0895-4356/91 $3.00 + 0.00 Pergamon Press plc
J CIin Epidemiol Vol. 44, Suppl. II, pp. 31S-38s. 1991 Printed in Great Britain
DRUG
UTILIZATION DAVID
IN PANAMA*
LEE
Department of Pharmacology, Faculty of Medicine, University of Panama and Pharmacotherapeutic Information Program, Medicines Commission, Social Security Institute, Apartado 1393, Panama 1, Republic of Panama
Abstract-The availability and use of therapeutic agents in Panama is critically reviewed. Of the 3800 drug products on the market, 50% are vitamins, tonics and fixed ratio combination products. Many drugs are of unproven efficacy and safety, not marketed in more developed countries. Hospital and outpatient studies have documented inappropriate prescribing habits. To improve drug utilization, regulatory and educational strategies have been implemented in the Panama Social Security Institute. Drugs of doubtful or no value and unnecessary duplications have been withdrawn from its therapeutic formulatory. Outreach services provided by the Panama Social Security Institute include the distribution of a drug bulletin, workshops, seminars and person to person drug information (counterdetailing) to health personnel. Drug information to patients is also included in the overall strategy to promote the rational use of drugs. Nevertheless, much work is still needed to formulate and implement an essential drugs and health policy in Panama. Drug utilization Drug information Essential drugs concept Rational drug use Therapeutic formulary
INTRODUCTION
Pharmacoepidemiology
in the World Health Organization’s definition of drug utilization: “the marketing, distribution, prescription and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequences” [2]. Two sets of contrasting concepts may be useful terms of reference in this analysis of drug utilization in Panama. The list of terms on the left in Table 1 characterize what may be considered the current drug situation even in the advanced industrialized nations. The set of terms on the right side constitute points of reference to assess rationality of drug utilization [3]. The essential drugs concept [2] evolved from the needs of developing countries, but is also applicable to the more privileged advanced industrialized nations, where the impact of the irrational use of drugs may increase costs, drug side effects and resistance to antimicrobial agents.
Therapeutic drugs play a central role in modern healthcare services. They are used in every medical, surgical and psychiatric discipline even though not justified by safety and efficacy. Beyond their role as therapeutic and diagnostic tools, drugs also reflect the attitudes and hopes of both physician and patient relative to the natural course of a disease. The way drugs are conceived, developed, promoted, prescribed and used reflects the state of development of the healthcare system. The use of therapeutic drugs has been claimed to represent a given society’s cultural approach to health [ 11. Thus, the points of interaction between use of drugs and the healthcare system are taken into consideration *The opinions expressed in this paper are those of the author and are not necessarily those of the Medicines Commission of the Panama Social Security Institute. 31s
DAVIDLEE
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Table 1.Contrasting terms that help to characterize drug utilization
Table 2. National
Demand Availability Therapeutic tradition Pharmaceutical speciality Promotion Anecdotal experience
Population: 2,376,OOO(1990); 52.9% urban, 47.1% rural Population density: 3 1.7 per km2 Age less than 15yr: 36%; greater than 65yr: 4.7% Crude birth rate: 25.3 per 1000 (1987) Mortality rate: 4.0 per 1000 (1987) Infant mortality: 19.4 per 1000 (1987); urban 18.1, rural 20.5 Life expectancy: 72.5 yr GNP per capita: U.S. $678 Educational system: compulsory 6 yr Adult literacy rate: 90%
vs vs vs vs vs vs
Need Selection Rational prescribing Essential drug Information Research
DEMOGRAPHIC, SOCIAL, ECONOMIC AND HEALTH SITUATION IN PANAMA
Panama is a nation in a stage of transition relative to health structures, as reflected in the indicators that are summarized in Tables 2 and 3. The country must face the challenge of both acute infectious diseases of developing nations and the chronic diseases of more affluent societies. Private and public healthcare services are available. Private healthcare covers about 15% of the population, made up of the more affluent population [4]. There are no data available on the private healthcare system. In the public sector healthcare services are provided by the Ministry of Health and the Social Security Institute. The Social Security Institute provides care for 62.5% of the population. Since 1972 Panama has been progressively moving towards establishing a national health system. Consequently, the country is currently divided into the capital city and eight integrated health systems. Parallel healthcare services (outpatient clinics and hospitals) are provided by both the Ministry of Health and the Social Security Institute in the capital city. In the rest of the country Ministry of Health and Social Security Institute resources (health personnel, administrators, clinics and hospitals) are shared under the structure of the integrated health system. The Social Security Institute is committed to providing pharmaceuticals to the integrated health sys-
demographic, economic indicators in Panama
Source: Refs [4-6].
terns, thus increasing coverage with pharmaceuticals to 85% of the country’s population. Pharmaceuticals are dispensed without charge through the Social Security pharmacies to its beneficiaries. The number of population served per cateogry of health worker is presented in Table 4. More than 50% of the physicians also have a private practice in addition to working with either the Ministry of Health or the Social Security Institute. THE PHARMACEUTICAL MARRET AND AVAILABILITY OF THERAPEUTIC DRUGS IN PANAMA Panama is primarily an importer of pharmaceutical products. There is very little local drug production or export (Table 5). Unpublished data indicate that drug prices may be three times as high as those in neighboring countries [8]. There are approx. 3800 drug products registered in Panama [9]. It is roughly estimated that 50% of these are combination drug products. Although no detailed information is currently available on the types of drugs and therapeutic classes, some limited data indicate that the market may not be as rational as it could (or should) be. There are many drugs of unproven efficacy and irrational drug combinations. Other
Table 3. Morbidity and mortality patterns: top 10 causes in Panama Rank morbidity (1984) 1. Acute respiratory infections 2. Trauma and poisonings 3. Bronchitis, emphysema, 4. 5. 6. 7.
asthma Ill-defined intestinal infection Intestinal parasitic disease Hypertensive disease Influenza
8. Other diseases, urinary tract 9. Diseases of the eye
10. Diseases of esophagus, stomach and duodenum
and health
Mortality (1986) Malignant tumors Accidents, suicide, violence Cerebrovascular disease Acute myocardial infarction Ailments in the < I-yr-old Other ischemic heart disease Diseases of the pulmonary circulation and other heart disease Pneumonia Ill-delIned intestinal infection Diabetes mellitus
Source: Ministerio de Salud, Direction de Planificacion, Departamento Estadistica.
de
Drug Utilization in Panama Table 4. Available health manpower in Panama Health worker Physician Pharmacist Pharmacy assistant Pharmacy personnel (total) Nurse Nursing assistant
No. of persons served per health worker (range) 888 (595-5373) 8574 (609342,987) 5584 (3618-11,462) 3381 (261342,987) 1000 Data not available
Source: Coordination de Comunicadores Cientificos, Dire&on National de Servicios y Prestaciones Mbdicas, Caja de Seguro Social.
drugs (for example, antiviral agents) are promoted for unproven indications [lo]. A recent study revealed that 50% of new drug introductions during a 3-year period (1985-1988) were not registered at the time in at least one of followiong countries with stricter drug evaluation authorities: the U.S., Great Britain and Sweden. Moreover, the majority of the new drug introductions did not constitute significant therapeutic gain over those already available in the market [ll, 121. The Department of Pharmacy and Drugs of the Ministry of Health is responsible for drug registration and control. The registration authority is severely understaffed and lacks the necessary expertise of professionals such as clinical pharmacologists and clinical experts. Drugs are registered primarily on the basis of the certificate of free sale in the country of origin of the drug product and verification of compliance with U.S. pharmacopoeia1 standards or the manufacturer’s specifications, whenever relevant. Although pharmacological and clinical studies are required by legislation dating back to 1962, it is questionable whether submitted clinical studies are critically evaluated. This is suggested by the number of drugs of unproven efficacy that are currently on the market. There are no data on how many drug applications (if Table 5. The pharmaceutical market in Panama 1988 Market: Private sector Public sector Total Pharmaceutical laboratories: National Private State Foreign Participation of national laboratories in sales (%): Private sector Public sector Import: Export: Source: Ref. [7].
U.S. $29 million U.S. $29 million U.S. $58 million 3 1 2 10 16 U.S. $46.5 million U.S. $5.0 million
33s
any) are rejected on the basis of safety or efficacy. It is likewise not known how many drug registration applications are rejected (if any) or merely delayed as a result of failure to comply with pharmacopoeia1 standards. It should be noted that the drug product analyses are performed on samples submitted by the pharmaceutical companies. Despite efforts in the past 10 years Panama has not yet adopted a national therapeutic formulary. In 1981 a common drug formulary for the Ministry of Health and the Social Security Institute [13, 141 was prepared with the collaboration of the Pan American Health Organization and distributed for consultation with the clinical specialists but was never officially adopted and implemented. However, because of the magnitude of the Social Security Institute’s pharmaceutical responsibilities, changes in its drug formulary may reflect the progress of the introduction of the essential drugs concept. From the registered drugs the Social Security Institute further selects those drugs (and drug products) to be procured, stored and distributed to its pharmacies to be dispensed free of charge. Drug selection and surveillance in the Social Security Institute is under the responsibility of a Medicines Commission, consisting of an 1lmember multidisciplinary committee. This committee is made up of representatives of the Social Security’s Board of Directors and its General Director, the Department of Medicine, Pediatrics, Surgery, Obstetrics-Gynecology, the National Medical Association, the Panamanian Society of General Practice, the Social Security Association of Physicians, Dentists and Allied Health Professionals, the National College of Pharmacists and the Director of the Ministry of Health’s Department of Pharmacy and Drugs. A full-time staff consisting of one clinical pharmacologist and four pharmacists currently provide technical support to the committee. These professionals evaluate new formulary drug applications, compile drug utilization data, analyze reports of problems with drugs and drug products and provide drug information to physicians and pharmacists. Thus, the Medicines Commission constitutes a second unofficial “regulatory body” in Panama. The Social Security drug formulary has been improved in the past two revisions. In 1986, there was a 28% reduction in drugs and dosage forms, resulting in a list of 398 drugs and 548 dosage forms [15]. Withdrawals from the formulary consisted of drugs lacking adequate
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DAVID LEE
evidence of efficacy and safety, irrational combination drugs and unnecessary duplications [ 161. More than 10% of the 1983 drug expenditures were invested in drugs of doubtful value (inadequate safety and efficacy or inappropriate combination drugs) [17]. In 1989, the list of 390 drugs and 522 dosage forms was further classified into priority levels for procurement, a step further in defining a truly “essential drug formulary” [18]. Currently there is renewed interest in adopting a common therapeutic drug formulary for the public sector [6]. The potential benefits of improved drug selection have not been translated into more tangible benefits such as increased availability and/or more rational use partly as a consequence of deficiencies in the logistics system: inadequate estimation of “needs”, inefficient procurement planning and procedures, warehousing limitations, distribution problems and financial constraints [8]. The lack of a quality assurance program, at the national or institutional levels, is another obstacle to a more rational use of pharmaceuticals. Studies in the Central American isthmus have revealed that even drug products from subsidiary laboratories of multinational companies may be deficient compared with the same drug products manufactured in the parent laboratories [19]. Although some drug product quality control is carried out by the Ministry of Health and by the Social Security Institute, this usually results as a reaction to specific complaints with specific drug products. A comprehensive quality assurance scheme has not been adopted despite demonstrated need and repeated calls for one. PRESCRIBING AND USE OF THERAPEUTIC DRUGS
Problems in the prescribing and use of pharmaceuticals have been documented in studies of patterns of drug distribution, prescription surveys and hospital chart review. For instance, in 1984, 50% of parenteral gentamicin was distributed to outpatient clinics [unpublished data]. Outpatient prescription surveys reveal that, on average, patients are prescribed 2.2 drugs per consultation. This apparently low number is mainly due to restrictions on the number of drugs allowed per prescription form [20]. Despite efforts to enforce prescribing by the generic name, trade names were used in 83% of prescriptions. Moreover, 20% of the top
20 prescribed drugs were drugs of doubtful value (antihistamine combination products for cold remedies, guaiphenesin, bromhexine). In a small survey of intramuscular immunoglobulin prescriptions, administered doses were eight times greater than recommended [21]. Piroxicam is a non-steroidal anti-inflammatory drug used in the treatment of symptoms of rheumatoid arthritis and related diseases. In a survey of piroxicam prescriptions [22], 34% of the prescriptions were for greater than the recommended maximum daily dose of 20 mg. In 28% of the prescriptions, piroxicam was inappropriately prescribed for less than 12 hour intervals. Piroxicam was prescribed most often for acute conditions (73% of the diagnoses were not related to rheumatic diseases, 42% of the prescriptions were for less than 10 days of treatment). However, only 23% of the prescriptions were filled for patients over 60 years, who are deemed to be at greater risk for gastrointestinal complications when taking non-steroidal anti-inflammatory agents [23]. This is indicative of physician compliance with promotional information [24]. In Panama piroxicam is also promoted for vague indications such as “acute musculoskeletal diseases ” , “arthrosis or joint diseases”. However, despite the inappropriate prescribing, increased morbidity from gastrointestinal complications was not detected in the Social Security referral hospital. Hospital chart review studies [25-291 revealed that 44% of adults hospitalized in internal medicine wards and up to 90% of children in pediatric wards received antimicrobials. Seventy-two to 85% of antimicrobial therapy in both adults and children were found to vary from recommended management as determined through process criteria for appropriateness of use [30]. In one study involving adults the main criteria which indicated inappropriate management were inappropriate antibiotic selection (14.2%), inappropriate length of treatment (18%), arbitrary (unjustified) changes in antibiotic therapy (11.3%) and lack of culture and sensitivity testing (9.4%) [25]. In a study of children receiving antimicrobial agents, in 31.8% of therapies there was no attempt to identify or to culture the pathogen, no monitoring for renal effects in 22.1%, lack of suflicient justification for initiating antimicrobial treatment in 14.2% and unjustified changes in antibiotic treatment in 13.6% [28%]. Results from another study assessing gentamicin usage
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Drug Utilization in Panama
revealed inadequate monitoring of renal function in 60% of the cases, inappropriate dosage interval and dose calculations, treatment duration too short or too long in 44%, no rational justification for use in 37%, empiric use or lack of sensitivity testing in 34% [31]. No studies have been conducted in Panama to evaluate compliance with prescribed treatment. However, there are data that suggest potential for problems in compliance that could result from inadequate communication between prescriber and patient. Evaluation of patient queries to pharmacists indicate that 32% of the 68,214 queries over a 4 year period concerned the indication for the prescription and 10% dealt with how to take the drug [Coordination de Comunicadores Cientificos, unpublished data]. Another 8% of the queries were related to changes in drug products as a consequence of the institution’s generic substitution policy. These data may not be representative of the patient population at large and it is not known if this is only the “tip of the iceberg”. Nor is it known what proportion of those who do not consult the pharmacist have problems in understanding the prescription. CLINICAL RESEARCH IN PANAMA
The quality of scientific publications provide an opportunity to review the state of development of a nation’s “medical culture”, the set of attitudes and guiding principles for the practice of medicine. There are three regularly published medical journals in Panama. A survey of the type of publications and clinical research designs documented a predominance of case reports, cases series, informal retrospective and descriptive surveys [32]. This underscores the difficulty in bridging the gap separating clinical practice and scientific concepts and principles. The demand from prescribers for formulary inclusion of drugs of unproven clinical efficacy, irrational combination drugs and more expensive therapeutic options are a clear indication of the need for improved education and information on the principles of scientific evaluation of clinical interventions [33], pharmacological or non-pharmacological. Drug utilization review programs (therapeutic audits) are still to be formally adopted [34]. Although some initial work in establishing a spontaneous adverse drug reaction reporting scheme has been reported [35,36], it still cannot be considered as effectively implemented. No reliable drug database is
available for large-scale analytical research. However, Panama currently participates in the WHO-EURO sponsored Drug Use in Pregnancy study [37], which aims to establish a permanent network for collaborative pharmacoepidemiological research. There is concern over the potential clinical implications resulting from ethnic differences in drug metabolism. A university-based population pharmacology and ethnopharmacokinetics research program is currently underway to assess differences and/or similarities among Panamanian Amerindian groups and between these groups and Caucasians [38-43]. The author is unaware of published studies on economic or social aspects of drug utilization in Panama. The current state of clinical research in general, and drug utilization research in particular, has (not) evolved in the absence of a national, or even an institutional, research policy. Most clinical “research” is the result of individual interest in publishing a paper on a particular clinical problem deemed to be of wider professional interest. The few pharmaceutical industry sponsored “research” programs submitted to the Medicines Commission are inadequately designed and could be considered primarily promotional, aimed at inducing prescribers to try new drugs claimed to be important therapeutic advances, or to discredit generic competition by attempts to demonstrate inequivalency with innovator products. THE INTERVENTIONS
Efforts to promote the rational use of pharmaceuticals have utilized both regulatory and educational and informational strategies. Regulatory measures involved the withdrawal of many drugs of doubtful therapeutic value and irrational combination drugs from the Social Security drug formulary, as mentioned above. Through critical evaluation of available clinical studies submitted with new formulary addition requests it has been possible to reject drugs with inadequate documentation of clinical efficacy (buflomedyl, tromantadine, amineptine) or questionable safety (indoprofen, which was later withdrawn worldwide). The improvement in drug selection in the public sector has not, however, been accompanied by a concomitant improvement in the private sector [44,45]. Information and educational efforts have been carried out intensively under a drug information program by the Medicines Commission
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DAVID LEE
of the Panama Social Security [46]. Educational outreach strategies have involved distribution of written material and a variety of face-toface methods, such as group meetings and professional visits to physicians on a person-toperson basis similar to those of pharmaceutical company representatives (“counterdetailing”). In 1983 and 1984 written material consisted of mimeographed 2-4 page articles on pharmacotherapeutics and related pharmaceutical topics. A drug bulletin has been published irregularly since 1985 with the collaboration of the Pan American Health Organization and the Pan American Health and Education Foundation [47]. The bulletin has consisted mainly of camera-ready translations of articles from The Medical Letter, Drug and Therapeutics Bulletin, Adverse Drug Reaction Bulletin and other publications. One issue was compiled locally, consisting of translations from other drug bulletins and several original articles, including drug utilization data. The bulletin was distributed free of charge to 2000 physicians and pharmacists throughout the country. Financial and administrative constraints during the past 2 years have adversely affected the continuity of this publication. Changes in the format, making the bulletin more streamlined and less costly, and more stringent selection of relevant articles are underway to reactivate the bulletin. The rational use of drugs has been promoted through several workshops and seminars for health workers of various disciplines (physicians, dentists, pharmacists, nurses, administrators). At interrupted intervals the drug information program has participated in the continuing education programs of several Social Security outpatient clinics with lectures Table 6. Pharmacotherapeutic
Information Program topics
Workshops and seminars: Managing drug supply Drug formularies and the essential drugs concept Drug epidemiology and adverse drug reactions Drugs in pregnancy and lactation Clinical pharmacology in pediatric dentistry Critical evaluation of the medical literature Contimdng medical education sessions: Principles of pediatric clinical pharmacology Drug interactions Use and misuse of antibiotics Rational use of aminoglycosides Rational use of immunoglobulins Use of antihypertensive agents in Panama Use of geriatric drugs or use of drugs in geriatric patients? Pseudo-allergic reactions to pencillin procaine New drug introductions in Panama
and discussions on pharmacotherapeutic topics on a monthly basis (Table 6). Whenever relevant, drug utilization data is also presented. Another modality has been “face to face” drug information [48]. During a 4 year period the pharmacotherapeutic information program employed a corps of seven pharmacists who were specially trained to visit physicians on a person-to-person basis to provide information on decisions of the Medicines Commission, therapeutic information relevant to problems detected in prescription surveys, and promote reporting of suspected adverse drug reactions and detected drug product problems. Currently this strategy is at a minimal level of activity for a number of reasons, mainly, loss of personnel and positions and need for improved competence levels. The effectiveness of these strategies has not been critically assessed. This has been partly due to significant confounding introduced by increasing drug shortages in the face of the deteriorating political and economic situation of the past 3 years. Subjectively, all these activities are considered to contribute to at least lay the cultural foundations necessary for ensuring the effectiveness of future interventions. In this context, a recent workshop formally introduced the essential drugs concept to leading members of the medical, pharmacy, dentistry and nursing schools and faculties [49]. Another recent positive development is the inclusion of clinical pharmacology topics and the essential drugs concept in the basic pharmacology and the therapeutics courses of the Faculty of Medicine. With regard to patient information a group of Social Security pharmacists (Scientific Communicators), administratively under another directorate, is responsible for providing drug information to patients. This is done through regularly scheduled oral presentations to patients waiting to fill their prescriptions in Social Security pharmacy lobbies. Additionally, in several Social Security outpatient clinics a pharmacist is available 8 hours daily for patient consultation, as mentioned previously. The effectiveness of this activity has not been evaluated. CONCLUSION Review of current drug utilization in Panama indicates that there is much work to be done in formulating and implementing an essential
Drug Utilization in Panama
drugs and health policy. Drug utilization research, descriptive, analytical and experimental, biomedical and social, will be fundamental to the implementation of this policy [50]. The current use of pharmaceutical agents in Panama thus constitutes a challenge not only to clinical pharmacology but also to the many other disciplines involved in drug utilization [51].
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39. Jorge LF, Arias TD, Inaba T, Jackson PR. Unimodal distribution of the metabolic ratio for debrisoquine in Cuna Amerindians of Panama. Br J Clln Pharmac 1990; 30: in press. 40. Arias TD, Jorge LF, Lee D, Barrantes R, Inaba T. The oxidative metabolism of sparteine in the Cuna Amerindians of Panama: absence of evidence for deficient metabolizers. Clin Pharmac Ther 1988; 43: 456465. 41. Inaba T, Jorge LF, Arias TD. Mephenytoin hydroxylation in the Cuna Amerindians of Panama. Br J CIin Pharmac 1988; 25: 75-79. 42. Arias TD, Barrantes R, Inaba T, Cooke RG, Jorge L. A preliminary note on the transient polymorphic oxidation of sparteine in the Ngawbt Guaymi Amerindians: a case of genetic divergence with tentative phylogenetic time frame for the pathway. CIln Warmac Ther 1988; 44: 343-352. 43. Inaba T, Arias TD. On phenotyping with isoniazid: the use of the urinary acetylation ration and the uniqueness of antimodes. A study in two Amerindian populations. ClIn Pharmac Ther 1987; 42: 493497. 44. Lee D, Rogers A, Robles RT, et al. Utilization de la estreptoquinasa-estreptodomasa en la Caja de Seguro Social. Rev M&i Caja Segnro Sot 1987; 19: 181-185. 45. Lee D. Continued marketing of a useless drug (‘Varidase’) in Panama. Lancet 1990; 335: 667.
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Comision National de Medicamentos. Programa de Informac%n, DlvnIgaci6n y Docencia. Panaml: Caja de Seguro Social; 1984. Lee D. Bulletins in developing countries: medicamentos y terapdutica. ISDB Newslett 1987; 2(12): 21-22. Avorn J, Harvey K, Soumerai S, Herxheimer A, Plumridge R, Bardelay G. Information and education as determinants of antibiotic use: report of Task Force 5. Rev Infect Dis 1987: 9: S286S296. Quintero EG. Introdu&ih de1 Concepto de Medicamentos Esenciales en 10s Curricula de las Facultades de Medicina y Fannacia. Informe Final del Taller. Panama: Universidad de Panama y Organization Panamericana de la Salud; 1989. Baksaas I, Lunde PKM. National drug policies: the need for drug utilization studies. Trends Pharmac Sci 1986; 7: 331-333. Lee D, Gan V, Quijano R, Uppal R. The challenge for clinical pharmacology in developing countries. In: Sterky G, Tomson G, Sachs L, Henningsson B, Bergman U, Eds Medicines & Society: a Challenge in Health Develonment. Stockholm: Karolinska Institutet, Department of International Health Care Research (IHCAR) and Department of Clinical Pharmacology, Huddinge University Hospital, 18 May-18 June; 1987: Appendix 2.
J CIin Epidemiol Vol. 44, Suppl. II, pp. 31S-38s. 1991 Printed in Great Britain
DRUG
UTILIZATION DAVID
IN PANAMA*
LEE
Department of Pharmacology, Faculty of Medicine, University of Panama and Pharmacotherapeutic Information Program, Medicines Commission, Social Security Institute, Apartado 1393, Panama 1, Republic of Panama
Abstract-The availability and use of therapeutic agents in Panama is critically reviewed. Of the 3800 drug products on the market, 50% are vitamins, tonics and fixed ratio combination products. Many drugs are of unproven efficacy and safety, not marketed in more developed countries. Hospital and outpatient studies have documented inappropriate prescribing habits. To improve drug utilization, regulatory and educational strategies have been implemented in the Panama Social Security Institute. Drugs of doubtful or no value and unnecessary duplications have been withdrawn from its therapeutic formulatory. Outreach services provided by the Panama Social Security Institute include the distribution of a drug bulletin, workshops, seminars and person to person drug information (counterdetailing) to health personnel. Drug information to patients is also included in the overall strategy to promote the rational use of drugs. Nevertheless, much work is still needed to formulate and implement an essential drugs and health policy in Panama. Drug utilization Drug information Essential drugs concept Rational drug use Therapeutic formulary
INTRODUCTION
Pharmacoepidemiology
in the World Health Organization’s definition of drug utilization: “the marketing, distribution, prescription and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequences” [2]. Two sets of contrasting concepts may be useful terms of reference in this analysis of drug utilization in Panama. The list of terms on the left in Table 1 characterize what may be considered the current drug situation even in the advanced industrialized nations. The set of terms on the right side constitute points of reference to assess rationality of drug utilization [3]. The essential drugs concept [2] evolved from the needs of developing countries, but is also applicable to the more privileged advanced industrialized nations, where the impact of the irrational use of drugs may increase costs, drug side effects and resistance to antimicrobial agents.
Therapeutic drugs play a central role in modern healthcare services. They are used in every medical, surgical and psychiatric discipline even though not justified by safety and efficacy. Beyond their role as therapeutic and diagnostic tools, drugs also reflect the attitudes and hopes of both physician and patient relative to the natural course of a disease. The way drugs are conceived, developed, promoted, prescribed and used reflects the state of development of the healthcare system. The use of therapeutic drugs has been claimed to represent a given society’s cultural approach to health [ 11. Thus, the points of interaction between use of drugs and the healthcare system are taken into consideration *The opinions expressed in this paper are those of the author and are not necessarily those of the Medicines Commission of the Panama Social Security Institute. 31s
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Table 1.Contrasting terms that help to characterize drug utilization
Table 2. National
Demand Availability Therapeutic tradition Pharmaceutical speciality Promotion Anecdotal experience
Population: 2,376,OOO(1990); 52.9% urban, 47.1% rural Population density: 3 1.7 per km2 Age less than 15yr: 36%; greater than 65yr: 4.7% Crude birth rate: 25.3 per 1000 (1987) Mortality rate: 4.0 per 1000 (1987) Infant mortality: 19.4 per 1000 (1987); urban 18.1, rural 20.5 Life expectancy: 72.5 yr GNP per capita: U.S. $678 Educational system: compulsory 6 yr Adult literacy rate: 90%
vs vs vs vs vs vs
Need Selection Rational prescribing Essential drug Information Research
DEMOGRAPHIC, SOCIAL, ECONOMIC AND HEALTH SITUATION IN PANAMA
Panama is a nation in a stage of transition relative to health structures, as reflected in the indicators that are summarized in Tables 2 and 3. The country must face the challenge of both acute infectious diseases of developing nations and the chronic diseases of more affluent societies. Private and public healthcare services are available. Private healthcare covers about 15% of the population, made up of the more affluent population [4]. There are no data available on the private healthcare system. In the public sector healthcare services are provided by the Ministry of Health and the Social Security Institute. The Social Security Institute provides care for 62.5% of the population. Since 1972 Panama has been progressively moving towards establishing a national health system. Consequently, the country is currently divided into the capital city and eight integrated health systems. Parallel healthcare services (outpatient clinics and hospitals) are provided by both the Ministry of Health and the Social Security Institute in the capital city. In the rest of the country Ministry of Health and Social Security Institute resources (health personnel, administrators, clinics and hospitals) are shared under the structure of the integrated health system. The Social Security Institute is committed to providing pharmaceuticals to the integrated health sys-
demographic, economic indicators in Panama
Source: Refs [4-6].
terns, thus increasing coverage with pharmaceuticals to 85% of the country’s population. Pharmaceuticals are dispensed without charge through the Social Security pharmacies to its beneficiaries. The number of population served per cateogry of health worker is presented in Table 4. More than 50% of the physicians also have a private practice in addition to working with either the Ministry of Health or the Social Security Institute. THE PHARMACEUTICAL MARRET AND AVAILABILITY OF THERAPEUTIC DRUGS IN PANAMA Panama is primarily an importer of pharmaceutical products. There is very little local drug production or export (Table 5). Unpublished data indicate that drug prices may be three times as high as those in neighboring countries [8]. There are approx. 3800 drug products registered in Panama [9]. It is roughly estimated that 50% of these are combination drug products. Although no detailed information is currently available on the types of drugs and therapeutic classes, some limited data indicate that the market may not be as rational as it could (or should) be. There are many drugs of unproven efficacy and irrational drug combinations. Other
Table 3. Morbidity and mortality patterns: top 10 causes in Panama Rank morbidity (1984) 1. Acute respiratory infections 2. Trauma and poisonings 3. Bronchitis, emphysema, 4. 5. 6. 7.
asthma Ill-defined intestinal infection Intestinal parasitic disease Hypertensive disease Influenza
8. Other diseases, urinary tract 9. Diseases of the eye
10. Diseases of esophagus, stomach and duodenum
and health
Mortality (1986) Malignant tumors Accidents, suicide, violence Cerebrovascular disease Acute myocardial infarction Ailments in the < I-yr-old Other ischemic heart disease Diseases of the pulmonary circulation and other heart disease Pneumonia Ill-delIned intestinal infection Diabetes mellitus
Source: Ministerio de Salud, Direction de Planificacion, Departamento Estadistica.
de
Drug Utilization in Panama Table 4. Available health manpower in Panama Health worker Physician Pharmacist Pharmacy assistant Pharmacy personnel (total) Nurse Nursing assistant
No. of persons served per health worker (range) 888 (595-5373) 8574 (609342,987) 5584 (3618-11,462) 3381 (261342,987) 1000 Data not available
Source: Coordination de Comunicadores Cientificos, Dire&on National de Servicios y Prestaciones Mbdicas, Caja de Seguro Social.
drugs (for example, antiviral agents) are promoted for unproven indications [lo]. A recent study revealed that 50% of new drug introductions during a 3-year period (1985-1988) were not registered at the time in at least one of followiong countries with stricter drug evaluation authorities: the U.S., Great Britain and Sweden. Moreover, the majority of the new drug introductions did not constitute significant therapeutic gain over those already available in the market [ll, 121. The Department of Pharmacy and Drugs of the Ministry of Health is responsible for drug registration and control. The registration authority is severely understaffed and lacks the necessary expertise of professionals such as clinical pharmacologists and clinical experts. Drugs are registered primarily on the basis of the certificate of free sale in the country of origin of the drug product and verification of compliance with U.S. pharmacopoeia1 standards or the manufacturer’s specifications, whenever relevant. Although pharmacological and clinical studies are required by legislation dating back to 1962, it is questionable whether submitted clinical studies are critically evaluated. This is suggested by the number of drugs of unproven efficacy that are currently on the market. There are no data on how many drug applications (if Table 5. The pharmaceutical market in Panama 1988 Market: Private sector Public sector Total Pharmaceutical laboratories: National Private State Foreign Participation of national laboratories in sales (%): Private sector Public sector Import: Export: Source: Ref. [7].
U.S. $29 million U.S. $29 million U.S. $58 million 3 1 2 10 16 U.S. $46.5 million U.S. $5.0 million
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any) are rejected on the basis of safety or efficacy. It is likewise not known how many drug registration applications are rejected (if any) or merely delayed as a result of failure to comply with pharmacopoeia1 standards. It should be noted that the drug product analyses are performed on samples submitted by the pharmaceutical companies. Despite efforts in the past 10 years Panama has not yet adopted a national therapeutic formulary. In 1981 a common drug formulary for the Ministry of Health and the Social Security Institute [13, 141 was prepared with the collaboration of the Pan American Health Organization and distributed for consultation with the clinical specialists but was never officially adopted and implemented. However, because of the magnitude of the Social Security Institute’s pharmaceutical responsibilities, changes in its drug formulary may reflect the progress of the introduction of the essential drugs concept. From the registered drugs the Social Security Institute further selects those drugs (and drug products) to be procured, stored and distributed to its pharmacies to be dispensed free of charge. Drug selection and surveillance in the Social Security Institute is under the responsibility of a Medicines Commission, consisting of an 1lmember multidisciplinary committee. This committee is made up of representatives of the Social Security’s Board of Directors and its General Director, the Department of Medicine, Pediatrics, Surgery, Obstetrics-Gynecology, the National Medical Association, the Panamanian Society of General Practice, the Social Security Association of Physicians, Dentists and Allied Health Professionals, the National College of Pharmacists and the Director of the Ministry of Health’s Department of Pharmacy and Drugs. A full-time staff consisting of one clinical pharmacologist and four pharmacists currently provide technical support to the committee. These professionals evaluate new formulary drug applications, compile drug utilization data, analyze reports of problems with drugs and drug products and provide drug information to physicians and pharmacists. Thus, the Medicines Commission constitutes a second unofficial “regulatory body” in Panama. The Social Security drug formulary has been improved in the past two revisions. In 1986, there was a 28% reduction in drugs and dosage forms, resulting in a list of 398 drugs and 548 dosage forms [15]. Withdrawals from the formulary consisted of drugs lacking adequate
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evidence of efficacy and safety, irrational combination drugs and unnecessary duplications [ 161. More than 10% of the 1983 drug expenditures were invested in drugs of doubtful value (inadequate safety and efficacy or inappropriate combination drugs) [17]. In 1989, the list of 390 drugs and 522 dosage forms was further classified into priority levels for procurement, a step further in defining a truly “essential drug formulary” [18]. Currently there is renewed interest in adopting a common therapeutic drug formulary for the public sector [6]. The potential benefits of improved drug selection have not been translated into more tangible benefits such as increased availability and/or more rational use partly as a consequence of deficiencies in the logistics system: inadequate estimation of “needs”, inefficient procurement planning and procedures, warehousing limitations, distribution problems and financial constraints [8]. The lack of a quality assurance program, at the national or institutional levels, is another obstacle to a more rational use of pharmaceuticals. Studies in the Central American isthmus have revealed that even drug products from subsidiary laboratories of multinational companies may be deficient compared with the same drug products manufactured in the parent laboratories [19]. Although some drug product quality control is carried out by the Ministry of Health and by the Social Security Institute, this usually results as a reaction to specific complaints with specific drug products. A comprehensive quality assurance scheme has not been adopted despite demonstrated need and repeated calls for one. PRESCRIBING AND USE OF THERAPEUTIC DRUGS
Problems in the prescribing and use of pharmaceuticals have been documented in studies of patterns of drug distribution, prescription surveys and hospital chart review. For instance, in 1984, 50% of parenteral gentamicin was distributed to outpatient clinics [unpublished data]. Outpatient prescription surveys reveal that, on average, patients are prescribed 2.2 drugs per consultation. This apparently low number is mainly due to restrictions on the number of drugs allowed per prescription form [20]. Despite efforts to enforce prescribing by the generic name, trade names were used in 83% of prescriptions. Moreover, 20% of the top
20 prescribed drugs were drugs of doubtful value (antihistamine combination products for cold remedies, guaiphenesin, bromhexine). In a small survey of intramuscular immunoglobulin prescriptions, administered doses were eight times greater than recommended [21]. Piroxicam is a non-steroidal anti-inflammatory drug used in the treatment of symptoms of rheumatoid arthritis and related diseases. In a survey of piroxicam prescriptions [22], 34% of the prescriptions were for greater than the recommended maximum daily dose of 20 mg. In 28% of the prescriptions, piroxicam was inappropriately prescribed for less than 12 hour intervals. Piroxicam was prescribed most often for acute conditions (73% of the diagnoses were not related to rheumatic diseases, 42% of the prescriptions were for less than 10 days of treatment). However, only 23% of the prescriptions were filled for patients over 60 years, who are deemed to be at greater risk for gastrointestinal complications when taking non-steroidal anti-inflammatory agents [23]. This is indicative of physician compliance with promotional information [24]. In Panama piroxicam is also promoted for vague indications such as “acute musculoskeletal diseases ” , “arthrosis or joint diseases”. However, despite the inappropriate prescribing, increased morbidity from gastrointestinal complications was not detected in the Social Security referral hospital. Hospital chart review studies [25-291 revealed that 44% of adults hospitalized in internal medicine wards and up to 90% of children in pediatric wards received antimicrobials. Seventy-two to 85% of antimicrobial therapy in both adults and children were found to vary from recommended management as determined through process criteria for appropriateness of use [30]. In one study involving adults the main criteria which indicated inappropriate management were inappropriate antibiotic selection (14.2%), inappropriate length of treatment (18%), arbitrary (unjustified) changes in antibiotic therapy (11.3%) and lack of culture and sensitivity testing (9.4%) [25]. In a study of children receiving antimicrobial agents, in 31.8% of therapies there was no attempt to identify or to culture the pathogen, no monitoring for renal effects in 22.1%, lack of suflicient justification for initiating antimicrobial treatment in 14.2% and unjustified changes in antibiotic treatment in 13.6% [28%]. Results from another study assessing gentamicin usage
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Drug Utilization in Panama
revealed inadequate monitoring of renal function in 60% of the cases, inappropriate dosage interval and dose calculations, treatment duration too short or too long in 44%, no rational justification for use in 37%, empiric use or lack of sensitivity testing in 34% [31]. No studies have been conducted in Panama to evaluate compliance with prescribed treatment. However, there are data that suggest potential for problems in compliance that could result from inadequate communication between prescriber and patient. Evaluation of patient queries to pharmacists indicate that 32% of the 68,214 queries over a 4 year period concerned the indication for the prescription and 10% dealt with how to take the drug [Coordination de Comunicadores Cientificos, unpublished data]. Another 8% of the queries were related to changes in drug products as a consequence of the institution’s generic substitution policy. These data may not be representative of the patient population at large and it is not known if this is only the “tip of the iceberg”. Nor is it known what proportion of those who do not consult the pharmacist have problems in understanding the prescription. CLINICAL RESEARCH IN PANAMA
The quality of scientific publications provide an opportunity to review the state of development of a nation’s “medical culture”, the set of attitudes and guiding principles for the practice of medicine. There are three regularly published medical journals in Panama. A survey of the type of publications and clinical research designs documented a predominance of case reports, cases series, informal retrospective and descriptive surveys [32]. This underscores the difficulty in bridging the gap separating clinical practice and scientific concepts and principles. The demand from prescribers for formulary inclusion of drugs of unproven clinical efficacy, irrational combination drugs and more expensive therapeutic options are a clear indication of the need for improved education and information on the principles of scientific evaluation of clinical interventions [33], pharmacological or non-pharmacological. Drug utilization review programs (therapeutic audits) are still to be formally adopted [34]. Although some initial work in establishing a spontaneous adverse drug reaction reporting scheme has been reported [35,36], it still cannot be considered as effectively implemented. No reliable drug database is
available for large-scale analytical research. However, Panama currently participates in the WHO-EURO sponsored Drug Use in Pregnancy study [37], which aims to establish a permanent network for collaborative pharmacoepidemiological research. There is concern over the potential clinical implications resulting from ethnic differences in drug metabolism. A university-based population pharmacology and ethnopharmacokinetics research program is currently underway to assess differences and/or similarities among Panamanian Amerindian groups and between these groups and Caucasians [38-43]. The author is unaware of published studies on economic or social aspects of drug utilization in Panama. The current state of clinical research in general, and drug utilization research in particular, has (not) evolved in the absence of a national, or even an institutional, research policy. Most clinical “research” is the result of individual interest in publishing a paper on a particular clinical problem deemed to be of wider professional interest. The few pharmaceutical industry sponsored “research” programs submitted to the Medicines Commission are inadequately designed and could be considered primarily promotional, aimed at inducing prescribers to try new drugs claimed to be important therapeutic advances, or to discredit generic competition by attempts to demonstrate inequivalency with innovator products. THE INTERVENTIONS
Efforts to promote the rational use of pharmaceuticals have utilized both regulatory and educational and informational strategies. Regulatory measures involved the withdrawal of many drugs of doubtful therapeutic value and irrational combination drugs from the Social Security drug formulary, as mentioned above. Through critical evaluation of available clinical studies submitted with new formulary addition requests it has been possible to reject drugs with inadequate documentation of clinical efficacy (buflomedyl, tromantadine, amineptine) or questionable safety (indoprofen, which was later withdrawn worldwide). The improvement in drug selection in the public sector has not, however, been accompanied by a concomitant improvement in the private sector [44,45]. Information and educational efforts have been carried out intensively under a drug information program by the Medicines Commission
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of the Panama Social Security [46]. Educational outreach strategies have involved distribution of written material and a variety of face-toface methods, such as group meetings and professional visits to physicians on a person-toperson basis similar to those of pharmaceutical company representatives (“counterdetailing”). In 1983 and 1984 written material consisted of mimeographed 2-4 page articles on pharmacotherapeutics and related pharmaceutical topics. A drug bulletin has been published irregularly since 1985 with the collaboration of the Pan American Health Organization and the Pan American Health and Education Foundation [47]. The bulletin has consisted mainly of camera-ready translations of articles from The Medical Letter, Drug and Therapeutics Bulletin, Adverse Drug Reaction Bulletin and other publications. One issue was compiled locally, consisting of translations from other drug bulletins and several original articles, including drug utilization data. The bulletin was distributed free of charge to 2000 physicians and pharmacists throughout the country. Financial and administrative constraints during the past 2 years have adversely affected the continuity of this publication. Changes in the format, making the bulletin more streamlined and less costly, and more stringent selection of relevant articles are underway to reactivate the bulletin. The rational use of drugs has been promoted through several workshops and seminars for health workers of various disciplines (physicians, dentists, pharmacists, nurses, administrators). At interrupted intervals the drug information program has participated in the continuing education programs of several Social Security outpatient clinics with lectures Table 6. Pharmacotherapeutic
Information Program topics
Workshops and seminars: Managing drug supply Drug formularies and the essential drugs concept Drug epidemiology and adverse drug reactions Drugs in pregnancy and lactation Clinical pharmacology in pediatric dentistry Critical evaluation of the medical literature Contimdng medical education sessions: Principles of pediatric clinical pharmacology Drug interactions Use and misuse of antibiotics Rational use of aminoglycosides Rational use of immunoglobulins Use of antihypertensive agents in Panama Use of geriatric drugs or use of drugs in geriatric patients? Pseudo-allergic reactions to pencillin procaine New drug introductions in Panama
and discussions on pharmacotherapeutic topics on a monthly basis (Table 6). Whenever relevant, drug utilization data is also presented. Another modality has been “face to face” drug information [48]. During a 4 year period the pharmacotherapeutic information program employed a corps of seven pharmacists who were specially trained to visit physicians on a person-to-person basis to provide information on decisions of the Medicines Commission, therapeutic information relevant to problems detected in prescription surveys, and promote reporting of suspected adverse drug reactions and detected drug product problems. Currently this strategy is at a minimal level of activity for a number of reasons, mainly, loss of personnel and positions and need for improved competence levels. The effectiveness of these strategies has not been critically assessed. This has been partly due to significant confounding introduced by increasing drug shortages in the face of the deteriorating political and economic situation of the past 3 years. Subjectively, all these activities are considered to contribute to at least lay the cultural foundations necessary for ensuring the effectiveness of future interventions. In this context, a recent workshop formally introduced the essential drugs concept to leading members of the medical, pharmacy, dentistry and nursing schools and faculties [49]. Another recent positive development is the inclusion of clinical pharmacology topics and the essential drugs concept in the basic pharmacology and the therapeutics courses of the Faculty of Medicine. With regard to patient information a group of Social Security pharmacists (Scientific Communicators), administratively under another directorate, is responsible for providing drug information to patients. This is done through regularly scheduled oral presentations to patients waiting to fill their prescriptions in Social Security pharmacy lobbies. Additionally, in several Social Security outpatient clinics a pharmacist is available 8 hours daily for patient consultation, as mentioned previously. The effectiveness of this activity has not been evaluated. CONCLUSION Review of current drug utilization in Panama indicates that there is much work to be done in formulating and implementing an essential
Drug Utilization in Panama
drugs and health policy. Drug utilization research, descriptive, analytical and experimental, biomedical and social, will be fundamental to the implementation of this policy [50]. The current use of pharmaceutical agents in Panama thus constitutes a challenge not only to clinical pharmacology but also to the many other disciplines involved in drug utilization [51].
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39. Jorge LF, Arias TD, Inaba T, Jackson PR. Unimodal distribution of the metabolic ratio for debrisoquine in Cuna Amerindians of Panama. Br J Clln Pharmac 1990; 30: in press. 40. Arias TD, Jorge LF, Lee D, Barrantes R, Inaba T. The oxidative metabolism of sparteine in the Cuna Amerindians of Panama: absence of evidence for deficient metabolizers. Clin Pharmac Ther 1988; 43: 456465. 41. Inaba T, Jorge LF, Arias TD. Mephenytoin hydroxylation in the Cuna Amerindians of Panama. Br J CIin Pharmac 1988; 25: 75-79. 42. Arias TD, Barrantes R, Inaba T, Cooke RG, Jorge L. A preliminary note on the transient polymorphic oxidation of sparteine in the Ngawbt Guaymi Amerindians: a case of genetic divergence with tentative phylogenetic time frame for the pathway. CIln Warmac Ther 1988; 44: 343-352. 43. Inaba T, Arias TD. On phenotyping with isoniazid: the use of the urinary acetylation ration and the uniqueness of antimodes. A study in two Amerindian populations. ClIn Pharmac Ther 1987; 42: 493497. 44. Lee D, Rogers A, Robles RT, et al. Utilization de la estreptoquinasa-estreptodomasa en la Caja de Seguro Social. Rev M&i Caja Segnro Sot 1987; 19: 181-185. 45. Lee D. Continued marketing of a useless drug (‘Varidase’) in Panama. Lancet 1990; 335: 667.
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Comision National de Medicamentos. Programa de Informac%n, DlvnIgaci6n y Docencia. Panaml: Caja de Seguro Social; 1984. Lee D. Bulletins in developing countries: medicamentos y terapdutica. ISDB Newslett 1987; 2(12): 21-22. Avorn J, Harvey K, Soumerai S, Herxheimer A, Plumridge R, Bardelay G. Information and education as determinants of antibiotic use: report of Task Force 5. Rev Infect Dis 1987: 9: S286S296. Quintero EG. Introdu&ih de1 Concepto de Medicamentos Esenciales en 10s Curricula de las Facultades de Medicina y Fannacia. Informe Final del Taller. Panama: Universidad de Panama y Organization Panamericana de la Salud; 1989. Baksaas I, Lunde PKM. National drug policies: the need for drug utilization studies. Trends Pharmac Sci 1986; 7: 331-333. Lee D, Gan V, Quijano R, Uppal R. The challenge for clinical pharmacology in developing countries. In: Sterky G, Tomson G, Sachs L, Henningsson B, Bergman U, Eds Medicines & Society: a Challenge in Health Develonment. Stockholm: Karolinska Institutet, Department of International Health Care Research (IHCAR) and Department of Clinical Pharmacology, Huddinge University Hospital, 18 May-18 June; 1987: Appendix 2.
