498
Return to Pakistan of
pipenzolate plus phenobarbitone
SIR,-Some time ago a 19-day-old baby was brought to this hospital seriously ill with abdominal distension and constipation. She had been irritable and had been taken to a local doctor who prescribed ’Piptal’ drops, after which she fell asleep. A few hours later abdominal distension developed. Her parents continued giving the drops but she became worse, at which point she was brought to us. The baby died. In those days I was working with Prof Tariq Iqbal Bhutta, and we were running a campaign against antimotility drugs, especially ’Imodium’ (loperamide). We also approached the manufacturers of piptal and the Pakistan Ministry of Health, seeking restrictions on the promotion of piptal drops. Our argument was that piptal overdosage in babies results in abdominal distension, drowsiness, and respiratory depression. The drops are not manufactured in any developed country. Ferozesons (the manufacturers in Pakistan) claim to have a licence from Lakeside Laboratories, USA, but that company does not produce the medicine for use in the United States. There is no published evidence available on the efficacy of this preparation. The dosage schedule is potentially dangerous-namely, 05 ml 15 min after every feed, irrespective of body weight and number of feeds. Piptal contains phenobarbitone and has a long duration of action: this may cause cumulative effects. We asked Ferozesons to stop production but had no response. Only when our observations were publicised outside Pakistan did the machinery begin to move. The Ministry of Health called a meeting of all manufacturers of antimotility drugs and the antispasmodic agent piptal on June 10, 1990, and the drugs were banned. A year later the Ministry of Health reissued a licence for the manufacturer of piptal drops (containing pipenzolate and phenobarbitone) and this product is freely available once again. Last year six babies were brought to this hospital with abdominal distension and a history of intake of piptal drops. One baby died and another was taken away against medical advice. Phenobarbitone has been added for its sedative properties. The other ingredient, pipenzolate, can cause distension of the intestines and abdomen, the consequences of which may be serious. Piptal at a dose of 6-5 ml contains 39 mg phenobarbitone and 26 mg pipenzolate. There are many reasons for a baby crying but true colic is rare. No textbook mentions pipenzolate for infantile colic, which should be managed by improved feeding techniques, winding, and
avoiding underfeeding or overfeeding. Subsequent inquiries revealed that Ferozesons appealed against the decision of Pakistan’s drug registration authority on the grounds that the drops were not antidiarrhoeal but anticholinergic, and that appeal had been accepted. I pointed out that we had never said that piptal was an antidiarrhoeal preparation. Every doctor knows full well that it is an anticholinergic drug, and this ground of appeal is spurious. At the 1990 meeting, in the presence of manufacturers, all hazards of these drugs were discussed. Anyway if piptal is being promoted as an anticholinergic drug why add phenobarbitone? Department of Paediatric Medicine, Hospital,
Nishtar
Multan, Pakistan
KHALID
IQBAL TAHIR
Ethics, clinical research, and clinical practice in obstetric anaesthesia SIR,-In obstetric anaesthesia it is not only clinical investigators but also practitioners who need to face up to the responsibilities outlined in your Feb 8 editorial. I was recently invited by Dr Felicity Reynolds, editor of the International Journal of Obstetric Anesthesia, to prepare a review article for the first volume of this new specialist publication, to encourage properly controlled trials in obstetric anaesthesia. Because the growth of the subspecialty of obstetric anaesthesia has been mirrored by an increased use of epidural block for pain relief in labour, Dr Howell and I’ reviewed what was known about the effects of this widely used form of pain relief. Analyses of observational data suggest that, compared with other methods of pain relief in labour, epidural block may increase the risks of maternal pyrexia,2 instrumental delivery,3,4 caesarean section for
dystocia,5 chronic backache,6 and chronic headacheSome analyses have also raised the possibility of adverse effects of epidural block on the baby. 8,9 Because selection biases may have accounted for the associations between these adverse outcomes and epidural block, Howell and I analysed the results of controlled trials comparing epidural block with alternative methods of pain relief in labour. Obstetric anaesthetists have done only nine reasonably well controlled trials and studied a total of fewer than 600 women in the 20 years or so since this form of pain relief was introduced for labour. Unfortunately, these trials tell us little about the effects of epidurals (apart from confirming the greatly increased likelihood that instruments will be used for delivery if epidural block is used during the second stage of labour). We suggested that, in view of the combination of very widespread use of epidural block during labour and the observational evidence suggesting that it might have serious maternal side-effects, there was a need for obstetric anaesthetists to do randomised trials to address these important uncertainties about the effects of their practice.’ Howell and I were surprised that, without waiting for reactions from their readers, Reynolds and her editorial colleagues felt it necessary to dissociate themselves from these conclusions. In an editorial published in the same issue of the journal they wrote that "the views expressed are those of the authors, the editors being only too aware that most mothers would not take kindly to receiving epidural analgesia on a random basis". Your editorial notes that "clinical investigators have an absolute responsibility to ensure that the protocol for their study fulfils scientific criteria, that a specific and appropriate question be posed, and that an answer is possible as a result of the proposed measurements". The statement made by the editors of the International Journal of Obstetric Anesthesia implies either that they encourage researchers to abrogate these responsibilities in respect of research to assess the effects of epidural block during labour, or that there is no longer any possibility of learning about the effects of a technique on which the growth of their subspecialty has depended so heavily. Perhaps the reason that they are so confident that women would not agree to take part in properly controlled trials is that they and other anaesthetists are less forthcoming than they should be about disclosing evidence that epidurals may have important adverse effects. Obstetric anaesthetists give the impression that they are not living up to their responsibilities, either as researchers or as clinicians. National Perinatal Epidemiology Unit, Radcliffe Infirmary, Oxford OX2 6HE, UK
IAIN CHALMERS
CJ, Chalmers I. A review of prospectively controlled comparisons of epidural with non-epidural forms of pain relief during labour. Int J Obstet Anesth 1992; 1: 93-110. 2. Fusi L, Steer PJ, Maresh MJA, Beard RW. Maternal pyrexia associated with theuse of epidural analgesia in labour. Lancet 1989; i: 1250-52. 3. Kaminski H, Stafl A, Aiman J. The effects of epidural analgesia on the frequency of instrumental obstetric delivery. Obstet Gynecol 1987; 69: 770-73. 4. Paterson C, Banfield P. Epidural analgesia and maternal satisfaction. Br Med J 1991; 302: 1079. 5. Thorp JA, Parisi VM, Boylan PC, Johnston DA. The effect of continuous epidural analgesia on caesarean section for dystocia in nulliparous women. Am J Obstet Gynecol 1989; 161: 670-75. 6. MacArthur C, Lewis M, Knox EG, Crawford JS. Epidural anaesthesia and long term backache after childbirth. Br Med J 1990; 301: 9-12. 7. MacArthur C, Lewis M, Knox EG. Health after childbirth. London: HMSO, 1991. 8. Scanlon JW. Effects of obstetric anesthesia and analgesia on the newborn: a select, annotated bibliography for the clinician. Clin Obstet Gynecol 1981; 24: 649-70. 9. Avard DM, Nimrod CM. Risks and benefits of obstetric epidural analgesia: a review. Birth 1985; 12: 215-25. 1. Howell
Patient referral and NHS reforms SjR,—Professor Benjamin (Jan 4, p 60) and Dr White (Jan 25, p 250) refer to delays and prolonged negotiations with purchasers over extracontractual referrals. Fortunately, those referrals went ahead eventually, but this is not always so in the new NHS. A patient, referred to me specifically because she was dissatisfied with the quality of the local services she had received for the same complaint, has recently been refused referral by her purchasing authority, on the grounds of cost.
499
In line with
most
other providers,
we are
charging
average
specialty cost this year and purchasers have been funded on this basis. Although this particular patient’s care is likely to cost the provider less than average, her purchasing authority have sent us a number of patients who cost far more than average. The purchasers are keen to negotiate a lower price for her care, and even to veto her referral, but they will not discuss higher prices for their more expensive cases. This "have your cake and eat it" attitude on the part of some purchasers can only lead to a reduction in the numbers of patients that hospitals--who must balance their budgets-are able to treat, as well as restricting patient choice. Are these the logical outcomes of the new system, or do they reveal something of its true nature? Department of Gastroenterology, St Bartholomew’s Hospital, London EC1A 7BE, UK
PETER D. FAIRCLOUGH
Regulation of assay kits SIR,-The difficulties and dangers that Dr S. L. Jeffcoate describes (Nov 9, p 1212) (caused by manufacturers’ undisclosed replacement of key components of immunodiagnostic kits) have long been known. But they are likely to become more serious as the generation of British scientists who both pioneered immunoassay development and initially fulfilled service needs in this area are replaced by users of commercial kits or machines having only superficial knowledge of the methodology, and who might therefore accept manufacturers’ product claims without question. Lancet readers may remember the controversy about the validity of so-called "labelled analogue" free thyroid hormone assay kits. Although the nomenclature committee of the American Thyroid Association recommended that they should not be so described,l and despite repeated protests by scientists and clinicians, manufacturers continue to label such kits in this misleading way. No effective mechanism exists in the UK to end this state of affairs, nor does there seem to be any legal remedy other than that provided by the Sale of Goods Act. Fortunately the regulatory system for which Jeffcoate calls is in part provided by the US Food and Drug Administration (FDA), since most major manufacturers view the American market as of key importance and go to considerable lengths to satisfy FDA regulations relating to diagnostic kits. But even regulatory bodies of this kind-generally staffed by non-experts, and inevitably somewhat bureaucratic--do not by themselves provide adequate safeguards against manufacturing malpractice. Nor do external quality assurance schemes run by central organisations (being mainly designed to monitor and keep to a minimum interlaboratory variation) satisfactorily fulfil this particular role. Such bodies have conspicuously failed to prevent situations of the kind described above, nor have they intervened in any way to bring them to an end. Meanwhile clinical chemists staffmg routine hospital laboratories generally have neither sufficient time nor detailed knowledge to keep up with scientific publications in many specialties, and therefore provide little check to manufacturers’ less scrupulous activities. In short, none of these regulatory mechanisms substitutes for the vigilant scrutiny of manufacturers’ claims and practices provided by independent scientists and clinicians with expert knowledge deriving from their own research and development activities in immunodiagnostics. This role has in the past largely been carried out in the UK by laboratories participating in the supraregional (hormone) assay service (SAS), these having been based in university departments that pioneered the methods. These laboratories were originally charged not only with providing rarely required and difficult assays on a routine basis, but with ancillary functions such as the development of new methods, the preparation of scarce reagents, teaching, and so on-activities that, amongst others, ensured the active participation of scientists and clinicians with specific research and development interests. Such interests underlay, for example, my own department’s unique understanding of the scientific basis of free hormone immunoassay methodology, and its survey of free thyroid hormone kits commissioned and later published by the Department of HealthWith the passage of time, SAS laboratories’ ability to undertake these (costly) ancillary activities has been
eroded, but attempts to fulfil them have continued in at least some centres. Regrettably the abrupt change in the method of funding of the SAS due to take place is likely to deliver the final coup degrace to these activities, and SAS centres will inevitably be further driven by financial pressure to adopt a factory-like approach, relying on commercial kits, automated machines, and inexperienced staff in order to compete with other National Health Service laboratories and private organisations in fulfilling a minimum service role. Gone, in short, will be one of the last repositories of independent expertise in immunodiagnostics, and kit manufacturers will be free to market what they will without effective let or hindrance. I therefore share Jeffcoate’s disquiet, and echo his fmal plea that something must be done if manufacturers’ activities are to be effectively monitored, and the public health and the public purse are to be adequetely protected. Department of Molecular Endocrinology, University College and Middlesex School of Medicine,
University College London, London W1 N 8AA, UK
ROGER EKINS
1. Larsen PR, Alexander NM, Chopra IJ, et al. Revised nomenclature for tests of
thyroid
hormones and thyroid-related proteins in serum. J Clin Endocrinol Metab 1987; 64: 1089. 2. Jackson T, Ekins RP. Comparative evaluation of free thyroxine assay kits. Evaluation report of the UK Department of Health and Social Security, London, 1986.
The Italian way of osteoporosis SiR,—The prescription of calcitonin is much more popular in Italy than it is in other European countries.’ Surprisingly, in January, 1989, the Ministry of Health criticised the high prescription of injectable calcitonins on the eve of allowing the marketing of spray calcitonins in April, 1989. In 1991, calcitonin was the most prescribed drug in terms of Italy’s National Health Service (NHS) expenditure, with a ratio of injectable to nasal preparations of 1 to 4. There are twenty-three manufacturers in Italy marketing 67 calcitonin formulations. Our analysis of drug use by general practitioners in Emilia Romagna (a region in northern Italy with about 4 million inhabitants) in the first half of 1991 revealed calcitonin as the drug ranking first in terms of an expenditure at £ 13 million or almost 5% of NHS drug costs. Record-linkage analysis on patients prescribed either calcitonin or conjugated oestrogens in general practice in the Imola area (100 000 inhabitants), showed that calcitonin is prescribed mainly in the elderly (fig 1), even though there is no evidence that it is beneficial in such patientsOestrogens were prescribed much less, and were used mostly in 50-60-year-old women. The percentage of the female population receiving at least one prescription of calcitonin during 1990 (fig 2) peaked at 18% in the 70-75 age group (12% spray, 6% subcutaneous); the age peak of oestrogen, in the 50-54 age group, was only 3%. Subsequent analysis revealed that calcitonin spray treatment lasted 45 days on average, reflecting the two cycles of 3 weeks per
DDD/1000 inhabitants/day
age groups
(upper limit)
Fig 1-Prescription of oestrogens and calcitonins in Imola area, Emilia Romagna, by age group in 1990.
Return to Pakistan of
pipenzolate plus phenobarbitone
SIR,-Some time ago a 19-day-old baby was brought to this hospital seriously ill with abdominal distension and constipation. She had been irritable and had been taken to a local doctor who prescribed ’Piptal’ drops, after which she fell asleep. A few hours later abdominal distension developed. Her parents continued giving the drops but she became worse, at which point she was brought to us. The baby died. In those days I was working with Prof Tariq Iqbal Bhutta, and we were running a campaign against antimotility drugs, especially ’Imodium’ (loperamide). We also approached the manufacturers of piptal and the Pakistan Ministry of Health, seeking restrictions on the promotion of piptal drops. Our argument was that piptal overdosage in babies results in abdominal distension, drowsiness, and respiratory depression. The drops are not manufactured in any developed country. Ferozesons (the manufacturers in Pakistan) claim to have a licence from Lakeside Laboratories, USA, but that company does not produce the medicine for use in the United States. There is no published evidence available on the efficacy of this preparation. The dosage schedule is potentially dangerous-namely, 05 ml 15 min after every feed, irrespective of body weight and number of feeds. Piptal contains phenobarbitone and has a long duration of action: this may cause cumulative effects. We asked Ferozesons to stop production but had no response. Only when our observations were publicised outside Pakistan did the machinery begin to move. The Ministry of Health called a meeting of all manufacturers of antimotility drugs and the antispasmodic agent piptal on June 10, 1990, and the drugs were banned. A year later the Ministry of Health reissued a licence for the manufacturer of piptal drops (containing pipenzolate and phenobarbitone) and this product is freely available once again. Last year six babies were brought to this hospital with abdominal distension and a history of intake of piptal drops. One baby died and another was taken away against medical advice. Phenobarbitone has been added for its sedative properties. The other ingredient, pipenzolate, can cause distension of the intestines and abdomen, the consequences of which may be serious. Piptal at a dose of 6-5 ml contains 39 mg phenobarbitone and 26 mg pipenzolate. There are many reasons for a baby crying but true colic is rare. No textbook mentions pipenzolate for infantile colic, which should be managed by improved feeding techniques, winding, and
avoiding underfeeding or overfeeding. Subsequent inquiries revealed that Ferozesons appealed against the decision of Pakistan’s drug registration authority on the grounds that the drops were not antidiarrhoeal but anticholinergic, and that appeal had been accepted. I pointed out that we had never said that piptal was an antidiarrhoeal preparation. Every doctor knows full well that it is an anticholinergic drug, and this ground of appeal is spurious. At the 1990 meeting, in the presence of manufacturers, all hazards of these drugs were discussed. Anyway if piptal is being promoted as an anticholinergic drug why add phenobarbitone? Department of Paediatric Medicine, Hospital,
Nishtar
Multan, Pakistan
KHALID
IQBAL TAHIR
Ethics, clinical research, and clinical practice in obstetric anaesthesia SIR,-In obstetric anaesthesia it is not only clinical investigators but also practitioners who need to face up to the responsibilities outlined in your Feb 8 editorial. I was recently invited by Dr Felicity Reynolds, editor of the International Journal of Obstetric Anesthesia, to prepare a review article for the first volume of this new specialist publication, to encourage properly controlled trials in obstetric anaesthesia. Because the growth of the subspecialty of obstetric anaesthesia has been mirrored by an increased use of epidural block for pain relief in labour, Dr Howell and I’ reviewed what was known about the effects of this widely used form of pain relief. Analyses of observational data suggest that, compared with other methods of pain relief in labour, epidural block may increase the risks of maternal pyrexia,2 instrumental delivery,3,4 caesarean section for
dystocia,5 chronic backache,6 and chronic headacheSome analyses have also raised the possibility of adverse effects of epidural block on the baby. 8,9 Because selection biases may have accounted for the associations between these adverse outcomes and epidural block, Howell and I analysed the results of controlled trials comparing epidural block with alternative methods of pain relief in labour. Obstetric anaesthetists have done only nine reasonably well controlled trials and studied a total of fewer than 600 women in the 20 years or so since this form of pain relief was introduced for labour. Unfortunately, these trials tell us little about the effects of epidurals (apart from confirming the greatly increased likelihood that instruments will be used for delivery if epidural block is used during the second stage of labour). We suggested that, in view of the combination of very widespread use of epidural block during labour and the observational evidence suggesting that it might have serious maternal side-effects, there was a need for obstetric anaesthetists to do randomised trials to address these important uncertainties about the effects of their practice.’ Howell and I were surprised that, without waiting for reactions from their readers, Reynolds and her editorial colleagues felt it necessary to dissociate themselves from these conclusions. In an editorial published in the same issue of the journal they wrote that "the views expressed are those of the authors, the editors being only too aware that most mothers would not take kindly to receiving epidural analgesia on a random basis". Your editorial notes that "clinical investigators have an absolute responsibility to ensure that the protocol for their study fulfils scientific criteria, that a specific and appropriate question be posed, and that an answer is possible as a result of the proposed measurements". The statement made by the editors of the International Journal of Obstetric Anesthesia implies either that they encourage researchers to abrogate these responsibilities in respect of research to assess the effects of epidural block during labour, or that there is no longer any possibility of learning about the effects of a technique on which the growth of their subspecialty has depended so heavily. Perhaps the reason that they are so confident that women would not agree to take part in properly controlled trials is that they and other anaesthetists are less forthcoming than they should be about disclosing evidence that epidurals may have important adverse effects. Obstetric anaesthetists give the impression that they are not living up to their responsibilities, either as researchers or as clinicians. National Perinatal Epidemiology Unit, Radcliffe Infirmary, Oxford OX2 6HE, UK
IAIN CHALMERS
CJ, Chalmers I. A review of prospectively controlled comparisons of epidural with non-epidural forms of pain relief during labour. Int J Obstet Anesth 1992; 1: 93-110. 2. Fusi L, Steer PJ, Maresh MJA, Beard RW. Maternal pyrexia associated with theuse of epidural analgesia in labour. Lancet 1989; i: 1250-52. 3. Kaminski H, Stafl A, Aiman J. The effects of epidural analgesia on the frequency of instrumental obstetric delivery. Obstet Gynecol 1987; 69: 770-73. 4. Paterson C, Banfield P. Epidural analgesia and maternal satisfaction. Br Med J 1991; 302: 1079. 5. Thorp JA, Parisi VM, Boylan PC, Johnston DA. The effect of continuous epidural analgesia on caesarean section for dystocia in nulliparous women. Am J Obstet Gynecol 1989; 161: 670-75. 6. MacArthur C, Lewis M, Knox EG, Crawford JS. Epidural anaesthesia and long term backache after childbirth. Br Med J 1990; 301: 9-12. 7. MacArthur C, Lewis M, Knox EG. Health after childbirth. London: HMSO, 1991. 8. Scanlon JW. Effects of obstetric anesthesia and analgesia on the newborn: a select, annotated bibliography for the clinician. Clin Obstet Gynecol 1981; 24: 649-70. 9. Avard DM, Nimrod CM. Risks and benefits of obstetric epidural analgesia: a review. Birth 1985; 12: 215-25. 1. Howell
Patient referral and NHS reforms SjR,—Professor Benjamin (Jan 4, p 60) and Dr White (Jan 25, p 250) refer to delays and prolonged negotiations with purchasers over extracontractual referrals. Fortunately, those referrals went ahead eventually, but this is not always so in the new NHS. A patient, referred to me specifically because she was dissatisfied with the quality of the local services she had received for the same complaint, has recently been refused referral by her purchasing authority, on the grounds of cost.
499
In line with
most
other providers,
we are
charging
average
specialty cost this year and purchasers have been funded on this basis. Although this particular patient’s care is likely to cost the provider less than average, her purchasing authority have sent us a number of patients who cost far more than average. The purchasers are keen to negotiate a lower price for her care, and even to veto her referral, but they will not discuss higher prices for their more expensive cases. This "have your cake and eat it" attitude on the part of some purchasers can only lead to a reduction in the numbers of patients that hospitals--who must balance their budgets-are able to treat, as well as restricting patient choice. Are these the logical outcomes of the new system, or do they reveal something of its true nature? Department of Gastroenterology, St Bartholomew’s Hospital, London EC1A 7BE, UK
PETER D. FAIRCLOUGH
Regulation of assay kits SIR,-The difficulties and dangers that Dr S. L. Jeffcoate describes (Nov 9, p 1212) (caused by manufacturers’ undisclosed replacement of key components of immunodiagnostic kits) have long been known. But they are likely to become more serious as the generation of British scientists who both pioneered immunoassay development and initially fulfilled service needs in this area are replaced by users of commercial kits or machines having only superficial knowledge of the methodology, and who might therefore accept manufacturers’ product claims without question. Lancet readers may remember the controversy about the validity of so-called "labelled analogue" free thyroid hormone assay kits. Although the nomenclature committee of the American Thyroid Association recommended that they should not be so described,l and despite repeated protests by scientists and clinicians, manufacturers continue to label such kits in this misleading way. No effective mechanism exists in the UK to end this state of affairs, nor does there seem to be any legal remedy other than that provided by the Sale of Goods Act. Fortunately the regulatory system for which Jeffcoate calls is in part provided by the US Food and Drug Administration (FDA), since most major manufacturers view the American market as of key importance and go to considerable lengths to satisfy FDA regulations relating to diagnostic kits. But even regulatory bodies of this kind-generally staffed by non-experts, and inevitably somewhat bureaucratic--do not by themselves provide adequate safeguards against manufacturing malpractice. Nor do external quality assurance schemes run by central organisations (being mainly designed to monitor and keep to a minimum interlaboratory variation) satisfactorily fulfil this particular role. Such bodies have conspicuously failed to prevent situations of the kind described above, nor have they intervened in any way to bring them to an end. Meanwhile clinical chemists staffmg routine hospital laboratories generally have neither sufficient time nor detailed knowledge to keep up with scientific publications in many specialties, and therefore provide little check to manufacturers’ less scrupulous activities. In short, none of these regulatory mechanisms substitutes for the vigilant scrutiny of manufacturers’ claims and practices provided by independent scientists and clinicians with expert knowledge deriving from their own research and development activities in immunodiagnostics. This role has in the past largely been carried out in the UK by laboratories participating in the supraregional (hormone) assay service (SAS), these having been based in university departments that pioneered the methods. These laboratories were originally charged not only with providing rarely required and difficult assays on a routine basis, but with ancillary functions such as the development of new methods, the preparation of scarce reagents, teaching, and so on-activities that, amongst others, ensured the active participation of scientists and clinicians with specific research and development interests. Such interests underlay, for example, my own department’s unique understanding of the scientific basis of free hormone immunoassay methodology, and its survey of free thyroid hormone kits commissioned and later published by the Department of HealthWith the passage of time, SAS laboratories’ ability to undertake these (costly) ancillary activities has been
eroded, but attempts to fulfil them have continued in at least some centres. Regrettably the abrupt change in the method of funding of the SAS due to take place is likely to deliver the final coup degrace to these activities, and SAS centres will inevitably be further driven by financial pressure to adopt a factory-like approach, relying on commercial kits, automated machines, and inexperienced staff in order to compete with other National Health Service laboratories and private organisations in fulfilling a minimum service role. Gone, in short, will be one of the last repositories of independent expertise in immunodiagnostics, and kit manufacturers will be free to market what they will without effective let or hindrance. I therefore share Jeffcoate’s disquiet, and echo his fmal plea that something must be done if manufacturers’ activities are to be effectively monitored, and the public health and the public purse are to be adequetely protected. Department of Molecular Endocrinology, University College and Middlesex School of Medicine,
University College London, London W1 N 8AA, UK
ROGER EKINS
1. Larsen PR, Alexander NM, Chopra IJ, et al. Revised nomenclature for tests of
thyroid
hormones and thyroid-related proteins in serum. J Clin Endocrinol Metab 1987; 64: 1089. 2. Jackson T, Ekins RP. Comparative evaluation of free thyroxine assay kits. Evaluation report of the UK Department of Health and Social Security, London, 1986.
The Italian way of osteoporosis SiR,—The prescription of calcitonin is much more popular in Italy than it is in other European countries.’ Surprisingly, in January, 1989, the Ministry of Health criticised the high prescription of injectable calcitonins on the eve of allowing the marketing of spray calcitonins in April, 1989. In 1991, calcitonin was the most prescribed drug in terms of Italy’s National Health Service (NHS) expenditure, with a ratio of injectable to nasal preparations of 1 to 4. There are twenty-three manufacturers in Italy marketing 67 calcitonin formulations. Our analysis of drug use by general practitioners in Emilia Romagna (a region in northern Italy with about 4 million inhabitants) in the first half of 1991 revealed calcitonin as the drug ranking first in terms of an expenditure at £ 13 million or almost 5% of NHS drug costs. Record-linkage analysis on patients prescribed either calcitonin or conjugated oestrogens in general practice in the Imola area (100 000 inhabitants), showed that calcitonin is prescribed mainly in the elderly (fig 1), even though there is no evidence that it is beneficial in such patientsOestrogens were prescribed much less, and were used mostly in 50-60-year-old women. The percentage of the female population receiving at least one prescription of calcitonin during 1990 (fig 2) peaked at 18% in the 70-75 age group (12% spray, 6% subcutaneous); the age peak of oestrogen, in the 50-54 age group, was only 3%. Subsequent analysis revealed that calcitonin spray treatment lasted 45 days on average, reflecting the two cycles of 3 weeks per
DDD/1000 inhabitants/day
age groups
(upper limit)
Fig 1-Prescription of oestrogens and calcitonins in Imola area, Emilia Romagna, by age group in 1990.
