Journal of Community Health Vol. 2, No. 2, Winter 1976
EVALUATING DRUGS AND DETERMINING THE DRUG NEEDS OF DEVELOPED AND DEVELOPING COUNTRIES Paul D. Stolley, M.D., M.P.H.
A B S T R A C T : The practice of reviewing drug utilization provides a surveillance system for m o n i t o r i n g the efficiency of drug distribution and drug c o n s u m p t i o n ; it also provides a data base for the interpretation of the f r e q u e n c y of adverse drug reactions and helps to identify gaps in the delivery o f a crucial aspect of health services: the provision of safe and efficacious medicines. M a l c o n s u m p t i o n (either over- or under-utilization or needless prescribing) can be identified and economies might be achieved, once these p r o b l e m s are corrected. Linking drug utilization with standard health indices, such as m o r b i d i t y and m o r t a l i t y rates, can help assess the effects of widely used drugs, b o t h adverse and beneficial. Drug utilization review should be considered an essential activity of a well-organized health delivery system; it has great potential for b o t h health planning and evaluation. These positions are discussed as they relate to developed and developing countries.
This article will consider some problems of drug utilization in both developed and less-developed nations and how many of these problems could be ameliorated by the use of data to help shape new policies. The data needed include drug utilization studies, epidemiologic investigations, controlled clinical trials, and economic analyses.
ASSESSING THE DRUG NEEDS OF POPULATIONS Drug Use in the Developed Countries
Developed countries are in a fortunate position, in that most of their public health agencies conduct periodic morbidity and mortality surveys of random samples of their populations. Thus, they have reasonably accurate estimates of the prevalent and incident diseases that are responsive to drug therapy. Of course, many of the most highly prevalent diseases (coronary heart disease, upper respiratory viral infections, adult-onset diabetes) are at present untreatable by means of oral drugs; however, many drugs are being Dr. Stolley is Professor in the Department of Research Medicine, University of Pennsylvania School of Medicine, 36th and Hamilton Walk, Philadelphia, Pennsylvania 19174. This work was supported by grant HS-00429 from the National Center for Health Services Research. This article is based on the presentation, "The Use of Data in Evaluating Drugs and in Determining the Drug Needs of Communities," presented at the Annual Meeting of the Association of Teachers of Preventive Medicine, Chicago, Illinois, November 16, 1975. The work reported was completed while the author was Associate Professor, Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland. The author wishes to acknowledge the advice and help of Philip Lee, Mark Novitch, George Silver, and Milton Silverman. Also, the preparation and editing of the manuscript by Kathy Kelly and Ann Rutledge is appreciated. 113
114
JOURNAL OF COMMUNITY HEALTH
marketed for these indications, despite their having no adequate proof of efficacy. Pharmaceutical firms in the developed countries have expended much money in the effort to promote drugs of an unproven efficacy for the treatment of highly prevalent conditions that are either currently unresponsive to therapy or trivial and self-limiting conditions that might better be left untreated. These efforts have contributed to the over-utilization of some drugs of questionable efficacy or of even significant toxicity with no concomitant proof of efficacy. Examples of this situation include the wide promotion and use of oral hypoglycemics, "long-acting" nitrates for ischemic heart disease, clofibrate for hypercholesterolemia, and antihistamines for respiratory infections of non-allergic etiology. A summary of the situation in many of the developed countries reads: 1. The research and promotional activities of large pharmaceutical companies are often directed at lucrative markets, although inefficacious, unnecessary, or duplicative drugs are all that may be available. 2. The promotional activities of large pharmaceutical companies are often designed to widen the indications for certain therapeutic drug classes. An example of this activity is how the exigencies and difficulties of daily living are redefined and relabeled as a disease that is treatable by the use of psychoactive agents. This effort has led to a striking increase in the use of psychoactive drugs, such that we had about 80 million prescriptions for diazepam and chlordiazepoxide (Valium and Librium) issued in the United States during 1 9 7 4 - f o r a population of about 210 million. The Lancet commented editorially: "at this rate the arrival of the millennium [i.e., the year 2000] will coincide with the total tranquilization of America". 1 3. The research activities of pharmaceutical companies are directed largely to the development of drugs for the symptomatic relief of such common, but essentially trivial and self-limiting, conditions as viral colds rather than to the development of agents for more serious, but less common, illnesses where the market for a useful drug would be smaller. 4. Patient " d e m a n d " for drugs has also contributed to overutilization, but much of this patient desire for medication has probably been stimulated by the promotional activities of the drug companies, by the public's unawareness about the risks involved with drugs, and by the desire of busy physicians to terminate patient interviews by issuing a prescription. 5. About 15% of the medical care dollar goes for drugs and drug sundries in developed nations; much of this expenditure is for needless, questionably efficacious, or toxic drugs. 6. The oligopolistic structure of the drug industry in much of the Western industrialized world has led to alleged episodes of price-fixing (with the tetracyclines, for example), high prices that are artificially maintained because of the way patent laws have been applied, and even alleged fraud in estimating production costs when prices have been set, particularly for government drug purchases that are paid for on the basis of production cost
Assessing Drug Needs
115
plus allowable markup. These practices are under investigation in England, where the National Health Service purchases drugs directly from the manufacturers. 7. The practice of permitting the licensing of multiple congeners with different proprietary names has produced a confusing drug nomenclature; this makes any understanding about drugs and drug action far more difficult than it need be. On the other hand, there are problems of under-utilization in developed countries. It is reported that many hypertensives go untreated, in spite of the proven efficacy of certain antihypertensive agents in preventing morbidity and mortality from the disease. Part of this under-utilization is due to poor patient compliance (possibly because of some of these drugs' undesirable side effects, such as impotence or orthostatic hypotension); other reasons include cost, lack of education, and lack of screening programs to detect treatable hypertensives. The Special Problems in Developing Countries Developing countries often lack the resources needed to assess accurately their health needs as they are related to drugs; thus, establishing priorities for drug requirements is difficult. Nonetheless, morbidity surveys and extant health records usually permit the setting of health care priorities, although the quantitative data used may often be of questionable accuracy. As with the developed countries, over-utilization of drugs and adverse drug reactions may occur, but they are of lower priority for those countries with limited economic and material resources or those where severe shortages of health personnel exist. The problems of greatest importance in the developing countries are: 1. Difficulties in obtaining and purchasing the required efficacious drugs in an adequate supply; 2. The lack of adequate drug transportation, distribution, and storage facilities; 3. General failure to establish national priorities for drugs and biologicals; 4. Lack of an indigenous drug industry (in those countries with the population or technological base to support it) to help guarantee the quality and the amount of drugs needed for the particular diseases that receive a high priority for treatment; 5. Inadequate expansion of drug distribution systems, other than the traditional physician-as-prescriber model--other alternatives would include pharmacists and other health workers, including traditional "healers"; 6. Insufficient political and economic cooperation among developing countries to provide the bargaining leverage needed with the large, multinational pharmaceutical cartels that supply many of the required drugs; 7. Inability to influence the larger pharmaceutical firms to conduct
116
JOURNAL OF COMMUNITY HEALTH
the research that would be designed to develop drugs specifically for the treatment of t h e diseases that are highly prevalent in the developing countries; 8. Lack of a regulatory apparatus to control the promotion, quality, and efficacy of drugs marketed by companies based in the developed countries; 9. Inadequate public education that would help to ensure compliance with efficacious therapies.
P O S S I B L E S O L U T I O N S TO D R U G
UTILIZATION PROBLEMS Methods are needed to correct under- and over-utilization and irrational prescribing, to reduce unnecessary expenditures for drugs in developed and developing countries, and to encourage the marketing of only safe and efficacious drugs. Some suggestions to achieve these goals follow: 1. Licensing should be limited to efficacious drugs that have been tested by the well-accepted principles embodied in the controlled clinical trial. This method is generally accepted, although some still follow the reasoning of Galen, who said, "All who drink of this remedy recover in a short time, except those whom it does not help, who all die. Therefore it is obvious that it fails only in incurable cases". 2 2. Drug promotion should be restricted so that drugs can be advertised only for indications where efficacy has been proven. The World Health Organization could devise a set of model legal regulations to control drug promotion. 3. Patent protection laws for the licensing of drugs should be altered and methods should be encouraged that would alter the oligopolistic economic structure of the industry to encourage price competition and that would prevent collusion in price-setting. 4. The adoption of a "relative efficacy" system for the licensing of new drugs should be encouraged. Such a system would not permit the licensing of a drug congener unless some distinct therapeutic or economic advantage over preexisting drugs for the same indication could be demonstrated. This would discourage the marketing of duplicative drugs and would encourage industry research in innovative areas for which there is a greater need for new and effective therapies. 5. National drug lists of efficacious drugs for particular conditions could be established, so that reimbursement of drug costs under national insurance schemes would not be available for inefficacious, unsafe, unnecessary, or needlessly expensive drugs. National or local health agencies should be encouraged to develop programs of drug education to discourage the taking of a pill for every ill and to substitute more healthful eating and living patterns instead (e.g., physical exercise). Governmental efforts should be
Assessing Drug Needs
117
encouraged in public education about the proper use of over-the-counter drugs. Authoritative and readable information about drugs should be provided }or patients, physicians, and pharmacists. 6. The role of the pharmacist as a member of the health care team could be expanded so that he or she may serve as a drug information specialist to physicians and patients-and also explain to patients why n o drug therapy at all may constitute good medical practice. 7. When safe and efficacious therapies are discovered, screening efforts should be organized to locate treatable cases and to provide adequate followup and compliance with therapy. 8. The effects of mass therapies should be evaluated by the use of epidemiological surveys and studies, such as analyses of vital statistics and morbidity surveys. 9. Drug utilization review in hospitals and clinics should be encouraged so that criteria for appropriate drug use may be set, using controlled clinical trials; periodic utilization review may then be employed to ensure adherence to the criteria. 10. Local and national systems of drug utilization review should be established using (a) pharmacy audits, (b) manufacturers' sales data, (c) hospital and clinic drug utilization data, (d) ad hoe studies and surveys, (e) marketing research firms' estimates, (f) government reporting systems, and (g) adverse drug reaction reporting systems or registries. Drug utilization data could be linked with health survey data so that an examination of disease incidence and prevalence would reveal areas of over- or under-utilization of drugs. For example, in a study conducted in the United States, nearly 3.5% of all prescriptions filled in pharmacies were for amphetamines, known to be addictive and of unproven efficacy in the long-term treatment of obesity. 3 Similarly, under-utilization may be detected, as a comparison of the use of antihypertensive medications and hypertension prevalence figures will reveal. 11. Periodic epidemiological surveillance of disease incidence and prevalence should be instituted for conditions where either beneficial or adverse drug effects might be anticipated. An interesting example of the application of these techniques is illustrated in Figure 1. An examination of the mortality rates attributed to asthma was correlated with the introduction of a new nebulizer therapy. As nebulizer use declined, so did the death rates. Further investigation revealed a doseresponse relationship, and a particularly potent formulation was further implicated. 4's Another example is the examination of the death rates due to thromboembolism during the years before and after the introduction of oral contraceptives, in both the United States and the United Kingdom. This review revealed the pattern of an increase in the death rates among females that was consistent with the hypothesis that the estrogen-containing oral contraceptives could cause fatal pulmonary embolism. 6 The examination of death rates due to bladder cancer in the United
118
JOURNAL OF COMMUNITY HEALTH
G O V E R N M E N T W A R N I N G ABOUT DANGERS OF N E B U L I Z E R S ISSUED; DECLINE IN S A L E S F O L L O W S ~
03 z
1 I m
o
oo ,.=, 0. I.iJ IZ:
I
-r
I.d c~
I 59
I 60
I, 61
I 62
1, 63
I 64
I 65
I 66
i
67
YEAR
FIGURE 1: Correlation of Asthma Nebulizer Sales and Asthma Death Rates--AnnuM Mortality Rate from Asthma, 1959 to 1967, for Persons 5 to 34 Years Old in England and Wales Kingdom provided no such support for the hypothesis that non-nutritive artificial sweeteners cause human bladder carcinoma. 7 An examination of death rates due to hypertensive disease, stroke, rheumatic heart disease, pneumococcal pneumonia, and poliomyelitis provided some evidence of the efficacy and the efficient use of appropriate therapies or vaccines in the United States (Figure 2). The decline in polio mortality rates after the introduction of successful vaccines is notable. Retrospective epidemiological investigations in the United States have led to the discovery of many cases of vaginal cancer among young w o m e n exposed to diethylstilbestrol in utero. 8 Post-marketing epidemiological surveillance of certain drugs or devices may contribute to the assessment of the true risk of more recent agents (e.g., oral contraceptives, intrauterine devices, depot progestogen contraceptives, and levodopa). In summary, epidemiological tools and methods, b o t h ad hoc studies and continuing intensive surveillance systems, could make an important
Assessing Drug Needs
119
Deaths / I00,000 3.0
m
POLIOM YELl TIS
2.0-
i
1.0-
0 1900
I
I
I
1920
l
I-
J
I
1940
I
I
1960
1980 Year
FIGURE 2: Decline in Poliomyelitis Mortality due to Introduction of Effective Vaccines--Poliomyelitis Deaths per 100,000 Population, Showing Impact of Salk and Sabin Vaccines
contribution to an identification of the under- and over-consumption of drugs. They would also provide a crude m e t h o d for assessing drug efficacy and the efficiency of drug distribution and could aid in the detection of adverse drug reactions. 9 Establishing Priorities for the Selection of Drugs and Biologicals j u s t as developed countries would do well to establish national drug lists that would contain only the approved, significant, safe, and efficacious drugs, such a list would assume an even greater importance for developing countries because of their more limited resources and less available funds for drug purchases. Experiences with military needs, hospitals, drug insurance programs, and with specific developing countries suggest that the list of drugs required for most treatable illnesses is not long--probably only about 200 to 500 different chemical entities. Both developed and developing countries are under great pressure from the influential and well-organized pharmaceutical industry (and an often uncritical cadre of medical practi-
120
J O U R N A L OF C O M M U N I T Y H E A L T H
tioners) to expand the list of available drugs. A carefully scrutinized and flexibly applied "relative efficacy" system, such as that of Norway, would help to limit the number of drugs purchased by developing countries to those that are primarily most efficacious and most congruent with the health needs of their populations 1° Indeed, the delivery of an inefficacious drug is wasteful of both intellectual and technological resources, since the false belief that the agent used is efficacious delays work on the development of a truly useful medication. It is hard to over-estimate the importance of obtaining evidence of efficacy from controlled clinical trials prior to purchasing and mass distribution of drugs in developing countries. And yet, if one examines the drugs available and widely used in developing countries, one finds numerous examples of inefficacious, yet costly drugs that will have no beneficial public health effects, no matter how efficiently they are distributed. This represents a waste of resources that must be corrected. The guiding principles for setting priorities in drug procurement for developing countries should not only include linking the drug to the prevalent disease patterns but also emphasize drug safety and efficacy, first and foremost. The developed countries have many examples of drugs efficiently produced, stored, and distributed-but they are relatively inefficacious, unsafe, or needlessly expensive. It is clear that developing countries cannot afford the luxury of inefficacious drugs.
REFERENCES 1. Benzodiazepines: Use, overuse, misuse, abuse? editorial. Lancet 1:1101-1102, 1973. 2. England J: Medical Research. London, Churchill & Livingstone, 1975. 3. Stolley PD, Becker MH, McEvilla JD, et ah Drug prescribing and use in an American community. A n n Intern Med 76:37-40, 1972. 4. Inman WH, Adelstein AM: Rise and fall of asthma mortality in England and Wales in relation to use of pressurized aerosols. Lancet 2:279-285, 1969. 5. Stolley PD: Asthma mortality: Why the United States was spared an epidemic of deaths due to asthma. A m Rev Respir Dis 105:883-890, 1972. 6. SartweU PE, Stolley PD, Tonascia JA, et al: Pulmonary embolism mortality in relation to oral contraceptive use. Prey M e d 5:15-19, 1976. 7. Burbank F, Fraumeni JF Jr: Synthetic sweetener consumption and bladder cancer trends in the United States. Nature 227: 296-297, 1970. 8. Herbst AL, Ulfelder H, Poskanzer DC: Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N E n g l J M e d 284:878-881, 1971. 9. Stolley PD: How study of geographic epidemiology of disease can help in detection of adverse drug reactions. Clin Pharm and Ther 19(Part 2):679-682, 1976. 10. Stolley PD, Goddard JL: A "relative efficacy" system for new drugs. A n n Intern Med 73:479--480, 1970.
EVALUATING DRUGS AND DETERMINING THE DRUG NEEDS OF DEVELOPED AND DEVELOPING COUNTRIES Paul D. Stolley, M.D., M.P.H.
A B S T R A C T : The practice of reviewing drug utilization provides a surveillance system for m o n i t o r i n g the efficiency of drug distribution and drug c o n s u m p t i o n ; it also provides a data base for the interpretation of the f r e q u e n c y of adverse drug reactions and helps to identify gaps in the delivery o f a crucial aspect of health services: the provision of safe and efficacious medicines. M a l c o n s u m p t i o n (either over- or under-utilization or needless prescribing) can be identified and economies might be achieved, once these p r o b l e m s are corrected. Linking drug utilization with standard health indices, such as m o r b i d i t y and m o r t a l i t y rates, can help assess the effects of widely used drugs, b o t h adverse and beneficial. Drug utilization review should be considered an essential activity of a well-organized health delivery system; it has great potential for b o t h health planning and evaluation. These positions are discussed as they relate to developed and developing countries.
This article will consider some problems of drug utilization in both developed and less-developed nations and how many of these problems could be ameliorated by the use of data to help shape new policies. The data needed include drug utilization studies, epidemiologic investigations, controlled clinical trials, and economic analyses.
ASSESSING THE DRUG NEEDS OF POPULATIONS Drug Use in the Developed Countries
Developed countries are in a fortunate position, in that most of their public health agencies conduct periodic morbidity and mortality surveys of random samples of their populations. Thus, they have reasonably accurate estimates of the prevalent and incident diseases that are responsive to drug therapy. Of course, many of the most highly prevalent diseases (coronary heart disease, upper respiratory viral infections, adult-onset diabetes) are at present untreatable by means of oral drugs; however, many drugs are being Dr. Stolley is Professor in the Department of Research Medicine, University of Pennsylvania School of Medicine, 36th and Hamilton Walk, Philadelphia, Pennsylvania 19174. This work was supported by grant HS-00429 from the National Center for Health Services Research. This article is based on the presentation, "The Use of Data in Evaluating Drugs and in Determining the Drug Needs of Communities," presented at the Annual Meeting of the Association of Teachers of Preventive Medicine, Chicago, Illinois, November 16, 1975. The work reported was completed while the author was Associate Professor, Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland. The author wishes to acknowledge the advice and help of Philip Lee, Mark Novitch, George Silver, and Milton Silverman. Also, the preparation and editing of the manuscript by Kathy Kelly and Ann Rutledge is appreciated. 113
114
JOURNAL OF COMMUNITY HEALTH
marketed for these indications, despite their having no adequate proof of efficacy. Pharmaceutical firms in the developed countries have expended much money in the effort to promote drugs of an unproven efficacy for the treatment of highly prevalent conditions that are either currently unresponsive to therapy or trivial and self-limiting conditions that might better be left untreated. These efforts have contributed to the over-utilization of some drugs of questionable efficacy or of even significant toxicity with no concomitant proof of efficacy. Examples of this situation include the wide promotion and use of oral hypoglycemics, "long-acting" nitrates for ischemic heart disease, clofibrate for hypercholesterolemia, and antihistamines for respiratory infections of non-allergic etiology. A summary of the situation in many of the developed countries reads: 1. The research and promotional activities of large pharmaceutical companies are often directed at lucrative markets, although inefficacious, unnecessary, or duplicative drugs are all that may be available. 2. The promotional activities of large pharmaceutical companies are often designed to widen the indications for certain therapeutic drug classes. An example of this activity is how the exigencies and difficulties of daily living are redefined and relabeled as a disease that is treatable by the use of psychoactive agents. This effort has led to a striking increase in the use of psychoactive drugs, such that we had about 80 million prescriptions for diazepam and chlordiazepoxide (Valium and Librium) issued in the United States during 1 9 7 4 - f o r a population of about 210 million. The Lancet commented editorially: "at this rate the arrival of the millennium [i.e., the year 2000] will coincide with the total tranquilization of America". 1 3. The research activities of pharmaceutical companies are directed largely to the development of drugs for the symptomatic relief of such common, but essentially trivial and self-limiting, conditions as viral colds rather than to the development of agents for more serious, but less common, illnesses where the market for a useful drug would be smaller. 4. Patient " d e m a n d " for drugs has also contributed to overutilization, but much of this patient desire for medication has probably been stimulated by the promotional activities of the drug companies, by the public's unawareness about the risks involved with drugs, and by the desire of busy physicians to terminate patient interviews by issuing a prescription. 5. About 15% of the medical care dollar goes for drugs and drug sundries in developed nations; much of this expenditure is for needless, questionably efficacious, or toxic drugs. 6. The oligopolistic structure of the drug industry in much of the Western industrialized world has led to alleged episodes of price-fixing (with the tetracyclines, for example), high prices that are artificially maintained because of the way patent laws have been applied, and even alleged fraud in estimating production costs when prices have been set, particularly for government drug purchases that are paid for on the basis of production cost
Assessing Drug Needs
115
plus allowable markup. These practices are under investigation in England, where the National Health Service purchases drugs directly from the manufacturers. 7. The practice of permitting the licensing of multiple congeners with different proprietary names has produced a confusing drug nomenclature; this makes any understanding about drugs and drug action far more difficult than it need be. On the other hand, there are problems of under-utilization in developed countries. It is reported that many hypertensives go untreated, in spite of the proven efficacy of certain antihypertensive agents in preventing morbidity and mortality from the disease. Part of this under-utilization is due to poor patient compliance (possibly because of some of these drugs' undesirable side effects, such as impotence or orthostatic hypotension); other reasons include cost, lack of education, and lack of screening programs to detect treatable hypertensives. The Special Problems in Developing Countries Developing countries often lack the resources needed to assess accurately their health needs as they are related to drugs; thus, establishing priorities for drug requirements is difficult. Nonetheless, morbidity surveys and extant health records usually permit the setting of health care priorities, although the quantitative data used may often be of questionable accuracy. As with the developed countries, over-utilization of drugs and adverse drug reactions may occur, but they are of lower priority for those countries with limited economic and material resources or those where severe shortages of health personnel exist. The problems of greatest importance in the developing countries are: 1. Difficulties in obtaining and purchasing the required efficacious drugs in an adequate supply; 2. The lack of adequate drug transportation, distribution, and storage facilities; 3. General failure to establish national priorities for drugs and biologicals; 4. Lack of an indigenous drug industry (in those countries with the population or technological base to support it) to help guarantee the quality and the amount of drugs needed for the particular diseases that receive a high priority for treatment; 5. Inadequate expansion of drug distribution systems, other than the traditional physician-as-prescriber model--other alternatives would include pharmacists and other health workers, including traditional "healers"; 6. Insufficient political and economic cooperation among developing countries to provide the bargaining leverage needed with the large, multinational pharmaceutical cartels that supply many of the required drugs; 7. Inability to influence the larger pharmaceutical firms to conduct
116
JOURNAL OF COMMUNITY HEALTH
the research that would be designed to develop drugs specifically for the treatment of t h e diseases that are highly prevalent in the developing countries; 8. Lack of a regulatory apparatus to control the promotion, quality, and efficacy of drugs marketed by companies based in the developed countries; 9. Inadequate public education that would help to ensure compliance with efficacious therapies.
P O S S I B L E S O L U T I O N S TO D R U G
UTILIZATION PROBLEMS Methods are needed to correct under- and over-utilization and irrational prescribing, to reduce unnecessary expenditures for drugs in developed and developing countries, and to encourage the marketing of only safe and efficacious drugs. Some suggestions to achieve these goals follow: 1. Licensing should be limited to efficacious drugs that have been tested by the well-accepted principles embodied in the controlled clinical trial. This method is generally accepted, although some still follow the reasoning of Galen, who said, "All who drink of this remedy recover in a short time, except those whom it does not help, who all die. Therefore it is obvious that it fails only in incurable cases". 2 2. Drug promotion should be restricted so that drugs can be advertised only for indications where efficacy has been proven. The World Health Organization could devise a set of model legal regulations to control drug promotion. 3. Patent protection laws for the licensing of drugs should be altered and methods should be encouraged that would alter the oligopolistic economic structure of the industry to encourage price competition and that would prevent collusion in price-setting. 4. The adoption of a "relative efficacy" system for the licensing of new drugs should be encouraged. Such a system would not permit the licensing of a drug congener unless some distinct therapeutic or economic advantage over preexisting drugs for the same indication could be demonstrated. This would discourage the marketing of duplicative drugs and would encourage industry research in innovative areas for which there is a greater need for new and effective therapies. 5. National drug lists of efficacious drugs for particular conditions could be established, so that reimbursement of drug costs under national insurance schemes would not be available for inefficacious, unsafe, unnecessary, or needlessly expensive drugs. National or local health agencies should be encouraged to develop programs of drug education to discourage the taking of a pill for every ill and to substitute more healthful eating and living patterns instead (e.g., physical exercise). Governmental efforts should be
Assessing Drug Needs
117
encouraged in public education about the proper use of over-the-counter drugs. Authoritative and readable information about drugs should be provided }or patients, physicians, and pharmacists. 6. The role of the pharmacist as a member of the health care team could be expanded so that he or she may serve as a drug information specialist to physicians and patients-and also explain to patients why n o drug therapy at all may constitute good medical practice. 7. When safe and efficacious therapies are discovered, screening efforts should be organized to locate treatable cases and to provide adequate followup and compliance with therapy. 8. The effects of mass therapies should be evaluated by the use of epidemiological surveys and studies, such as analyses of vital statistics and morbidity surveys. 9. Drug utilization review in hospitals and clinics should be encouraged so that criteria for appropriate drug use may be set, using controlled clinical trials; periodic utilization review may then be employed to ensure adherence to the criteria. 10. Local and national systems of drug utilization review should be established using (a) pharmacy audits, (b) manufacturers' sales data, (c) hospital and clinic drug utilization data, (d) ad hoe studies and surveys, (e) marketing research firms' estimates, (f) government reporting systems, and (g) adverse drug reaction reporting systems or registries. Drug utilization data could be linked with health survey data so that an examination of disease incidence and prevalence would reveal areas of over- or under-utilization of drugs. For example, in a study conducted in the United States, nearly 3.5% of all prescriptions filled in pharmacies were for amphetamines, known to be addictive and of unproven efficacy in the long-term treatment of obesity. 3 Similarly, under-utilization may be detected, as a comparison of the use of antihypertensive medications and hypertension prevalence figures will reveal. 11. Periodic epidemiological surveillance of disease incidence and prevalence should be instituted for conditions where either beneficial or adverse drug effects might be anticipated. An interesting example of the application of these techniques is illustrated in Figure 1. An examination of the mortality rates attributed to asthma was correlated with the introduction of a new nebulizer therapy. As nebulizer use declined, so did the death rates. Further investigation revealed a doseresponse relationship, and a particularly potent formulation was further implicated. 4's Another example is the examination of the death rates due to thromboembolism during the years before and after the introduction of oral contraceptives, in both the United States and the United Kingdom. This review revealed the pattern of an increase in the death rates among females that was consistent with the hypothesis that the estrogen-containing oral contraceptives could cause fatal pulmonary embolism. 6 The examination of death rates due to bladder cancer in the United
118
JOURNAL OF COMMUNITY HEALTH
G O V E R N M E N T W A R N I N G ABOUT DANGERS OF N E B U L I Z E R S ISSUED; DECLINE IN S A L E S F O L L O W S ~
03 z
1 I m
o
oo ,.=, 0. I.iJ IZ:
I
-r
I.d c~
I 59
I 60
I, 61
I 62
1, 63
I 64
I 65
I 66
i
67
YEAR
FIGURE 1: Correlation of Asthma Nebulizer Sales and Asthma Death Rates--AnnuM Mortality Rate from Asthma, 1959 to 1967, for Persons 5 to 34 Years Old in England and Wales Kingdom provided no such support for the hypothesis that non-nutritive artificial sweeteners cause human bladder carcinoma. 7 An examination of death rates due to hypertensive disease, stroke, rheumatic heart disease, pneumococcal pneumonia, and poliomyelitis provided some evidence of the efficacy and the efficient use of appropriate therapies or vaccines in the United States (Figure 2). The decline in polio mortality rates after the introduction of successful vaccines is notable. Retrospective epidemiological investigations in the United States have led to the discovery of many cases of vaginal cancer among young w o m e n exposed to diethylstilbestrol in utero. 8 Post-marketing epidemiological surveillance of certain drugs or devices may contribute to the assessment of the true risk of more recent agents (e.g., oral contraceptives, intrauterine devices, depot progestogen contraceptives, and levodopa). In summary, epidemiological tools and methods, b o t h ad hoc studies and continuing intensive surveillance systems, could make an important
Assessing Drug Needs
119
Deaths / I00,000 3.0
m
POLIOM YELl TIS
2.0-
i
1.0-
0 1900
I
I
I
1920
l
I-
J
I
1940
I
I
1960
1980 Year
FIGURE 2: Decline in Poliomyelitis Mortality due to Introduction of Effective Vaccines--Poliomyelitis Deaths per 100,000 Population, Showing Impact of Salk and Sabin Vaccines
contribution to an identification of the under- and over-consumption of drugs. They would also provide a crude m e t h o d for assessing drug efficacy and the efficiency of drug distribution and could aid in the detection of adverse drug reactions. 9 Establishing Priorities for the Selection of Drugs and Biologicals j u s t as developed countries would do well to establish national drug lists that would contain only the approved, significant, safe, and efficacious drugs, such a list would assume an even greater importance for developing countries because of their more limited resources and less available funds for drug purchases. Experiences with military needs, hospitals, drug insurance programs, and with specific developing countries suggest that the list of drugs required for most treatable illnesses is not long--probably only about 200 to 500 different chemical entities. Both developed and developing countries are under great pressure from the influential and well-organized pharmaceutical industry (and an often uncritical cadre of medical practi-
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tioners) to expand the list of available drugs. A carefully scrutinized and flexibly applied "relative efficacy" system, such as that of Norway, would help to limit the number of drugs purchased by developing countries to those that are primarily most efficacious and most congruent with the health needs of their populations 1° Indeed, the delivery of an inefficacious drug is wasteful of both intellectual and technological resources, since the false belief that the agent used is efficacious delays work on the development of a truly useful medication. It is hard to over-estimate the importance of obtaining evidence of efficacy from controlled clinical trials prior to purchasing and mass distribution of drugs in developing countries. And yet, if one examines the drugs available and widely used in developing countries, one finds numerous examples of inefficacious, yet costly drugs that will have no beneficial public health effects, no matter how efficiently they are distributed. This represents a waste of resources that must be corrected. The guiding principles for setting priorities in drug procurement for developing countries should not only include linking the drug to the prevalent disease patterns but also emphasize drug safety and efficacy, first and foremost. The developed countries have many examples of drugs efficiently produced, stored, and distributed-but they are relatively inefficacious, unsafe, or needlessly expensive. It is clear that developing countries cannot afford the luxury of inefficacious drugs.
REFERENCES 1. Benzodiazepines: Use, overuse, misuse, abuse? editorial. Lancet 1:1101-1102, 1973. 2. England J: Medical Research. London, Churchill & Livingstone, 1975. 3. Stolley PD, Becker MH, McEvilla JD, et ah Drug prescribing and use in an American community. A n n Intern Med 76:37-40, 1972. 4. Inman WH, Adelstein AM: Rise and fall of asthma mortality in England and Wales in relation to use of pressurized aerosols. Lancet 2:279-285, 1969. 5. Stolley PD: Asthma mortality: Why the United States was spared an epidemic of deaths due to asthma. A m Rev Respir Dis 105:883-890, 1972. 6. SartweU PE, Stolley PD, Tonascia JA, et al: Pulmonary embolism mortality in relation to oral contraceptive use. Prey M e d 5:15-19, 1976. 7. Burbank F, Fraumeni JF Jr: Synthetic sweetener consumption and bladder cancer trends in the United States. Nature 227: 296-297, 1970. 8. Herbst AL, Ulfelder H, Poskanzer DC: Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N E n g l J M e d 284:878-881, 1971. 9. Stolley PD: How study of geographic epidemiology of disease can help in detection of adverse drug reactions. Clin Pharm and Ther 19(Part 2):679-682, 1976. 10. Stolley PD, Goddard JL: A "relative efficacy" system for new drugs. A n n Intern Med 73:479--480, 1970.
