The cost-effectiveness of policies for the safe and appropriate use of injection in healthcare settings.

The cost-effectiveness of policies for the safe and appropriate use of injection in healthcare settings Gerald Dziekan,1 Daniel Chisholm,2 Benjamin Johns,2 Juan Rovira,3 & Yvan J.F. Hutin1 Objective Poor injection practices transmit potentially life-threatening pathogens. We modelled the cost-effectiveness of policies for the safe and appropriate use of injections in ten epidemiological subregions of the world in terms of cost per disability-adjusted life year (DALY) averted. Methods The incidence of injection-associated hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections was modelled for a year 2000 cohort over a 30-year time horizon. The consequences of a ‘‘do nothing’’ scenario were compared with a set of hypothetical scenarios that incorporated the health gains of effective interventions. Resources needed to implement effective interventions were costed for each subregion and expressed in international dollars (I$). Findings Worldwide, the reuse of injection equipment in the year 2000 accounted for 32%, 40%, and 5% of new HBV, HCV and HIV infections, respectively, leading to a burden of 9.18 million DALYs between 2000 and 2030. Interventions implemented in the year 2000 for the safe (provision of single-use syringes, assumed effectiveness 95%) and appropriate (patients–providers interactional group discussions, assumed effectiveness 30%) use of injections could reduce the burden of injection-associated infections by as much as 96.5% (8.86 million DALYs) for an average yearly cost of I$ 905 million (average cost per DALY averted, 102; range by region, 14–2293). Attributable fractions and the number of syringes and needles required represented the key sources of uncertainty. Conclusion In all subregions studied, each DALY averted through policies for the safe and appropriate use of injections costs considerably less than one year of average per capita income, which makes such policies a sound investment for health care. Keywords Injections/adverse effects; Equipment reuse/economics; Equipment contamination/prevention and control; Health policy; Syringes/adverse effects; Needles/adverse effects; Hepatitis B/etiology; Hepatitis C/etiology; HIV infections/etiology; Cost of illness; Cost-benefit analysis; Models, Theoretical; Cohort studies (source: MeSH, NLM ). Mots cle´s Injection/effets inde´sirables; Re´utilisation mate´riel/e´conomie; Contamination mate´riel/pre´vention et controˆle; Politique sanitaire; Seringue/effets inde´sirables; Aiguille/effets inde´sirables; He´patite B/e´tiologie; He´patite C/e´tiologie; HIV, Infection/e´tiologie; Couˆt maladie; Analyse couˆt-be´ne´fice; Mode`le the´orique; Etude cohorte (source: MeSH, INSERM ). Palabras clave Inyecciones/efectos adversos; Equipo reutilizado/economı´a; Contaminacio´n de equipos/prevencio´n y control; Polı´tica de salud; Jeringas/efectos adversos; Agujas/efectos adversos; Hepatitis B/etiologı´a; Hepatitis C/etiologı´a; Infecciones por VIH/etiologı´a; Costo de la enfermedad; Ana´lisis de costo-beneficio; Modelos teo´ricos; Estudios de cohortes (fuente: DeCS, BIREME ). Bulletin of the World Health Organization 2003;81:277-285. Voir page 283 le re´sume´ en franc¸ais. En la pa´gina 283 figura un resumen en espan˜ol. Introduction Poor injection practices lead to infections with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immuno- deficiency virus (HIV) (1). In addition, unsafe injections have been important vectors for the introduction of HCV to patients in some countries, including Egypt and Pakistan (2– 4). However, the burden of cirrhosis, hepatocellular carcino- ma, and acquired immunodeficiency syndrome (AIDS) associated with unsafe injections is delayed and may not be directly apparent. Although injection-associated infections constitute a silent epidemic, effective interventions are available to reduce injection use and unsafe practices (G. Dziekan & Y.J.F. Hutin, unpublished data, 2002). First, information, education and communication (IEC) targeting prescribers, including patient– prescribers interactional group discussions, reduces injection use. Second, the provision of single-use injection equipment improves safety. For national stakeholders faced with competing prio- rities, the availability of effective interventions to prevent a hidden epidemicmight not be sufficient to justify investing in a policy for the safe and appropriate use of injections. Economic considerations also enter the debate. Accordingly, we set out to estimate the sectoral cost-effectiveness of policies for the safe and appropriate use of injections in terms of cost per disability- adjusted life year (DALY) averted. 1 Department of Blood Safety and Clinical Technology (BCT), World Health Organization, CH-1211 Geneva 27, Switzerland. Correspondence should be addressed to Dr Hutin (email: hutiny@who.int). 2 Global Programme on Evidence for Health Policy (GPE), World Health Organization, Geneva, Switzerland. 3 Health, Nutrition and Population Network, World Bank, Washington, DC, USA. Ref. No. 02-0444 277Bulletin of the World Health Organization 2003, 81 (4) Methods Study populations The six regions of WHO were separated into subgroups of countries on the basis of having similar rates of child and adult mortality. This resulted in 14 Global Burden of Disease 2000 epidemiological subregions characterized by the WHO region acronyms (AFR (African Region); AMR (Region of the Americas); EMR (Eastern Mediterranean Region); EUR (European Region); SEAR (South-East Asia Region); and WPR (Western Pacific Region)) and a letter for the mortality stratum (Table 1) (5). Four subregions in which the reuse of injection equipment in the absence of sterilization is negligible were excluded from the analysis (AMRA, EMRB, EURA and WPR A). Effectiveness model We considered a theoretical cohort of the population living in the year 2000 in subregionswhere reuse of injection equipment has been reported (figures provided by the Global Burden of Disease study group). We first applied a current, ‘‘do nothing’’ scenario where persons were injected using contaminated needles and consequently acquired infections. Second, we applied a series of hypothetical intervention scenarios for the year 2000, taking into account the effect of these interventions on the incidence of infections. DALYs attributable to poor injection practices We modelled the fraction of incident HBV, HCV, and HIV infections attributable to contaminated injections on the basis of the annual number of injections per person, the proportion of injections administered with equipment reused in the absence of sterilization, the probability of transmission following percutaneous exposure, the prevalence of active infection, the prevalence of immunity, and the incidence (6). The burden in DALYs for the years 2000–30 due to infections in the year 2000 was estimated on the basis of the natural history of viral infections (6), background mortality, Global Burden of Disease life tables (7), and the average duration and disability weights of acute hepatitis, cirrhosis, hepatocellular carcinoma, and AIDS — the four sequelae of interest (8). DALYs were age-weighted and 3% discounted (7). Effectiveness of interventions We examined interventions for reducing the unsafe use of injections, interventions for reducing injection use, and the effect of these two interventions when implemented jointly (G. Dziekan & Y.J.F. Hutin, unpublished data, 2002). For interventions to reduce the unsafe use of injections, we considered the effectiveness of interventions on the basis of provision of single-use injection equipment (9, 10). The effectiveness of interventions to reduce injection frequency was highly variable (1–53%) due to the variability in approaches and study designs (S. Luby, F. Hoodbhoy, A. Shah, unpublished data) (11–26). In our model, we used the estimate of effectiveness reported for interactional group discussions (30%) — a well-designed, well-evaluated inter- vention that has been used in developing countries (23). Interactional group discussions consist of moderated patient– prescriber discussions on the topic of injection use, during which the prescribers are confrontedwith the actual absence of preference for injections among patients. Our disease model was based on the number of contaminated injections — a product of the number of injections received and the proportion of these given with reused equipment. Thus, we assumed that the effectiveness of the combined interventions was a multiplication of the effect of the two. In the absence of evidence suggesting the contrary, we also assumed that intervention effectiveness did not differ with respect to the underlying magnitude of the burden under the ‘‘do nothing’’ scenario. Cost of interventions Quantification First, we identified the activities required for each intervention at the national and subnational level for an implementation period of ten years (27) (Table 2). Each of these activities was assigned to the intervention to reduce injection use or to the intervention to reduce unsafe practices, or both (in the case of the latter, activities necessary in the two interventions were counted only once). We then estimated the quantity of full- time-equivalent staff members and the material resources required to conduct these activities. Third, we estimated the needs of single-use syringe and needle sets on the basis of the number of injections administered and the proportion already given using sterile injection equipment (6). Fourth, the resources required for safe sharps waste collection and management was taken into account as part of the interven- tion. The needs quantified for 10 years were then averaged to obtain a yearly estimate that we used to cost the hypothetical intervention in the year 2000. Costing We estimated the average yearly programme cost for human resources and associated materials for the year 2000 by costing studies conducted in each subregion as part of the WHO- CHOICE (Choosing Interventions that are Cost Effective) project (27). The cost of injection equipment was calculated on the basis of international retail prices and the cost of distribution. First, we estimated international retail market prices among main international wholesalers. Second, we estimated international distribution costs on a standardized mark-up, taking into account the average difference between international free on board (FOB) and cost, insurance and freight (CIF) prices, as well as additional trade-related international distribution costs (28). Third, we estimated the cost of domestic distribution on the basis of a hexagon-shaped subregional distribution model that calculated the distances between the theoretical centre of a country with the highest population densities and a periphery with the lowest popula- tion density (29). The cost of personnel, capital, and fuel was estimated from a database to which fuel efficiency and maintenance cost was added (30). Finally, we used costing studies conducted by WHO to estimate the costs per syringe and needle set of sharps waste collection and disposal through incineration (Ulla Kou & Patrick Lydon, personal commu- nication). All costs were expressed in international dollars (I$) for the year 2000 (27). An international dollar has the same purchasing power as the US dollar has in the United States, and is derived via the application of purchasing power parity exchange rates. We assumed 100% coverage of all situations where injections were given in the formal public sector (e.g. hospitals, clinics). 278 Bulletin of the World Health Organization 2003, 81 (4) Research Uncertainty analysis We first tested the upper and lower values of the attributable fraction of the comparative risk assessment (6). Second, we assumed that the effectiveness of interventions was only 7% for reducing injection use (the lowest effectiveness reported for an intervention targeting patients and providers) and 50% for reducing unsafe use of injections. Third, we ran the analysis using an upper value of the number of syringes and needle sets required. Fourth, we ran an analysis that did not take into account the additional cost of safe sharps waste collection and management. Finally, total estimated costs and effects (each simulated to have a truncated normal distribution and a coefficient of variation of 0.5) were entered into the software package MCLeague (31), which uses Monte Carlo simulation (1000 runs) to perform a stochastic uncertainty analysis of the probability that interventions represent a cost-effective use of resources given a specified budget constraint. Results Effectiveness of interventions Burden of disease attributable to contaminated injections in 2000 The number of injections per person per year was estimated to range from 1.7 in AMR B to 11.3 in EUR C, of which a proportion ranging from 1.2% in EUR B and 75% in SEARD was administered with injection equipment reused in the absence of sterilization (Table 1). Overall, contaminated injections caused 21 million HBV infections, two million HCV infections and 260 000 HIV infections. These infections led to 49 000, 24 000, and 210 000 deaths, respectively, between the years 2000 and 2030, for a total of 9 177 679 dis- counted and age-weighted DALYs (non-discounted, unad- justed DALYs, 48 541 032). HIV infections accounted for the highest proportion of DALYs (63%), whereas HBV and HCV infections accounted for 34% and 4%of the total, respectively. Most of this burden was caused by early death rather than by disability. Burden of disease preventable through interventions We assumed the effectiveness of interactional group discus- sion to be 30% on injection use (23). This effectiveness translated directly into projected burden of disease reduction as the incidence of injection-associated infections in the present disease model was proportional to the annual number of injections per person and the proportion of injections given with reused equipment (6). Implementation of interventions to reduce injection use would lead to a reduction of 2 753 304 DALYs. The effectiveness of provision of single- use injection equipment was assumed to be 95% on the unsafe use of injections. Implementation of interventions to reduce the unsafe use of injections would lead to a reduction of 8 718 795 DALYs. When combined, the two interventions would lead to a reduction of 8 856 461 DALYs. Costs of interventions The expected annual cost of the intervention to reduce injection use (Table 3) ranged from I$ 1.1million in AMRD to I$ 26 million in WPR B (cost per capita, I$ 0.009–0.024). The cost of the intervention to reduce the unsafe use of injections ranged from I$ 2.5 million in AMR D to I$ 459 million in SEAR D (cost per capita, I$ 0.01–0.44). A high proportion of these costs (83–99% in all subregions other than AMR B and EUR B) consisted of injection equipment, including interna- tional retail price, international transport, and waste manage- ment. Overall, the international retail price accounted for 40% of the total injection equipment costs (Fig. 1). The estimated yearly cost of combined interventions ranged from I$ 3million in AMR D to I$ 466 million in SEAR D (cost per capita, I$ 0.03–0.45). Cost-effectiveness of interventions The average cost-effectiveness ratio (CER; total costs divided by total effects) for interventions to reduce injection use was I$ 7 to I$ 5124 per DALY averted according to the region (Table 3). The average CER for interventions to reduce unsafe use of injections, including waste management, was I$ 12 to I$ 1107 per DALY averted according to the region. The Table 1. Contaminated injections in the year 2000, attributable and preventable burden of disease for the period 2000–30 African Region of Eastern Medi- European South-East Western Pacific All Region the Americas terranean Region Asia Region Region Region AFR Da AFR Ea AMR Ba AMR Da EMR Da EUR Ba EUR Ca SEAR Ba SEAR Da WPR Ba Mortality in children High High Low High High Low Low Low High Low Mortality in adults High Very high Low High High Low Low Low High Low Injections per person per yearb 2.2 2.0 1.7 1.9 4.3 5.2 11.3 2.1 4.0 2.4 3.4 Proportion of reuse (%)b 19 17 1.2 11 70 1.2 11 30 75 30 39.8 Total burden 2000–30b 555 644 1 668 583 9 083 27 332 559 702 3 479 64 733 280 789 4 720 866 1 287 470 9 177 679 Preventable burden 2000–30 Reduction of injection usec 166 693 500 575 2 725 8 200 167 911 1 044 19 420 84 237 1 416 260 386 241 2 753 304 Reduction of unsafe used 527 862 1 585 154 8 629 25 965 531 717 3 305 61 496 266 749 4 484 823 1 223 096 8 718 795 Combined interventionse 536 197 1 610 182 8 765 26 375 540 112 3 357 62 467 270 961 4 555 636 1 242 408 8 856 461 a Global Burden of Disease 2000 epidemiological subregions are characterized by the World Health Organization region acronym and a letter for the mortality stratum (5). b ‘‘Do nothing’’ scenario. c Interactional group discussions between patients and providers to reduce injection use. d Provision of single-use, disposable syringes and needles for all injections. e Safe and appropriate use of injection policies combining the two interventions above. 279Bulletin of the World Health Organization 2003, 81 (4) Cost-effectiveness of policies for injection use average CER for combined interventions for the safe and appropriate use of injections, including waste management, was I$ 14 to I$ 2293 per DALY averted according to the region. Incremental analysis (Table 3) suggested that in the six subregions in which the proportion of reuse of injection equipment exceeds 15% (Table 1), the intervention to reduce injection use represents the single most cost-effective strategy. In the four other subregions, the reduction of unsafe use was the most efficient strategy. However, in all regions, the average CER of the combined intervention strategy remained under the threshold of one year of average per capita income. Uncertainty analysis Five scenarios were assessed in the sensitivity analysis (Table 4). Higher attributable fraction reduced the average cost per DALY averted by 19–86% compared with the base case, but removing the costs of sharps waste management had little additional influence on baseline results (scenarios 1 and 2, with the latter representing the best case). Attribution of a lower fraction of injection-related infections raised the average cost per DALY averted (scenario 3). Using the minimum estimates for intervention effectiveness in addition to the lower attributable fractions increased CER ratios further, particularly for the intervention to reduce injection use (scenario 4). Finally, a scenario incorporating the lower attributable fraction, minimum effectiveness, and a doubled number of syringe and needle sets (scenario 5) resulted in a four- to ten-fold increase in the average cost per DALY averted, compared with initial baseline estimates. However, even in this worst-case scenario, the average cost-effectiveness ratio of all interventions remained below the threshold of average annual income per capita (Table 4). Inclusion of best- and worst-case total costs and effects in the stochastic uncertainty analysis showed that at very low levels of resource availability, reduction of injection use represents the most cost-effective strategy in most subregions (a small health gain, but achieved at a low cost). At higher levels of resource availability, a combination approach would be the most efficient choice (considerably greater health gains at an increased but still cost-effective level of investment). Discussion The average cost of a policy by which single-use syringes and needles are used for all injections amounts to less than I$ 0.50 per person per year. This may seem an unaffordable gold standard where sterilizable injection equipment is still in use, particularly because the benefits of safe injections in terms of death and disability prevented are far ahead in the future (32). However, in Burkina Faso, it was estimated that purchasing injection equipment in quantities that match injectable medicines increased essential drug expenditures by only 2.2% (WHO, unpublished data). Supplying sufficient quantities of single-use injection equipment is cost-effective. Implemented jointly with interventions to reduce injection use, injection safety interventions can prevent more death and disability while remaining a sound investment in public health. In addition, policies for the safe and appropriate use of injections can lead to savings in the cost of injectable medicines. These savings could be redirected to finance injection equipment for injectable medicines that are essential. In all subregions analysed, the cost of each DALY averted through national policies for the safe and appropriate use of injections is considerably less than one year of average per capita income, which is the threshold for an intervention being highly cost-effective proposed recently by the WHO Commission on Macroeconomics and Health (33). When recently compared with other strategies to reduce leading risk factors for disease, the safe and appropriate use of injections was found to cause a modest reduction in DALYs but was one of the most cost-effective interventions (5). When compared with other modes of preventing HIV infection in sub-Saharan Africa, the cost-effectiveness ratio of policies for the safe and Table 2. Activities included in interventions for the safe and appropriate use of injectiona Activity Intervention Timing Level Start-upb Years 1 2 3 4 5 6 7 8 9 10 National planning workshop Appropriate use Start-up Nationalc X – – – – – – – – – – Development of IECd material Appropriate use Start-up Nationalc X – – – – – – – – – – Training of the trainers Appropriate use Start-up Nationalc X – – – – – – – – – – Training of the procurement officer Safe use Start-up Nationalc X – – – – – – – – – – District planning workshops Appropriate use Start-up Subnationalc X – – – – – – – – – – Supplying injection equipmente Safe use Post start-up Subnationalc – X X X X X X X X X X Annual national follow-up workshop Appropriate use Post start-up Nationalc – X X X X X X X X X X Interactional group discussions Appropriate use Post start-up Subnationalc – X X X X X X X X X X Annual monitoring surveys Bothf Post start-up Subnationalc – X X X X X X X X X X a The analysis considered the 3% discounted average yearly cost of a 10 year intervention. Safe and appropriate use interventions were considered separately and combined. b Included in year one. c According to WHO-CHOICE (Choosing Interventions that are Cost Effective) methods (5). d IEC = Information, education, and communication. e With and without safe sharps waste management in the sensitivity analysis. f This activity appears twice, once for the appropriate use and once for the safe use intervention, but is counted only once in the hypothesis of the combined intervention. 280 Bulletin of the World Health Organization 2003, 81 (4) Research appropriate use of injections remained under the threshold of I$ 50 per DALY averted, which was in the range of the most cost-effective interventions for preventing HIV infection (e.g. blood safety, targeted condom distribution, and treatment of sexually transmitted diseases) (34). A safe injection is defined as one that does not harm the recipient, the provider and the members of the community (35). Therefore, the costs of sharps waste collection andmanagement were included as part of programme costs. However, the effect of safe sharps waste collection and management in terms of burden of disease secondary to needlestick injuries among healthcare workers or the community prevented could not be estimated. Thus, such a policy may be more cost-effective than the present results indicate. The sensitivity analysis indicates that the cost per DALY averted decreased by 36% to 39% if the costs of safe sharps waste collection and management were excluded to match costs and effects. Policies for the safe and appropriate use of injections are natural additions to universal infant vaccination against hepatitis B in a national strategy to prevent HBV infection. Infant immunization against hepatitis B is probably more cost- effective than safe and appropriate use of injections, with cost per life year saved ranging from I$ 4 to I$ 36 (36).When global efforts for universal vaccination of infants have reached adequate coverage for a sufficient period of time, high levels of Table 3. Costs and cost-effectiveness of policies for the safe and appropriate use of injectionsa, 2000 African Region of Eastern European South-East Asia Western Region the Americas Mediterranean Region Region Pacific Region Region AFR Db AFR Eb AMR Bb AMR Db EMR Db EUR Bb EUR Cb SEAR Bb SEAR Db WPR Bb Total population (million) 294 346 431 71 343 218 243 294 1242 1533 Gross domestic product per capita 1381 1576 7833 3837 2393 7294 6916 2545 1449 4186 Syringes/needlesc Syringe/needle sets needed 122 924 628 117 475 114 8 791 014 14 887 078 1 031 154 040 6 553 752 93 625 680 185 105 732 3 725 419 491 1 103 711 844 Syringe/needle costs 19 176 242 18 208 643 1 116 459 2 084 191 148 486 182 773 343 11 422 333 25 544 591 454 501 178 144 586 252 Programme costsd Reduction of injection use 2 738 289 3 308 975 10 524 021 1 080 717 3 876 085 5 349 039 5 298 743 3 568 129 10 599 413 25 579 948 Reduction of unsafe use 1 602 096 1 391 325 3 189 442 434 498 1 542 952 2 884 373 1 692 560 1 218 867 4 402 415 8 452 776 Combination 3 553 983 3 711 160 11 020 206 1 205 776 4 234 537 6 922 989 5 554 346 3 757 891 11 812 493 27 164 652 Total cost per year Reduction of injection use 2 738 289 3 308 975 10 524 021 1 080 717 3 876 085 5 349 039 5 298 743 3 568 129 10 599 413 25 579 948 Reduction of unsafe use 20 778 338 19 601 204 4 305 901 2 518 893 150 029 134 3 657 716 13 114 893 26 763 458 458 903 593 153 039 028 Combination 22 730 225 21 922 514 12 136 665 3 290 463 152 720 719 7 696 332 16 976 679 29 302 482 466 313 671 171 750 904 Average CER (I$ per DALY averted)e Reduction of injection use 16 7 3862 132 23 5124 273 42 7 66 Reduction of unsafe use 39 12 499 97 282 1107 213 100 102 125 Combination 42 14 1385 125 283 2293 272 108 102 138 Incremental CER (I$ per DALY averted)e,f Reduction of injection use 16 7 – – 23 – – 42 7 66 Reduction of unsafe use 50 15 499 97 – 1107 213 127 – 152 Combination 234 93 57 579 1882 400 77 666 3977 603 145 969 a Costs are in international dollars (I$). b Global Burden of Disease 2000 epidemiological subregions are characterized by the World Health Organization region acronym and a letter for the mortality stratum (5). c Syringes and needle costs include the international retail price, international transport, and waste management (domestic transport included under programme costs). Not applicable to intervention to reduce injection use. d Programme costs include personnel, transport, equipment, and supplies but exclude syringes and needles sets. e CER = cost-effectiveness ratio. DALY = disability-adjusted life year. f Lowest value represents most cost-effective option relative to doing nothing; next-lowest value represents next most cost-effective option. 281Bulletin of the World Health Organization 2003, 81 (4) Cost-effectiveness of policies for injection use immunity against HBV infection will ultimately protect populations from injection-associated HBV infection. This study was not an attempt to compare various injection technologies. The present model did not consider the use of sterilizable injection equipment in any of the interventions because there are no data available to indicate that it can lead to safe injection practices. In fact, the use of sterilizable injection equipment has been specifically asso- ciated with infections with bloodborne pathogens (37–41), and health systems using sterilizable syringes have poorer practices than those using single-use equipment (42). No special reference was made to the use of autodisable (AD) injection equipment that inactivates itself after one use (43). AD syringes offer the highest level of safety and are now considered to be the standard for administering vaccines (44). However, immunization injections account for fewer than 10% of all injections (1). Thus, introducing AD syringes in immunization services will address only a small proportion of the burden of disease associated with unsafe injections. With respect to using AD syringes in curative services, although single-use syringes can be reused, effectiveness data indicating that AD syringes would be associated with safer injection practices compared with standard single-use syringes made available in sufficient quantities could not be identified. Nevertheless, AD syringes should be considered for use in settings where unsafe practices are common, particularly in the non-formal sector that is staffed with unqualified health-care workers, specifically in South Asia (4, 45). In such cases, the results of our analysis could be easily extrapolated to AD syringes because they are now available at a cost that is very close to the one of standard single-use syringes. In 2002, the international retail price for an immunization AD syringe was five to seven US cents, whereas international retail prices for single use syringes ranged from four (2 ml) to eight (5 ml) US cents. The present study presented several limitations. First, the model did not take into account any longer-term dynamic effects that reducing transmission of infection would have on the prevalence of infections with bloodborne pathogens. This could be a problem in the case of HCV infection because contaminated injections account for a high proportion of new infections. This limitation could also lead to an under- estimation of the effect size, hence these interventions might be described as being less cost-effective than they really are. Second, the specific issues associated with working in the private sector were not addressed. The provision of sufficient quantities of single-use injection equipment and interactional group discussion might not be sufficient where the informal private sector accounts for a high proportion of healthcare services delivery. In such settings, demonstration projects should identify effective strategies, some of which might include the use of AD syringes in curative services or addressing financial incentives to overprescribing injections, or both. Table 4. Sensitivity analyses for the estimate of the average cost-effectiveness ratios of interventions for the safe and appropriate use of injections per DALY averteda Sensitivity scenario African Region Eastern European South-East Western Region of the Mediterra- Region Asia Region Pacific Americas nean Region Region AFR Db AFR Eb AMR Bb AMR Db EMR Db EUR Bb EUR Cb SEAR Bb SEAR Db WPR Bb Higher attributable fractionc Reduction of injection use 13 5 523 44 17 1394 140 33 6 28 Reduction of unsafe use 32 10 68 33 210 301 109 79 78 53 Combination 34 11 187 42 210 624 139 85 78 59 Higher attributable fraction, no sharps waste management Reduction of injection use 13 5 523 44 17 1394 140 33 6 28 Reduction of unsafe use 20 6 61 22 127 276 71 49 47 33 Combination 23 7 181 31 129 599 102 55 48 39 Lower attributable fraction Reduction of injection use 22 9 NA NA 45 NA 970 57 11 NA Reduction of unsafe use 52 16 NA NA 544 NA 758 136 156 NA Combination 56 18 NA NA 546 NA 967 146 156 NA Lower attributable fraction, minimum effectiveness Reduction of injection use 93 37 NA NA 191 NA 4159 245 49 NA Reduction of unsafe use 99 31 NA NA 1035 NA 1441 258 296 NA Combination 106 34 NA NA 1038 NA 1838 278 296 NA Lower attributable fraction, minimum effect, double injection sets Reduction of injection use 93 37 NA NA 191 NA 4159 245 49 NA Reduction of unsafe use 190 60 NA NA 2058 NA 2696 504 589 NA Combination 196 62 NA NA 2046 NA 3074 520 585 NA a Results are in international dollars (I$). Not applicable (NA) refers to lower attributable fraction equals to zero; cost-effectiveness ratio (CER) cannot therefore be calculated. DALY = disability-adjusted life year. b Global Burden of Disease 2000 epidemiological subregions are characterized by the World Health Organization region acronym and a letter for the mortality stratum (5). c Attributable fraction refers to the fraction of new hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infections attributable to contaminated injections. 282 Bulletin of the World Health Organization 2003, 81 (4) Research Poor injection practice is not a leading cause of disability and death worldwide. However, the safe and appropriate use of injection equipment represents an opportunity to avert a substantial number of DALYs at a relatively low cost. Improved injection practice can be recommended for implementation worldwide, particularly in settings where the reuse of injection equipment is common and where the HIV prevalence in the general population exceeds 1%. Such policies can be developed through a better coordination of already existing programmes to facilitate implementation. Finally, in addition to being cost- effective, the safe and appropriate use of injections is an attainableway of applying the ‘‘first do no harm’’ principle as part of the ethics of healthcare service delivery. n Acknowledgements We are grateful to Andrew Creese, Majid Ezzati and Tessa Tan Tores for general guidance throughout this project; Niels Tomijima and Stephen Vanderhoorn for assistance in the calculation of the DALYs; and Ulla Kou and Patrick Lydon for the costing estimates for sharps waste collection and management. Funding: This work was supported by a grant from the United States National Vaccine Program Office (NVPO), made available through WHO by the United States Agency for International Development (USAID). Conflicts of interest: none declared. Re´sume´ Couˆt-efficacite´ des politiques en faveur de l’utilisation suˆre et approprie´e des injections dans les e´tablissements de soins de sante´ Objectif Des pratiques d’injection de´fectueuses sont a` l’origine de la transmission d’agents pathoge`nes potentiellement mortels. Nous avons effectue´ une mode´lisation du rapport couˆt-efficacite´ des politiques en faveur d’une utilisation suˆre et approprie´e des injections dans dix sous-re´gions e´pide´miologiques du monde, les re´sultats e´tant exprime´s en couˆt par anne´e de vie ajuste´e sur l’incapacite´ (DALY) e´vite´e. Me´thodes L’incidence des infections par le virus de l’he´patite B (VHB), le virus de l’he´patite C (VHC) et le virus de l’immunode´- ficience humaine (VIH) associe´es aux injections a e´te´ mode´lise´e pour une cohorte de l’an 2000 sur une dure´e prospective de 30 ans. Les conse´quences d’un sce´nario « statu quo » ont e´te´ compare´es a` une se´rie de sce´narios hypothe´tiques inte´grant les gains, en termes de sante´, d’interventions efficaces. Le montant des ressources ne´cessaires pour la mise en œuvre des interventions efficaces a e´te´ e´value´ pour chaque sous-re´gion et exprime´ en dollars inter- nationaux (I $). Re´sultats A l’e´chelle mondiale, la re´utilisation du mate´riel d’injection a e´te´ a` l’origine, en 2000, de 32 %, 40 % et 5 %, respectivement, des nouvelles infections par le VHB, le VHC et le VIH, ce qui conduirait a` une charge de 9,18 millions de DALY entre 2000 et 2030. Des interventions mises en œuvre en 2000 en vue de l’utilisation suˆre et approprie´e des injections (graˆce a` la fourniture de seringues a` usage unique, d’une efficacite´ suppose´e de 95 %, et a` des groupes de discussion patients-dispensateurs de soins, d’une efficacite´ suppose´e de 30 %) pourraient re´duire la charge des infections associe´es aux injections de 96,5 % (8,86 millions de DALY) pour un couˆt annuel moyen de I $ 905 millions (rapport couˆt-efficacite´ moyen par DALY e´vite´e : 102 ; intervalle selon les re´gions : 14-2293). Les principales sources d’incertitude concer- naient la fraction attribuable et le nombre de seringues et d’aiguilles ne´cessaires. Conclusion Dans toutes les sous-re´gions e´tudie´es, chaque DALY e´vite´e graˆce a` des politiques en faveur de l’utilisation suˆre et approprie´e des injections couˆterait nettement moins d’une anne´e de revenu moyen par habitant ; ces politiques repre´sentent donc un excellent investissement en termes de soins de sante´. Resumen Costoeficacia de las polı´ticas de fomento del uso seguro y apropiado de las inyecciones en los entornos de atencio´n de salud Objetivo Las malas pra´cticas de inyeccio´n transmiten agentes pato´genos potencialmente mortales. Procedimos a modelizar la costoeficacia de las polı´ticas de fomento del uso seguro e ido´neo de las inyecciones en diez subregiones epidemiolo´gicas del mundo, teniendo en cuenta el costo de evitar la pe´rdida de un an˜o de vida ajustado en funcio´n de la discapacidad (AVAD). Me´todos Se modelizo´ la incidencia de infecciones asociadas a inyecciones por virus de la hepatitis B (VHB), virus de la hepatitis C (VHC) y virus de la inmunodeficiencia humana (VIH) para una cohorte del an˜o 2000 con un horizonte temporal de 30 an˜os. Las consecuencias de un escenario de «inaccio´n» se compararon con las de un conjunto de escenarios hipote´ticos que incorporaban los beneficios sanitarios de las intervenciones eficaces. Se evaluaron para cada subregio´n los recursos necesarios para ejecutar las intervencio- nes eficaces, expresa´ndolos en do´lares internacionales (I$). Resultados A nivel mundial, la reutilizacio´n de material de inyeccio´n en el an˜o 2000 represento´ el 32%, 40% y 5% de las infecciones nuevas por VHB, VHC y VIH, respectivamente, lo que entran˜arı´a una carga de 9,18 millones de AVAD entre 2000 y 2030. Las intervenciones llevadas a cabo en 2000 para fomentar el uso seguro (suministro de jeringas monouso, suponiendo una eficacia del 95%) y apropiado (discusiones de grupo interactivas pacientes-dispensadores, suponiendo una eficacia del 30%) del material de inyeccio´n podrı´an reducir la carga de infecciones asociadas a las inyecciones nada menos que en un 96,5% (8,86 millones de AVAD) por un costo anual promedio de I$ 905 millones (costoeficacia promedio por AVAD evitado: 102; intervalo por regiones, 14–2293). Las fracciones atribuibles y el nu´mero de jeringuillas y agujas requerido son las principales fuentes de incertidumbre. 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