- Email: [email protected]
Improving drug safety
1333
Medicine and the Law Automatism and disorder
post-traumatic stress
The categories of automatism are not closed. The latest addition is post-traumatic stress disorder. When an accused person can be shown to have committed an offence without the evil intent, he or she may be acquitted, unless there is strict liability (eg, a motoring offence). Whether a defence of automatism ("non-insane" or "insane") is put to the jury is a matter for the judge alone. "Non-insane" automatism is the preferred defence since "insane automatism" automatically results in a verdict of "not guilty by reason of insanity" and detention in a special hospital for an indeterminate period. An important issue is whether the stimulus that creates the state of automatism emanates from within the mind of the defendant ("insane") or by way of an outside event ("sane"). Insanity here is not synonymous with a medical diagnosis of insanity. Loss of cognitive control and reason caused by, say, epilepsy or diabetes, will, even if shortlived, be regarded in law as indicating "insanity". Many defendants, faced with the choice of this plea or a guilty plea and mitigation will opt for the latter.1 Non-insane automatism offers a complete defence without the stigma of insanity. Most commonly there is an outside stimulus, such as a blow on the head or adverse reaction to a prescribed drug; incapacity due to alcohol or unlawful drugs does not count. Dr Peter Fenwick argues that the legal distinctions between sane and insane automatism are "nonsensical" and "medically unsatisfactory" and invites doctors and pressure groups to seek to influence Parliament to change the law or to petition the Law Reform Committee.2 Insanity for legal purposes (to avoid the consequences of an unlawful act), as Fenwick points out, is not synonymous with a medical diagnosis of insanity. Loss of cognitive control and reason due to, say, epilepsy or diabetes, will be regarded in law as "insane". In a case heard at Snaresbrook Crown Court on Feb 7, 1989,3the defendant, a 23-year-old Frenchwoman, was charged with robbery and causing bodily harm. The judge allowed the defence of non-insane automatism to go before the jury because a psychiatrist who had examined the woman in prison said that at the time of the alleged offences she had post-traumatic stress disorder caused by rape 3 days earlier. The prosecution alleged that the woman had, with two others also charged, robbed two women of their handbags while armed with knives. The charge of bodily harm stemmed from the second act of a complex incident (these were two attempts at robbery), during which the defendant approached a woman standing beside a car. When asked what she was doing the defendant stabbed her in the stomach with a penknife and demanded the handbag of another woman sitting in the car. The assailants ran off and the victims drove away. All three assailants were later arrested, the defendant
being detained while standing at the side of the road. remember all the
events.
7
days later she
was
examined
by
a
doctor at Holloway Prison who found that her hymen was ruptured and bleeding and that there were injuries to the posterior of the hymen. (Some months earlier the hymen had been reconstructed to restore the woman’s
virginal status.) The woman complained that 3 her arrest she had been raped but she had not told anyone about it. She was then examined three times by a psychiatrist, who diagnosed post-traumatic stress disorder and gave the opinion that at the time of the offences she had been in a dissociative state and had not been acting consciously. days before
Diana Brahams
1. Brahams D. Epilepsy is mental illness. Lancet 1983; ii: 116. 2. Fenwick P. Automatism and the law. Psychol Med (monogr supply no 17) 1990: 23. 3. R v T. [1990] Crim LR 256. 4. R v Quick [1973] QB 910. 5. R v Hennessy. [1989] 1 WLR 287 at 294; see also Brahams D. Hyperglycaemia and plea of automatism. Lancet 1989; i: 912. Compare Canadian cases of R v Rabey, per Martin J, 79 DLR 435 (Ontario Court of Appeal) Broom v Perkins (1987) 85 Crim App R 321, and R v Issit [1977] RTR 211.
Conference Improving drug safety The conference
on Improving Drug Safety, held at Wolfsberg, Switzerland, from April 17 to 20, was the second major event of the so-called RAD-AR initiative (Risk/ Benefit Assessment of Drugs-Analysis and Response). Founded in 1988 by Ciba Geigy, RAD-AR is still supported mainly by its initiators, but other companies now join in. RAD-AR might evolve into the industry’s most important effort in improving drug safety. The gathering was attended by representatives from industry, regulatory agencies, academia, the media, and consumer organisations from most Western countries and from Japan. The aim of the conference was to review existing means of analysis, assessment, and communication of drug risks and to generate new ideas on these subjects.
The first part of the conference centred on ethical on improving drug safety. Medical decisions not only derive from risk/benefit estimation but include considerations of the patient’s autonomy and the fair use of resources. A speaker from a pharmaceutical company pointed out that the principle "good ethics equals good business" is not yet standard within the industry. One day was dedicated to the generation and assessment of reliable information about drug risks and benefits. Of the various means of generating information on adverse drug reactions, spontaneous reporting is still the cheapest and perhaps the best. However, no scientifically sound conclusions can be based on spontaneous reports only.
perspectives
On the night of her arrest the woman was described as passive and "indifferent to what was happening". At a later interview she could not
At trial, before Soudian,7, the defence submitted that a defence of non-insane automatism was not limited to cases where a blow had caused concussion or where insulin or an anaesthetic had been given or where there had been sleep walking.’ Rape was an extraordinary event with features not likely to recur-unlike normal stress, anxiety, or depression caused by external factors, which were likely to recur and which could not therefore, in law, be accepted as automatism. The prosecution contended that the defendant had some recollection of what had happened and that the opening of a penknife blade required a controlled, positive action on her part. The only defence, therefore, was insane automatism. The judge said that there had been no previous case in which rape had been held to be an external factor causing a malfunctioning of the mind within the definition laid down in R v Quick.’ If what the defendant had said about the rape were true the incident could have an appalling effect on her, however well balanced she usually was. A condition of post-traumatic stress involving a normal person in an act of violence was not itself a disease of the mind, even if there were a delay before the dissociation manifested itself. If the medical evidence were correct this case was distinguishable from those where there was only a partial loss of control.5 The jury failed to agree. At re-trial the defendant was convicted (on a majority verdict) but her sentence was lighter than it might otherwise have been.
1334
Additional efforts should be channelled towards early recognition of rare, unpredictable (type B) reactions. In the assessment of the risk/benefit ratio, simple tests for quality of life would help to give a more meaningful definition of benefit. Participants agreed that "above all, do no harm" can no longer be interpreted in a simplistic way, since no medical intervention is without risk. Communication about drug safety was another theme. As one speaker expressed it, the industry does a good job in producing the hardware (the drugs) but fails in providing adequate software (drug information). Informational needs of patients and doctors must be better analysed and satisifed. More varied methods, such as patient help groups and telephone access to pharmaceutical companies’ information services, might be used. Mass media could provide excellent help if unbiased, easy-to-read information were available. However, the most important exchange of information takes place when doctors discuss treatments with their patients. The specific needs of individual doctors were given scant attention at the conference. Developing countries were also largely ignored. One thing became very clear: the collection and transmission of information on adverse drug reactions vary widely between countries and need to be standardised. It is high time the industry recognised adverse drug reactions as legitimate offspring of its products. Brainstorming should now be followed by tangible changes in the industry’s attitudes. If this happens, the three days at Wolfsberg were time well spent. Etzel
Gysling
Noticeboard Breast
cancer
and oral
contraceptives
The Institute of Medicine (IOM) is the arm of the US National Academy of Sciences that focuses on the development of public policy in health issues. On May 3 and 4, a conference held at the Arnold and Mabel Beckman Center in Irvine, California, on the relation between oral contraceptives and breast cancer was one step in the IOM’s twelve-month study of this subject. The study will review policy options, suggest future research, and make recommendations for doctors. (A report on the Irvine meeting and the IOM Committee findings will be published in 1991.) The confusing epidemiological data on breast cancer and oral contraceptive use have been widely reviewed, but the strength of the IOM gathering was the interdisciplinary nature of the participants-specialists in tissue culture, biological markers for breast cancer, biochemistry, endocrinology, and epidemiology forgathered. Their collective opinion was that oral contraceptives, if they have any effect at all, are more likely to accelerate or retard the growth of an existing cancer than to initiate malignant change. An interpretation of the existing epidemiological data is that there is a small rise in relative risk among some subgroups, perhaps with a possible reduction in relative risk in others. Nevertheless, the most important factor in modelling any putative effect is likely to be the duration of any adverse or beneficial effect after oral contraceptive use has ceased. Breast cancer has become more common in every decade of the twentieth century-American women today have a one in ten chance of getting the disease and a one in eighteen chance of dying from it. Although the overwhelming majority of women who now have breast cancer were too old to have taken oral contraceptives, the relation between these agents and breast cancer warrants continued study, both as an important clinical question per se and for any light such investigations might throw on the aetiology of breast cancer. However, such studies are likely to be large, expensive, and long term. From this perspective, the Royal College of General Practitioners cohort study is immensely important. This
study may be the only one in our generation that could eventually the subtle but key question: For how long do any effects of oral contraceptives on ovarian, endometrial, and possibly breast cancer persist after taking the last pill? The Medical Research Council will no longer fund the RCGP Study, but support has been secured from the pharmaceutical industry and from other sources for a further three years of data collection followed by two of data analysis. answer
Breastfeeding and fertility Breastfeeding
not
only contributes
to
lower
fertility but also
increases the birth interval, and in many developing countries more women are protected from pregnancy by breastfeeding than by all other contraceptive methods combined. Gray and colleagues1 have
recently supported the consensus statement that breastfeeding provides more than 98% protection from pregnancy in the first six months post partum.2 The maximum birth spacing effect, said the statement, is achieved when a mother fully or nearly fully breastfeeds and remains amenorrhoeic (bleeding before the 56th post-partum day being ignored). Why, then, has breastfeeding often not been promoted for its contraceptive effect in projects aimed at limiting fertility? Three assumptions that may have obstructed the promotion of breastfeeding in such projects have now been challenged in a World Bank report.3 First, promotive efforts might be regarded as unnecessary in countries where breastfeeding is still the usual form of contraception. But, say Berg and Brems,3promotion should centre on the type of breastfeeding practices used, since the contraceptive effect is related to duration of breastfeeding, frequency and duration of suckling, administration of supplements to the infant, nutritional status of the mother, and geographic, social, and cultural factors. They also emphasise the importance of a supportive environment for the woman: environmental pressures, such as negative influences in the mass media and migration that removes women from traditional support networks, weaken breastfeeding practices. Secondly, a decline in breastfeeding is often assumed to be an inevitable part of "modernisation" and to have negligible demographic impact if there is a corresponding increase in the use of "modem" contraceptives. Berg and Brems cite the recent reversal of declines in breastfeeding in industrialised countries, such as the US, Scandinavia, Australia, and Eastern Europe, as evidence to refute this notion. They emphasise that the types of decline are important: for example, whereas some shortening of the duration of exclusive breastfeeding may be acceptable or even recommended in view of the increased nutritional needs of the growing infant, a fall in the prevalence of breastfeeding or a dramatic reduction in duration can lead to loss of contraceptive protection and greater demands on family planning services than can be met, and health and nutrition of the infant may then be at risk. Berg and Brems suggest that promotion of breastfeeding practices is essential, since modem contraception is neither universally available nor widely used, perhaps for religious or cultural reasons; for these women breastfeeding promotion can help to reduce the risk of pregnancy. Last, that breastfeeding is not regarded as a completely reliable contraceptive for the individual woman after the first few months post partum is not the same, say Berg and Brems, as concluding that breastfeeding has no part in population programmes. Family planning services, they suggest, could work to reduce barriers to breastfeeding, especially where modem contraceptives are unavailable or unacceptable. The financial costs of infant feeding have to be taken into account in assessment of the benefits of breastfeeding. Despite the increased nutritional needs of a lactating woman, it is cheaper, say Berg and Brems, to supplement her diet than to buy and prepare breast-milk substitutes. Additionally, the time breastfeeding demands from must compete with the time demands for other tasks such as child care, household management, food production, fuel and water acquisition, and income-generating activities. Although the need to return to work can interfere with breastfeeding, modifications of the women
Medicine and the Law Automatism and disorder
post-traumatic stress
The categories of automatism are not closed. The latest addition is post-traumatic stress disorder. When an accused person can be shown to have committed an offence without the evil intent, he or she may be acquitted, unless there is strict liability (eg, a motoring offence). Whether a defence of automatism ("non-insane" or "insane") is put to the jury is a matter for the judge alone. "Non-insane" automatism is the preferred defence since "insane automatism" automatically results in a verdict of "not guilty by reason of insanity" and detention in a special hospital for an indeterminate period. An important issue is whether the stimulus that creates the state of automatism emanates from within the mind of the defendant ("insane") or by way of an outside event ("sane"). Insanity here is not synonymous with a medical diagnosis of insanity. Loss of cognitive control and reason caused by, say, epilepsy or diabetes, will, even if shortlived, be regarded in law as indicating "insanity". Many defendants, faced with the choice of this plea or a guilty plea and mitigation will opt for the latter.1 Non-insane automatism offers a complete defence without the stigma of insanity. Most commonly there is an outside stimulus, such as a blow on the head or adverse reaction to a prescribed drug; incapacity due to alcohol or unlawful drugs does not count. Dr Peter Fenwick argues that the legal distinctions between sane and insane automatism are "nonsensical" and "medically unsatisfactory" and invites doctors and pressure groups to seek to influence Parliament to change the law or to petition the Law Reform Committee.2 Insanity for legal purposes (to avoid the consequences of an unlawful act), as Fenwick points out, is not synonymous with a medical diagnosis of insanity. Loss of cognitive control and reason due to, say, epilepsy or diabetes, will be regarded in law as "insane". In a case heard at Snaresbrook Crown Court on Feb 7, 1989,3the defendant, a 23-year-old Frenchwoman, was charged with robbery and causing bodily harm. The judge allowed the defence of non-insane automatism to go before the jury because a psychiatrist who had examined the woman in prison said that at the time of the alleged offences she had post-traumatic stress disorder caused by rape 3 days earlier. The prosecution alleged that the woman had, with two others also charged, robbed two women of their handbags while armed with knives. The charge of bodily harm stemmed from the second act of a complex incident (these were two attempts at robbery), during which the defendant approached a woman standing beside a car. When asked what she was doing the defendant stabbed her in the stomach with a penknife and demanded the handbag of another woman sitting in the car. The assailants ran off and the victims drove away. All three assailants were later arrested, the defendant
being detained while standing at the side of the road. remember all the
events.
7
days later she
was
examined
by
a
doctor at Holloway Prison who found that her hymen was ruptured and bleeding and that there were injuries to the posterior of the hymen. (Some months earlier the hymen had been reconstructed to restore the woman’s
virginal status.) The woman complained that 3 her arrest she had been raped but she had not told anyone about it. She was then examined three times by a psychiatrist, who diagnosed post-traumatic stress disorder and gave the opinion that at the time of the offences she had been in a dissociative state and had not been acting consciously. days before
Diana Brahams
1. Brahams D. Epilepsy is mental illness. Lancet 1983; ii: 116. 2. Fenwick P. Automatism and the law. Psychol Med (monogr supply no 17) 1990: 23. 3. R v T. [1990] Crim LR 256. 4. R v Quick [1973] QB 910. 5. R v Hennessy. [1989] 1 WLR 287 at 294; see also Brahams D. Hyperglycaemia and plea of automatism. Lancet 1989; i: 912. Compare Canadian cases of R v Rabey, per Martin J, 79 DLR 435 (Ontario Court of Appeal) Broom v Perkins (1987) 85 Crim App R 321, and R v Issit [1977] RTR 211.
Conference Improving drug safety The conference
on Improving Drug Safety, held at Wolfsberg, Switzerland, from April 17 to 20, was the second major event of the so-called RAD-AR initiative (Risk/ Benefit Assessment of Drugs-Analysis and Response). Founded in 1988 by Ciba Geigy, RAD-AR is still supported mainly by its initiators, but other companies now join in. RAD-AR might evolve into the industry’s most important effort in improving drug safety. The gathering was attended by representatives from industry, regulatory agencies, academia, the media, and consumer organisations from most Western countries and from Japan. The aim of the conference was to review existing means of analysis, assessment, and communication of drug risks and to generate new ideas on these subjects.
The first part of the conference centred on ethical on improving drug safety. Medical decisions not only derive from risk/benefit estimation but include considerations of the patient’s autonomy and the fair use of resources. A speaker from a pharmaceutical company pointed out that the principle "good ethics equals good business" is not yet standard within the industry. One day was dedicated to the generation and assessment of reliable information about drug risks and benefits. Of the various means of generating information on adverse drug reactions, spontaneous reporting is still the cheapest and perhaps the best. However, no scientifically sound conclusions can be based on spontaneous reports only.
perspectives
On the night of her arrest the woman was described as passive and "indifferent to what was happening". At a later interview she could not
At trial, before Soudian,7, the defence submitted that a defence of non-insane automatism was not limited to cases where a blow had caused concussion or where insulin or an anaesthetic had been given or where there had been sleep walking.’ Rape was an extraordinary event with features not likely to recur-unlike normal stress, anxiety, or depression caused by external factors, which were likely to recur and which could not therefore, in law, be accepted as automatism. The prosecution contended that the defendant had some recollection of what had happened and that the opening of a penknife blade required a controlled, positive action on her part. The only defence, therefore, was insane automatism. The judge said that there had been no previous case in which rape had been held to be an external factor causing a malfunctioning of the mind within the definition laid down in R v Quick.’ If what the defendant had said about the rape were true the incident could have an appalling effect on her, however well balanced she usually was. A condition of post-traumatic stress involving a normal person in an act of violence was not itself a disease of the mind, even if there were a delay before the dissociation manifested itself. If the medical evidence were correct this case was distinguishable from those where there was only a partial loss of control.5 The jury failed to agree. At re-trial the defendant was convicted (on a majority verdict) but her sentence was lighter than it might otherwise have been.
1334
Additional efforts should be channelled towards early recognition of rare, unpredictable (type B) reactions. In the assessment of the risk/benefit ratio, simple tests for quality of life would help to give a more meaningful definition of benefit. Participants agreed that "above all, do no harm" can no longer be interpreted in a simplistic way, since no medical intervention is without risk. Communication about drug safety was another theme. As one speaker expressed it, the industry does a good job in producing the hardware (the drugs) but fails in providing adequate software (drug information). Informational needs of patients and doctors must be better analysed and satisifed. More varied methods, such as patient help groups and telephone access to pharmaceutical companies’ information services, might be used. Mass media could provide excellent help if unbiased, easy-to-read information were available. However, the most important exchange of information takes place when doctors discuss treatments with their patients. The specific needs of individual doctors were given scant attention at the conference. Developing countries were also largely ignored. One thing became very clear: the collection and transmission of information on adverse drug reactions vary widely between countries and need to be standardised. It is high time the industry recognised adverse drug reactions as legitimate offspring of its products. Brainstorming should now be followed by tangible changes in the industry’s attitudes. If this happens, the three days at Wolfsberg were time well spent. Etzel
Gysling
Noticeboard Breast
cancer
and oral
contraceptives
The Institute of Medicine (IOM) is the arm of the US National Academy of Sciences that focuses on the development of public policy in health issues. On May 3 and 4, a conference held at the Arnold and Mabel Beckman Center in Irvine, California, on the relation between oral contraceptives and breast cancer was one step in the IOM’s twelve-month study of this subject. The study will review policy options, suggest future research, and make recommendations for doctors. (A report on the Irvine meeting and the IOM Committee findings will be published in 1991.) The confusing epidemiological data on breast cancer and oral contraceptive use have been widely reviewed, but the strength of the IOM gathering was the interdisciplinary nature of the participants-specialists in tissue culture, biological markers for breast cancer, biochemistry, endocrinology, and epidemiology forgathered. Their collective opinion was that oral contraceptives, if they have any effect at all, are more likely to accelerate or retard the growth of an existing cancer than to initiate malignant change. An interpretation of the existing epidemiological data is that there is a small rise in relative risk among some subgroups, perhaps with a possible reduction in relative risk in others. Nevertheless, the most important factor in modelling any putative effect is likely to be the duration of any adverse or beneficial effect after oral contraceptive use has ceased. Breast cancer has become more common in every decade of the twentieth century-American women today have a one in ten chance of getting the disease and a one in eighteen chance of dying from it. Although the overwhelming majority of women who now have breast cancer were too old to have taken oral contraceptives, the relation between these agents and breast cancer warrants continued study, both as an important clinical question per se and for any light such investigations might throw on the aetiology of breast cancer. However, such studies are likely to be large, expensive, and long term. From this perspective, the Royal College of General Practitioners cohort study is immensely important. This
study may be the only one in our generation that could eventually the subtle but key question: For how long do any effects of oral contraceptives on ovarian, endometrial, and possibly breast cancer persist after taking the last pill? The Medical Research Council will no longer fund the RCGP Study, but support has been secured from the pharmaceutical industry and from other sources for a further three years of data collection followed by two of data analysis. answer
Breastfeeding and fertility Breastfeeding
not
only contributes
to
lower
fertility but also
increases the birth interval, and in many developing countries more women are protected from pregnancy by breastfeeding than by all other contraceptive methods combined. Gray and colleagues1 have
recently supported the consensus statement that breastfeeding provides more than 98% protection from pregnancy in the first six months post partum.2 The maximum birth spacing effect, said the statement, is achieved when a mother fully or nearly fully breastfeeds and remains amenorrhoeic (bleeding before the 56th post-partum day being ignored). Why, then, has breastfeeding often not been promoted for its contraceptive effect in projects aimed at limiting fertility? Three assumptions that may have obstructed the promotion of breastfeeding in such projects have now been challenged in a World Bank report.3 First, promotive efforts might be regarded as unnecessary in countries where breastfeeding is still the usual form of contraception. But, say Berg and Brems,3promotion should centre on the type of breastfeeding practices used, since the contraceptive effect is related to duration of breastfeeding, frequency and duration of suckling, administration of supplements to the infant, nutritional status of the mother, and geographic, social, and cultural factors. They also emphasise the importance of a supportive environment for the woman: environmental pressures, such as negative influences in the mass media and migration that removes women from traditional support networks, weaken breastfeeding practices. Secondly, a decline in breastfeeding is often assumed to be an inevitable part of "modernisation" and to have negligible demographic impact if there is a corresponding increase in the use of "modem" contraceptives. Berg and Brems cite the recent reversal of declines in breastfeeding in industrialised countries, such as the US, Scandinavia, Australia, and Eastern Europe, as evidence to refute this notion. They emphasise that the types of decline are important: for example, whereas some shortening of the duration of exclusive breastfeeding may be acceptable or even recommended in view of the increased nutritional needs of the growing infant, a fall in the prevalence of breastfeeding or a dramatic reduction in duration can lead to loss of contraceptive protection and greater demands on family planning services than can be met, and health and nutrition of the infant may then be at risk. Berg and Brems suggest that promotion of breastfeeding practices is essential, since modem contraception is neither universally available nor widely used, perhaps for religious or cultural reasons; for these women breastfeeding promotion can help to reduce the risk of pregnancy. Last, that breastfeeding is not regarded as a completely reliable contraceptive for the individual woman after the first few months post partum is not the same, say Berg and Brems, as concluding that breastfeeding has no part in population programmes. Family planning services, they suggest, could work to reduce barriers to breastfeeding, especially where modem contraceptives are unavailable or unacceptable. The financial costs of infant feeding have to be taken into account in assessment of the benefits of breastfeeding. Despite the increased nutritional needs of a lactating woman, it is cheaper, say Berg and Brems, to supplement her diet than to buy and prepare breast-milk substitutes. Additionally, the time breastfeeding demands from must compete with the time demands for other tasks such as child care, household management, food production, fuel and water acquisition, and income-generating activities. Although the need to return to work can interfere with breastfeeding, modifications of the women