1352 PRODUCING THE FORMULARY
Choice of Drugs A THERAPEUTIC FORMULARY FOR ITALIAN GENERAL PRACTITIONERS
GIANNI TOGNONI
Laboratory of Clinical Pharmacology, Istituto di Ricerche Farmacologiche "M. Negri", and Lombardy Regional Centre for Drug Information, Milan, Italy. INTRODUCTION
OUTPATIENT practice consumes a large portion of health-care resources and is the broadest area of contact between the public and health workers. Drug therapy is a major component of outpatient practice, with costs around 10-15% of the annual budget of developed countries, and drugs accompany or follow almost every medical act either as a physician’s prescription or a consumer’s request, or both. Only 4-8% of outpatient visits in Italy end without a drug prescription.’ Increasing interest is aroused by programmes of drug use,2,3 drug selection and monitoring inside and outside hospitals,4.5 and the policy on essential drugs adopted by the
W.H.O.6,7 I describe here how
therapeutic formulary for produced by the union representgeneral practice8 ing general practitioners (Federazione Italiana Medici Mutualistici) working in the N.H.S. in Italy. a
was
BACKGROUND
Drugs available in Italy are predominantly pharmaceutical products marketed by more than 400 firms:9 14 176 products are marketed under 7812 brand names. In the Minisiry of Health’s 1977 national formulary for outpatient practice, drugs were divided into categories A, B, and C corresponding to scientific reliability and clinical importance. Category A contained 3236 products under 1763 brand names, category B 5948 products (3626 names), and category C 4992 products (2423 names). In practice, however, drugs did not seem to be selected for use on these criteria of reliability and worth, and because the pharmaceutical products were listed and indexed only by their brand names the national formulary did not aid more rational prescribing. 75-80% of more than 12 000 outpatient drug prescriptions in seven Italian towns included useless, irrational, or even dangerous drugs or drug combinations.’ In hospital practice standards are set by therapeutic hospital formularies which since 1975 have been central to the drug policy of northern and central regions of Italy. Regional guide= lines at various levels of hospital care have been more widely accepted than was hoped.’,1o
In 1977 a working group from the National Commission of General Practitioners and clinical pharmacologists of the Istituto di Ricerche Farmacologiche "Mario Negri", associated with the Lombardy Regional Centre for Drug Information (C.R.I.F.), met to prepare a list of drugs to be recommended for outpatient practice. C.R.I.F. has been monitoring the use of therapeutic formularies in regional hospitals since 1975.4 The original idea of a simple list of active principles and drug products turned out to be unsatisfactory because the application of stringent criteria for selecting effective drugs would have required too many basic changes in common therapeutic practice. An annotated text was chosen, therefore, which ensured consistency between rigorous scientific standards, met the needs of daily practice, and used straightforward language. For each therapeutic class a text was agreed by the
pharmacologists and general practitioners and revised by an independent expert in the field. Decisions lIkely to be controversial or too radical for general prescribing habits and current medical knowledge were tested in daily practice by the members of the working group. This procedure lasted ten months and the text was published in January, 1978. In the formulary drugs were classified according to their therapeutic value (see table). Drugs and treatments used only in hospitals (e.g., general anaesthetics and parenteral solutions) and cancer treatments, for which referral to specialised organisations and adherence to well-defined protocols were considered necessary, were not assessed. Warnings were given on the irrational prescribing of pharmacological treatments which required specialised diagnostic competence in their use (e.g., acute and long-term treatments for hxmostatic problems, major tranquillisers and antidepressants, and treatments for real or supposed endocrinological disorders). Widely prescribed classes of drugs of doubtful value (e.g., cerebral vasodilators) and useless drugs (e.g., liver factors, organ extracts, fortifiers) were discussed in detail to emphasise their inadequacy. Within widely used therapeutic classes a few active principles were selected when many alternatives were available-e.g., cephalosporins had 8 alternatives, benzodiazepines 16, neuroleptics 27, and non-steroidal antiinflammatory agents 30. Fixed-dose combinations were excluded as first-choice drugs. Within each chapter special emphasis was given to therapeutic strategies, mechanisms of action, side-effects, and comparison of pharmacological and alternative treatments. A full chapter was devoted to placebo therapy and the final section gave an annotated list of references on topics which posed problems DRUG CLASSIFICATION IN THE FORMULARY
R. N., Agnew, C. H., Rios, G. Am. J. Roentgen. 1960, 84, 316. Saunders, C. G., MacEwen, D. W. Radiology, 1971, 101, 207. Shanks, S. C., Kerley, P. in Text Book of X-ray Diagnosis (edited by S. C. Shanks and P. Kerley), p. 484. London, 1969. 9. Overholt, B. F. Gastroenterology, 1975, 68, 1308. 10. Dick, A. P., Berridge, F. R., Grayson, M. J. Br. J. Radiol. 1959, 32, 432. 11. Warwick, R. R. G., Sumerling, M. D., Gilmour, H. M., Shearman, D. J. C. Am. J. Roentgen. 1973,117, 292. 12. Dilawari, J. B., Parkinson, C., Riddell, R. H., Loose, H., Williams, C. Gut, 1973, 14, 426. 13. Williams, C. B. in Advanced Medicine (edited by Michael Besser); p. 369. London, 1977. 6. 7. 8.
Cooley,
Some drugs with no therapeutic value are widely used and were cited to discourage their use. Brand names were numerous (e.g., 18 for chlordiazepoxide, 33 for nalidixic acid, 42 for ampicillin, 219 for tetracyclines) because so many firms sell the same drug.
1353 for practising physicians. The cross-index of generic and brand names was arranged so that the list of generics had to be consulted for references to the pages in the text.
continuing education. How effective it is is now being assessed through prospective studies of drug use at various levels of outpatient practice. This will permit future editions of the formulary to be improved.
DISCUSSION
Therapeutic formularies for outpatient care are not a new idea" but some features of this project deserve comment and may be of interest outside Italy. It is the first time that an organisation representing the majority of general practitioners has taken an initiative which implies strong criticism of existing medical practice, a clear contradiction of government policy on drugs, and an agreement on regular monitoring of future practice. The interest in this approach is indicated by the wide acceptance of the formulary: the Italian Medical Association has recommended it and the Lombardy region has given copies to its health centres. There has been some strong
criticism from
industry and from academic medicine, technical grounds but about curbs on the freedom of the drug market and prescribing powers. The formulary was not intended as a compulsory guide to prescription but as part of a programme of not on
Requests for reprints to G. T., Laboratory of Clinical Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri", Via Emtrea 62, 20157 Milan, Italy. REFERENCES 1. 2.
Franzosi, M. G., Tognoni, G. Riv. Ital. Pediatr. (in the press). Lunde, P. K. M. in Epidemiological Evaluation of Drugs (edited by F. Colombo, S. Shapiro, D. Slone, and G. Tognoni); p. 3. Amsterdam, 1977. 3. Kunin, C. M, J. Am. med. Assoc. 1977, 237. 4. Tognoni, G., Benedetti, F., Colombo, F., Ferrario, L., Franzosi, M. G., Mancini, M., Mandelli, M. in Epidemiological Evaluation of Drugs (edited by F. Colombo, S. Shapiro, D. Slone, and G. Tognoni); p. 17. Amsterdam, 1977. 5. Gross, F., Inman, W. H. W. (editors) Drug Monitoring. London, 1977. 6. The selection of essential drugs. W.H.O. Techn. Rep. Ser. No. 615. Geneva, 1977. 7. Lancet, 1978, i, 423. 8. Federazione Italiana Medici Mutualistici; Lombardy Regional Centre for Drug information; Instituto di Ricerche Farmacologiche "M. Negri". Prontuario 1978 per la pratica terapeutica extraospedaliera. Rome, 1978. 9. Del Favero, A. Il problema dei farmaci. Rome, 1977. 10. Martini, N. in Clinical Pharmacy (edited by E. van der Kleijn and J. R. Jonkers); p. 195. Amsterdam, 1977. 11. British National Formulary 1976-1978. British Medical Association.
Points of View NUTRITIONAL VALUE OF MULTIVITAMIN PREPARATIONS BECAUSE the diet in developing countries is often unbalanced and deficient in vitamins, multivitamin preparations are commonly prescribed. Since the major deficiencies in Iran are of riboflavin, vitamin A, and ascorbic acid,’ preparations rich in these are preferable. However, failing these, preparations should be nutri-, tionally balanced because vitamin toxicities and interactions between vitamins (such as the precipitation by folic acid of subacute combined degeneration in vitamin B12 deficiency) are known to occur. We propose a simple method of assessing multivitamins and we present the results of a survey in Iran. We took as an unbiased sample the 24 preparations which formed the total stock of a large city pharmacy in Isfahan. The composition of each product was obtained from the leaflet accompany-
ing the package. An index
was
calculated for each
The accepted requirements used are those given in Nutritioiz Reviews,2 preference being given to F.A.O./W.H.O. recommendations. For vitamins whose requirements are not given by F.A.O./W.H.O., for example, vitamin E and pyndoxme, U.S. allowances were used. Because dietary deficiencies oi panlo thenic acid, biotin, or vitamin K are so unlikely,"’ theB BBcrc
excluded from the calculation
even
it they
were
prescnt
111 a
product. A fully balanced product would have an index of 0, that is, all vitamins contained in the product are present in amounts just sufficient to meet the requirements of an equal period of time. However, we found that the indices of the products examined ranged from 3.3to 10 (median 3-1). For example, one 1975, 33, 147 S., Passmore, R., Brock, J. F, Truswell, A S. editors in Human Nutrition and Dietrics, pp. 153 and 180 Edinburgh, 1975
2. Nutr. Rev. 3. Davidson,
ORDER OF IMPORTANCE WHICH MANUFACTURERS PLACE ON VITAMINS AND RELATIVE
REQUIREMENTS
OF EACH VITAMIN BY
SPECIAL GROUPS OF PEOPLE
product according
to
the
following equation:
where the straight brackets define the absolute values of the deviations from the mean, and D=no. of days’ requirement of each vitamin present in a unit of the product calculated such that — TO=D, and N=no. of vitamins in the product. This index is actually the average deviation about D. The following is an example of how the index is calculated:
of products containing a specific vitamin. d=median no. of days’ requirements of a vitamin supplied in all the products containing that vitamin. Vitamin requirements of special groups of people are relative to that of adult male. n=no.
1
Hedayat, H , Bastani, J., Hormozdiari, H., Amouri, M, Fmami, A , Donoso, G. J. trop Pediat. 1969, 15, 125
Choice of Drugs A THERAPEUTIC FORMULARY FOR ITALIAN GENERAL PRACTITIONERS
GIANNI TOGNONI
Laboratory of Clinical Pharmacology, Istituto di Ricerche Farmacologiche "M. Negri", and Lombardy Regional Centre for Drug Information, Milan, Italy. INTRODUCTION
OUTPATIENT practice consumes a large portion of health-care resources and is the broadest area of contact between the public and health workers. Drug therapy is a major component of outpatient practice, with costs around 10-15% of the annual budget of developed countries, and drugs accompany or follow almost every medical act either as a physician’s prescription or a consumer’s request, or both. Only 4-8% of outpatient visits in Italy end without a drug prescription.’ Increasing interest is aroused by programmes of drug use,2,3 drug selection and monitoring inside and outside hospitals,4.5 and the policy on essential drugs adopted by the
W.H.O.6,7 I describe here how
therapeutic formulary for produced by the union representgeneral practice8 ing general practitioners (Federazione Italiana Medici Mutualistici) working in the N.H.S. in Italy. a
was
BACKGROUND
Drugs available in Italy are predominantly pharmaceutical products marketed by more than 400 firms:9 14 176 products are marketed under 7812 brand names. In the Minisiry of Health’s 1977 national formulary for outpatient practice, drugs were divided into categories A, B, and C corresponding to scientific reliability and clinical importance. Category A contained 3236 products under 1763 brand names, category B 5948 products (3626 names), and category C 4992 products (2423 names). In practice, however, drugs did not seem to be selected for use on these criteria of reliability and worth, and because the pharmaceutical products were listed and indexed only by their brand names the national formulary did not aid more rational prescribing. 75-80% of more than 12 000 outpatient drug prescriptions in seven Italian towns included useless, irrational, or even dangerous drugs or drug combinations.’ In hospital practice standards are set by therapeutic hospital formularies which since 1975 have been central to the drug policy of northern and central regions of Italy. Regional guide= lines at various levels of hospital care have been more widely accepted than was hoped.’,1o
In 1977 a working group from the National Commission of General Practitioners and clinical pharmacologists of the Istituto di Ricerche Farmacologiche "Mario Negri", associated with the Lombardy Regional Centre for Drug Information (C.R.I.F.), met to prepare a list of drugs to be recommended for outpatient practice. C.R.I.F. has been monitoring the use of therapeutic formularies in regional hospitals since 1975.4 The original idea of a simple list of active principles and drug products turned out to be unsatisfactory because the application of stringent criteria for selecting effective drugs would have required too many basic changes in common therapeutic practice. An annotated text was chosen, therefore, which ensured consistency between rigorous scientific standards, met the needs of daily practice, and used straightforward language. For each therapeutic class a text was agreed by the
pharmacologists and general practitioners and revised by an independent expert in the field. Decisions lIkely to be controversial or too radical for general prescribing habits and current medical knowledge were tested in daily practice by the members of the working group. This procedure lasted ten months and the text was published in January, 1978. In the formulary drugs were classified according to their therapeutic value (see table). Drugs and treatments used only in hospitals (e.g., general anaesthetics and parenteral solutions) and cancer treatments, for which referral to specialised organisations and adherence to well-defined protocols were considered necessary, were not assessed. Warnings were given on the irrational prescribing of pharmacological treatments which required specialised diagnostic competence in their use (e.g., acute and long-term treatments for hxmostatic problems, major tranquillisers and antidepressants, and treatments for real or supposed endocrinological disorders). Widely prescribed classes of drugs of doubtful value (e.g., cerebral vasodilators) and useless drugs (e.g., liver factors, organ extracts, fortifiers) were discussed in detail to emphasise their inadequacy. Within widely used therapeutic classes a few active principles were selected when many alternatives were available-e.g., cephalosporins had 8 alternatives, benzodiazepines 16, neuroleptics 27, and non-steroidal antiinflammatory agents 30. Fixed-dose combinations were excluded as first-choice drugs. Within each chapter special emphasis was given to therapeutic strategies, mechanisms of action, side-effects, and comparison of pharmacological and alternative treatments. A full chapter was devoted to placebo therapy and the final section gave an annotated list of references on topics which posed problems DRUG CLASSIFICATION IN THE FORMULARY
R. N., Agnew, C. H., Rios, G. Am. J. Roentgen. 1960, 84, 316. Saunders, C. G., MacEwen, D. W. Radiology, 1971, 101, 207. Shanks, S. C., Kerley, P. in Text Book of X-ray Diagnosis (edited by S. C. Shanks and P. Kerley), p. 484. London, 1969. 9. Overholt, B. F. Gastroenterology, 1975, 68, 1308. 10. Dick, A. P., Berridge, F. R., Grayson, M. J. Br. J. Radiol. 1959, 32, 432. 11. Warwick, R. R. G., Sumerling, M. D., Gilmour, H. M., Shearman, D. J. C. Am. J. Roentgen. 1973,117, 292. 12. Dilawari, J. B., Parkinson, C., Riddell, R. H., Loose, H., Williams, C. Gut, 1973, 14, 426. 13. Williams, C. B. in Advanced Medicine (edited by Michael Besser); p. 369. London, 1977. 6. 7. 8.
Cooley,
Some drugs with no therapeutic value are widely used and were cited to discourage their use. Brand names were numerous (e.g., 18 for chlordiazepoxide, 33 for nalidixic acid, 42 for ampicillin, 219 for tetracyclines) because so many firms sell the same drug.
1353 for practising physicians. The cross-index of generic and brand names was arranged so that the list of generics had to be consulted for references to the pages in the text.
continuing education. How effective it is is now being assessed through prospective studies of drug use at various levels of outpatient practice. This will permit future editions of the formulary to be improved.
DISCUSSION
Therapeutic formularies for outpatient care are not a new idea" but some features of this project deserve comment and may be of interest outside Italy. It is the first time that an organisation representing the majority of general practitioners has taken an initiative which implies strong criticism of existing medical practice, a clear contradiction of government policy on drugs, and an agreement on regular monitoring of future practice. The interest in this approach is indicated by the wide acceptance of the formulary: the Italian Medical Association has recommended it and the Lombardy region has given copies to its health centres. There has been some strong
criticism from
industry and from academic medicine, technical grounds but about curbs on the freedom of the drug market and prescribing powers. The formulary was not intended as a compulsory guide to prescription but as part of a programme of not on
Requests for reprints to G. T., Laboratory of Clinical Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri", Via Emtrea 62, 20157 Milan, Italy. REFERENCES 1. 2.
Franzosi, M. G., Tognoni, G. Riv. Ital. Pediatr. (in the press). Lunde, P. K. M. in Epidemiological Evaluation of Drugs (edited by F. Colombo, S. Shapiro, D. Slone, and G. Tognoni); p. 3. Amsterdam, 1977. 3. Kunin, C. M, J. Am. med. Assoc. 1977, 237. 4. Tognoni, G., Benedetti, F., Colombo, F., Ferrario, L., Franzosi, M. G., Mancini, M., Mandelli, M. in Epidemiological Evaluation of Drugs (edited by F. Colombo, S. Shapiro, D. Slone, and G. Tognoni); p. 17. Amsterdam, 1977. 5. Gross, F., Inman, W. H. W. (editors) Drug Monitoring. London, 1977. 6. The selection of essential drugs. W.H.O. Techn. Rep. Ser. No. 615. Geneva, 1977. 7. Lancet, 1978, i, 423. 8. Federazione Italiana Medici Mutualistici; Lombardy Regional Centre for Drug information; Instituto di Ricerche Farmacologiche "M. Negri". Prontuario 1978 per la pratica terapeutica extraospedaliera. Rome, 1978. 9. Del Favero, A. Il problema dei farmaci. Rome, 1977. 10. Martini, N. in Clinical Pharmacy (edited by E. van der Kleijn and J. R. Jonkers); p. 195. Amsterdam, 1977. 11. British National Formulary 1976-1978. British Medical Association.
Points of View NUTRITIONAL VALUE OF MULTIVITAMIN PREPARATIONS BECAUSE the diet in developing countries is often unbalanced and deficient in vitamins, multivitamin preparations are commonly prescribed. Since the major deficiencies in Iran are of riboflavin, vitamin A, and ascorbic acid,’ preparations rich in these are preferable. However, failing these, preparations should be nutri-, tionally balanced because vitamin toxicities and interactions between vitamins (such as the precipitation by folic acid of subacute combined degeneration in vitamin B12 deficiency) are known to occur. We propose a simple method of assessing multivitamins and we present the results of a survey in Iran. We took as an unbiased sample the 24 preparations which formed the total stock of a large city pharmacy in Isfahan. The composition of each product was obtained from the leaflet accompany-
ing the package. An index
was
calculated for each
The accepted requirements used are those given in Nutritioiz Reviews,2 preference being given to F.A.O./W.H.O. recommendations. For vitamins whose requirements are not given by F.A.O./W.H.O., for example, vitamin E and pyndoxme, U.S. allowances were used. Because dietary deficiencies oi panlo thenic acid, biotin, or vitamin K are so unlikely,"’ theB BBcrc
excluded from the calculation
even
it they
were
prescnt
111 a
product. A fully balanced product would have an index of 0, that is, all vitamins contained in the product are present in amounts just sufficient to meet the requirements of an equal period of time. However, we found that the indices of the products examined ranged from 3.3to 10 (median 3-1). For example, one 1975, 33, 147 S., Passmore, R., Brock, J. F, Truswell, A S. editors in Human Nutrition and Dietrics, pp. 153 and 180 Edinburgh, 1975
2. Nutr. Rev. 3. Davidson,
ORDER OF IMPORTANCE WHICH MANUFACTURERS PLACE ON VITAMINS AND RELATIVE
REQUIREMENTS
OF EACH VITAMIN BY
SPECIAL GROUPS OF PEOPLE
product according
to
the
following equation:
where the straight brackets define the absolute values of the deviations from the mean, and D=no. of days’ requirement of each vitamin present in a unit of the product calculated such that — TO=D, and N=no. of vitamins in the product. This index is actually the average deviation about D. The following is an example of how the index is calculated:
of products containing a specific vitamin. d=median no. of days’ requirements of a vitamin supplied in all the products containing that vitamin. Vitamin requirements of special groups of people are relative to that of adult male. n=no.
1
Hedayat, H , Bastani, J., Hormozdiari, H., Amouri, M, Fmami, A , Donoso, G. J. trop Pediat. 1969, 15, 125
