Br. J. clin. Pharmac. (1978), 6, 191-192
POST-MARKETING DRUG SURVEILLANCE The recent debate on the need for monitored release of new drugs has produced several possible ways and means. The essential aims of the different schemes are similar; early detection of adverse drug reactions by recording all adverse events occurring in a specified number of patients for an appropriate period of time; under conditions resembling as far as possible those in which the new drug will be used; endeavouring to avoid collecting masses of unusable data and minimising costs. 1 The registered release scheme of Dollery & Rawlins (1977) requires the prescribing doctor to complete a special four part form, a copy of which goes to the central agency. Follow up questionnaires are sent from the agency to the doctor and also to the patient. With this scheme normal commercial promotion would be difficult, or as is proposed, excluded for a period. Patient selection is likely to be influenced by excluding patients thought unsuitable to receive a questionnaire. 2 The recorded release scheme of Inman (1977) entails the use of a special general practitioner prescription form (FP 10), a copy going to a central agency from where questionnaires emanate at intervals to the doctor. Normal marketing is possible although the doctors prescribing habit may be altered, by having to use a special general practitioner prescription form, and having to handle the subsequent questionnaires. 3 The monitored release scheme of Lawson & Henry (1977) requires a transcription by the retail pharmacist of the doctors normal general practitioner prescription form on to a simple form. This is forwarded to a central agency. As with the recorded release proposal this scheme has the advantage of less interference with both the doctors usual prescribing and the Company's promotion routine. It has the disadvantage that it is necessary to copy the general practitioner prescription form. 4 The proposals for post-marketing surveillance by Wilson (1977) on behalf of the pharmaceutical industry, are similar to those of Lawson & Henry (1977) with the variation that the general practitioner prescription form would be identified and copied by the Prescription Pricing Authority. 5 Recently the Committee of Safety of Medicines have issued proposals for a 'recorded release' scheme. Identification of patients and their doctors is achieved by the Prescription Pricing Authority from normal general practitioner prescription forms or by the hospital pharmacist using a special form, as appropriate. Follow up on three-
four occasions of 5,000-10,000 cases is being suggested. The nature of the monitoring centre is not mentioned. A feasibility study is to be carried out. The five schemes outlined would all satisfy the requirement for monitoring of new drugs as they pass into general and unrestricted use. How well they would function in practice would depend to a great degree on the general willingness of doctors to take on the additional commitments. It is likely that any worthwhile scheme will require extra work and demand extra therapeutic interest from the prescribing doctors during the period of surveillance and this is best fully recognised. A case could be made for an intermediate or restricted release system for the introduction of new drugs before their widespread use, half way between clinical trials and the monitored release proposals. Because of inevitable delays it is possible that by the time 5,000-10,000 cases have been fully monitored by any of the above schemes, many more patients will have been exposed to the drug so that any serious adverse reactions in the monitored group are duplicated in those patients not fully monitored. The duration of the 'restricted release' phase would depend on the drug and disease concerned. Monitoring of patients would continue, when appropriate after the drug became generally available. The restricted release system might entail the use of specially marked general practitioner prescription forms, involve a central agency and the pharmaceutical company concerned and the use of a simple case report form giving the results of efficacy as well as safety. The scheme would ensure that all patients receiving the drug would be monitored and produce useful and reliable data from each case. Participation might reasonably be confined to the patients of doctors who had a special interest in new drugs and attended some sort of postgraduate training courses in clinical pharmacology and had a minimum number of years experience as specialist or general practitioner. Fewer doctors would be involved than in the previously proposed scheme, reducing the problems of surveillance. A fee for completion of case reports would probably be needed and the cost of the exercise paid for by the pharmaceutical company concerned whilst the cost of the drug would be paid in the usual way by the NHS. Limited advertising of the drug through the medium of company representatives would be possible. It would be fair to extend the effective patent life of the drug to compensate the manufacturer for the further delay and expense in development. Although it is not the main subject of this editorial it is perhaps
192
high time, with the increasing demands of advancing techniques and drug regulatory bodies, that the patent life of a new drug was related in some way to the time when it has been licenced for marketing. In the process of producing simple but reliable results from a larger number of patients than is normally possible, there would be the added advantage of improving knowledge of and interest in clinical pharmacology, thus enhancing the skill of the prescribing doctor. There is indeed a need for a greater
emphasis on scientifically based drug therapeutics in continuing postgraduate education for until recently, as a legacy from the past when there were few active chemicals available for use, insufficient emphasis has been given to the subject both at under and postgraduate level. RJ. WALDEN& B.N.C. PRICHARD Department of Clinical Pharmacology, University College Hospital Medical School, WCIE 6JJ
References COMMITTEE ON SAFETY OF MEDICINES (1978).
Proposals for improved post-marketing surveillance. Pharm. J., 220, 193. DOLLERY, C.T. & RAWLINS, M.D. (1977). Monitoring adverse reactions to drugs. Br. med.J., 1, 96-97. INMAN, W.H.W. (1977). Recorded release. In Drug monitoring, eds. Gross, F.M. & Inman, W.H.W. pp.
65-78. London: Academic Press. LAWSON, D.H. & HENRY, D.A. (1977). Monitoring adverse reactions to new drugs: 'Restricted release' or 'Monitored release'. Br. med.J., 1, 691-692. WILSON, A.B. (1977). Post-marketing surveillance of adverse reactions to new medicines. Br. med. J., 2, 1001-1003.
POST-MARKETING DRUG SURVEILLANCE The recent debate on the need for monitored release of new drugs has produced several possible ways and means. The essential aims of the different schemes are similar; early detection of adverse drug reactions by recording all adverse events occurring in a specified number of patients for an appropriate period of time; under conditions resembling as far as possible those in which the new drug will be used; endeavouring to avoid collecting masses of unusable data and minimising costs. 1 The registered release scheme of Dollery & Rawlins (1977) requires the prescribing doctor to complete a special four part form, a copy of which goes to the central agency. Follow up questionnaires are sent from the agency to the doctor and also to the patient. With this scheme normal commercial promotion would be difficult, or as is proposed, excluded for a period. Patient selection is likely to be influenced by excluding patients thought unsuitable to receive a questionnaire. 2 The recorded release scheme of Inman (1977) entails the use of a special general practitioner prescription form (FP 10), a copy going to a central agency from where questionnaires emanate at intervals to the doctor. Normal marketing is possible although the doctors prescribing habit may be altered, by having to use a special general practitioner prescription form, and having to handle the subsequent questionnaires. 3 The monitored release scheme of Lawson & Henry (1977) requires a transcription by the retail pharmacist of the doctors normal general practitioner prescription form on to a simple form. This is forwarded to a central agency. As with the recorded release proposal this scheme has the advantage of less interference with both the doctors usual prescribing and the Company's promotion routine. It has the disadvantage that it is necessary to copy the general practitioner prescription form. 4 The proposals for post-marketing surveillance by Wilson (1977) on behalf of the pharmaceutical industry, are similar to those of Lawson & Henry (1977) with the variation that the general practitioner prescription form would be identified and copied by the Prescription Pricing Authority. 5 Recently the Committee of Safety of Medicines have issued proposals for a 'recorded release' scheme. Identification of patients and their doctors is achieved by the Prescription Pricing Authority from normal general practitioner prescription forms or by the hospital pharmacist using a special form, as appropriate. Follow up on three-
four occasions of 5,000-10,000 cases is being suggested. The nature of the monitoring centre is not mentioned. A feasibility study is to be carried out. The five schemes outlined would all satisfy the requirement for monitoring of new drugs as they pass into general and unrestricted use. How well they would function in practice would depend to a great degree on the general willingness of doctors to take on the additional commitments. It is likely that any worthwhile scheme will require extra work and demand extra therapeutic interest from the prescribing doctors during the period of surveillance and this is best fully recognised. A case could be made for an intermediate or restricted release system for the introduction of new drugs before their widespread use, half way between clinical trials and the monitored release proposals. Because of inevitable delays it is possible that by the time 5,000-10,000 cases have been fully monitored by any of the above schemes, many more patients will have been exposed to the drug so that any serious adverse reactions in the monitored group are duplicated in those patients not fully monitored. The duration of the 'restricted release' phase would depend on the drug and disease concerned. Monitoring of patients would continue, when appropriate after the drug became generally available. The restricted release system might entail the use of specially marked general practitioner prescription forms, involve a central agency and the pharmaceutical company concerned and the use of a simple case report form giving the results of efficacy as well as safety. The scheme would ensure that all patients receiving the drug would be monitored and produce useful and reliable data from each case. Participation might reasonably be confined to the patients of doctors who had a special interest in new drugs and attended some sort of postgraduate training courses in clinical pharmacology and had a minimum number of years experience as specialist or general practitioner. Fewer doctors would be involved than in the previously proposed scheme, reducing the problems of surveillance. A fee for completion of case reports would probably be needed and the cost of the exercise paid for by the pharmaceutical company concerned whilst the cost of the drug would be paid in the usual way by the NHS. Limited advertising of the drug through the medium of company representatives would be possible. It would be fair to extend the effective patent life of the drug to compensate the manufacturer for the further delay and expense in development. Although it is not the main subject of this editorial it is perhaps
192
high time, with the increasing demands of advancing techniques and drug regulatory bodies, that the patent life of a new drug was related in some way to the time when it has been licenced for marketing. In the process of producing simple but reliable results from a larger number of patients than is normally possible, there would be the added advantage of improving knowledge of and interest in clinical pharmacology, thus enhancing the skill of the prescribing doctor. There is indeed a need for a greater
emphasis on scientifically based drug therapeutics in continuing postgraduate education for until recently, as a legacy from the past when there were few active chemicals available for use, insufficient emphasis has been given to the subject both at under and postgraduate level. RJ. WALDEN& B.N.C. PRICHARD Department of Clinical Pharmacology, University College Hospital Medical School, WCIE 6JJ
References COMMITTEE ON SAFETY OF MEDICINES (1978).
Proposals for improved post-marketing surveillance. Pharm. J., 220, 193. DOLLERY, C.T. & RAWLINS, M.D. (1977). Monitoring adverse reactions to drugs. Br. med.J., 1, 96-97. INMAN, W.H.W. (1977). Recorded release. In Drug monitoring, eds. Gross, F.M. & Inman, W.H.W. pp.
65-78. London: Academic Press. LAWSON, D.H. & HENRY, D.A. (1977). Monitoring adverse reactions to new drugs: 'Restricted release' or 'Monitored release'. Br. med.J., 1, 691-692. WILSON, A.B. (1977). Post-marketing surveillance of adverse reactions to new medicines. Br. med. J., 2, 1001-1003.
