and other regulatory agencies (Lancet July 27, p 240) but pictures
IVF
legislation: error causes confidentiality
trap Few Acts of Parliament have been preceded by greater debate than the Human Fertilisation and Embryology Act 1990. Passed six years after the Government-commissioned Warnock report was published1 the Act was generally regarded as providing a reasonable, workable compromise. The main subject matter of this Act was the creation of embryos by in-vitro fertilisation (IVF), and, understandably, concern focused on the morality of IVF and of research on human embryos and on matters such as the disposal of embryos. There was also a furious tug-of-war on the abortion provisions which were, at a late stage,
There
was a
small window
on
the side of the truck and
we
peered out. The road was full of holes and patients cried and started bleeding. Soon we arrived in the Chetniks’ village of Negoslavei. The cars stopped, and we heard voices, shouting "Ustashas (Croatian fascists from World War II; Serbs used to call all Croatians that name), no one will leave the village alive!"They accused us of murdering Serbs in the hospital. I sat by the door to protect the patients. Somebody from outside opened the door and asked what we were doing with Ustashas. We said neither we nor our patients were Ustashas. "Good", said a man with a white eagle insignia. "We will not dirty our hands with your blood when we slaughter you." Our vehicles were stoned and individuals were Several had attacked. patients and the smell of Pseudomonas post amputation infections, aeruginosa was nauseating. Despite these adverse circumstances, the medical service and patient survival were highly satisfactory, even excellent. Up to the last moment, we received medical supplies from outside. It was not enough, but it came-we knew the difficulties of such transport. Civilians collected medicines from their houses and brought them to the hospital. The spirit of the wounded cannot be described.
Germany: The nomifensine affair Hoechst’s antidepressant drug nomifensine (’Merital’, ’Alival’) was introduced to the German market in 1976 and marketed for almost a decade, even though it was soon
observed that it could induce severe immune reactions such ’flu-like syndrome with hepatitis, alveolitis, haemolytic anaemia, and impaired renal function. The drug was withdrawn world wide in January, 1986, after analysis of risk data by the UK Committee on Safety of Medicines and subsequent communications between the British authorities and Hoechst. The drug bulletin Arznei- Telegramm (1991; 9: 93--97) has published an account of the events and the factors involved in the failure of the German health office (BGA) and Hoechst to react adequately to the risks. The account was based on the report of investigators from the Hessen state criminal office in Frankfurt, which had been known about and discussed in the media for some time. The investigators searched Hoechst by court order in December, 1986, and confiscated reports on 612 cases of adverse events. In their evaluation of the data the investigators stated that Hoechst had received the first report on drug fever in January, 1977 and two reports of fatal hepatitis in October and December, 1977. Haemolytic anaemia was reported from the UK (3 cases) and France (1 case) in May, 1978. Deaths from haemolytic anaemia were reported from Switzerland in 1979 and from Germany in 1980. Immune-allergic lung disease (pneumonitis, alveolitis) was reported in 1978. The investigators found that, up to 1984, Hoechst failed to include information on the severity of such adverse reactions in the data sheet and to satisfy the reporting requirements of the German health authorities. Of 556 adverse events 102 were reported to the BGA after a delay of more than a year and 65 after more than 2 years. 123 were not reported at all. Hoechst were also found to have made false statements. On Aug 24, 1984, Hoechst stated in a letter to the BGA that there was no case report on haemolytic anaemia with ’Psyton’, a combination of nomifensine and clobazam, as a
although it had already received the first report of such an in December, 1982. In a sworn statement of June 13, 1985, Hoechst officials denied any knowledge of nomifensine-induced Guillain-Barré syndrome, but such a case had been reported to the US Food and Drug Administration in May, 1984. In a public statement in June, 1986, Hoechst maintained that the first fatal events were reported in March, 1985, when they had in fact received the first report in October, 1977. The investigators also expressed concern at the failure of the BGA to respond adequately to the reports of adverse events and to the strategies used by the company. The head of the department responsible "clearly misjudged the situation". He neither intervened against the concealment of information nor imposed regulatory measures to ensure event
sufficient information in the data sheet. For years he took no notice of the apparent discrepancies in the number of adverse event reports between the BGA (395 cases) and the company (556 cases). Hoechst acted similarly in relation to other national drug regulatory agencies. The Committee on Government Operations of the US House of Representatives investigated the licensing of nomifensine by the FDA and recommended legal action against Hoechst. The company was prosecuted in the district court in New Jersey for withholding from the FDA essential information on the safety of nomifensine, including fatal events. Hoechst pleaded guilty and, in April 1991, was fined the maximum penalty (US$202 000). The court in Frankfurt has now to decide on an indictment against Hoechst, since pharmaceutical companies are obliged by law to report to the BGA. The reason for delay may be the fact that German drug law does not provide an efficient legal basis for the prosecution of a pharmaceutical company; but political influences cannot be excluded. However, it should be pointed out that the inactivity of the BGA made it possible for Hoechst to continue its strategy of concealment. This strategy collapsed as soon as the British authorities took a strong stand. This appears to be the main lesson from the nomifensine case. But there are doubts that this lesson has been learnt by European or EC administrators. After the British authorities suspended licences for triazolam two months ago the Committee for Proprietary Medicinal Products reacted with window dressing on drug safety, and postponed a decision until, reportedly, Dec 11. Drug safety in the EC would be seriously threatened if decisions were to be adjusted to the lowest standards of regulatory activity in the member states. There are indications that Hoechst has learnt from the nomifensine affair by changing its management, strengthening reporting procedures, and opening up to critical judgment-at least in Germany. Furthermore, in view of this and the pending court action, any patient who suffered adverse effects from nomifensine should have a good chance of recovering damages from the company. Peter S. Schönhöfer
Australia: Rational
prescribing
in
general
practice A medical educator within the Royal Australian College of General Practitioners (RACGP) has asserted that more attention needs to be paid in graduate and undergraduate education to the principles of prescribing in general practice.
1449
Dr Nicholas Zwar is a medical educator within the College’s Family Medicine Programme (FMP), which educates graduates in the theory and practical aspects of general practice. He expressed his views in an article in Australian Prescriber (1991; 14: 75-78). Chief among the points he makes is that up to 70% of GP consultations result in a prescription, yet "scant attention is paid to principles of prescribing in medical education". Dr Zwar contends that prescribing behaviour among doctors needs to be rationalised, because it varies widely and depends on non-medical as well as medical factors. He implies that better communication skills, improvement of compliance, and the critical appraisal of drug information could alter general prescribing habits for the better. Dr Zwar suggests several non-medical factors that need to be considered more carefully by medical educators. They include the age and sex of the doctor; the level of doctors’ communication skills; their knowledge of and confidence in
in full accord with Dr Kessler on new drug rules. approval That was made clear at a press conference on Nov 13 where Mr Quayle, Dr Kessler, and Health Secretary Louis Sullivan unanimously agreed that the new rules should halve approval time. Whatever else may be said about these rules, they constitute a drastic change from the often cumbersome and drawn-out procedures of past decades. As one example, drugs that are supposedly easily and routinely reviewed-anti-allergy drugs, analgesics, antiinflammatory drugs, and antibiotics-would henceforth be consigned for review and approval to private contractors. The logic is that this would free FDA reviewers to focus on drugs for serious illnesses such as cancer and AIDS. Gay rights groups, impatient with FDA delays, support these changes. Within the Weiss subcommittee, the belief is that the assignment of some drugs to perfunctory review contradicts the FDA doctrine that there is no such thing as a
non-drug therapies; their perception of patient expectations of a prescription; and the use of a prescription to end a
risk-free drug. Another Quayle report
consultation.
Drugs most often prescribed, according to Dr Zwar, antibiotics, antihypertensives, respiratory drugs, psychotropics, NSAIDS, and analgesics. He highlights the potential and relative danger for the elderly in "irrational" prescribing, citing compliance and altered pharmacokinetics and pharmacodynamics as factors that must attract more attention in education and in practice. The critical appraisal of efficacy claims made for drugs is crucial in Dr Zwar’s scheme of things. He bravely suggests that questions should be asked about the qualifications of the researchers who make the claims; and that the information itself should be up to date, referenced, and not based only on restricted clinical experience. Dr Zwar also makes the very practical observation that the outcomes and subjects of clinical trials, to be of real value, should be readily identifiable in the reader’s own empirical experience. Dr Zwar agrees that this rational approach to prescribing should be taught to undergraduates as early as practicable in their course. Furthermore, he does not disallow that general practitioners who act as tutors for FMP trainees may themselves need to be tutored in this process. To this end, are
the FMP has invited Prof David Sackett of McMaster University in Canada to address seminars on the critical appraisal of published and other drug information. Peter
himself
as
provision says that the US "will place high priority on achieving harmonization that will enable the US to recognize foreign approval of drugs". The idea of a drug being sold here as safe because a foreign government says it is has furrowed some brows at the Weiss subcommittee. "The corollary to this is: We don’t need FDA", a subcommittee source told me last week. Peter Barton Hutt, a former chief counsel at FDA, on the other hand, thought it could take as long as a decade to draw up reciprocal agreements to implement this provision. According to Sidney Wolfe, director of the activist Public Citizen Health Research Group, the new plan also cuts FDA out of the loop in testing dangerous drugs. Currently, the FDA reviews animal studies for safety before the drugs are tested in man. Now, he says, this authority is to be given to a private reviewing board financed by a drug company. The consequences, he says, could be "devastating". The FDA can put most of the new drug procedure changes into effect without legislation, but Congress probably won’t leave it at that. Relations between the Weiss subcommittee and the FDA have become so strained that Mr Weiss’s staff have had to threaten the agency with a subpoena to obtain the documents used in the negotiations with Mr Quayle’s council.
J. B. Sibbison
Harrigan
Medicine and the Law USA: Short cuts to drug approval Congressional investigators are seeking to determine whether Vice President Dan Quayle improperly interfered with the decision-making process at the Food and Drug Administration. A subcommittee headed by Representative Ted Weiss of New York believes Mr Quayle may have required FDA Commissioner David A. Kessler to make his new plan to accelerate the prescription drug approval process more acceptable to the pharmaceutical industry. As chairman of the President’s Council on Competitiveness, Mr Quayle readily acknowledges that he asks for rule changes on industry’s behalf at the FDA and other regulatory agencies (Lancet July 27, p 240) but pictures
IVF
legislation: error causes confidentiality
trap Few Acts of Parliament have been preceded by greater debate than the Human Fertilisation and Embryology Act 1990. Passed six years after the Government-commissioned Warnock report was published1 the Act was generally regarded as providing a reasonable, workable compromise. The main subject matter of this Act was the creation of embryos by in-vitro fertilisation (IVF), and, understandably, concern focused on the morality of IVF and of research on human embryos and on matters such as the disposal of embryos. There was also a furious tug-of-war on the abortion provisions which were, at a late stage,