Day-to-day experience I
I
The supply of antituberculosis drugs and national drugs policies P. Chauiet Clinique de Pneumo-Phtisiologie Ouesf, Algiers. Algeria
Matiben, Hbpital de B.&i-Messous,
Centre Hospitalier
Universitairr
d’illger-
S UMMA R Y. The money necessary for purchasing antituberculosis drugs in a national programme comes from the Public Health Services budget, funds from the health insurance scheme (when it exists) and household budgets. The Public Health Services budget is on average $2-23 US per year and per person in low or middle income countries. Average drug consumption in these groups of countries was from $2-26 US per person in 1990, The number of patients to be treated depends on the annual risk of tuberculous infection (ARTI) and the case detection rate: it is the same when the ART1 is 1% and the detection rate lOO%,and when the ART1 is 2% and the detection rate 50% of cases. The supply of antituberculosis drugs has a real cost representing around 3% of global drug consumption in low income countries and is always less than 1% of global drug consumption in middle income countries. In most developing countries it could be covered with the aid of national financial resources, on condition that it is integrated into a coherent national drugs policy aimed at guaranteeing the continued availability of essential drugs. R .!? S U M 8. L’argent necessaire pour acheter les medicaments antituberculeux d’un programme national
provient du budget des services de Sante Publique, des fonds de l’assurance maladie (lorsqu’elle existe) et du budget des menages. Le budget des services de Sante publique est en moyenne de $2 a $23 US par an et par habitant dans les pays 31faible revenu ou 1 revenu intermediaire. La consommation pharmaceutique moyenne dans les mcmes groupes de pays est de $2 5 $26 US par habitant en 1990. Le nombre de malades a traiter depend du risque annuel d’infection tuberculeuse (RAI) et du taux du detection des cas : il est le m&melorsque le RAI est de 1% et le taux de detection de lOO%, et lorsque le RAI est de 2% et le taux de detection de 50% des cas. L’approvisionnement en medicaments antituberculeux a un prix reel qui represente environ 3% de la consommation pharmaceutique globale dans les pays a faible revenu, et toujours moins de 1% de la consommation pharmaceutique globale dans les pays a revenu intermediaire. I1 pourrait bre assure, dans le plupart des pays en developpement, grace aux ressources financieres nationales, 21condition d’etre integre dans une politique pharmaceutique nationale coherente, visant a garantir la disponibilite permanente des medicaments essentiels. _ R ES iJ M E N , El dinero necesario para comprar 10s medicamentos antituberculosos de un programa national proviene de1 presupuesto de 10s Servicios de Salud Ptiblica, de 10s fondos de1 Sistema de Seguros de Salud (cuando existe) y de1 presupuesto de 10s hogares. El presupuesto de 10s Servicios de Salud Ptiblica es, en promedio, de $2 a $23 US por aiio y por habitante en 10s pa&es con recursos escasos o intermedios. El consumo farmaceutico promedio en 10s mismos grupos de paises era de $2 a $26 US por habitante en 1990. El ntimero de enfermos que deben ser tratados depende de1 riesgo anual de infection tuberculosa (RAIT) y de la tasa de deteccidn de cases : es el mismo cuando el RAIT es de 1 % y la tasa de detecci6n de 100 % y cuando el RAIT es de 2 % y la tasa de detection de 50 % de 10s cases. El cost0 real de1 aprovisionamiento de medicamentos antituberculosos representa alrededor de un 3 % de1 consumo farmaceutico global en 10s paises de escasos recursos y siempre menos de 1 % de1 consumo farmaceutico global en 10s paises de recursos intermedios. En la
Correspondence to: Professeur Pierre Chaulet MD, FCCP,Clinique Pneumo-Phtisiologie Matiben, HBpital de B&i-Messous, Centre Hospitalier Universitaire d’Alger-Ouest, Algiers, Algeria.
de
With the collaboration of Professor Fatma Zohra Oufriha, Insitute of Economic Science. Algiers. 295
296
Tubercle and Lung Disease
mayor parte de 10s pa&es en desarrollo este costo podria ser cubierto por 10s recursos Anancieros nacionales, a condition de ser integrado en una politica farmaceutica national coherente, que tienda a garantizar una disponibilidad permanente de 10s medicamentos esenciales.
INTRODUCTION For a long time, the price of the most costly antituberculosis drugs, rifampicin and pyrazinamide, was considered a major obstacle to the adoption of shortcourse chemotherapy regimens in tuberculosis control programmes applied in developing countries. Because of this, in some of these countries those responsible for national programmes relied on international aid to obtain free of charge the antituberculosis drugs necessary for the introduction of modern chemotherapy regimens. Today, in the context of the World Health Organization’s new antituberculosis strategy,’ short-course chemotherapy regimens are recommended for the treatment of all forms of tuberculosis, in children as well as in adults.** 3 It has in fact been proven that short-course chemotherapy of tuberculosis is one of the most efficient health interventions in terms of cost per case cured, per death avoided and per transmission avoided.4,5 That is why, in a global context marked by the need to strengthen national antituberculosis programmes because of the social consequences of the economic crisis and the spread of the HIV epidemic, the problem of a continued supply of drugs has arisen sharply and simultaneously in all the developing countries in the world.6 How can one estimate the need for antituberculosis drugs and their cost in a developing country? How can one ensure continued supply of this category of essential drugs? What role could international cooperation play in this field? These are the main questions asked, for which realistic answers, adapted to the context of each nation, must be found in order to meet the challenge of the year 2000: to halve the incidence of tuberculous in the developing world in 8-12 years.’
HOW TO ESTIMATE THE NEED FOR ANTITUBERCULOSIS DRUGS AND THEIR BASIC COST
of tuberculosis (pulmonary or extrapulmonary). These patients must receive either a chemotherapy regimen of 6 months containing rifampicin throughout treatment, or a chemotherapy regimen of 8 months containing rifampicin during the first 2 months only. Another high priority category is that of pulmonary tuberculosis cases already treated by a previous course of chemotherapy (failure or relapse) who are still excreting bacilli and who must follow another standard chemotherapy regimen of 8 months, with rifampicin throughout. The third category regroups new cases of sputumnegative pulmonary tuberculosis (with moderate or limited parenchymal lesions) and the majority of cases of extrapulmonary tuberculosis: this group thus contains almost all cases of childhood tuberculosis, with the exception of meningitis and miliary disease. These patients must receive either a treatment regimen of 4 months with rifampicin throughout treatment (possibly completed by 4 supplementary months with isoniazid alone) or a treatment regimen of 8 months with rifampicin for the first 2 months only. The last category is that of chronic cases of pulmonary tuberculosis, who continue to excrete bacilli after 2 completed chemotherapy courses: these bacilli are often resistant to isoniazid and rifampicin. Such patients can only be cured with minor drugs not included in the list of essential drugs.’ The basic price of the drugs (Table 1) composing the chemotherapy regimens applicable in the first three categories of patients can be calculated with reference to the price list of essential drugs published every year by UNICEF.8 The different regimens recommended have a different basic price depending on their duration and the nature of the drugs used (Table 2).
How to assess the respective sizes of the different patient categories The number of new cases of smear-positive
The need for antituberculosis drugs is defined by the type of chemotherapy regimens chosen for inclusion in a national tuberculosis treatment strategy and by the number of tuberculosis cases expected to be treated each year under the programme.
Patient categories, treatment regimen categories According to the WHO directives, tuberculosis patients are divided into four broad categories for which different treatment regimens are recommended.* The first - and main - category is that of new cases of smear-positive pulmonary tuberculosis and severe forms
pulmonary tuberculosis is directly proportional to the annual risk of tuberculous infection, measured by tuberculin prevalence surveys.‘,” For an annual tuberculous infection risk of 1% there is a corresponding average incidence of 50 cases of smear-positive pulmonary tuberculosis per 100 000 inhabitants: the CI at 95% is 39-59 cases.4 This incidence corresponds to a 45% incidence of all types of tuberculosis in technically advanced countries, and a 54% incidence of all types of tuberculosis in countries such as Tanzania or Algeria where means of radiodiagnostic investigation are not as widely available.4,5 If to new cases of smear-positive pulmonary tuberculosis are added severe forms of pulmonary tuberculosis (such as
The supply of antituberculosis
Table 1. Basic prices of eqsential anti tuberculosis (separate drugs and principal combinations Presentation
Dmgs
drugs in 1991 in fixed proportions) UNICEF list
., June 1991’ in $US
Isolated Ethambutol Isoniazid Isoniazid Pyrazinamide Rifampicin Rifampicin Sueptomycin Distjlled water for injection Fixed proportion Isoniazid Thiacetazone Rifampicin Isoniazid Rifampicin Isoniazid Rifampicin Isoniazid Pyrazinamide
mmg IOOmg 300mg 500 mg 150 mg 300mg 1g 5ml
combinations 300 mg 150 mg 150mg 1OOmg 300 mg 150mg 120mg 50 mg 300 mg
IDA list May 1991t in DFI
1000 1000 1000 1000 100 100 50 50
23.80 3.95 11.87 43.00 4.83 9.87 13.37 1.65
43.50 6.60
1000
11.34
20.40
1000
61.48
99.50
1000
108.12
168
1000
115.00
(110)1
56 8.50 16 I
*Essential Drugs, price list, UNICEF, February-June 1991. +Intemational Dispensary Association, price indicator, May 1991 in Dutch Florins ($1 US = 1.9 DFl). iEstimate for 199 1.
Table 2. Principal antituberculosis chemotherapy regimens recommended for national programmes and their basic unit price according to the UNICEF 1991 price list2 Chemotherapy
regimens
Basic regimens for new cases of tuberculosis and severe forms of 6 months 2 SRHZ14 RH (or 2 ERHZ/4 RH (or 8 months 2 SRHZ/6 TH (or
Price in $US smear-positive tuberculosis 4 R3 H3) 4 R3 H3) 6 EH)
pulmonary 66 (or 53) 52 (or 39) 43 (or 52)
Basic regimens for new cases of smear negative pulmonary tuberculosis (and minimal lesions) and for most new cases of extrapulmonary tuberculosis 4 months 2 RHiY2 RH (or 2 R3 H3) 35.5 (or 29) (8 months) 2 RHZ/6TH (or 6 EH) 31 8 months 2 RHZ/6 TH (or 6 EH) 25 (or 34) Retreatment regimens for failure and relapse cases of bacteriologically proven pulmonary tuberculosis (after a first course of chemotherapy) 8 months 2 SREZ0 RHEZ/5 RHE (or 5 R3 H3 E3) 96 (or 79) Each letter represents a drug: R=rifampicin, H=isoniazid, Z=pyrazinamide, S=streptomycin, E=ethambutol, T=thiacetazone. The number preceding a group of letters represents the number of months during which the drugs are administered. The number following a letter represents the number of weekly doses of the drug. Where there is no number following the letter the drug is administered on a daily basis.
miliary disease) or extrapulmonary tuberculosis (such as meningitis, pericarditis and other extensive se&is, renal tuberculosis, tuberculosis of the spine with neurological complications), it is reasonable to estimate that the first category of patients comprises approximately half of the new cases who will need to be treated. The other half of new cases is made up of smearnegative cases of pulmonary tuberculosis and the majority
drugs and national drugs policies
297
of extrapulmonary tuberculosis cases (notably tuberculosis of the lymph nodes and of the bones and joints). Theoretically, when the annual risk of tuberculous infection is 1% in a community, one can expect a minimum of 100 new cases to treat per 100 000 inhabitants. To this first total we must add a variable number of old cases of pulmonary tuberculosis who have already been treated but are again excreting bacilli and who must receive a standardized ‘retreatment’ regimen: progressive resumption of the disease after premature interruption of initial treatment, failure or relapse cases after initial chemotherapy treatment, chronic cases continuing to excrete bacilli after 2 or more chemotherapy courses. In the absence of an antituberculosis programme or standardization of chemotherapy regimens, the number of old cases can be high: it is a reflection of disorganized tuberculosis treatments applied in recent years in the communities in question. On the other hand, in countries where standardized short-course chemotherapy regimens (of 6 or 8 months) have for several years been routinely applied to all new cases, ‘previously treated’ cases of pulmonary tuberculosis requiring ‘retreatment’ constitute an extra but limited group of patients to be treated, equal to around 10% of total new smear-positive cases: 7% in Algeria and Tanzania,” 13% in Malawi.” In other words, in the case of regularly applied programmes, to 50 new cases of smear-positive pulmonary tuberculosis to be treated each year, a second chemotherapy treatment for 5 extra cases previously treated for pulmonary tuberculosis must be provided for. Amongst those previously treated within modern national programmes, the proportion of ‘chronic’ cases with bacilli resistant at least to isoniazid and rifampicin, is from 10 to 15%: 11.5% in Algeria,” 12% in Tanzania,14 15.4% in Korea.” In short, the total theoretical number of tuberculosis cases to be included in the different categories of patients to be treated comes to a minimum of 105 if the annual risk of tuberculous infection is I%, 210 if the annual risk of tuberculous infection is 2%. These estimates must be reappraised in countries where there is a high rate of HIV positivity. Finally, in every 10 ‘previously treated’ cases, 1 or 2 ‘chronic cases’ can be found, very probably chronic excretors of bacilli resistant to isoniazid and rifampicin. These chronic cases cannot be cured without a 12-month course which combines minor drugs such as ethionamide or prothionamide, cycloserin, kanamycin or capreomycin.’ As these chronic cases represent less than 1% of cases to be treated, chemotherapy strategies must be worked out to give priority to the first three categories of patients and of chemotherapy regimens, which cover 99% of patients.
The basic cost of a modern chemotherapy
strategy
A theoretical estimate of the total number of patients to be treated taken from the annual risk of tuberculosis
298
Tubercle and Lung Disease
infection is misleading. In practice one must also take into account the real detection rate which depends on the population’s health coverage by the health services and the technical qualifications of the health personnel in the field. The detection rate is unequal, changing according to the country or region of the developing world: 27% and 28% of expected cases in sub-$&ran Africa and Central America, 60-70% of expected cases in South America, Asia, North Africa and the Middle East: 55% on average throughout all of the developing countriese4 Because of this, the actual number of cases to be treated is the same when the annual risk of tuberculous infection is 1% and the detection rate of new cases is lOO%, or when the annual risk of tuberculous infections is 2% and the detection rate of new cases is 50%. However many patients there may be to treat, different strategies of effective chemotherapy can be adopted, whose basic costs are different. To estimate the basic cost of the different strategies possible, the total cost of drugs necessary for treating patients was estimated in a simulated epidemiological situation where the annual risk of tuberculous infection would be 1% and the detection rate of new cases 100%. If the most costly chemotherapy strategy is adopted (based on regimens containing rifampicin throughout treatment for all categories of patients) the total cost of drugs necessary for treating 105 patients (per 100 000 inhabitants) is $5582 US, i.e. $0.055 US per inhabitant (Table 3). If the least costly chemotherapy strategy is adopted (based on effective short-course regimens containing the smallest quantity possible of rifampicin) the total cost of drugs necessary for treating 105 patients (per 100000 inhabitants) is $3795 US, i.e. $0.037 US per inhabitant (Table 4). Other strategies of moderate cost can be selected depending on the national context: by replacing strepto-
Table 3. The basic price of the most costly antituberculosis chemotherapy strategy (excluding chronic cases) Drug prices in $LJS (UNICEF 1991 price list)
Patients to treat Categories Smear-positive pulmonary tuberculosis and severe forms Smear negative pulmonary tuberculosis and extrapulmonary tuberculosis Failures and relapse cases Total for 100 000 inhabitants Price of antituberculosis
Number*
50
50
Unit price
Total price
x 66
= 3300
x 35.5 x 37 average
5
x 96
105
= 480 = 5582
drugs per inhabitant
*For an annual risk of tuberculous of 100% of new cases.
= 1775 = 1850 = 1812
in $US
= 0.055
infection of 1% and a detection rate
Table 4. The basic price of the least costly antituberculosis chemotherapy
strategy (excluding
chronic cases)
Patients to treat Categories Smear-positive pulmonary tuberculosis and severe forms Smear-negative pulmonary tuberculosis and extrapulmonary tuberculosis Failures and relapse cases Total for 100 000 inhabitants Price of antituberculosis
Drug prices in $US (UNICEF 1991 price list) Number*
Unit price
Total price
50
x 43
= 2150
50
x 25
= 1250
5
x 79
= 395
105
= 3795
drugs per inhabitant
*For an annual risk of tuberculous of 100% of new cases.
in $US
= 0.037
infection of 1% and a detection rate
mycin in the initial phase or thiacetazone in the continuation phase by ethambutol; or otherwise by administering the drugs 3 times per week under direct supervision by health personnel, when this can be organized.
CALCULATING THE REAL COST OF ANTITUBERCULOSIS DRUGS The basic price of drugs used in the two different strategies (Tables 3 and 4) was calculated according to the prices of essential drugs indicated in the UNICEF 1991 list.‘F8 However these basic prices do not correspond to the final real price of the drugs when they are given to patients. In fact, the prices on the UNICEF list are prices agreed by certain manufacturers, for bulk purchase destined for health programmes in developing countries. To these minimum prices or production prices must be added other costs which go towards making up the final cost of the drugs.16 The import price in developing countries (which on the whole produce no antituberculosis drugs and therefore buy them on the international market and then import them before distribution in the internal network) is expressed in two ways: 1. the FOB (free on board) price, which is the price of the drug ready for export. This FOB price raises the basic or production price by 4-6%. 2. the CIF (cost, insurance, freight) price, which adds to the FOB price the cost of insurance and transport to the importing country. The cost thus added to the FOB price is variable: it depends on the distance separating the exporting country and the importing country and the method of transport used (rail, road, sea, air). By definition the CIF price is superior both to the FOB price and to the production price. It is
The supply of antituberculosis
reasonable to add 20-30% to the FOB to estimate the CIF price (International Price Indicator Guide 1990, Management Sciences for Health 1991). The price at distribution (through health services or private pharmacies) is higher. In the make-up of the final price, to the CIF price is added a variety of taxes (calculated as a percentage of the CIF price) and the commercial margins of the intermediaries (the wholesalers) and the retail pharmacists: the taxes and margins are set out by the national legislation of the different countries.‘” Thus in 1991 in Algeria (a middle income country), the CIF price of drugs, augmented by 27% (taxes and customs duty), constitutes the cost price of the drug for the wholesalers (which are state enterprises or private dealers). To this cost price must be added the commercial margin of the wholesalers (20% of the CIF price) and that of the retailers (40% of the CIF price or 27% of the cost price) to obtain the public selling price. In other words, the final price of the drug sold to the patient in a distribution agency is equal to the CIF price multiplied by a coefficient of 1.87. In the case of antituberculosis drugs delivered free of charge to patients in the Public Health Services supplied by state enterprises (which play the role of wholesalers), the cost of the drug is equal to the CIF price multiplied by a coefficient of 1.47. Another example: in 1990, in Mali (a low income country), the final price of the drug when sold to the public was equal to the CIF price multiplied by a coefficient of 1.95.” These two examples illustrate the differences between the basic price and the real final price of antituberculosis drugs at the moment of their use in national programmes. In the simulated epidemiological situation described above, and for the two chemotherapy strategies whose basic price has been evaluated (Tables 3 and 4) the ‘real’ price of antituberculosis drugs has been calculated by adopting the following hypotheses: l
l
l
The CIF price adopted was the basic price from the UNICEF 1991 list, arbitrarily augmented by 25% . The price at distribution in the Public Health Services was a ‘wholesale’ price, i.e. the CIF price multiplied by the coefficient of 1.47 (applied in Algeria). The price at distribution in drug distribution agencies was the CIF price multiplied by the coefficient of 1.90 (halfway between the coefficient of 1.87 for Algeria and the coefficient of 1.95 for Mali).
The end price of antituberculosis drugs per inhabitant would be from 10.25 or 13.25 US cents if the most expensive chemotherapy strategy was adopted, and 6.96 or 9.0 US cents if the least expensive chemotherapy strategy was adopted (Table 5). In each strategy, the end price is different depending on whether the drugs are bought wholesale and distributed to patients by government health services or if they are sold to patients in the public drug distribution agencies.
drugs and national drugs policies
Table 5. The final real price of antituberculosis the application of 2 different chemotherapy chronic cases)
drugs necessary strategies (excluding
299 for
Drug prices, in US cents, per inhabitant* Least costly Most costly strategy strategy UNICEF 1991 price list Estimated import price (CIF)+ Consumer price Drugs bought wholesale by health services and delivered directly to patients (CIF price x 1.47) Drugs delivered at retail price in dispensaries (CIF price x 1.90)
5.58 6.97
3.79 4.73
10.25
6.96
13.25
9.00
*For an annual risk of tuberculous infection of I%, and a detection of 100% new cases. +The FOB price is calculated by adding 4-6% to the basic price from the UNICEF list; the CIF price including the cost of transport to the import country adds a variable percentage to the FOB price depending on the distance and means of transport. It is reasonable to add 20-30% to the FOB price to estimate the CIF price (International Price Indicator Guide 1990, Management Sciences for Health 1991). In the example given, the CIF price estimated has been calculated by adding 25% to the basic price, from the UNICEF price list.
All of these calculations are based on hypotheses established from two concrete examples in order to support the approach adopted: they need to be reassessed in each national context in order to receive the necessary adjustments.
NATIONAL DRUGS
RESOURCES
FOR THE SUPPLY
OF
National resources available for drug purchasing (among which are antituberculosis drugs) come from the budget allocated by the State to government health services, sums provided by health insurance systems (when they exist, and for the population they cover) and sums paid directly by the population which pays for the drugs either wholly or in part when purchased in the drug distribution agencies.
Limited government health budgets In low income developing countries, the purchase of antituberculosis drugs is not always covered by government health budgets. To this limit of an internal nature is added a restriction of an external nature: a limitation on the availability of hard currency, aggravated by the irregular and at times irrational allocation of this currency. For more than 20 years, in all the developing countries of the world, government health budgets have represented only a small fraction of the central administration’s working budget, and a minimal proportion of the GDP. Since the beginning of the 1980s these
300
Tubercle and Lung Disease
budgets have shrunk from year to year due to structural adjustment programmes applied in order to confront the world economic recession: devaluation of national currencies, reduction in public spending in an effort to balance budgets, and, as a consequence, a diminution of government support for health action programmes.‘* The recent reports of the World Bank’9.20 allow one to evaluate the level of government health spending and to measure the huge disparities which exist even between the different developing countries. Thus in 1988 government health spending per inhabitant was, on average, $2 US in the group of low income countries (characterized by an average annual GNP per inhabitant inferior to $500 US); $23 US in middle income countries (where the average annual GNP per inhabitant is between $600 and $5300 US), whereas it was $612 US in high income countries (Table 6). In these budgets the proportion allocated to the purchase of drugs distributed in the Public Health Services is situated between 10% and 30%; one can deduce from this that in the counties where the government health budgets are below $3 US per inhabitant, it is unlikely that the cost of a continued supply of essential drugs (and hence of antituberculosis drugs) would be covered uniquely by the government health budget. It is in this context that in the last 10 years there has begun to be a shortage of antituberculosis drugs delivered in the Public Health Services and these have at times had to be paid for by patients.
Table 6. Government groups of countries
health
Groups of countrtes
Low income countries Total China India Other Middle income countries Total
spending per inhabitant in the different
Population in millions I989*
GNP per inhabitant in $US 1989’
Government health spending per inhabitant in $US 1988’
2948.4
330
2
I 113.9
3
832.5 1002
350 340 300
I 1.9
1104.5
2040
23
Lower bracket Higher bracket
68 I .8 422.7
1360 3150
8.5 43
High income countries
830.4
18330
612
‘World Bank 1991.zo ‘Spending calculated from data published in World Bank 1990.t9
National drug consumption The resources coming from health insurance schemes or family budgets are not always easily identifiable. However, in the majority of developing countries, each year information is made available on the total amount of drugs sales, whether they are distributed in hospitals
Table 7. Drug consumption groups of countries Groups of countries
Low income countries Total China India Other Middle incdme countries Total
per inhabitant in 1990 in the different
Population in millions 1989’
Drug corlsumption in 1990’ *otal in Per inhabitant mfllions in $US of SUS
2791.8
7440
2.6
I 113.9 832.5 845.4
4200 la 17%
3.7 1.7 2.1
872.6
16952.1
19.4
Lower bracket Higher bracket
549.6 323
8567.5 8384.6
15.5 25.9
High income coantries
791.2
132354,
167
‘World Bank 1991.m ‘The data were added together for 17 low income countries, 30 middle income countries and 15 high income countries, i.e. for 9 1%of the world’s population. according to the World Drug Market Manual, 1991.2’
Table 8. Drug consumption per inhabitan (in $US) by country and by groups of countries in 1990 (from the World Drug Market Manual 1991) Group of low income countries (Gross National Product from $80-500 0.6 .Myanmar Ethiopia 0.8 I Nepal 1 Tanzania 1.4 Nigeria 1.6 Bangladesh 1.6 Zaire 1.7 India Sudan 1.8
US per capita) Ghana Sri Lanka Indonesia Vietnam Kenya China Korea(North) Pakistan Pakistan
Group of middle income countries (Gross National Product from $600-5300 I Nicaragua Bolivia 3 Zimbabwe 5.1 5.1 Yemen 7.1 Syria 8.1 Malaysia 8.5 Egypt Thailand 8.6 9 Ecuador 10 .Morocco II Guatemala 12 Peru 12 Jordan 13 Iran 14 Tunisia
2 2 3 3 3 3.7 4 4.5 4.5
US per capita) Paraguay Algeria Turkey Chile Colombia Venezuela Iraq Libya Brazil Mexico South Africa Uruguay Argentina Korea(South)
15 15 17 17 17 18 18 18 23 25 26 41 48 57
Group of high income countries (Gross National Product from $6000-29000 US per capita) 27 Spain Singapore 27 Canada Hong Kong 40 Italy Tatwan Saudi Arabia 40 Germany us United Arab Emirates 53 France Great Britain 96 99 Japan New Zealand
I14 147 191 201 201 214 234
The listing of countries according to their GNP is taken from the World Development Report 199 1,World Bank, Washington 1991.
or Public Health Services, health institutions.2’
private
chemists
or private
The supply of antituberculosis
If the total sales, whatever the channel of distribution and whatever the mode of payment, is considered in relation to the number of inhabitants in the country in the year in question, an indicator is obtained: the average drug consumption per year and per inhabitant, widely used in health planning and market studies. This consumption is loosely linked to national wealth (measured by GNP per inhabitant) and especially with health services development. In 1990 it was on average $2.6 US in the group of low income countries and $19.4 US in the group of middle income countries, while it was $167 US in high income countries (Table 7). The average drug consumption per inhabitant differs widely from one country to the next, even in the developing world (Table 8). But if the data available by groups of countries are added together, it can be noted that the average drug consumption per inhabitant is higher than government health spending per inhabitant in the low income countries and in the lower bracket of middle income countries.
This comparison made:
several
China India Other Middle income countries Total Lower bracket Higher bracket High income countries
drugs compared health spending
to drug consumption,
by
2
2.6
0.07
0.09
3 1 1.9
3.1 1.7 2.1
0.07 0.07 0.07
0.09 0.09 0.09
23
19.4
0.10
0.13
8.5 43
15.5 25.9
0.10 0.10
0.13 0.13
0.10
0. I3
612
to be
In the context of national health action programmes, antituberculosis drugs should be distributed free of charge to patients because of their major epidemiological impact and their considerable efficiency. This basic principle, affirmed since 1964 in all the WHO’s expert reports, 22.23,24has been reinforced by recent economic analysis.2s
Spending per inhabitant (in US dollars) Govt health Consumer price in 199 I Drug spending consumption for antituberculosis drugs” (1988) low? high* (1990) Low income countries Total
observations
The promotion of national drugs policies
Table 9. The final price of antituberculosis groups of countries and government
allows
301
In the group of low income countries the least costly chemotherapy strategy must always be adopted. The price of essential antituberculosis drugs represents 2.7% or 3.4% of the average drug consumption (this becomes 5.4% or 6.8% if the annual risk of tuberculous infection is 2% and the detection rate 100% of cases). In the group of middle income countries the most costly chemotherapy strategy can be adopted in the majority of cases. The price of essential antituberculosis drugs always represents less than 1% of average drug consumption per inhabitant: 0.6% or 0.8% in lower bracket countries (whose average GNP per inhabitant is $60&2400 US per year) and 0.38% or 0.50% in the higher bracket countries (whose average GNP per inhabitant is from $2500-5300 US). In most countries, regardless of income level and epidemiological situation, the real price of antituberculosis drugs could be integrated into the average drug consumption per inhabitant if the latter were oriented in priority towards the consumption of essential drugs. In most middle income countries, the real price of antituberculosis drugs could be integrated into the government health budget.
THE NEED FOR ANTITUBERCULOSIS DRUGS AND NATIONAL RESOURCES ALLOCATED TO DRUG PURCHASES In the epidemiological situation which served as a basic hypothesis for the calculation of the real cost of antituberculosis drugs (annual risk of tuberculous infection 1%: detection of 100% of new cases), one can compare the total amount of government health spending per year and per inhabitant (of which part is used for buying drugs) and the average drug consumption per inhabitant on one hand, and the real cost of antituberculosis drugs indispensable in a modern chemotherapy strategy on the other hand (Table 9).
drugs and national drugs policies
167
*For an annual risk of tuberculous infection of 1% and a detection rate of 100% of new cases (or for an annual risk of tuberculous infection of 2% and a detection rate of 50% of new cases). +Drugs distributed in Public Health Services. iDrugs delivered to the public by drug distribution agencies.
302
Tubercle and Lung Disease
However, in developing countries disparate situations can be observed.
in 1992 some very
Anarchic distribution and epidemiological chaos Several distribution systems for antituberculosis drugs can coexist in a single country: In the public services or in institutions managed by health insurance schemes or NGOs: distribution of drugs free of charge or in exchange for a lump sum of varying amounts giving rights to all the essential drugs or only to antituberculosis drugs; or distribution free of charge of certain of the least costly drugs (isoniazid-thiacetazone); or, which frequently occurs, irregular distribution due to funds not being freed in time for supplies to be bought; or finally, total and definitive discontinuation of drug distribution due to lack of government support for the programme. In private drug distribution agencies, which proliferate in the areas of the country where some of the population has access to money allowing them to buy drugs (particularly in countries where government health action programmes have been cut back after the enforcement of structural adjustment measures), antituberculosis drugs are sold simply by doctor’s prescription without diagnostic verification or case notification, without follow-up of compliance with the treatment, on the basis of instant profit (without considering that patients usually don’t have sufficient resources to buy the complete supply of drugs necessary to cure them) and even when the drugs (or chemotherapy regimens) prescribed are different from those intended in the national programme. This anarchy in the distribution of antituberculosis drugs is a result of the indiscriminate application of one of the political principles of economic reform advocated by international financial institutions: ‘the complementarity of the public and private sectors.’ It compromises the results of the antituberculosis programme by encouraging ‘epidemiological mess’26 illustrated by the proliferation of chronic tuberculosis cases with bacilli resistant to antibiotics, particularly isoniazid and rifampicin, observed in many Asian and Latin American countries. To rectify such situations, where economic chaos gives rise to epidemiological chaos, a variety of approaches have been adopted in the developing world.
Support of national health programmes In certain low income countries, national antituberculosis programmes have been supported by intemational27 or national NGOS,~’ with external aid ensuring free delivery (at the CIF price) of antituberculosis drugs to countries and offering technical and organizational support for the application of the programme. This solution has given rise to some brilliant results. But it has the drawback of not being able to reach all low income countries
(especially the most heavily populated) and, not being able to aid them for a long period, it creates a situation where the continuation of the activities of the antituberculosis programme depends on the continuation of external donations. In middle income countries other solutions have been adopted; they have appealed to international agencies (such as the WHO, UNICEF) or to non-profit making organizations (such as the International Dispensary Association) to obtain antituberculosis drugs of guaranteed quality for a reasonable price (Table 1); they have appealed to regional or international finance institutions (such as the World Bank) for low-interest loans for national programmes that are well planned and regularly supervised and evaluated. These solutions have the advantage of engaging national responsibility in the purchase of antituberculosis drugs, even on credit. But they can have the disadvantage of isolating the antituberculosis programme (regularly supplied with drugs) from other health action programmes (primary health care, acute respiratory infection, chronic diseases) for which drug supplies would be irregular.
Integrating antituberculosis drug supplies into the national drugs policy More recently, another promising approach has been adopted in China: a loan from an international finance organization is helping to support a global project, including the antituberculosis programme in the primary health care programme.” This approach has the merit of stimulating awareness of one of the often neglected aspects of integration: the integration of drug supplies. In fact the problems presented by the supply of antituberculosis drugs in developing countries are no different from those presented also by the supply of vaccines and other essential drugs. The limited nature of the hard currency which each national community can allocate to the purchase of drugs should impose judicious use of these sums, and priority purchase of essential (vital and indispensable) drugs. But it must be considered that the organizations who buy wholesale for the Public Health Services on one hand and the wholesalers on the other are not complementary, but rather compete for access to the use of hard currency. The final channeling of available funds in each country depends on the specific weight of those two groups in the minds of the decision-makers, i.e. the government (Minister of Finance and Minister of Health); this is what explains the diversity of situations observed in the developing world. The national drugs policy (importation and/or production, distribution, financing) comes from government prerogatives. The supply of antituberculosis drugs and other important drugs reflects political choice or wi11.29 Whatever the economic situation might be, budgetary restrictions influence the planning of a national drugs policy18,3o at every stage:
The supply of antituberculosis
During the selection of the national list of essential drugs (based on health problems encountered in the country) and need forecasting, the profitability criterion (cost/efficiency) is important in the choice of drugs. Whatever the size of the list established (250, 400 or 600 drugs), the key antituberculosis drugs are part of it and those responsible for the antituberculosis programme must ensure that the basic drugs (separate or preferably combined) imported or produced in the country, are the same, both in the Public Health Services and in the private distribution sector, where it exists. During the purchase of drugs or intermediate substances allowing them to be produced in the country, the price established by UNICEF or the IDA (Table 1) is a reference list for CIF prices, but lower prices can sometimes be obtained by means of group purchases organized between several neighbouring countries (South America, North Africa), long-term purchase orders (for example over 3 years, renewable), or national production. Furthermore it must be ensured that producers respect correct fabrication procedures, apply the WHO system of quality control of drug products, and in particular verify the bioavailability of antituberculosis drugs, especially when combinations of 2 or 3 drugs in fixed proportions are bought.2,“,3’ When it is decided, for practical reasons, to buy combinations in fixed proportions of 2 drugs, the order (or international tender) must specify that the presentation (shape and colour of the pill or capsule) must be different for each different combination of dosages. It must be stressed that in 1991 the price of fixed proportion combinations purchased through a non-profit making organization was nearly equal to that of separate drugs (Table 1). At the stage of drug distributio~t. The problem of the conditioning of antituberculosis drugs must be resolved: drugs delivered in bands or in strips (each pill isolated by an aluminium foil envelope) are more expensive than drugs delivered in boxes of 1000. If the economic solution has been adopted, the provision of smaller boxes to contain 50 or 100 pills or capsules must be anticipated. This problem concerns both antituberculosis drugs and other basic drugs. At the stage of the use of the drugs, the standardized tuberculosis treatment schemes proposed by the WHO allow for the definition of adapted national guidelines. The national technical guidelines, widely distributed to health personnel responsible for primary health care, codify treatment indications and treatment regimens: they thus help to reduce waste. The Jinancing of a realistic national drugs policy, i.e. founded on the continued supply of essential drugs, can be ensured for the most part by national resources: by the government health services budget alone or with financial participation from the population, if
drugs and national drugs policies
303
one considers the level of drug consumption per inhabitant in each country. The methods of this financial participation are to be discussed in each country so that they are socially tolerable and acceptable according to the objectives desired. Unfortunately, in many developing countries, it is observed that the logic of immediate profit is more powerful than the logic of a health policy. It is thus that even in the poorest countries, non-essential (even useless) drugs are imported with the use of hard currency, and sold in drug distribution agencies to the public (and sometimes even reimbursed by the health insurance systems), whereas in the Public Health Services the essential drugs for treating tuberculosis, acute respiratory infection, or prevalent chronic diseases such as asthma, diabetes mellitus or hypertension are lacking.
Reinforcing international cooperation In the worldwide effort undertaken to support national tuberculosis programmes, particular attention is given to the continued supply of antituberculosis drugs. Direct assistance of national programmes by free or long-term repayment provision of antituberculosis drugs and by the operational backing of programmes will still be necessary for several years in the majority of low income countries: it would be desirable to integrate it into more comprehensive backing of the promotion of primary health care. In middle income countries, available financial resources are generally sufficient for the supply of essential drugs. When the drugs are lacking, it is due to errors in central planning and management of drug products. In this context, international cooperation must be oriented primarily towards informing the decisionmakers and training the health programme (and drug procurement) planners.
CONCLUSION In a national tuberculosis programme, regular supplies of drugs can be financed by a minimal proportion of the average drug consumption per inhabitant in each country: less than 5% in low income countries, less than 1% in middle income countries, whatever the chemotherapy strategy chosen and whatever the need. In time, this supply will be assured by national financial resources when it is fully integrated into a coherent national drugs policy geared towards the continued availability of essential drugs. International cooperation is indispensable to encourage the rational use of available resources on a national and international scale.
304
Tubercle @id Lung Disease
References 1. Kochi A. The global tuberuilosis sltuation and the new control strategy of the World Health Organization. Tubercle 1991;
72 143. 2. TubercuIosis Unit, WHO. Guidelines for tuberculosis treatment in ad&s and children in national tuberculosis programmes. Dot. WHOm/91-161, Geneva, 1991. 3. Anti-tirculosis regimens of chemotherapy: recommendations from the Committee on Treatment of the Intemationd Union Age&t Tuberculosis and Lung Disease. Bull Int Union Tuberc Lung Did 1988; 63: 60-64. 4. Murray C J L, Styblo K, Rouillcm A. Tuberculosis in developing countries: burden, intervention and cost. Bull Int Union Tuberc Ludg Dis 1990,65: 624. 5. Chairlet P. La lutte antituberculeuse dam le monde: strategies et actins snrle terrain. Respiration 1990,57: 145-159. 6. Chauler P, Helah A. L’approvisionnement en medicaments antituberculeux en 1991 : un problbme mondial, un probleme na&ond(in press, Algiers 1992). 7. Cn&n 1, Home N, Miller F. Clinical tuberculosis. Macmillan: London, 1992. 8. UNICEF. Essential drugs, price list, February-June 1991. 9. Bleiker MA, Sutherland I, Styblo K, ten Dam H G, Misljenovic 0. Guidelines for estimating the risk of tuberculous infection from tuberculin tests results in a representative sample of children. Bull Int Union Tuberc Lung Dis 1989; 64: 7-12. 10. Bleiker M A. The annual tuberculosis infection rate, the tuberculin survey and the tuberculin test. Bull Int Union Tuberc Lung Dis 199i; 66: 53-56. 11. Chum H J. Ten years of the National Tuberculosis/Leprosy Programme in Tanzania. Bull Int Union Tuberc Lung Dis 1989; 64: 34-36. 12. Salaniponi F L M. The Malawi National Tuberculosis Programme. Bull Int Union Tuberc Lung Dis 1989; 64: 4@4 I. 13. Boulahbal’F, Khaled S, Tazir M. The interest of follow-up of resistance of the tubercle bacillus in the evaluation of a programme. Bull Int Union Tuberc Lung Dis 1989,64: 23-25. 14. Chonde T M. The role of bacteriological services in the National Tuberculosis and Leprosy Programme in Tanzania. Bull Int Union Tuberc Lung Dis 1989; 64: 37-39.
15. Kim S J, Hong Y P, Drug resistance of Mycobacretium tuberculosis in Korea. In Tuberculosis Surveillance Research Unit of the IUATLD Progress report Vol 1, 1989: 138-140. 16. Chaulet P, Benachenhoa A, Virot J P, Fekar A, Ait Khaled N. Results of the international cooperative inquiry into the cost of antituberculosis drugs. Bull Int Union Tuberc Lung Dis 1978; 53: 247-253. 17. Mariko M. Drugs; towards sound prescribing and pricing. World Health Forum 1991; 12: 34-37. 18. WHO. Economic Support for National Health for all Strategies, background document, 40th World Health Assembly, Geneva, 1987. 19. World Bank. World Development Report June 1990, Washington. 20. World Bank. World Development Report June 1991, Washington. 21. IMS, World drug market manual 1991, London. 22. WHO Expert Committee on Tuberculosis, Eighth Report, Technical Report Series 1964 no. 210. 23. WHO Expert Committee on Tuberculosis, Ninth Report, Technical Report Series 1974 no. 552. 24. WHO Tuberculosis Control. Report of a joint IUAT/WHO study group, Technical Report Series 1982, no. 671. 25. Murray C I J. Social, economic and operational research on tuberculosis: recent studies and some priority questions. Bull Int Union Tuberc Lung Dis 1991; 66: 149-156. 26. Grzybowski S. Natural history of tuberculosis. Bull Int Union Tuberc Lung Dis 1991; 66: 193-194. 27. Rouillon A. The mutual assistance programme of the IUATLD. Development, contribution and significance. Bull Int Union Tuberc Lung Dis 1991; 66: 159-172. 28. Broekmans J F. The point of view of a low prevalence country The Netherlands. Bull Int Union Tuberc Lung Dis 1991; 66: 179-184. 29. Chaulet P. Compliance with chemotherapy for tuberculosis. The responsibilities of the Health Ministry and of physicians. Bull Int Union Tuberc Lung Dis 66; (suppl) 90/9 1: 33-36. 30. Catsambus T, Foster S. Spending money sensibly: the case of essential drugs. Finance and Development 1986: 30-32. 31. WHO The use of essential drugs. Third report of the WHO Expert Committee. Model list of essential drugs (fifth list). Technical Report Series 1988, no. 770.
I
The supply of antituberculosis drugs and national drugs policies P. Chauiet Clinique de Pneumo-Phtisiologie Ouesf, Algiers. Algeria
Matiben, Hbpital de B.&i-Messous,
Centre Hospitalier
Universitairr
d’illger-
S UMMA R Y. The money necessary for purchasing antituberculosis drugs in a national programme comes from the Public Health Services budget, funds from the health insurance scheme (when it exists) and household budgets. The Public Health Services budget is on average $2-23 US per year and per person in low or middle income countries. Average drug consumption in these groups of countries was from $2-26 US per person in 1990, The number of patients to be treated depends on the annual risk of tuberculous infection (ARTI) and the case detection rate: it is the same when the ART1 is 1% and the detection rate lOO%,and when the ART1 is 2% and the detection rate 50% of cases. The supply of antituberculosis drugs has a real cost representing around 3% of global drug consumption in low income countries and is always less than 1% of global drug consumption in middle income countries. In most developing countries it could be covered with the aid of national financial resources, on condition that it is integrated into a coherent national drugs policy aimed at guaranteeing the continued availability of essential drugs. R .!? S U M 8. L’argent necessaire pour acheter les medicaments antituberculeux d’un programme national
provient du budget des services de Sante Publique, des fonds de l’assurance maladie (lorsqu’elle existe) et du budget des menages. Le budget des services de Sante publique est en moyenne de $2 a $23 US par an et par habitant dans les pays 31faible revenu ou 1 revenu intermediaire. La consommation pharmaceutique moyenne dans les mcmes groupes de pays est de $2 5 $26 US par habitant en 1990. Le nombre de malades a traiter depend du risque annuel d’infection tuberculeuse (RAI) et du taux du detection des cas : il est le m&melorsque le RAI est de 1% et le taux de detection de lOO%, et lorsque le RAI est de 2% et le taux de detection de 50% des cas. L’approvisionnement en medicaments antituberculeux a un prix reel qui represente environ 3% de la consommation pharmaceutique globale dans les pays a faible revenu, et toujours moins de 1% de la consommation pharmaceutique globale dans les pays a revenu intermediaire. I1 pourrait bre assure, dans le plupart des pays en developpement, grace aux ressources financieres nationales, 21condition d’etre integre dans une politique pharmaceutique nationale coherente, visant a garantir la disponibilite permanente des medicaments essentiels. _ R ES iJ M E N , El dinero necesario para comprar 10s medicamentos antituberculosos de un programa national proviene de1 presupuesto de 10s Servicios de Salud Ptiblica, de 10s fondos de1 Sistema de Seguros de Salud (cuando existe) y de1 presupuesto de 10s hogares. El presupuesto de 10s Servicios de Salud Ptiblica es, en promedio, de $2 a $23 US por aiio y por habitante en 10s pa&es con recursos escasos o intermedios. El consumo farmaceutico promedio en 10s mismos grupos de paises era de $2 a $26 US por habitante en 1990. El ntimero de enfermos que deben ser tratados depende de1 riesgo anual de infection tuberculosa (RAIT) y de la tasa de deteccidn de cases : es el mismo cuando el RAIT es de 1 % y la tasa de detecci6n de 100 % y cuando el RAIT es de 2 % y la tasa de detection de 50 % de 10s cases. El cost0 real de1 aprovisionamiento de medicamentos antituberculosos representa alrededor de un 3 % de1 consumo farmaceutico global en 10s paises de escasos recursos y siempre menos de 1 % de1 consumo farmaceutico global en 10s paises de recursos intermedios. En la
Correspondence to: Professeur Pierre Chaulet MD, FCCP,Clinique Pneumo-Phtisiologie Matiben, HBpital de B&i-Messous, Centre Hospitalier Universitaire d’Alger-Ouest, Algiers, Algeria.
de
With the collaboration of Professor Fatma Zohra Oufriha, Insitute of Economic Science. Algiers. 295
296
Tubercle and Lung Disease
mayor parte de 10s pa&es en desarrollo este costo podria ser cubierto por 10s recursos Anancieros nacionales, a condition de ser integrado en una politica farmaceutica national coherente, que tienda a garantizar una disponibilidad permanente de 10s medicamentos esenciales.
INTRODUCTION For a long time, the price of the most costly antituberculosis drugs, rifampicin and pyrazinamide, was considered a major obstacle to the adoption of shortcourse chemotherapy regimens in tuberculosis control programmes applied in developing countries. Because of this, in some of these countries those responsible for national programmes relied on international aid to obtain free of charge the antituberculosis drugs necessary for the introduction of modern chemotherapy regimens. Today, in the context of the World Health Organization’s new antituberculosis strategy,’ short-course chemotherapy regimens are recommended for the treatment of all forms of tuberculosis, in children as well as in adults.** 3 It has in fact been proven that short-course chemotherapy of tuberculosis is one of the most efficient health interventions in terms of cost per case cured, per death avoided and per transmission avoided.4,5 That is why, in a global context marked by the need to strengthen national antituberculosis programmes because of the social consequences of the economic crisis and the spread of the HIV epidemic, the problem of a continued supply of drugs has arisen sharply and simultaneously in all the developing countries in the world.6 How can one estimate the need for antituberculosis drugs and their cost in a developing country? How can one ensure continued supply of this category of essential drugs? What role could international cooperation play in this field? These are the main questions asked, for which realistic answers, adapted to the context of each nation, must be found in order to meet the challenge of the year 2000: to halve the incidence of tuberculous in the developing world in 8-12 years.’
HOW TO ESTIMATE THE NEED FOR ANTITUBERCULOSIS DRUGS AND THEIR BASIC COST
of tuberculosis (pulmonary or extrapulmonary). These patients must receive either a chemotherapy regimen of 6 months containing rifampicin throughout treatment, or a chemotherapy regimen of 8 months containing rifampicin during the first 2 months only. Another high priority category is that of pulmonary tuberculosis cases already treated by a previous course of chemotherapy (failure or relapse) who are still excreting bacilli and who must follow another standard chemotherapy regimen of 8 months, with rifampicin throughout. The third category regroups new cases of sputumnegative pulmonary tuberculosis (with moderate or limited parenchymal lesions) and the majority of cases of extrapulmonary tuberculosis: this group thus contains almost all cases of childhood tuberculosis, with the exception of meningitis and miliary disease. These patients must receive either a treatment regimen of 4 months with rifampicin throughout treatment (possibly completed by 4 supplementary months with isoniazid alone) or a treatment regimen of 8 months with rifampicin for the first 2 months only. The last category is that of chronic cases of pulmonary tuberculosis, who continue to excrete bacilli after 2 completed chemotherapy courses: these bacilli are often resistant to isoniazid and rifampicin. Such patients can only be cured with minor drugs not included in the list of essential drugs.’ The basic price of the drugs (Table 1) composing the chemotherapy regimens applicable in the first three categories of patients can be calculated with reference to the price list of essential drugs published every year by UNICEF.8 The different regimens recommended have a different basic price depending on their duration and the nature of the drugs used (Table 2).
How to assess the respective sizes of the different patient categories The number of new cases of smear-positive
The need for antituberculosis drugs is defined by the type of chemotherapy regimens chosen for inclusion in a national tuberculosis treatment strategy and by the number of tuberculosis cases expected to be treated each year under the programme.
Patient categories, treatment regimen categories According to the WHO directives, tuberculosis patients are divided into four broad categories for which different treatment regimens are recommended.* The first - and main - category is that of new cases of smear-positive pulmonary tuberculosis and severe forms
pulmonary tuberculosis is directly proportional to the annual risk of tuberculous infection, measured by tuberculin prevalence surveys.‘,” For an annual tuberculous infection risk of 1% there is a corresponding average incidence of 50 cases of smear-positive pulmonary tuberculosis per 100 000 inhabitants: the CI at 95% is 39-59 cases.4 This incidence corresponds to a 45% incidence of all types of tuberculosis in technically advanced countries, and a 54% incidence of all types of tuberculosis in countries such as Tanzania or Algeria where means of radiodiagnostic investigation are not as widely available.4,5 If to new cases of smear-positive pulmonary tuberculosis are added severe forms of pulmonary tuberculosis (such as
The supply of antituberculosis
Table 1. Basic prices of eqsential anti tuberculosis (separate drugs and principal combinations Presentation
Dmgs
drugs in 1991 in fixed proportions) UNICEF list
., June 1991’ in $US
Isolated Ethambutol Isoniazid Isoniazid Pyrazinamide Rifampicin Rifampicin Sueptomycin Distjlled water for injection Fixed proportion Isoniazid Thiacetazone Rifampicin Isoniazid Rifampicin Isoniazid Rifampicin Isoniazid Pyrazinamide
mmg IOOmg 300mg 500 mg 150 mg 300mg 1g 5ml
combinations 300 mg 150 mg 150mg 1OOmg 300 mg 150mg 120mg 50 mg 300 mg
IDA list May 1991t in DFI
1000 1000 1000 1000 100 100 50 50
23.80 3.95 11.87 43.00 4.83 9.87 13.37 1.65
43.50 6.60
1000
11.34
20.40
1000
61.48
99.50
1000
108.12
168
1000
115.00
(110)1
56 8.50 16 I
*Essential Drugs, price list, UNICEF, February-June 1991. +Intemational Dispensary Association, price indicator, May 1991 in Dutch Florins ($1 US = 1.9 DFl). iEstimate for 199 1.
Table 2. Principal antituberculosis chemotherapy regimens recommended for national programmes and their basic unit price according to the UNICEF 1991 price list2 Chemotherapy
regimens
Basic regimens for new cases of tuberculosis and severe forms of 6 months 2 SRHZ14 RH (or 2 ERHZ/4 RH (or 8 months 2 SRHZ/6 TH (or
Price in $US smear-positive tuberculosis 4 R3 H3) 4 R3 H3) 6 EH)
pulmonary 66 (or 53) 52 (or 39) 43 (or 52)
Basic regimens for new cases of smear negative pulmonary tuberculosis (and minimal lesions) and for most new cases of extrapulmonary tuberculosis 4 months 2 RHiY2 RH (or 2 R3 H3) 35.5 (or 29) (8 months) 2 RHZ/6TH (or 6 EH) 31 8 months 2 RHZ/6 TH (or 6 EH) 25 (or 34) Retreatment regimens for failure and relapse cases of bacteriologically proven pulmonary tuberculosis (after a first course of chemotherapy) 8 months 2 SREZ0 RHEZ/5 RHE (or 5 R3 H3 E3) 96 (or 79) Each letter represents a drug: R=rifampicin, H=isoniazid, Z=pyrazinamide, S=streptomycin, E=ethambutol, T=thiacetazone. The number preceding a group of letters represents the number of months during which the drugs are administered. The number following a letter represents the number of weekly doses of the drug. Where there is no number following the letter the drug is administered on a daily basis.
miliary disease) or extrapulmonary tuberculosis (such as meningitis, pericarditis and other extensive se&is, renal tuberculosis, tuberculosis of the spine with neurological complications), it is reasonable to estimate that the first category of patients comprises approximately half of the new cases who will need to be treated. The other half of new cases is made up of smearnegative cases of pulmonary tuberculosis and the majority
drugs and national drugs policies
297
of extrapulmonary tuberculosis cases (notably tuberculosis of the lymph nodes and of the bones and joints). Theoretically, when the annual risk of tuberculous infection is 1% in a community, one can expect a minimum of 100 new cases to treat per 100 000 inhabitants. To this first total we must add a variable number of old cases of pulmonary tuberculosis who have already been treated but are again excreting bacilli and who must receive a standardized ‘retreatment’ regimen: progressive resumption of the disease after premature interruption of initial treatment, failure or relapse cases after initial chemotherapy treatment, chronic cases continuing to excrete bacilli after 2 or more chemotherapy courses. In the absence of an antituberculosis programme or standardization of chemotherapy regimens, the number of old cases can be high: it is a reflection of disorganized tuberculosis treatments applied in recent years in the communities in question. On the other hand, in countries where standardized short-course chemotherapy regimens (of 6 or 8 months) have for several years been routinely applied to all new cases, ‘previously treated’ cases of pulmonary tuberculosis requiring ‘retreatment’ constitute an extra but limited group of patients to be treated, equal to around 10% of total new smear-positive cases: 7% in Algeria and Tanzania,” 13% in Malawi.” In other words, in the case of regularly applied programmes, to 50 new cases of smear-positive pulmonary tuberculosis to be treated each year, a second chemotherapy treatment for 5 extra cases previously treated for pulmonary tuberculosis must be provided for. Amongst those previously treated within modern national programmes, the proportion of ‘chronic’ cases with bacilli resistant at least to isoniazid and rifampicin, is from 10 to 15%: 11.5% in Algeria,” 12% in Tanzania,14 15.4% in Korea.” In short, the total theoretical number of tuberculosis cases to be included in the different categories of patients to be treated comes to a minimum of 105 if the annual risk of tuberculous infection is I%, 210 if the annual risk of tuberculous infection is 2%. These estimates must be reappraised in countries where there is a high rate of HIV positivity. Finally, in every 10 ‘previously treated’ cases, 1 or 2 ‘chronic cases’ can be found, very probably chronic excretors of bacilli resistant to isoniazid and rifampicin. These chronic cases cannot be cured without a 12-month course which combines minor drugs such as ethionamide or prothionamide, cycloserin, kanamycin or capreomycin.’ As these chronic cases represent less than 1% of cases to be treated, chemotherapy strategies must be worked out to give priority to the first three categories of patients and of chemotherapy regimens, which cover 99% of patients.
The basic cost of a modern chemotherapy
strategy
A theoretical estimate of the total number of patients to be treated taken from the annual risk of tuberculosis
298
Tubercle and Lung Disease
infection is misleading. In practice one must also take into account the real detection rate which depends on the population’s health coverage by the health services and the technical qualifications of the health personnel in the field. The detection rate is unequal, changing according to the country or region of the developing world: 27% and 28% of expected cases in sub-$&ran Africa and Central America, 60-70% of expected cases in South America, Asia, North Africa and the Middle East: 55% on average throughout all of the developing countriese4 Because of this, the actual number of cases to be treated is the same when the annual risk of tuberculous infection is 1% and the detection rate of new cases is lOO%, or when the annual risk of tuberculous infections is 2% and the detection rate of new cases is 50%. However many patients there may be to treat, different strategies of effective chemotherapy can be adopted, whose basic costs are different. To estimate the basic cost of the different strategies possible, the total cost of drugs necessary for treating patients was estimated in a simulated epidemiological situation where the annual risk of tuberculous infection would be 1% and the detection rate of new cases 100%. If the most costly chemotherapy strategy is adopted (based on regimens containing rifampicin throughout treatment for all categories of patients) the total cost of drugs necessary for treating 105 patients (per 100 000 inhabitants) is $5582 US, i.e. $0.055 US per inhabitant (Table 3). If the least costly chemotherapy strategy is adopted (based on effective short-course regimens containing the smallest quantity possible of rifampicin) the total cost of drugs necessary for treating 105 patients (per 100000 inhabitants) is $3795 US, i.e. $0.037 US per inhabitant (Table 4). Other strategies of moderate cost can be selected depending on the national context: by replacing strepto-
Table 3. The basic price of the most costly antituberculosis chemotherapy strategy (excluding chronic cases) Drug prices in $LJS (UNICEF 1991 price list)
Patients to treat Categories Smear-positive pulmonary tuberculosis and severe forms Smear negative pulmonary tuberculosis and extrapulmonary tuberculosis Failures and relapse cases Total for 100 000 inhabitants Price of antituberculosis
Number*
50
50
Unit price
Total price
x 66
= 3300
x 35.5 x 37 average
5
x 96
105
= 480 = 5582
drugs per inhabitant
*For an annual risk of tuberculous of 100% of new cases.
= 1775 = 1850 = 1812
in $US
= 0.055
infection of 1% and a detection rate
Table 4. The basic price of the least costly antituberculosis chemotherapy
strategy (excluding
chronic cases)
Patients to treat Categories Smear-positive pulmonary tuberculosis and severe forms Smear-negative pulmonary tuberculosis and extrapulmonary tuberculosis Failures and relapse cases Total for 100 000 inhabitants Price of antituberculosis
Drug prices in $US (UNICEF 1991 price list) Number*
Unit price
Total price
50
x 43
= 2150
50
x 25
= 1250
5
x 79
= 395
105
= 3795
drugs per inhabitant
*For an annual risk of tuberculous of 100% of new cases.
in $US
= 0.037
infection of 1% and a detection rate
mycin in the initial phase or thiacetazone in the continuation phase by ethambutol; or otherwise by administering the drugs 3 times per week under direct supervision by health personnel, when this can be organized.
CALCULATING THE REAL COST OF ANTITUBERCULOSIS DRUGS The basic price of drugs used in the two different strategies (Tables 3 and 4) was calculated according to the prices of essential drugs indicated in the UNICEF 1991 list.‘F8 However these basic prices do not correspond to the final real price of the drugs when they are given to patients. In fact, the prices on the UNICEF list are prices agreed by certain manufacturers, for bulk purchase destined for health programmes in developing countries. To these minimum prices or production prices must be added other costs which go towards making up the final cost of the drugs.16 The import price in developing countries (which on the whole produce no antituberculosis drugs and therefore buy them on the international market and then import them before distribution in the internal network) is expressed in two ways: 1. the FOB (free on board) price, which is the price of the drug ready for export. This FOB price raises the basic or production price by 4-6%. 2. the CIF (cost, insurance, freight) price, which adds to the FOB price the cost of insurance and transport to the importing country. The cost thus added to the FOB price is variable: it depends on the distance separating the exporting country and the importing country and the method of transport used (rail, road, sea, air). By definition the CIF price is superior both to the FOB price and to the production price. It is
The supply of antituberculosis
reasonable to add 20-30% to the FOB to estimate the CIF price (International Price Indicator Guide 1990, Management Sciences for Health 1991). The price at distribution (through health services or private pharmacies) is higher. In the make-up of the final price, to the CIF price is added a variety of taxes (calculated as a percentage of the CIF price) and the commercial margins of the intermediaries (the wholesalers) and the retail pharmacists: the taxes and margins are set out by the national legislation of the different countries.‘” Thus in 1991 in Algeria (a middle income country), the CIF price of drugs, augmented by 27% (taxes and customs duty), constitutes the cost price of the drug for the wholesalers (which are state enterprises or private dealers). To this cost price must be added the commercial margin of the wholesalers (20% of the CIF price) and that of the retailers (40% of the CIF price or 27% of the cost price) to obtain the public selling price. In other words, the final price of the drug sold to the patient in a distribution agency is equal to the CIF price multiplied by a coefficient of 1.87. In the case of antituberculosis drugs delivered free of charge to patients in the Public Health Services supplied by state enterprises (which play the role of wholesalers), the cost of the drug is equal to the CIF price multiplied by a coefficient of 1.47. Another example: in 1990, in Mali (a low income country), the final price of the drug when sold to the public was equal to the CIF price multiplied by a coefficient of 1.95.” These two examples illustrate the differences between the basic price and the real final price of antituberculosis drugs at the moment of their use in national programmes. In the simulated epidemiological situation described above, and for the two chemotherapy strategies whose basic price has been evaluated (Tables 3 and 4) the ‘real’ price of antituberculosis drugs has been calculated by adopting the following hypotheses: l
l
l
The CIF price adopted was the basic price from the UNICEF 1991 list, arbitrarily augmented by 25% . The price at distribution in the Public Health Services was a ‘wholesale’ price, i.e. the CIF price multiplied by the coefficient of 1.47 (applied in Algeria). The price at distribution in drug distribution agencies was the CIF price multiplied by the coefficient of 1.90 (halfway between the coefficient of 1.87 for Algeria and the coefficient of 1.95 for Mali).
The end price of antituberculosis drugs per inhabitant would be from 10.25 or 13.25 US cents if the most expensive chemotherapy strategy was adopted, and 6.96 or 9.0 US cents if the least expensive chemotherapy strategy was adopted (Table 5). In each strategy, the end price is different depending on whether the drugs are bought wholesale and distributed to patients by government health services or if they are sold to patients in the public drug distribution agencies.
drugs and national drugs policies
Table 5. The final real price of antituberculosis the application of 2 different chemotherapy chronic cases)
drugs necessary strategies (excluding
299 for
Drug prices, in US cents, per inhabitant* Least costly Most costly strategy strategy UNICEF 1991 price list Estimated import price (CIF)+ Consumer price Drugs bought wholesale by health services and delivered directly to patients (CIF price x 1.47) Drugs delivered at retail price in dispensaries (CIF price x 1.90)
5.58 6.97
3.79 4.73
10.25
6.96
13.25
9.00
*For an annual risk of tuberculous infection of I%, and a detection of 100% new cases. +The FOB price is calculated by adding 4-6% to the basic price from the UNICEF list; the CIF price including the cost of transport to the import country adds a variable percentage to the FOB price depending on the distance and means of transport. It is reasonable to add 20-30% to the FOB price to estimate the CIF price (International Price Indicator Guide 1990, Management Sciences for Health 1991). In the example given, the CIF price estimated has been calculated by adding 25% to the basic price, from the UNICEF price list.
All of these calculations are based on hypotheses established from two concrete examples in order to support the approach adopted: they need to be reassessed in each national context in order to receive the necessary adjustments.
NATIONAL DRUGS
RESOURCES
FOR THE SUPPLY
OF
National resources available for drug purchasing (among which are antituberculosis drugs) come from the budget allocated by the State to government health services, sums provided by health insurance systems (when they exist, and for the population they cover) and sums paid directly by the population which pays for the drugs either wholly or in part when purchased in the drug distribution agencies.
Limited government health budgets In low income developing countries, the purchase of antituberculosis drugs is not always covered by government health budgets. To this limit of an internal nature is added a restriction of an external nature: a limitation on the availability of hard currency, aggravated by the irregular and at times irrational allocation of this currency. For more than 20 years, in all the developing countries of the world, government health budgets have represented only a small fraction of the central administration’s working budget, and a minimal proportion of the GDP. Since the beginning of the 1980s these
300
Tubercle and Lung Disease
budgets have shrunk from year to year due to structural adjustment programmes applied in order to confront the world economic recession: devaluation of national currencies, reduction in public spending in an effort to balance budgets, and, as a consequence, a diminution of government support for health action programmes.‘* The recent reports of the World Bank’9.20 allow one to evaluate the level of government health spending and to measure the huge disparities which exist even between the different developing countries. Thus in 1988 government health spending per inhabitant was, on average, $2 US in the group of low income countries (characterized by an average annual GNP per inhabitant inferior to $500 US); $23 US in middle income countries (where the average annual GNP per inhabitant is between $600 and $5300 US), whereas it was $612 US in high income countries (Table 6). In these budgets the proportion allocated to the purchase of drugs distributed in the Public Health Services is situated between 10% and 30%; one can deduce from this that in the counties where the government health budgets are below $3 US per inhabitant, it is unlikely that the cost of a continued supply of essential drugs (and hence of antituberculosis drugs) would be covered uniquely by the government health budget. It is in this context that in the last 10 years there has begun to be a shortage of antituberculosis drugs delivered in the Public Health Services and these have at times had to be paid for by patients.
Table 6. Government groups of countries
health
Groups of countrtes
Low income countries Total China India Other Middle income countries Total
spending per inhabitant in the different
Population in millions I989*
GNP per inhabitant in $US 1989’
Government health spending per inhabitant in $US 1988’
2948.4
330
2
I 113.9
3
832.5 1002
350 340 300
I 1.9
1104.5
2040
23
Lower bracket Higher bracket
68 I .8 422.7
1360 3150
8.5 43
High income countries
830.4
18330
612
‘World Bank 1991.zo ‘Spending calculated from data published in World Bank 1990.t9
National drug consumption The resources coming from health insurance schemes or family budgets are not always easily identifiable. However, in the majority of developing countries, each year information is made available on the total amount of drugs sales, whether they are distributed in hospitals
Table 7. Drug consumption groups of countries Groups of countries
Low income countries Total China India Other Middle incdme countries Total
per inhabitant in 1990 in the different
Population in millions 1989’
Drug corlsumption in 1990’ *otal in Per inhabitant mfllions in $US of SUS
2791.8
7440
2.6
I 113.9 832.5 845.4
4200 la 17%
3.7 1.7 2.1
872.6
16952.1
19.4
Lower bracket Higher bracket
549.6 323
8567.5 8384.6
15.5 25.9
High income coantries
791.2
132354,
167
‘World Bank 1991.m ‘The data were added together for 17 low income countries, 30 middle income countries and 15 high income countries, i.e. for 9 1%of the world’s population. according to the World Drug Market Manual, 1991.2’
Table 8. Drug consumption per inhabitan (in $US) by country and by groups of countries in 1990 (from the World Drug Market Manual 1991) Group of low income countries (Gross National Product from $80-500 0.6 .Myanmar Ethiopia 0.8 I Nepal 1 Tanzania 1.4 Nigeria 1.6 Bangladesh 1.6 Zaire 1.7 India Sudan 1.8
US per capita) Ghana Sri Lanka Indonesia Vietnam Kenya China Korea(North) Pakistan Pakistan
Group of middle income countries (Gross National Product from $600-5300 I Nicaragua Bolivia 3 Zimbabwe 5.1 5.1 Yemen 7.1 Syria 8.1 Malaysia 8.5 Egypt Thailand 8.6 9 Ecuador 10 .Morocco II Guatemala 12 Peru 12 Jordan 13 Iran 14 Tunisia
2 2 3 3 3 3.7 4 4.5 4.5
US per capita) Paraguay Algeria Turkey Chile Colombia Venezuela Iraq Libya Brazil Mexico South Africa Uruguay Argentina Korea(South)
15 15 17 17 17 18 18 18 23 25 26 41 48 57
Group of high income countries (Gross National Product from $6000-29000 US per capita) 27 Spain Singapore 27 Canada Hong Kong 40 Italy Tatwan Saudi Arabia 40 Germany us United Arab Emirates 53 France Great Britain 96 99 Japan New Zealand
I14 147 191 201 201 214 234
The listing of countries according to their GNP is taken from the World Development Report 199 1,World Bank, Washington 1991.
or Public Health Services, health institutions.2’
private
chemists
or private
The supply of antituberculosis
If the total sales, whatever the channel of distribution and whatever the mode of payment, is considered in relation to the number of inhabitants in the country in the year in question, an indicator is obtained: the average drug consumption per year and per inhabitant, widely used in health planning and market studies. This consumption is loosely linked to national wealth (measured by GNP per inhabitant) and especially with health services development. In 1990 it was on average $2.6 US in the group of low income countries and $19.4 US in the group of middle income countries, while it was $167 US in high income countries (Table 7). The average drug consumption per inhabitant differs widely from one country to the next, even in the developing world (Table 8). But if the data available by groups of countries are added together, it can be noted that the average drug consumption per inhabitant is higher than government health spending per inhabitant in the low income countries and in the lower bracket of middle income countries.
This comparison made:
several
China India Other Middle income countries Total Lower bracket Higher bracket High income countries
drugs compared health spending
to drug consumption,
by
2
2.6
0.07
0.09
3 1 1.9
3.1 1.7 2.1
0.07 0.07 0.07
0.09 0.09 0.09
23
19.4
0.10
0.13
8.5 43
15.5 25.9
0.10 0.10
0.13 0.13
0.10
0. I3
612
to be
In the context of national health action programmes, antituberculosis drugs should be distributed free of charge to patients because of their major epidemiological impact and their considerable efficiency. This basic principle, affirmed since 1964 in all the WHO’s expert reports, 22.23,24has been reinforced by recent economic analysis.2s
Spending per inhabitant (in US dollars) Govt health Consumer price in 199 I Drug spending consumption for antituberculosis drugs” (1988) low? high* (1990) Low income countries Total
observations
The promotion of national drugs policies
Table 9. The final price of antituberculosis groups of countries and government
allows
301
In the group of low income countries the least costly chemotherapy strategy must always be adopted. The price of essential antituberculosis drugs represents 2.7% or 3.4% of the average drug consumption (this becomes 5.4% or 6.8% if the annual risk of tuberculous infection is 2% and the detection rate 100% of cases). In the group of middle income countries the most costly chemotherapy strategy can be adopted in the majority of cases. The price of essential antituberculosis drugs always represents less than 1% of average drug consumption per inhabitant: 0.6% or 0.8% in lower bracket countries (whose average GNP per inhabitant is $60&2400 US per year) and 0.38% or 0.50% in the higher bracket countries (whose average GNP per inhabitant is from $2500-5300 US). In most countries, regardless of income level and epidemiological situation, the real price of antituberculosis drugs could be integrated into the average drug consumption per inhabitant if the latter were oriented in priority towards the consumption of essential drugs. In most middle income countries, the real price of antituberculosis drugs could be integrated into the government health budget.
THE NEED FOR ANTITUBERCULOSIS DRUGS AND NATIONAL RESOURCES ALLOCATED TO DRUG PURCHASES In the epidemiological situation which served as a basic hypothesis for the calculation of the real cost of antituberculosis drugs (annual risk of tuberculous infection 1%: detection of 100% of new cases), one can compare the total amount of government health spending per year and per inhabitant (of which part is used for buying drugs) and the average drug consumption per inhabitant on one hand, and the real cost of antituberculosis drugs indispensable in a modern chemotherapy strategy on the other hand (Table 9).
drugs and national drugs policies
167
*For an annual risk of tuberculous infection of 1% and a detection rate of 100% of new cases (or for an annual risk of tuberculous infection of 2% and a detection rate of 50% of new cases). +Drugs distributed in Public Health Services. iDrugs delivered to the public by drug distribution agencies.
302
Tubercle and Lung Disease
However, in developing countries disparate situations can be observed.
in 1992 some very
Anarchic distribution and epidemiological chaos Several distribution systems for antituberculosis drugs can coexist in a single country: In the public services or in institutions managed by health insurance schemes or NGOs: distribution of drugs free of charge or in exchange for a lump sum of varying amounts giving rights to all the essential drugs or only to antituberculosis drugs; or distribution free of charge of certain of the least costly drugs (isoniazid-thiacetazone); or, which frequently occurs, irregular distribution due to funds not being freed in time for supplies to be bought; or finally, total and definitive discontinuation of drug distribution due to lack of government support for the programme. In private drug distribution agencies, which proliferate in the areas of the country where some of the population has access to money allowing them to buy drugs (particularly in countries where government health action programmes have been cut back after the enforcement of structural adjustment measures), antituberculosis drugs are sold simply by doctor’s prescription without diagnostic verification or case notification, without follow-up of compliance with the treatment, on the basis of instant profit (without considering that patients usually don’t have sufficient resources to buy the complete supply of drugs necessary to cure them) and even when the drugs (or chemotherapy regimens) prescribed are different from those intended in the national programme. This anarchy in the distribution of antituberculosis drugs is a result of the indiscriminate application of one of the political principles of economic reform advocated by international financial institutions: ‘the complementarity of the public and private sectors.’ It compromises the results of the antituberculosis programme by encouraging ‘epidemiological mess’26 illustrated by the proliferation of chronic tuberculosis cases with bacilli resistant to antibiotics, particularly isoniazid and rifampicin, observed in many Asian and Latin American countries. To rectify such situations, where economic chaos gives rise to epidemiological chaos, a variety of approaches have been adopted in the developing world.
Support of national health programmes In certain low income countries, national antituberculosis programmes have been supported by intemational27 or national NGOS,~’ with external aid ensuring free delivery (at the CIF price) of antituberculosis drugs to countries and offering technical and organizational support for the application of the programme. This solution has given rise to some brilliant results. But it has the drawback of not being able to reach all low income countries
(especially the most heavily populated) and, not being able to aid them for a long period, it creates a situation where the continuation of the activities of the antituberculosis programme depends on the continuation of external donations. In middle income countries other solutions have been adopted; they have appealed to international agencies (such as the WHO, UNICEF) or to non-profit making organizations (such as the International Dispensary Association) to obtain antituberculosis drugs of guaranteed quality for a reasonable price (Table 1); they have appealed to regional or international finance institutions (such as the World Bank) for low-interest loans for national programmes that are well planned and regularly supervised and evaluated. These solutions have the advantage of engaging national responsibility in the purchase of antituberculosis drugs, even on credit. But they can have the disadvantage of isolating the antituberculosis programme (regularly supplied with drugs) from other health action programmes (primary health care, acute respiratory infection, chronic diseases) for which drug supplies would be irregular.
Integrating antituberculosis drug supplies into the national drugs policy More recently, another promising approach has been adopted in China: a loan from an international finance organization is helping to support a global project, including the antituberculosis programme in the primary health care programme.” This approach has the merit of stimulating awareness of one of the often neglected aspects of integration: the integration of drug supplies. In fact the problems presented by the supply of antituberculosis drugs in developing countries are no different from those presented also by the supply of vaccines and other essential drugs. The limited nature of the hard currency which each national community can allocate to the purchase of drugs should impose judicious use of these sums, and priority purchase of essential (vital and indispensable) drugs. But it must be considered that the organizations who buy wholesale for the Public Health Services on one hand and the wholesalers on the other are not complementary, but rather compete for access to the use of hard currency. The final channeling of available funds in each country depends on the specific weight of those two groups in the minds of the decision-makers, i.e. the government (Minister of Finance and Minister of Health); this is what explains the diversity of situations observed in the developing world. The national drugs policy (importation and/or production, distribution, financing) comes from government prerogatives. The supply of antituberculosis drugs and other important drugs reflects political choice or wi11.29 Whatever the economic situation might be, budgetary restrictions influence the planning of a national drugs policy18,3o at every stage:
The supply of antituberculosis
During the selection of the national list of essential drugs (based on health problems encountered in the country) and need forecasting, the profitability criterion (cost/efficiency) is important in the choice of drugs. Whatever the size of the list established (250, 400 or 600 drugs), the key antituberculosis drugs are part of it and those responsible for the antituberculosis programme must ensure that the basic drugs (separate or preferably combined) imported or produced in the country, are the same, both in the Public Health Services and in the private distribution sector, where it exists. During the purchase of drugs or intermediate substances allowing them to be produced in the country, the price established by UNICEF or the IDA (Table 1) is a reference list for CIF prices, but lower prices can sometimes be obtained by means of group purchases organized between several neighbouring countries (South America, North Africa), long-term purchase orders (for example over 3 years, renewable), or national production. Furthermore it must be ensured that producers respect correct fabrication procedures, apply the WHO system of quality control of drug products, and in particular verify the bioavailability of antituberculosis drugs, especially when combinations of 2 or 3 drugs in fixed proportions are bought.2,“,3’ When it is decided, for practical reasons, to buy combinations in fixed proportions of 2 drugs, the order (or international tender) must specify that the presentation (shape and colour of the pill or capsule) must be different for each different combination of dosages. It must be stressed that in 1991 the price of fixed proportion combinations purchased through a non-profit making organization was nearly equal to that of separate drugs (Table 1). At the stage of drug distributio~t. The problem of the conditioning of antituberculosis drugs must be resolved: drugs delivered in bands or in strips (each pill isolated by an aluminium foil envelope) are more expensive than drugs delivered in boxes of 1000. If the economic solution has been adopted, the provision of smaller boxes to contain 50 or 100 pills or capsules must be anticipated. This problem concerns both antituberculosis drugs and other basic drugs. At the stage of the use of the drugs, the standardized tuberculosis treatment schemes proposed by the WHO allow for the definition of adapted national guidelines. The national technical guidelines, widely distributed to health personnel responsible for primary health care, codify treatment indications and treatment regimens: they thus help to reduce waste. The Jinancing of a realistic national drugs policy, i.e. founded on the continued supply of essential drugs, can be ensured for the most part by national resources: by the government health services budget alone or with financial participation from the population, if
drugs and national drugs policies
303
one considers the level of drug consumption per inhabitant in each country. The methods of this financial participation are to be discussed in each country so that they are socially tolerable and acceptable according to the objectives desired. Unfortunately, in many developing countries, it is observed that the logic of immediate profit is more powerful than the logic of a health policy. It is thus that even in the poorest countries, non-essential (even useless) drugs are imported with the use of hard currency, and sold in drug distribution agencies to the public (and sometimes even reimbursed by the health insurance systems), whereas in the Public Health Services the essential drugs for treating tuberculosis, acute respiratory infection, or prevalent chronic diseases such as asthma, diabetes mellitus or hypertension are lacking.
Reinforcing international cooperation In the worldwide effort undertaken to support national tuberculosis programmes, particular attention is given to the continued supply of antituberculosis drugs. Direct assistance of national programmes by free or long-term repayment provision of antituberculosis drugs and by the operational backing of programmes will still be necessary for several years in the majority of low income countries: it would be desirable to integrate it into more comprehensive backing of the promotion of primary health care. In middle income countries, available financial resources are generally sufficient for the supply of essential drugs. When the drugs are lacking, it is due to errors in central planning and management of drug products. In this context, international cooperation must be oriented primarily towards informing the decisionmakers and training the health programme (and drug procurement) planners.
CONCLUSION In a national tuberculosis programme, regular supplies of drugs can be financed by a minimal proportion of the average drug consumption per inhabitant in each country: less than 5% in low income countries, less than 1% in middle income countries, whatever the chemotherapy strategy chosen and whatever the need. In time, this supply will be assured by national financial resources when it is fully integrated into a coherent national drugs policy geared towards the continued availability of essential drugs. International cooperation is indispensable to encourage the rational use of available resources on a national and international scale.
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Tubercle @id Lung Disease
References 1. Kochi A. The global tuberuilosis sltuation and the new control strategy of the World Health Organization. Tubercle 1991;
72 143. 2. TubercuIosis Unit, WHO. Guidelines for tuberculosis treatment in ad&s and children in national tuberculosis programmes. Dot. WHOm/91-161, Geneva, 1991. 3. Anti-tirculosis regimens of chemotherapy: recommendations from the Committee on Treatment of the Intemationd Union Age&t Tuberculosis and Lung Disease. Bull Int Union Tuberc Lung Did 1988; 63: 60-64. 4. Murray C J L, Styblo K, Rouillcm A. Tuberculosis in developing countries: burden, intervention and cost. Bull Int Union Tuberc Ludg Dis 1990,65: 624. 5. Chairlet P. La lutte antituberculeuse dam le monde: strategies et actins snrle terrain. Respiration 1990,57: 145-159. 6. Chauler P, Helah A. L’approvisionnement en medicaments antituberculeux en 1991 : un problbme mondial, un probleme na&ond(in press, Algiers 1992). 7. Cn&n 1, Home N, Miller F. Clinical tuberculosis. Macmillan: London, 1992. 8. UNICEF. Essential drugs, price list, February-June 1991. 9. Bleiker MA, Sutherland I, Styblo K, ten Dam H G, Misljenovic 0. Guidelines for estimating the risk of tuberculous infection from tuberculin tests results in a representative sample of children. Bull Int Union Tuberc Lung Dis 1989; 64: 7-12. 10. Bleiker M A. The annual tuberculosis infection rate, the tuberculin survey and the tuberculin test. Bull Int Union Tuberc Lung Dis 199i; 66: 53-56. 11. Chum H J. Ten years of the National Tuberculosis/Leprosy Programme in Tanzania. Bull Int Union Tuberc Lung Dis 1989; 64: 34-36. 12. Salaniponi F L M. The Malawi National Tuberculosis Programme. Bull Int Union Tuberc Lung Dis 1989; 64: 4@4 I. 13. Boulahbal’F, Khaled S, Tazir M. The interest of follow-up of resistance of the tubercle bacillus in the evaluation of a programme. Bull Int Union Tuberc Lung Dis 1989,64: 23-25. 14. Chonde T M. The role of bacteriological services in the National Tuberculosis and Leprosy Programme in Tanzania. Bull Int Union Tuberc Lung Dis 1989; 64: 37-39.
15. Kim S J, Hong Y P, Drug resistance of Mycobacretium tuberculosis in Korea. In Tuberculosis Surveillance Research Unit of the IUATLD Progress report Vol 1, 1989: 138-140. 16. Chaulet P, Benachenhoa A, Virot J P, Fekar A, Ait Khaled N. Results of the international cooperative inquiry into the cost of antituberculosis drugs. Bull Int Union Tuberc Lung Dis 1978; 53: 247-253. 17. Mariko M. Drugs; towards sound prescribing and pricing. World Health Forum 1991; 12: 34-37. 18. WHO. Economic Support for National Health for all Strategies, background document, 40th World Health Assembly, Geneva, 1987. 19. World Bank. World Development Report June 1990, Washington. 20. World Bank. World Development Report June 1991, Washington. 21. IMS, World drug market manual 1991, London. 22. WHO Expert Committee on Tuberculosis, Eighth Report, Technical Report Series 1964 no. 210. 23. WHO Expert Committee on Tuberculosis, Ninth Report, Technical Report Series 1974 no. 552. 24. WHO Tuberculosis Control. Report of a joint IUAT/WHO study group, Technical Report Series 1982, no. 671. 25. Murray C I J. Social, economic and operational research on tuberculosis: recent studies and some priority questions. Bull Int Union Tuberc Lung Dis 1991; 66: 149-156. 26. Grzybowski S. Natural history of tuberculosis. Bull Int Union Tuberc Lung Dis 1991; 66: 193-194. 27. Rouillon A. The mutual assistance programme of the IUATLD. Development, contribution and significance. Bull Int Union Tuberc Lung Dis 1991; 66: 159-172. 28. Broekmans J F. The point of view of a low prevalence country The Netherlands. Bull Int Union Tuberc Lung Dis 1991; 66: 179-184. 29. Chaulet P. Compliance with chemotherapy for tuberculosis. The responsibilities of the Health Ministry and of physicians. Bull Int Union Tuberc Lung Dis 66; (suppl) 90/9 1: 33-36. 30. Catsambus T, Foster S. Spending money sensibly: the case of essential drugs. Finance and Development 1986: 30-32. 31. WHO The use of essential drugs. Third report of the WHO Expert Committee. Model list of essential drugs (fifth list). Technical Report Series 1988, no. 770.
