18 months of Insite’s operation (1.33 per 1,000 injections), none resulted in a fatality [15]. Despite the international evidence suggesting a beneficial effect of SIF on overdose mortality [16–18], we are unaware of any peer-reviewed studies that quantify the number of deaths prevented by such a facility. These estimates are obviously important for cost-effectiveness studies and other indicators. Thus, we sought to estimate the number of overdose fatalities averted in Vancouver’s SIF. Results From the initiation of the SIF database on March 1, 2004 until February 6, 2008, there were 766,486 injections in the facility, resulting in 1004 overdose events (1.31 per 1,000 injections, or 0.63 per day) in the facility. None resulted in death. The physical manifestations, the substances consumed and the responses taken by staff to these overdose events are shown in Table 1. Of the 1004 overdose events, 453 (45.1% or 0.28 per day) required the provision of naloxone, a 911 call and/or an ambulance, and were included as potential fatal overdoses in our analysis. In approximately 68% of on-site overdose events during the study period, the primary substance injected was heroin, followed by cocaine (17%). From 2004 to 2006, the British Columbia Vital Statistics Agency reported 32, 37 and 38 annual drug-induced deaths in the Downtown Eastside. The median number of drug-induced deaths per annum from 1998 to 2006 was 38.3. The model inputs for the number of fatal overdoses for each year of the study period, as well as all other model inputs, are reported in Table 2. Model results, including the DTES fatal overdose rate, the estimated ratio of fatal to non-fatal overdoses in the DTES, the estimated number of non-fatal overdoses in the DTES, and the estimated number of on-site deaths averted, expressed as both a count and a proportion of DTES overdose deaths, are presented in Table 3. The fatal overdose rate in the DTES over the study period was 5.6 per 1,000 person years. Over the same period, the estimated ratio of non-fatal to fatal overdose ranged from 8.9:1 (given a non-fatal overdose ratio of 50 per 1,000 person years) to 53.8:1 (given 300 per 1,000 person years). Using these inputs, the number of overdose deaths averted in the SIF over the study period was 50.9 (95% CI: 23.6–78.1); 12.6 (9.6–15.7); 8.4 (6.5–10.4) given different estimated rates of non- fatal overdose. The number of averted deaths is equal to between two and 12 per annum over the study period. Discussion Using data from North America’s first SIF and published estimates of the rate of non-fatal overdose among active IDU, we derived an estimate of the number of fatal overdoses averted by a supervised injecting facility. Following a Monte Carlo simulation and a three-part sensitivity analysis, the estimates of the number of prevented deaths ranged from eight to 51 from March 1, 2004 to July 1, 2008. The estimate of the number of deaths prevented is equal to a substantial proportion of the total burden of overdose mortality in the area during the study period. Despite the pilot facility only hosting, by design, approximately five per cent of the daily injections in the DTES, the estimated number of averted deaths was equal to between 6.1 and 37.0 per cent of the total overdose burden in the area during the study period. It is impossible to declare with certainty if the SIF prevented these fatalities as it is not possible to know if overdoses occurring in the SIF would have occurred elsewhere. However, despite charges to the contrary [19], a longitudinal analysis of overdose patterns in a represen- tative sample of SIF clients did not demonstrate that individuals OD Deaths Averted in SIF took greater risks—i.e., in drug choice, mode of administration or dose—within the apparent safety of an SIF [14]. Our results are similar to those in an evaluation of the medically supervised injection centre (MSIC) in Sydney, Australia [16]. Using a similar method, they estimated that six of the 81 non-fatal overdoses in the MSIC that required naloxone during its first 18 months of operation would have resulted in a fatality, or between four and nine deaths prevented per annum, given different methodological assumptions. This rate is within the range of two to 12 per annum estimated by our methodology. Our results differ from those in an unpublished cost-effectiveness report prepared for Canada’s federal health minister [20] that estimated Insite prevented 1.08 deaths per year, an estimate below the range of the per annum calculation of our model. However, it should be noted that the report’s figure was the result of an extrapolation of published and aggregated data from the first 18 months of operation; the authors were unable to benefit from SIF data from the first four years of operation; nor did their methodology account for the uncertainty surrounding several parameters. We believe the authors’ population-level estimates of overdose risk differed due to the above issues as well as failure to account for the higher risk drug-using patterns of the SIF clientele [10,21]. Obviously, the optimal strategy to evaluate the impact of the SIF on overdose rates would be to randomize participants to use (versus restricted use) of the SIF. This approach has been deemed unethical [9]. In the absence of a randomized trial, there are several approaches to assess possible effects on fatal overdose including modelling, as we have employed, and crude time series analyses comparing year-to-year changes in mortality rates. With respect to time-series approaches, previous work has identified how overdose rates are influenced by a diverse array of factors which change over time, such as drug purity. We have recently shown large fluctuations in local drug purity[22]. Other factors affecting overdose risk include age [23], drug choice [24], exposure to addiction treatment [25] and incarceration history [26]. While little work has been done on the population-level determinants of overdose mortality rates, it is reasonable to assume analogous factors are at work, including drug market dynamics, law enforcement patterns and the coverage of harm reduction measures. Because of this multiplicity of effects and the potential for unmeasured confounding due to drug supply changes in crude time series analyses, we are unaware of any method using available data that could identify the impact of the SIF on population-level overdose rates. Thus, we chose to estimate the number of averted overdose deaths using published estimates and observed, individ- ual-level data from the SIF. These findings have immediate policy implications. First, despite initially expressing interest in analyses of Insite’s impact on local patterns of overdose [27], Canada’s federal government more recently announced its opposition to the continued operation of the facility and appealed a local court ruling blocking its closure [28]. Regardless of these partisan political developments, this analysis provides evidence of the likely beneficial effect of the facility on the risk of overdose death in the DTES and echoes previous findings from Sydney’s MSIC [16]. Together, these findings support the increasingly prevalent conclusion that supervised injection facilities are an effective and appropriate intervention in urban settings suffering from high levels of overdose deaths. Our analysis has several limitations, chiefly the reliance on estimates to inform several model parameters, specifically the number of IDU in the DTES and the incidence of non-fatal overdose in the community. For the former, we relied on two previous capture-recapture studies [29,30] and included a wide confidence interval in the Monte Carlo simulation. For the latter, PLoS ONE | www.plosone.org 2 October 2008 | Volume 3 | Issue 10 | e3351