PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1146740)

Clipboard (0)
None

Related Articles

1.  Schistosomiais and Soil-Transmitted Helminth Control in Niger: Cost Effectiveness of School Based and Community Distributed Mass Drug Administration 
Background
In 2004 Niger established a large scale schistosomiasis and soil-transmitted helminths control programme targeting children aged 5–14 years and adults. In two years 4.3 million treatments were delivered in 40 districts using school based and community distribution.
Method and Findings
Four districts were surveyed in 2006 to estimate the economic cost per district, per treatment and per schistosomiasis infection averted. The study compares the costs of treatment at start up and in a subsequent year, identifies the allocation of costs by activity, input and organisation, and assesses the cost of treatment. The cost of delivery provided by teachers is compared to cost of delivery by community distributers (CDD).
The total economic cost of the programme including programmatic, national and local government costs and international support in four study districts, over two years, was US$ 456,718; an economic cost/treatment of $0.58. The full economic delivery cost of school based treatment in 2005/06 was $0.76, and for community distribution was $0.46. Including only the programme costs the figures are $0.47 and $0.41 respectively. Differences at sub-district are more marked. This is partly explained by the fact that a CDD treats 5.8 people for every one treated in school.
The range in cost effectiveness for both direct and direct and indirect treatments is quantified and the need to develop and refine such estimates is emphasised.
Conclusions
The relative cost effectiveness of school and community delivery differs by country according to the composition of the population treated, the numbers targeted and treated at school and in the community, the cost and frequency of training teachers and CDDs. Options analysis of technical and implementation alternatives including a financial analysis should form part of the programme design process.
Author Summary
Schistosomiasis and soil-transmitted helminth control programmes are important, relatively low cost means to improve the health of those affected, in particular rural school age children. It can also reduce schistosomiasis related morbidity in their later lives. The paper presents information on the implementation and costs of a large scale national programme in Niger. The total economic cost per treatment was $0.58. This includes programme, government and international costs. Two systems, school based and community delivery were used to treat children and targeted adults. Contrary to findings in some countries we find that school based delivery is less cost effective than community delivery. This is due to the low proportion of the population targeted and treated by the school based system. Treating adults as well as children increased the numbers treated and reduced the overall cost per treatment. Prevalence and infection is higher in children than adults and overall effectiveness in terms of infection averted is affected. The cost per infection averted is assessed for direct treatment and direct and indirect treatment effects. The study expands the evidence available for decision makers involved in programme planning and design, funding and implementation.
doi:10.1371/journal.pntd.0001326
PMCID: PMC3191121  PMID: 22022622
2.  The Cost and Impact of Scaling Up Pre-exposure Prophylaxis for HIV Prevention: A Systematic Review of Cost-Effectiveness Modelling Studies 
PLoS Medicine  2013;10(3):e1001401.
Gabriela Gomez and colleagues systematically review cost-effectiveness modeling studies of pre-exposure prophylaxis (PrEP) for preventing HIV transmission and identify the main considerations to address when considering the introduction of PrEP to HIV prevention programs.
Background
Cost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions.
Methods and Findings
We conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP.
Conclusions
Our review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention—cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year approximately 2.5 million people are infected with HIV, the virus that causes AIDS. Behavioral strategies like condom use and reduction of sexual partners have been the hallmarks of HIV prevention efforts. However, biological prevention measures have also recently been shown to be effective. These include male circumcision, treatment as prevention (treating HIV-infected people with antiretroviral drugs to reduce transmission), and pre-exposure prophylaxis (PrEP), where people not infected with HIV take antiretroviral drugs to reduce the probability of transmission. Strategies such as PrEP may be viable prevention measure for couples in long-term relationships where one partner is HIV-positive and the other is HIV-negative (HIV serodiscordant couples) or groups at higher risk of HIV infection, such as men who have sex with men, and injection drug users.
Why Was This Study Done?
The findings from recent clinical trials that demonstrate PrEP can reduce HIV transmission have led to important policy discussions and in the US, Southern Africa, and the UK new clinical guidelines have been developed on the use of PrEP for the prevention of HIV infection. For those countries that are considering whether to introduce PrEP into HIV prevention programs, national policy and decision makers need to determine potential costs and health outcomes. Cost-effectiveness models—mathematical models that simulate cost and health effects of different interventions—can help inform such decisions. However, the cost-effectiveness estimates that could provide guidance for PrEP programs are dependent on, and limited by, the assumptions included in the models, which can make their findings difficult to generalize. A systematic comparison of published cost-effectiveness models of HIV PrEP interventions would be useful for policy makers who are considering introducing PrEP intervention programs.
What Did the Researchers Do and Find?
The researchers performed a systematic review to identify published cost-effectiveness models that evaluated the health gains and costs of HIV PrEP interventions. Systematic reviews attempt to identify, appraise, and synthesize all the empirical evidence that meets pre-specified eligibility criteria to answer a given research question by using explicit methods aimed at minimizing bias. By searching databases the authors identified 13 published studies that evaluated the impact of PrEP in different populations (heterosexual couples, men who have sex with men, and injection drug users) in different geographic settings, which included Southern Africa, Ukraine, US, and Peru.
The authors identified seven studies that assessed the introduction of PrEP into generalized HIV epidemics in Southern Africa. These studies suggest that PrEP may be a cost effective intervention to prevent heterosexual transmission. However, the authors note that funding PrEP while other cost-effective HIV prevention methods are underfunded in this setting may have high opportunity costs. The authors identified five studies where PrEP was introduced for concentrated epidemics among men who have sex with men (four studies in the US and one in Peru). These studies suggest that PrEP may have a substantial impact on the HIV epidemic but may not be affordable at current drug prices. The authors also identified a single study that modeled the introduction of PrEP for people who inject drugs in the Ukraine, which found PrEP not to be cost effective.
In all settings the price of antiretroviral drugs was found to be a limiting factor in terms of affordability of PrEP programs. Behavioral changes and adherence to PrEP were estimated to have potentially significant impacts on program effectiveness but the emergence of drug resistance or PrEP-related toxicity did not significantly affect cost-effectiveness estimates. Several PrEP prioritization strategies were explored in included studies and delivering PrEP to populations at highest risk of HIV exposure was shown to improve cost-effectiveness estimates. However, the extra costs of identifying and engaging with high-risk populations were not taken into consideration. The authors note that the geographic coverage of identified studies was limited and that the findings are very dependent on the setting which limits generalizability.
What Do these Findings Mean?
These findings suggest that PrEP could be a cost-effective tool to reduce new HIV infections in some settings. However, the cost-effectiveness of PrEP is dependent upon cost, the epidemic context, program coverage and prioritization strategies, participants' adherence to the drug regimen, and PrEP efficacy estimates. These findings will aid decision makers quantify and compare the reductions in HIV incidence that could be achieved by implementing a PrEP program.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001401.
The US National Institute of Allergy and Infectious Diseases has information on HIV/AIDS
aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and has a section on PrEP
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including HIV prevention
AVAC Global Advocacy for HIV Prevention provides information on HIV prevention, including PrEP
The US Centers for Disease Control and Prevention also has information on PrEP
The World Health Organization has a page on its WHO-CHOICE criteria for cost-effectiveness
doi:10.1371/journal.pmed.1001401
PMCID: PMC3595225  PMID: 23554579
3.  The Impact of eHealth on the Quality and Safety of Health Care: A Systematic Overview 
PLoS Medicine  2011;8(1):e1000387.
Aziz Sheikh and colleagues report the findings of their systematic overview that assessed the impact of eHealth solutions on the quality and safety of health care.
Background
There is considerable international interest in exploiting the potential of digital solutions to enhance the quality and safety of health care. Implementations of transformative eHealth technologies are underway globally, often at very considerable cost. In order to assess the impact of eHealth solutions on the quality and safety of health care, and to inform policy decisions on eHealth deployments, we undertook a systematic review of systematic reviews assessing the effectiveness and consequences of various eHealth technologies on the quality and safety of care.
Methods and Findings
We developed novel search strategies, conceptual maps of health care quality, safety, and eHealth interventions, and then systematically identified, scrutinised, and synthesised the systematic review literature. Major biomedical databases were searched to identify systematic reviews published between 1997 and 2010. Related theoretical, methodological, and technical material was also reviewed. We identified 53 systematic reviews that focused on assessing the impact of eHealth interventions on the quality and/or safety of health care and 55 supplementary systematic reviews providing relevant supportive information. This systematic review literature was found to be generally of substandard quality with regards to methodology, reporting, and utility. We thematically categorised eHealth technologies into three main areas: (1) storing, managing, and transmission of data; (2) clinical decision support; and (3) facilitating care from a distance. We found that despite support from policymakers, there was relatively little empirical evidence to substantiate many of the claims made in relation to these technologies. Whether the success of those relatively few solutions identified to improve quality and safety would continue if these were deployed beyond the contexts in which they were originally developed, has yet to be established. Importantly, best practice guidelines in effective development and deployment strategies are lacking.
Conclusions
There is a large gap between the postulated and empirically demonstrated benefits of eHealth technologies. In addition, there is a lack of robust research on the risks of implementing these technologies and their cost-effectiveness has yet to be demonstrated, despite being frequently promoted by policymakers and “techno-enthusiasts” as if this was a given. In the light of the paucity of evidence in relation to improvements in patient outcomes, as well as the lack of evidence on their cost-effectiveness, it is vital that future eHealth technologies are evaluated against a comprehensive set of measures, ideally throughout all stages of the technology's life cycle. Such evaluation should be characterised by careful attention to socio-technical factors to maximise the likelihood of successful implementation and adoption.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
There is considerable international interest in exploiting the potential of digital health care solutions, often referred to as eHealth—the use of information and communication technologies—to enhance the quality and safety of health care. Often accompanied by large costs, any large-scale expenditure on eHealth—such as electronic health records, picture archiving and communication systems, ePrescribing, associated computerized provider order entry systems, and computerized decision support systems—has tended to be justified on the grounds that these are efficient and cost-effective means for improving health care. In 2005, the World Health Assembly passed an eHealth resolution (WHA 58.28) that acknowledged, “eHealth is the cost-effective and secure use of information and communications technologies in support of health and health-related fields, including health-care services, health surveillance, health literature, and health education, knowledge and research,” and urged member states to develop and implement eHealth technologies. Since then, implementing eHealth technologies has become a main priority for many countries. For example, England has invested at least £12.8 billion in a National Programme for Information Technology for the National Health Service, and the Obama administration in the United States has committed to a US$38 billion eHealth investment in health care.
Why Was This Study Done?
Despite the wide endorsement of and support for eHealth, the scientific basis of its benefits—which are repeatedly made and often uncritically accepted—remains to be firmly established. A robust evidence-based perspective on the advantages on eHealth could help to suggest priority areas that have the greatest potential for benefit to patients and also to inform international eHealth deliberations on costs. Therefore, in order to better inform the international community, the authors systematically reviewed the published systematic review literature on eHealth technologies and evaluated the impact of these technologies on the quality and safety of health care delivery.
What Did the Researchers Do and Find?
The researchers divided eHealth technologies into three main categories: (1) storing, managing, and transmission of data; (2) clinical decision support; and (3) facilitating care from a distance. Then, implementing methods based on those developed by the Cochrane Collaboration and the NHS Service Delivery and Organisation Programme, the researchers used detailed search strategies and maps of health care quality, safety, and eHealth interventions to identify relevant systematic reviews (and related theoretical, methodological, and technical material) published between 1997 and 2010. Using these techniques, the researchers retrieved a total of 46,349 references from which they identified 108 reviews. The 53 reviews that the researchers finally selected (and critically reviewed) provided the main evidence base for assessing the impact of eHealth technologies in the three categories selected.
In their systematic review of systematic reviews, the researchers included electronic health records and picture archiving communications systems in their evaluation of category 1, computerized provider (or physician) order entry and e-prescribing in category 2, and all clinical information systems that, when used in the context of eHealth technologies, integrate clinical and demographic patient information to support clinician decision making in category 3.
The researchers found that many of the clinical claims made about the most commonly used eHealth technologies were not substantiated by empirical evidence. The evidence base in support of eHealth technologies was weak and inconsistent and importantly, there was insubstantial evidence to support the cost-effectiveness of these technologies. For example, the researchers only found limited evidence that some of the many presumed benefits could be realized; importantly, they also found some evidence that introducing these new technologies may on occasions also generate new risks such as prescribers becoming over-reliant on clinical decision support for e-prescribing, or overestimate its functionality, resulting in decreased practitioner performance.
What Do These Findings Mean?
The researchers found that despite the wide support for eHealth technologies and the frequently made claims by policy makers when constructing business cases to raise funds for large-scale eHealth projects, there is as yet relatively little empirical evidence to substantiate many of the claims made about eHealth technologies. In addition, even for the eHealth technology tools that have proven to be successful, there is little evidence to show that such tools would continue to be successful beyond the contexts in which they were originally developed. Therefore, in light of the lack of evidence in relation to improvements in patient outcomes, as well as the lack of evidence on their cost-effectiveness, the authors say that future eHealth technologies should be evaluated against a comprehensive set of measures, ideally throughout all stages of the technology's life cycle, and include socio-technical factors to maximize the likelihood of successful implementation and adoption in a given context. Furthermore, it is equally important that eHealth projects that have already been commissioned are subject to rigorous, multidisciplinary, and independent evaluation.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000387.
The authors' broader study is: Car J, Black A, Anandan C, Cresswell K, Pagliari C, McKinstry B, et al. (2008) The Impact of eHealth on the Quality and Safety of Healthcare. Available at: http://www.haps.bham.ac.uk/publichealth/cfhep/001.shtml
More information is available on the World Health Assembly eHealth resolution
The World Health Organization provides information at the Global Observatory on eHealth, as well as a global insight into eHealth developments
The European Commission provides Information on eHealth in Europe and some examples of good eHealth practice
More information is provided on NHS Connecting for Health
doi:10.1371/journal.pmed.1000387
PMCID: PMC3022523  PMID: 21267058
4.  Effectiveness and Cost Effectiveness of Expanding Harm Reduction and Antiretroviral Therapy in a Mixed HIV Epidemic: A Modeling Analysis for Ukraine 
PLoS Medicine  2011;8(3):e1000423.
A cost-effectiveness study by Sabina Alistar and colleagues evaluates the effectiveness and cost effectiveness of different levels of investment in methadone, ART, or both, in the mixed HIV epidemic in Ukraine.
Background
Injection drug use (IDU) and heterosexual virus transmission both contribute to the growing mixed HIV epidemics in Eastern Europe and Central Asia. In Ukraine—chosen in this study as a representative country—IDU-related risk behaviors cause half of new infections, but few injection drug users (IDUs) receive methadone substitution therapy. Only 10% of eligible individuals receive antiretroviral therapy (ART). The appropriate resource allocation between these programs has not been studied. We estimated the effectiveness and cost-effectiveness of strategies for expanding methadone substitution therapy programs and ART in mixed HIV epidemics, using Ukraine as a case study.
Methods and Findings
We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs using opiates, and IDUs on methadone substitution therapy, stratified by HIV status, and populated it with data from the Ukraine. We considered interventions expanding methadone substitution therapy, increasing access to ART, or both. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost-effectiveness. Without incremental interventions, HIV prevalence reached 67.2% (IDUs) and 0.88% (non-IDUs) after 20 years. Offering methadone substitution therapy to 25% of IDUs reduced prevalence most effectively (to 53.1% IDUs, 0.80% non-IDUs), and was most cost-effective, averting 4,700 infections and adding 76,000 QALYs compared with no intervention at US$530/QALY gained. Expanding both ART (80% coverage of those eligible for ART according to WHO criteria) and methadone substitution therapy (25% coverage) was the next most cost-effective strategy, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy and averting 8,300 infections versus no intervention. Expanding only ART (80% coverage) added 38,000 QALYs at US$2,240/QALY gained versus the methadone substitution therapy-only strategy, and averted 4,080 infections versus no intervention. Offering ART to 80% of non-IDUs eligible for treatment by WHO criteria, but only 10% of IDUs, averted only 1,800 infections versus no intervention and was not cost effective.
Conclusions
Methadone substitution therapy is a highly cost-effective option for the growing mixed HIV epidemic in Ukraine. A strategy that expands both methadone substitution therapy and ART to high levels is the most effective intervention, and is very cost effective by WHO criteria. When expanding ART, access to methadone substitution therapy provides additional benefit in infections averted. Our findings are potentially relevant to other settings with mixed HIV epidemics.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
HIV epidemics in Eastern Europe and Central Asia are mainly driven by increasing use of injection drugs combined with heterosexual transmission. In the Ukraine, in 2007, there were 82,000 officially registered people living with HIV—three times the number registered in 1999—and an estimated 395,000 HIV infected adults. The epidemic in Ukraine, like other countries in the region, is concentrated in at-risk populations, particularly people who inject drugs: in 2007, an estimated 390,000 Ukrainians were injecting drugs, an increase in drug use over the previous decade, not only in Ukraine, but in other former USSR states, owing to the easy availability of precursors for injection drugs in a climate of economic collapse.
The common practices of people who inject drugs in Ukraine and in other countries in the region, such as social injecting, syringe sharing, and using common containers, increase the risk of transmitting HIV. Public health interventions such as needle exchange can limit these risk factors and have been gradually implemented in these countries. In 2007, Ukraine approved the use of methadone substitution therapy and the current target is for 11,000 people who inject drugs to be enrolled in substitution therapy by 2011. Furthermore, since treatment for HIV-infected individuals is also necessary, national HIV control plans included a target of 90% antiretroviral therapy (ART) coverage by 2010 but in 2007 less than 10% of the 91,000 eligible people received treatment. Although the number of people who inject drugs and who receive ART is unknown, physicians are often reluctant to treat people who inject drugs using ART owing to alleged poor compliance.
Why Was This Study Done?
As resources for HIV interventions in the region are limited, it is important to investigate the appropriate balance between investments in methadone substitution therapy and ART in order to maximize benefits to public health. Several studies have analyzed the cost effectiveness of methadone substitution therapy in similar settings but have not considered tradeoffs between ART and methadone substitution therapy. Therefore, to provide insights into the appropriate public health investment in methadone substitution therapy and ART in Ukraine, the researchers evaluated the public health effectiveness and cost effectiveness of different strategies for scaling up methadone substitution therapy and/or expanding ART.
What Did the Researchers Do and Find?
The researchers developed a model to accommodate different population groups: people who inject drugs on substitution therapy with methadone; people who inject opiates and do not take any substitution therapy; and people who do not inject any drugs, hence do not need substitution therapy. The researchers inputted Ukraine country-level data into this model and used current HIV trends in Ukraine to make rational assumptions on possible future trends and scenarios. They considered scenarios expanding methadone substitution therapy availability, increasing acces to ART, or both. Then, the researchers measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost effectiveness for the different scenarios. They found that after 20 years, HIV prevalence reached 67.2% in people who inject drugs and 0.88% in people who do not inject drugs without further interventions. Offering methadone substitution therapy to 25% of people who inject drugs was the most effective strategy in reducing prevalence of HIV and was also the most cost effective, averting 4,700 infections and adding 75,700 QALYs versus the status quo at $530/QALY gained. Expanding both methadone substitution therapy and ART was also a highly cost effective option, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy. Offering ART to 80% of eligible people who did not inject drugs, and 10% of people who injected drugs averted only 1,800 infections, and added 76,400 QALYs at $1,330/QALY gained.
What Do These Findings Mean?
The results show that methadone substitution-focused therapeutic scenarios are the most cost effective, and that benefits increase with the scale of the project, even among people who do not inject drugs. This makes a methadone substitution strategy a highly cost-effective option for addressing the growing HIV epidemic in Ukraine. Therefore, if it is not feasible to invest in large-scale methadone substitution programs for any reason, political circumstances for example, providing as much methadone substitution as is acceptable is still desirable. While substitution therapy appears to avert the most HIV infections, expanded ART provides the largest total increase in QALYs. Thus, methadone substitution therapy and ART offer complementary benefits. Because the HIV epidemic in Ukraine is representative of the HIV epidemic in Eastern Europe and Central Asia, the cost-effective strategies that the researchers have identified may help inform all decision makers faced with a mixed HIV epidemic.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000423.
Alliance provides information on its work supporting community action on AIDS in Ukraine
USAID provides an HIV/AIDS Health Profile for Ukraine
UNICEF provides information about its activities to help Ukraine fight rising HIV/AIDS infection rates
International Harm Reduction Association provides information about the status of harm reduction interventions such as methadone substitution therapy around the world
doi:10.1371/journal.pmed.1000423
PMCID: PMC3046988  PMID: 21390264
5.  The Potential Impact of Pre-Exposure Prophylaxis for HIV Prevention among Men Who Have Sex with Men and Transwomen in Lima, Peru: A Mathematical Modelling Study 
PLoS Medicine  2012;9(10):e1001323.
Gabriela Gomez and colleagues developed a mathematical model of the HIV epidemic among men who have sex with men and transwomen in Lima, Peru to explore whether HIV pre-exposure prophylaxis could be a cost-effective addition to existing HIV prevention strategies.
Background
HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations.
Methods and Findings
We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a “conditional efficacy” parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036–US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained.
Conclusions
A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Without a vaccine, the only ways to halt the global HIV epidemic are prevention strategies that reduce transmission of the HIV virus. Up until recently, behavioral strategies such as condom use and reduction of sexual partners have been at the center of HIV prevention. In the past few years, several biological prevention measures have also been shown to be effective in reducing (though not completely preventing) HIV transmission. These include male circumcision, treatment for prevention (giving antiretroviral drugs to HIV-infected people, before they need it for their own health, to reduce their infectiousness) and pre-exposure prophylaxis (or PrEP), in which HIV-negative people use antiretroviral drugs to protect themselves from infection. One PrEP regimen (a daily pill containing two different antiretrovirals) has been shown in a clinical trial to reduce new infections by 44% in of men who have sex with men (MSM). In July 2012, the US Food and Drug Administration approved this PrEP regimen to reduce the risk of HIV infection in uninfected men and women who are at high risk of HIV infection and who may engage in sexual activity with HIV-infected partners. The approval makes it clear that PrEP needs to be used in combination with safe sex practices.
Why Was This Study Done?
Clinical trials have shown that PrEP can reduce HIV infections among participants, but they have not examined the consequences PrEP could have at the population level. Before decision-makers can decide whether to invest in PrEP programs, they need to know about the costs and benefits at the population level. Besides the price of the drug itself, the costs include HIV testing before starting PrEP, as well as regular tests thereafter. The health benefits of reducing new HIV infections are calculated in “disability-adjusted life years” (or DALYs) averted. One DALY is equal to one year of healthy life lost. Other benefits include future savings in lifelong HIV/AIDS treatment for every person whose infection is prevented by PrEP.
This study estimates the potential costs and health benefits of several hypothetical PrEP roll-out scenarios among the community of MSM in Lima, Peru. The scientists chose this community because many of the participants in the clinical trial that showed that PrEP can reduce infections came from this community, and they therefore have some knowledge on how PrEP affects HIV infection rates and behavior in this population. Because the HIV epidemic in Lima is concentrated among MSM, similar to most of Latin America and several other developed countries, the results might also be relevant for the evaluation of PrEP in other places.
What Did the Researchers Do and Find?
For their scenarios, the researchers looked at “high coverage” and “low coverage” scenarios, in which 20% and 5% of uninfected individuals use PrEP, respectively. They also divided the MSM community into those at lower risk of becoming infected and those at higher risk. The latter group consisted of transwomen at higher risk (transsexuals and transvestites with many sexual partners) and male sex workers. In a “uniform coverage” scenario, PrEP is equally distributed among all MSM. “Prioritized scenarios” cover transwomen at higher risk and sex workers preferentially. Two additional important factors for the estimated benefits are treatment adherence (i.e., whether people take the pills they have been prescribed faithfully over long periods of time even though they are not sick) and changes in risk behavior (i.e., whether the perceived protection provided by PrEP leads to more unprotected sex).
The cost estimates for PrEP included the costs of the drug itself and HIV tests prior to PrEP prescription and at three-month intervals thereafter, as well as outreach and counseling services and condom and lubricant promotion and provision.
To judge whether under the various scenarios PrEP is cost-effective, the researchers applied two commonly used but different cost-effectiveness thresholds. The World Health Organization's WHO-CHOICE initiative considers an intervention cost-effective if its cost is less than three times the gross domestic product (GDP) per capita per DALY averted. For Peru, this means an intervention should cost less than US$16,302 per DALY. The World Bank has more stringent criteria: it considers an intervention cost-effective for a middle-income country like Peru if it costs less than US$500 per DALY averted.
The researchers estimate that PrEP is cost-effective in Lima's MSM population for most scenarios by WHO-CHOICE guidelines. Only scenarios that prioritize PrEP to those most likely to become infected (i.e., transwomen at higher risk and sex workers) are cost-effective (and only barely) by the more stringent World Bank criteria. If the savings on antiretroviral drugs to treat people with HIV (those who would have become infected without PrEP) are included in the calculation, most scenarios become cost-effective, even under World Bank criteria.
The most cost-effective scenario, namely, having a modest coverage of 5%, prioritizing PrEP to transwomen at higher risk and sex workers, and assuming fairly high adherence levels among PrEP recipients, is estimated to avert about 8% of new infections among this community over ten years.
What Do these Findings Mean?
These findings suggest that under some circumstances, PrEP could be a cost-effective tool to reduce new HIV infections. However, as the researchers discuss, PrEP is expensive and only partly effective. Moreover, its effectiveness depends on two behavioral factors—adherence to a strict drug regimen and continued practicing of safe sex—both of which remain hard to predict. As a consequence, PrEP alone is not a valid strategy to prevent new HIV infections. It needs instead to be considered as one of several available tools. If and when PrEP is chosen as part of an integrated prevention strategy will depend on the specific target population, the overall funds available, and how well its cost-effectiveness compares with other prevention measures.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001323.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and a section on PrEP
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including HIV prevention
AVAC Global Advocacy for HIV Prevention provides up-to-date information on HIV prevention, including PrEP
The US Centers for Disease Control and Prevention also has information on PrEP
The World Health Organization has a page on its WHO-CHOICE criteria for cost-effectiveness
doi:10.1371/journal.pmed.1001323
PMCID: PMC3467261  PMID: 23055836
6.  Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis 
PLoS Medicine  2012;9(9):e1001316.
David Boulware and colleagues assess the cost effectiveness of different treatment strategies in low- and middle-income countries for cryptococcal meningitis, one of the most common opportunistic infections of people with HIV.
Background
Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.
Methods and Findings:
We conducted a decision analysis to estimate the incremental cost-effectiveness ratio (ICER) of six CM induction regimens: fluconazole (800–1,200 mg/d) monotherapy, fluconazole + flucytosine (5FC), short-course amphotericin (7-d) + fluconazole, 14-d of amphotericin alone, amphotericin + fluconazole, and amphotericin + 5FC. We computed actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries. A systematic review of cryptococcal treatment trials in resource-limited areas summarized 10-wk survival outcomes. We modeled one-year survival based on South African, Ugandan, and Thai CM outcome data, and survival beyond one-year on Ugandan and Thai data. Quality-adjusted life years (QALYs) were determined and used to calculate the cost-effectiveness ratio and ICER. The cost of hospital care ranged from $154 for fluconazole monotherapy to $467 for 14 d of amphotericin + 5FC. Based on 18 studies investigating outcomes for HIV-infected individuals with CM in resource-limited settings, the estimated mean one-year survival was lowest for fluconazole monotherapy, at 40%. The cost-effectiveness ratio ranged from $20 to $44 per QALY. Overall, amphotericin-based regimens had higher costs but better survival. Short-course amphotericin (1 mg/kg/d for 7 d) with fluconazole (1,200 mg/d for14 d) had the best one-year survival (66%) and the most favorable cost-effectiveness ratio, at $20.24/QALY, with an ICER of $15.11 per additional QALY over fluconazole monotherapy. The main limitation of this study is the pooled nature of a systematic review, with a paucity of outcome data with direct comparisons between regimens.
Conclusions
Short-course (7-d) amphotericin induction therapy coupled with high-dose (1,200 mg/d) fluconazole is “very cost effective” per World Health Organization criteria and may be a worthy investment for policy-makers seeking cost-effective clinical outcomes. More head-to-head clinical trials are needed on treatments for this neglected tropical disease.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Cryptococcal meningitis, a fungal infection of the membranes around the brain and spinal cord, affects about a million people every year (most of them living in sub-Saharan Africa and Southeast Asia) and kills about 640,000 people annually. People become infected with Cryptococcus neoformans, the fungus that causes cryptococcal meningitis and which is found in soil and dirt, by breathing it in. In healthy individuals, infection rarely causes disease. But in people living with AIDS, whose immune system has been damaged by HIV infection, and in people whose immune system is compromised for other reasons, the fungus can invade and damage many organs, including the brain. Cryptococcal meningitis, the symptoms of which include fever, stiff neck, headache, and vomiting, is diagnosed by looking for the fungus in fluid taken from the spinal cord in a procedure called a lumbar puncture. Cryptococcal meningitis is treated with antifungal drugs such as amphotericin, fluconazole, and flucytosine (induction therapy); recurrence of the infection is prevented by taking fluconazole daily for life or until the immune system recovers.
Why Was This Study Done?
The World Health Organization (WHO) recommends a 14-day regimen of intravenous (injected) amphotericin and oral flucytosine or fluconazole for induction therapy of cryptococcal meningitis. Unfortunately, this regimen is impractical in many resource-limited settings because of the cost of the drugs and hospital care and the need for intensive monitoring—amphotericin is extremely toxic. Consequently, high-dose fluconazole monotherapy is the usual treatment for cryptococcal meningitis in resource-limited countries, although this regimen is much less effective. Another regimen that has improved survival in trials is flucytosine with fluconazole for two weeks. However, flucytosine is very expensive and is not licensed in most sub-Saharan African countries. Stakeholders in developing countries badly need guidance, therefore, on which induction treatment for cryptococcal meningitis they should recommend to optimize outcomes in their particular countries. In this cost-effectiveness analysis (a study that compares the costs and health effects of different interventions), the researchers use costs in Uganda to estimate the survival, cost, and cost per benefit associated with various induction treatments for cryptococcal meningitis in HIV-infected patients.
What Did the Researchers Do and Find?
The researchers calculated the overall cost of six induction treatments using 2012 healthcare costs in Uganda for medications, supplies, and hospital care, and average laboratory costs for monitoring treatment from three African countries. They used data from published trials of cryptococcal meningitis treatment in resource-limited areas to estimate ten-week and one-year survival, life expectancy, and quality-adjusted life years (QALYs, the number of years of life added by an intervention, adjusted for the quality of life) for each intervention. Finally, they calculated the cost-effectiveness ratio (cost per QALY gained) and the incremental cost effectiveness ratio (ICER, the additional cost of a treatment strategy compared to fluconazole monotherapy divided by the incremental improvement in QALYs) for each intervention. The estimated costs per person for each induction treatment strategy ranged from US$154 for 14 days of fluconazole monotherapy to US$467 for 14 days of amphotericin plus flucytosine. Estimated average one-year survival was lowest for fluconazole (40%) and highest for short-course (seven days) amphotericin plus 14 days of fluconazole (66%), similar to other amphotericin-based treatments. Cost-effectiveness ratios ranged from US$20 per QALY for short-course amphotericin plus fluconazole to US$44 per QALY for 14 days of amphotericin plus flucytosine. Short-course amphotericin plus fluconazole had the lowest ICER (US$15.11 per additional QALY over fluconazole monotherapy).
What Do These Findings Mean?
These findings suggest that, among the treatments investigated, a seven-day course of amphotericin with high-dose fluconazole for at least two weeks is the most cost-effective induction treatment for cryptococcal meningitis in Uganda. Although this result should be generalizable to other African countries, it needs to be treated with caution because very few trials have actually looked at the clinical effectiveness of this particular regimen. While short short-course amphotericin appears to be substantially more effective than fluconazole monotherapy, large-scale trials comparing short-course amphotericin regimens with more traditional 14-day regimens in resource-limited countries must be undertaken before short-course amphotericin-based treatments are adopted. Notably, however, if these trials confirm that survival with short-course amphotericin with fluconazole is about 30% better than with fluconazole alone, the researchers calculate that moving to short-course amphotericin could save about 150,000 lives every year in sub-Saharan Africa at a cost of US$220 per life saved.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001316.
This study is further discussed in a PLOS Medicine Perspective by Andrew Farlow
Preventcrypto.org provides a clearinghouse for updated guidelines for cryptococcal diagnosis and treatment.
The US Centers for Disease Control and Prevention provides information on Cryptococcus neoformans and a training manual called the Cryptococcal Screening Program Training Manual for Healthcare Providers
NAM/aidsmap provides information about all aspects of infection with Cryptococcus neoformans, including a personal story about cryptococcal meningitis
AIDS InfoNet has a fact sheet on cryptococcal meningitis (in several languages)
The not-for-profit organization Project Inform, which provides information, inspiration, and advocacy for people with HIV/AIDS and hepatitis C (in English and Spanish), has a fact sheet on cryptococcal meningitis
The MedlinePlus encyclopedia has a page on cryptococcal meningitis (in English and Spanish)
doi:10.1371/journal.pmed.1001316
PMCID: PMC3463510  PMID: 23055838
7.  Robotic-Assisted Minimally Invasive Surgery for Gynecologic and Urologic Oncology 
Executive Summary
Objective
An application was received to review the evidence on the ‘The Da Vinci Surgical System’ for the treatment of gynecologic malignancies (e.g. endometrial and cervical cancers). Limitations to the current standard of care include the lack of trained physicians on minimally invasive surgery and limited access to minimally invasive surgery for patients. The potential benefits of ‘The Da Vinci Surgical System’ include improved technical manipulation and physician uptake leading to increased surgeries, and treatment and management of these cancers.
The demand for robotic surgery for the treatment and management of prostate cancer has been increasing due to its alleged benefits of recovery of erectile function and urinary continence, two important factors of men’s health. The potential technical benefits of robotic surgery leading to improved patient functional outcomes are surgical precision and vision.
Clinical Need
Uterine and cervical cancers represent 5.4% (4,400 of 81,700) and 1.6% (1,300 of 81,700), respectively, of incident cases of cancer among female cancers in Canada. Uterine cancer, otherwise referred to as endometrial cancer is cancer of the lining of the uterus. The most common treatment option for endometrial cancer is removing the cancer through surgery. A surgical option is the removal of the uterus and cervix through a small incision in the abdomen using a laparoscope which is referred to as total laparoscopic hysterectomy. Risk factors that increase the risk of endometrial cancer include taking estrogen replacement therapy after menopause, being obese, early age at menarche, late age at menopause, being nulliparous, having had high-dose radiation to the pelvis, and use of tamoxifen.
Cervical cancer occurs at the lower narrow end of the uterus. There are more treatment options for cervical cancer compared to endometrial cancer, however total laparoscopic hysterectomy is also a treatment option. Risk factors that increase the risk for cervical cancer are multiple sexual partners, early sexual activity, infection with the human papillomavirus, and cigarette smoking, whereas barrier-type of contraception as a risk factor decreases the risk of cervical cancer.
Prostate cancer is ranked first in men in Canada in terms of the number of new cases among all male cancers (25,500 of 89,300 or 28.6%). The impact on men who develop prostate cancer is substantial given the potential for erectile dysfunction and urinary incontinence. Prostate cancer arises within the prostate gland, which resides in the male reproductive system and near the bladder. Radical retropubic prostatectomy is the gold standard treatment for localized prostate cancer. Prostate cancer affects men above 60 years of age. Other risk factors include a family history of prostate cancer, being of African descent, being obese, consuming a diet high in fat, physical inactivity, and working with cadium.
The Da Vinci Surgical System
The Da Vinci Surgical System is a robotic device. There are four main components to the system: 1) the surgeon’s console, where the surgeon sits and views a magnified three-dimensional image of the surgical field; 2) patient side-cart, which sits beside the patient and consists of three instrument arms and one endoscope arm; 3) detachable instruments (endowrist instruments and intuitive masters), which simulate fine motor human movements. The hand movements of the surgeon’s hands at the surgeon’s console are translated into smaller ones by the robotic device and are acted out by the attached instruments; 4) three-dimensional vision system: the camera unit or endoscope arm. The main advantages of use of the robotic device are: 1) the precision of the instrument and improved dexterity due to the use of “wristed” instruments; 2) three-dimensional imaging, with improved ability to locate blood vessels, nerves and tissues; 3) the surgeon’s console, which reduces fatigue accompanied with conventional laparoscopy surgery and allows for tremor-free manipulation. The main disadvantages of use of the robotic device are the costs including instrument costs ($2.6 million in US dollars), cost per use ($200 per use), the costs associated with training surgeons and operating room personnel, and the lack of tactile feedback, with the trade-off being increased visual feedback.
Research Questions
For endometrial and cervical cancers,
1. What is the effectiveness of the Da Vinci Surgical System vs. laparoscopy and laparotomy for women undergoing any hysterectomy for the surgical treatment and management of their endometrial and cervical cancers?
2. What are the incremental costs of the Da Vinci Surgical System vs. laparoscopy and laparotomy for women undergoing any hysterectomy for the surgical treatment and management of their endometrial and cervical cancers?
For prostate cancer,
3. What is the effectiveness of robotically-assisted radical prostatectomy using the Da Vinci Surgical System vs. laparoscopic radical prostatectomy and retropubic radical prostatectomy for the surgical treatment and management of prostate cancer?
4. What are the incremental costs of robotically-assisted radical prostatectomy using the Da Vinci Surgical System vs. laparoscopic radical prostatectomy and retropubic radical prostatectomy for the surgical treatment and management of prostate cancer?
Research Methods
Literature Search
Search Strategy
A literature search was performed on May 12, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, Wiley Cochrane, CINAHL, Centre for Reviews and Dissemination/International Agency for Health Technology Assessment for studies published from January 1, 2000 until May 12, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Inclusion Criteria
English language articles (January 1, 2000-May 12, 2010)
Journal articles that report on the effectiveness or cost-effectiveness for the comparisons of interest using a primary data source (e.g. obtained in a clinical setting)
Journal articles that report on the effectiveness or cost-effectiveness for the comparisons of interest using a secondary data source (e.g. hospital- or population-based registries)
Study design and methods must be clearly described
Health technology assessments, systematic reviews, randomized controlled trials, non-randomized controlled trials and/or cohort studies, case-case studies, regardless of sample size, cost-effectiveness studies
Exclusion Criteria
Duplicate publications (with the more recent publication on the same study population included)
Non-English papers
Animal or in-vitro studies
Case reports or case series without a referent or comparison group
Studies on long-term survival which may be affected by treatment
Studies that do not examine the cancers (e.g. advanced disease) or outcomes of interest
Outcomes of Interest
For endometrial and cervical cancers,
Primary outcomes:
Morbidity factors
- Length of hospitalization
- Number of complications*
Peri-operative factors
- Operation time
- Amount of blood loss*
- Number of conversions to laparotomy*
Number of lymph nodes recovered
For prostate cancer,
Primary outcomes:
Morbidity factors
- Length of hospitalization
- Amount of morphine use/pain*
Peri-operative factors
- Operation time
- Amount of blood loss*
- Number of transfusions*
- Duration of catheterization
- Number of complications*
- Number of anastomotic strictures*
Number of lymph nodes recovered
Oncologic factors
- Proportion of positive surgical margins
Long-term outcomes
- Urinary continence
- Erectile function
Summary of Findings
Robotic use for gynecologic oncology compared to:
Laparotomy: benefits of robotic surgery in terms of shorter length of hospitalization and less blood loss. These results indicate clinical effectiveness in terms of reduced morbidity and safety, respectively, in the context of study design limitations.
The beneficial effect of robotic surgery was shown in pooled analysis for complications, owing to increased sample size.
More work is needed to clarify the role of complications in terms of safety, including improved study designs, analysis and measurement.
Laparoscopy: benefits of robotic surgery in terms of shorter length of hospitalization, less blood loss and fewer conversions to laparotomy likely owing to the technical difficulty of conventional laparoscopy, in the context of study design limitations.
Clinical significance of significant findings for length of hospitalizations and blood loss is low.
Fewer conversions to laparotomy indicate clinical effectiveness in terms of reduced morbidity.
Robotic use for urologic oncology, specifically prostate cancer, compared to:
Retropubic surgery: benefits of robotic surgery in terms of shorter length of hospitalization and less blood loss/fewer individuals requiring transfusions. These results indicate clinical effectiveness in terms of reduced morbidity and safety, respectively, in the context of study design limitations. There was a beneficial effect in terms of decreased positive surgical margins and erectile dysfunction. These results indicate clinical effectiveness in terms of improved cancer control and functional outcomes, respectively, in the context of study design limitations.
Surgeon skill had an impact on cancer control and functional outcomes.
The results for complications were inconsistent when measured as either total number of complications, pain management or anastomosis. There is some suggestion that robotic surgery is safe with respect to less post-operative pain management required compared to retropubic surgery, however improved study design and measurement of complications need to be further addressed.
Clinical significance of significant findings for length of hospitalizations is low.
Laparoscopy: benefits of robotic surgery in terms of less blood loss and fewer individuals requiring transfusions likely owing to the technical difficulty of conventional laparoscopy, in the context of study design limitations.
Clinical significance of significant findings for blood loss is low.
The potential link between less blood loss, improved visualization and improved functional outcomes is an important consideration for use of robotics.
All studies included were observational in nature and therefore the results must be interpreted cautiously.
Economic Analysis
The objective of this project was to assess the economic impact of robotic-assisted laparoscopy (RAL) for endometrial, cervical, and prostate cancers in the province of Ontario.
A budget impact analysis was undertaken to report direct costs associated with open surgery (OS), endoscopic laparoscopy (EL) and robotic-assisted laparoscopy (RAL) based on clinical literature review outcomes, to report a budget impact in the province based on volumes and costs from administrative data sets, and to project a future impact of RAL in Ontario. A cost-effectiveness analysis was not conducted because of the low quality evidence from the clinical literature review.
Hospital costs were obtained from the Ontario Case Costing Initiative (OCCI) for the appropriate Canadian Classification of Health Intervention (CCI) codes restricted to selective ICD-10 diagnostic codes after consultation with experts in the field. Physician fees were obtained from the Ontario Schedule of Benefits (OSB) after consultation with experts in the field. Fees were costed based on operation times reported in the clinical literature for the procedures being investigated. Volumes of procedures were obtained from the Ministry of Health and Long-Term Care (MOHLTC) administrative databases.
Direct costs associated with RAL, EL and OS included professional fees, hospital costs (including disposable instruments), radiotherapy costs associated with positive surgical margins in prostate cancer and conversion to OS in gynecological cancer. The total cost per case was higher for RAL than EL and OS for both gynecological and prostate cancers. There is also an acquisition cost associated with RAL. After conversation with the only supplier in Canada, hospitals are looking to spend an initial 3.6M to acquire the robotic surgical system
Previous volumes of OS and EL procedures were used to project volumes into Years 1-3 using a linear mathematical expression. Burden of OS and EL hysterectomies and prostatectomies was calculated by multiplying the number of cases for that year by the cost/case of the procedure.
The number of procedures is expected to increase in the next three years based on historical data. RAL is expected to capture this market by 65% after consultation with experts. If it’s assumed that RAL will capture the current market in Ontario by 65%, the net impact is expected to be by Year 3, 3.1M for hysterectomy and 6.7M for prostatectomy procedures respectively in the province.
RAL has diffused in the province with four surgical systems in place in Ontario, two in Toronto and two in London. RAL is a more expensive technology on a per case basis due to more expensive robot specific instrumentation and physician labour reflected by increased OR time reported in the clinical literature. There is also an upfront cost to acquire the machine and maintenance contract. RAL is expected to capture the market at 65% with project net impacts by Year 3 of 3.1M and 6.7M for hysterectomy and prostatectomy respectively.
PMCID: PMC3382308  PMID: 23074405
8.  Clinical Benefits, Costs, and Cost-Effectiveness of Neonatal Intensive Care in Mexico 
PLoS Medicine  2010;7(12):e1000379.
Joshua Salomon and colleagues performed a cost-effectiveness analysis using health and economic outcomes following preterm birth in Mexico and showed that neonatal intensive care provided high value for the money in this setting.
Background
Neonatal intensive care improves survival, but is associated with high costs and disability amongst survivors. Recent health reform in Mexico launched a new subsidized insurance program, necessitating informed choices on the different interventions that might be covered by the program, including neonatal intensive care. The purpose of this study was to estimate the clinical outcomes, costs, and cost-effectiveness of neonatal intensive care in Mexico.
Methods and Findings
A cost-effectiveness analysis was conducted using a decision analytic model of health and economic outcomes following preterm birth. Model parameters governing health outcomes were estimated from Mexican vital registration and hospital discharge databases, supplemented with meta-analyses and systematic reviews from the published literature. Costs were estimated on the basis of data provided by the Ministry of Health in Mexico and World Health Organization price lists, supplemented with published studies from other countries as needed. The model estimated changes in clinical outcomes, life expectancy, disability-free life expectancy, lifetime costs, disability-adjusted life years (DALYs), and incremental cost-effectiveness ratios (ICERs) for neonatal intensive care compared to no intensive care. Uncertainty around the results was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. In the base-case analysis, neonatal intensive care for infants born at 24–26, 27–29, and 30–33 weeks gestational age prolonged life expectancy by 28, 43, and 34 years and averted 9, 15, and 12 DALYs, at incremental costs per infant of US$11,400, US$9,500, and US$3,000, respectively, compared to an alternative of no intensive care. The ICERs of neonatal intensive care at 24–26, 27–29, and 30–33 weeks were US$1,200, US$650, and US$240, per DALY averted, respectively. The findings were robust to variation in parameter values over wide ranges in sensitivity analyses.
Conclusions
Incremental cost-effectiveness ratios for neonatal intensive care imply very high value for money on the basis of conventional benchmarks for cost-effectiveness analysis.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Most pregnancies last about 40 weeks but increasing numbers of babies are being born preterm, before they reach 37 weeks of gestation (the period during which a baby develops in its mother). In developed countries and some middle-income countries such as Mexico, improvements in the care of newborn babies (neonatal intensive care) mean that more preterm babies survive now than in the past. Nevertheless, preterm birth is still a major cause of infant death worldwide that challenges attainment of Target 5 of Millennium Development Goal 4—the reduction of the global under-five mortality rate by two-thirds of the 1990 rate by 2015 (the Millennium Development Goals, which were agreed by world leaders in 2000, aim to reduce world poverty). Furthermore, many preterm babies who survive have long-term health problems and disabilities such as cerebral palsy, deafness, or learning difficulties. The severity of these disabilities and their long-term costs to families and to society depend on the baby's degree of prematurity.
Why Was This Study Done?
Mexico recently reformed its health system in an effort to improve access to care, particularly for the poorest sections of its population, and to improve the quality of its health care. The central component of this health care reform is the System of Social Protection of Health (SSPH). The SSPH contains a family health insurance program—Seguro Popular—that aims to provide the 50 million uninsured people living in Mexico with free access to an explicit set of health care interventions. As with any insurance program, decisions have to be made about which interventions Seguro Poplar should cover. Should neonatal intensive care be covered, for example? Do the benefits of this intervention (increased survival of babies) outweigh the costs of neonatal care and of long-term care for survivors with disabilities? In other words, is neonatal intensive care cost-effective? In this study, the researchers investigate this question by estimating the clinical benefits, costs, and cost-effectiveness of neonatal intensive care in Mexico.
What Did the Researchers Do and Find?
The researchers built a decision analytic model, a mathematical model that combines evidence on the outcomes and costs of alternative treatments to help inform decisions about health care policy. They gathered data about the health outcomes of preterm births in Mexico from registers of births and deaths and from hospital discharge databases, and estimated the costs of neonatal intensive care and long-term care for disabled survivors using data from the Mexican Ministry of Health and the World Health Organization. They then applied their model, which estimates changes in parameters such as life expectancy, lifetime costs, disability-adjusted life years (DALYs; one DALY represents the loss of a year of healthy life), and incremental cost-effectiveness ratios (ICERs; the additional cost expended for each DALY averted) for neonatal intensive care compared to no intensive care, to a group of 2 million infants. Neonatal intensive care for infants born at 24–26, 27–29, and 30–33 weeks gestation prolonged life expectancy by 28, 43, and 34 years and averted 9, 15, and 12 DALYs at incremental costs of US$11,000, US$10,000, and US$3000, respectively, compared to no intensive care. The ICERs of neonatal intensive care for babies born at these times were US$1200, US$700, and US$300 per DALY averted, respectively.
What Do These Findings Mean?
Interventions with ICERs of less than a country's per capita gross domestic product (GDP) are highly cost-effective; those with ICERs of 1–3 times the per capita GDP are potentially cost-effective. Mexico's per capita GDP in 2005 was approximately US$8,200. Thus, neonatal intensive care could provide exceptional value for money in Mexico (and maybe in other middle-income countries), even for very premature babies. The accuracy of these findings inevitably depends on the assumptions used to build the decision analytic model and on the accuracy of the data fed into it, but the findings were little changed by a wide range of alterations that the researchers made to the model. Importantly, however, this cost-effectiveness analysis focuses on health and economic consequences of different intervention choices, and does not capture all aspects of well-being. Decisions regarding neonatal intensive care will need to be based on a full consideration of all relevant factors, including ethical issues, and cost-effectiveness analyses should continue to be updated as new data emerge on health outcomes and costs associated with neonatal intensive care.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000379.
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
The Nemours Foundation, another nonprofit organization for child health, also provides information on premature babies (in English and Spanish)
MedlinePlus provides links to other information on premature babies (in English and Spanish)
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development and protection around the world; it provides information on Millennium Development Goal 4 and its Childinfo website provides detailed statistics about child survival and health (some information in several languages)
A PLoS Medicine Policy Forum by Núria Homedes and Antonio Ugalde discusses health care reforms in Mexico
doi:10.1371/journal.pmed.1000379
PMCID: PMC3001895  PMID: 21179496
9.  Economic evaluation of a community based exercise programme to prevent falls 
OBJECTIVE—To assess the incremental costs and cost effectiveness of implementing a home based muscle strengthening and balance retraining programme that reduced falls and injuries in older women.
DESIGN—An economic evaluation carried out within a randomised controlled trial with two years of follow up. Participants were individually prescribed an exercise programme (exercise group, n=116) or received usual care and social visits (control group, n=117).
SETTING—17 general practices in Dunedin, New Zealand.
PARTICIPANTS—Women aged 80 years and older living in the community and invited by their general practitioner to take part.
MAIN OUTCOME MEASURES—Number of falls and injuries related to falls, costs of implementing the intervention, healthcare service costs resulting from falls and total healthcare service costs during the trial. Cost effectiveness was measured as the incremental cost of implementing the exercise programme per fall event prevented.
MAIN RESULTS—27% of total hospital costs during the trial were related to falls. However, there were no significant differences in health service costs between the two groups. Implementing the exercise programme for one and two years respectively cost $314 and $265 (1995 New Zealand dollars) per fall prevented, and $457 and $426 per fall resulting in a moderate or serious injury prevented.
CONCLUSIONS—The costs resulting from falls make up a substantial proportion of the hospital costs for older people. Despite a reduction in falls as a result of this home exercise programme there was no significant reduction in healthcare costs. However, the results reported will provide information on the cost effectiveness of the programme for those making decisions on falls prevention strategies.


Keywords: falls; exercise; elderly
doi:10.1136/jech.55.8.600
PMCID: PMC1731948  PMID: 11449021
10.  Economic evaluation of arthritis self management in primary care 
Objective To assess the cost effectiveness of a self management programme plus education booklet for arthritis in primary care.
Design Cost effectiveness and cost utility analysis from health and social care and societal perspectives alongside a randomised controlled trial.
Setting 74 general practices in the United Kingdom.
Participants 812 patients aged 50 or more with osteoarthritis of the hips or knees, or both, and pain or disability, or both.
Interventions Randomisation to either six sessions of an arthritis self management programme plus an education booklet (intervention group) or the education booklet alone (standard care control group).
Main outcome measures Total health and social care costs and total societal costs at 12 months; cost effectiveness (incremental cost effectiveness ratios and cost effectiveness acceptability curves) on basis of quality of life (SF-36, primary outcome measure), EuroQol visual analogue scale, and quality adjusted life years (QALYs).
Results At 12 months health and social care costs in the intervention group were £101 higher (95% confidence interval £3 to £176) than those in the control group because the additional costs of the arthritis self management programme did not seem to be fully offset by savings elsewhere. There were no significant differences in societal costs (which were up to 13 times the size of health and social care costs) or any of the outcomes. From the health and social care perspective the intervention was dominated by the control on the basis of QALYs (which were non-significantly lower in the intervention group) and had incremental cost effectiveness ratios between £279 and £13 473 for the other outcomes. From the societal perspective the intervention seemed superior to the control owing to non-significantly lower costs and non-significantly better outcomes on all measures except QALYs. Probabilities of the arthritis self management programme’s cost effectiveness ranged between 12% and 97% (for thresholds ranging £0 to £1000) based on one point improvements in SF-36 outcomes, but the clinical significance of this is debatable. Probabilities of cost effectiveness on the basis of the visual analogue scale and QALYs were low.
Conclusions Cost effectiveness of an arthritis self management programme is not suggested on the basis of current National Institute for Health and Clinical Excellence cost perspectives and QALY thresholds. The probability of cost effectiveness is greater when broader costs and other quality of life outcomes are considered. These results suggest that the cost effectiveness of the Department of Health’s expert patients programme cannot be assumed across all clinical conditions and that further rigorous evaluations for other conditions may be needed.
Trial registration Current Controlled Trials ISRCTN79115352.
doi:10.1136/bmj.b3532
PMCID: PMC2749163  PMID: 19773329
11.  Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti 
PLoS Medicine  2011;8(9):e1001095.
This cost-effectiveness study comparing early versus standard antiretroviral treatment (ART) for HIV, based on randomized clinical trial data from Haiti, reveals that the new WHO guidelines for early ART initiation can be cost-effective in resource-poor settings.
Background
In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial.
Methods and Findings
Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS).
Conclusions
Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests.
Trial registration
ClinicalTrials.gov NCT00120510
Please see later in the article for the Editors' Summary
Editors' Summary
Background
AIDS has killed more than 25 million people since 1981, and about 33 million people (most of them living in low- and middle-income countries) are now infected with HIV, the virus that causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (ART) became available and, for people living in affluent countries HIV/AIDS became a chronic condition. However, ART was extremely expensive and so a diagnosis of HIV infection remained a death sentence for people living in developing countries. In 2003, this situation was declared a global health emergency, and governments, international agencies, and funding bodies began to implement plans to increase ART coverage in developing countries. In 2009, more than a third of people in low- and middle-income countries who needed ART were receiving it, on the basis of guidelines that were in place at that time.
Why Was This Study Done?
Until recently, the World Health Organization (WHO) recommended that all HIV-positive patients with CD4 cell count below 200/mm3 blood or an AIDS-defining illness such as Kaposi's sarcoma should be given ART. Then, in 2009, the CIPRA HT-001 randomized clinical trial, which was undertaken in Haiti, reported that patients who started ART when their CD4 cell count was between 200 and 350 cells/mm3 (“early ART”) had a higher survival rate than patients who started ART according to the WHO guidelines (“standard ART”). As a result, WHO now recommends that ART is started in HIV-infected people when their CD4 cell count falls below 350 cells/mm3. But is this new recommendation cost-effective? Do its benefits outweigh its costs? Policy-makers need to know the cost-effectiveness of interventions so that they can allocate their limited resources wisely. A medical intervention is generally considered cost-effective if it costs less than three times a country's per capita gross domestic product (GDP) per year of life saved (YLS). In this study, the researchers assess the cost-effectiveness of early versus standard ART in the CIPRA HT-001 trial.
What Did the Researchers Do and Find?
The researchers used trial data on the use and costs of ART, other medications, laboratory tests, outpatient visits, radiography, procedures, and hospital services to evaluate the costs associated with early ART and standard ART among the 816 CIPRA HT-001 trial participants. The average total costs per patient after a maximum of 3 years treatment were US$1,381 for early ART and US$1,033 for standard ART. These figures dropped to US$1,158 and US$979, respectively, when the costs of research-related tests without clinical benefit were excluded. Patients who received early ART had higher average costs for ART but lower costs for other aspects of their treatment than patients who received standard ART. The incremental cost-effectiveness ratio after 3 years for early ART compared to standard ART was US$3,975/YLS if the costs of research-related tests were included in the calculation. That is, the cost of saving one year of life by starting ART early instead of when the CD4 cell count dropped below 200/mm3 was nearly US$4,000. Importantly, exclusion of the costs of research-related tests reduced the incremental cost-effectiveness ratio of early ART compared to standard ART to US$2,050/YLS.
What Do These Findings Mean?
Because the Haitian GDP per capita is US$785, these findings suggest that, in Haiti, early ART is a cost-effective intervention over a 3-year period. That is, the incremental cost per year of life saved of early ART compared to standard ART after exclusion of research-related tests is less than three times Haiti's per capita GDP. The researchers note that their incremental cost-effectiveness ratios are likely to be conservative because they did not consider the clinical benefits of early ART that continue beyond 3 years—early ART is associated with lower longer-term mortality than standard ART—or the effect of early ART on disability and quality of life. Cost-effectiveness studies now need to be undertaken at different sites to determine whether these findings are generalizable but, for now, this cost-effectiveness study suggests that the new WHO guidelines for ART initiation can be cost-effective in resource-poor settings, information that should help policy-makers in developing countries allocate their limited resources.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001095.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the HIV/AIDS in the Caribbean, and on HIV/AIDS treatment and care (in English and Spanish)
WHO provides information about universal access to AIDS treatment (in English, French and Spanish); its 2010 ART guidelines can be downloaded
More information about the CIPRA HT-001 clinical trial is available
Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline
More information about GHESKIO is available from Weill Cornell Global Health
doi:10.1371/journal.pmed.1001095
PMCID: PMC3176754  PMID: 21949643
12.  The cost-effectiveness of exercise referral schemes 
BMC Public Health  2011;11:954.
Background
Exercise referral schemes (ERS) aim to identify inactive adults in the primary care setting. The primary care professional refers the patient to a third party service, with this service taking responsibility for prescribing and monitoring an exercise programme tailored to the needs of the patient. This paper examines the cost-effectiveness of ERS in promoting physical activity compared with usual care in primary care setting.
Methods
A decision analytic model was developed to estimate the cost-effectiveness of ERS from a UK NHS perspective. The costs and outcomes of ERS were modelled over the patient's lifetime. Data were derived from a systematic review of the literature on the clinical and cost-effectiveness of ERS, and on parameter inputs in the modelling framework. Outcomes were expressed as incremental cost per quality-adjusted life-year (QALY). Deterministic and probabilistic sensitivity analyses investigated the impact of varying ERS cost and effectiveness assumptions. Sub-group analyses explored the cost-effectiveness of ERS in sedentary people with an underlying condition.
Results
Compared with usual care, the mean incremental lifetime cost per patient for ERS was £169 and the mean incremental QALY was 0.008, generating a base-case incremental cost-effectiveness ratio (ICER) for ERS at £20,876 per QALY in sedentary individuals without a diagnosed medical condition. There was a 51% probability that ERS was cost-effective at £20,000 per QALY and 88% probability that ERS was cost-effective at £30,000 per QALY. In sub-group analyses, cost per QALY for ERS in sedentary obese individuals was £14,618, and in sedentary hypertensives and sedentary individuals with depression the estimated cost per QALY was £12,834 and £8,414 respectively. Incremental lifetime costs and benefits associated with ERS were small, reflecting the preventative public health context of the intervention, with this resulting in estimates of cost-effectiveness that are sensitive to variations in the relative risk of becoming physically active and cost of ERS.
Conclusions
ERS is associated with modest increase in lifetime costs and benefits. The cost-effectiveness of ERS is highly sensitive to small changes in the effectiveness and cost of ERS and is subject to some significant uncertainty mainly due to limitations in the clinical effectiveness evidence base.
doi:10.1186/1471-2458-11-954
PMCID: PMC3268756  PMID: 22200193
13.  Feasibility and Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis: A Cohort Study in the Philippines 
PLoS Medicine  2006;3(9):e352.
Background
Multidrug-resistant tuberculosis (MDR-TB) is an important global health problem, and a control strategy known as DOTS-Plus has existed since 1999. However, evidence regarding the feasibility, effectiveness, cost, and cost-effectiveness of DOTS-Plus is still limited.
Methodology/Principal Findings
We evaluated the feasibility, effectiveness, cost, and cost-effectiveness of a DOTS-Plus pilot project established at Makati Medical Center in Manila, the Philippines, in 1999. Patients with MDR-TB are treated with regimens, including first- and second-line drugs, tailored to their drug susceptibility pattern (i.e., individualised treatment). We considered the cohort enrolled between April 1999 and March 2002. During this three-year period, 118 patients were enrolled in the project; 117 were considered in the analysis. Seventy-one patients (61%) were cured, 12 (10%) failed treatment, 18 (15%) died, and 16 (14%) defaulted. The average cost per patient treated was US$3,355 from the perspective of the health system, of which US$1,557 was for drugs, and US$837 from the perspective of patients. The mean cost per disability-adjusted life year (DALY) gained by the DOTS-Plus project was US$242 (range US$85 to US$426).
Conclusions
Treatment of patients with MDR-TB using the DOTS-Plus strategy and individualised drug regimens can be feasible, comparatively effective, and cost-effective in low- and middle-income countries.
Evaluation of 117 patients enrolled in a DOTS-Plus pilot project in the Philippines showed that in this setting the strategy is feasible.
Editors' Summary
Background.
Tuberculosis (TB) causes the death of some 2 million people each year. An estimated one in three people worldwide are infected with Mycobacterium tuberculosis, the bacterium that causes the disease. Because single-drug treatment leads to treatment failure and antibiotic resistance, treatment for active TB is complicated, usually involving four different antibiotics, at least two of which are continued for six months or more. The World Health Organization (WHO) recommends a specific strategy (DOTS) for diagnosing and treating TB (see Web link below).
The DOTS approach includes standard regimens of first-line drugs which cure about 90% of patients with drug-susceptible TB, and which cost as little as US$10 per patient. Unfortunately, TB resistance to at least two of the most effective DOTS drugs has developed at sites in both industrialized and developing countries, causing approximately 460,000 cases of multidrug-resistant TB (MDR-TB) per year. Second-line antibiotics, which tend to be more expensive or more difficult to take, can effectively treat many cases of MDR-TB. “DOTS-Plus” programmes, which use combinations of first- and second-line drugs to treat MDR-TB, are therefore becoming increasingly important in controlling TB worldwide. A recent study found DOTS-Plus strategies to be cost-effective in Peru, but cure rates of MDR-TB were relatively low.
Why Was This Study Done?
Because the use of second-line antibiotics is costly and the treatment of MDR-TB has a higher failure rate than that of fully drug-susceptible TB, policymakers responsible for allocation of limited healthcare resources need information on how well DOTS-Plus programmes work and how much they cost to operate. This study was undertaken to assess the feasibility, effectiveness, and cost-effectiveness of a DOTS-Plus project in the Philippines, a lower middle–income country with a high rate of TB and approximately 25,000 cases of MDR-TB.
What Did the Researchers Do and Find? 
The researchers reported on a DOTS-Plus pilot project at Makati Medical Center in Manila, analyzing information from 118 patients enrolled in the project between 1999 and 2002. The diagnosis of MDR-TB was based on laboratory culture and antibiotic resistance testing of specimens from patients who had continued symptoms of TB following DOTS treatment, or other evidence of possible MDR-TB. Patients were treated with five-drug combinations individually selected based on resistance testing results, and administered under direct observation. After cultures had remained consistently negative for six months, patients were switched to a four-drug regimen with intermittent clinic observation until cultures remained negative for at least 18 months.
Cost-effectiveness was assessed by comparing the costs and effects of the project to the costs and effects that would have applied in the absence of the project, namely, no treatment of MDR-TB (except what patients could have purchased privately), or standard first-line DOTS treatment (which would not cure the majority of patients with MDR-TB, and is associated with a high chance of relapse in those who do appear cured). Costs of the DOTS-Plus project were based on expenditure records, project records, and interviews with staff, patients, and funding agencies. Effects of the project were based on treatment outcomes observed among enrolled patients, as well as on data on long-term outcomes among patients treated for MDR-TB in the US who were followed for up to ten years. Treatment costs for the situation in which no DOTS-Plus project exists were estimated using national data reported to WHO, as well as questionnaires administered to local patients in whom DOTS treatment had failed. Treatment outcomes where DOTS-Plus is not available were estimated from studies done in other TB-affected countries.
The researchers found that the cure rate of MDR-TB in this project was 61%. The cost per patient treated was US$4,192. They also calculated that the cost-effectiveness of the DOTS-Plus strategy was US$242 per disability-adjusted life year (DALY) gained, of which US$179 was paid by the healthcare system.
What Do These Findings Mean?
The cure rate for MDR-TB in this project compares favourably to rates in other resource-limited settings where second-line TB drugs are used, and is much higher than in areas where these drugs are not available. From the standpoint of efficacy and patient well-being, then, this study supports the necessity of DOTS-Plus treatment. In purely economic terms, the cost of US$200–US$250 per DALY gained is cost-effective in comparison with other healthcare interventions. Specifically, because the gross national income per person in the Philippines is US$1,080, someone who can return to work following MDR-TB treatment costing US$250 per year gained of working life will provide work that is worth four times more, on average, than the cost of the treatment.
Although this study provides encouraging confirmation that DOTS-Plus programmes can be effective and cost-effective in a resource-limited setting, these findings are subject to several limitations. First, the data used to estimate treatment outcomes and the costs associated with chronic MDR-TB when DOTS-Plus treatment is not available were limited. Also, the pilot project in this study included only 118 of 171 eligible patients, leaving open the possibility that the other 53 patients might have had different outcomes. In addition, the long-term relapse rate in the treated patients is unknown. Finally, the conclusion that one model programme is effective does not mean that other programmes will do well under less favourable circumstances. Nonetheless, as MDR-TB continues to spread in the developing world, a good example is good news. A Perspective by Paul Garner and colleagues in this issue of PLoS Medicine (DOI: 10.1371/journal.pmed.0030350) discusses the study further.
Additional Information. 
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030352.
Basic information about tuberculosis can be found on the Web site of the US National Institute of Allergy and Infectious Diseases (NIAID)
The Web site of the World Health Organization's Stop TB department outlines both the DOTS and DOTS-Plus strategies
TB Alert, a UK-based charity that promotes TB awareness worldwide, has information on TB in several European, African, and Asian languages
doi:10.1371/journal.pmed.0030352
PMCID: PMC1564168  PMID: 16968123
14.  Serological Testing Versus Other Strategies for Diagnosis of Active Tuberculosis in India: A Cost-Effectiveness Analysis 
PLoS Medicine  2011;8(8):e1001074.
This cost-effectiveness study shows that sputum smear microscopy is the most cost-effective test for active tuberculosis (TB) in India, and liquid culture plus microscopy is more cost-effective for TB diagnosis than serological tests.
Background
Undiagnosed and misdiagnosed tuberculosis (TB) drives the epidemic in India. Serological (antibody detection) TB tests are not recommended by any agency, but widely used in many countries, including the Indian private sector. The cost and impact of using serology compared with other diagnostic techniques is unknown.
Methods and Findings
Taking a patient cohort conservatively equal to the annual number of serological tests done in India (1.5 million adults suspected of having active TB), we used decision analysis to estimate costs and effectiveness of sputum smear microscopy (US$3.62 for two smears), microscopy plus automated liquid culture (mycobacterium growth indicator tube [MGIT], US$20/test), and serological testing (anda-tb ELISA, US$20/test). Data on test accuracy and costs were obtained from published literature. We adopted the perspective of the Indian TB control sector and an analysis frame of 1 year. Our primary outcome was the incremental cost per disability-adjusted life year (DALY) averted. We performed one-way sensitivity analysis on all model parameters, with multiway sensitivity analysis on variables to which the model was most sensitive.
If used instead of sputum microscopy, serology generated an estimated 14,000 more TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs averted, and 32,000 more secondary TB cases than microscopy, at approximately four times the incremental cost (US$47.5 million versus US$11.9 million). When added to high-quality sputum smears, MGIT culture was estimated to avert 130,000 incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was dominated by (i.e., more costly and less effective than) MGIT culture and remained less economically favorable than sputum smear or TB culture in one-way and multiway sensitivity analyses.
Conclusions
In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy should take priority. In areas where high-quality microscopy exists and resources are sufficient, MGIT culture is more cost-effective than serology as an additional diagnostic test for TB. These data informed a recently published World Health Organization policy statement against serological tests.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 2 million people develop tuberculosis in India—a fifth of the global incidence of this highly contagious bacterial infection. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze and usually infects the lungs although it can also infect other organs. The characteristic symptoms of tuberculosis are a persistent cough, weight loss, and night sweats. Diagnostic tests for tuberculosis include sputum smear microscopy (microscopic analysis of mucus brought up from the lungs by coughing), culture (growth) of M. tuberculosis from sputum samples in liquid media (using, for example, a commercial product called the mycobacteria growth indicator tube or MGIT), and nucleic acid amplification tests (which detect the bacterium's genome in patient samples) such as the Xpert MTB/RIF system. Tuberculosis can usually be cured by taking several powerful antibiotics daily for at least 6 months.
Why Was This Study Done?
In India, as elsewhere, undiagnosed and misdiagnosed tuberculosis drives the tuberculosis epidemic by increasing the transmission of M. tuberculosis. Unfortunately, sputum smear microscopy, the current mainstay of tuberculosis diagnosis worldwide, detects only half of tuberculosis cases, mycobacterial culture can take weeks to provide a diagnosis, and rapid techniques such as nucleic acid amplification require infrastructure that is often not available in developing countries. Consequently, in India and other developing countries, serological tests are widely used for the diagnosis of tuberculosis. Serological tests detect antibodies against M. tuberculosis in the blood (antibodies are proteins made by the immune system in response to infections). Serological tests are fast and simple to perform, but they are not recommended for clinical use, and the available evidence suggests that they do not diagnose tuberculosis accurately. Even so, and in the absence of information about the cost and impact (cost-effectiveness) of serological testing, about 1.5 million serological tests for tuberculosis are conducted every year in India at a cost of more than US$15 million. Here, the researchers analyze the cost-effectiveness of serological tests compared to other diagnostic tests from the perspective of tuberculosis control in India.
What Did the Researchers Do and Find?
The researchers used “decision analysis” to estimate the cost-effectiveness of sputum smear microscopy, microscopy plus liquid culture using the MGIT system, and serological testing using the widely used anda-tb ELISA commercial test in a hypothetical group of 1.5 million people suspected of having tuberculosis. Decision analysis formally assesses the decision-making process by using models that evaluate outcomes under different scenarios. By feeding data on the costs and accuracy of different diagnostic tests into their decision-analysis model, the researchers estimate that, over a year, serology would generate 14,000 more tuberculosis diagnoses than sputum microscopy. However, it would also generate 121,000 more false-positive diagnoses and 32,000 more tuberculosis transmissions to other people (secondary transmissions), and avert 102,000 fewer disability-adjusted life years (DALYs; a DALY is a year of healthy life lost because of premature death or disability) at four times the incremental cost of sputum microscopy. MGIT culture added to sputum smear microscopy would avert 130,000 DALYs at an incremental cost of US$213 per DALY averted. Finally, sensitivity analyses (reruns of the decision-analysis model using different values for test costs and accuracy) identified no scenario in which serology was either less costly or more effective than sputum smear microscopy alone or in which serology plus sputum microscopy was more cost-effective than MGIT culture plus sputum microscopy.
What Do These Findings Mean?
These findings identify sputum smear microscopy as the most cost-effective existing diagnostic test for tuberculosis in India. Moreover, they suggest that in areas where high-quality microscopy is available, resources are sufficient, and infrastructure to effectively use culture exists, the addition of MGIT culture to sputum smear microscopy would be more cost-effective than the addition of serology. Importantly, these findings suggest that, if used as an initial test for tuberculosis in India, serology would result in more DALYs, more secondary infections, and more false-positive diagnoses than sputum smear microscopy while increasing per-patient costs to the Indian tuberculosis control sector. Given these findings and the results of a recent updated systematic review on the accuracy of serological tests, the World Health Organization's Strategic and Technical Advisory Group for Tuberculosis recently advised against the use of currently available serological tests for the diagnosis of tuberculosis. The WHO negative policy against serological tests must now be implemented in India.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001074.
Details of the recent systematic review of serological tests for tuberculosis diagnosis are available in a PLoS Medicine Research Article by Steingart et al.
The World Health Organization provides information on all aspects of tuberculosis, including tuberculosis diagnostics and the Stop TB Partnership (some information is in several languages); its Strategic and Technical Advisory Group for Tuberculosis recommendations on tuberculosis diagnosis are available
The Evidence-based TB Diagnosis Web site by the Stop TB Partnership's New Diagnostics Working Group provides evidence syntheses on various TB tests, along with guidelines, resources, and training materials
The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the diagnosis of tuberculosis disease
The US National Institute of Allergy and Infectious Diseases also has information on all aspects of tuberculosis
MedlinePlus has links to further information about tuberculosis (in English and Spanish)
doi:10.1371/journal.pmed.1001074
PMCID: PMC3153451  PMID: 21857810
15.  Behavioural and skill-based early interventions in children with autism spectrum disorders 
Introduction
Autism spectrum disorders (ASD) comprise typical or infantile autism (Kanner syndrome), Asperger’s disorder and atypical autism or pervasive developmental disorder - not otherwise specified. The syndrome is characterized by deficits in (1) verbal and nonverbal communication, (2) reciprocal social interaction and (3) repetitive patterns of behaviour, interests and activities.
Early behavioural interventions are based on learning theory and behaviour therapy. They take into account specific deficits in perception, emotional reactions, social interaction and communication. In Germany, these comprehensive models are not widely evaluated and implemented.
Research questions
What are the clinical effectiveness and safety of early behavioural or skills-based early interventions in autism compared to other interventions or to treatment as usual?What are specific factors responsible for the effectiveness?What are the cost-effectiveness and cost consequences of different early interventions in autism?Which legal, social and ethical aspects are relevant with regard to the implementation of the respective interventions in persons with autism?
Methods
Following a systematic review of the literature, controlled studies on early behavioural or skills-based interventions published since 2000 in English or German with children until the age of twelve are included and critically appraised. Studies must have at least ten participants per intervention group.
Results
In total, 15 publications based on 14 studies, eight systematic reviews and one health economic study are included. Most studies evaluate early interventions based upon the Lovaas model (Early intensive behavioural treatment (EIBT), Applied behavioural analysis (ABA)). Other evaluate pragmatic interventions or interventions based on other theoretical models like specific parent interventions, responsive education and prelinguistic milieu teaching, joint attention, symbolic play, and picture exchange communication system. Behaviour analytic interventions referring to the Lovaas model remain the most empirically evaluated early interventions in autism. Preschool children with autism can achieve improvements in cognitive and functional domains when treated within behavioural interventions with a frequency of at least 20 hours per week. It is not clear which is the minimum duration of effective interventions, and which active components are necessary for the effectiveness. There was no high quality evidence for other comprehensive early interventions. The identified health economic study is not suitable to evaluate the cost-effectiveness or cost consequences of early interventions. No publications concerning legal, ethical or social aspects were identified. The financial situation of persons with autisms and their families will be improved through the implementation of the “Pflege-Weiterententwicklungsgesetz” (Pf-WG). Further questions concern the organisation of care and the legal representation of autistic patients. Ethical questions arise mainly in the context of the equal supply of care to each individual patient in all regions of the country and the situation of the caregivers.
Discussion
There are only a few studies with high methodology evaluating early interventions in children with autism. Most studies have a short duration with a lack of blinded outcome assessment in many cases. The lack of high quality comparative studies does not allow answering questions of comparative effectiveness of early interventions in autism. It can be concluded that interventions referring to the Lovaas model seem to have the highest effectiveness. This seems to be especially true when they are run clinic-based. However, there was no solid evidence with regard to factors responsible for the effectiveness of programms according to the ABA model. With regard to communication improvement, a systematic parent training seems to be superior to treatment as usual where a mixture of therapeutic elements is used. As well for clinical and health economic studies there is a substantial problem of generalisability into the German context. The identified health economic study is not suitable to evaluate the cost-effectiveness or cost consequences of early interventions.
Conclusion
Based on the available studies, there is no sufficient evidence for any of the evaluated behavioural early intervention programmes. Studies suggest that preschool children with autism in behavioural intervention programmes with a frequency of at least 20 hours per week can achieve improvements in cognitive and functional domains. There is no evidence that in a substantial portion of the children a normal development can be achieved by early interventions. Most research evidence is available for ABA. A minimal necessary intensity of interventions to achieve positive outcomes cannot be derived from literature. There are no valid statements possible as to cost-effectiveness or consequences of these interventions. Effective early interventions may reduce total autism costs in the long run. This may be achieved when the initial high treatment expenditures are more than compensated later if persons with this disorder have better social functioning.
doi:10.3205/hta000072
PMCID: PMC3011283  PMID: 21289897
16.  Cost-Effectiveness Analysis of Combination Therapies for Visceral Leishmaniasis in the Indian Subcontinent 
Background
Visceral leishmaniasis is a systemic parasitic disease that is fatal unless treated. We assessed the cost and cost-effectiveness of alternative strategies for the treatment of visceral leishmaniasis in the Indian subcontinent. In particular we examined whether combination therapies are a cost-effective alternative compared to monotherapies.
Methods and Findings
We assessed the cost-effectiveness of all possible mono- and combination therapies for the treatment of visceral leishmaniasis in the Indian subcontinent (India, Nepal and Bangladesh) from a societal perspective using a decision analytical model based on a decision tree. Primary data collected in each country was combined with data from the literature and an expert poll (Delphi method). The cost per patient treated and average and incremental cost-effectiveness ratios expressed as cost per death averted were calculated. Extensive sensitivity analysis was done to evaluate the robustness of our estimations and conclusions. With a cost of US$92 per death averted, the combination miltefosine-paromomycin was the most cost-effective treatment strategy. The next best alternative was a combination of liposomal amphotericin B with paromomycin with an incremental cost-effectiveness of $652 per death averted. All other strategies were dominated with the exception of a single dose of 10mg per kg of liposomal amphotericin B. While strategies based on liposomal amphotericin B (AmBisome) were found to be the most effective, its current drug cost of US$20 per vial resulted in a higher average cost-effectiveness. Sensitivity analysis showed the conclusion to be robust to variations in the input parameters over their plausible range.
Conclusions
Combination treatments are a cost-effective alternative to current monotherapy for VL. Given their expected impact on the emergence of drug resistance, a switch to combination therapy should be considered once final results from clinical trials are available.
Author Summary
Visceral leishmaniasis (VL) is a serious health problem in the Indian subcontinent affecting the rural poor. It has a significant economic impact on concerned households. The development of drug resistance is a major problem and threatens control efforts under the VL elimination initiative. With an unprecedented choice of antileishmanial drugs (but no newer compound in clinical development), policies that protect these drugs against the emergence of resistance are required. A possible strategy that has been successfully used for malaria and tuberculosis is the use of combination therapies. This study is the first comprehensive assessment of the cost-effectiveness of all possible mono- and combination therapies for the treatment of visceral leishmaniasis in the Indian subcontinent. The analysis was done from the societal perspective, including both health provider and household costs. The present work shows that combination treatments are a cost-effective alternative to current monotherapy for VL. Given their expected impact on emergence of drug resistance, the use of combination therapy should be considered in the context of the VL elimination programme in the Indian subcontinent.
doi:10.1371/journal.pntd.0000818
PMCID: PMC2935395  PMID: 20838649
17.  Early and Late Direct Costs in a Southern African Antiretroviral Treatment Programme: A Retrospective Cohort Analysis 
PLoS Medicine  2009;6(12):e1000189.
Gary Maartens and colleagues describe the direct heath care costs and identify the drivers of cost over time in an HIV managed care program in Southern Africa.
Background
There is a paucity of data on the health care costs of antiretroviral therapy (ART) programmes in Africa. Our objectives were to describe the direct heath care costs and establish the cost drivers over time in an HIV managed care programme in Southern Africa.
Methods/Findings
We analysed the direct costs of treating HIV-infected adults enrolled in the managed care programme from 3 years before starting non-nucleoside reverse transcriptase inhibitor-based ART up to 5 years afterwards. The CD4 cell count criterion for starting ART was <350 cells/µl. We explored associations between variables and mean total costs over time using a generalised linear model with a log-link function and a gamma distribution. Our cohort consisted of 10,735 patients (59.4% women) with 594,497 mo of follow up data (50.9% of months on ART). Median baseline CD4+ cell count and viral load were 125 cells/µl and 5.16 log10 copies/ml respectively. There was a peak in costs in the period around ART initiation (from 4 mo before until 4 mo after starting ART) driven largely by hospitalisation, following which costs plateaued for 5 years. The variables associated with changes in mean total costs varied with time. Key early associations with higher costs were low baseline CD4+ cell count, high baseline HIV viral load, and shorter duration in HIV care prior to starting ART; whilst later associations with higher costs were lower ART adherence, switching to protease inhibitor-based ART, and starting ART at an older age.
Conclusions
Drivers of mean total costs changed considerably over time. Starting ART at higher CD4 counts or longer pre-ART care should reduce early costs. Monitoring ART adherence and interventions to improve it should reduce later costs. Cost models of ART should take into account these time-dependent cost drivers, and include costs before starting ART.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 30 million people (22 million people in sub-Saharan Africa alone) are infected with the human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS). HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, on average HIV-positive people died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (ART; combinations of powerful antiretroviral drugs) was developed. For people living in affluent, developed countries HIV/AIDS became a chronic, treatable condition, but for the millions of HIV-infected people living in low- and middle-income countries, effective treatment was unavailable and HIV/AIDS remained a fatal illness. In 2003, this situation was declared a global health emergency and governments, international agencies, and funding bodies began to implement plans to increase ART coverage in developing countries. By the end of 2008, of the 9.5 million people in need of ART in low- and middle-income countries, more than 4 million people were receiving treatment.
Why Was This Study Done?
Good progress is being made towards achieving universal access to ART, partly because the cost of antiretroviral drugs has plummeted in developing countries. But the provision of antiretroviral drugs is not the only direct cost associated with ART. General practitioner, specialist, and maternity-related care for patients receiving ART, hospital accommodation when necessary, and the investigations that are needed to monitor the progress of HIV infection such as CD4 cell counts and viral load measurements all incur considerable costs. To use their limited resources effectively, public-health officials in developing countries need to know as much as possible about the direct costs of HIV health care but few studies have investigated these costs, particularly those incurred before an individual starts taking ART. In this study, the researchers explore health care costs in a South African private-sector HIV/AIDS program and examine the variables that drive the costs of HIV health care around the time of ART initiation and during later phases of ART.
What Did the Researchers Do and Find?
The researchers analyzed the direct costs of treating more than 100,000 HIV-infected adults enrolled in a private HIV care program in South Africa from 3 years before they started ART until up to 5 years after ART initiation; within this program, individuals began to receive ART when their CD4 cell count fell below 350 cells/µl of blood. The researchers found a peak in direct health costs from 4 months before to 4 months after starting ART (the “peri-ART” period), which was driven mainly by hospital costs. After the peri-ART period, costs dropped (although not to the levels seen before this period) and stabilized at an intermediate level for the next 5 years. Detailed statistical analyses suggest that the key variables associated with higher costs in the peri-ART period were a low baseline CD4 cell count, a high baseline HIV viral load, and a shorter time in HIV care before ART initiation. The key variable associated with higher costs later in ART was lower adherence to the drug therapy. That is, costs were higher among patients who did not take their antiretroviral drugs regularly.
What Do These Findings Mean?
This study involved patients enrolled in a private health care program in which the criteria for initiating ART differed somewhat from those recommended by the World Health Organization for ART initiation in resource-limited settings. Thus, the absolute mean total costs calculated by the researchers are unlikely to be generalizable to public HIV care systems in South Africa and in other resource-poor settings. However, the finding that the drivers of mean total costs change considerably over time may be generalizable and provides some useful information for public-health planners that can now be tested in other, more resource-limited patient populations. In particular, the findings of this study suggest that the high early costs of ART programs could be reduced by starting ART at higher CD4 cell counts or by providing longer pre-ART care. In addition, the findings suggest that monitoring ART adherence and introducing interventions to improve ART adherence could reduce the later direct costs of ART programs.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000189.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the HIV and AIDS in Africa, and on universal access to AIDS treatment (in English and Spanish)
The World Health Organization provides information about universal access to AIDS treatment, including the September 2009 progress report (in English and French)
The US Centers for Disease Control and Prevention also provides information on global efforts to deal with the HIV/AIDS epidemic
doi:10.1371/journal.pmed.1000189
PMCID: PMC2777319  PMID: 19956658
18.  Physical activity on prescription (PAP): Costs and consequences of a randomized, controlled trial in primary healthcare 
Objectives
To analyse costs and consequences of changing physical activity behaviour due to the “Physical Activity on Prescription” (PAP) programme.
Design
A randomized controlled trial with a four-month intervention, with comparison between intervention and control group.
Intervention
The PAP programme, with exercise twice a week, education, and motivational counselling.
Subjects
525 sedentary individuals, 20–80 years (intervention group n = 268, control group n = 257), with lifestyle-related health problems. A total of 245 returned for the four-month assessment.
Main outcome measure
Programme costs based on intention-to-treat estimations, direct and indirect costs of inactivity, and physical activity behaviour analysed with IPAQ (International Physical Activity Questionnaire), self-reported physical activity, and measures of functional capacity.
Results
The intention-to-treat programme costs for the four-month programme period was SEK (Swedish Kronor) 6475 (€ [Euro] 684) for the intervention group and SEK 3038 (€ 321) for the control group. Of this, healthcare providers’ costs were 24% in the intervention group, and 31% in the control group. The physical activity behaviour was significantly improved in both groups, but no differences were found between the groups.
Implications
The largest share of the PAP programme costs was the participants’ costs. Significant improvements were shown in physical activity behaviour in both groups, but no differences were found between the intervention and control groups. Due to many non-completers, the potential for improvements of the motivating assignment with sedentary individuals in primary healthcare is obvious. Long-term follow-up can determine the sustainability of the results, and can be used in a future cost-effectiveness analysis.
doi:10.3109/02813430903438734
PMCID: PMC3413913  PMID: 19929183
Costs; primary healthcare; Physical Activity on Prescription; RCT study
19.  Why Do Women Not Use Antenatal Services in Low- and Middle-Income Countries? A Meta-Synthesis of Qualitative Studies 
PLoS Medicine  2013;10(1):e1001373.
In a synthesis of 21 qualitative studies representing the views of more than 1,230 women from 15 countries, Kenneth Finlayson and Soo Downe examine the reasons why many women in low- and middle-income countries do not receive adequate antenatal care.
Background
Almost 50% of women in low- and middle-income countries (LMICs) don't receive adequate antenatal care. Women's views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies.
Methods and Findings
Using a predetermined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMICs who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line-of-argument synthesis. We derived policy-relevant hypotheses from the findings. We included 21 papers representing the views of more than 1,230 women from 15 countries. Three key themes were identified: “pregnancy as socially risky and physiologically healthy”, “resource use and survival in conditions of extreme poverty”, and “not getting it right the first time”. The line-of-argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralised, risk-focused antenatal care programmes may be at odds with the resources, beliefs, and experiences of pregnant women who underuse antenatal services.
Conclusions
Our findings suggest that there may be a misalignment between current antenatal care provision and the social and cultural context of some women in LMICs. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences is likely to be underused, especially when attendance generates increased personal risks of lost family resources or physical danger during travel, when the promised care is not delivered because of resource constraints, and when women experience covert or overt abuse in care settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Although maternal deaths worldwide have almost halved since 1990, according to the latest figures, every day roughly 800 women and adolescent girls still die from the complications of pregnancy or childbirth: in 2010, 287,000 women died during or following pregnancy and childbirth, with almost all of these deaths (99%) occurring in low-resource settings. Most maternal deaths are avoidable, as the interventions to prevent or manage the most common complications (severe bleeding, infections, high blood pressure during pregnancy, and unsafe abortion) are well known. Furthermore, many of these complications can be prevented, detected, or treated during antenatal care visits with trained health workers.
Why Was This Study Done?
The World Health Organization (WHO) recommends a minimum of four antenatal visits per pregnancy, but according to WHO figures, between 2005 and 2010 only 53% of pregnant women worldwide attended the recommended four antenatal visits; in low-income countries, this figure was a disappointing 36%. Unfortunately, despite huge international efforts to promote and provide antenatal care, there has been little improvement in these statistics over the past decade. It is therefore important to investigate the reasons for poor antenatal attendance and to seek the views of users of antenatal care. In this study, the researchers combined studies from low- and middle-income countries (LMICs) that included women's views on antenatal care in a meta-synthesis of qualitative studies (qualitative research uses techniques, such as structured interviews, to gather an in-depth understanding of human behaviour, and a meta-synthesis combines and interprets information across studies, contexts, and populations).
What Did the Researchers Do and Find?
The researchers searched several medical, sociological, and psychological databases to find appropriate qualitative studies published between January 1980 and February 2012 that explored the antenatal care experiences, attitudes, and beliefs of women from LMICs who had chosen to access antenatal care late (after 12 weeks' gestation), infrequently (less than four times), or not at all. The researchers included 21 studies (out of the 2,997 initially identified) in their synthesis, representing the views of 1,239 women from 15 countries (Bangladesh, Benin, Cambodia, Gambia, India, Indonesia, Kenya, Lebanon, Mexico, Mozambique, Nepal, Pakistan, South Africa, Tanzania, and Uganda) who were either interviewed directly or gave their opinion as part of a focus group.
The researchers identified three main themes. The first theme reflects women's views that pregnancy is a healthy state and so saw little reason to visit health professionals when they perceived no risk to their well-being—the researchers called this theme, “pregnancy as socially contingent and physiologically healthy.” The second theme relates to women's limited financial resources, so that even when antenatal care was offered free of charge, the cost of transport to get there, the loss of earnings associated with the visit, and the possibility of having to pay for medicines meant that women were unable to attend—the researchers called this theme “resource use and survival in conditions of extreme poverty.” The third theme the researchers identified related to women's views that the antenatal services were inadequate and that the benefits of attending did not outweigh any potential harms. For example, pregnant women who initially recognized the benefits of antenatal care were often disappointed by the lack of resources they found when they got there and, consequently, decided not to return. The researchers called this theme “not getting it right the first time.”
What Do These Findings Mean?
These findings suggest that there may be a misalignment between the principles that underpin the provision of antenatal care and the beliefs and socio-economic contexts of pregnant women in LMICs, meaning that even high-quality antenatal care may not be used by some pregnant women unless their views and concerns are addressed. The themes identified in this meta-synthesis could provide the basis for a new approach to the design and delivery of antenatal care that takes local beliefs and values and resource availability into account. Such programs might help ensure that antenatal care meets pregnant women's expectations and treats them appropriately so that they want to regularly attend antenatal care.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001373.
Wikipedia describes antenatal care (note that Wikipedia is a free online encyclopedia that anyone can edit)
The World Health Organization has a wealth of information relating to pregnancy, including antenatal care
The UK National Institute for Health and Clinical Excellence has evidence-based guidelines on antenatal care
The White Ribbon Alliance for Safe Motherhood has a series of web pages and links relating to respectful maternity care in LMICs
International Federation of Gynecology and Obstetrics is an international organization with connections to various maternity initiatives in LMICs
International Confederation of Midwives has details of the Millennium Development Goals relating to maternity care
doi:10.1371/journal.pmed.1001373
PMCID: PMC3551970  PMID: 23349622
20.  Newborn screening by tandem mass spectrometry for glutaric aciduria type 1: a cost-effectiveness analysis 
Background
Glutaric aciduria type I (GA-I) is a rare metabolic disorder caused by inherited deficiency of glutaryl-CoA dehydrogenase. Despite high prognostic relevance of early diagnosis and start of metabolic treatment as well as an additional cost saving potential later in life, only a limited number of countries recommend newborn screening for GA-I. So far only limited data is available enabling health care decision makers to evaluate whether investing into GA-I screening represents value for money. The aim of our study was therefore to assess the cost-effectiveness of newborn screening for GA-I by tandem mass spectrometry (MS/MS) compared to a scenario where GA-I is not included in the MS/MS screening panel.
Methods
We assessed the cost-effectiveness of newborn screening for GA-I against the alternative of not including GA-I in MS/MS screening. A Markov model was developed simulating the clinical course of screened and unscreened newborns within different time horizons of 20 and 70 years. Monte Carlo simulation based probabilistic sensitivity analysis was used to determine the probability of GA-I screening representing a cost-effective therapeutic strategy.
Results
Within a 20 year time horizon, GA-I screening averts approximately 3.7 DALYs (95% CI 2.9 – 4.5) and about one life year is gained (95% CI 0.7 – 1.4) per 100,000 neonates screened initially . Moreover, the screening programme saves a total of around 30,682 Euro (95% CI 14,343 to 49,176 Euro) per 100,000 screened neonates over a 20 year time horizon.
Conclusion
Within the limitations of the present study, extending pre-existing MS/MS newborn screening programmes by GA-I represents a highly cost-effective diagnostic strategy when assessed under conditions comparable to the German health care system.
doi:10.1186/1750-1172-8-167
PMCID: PMC4015693  PMID: 24135440
Newborn screening GA-I; Glutaric aciduria type 1; Cost-effectiveness
21.  The management of cardiovascular disease in the Netherlands: analysis of different programmes 
Background
Disease management programmes are increasingly used to improve the efficacy and effectiveness of chronic care delivery. But, disease management programme development and implementation is a complex undertaking that requires effective decision-making. Choices made in the earliest phases of programme development are crucial, as they ultimately impact costs, outcomes and sustainability.
Methods
To increase our understanding of the choices that primary healthcare practices face when implementing such programmes and to stimulate successful implementation and sustainability, we compared the early implementation of eight cardiovascular disease management programmes initiated and managed by healthcare practices in various regions of the Netherlands. Using a mixed-methods design, we identified differences in and challenges to programme implementation in terms of context, patient characteristics, disease management level, healthcare utilisation costs, development costs and health-related quality of life.
Results
Shifting to a multidisciplinary, patient-centred care pathway approach to disease management is demanding for organisations, professionals and patients, and is especially vulnerable when sustainable change is the goal. Funding is an important barrier to sustainable implementation of cardiovascular disease management programmes, although development costs of the individual programmes varied considerably in relation to the length of the development period. The large number of professionals involved in combination with duration of programme development was the largest cost drivers. While Information and Communication Technology systems to support the new care pathways did not directly contribute to higher costs, delays in implementation indirectly did.
Conclusions
Developing and implementing cardiovascular disease management programmes is time-consuming and challenging. Multidisciplinary, patient-centred care demands multifaceted changes in routine care. As care pathways become more complex, they also become more expensive. Better preparedness and training can prevent unnecessary delays during the implementation period and are crucial to reducing costs.
PMCID: PMC3807633  PMID: 24167456
cardiovascular disease management; integrated care pathways; chronic care delivery; programme implementation; the Netherlands
22.  Patented Drug Extension Strategies on Healthcare Spending: A Cost-Evaluation Analysis 
PLoS Medicine  2013;10(6):e1001460.
In a cost-evaluation analysis of pharmacy invoice data in one Canton in Switzerland, Nathalie Vernaz and colleagues find that “evergreening” strategies pursued by drug manufacturers have been successful in maintaining market share and contribute to increased overall healthcare costs.
Please see later in the article for the Editors' Summary
Background
Drug manufacturers have developed “evergreening” strategies to compete with generic medication after patent termination. These include marketing of slightly modified follow-on drugs. We aimed to estimate the financial impact of these drugs on overall healthcare costs and also to examine the impact of listing these drugs in hospital restrictive drug formularies (RDFs) on the healthcare system as a whole (“spillover effect”).
Methods and Findings
We used hospital and community pharmacy invoice office data in the Swiss canton of Geneva to calculate utilisation of eight follow-on drugs in defined daily doses between 2000 and 2008. “Extra costs” were calculated for three different scenarios assuming replacement with the corresponding generic equivalent for prescriptions of (1) all brand (i.e., initially patented) drugs, (2) all follow-on drugs, or (3) brand and follow-on drugs. To examine the financial spillover effect we calculated a monthly follow-on drug market share in defined daily doses for medications prescribed by hospital physicians but dispensed in community pharmacies, in comparison to drugs prescribed by non-hospital physicians in the community.
Estimated “extra costs” over the study period were €15.9 (95% CI 15.5; 16.2) million for scenario 1, €14.4 (95% CI 14.1; 14.7) million for scenario 2, and €30.3 (95% CI 29.8; 30.8) million for scenario 3. The impact of strictly switching all patients using proton-pump inhibitors to esomeprazole at admission resulted in a spillover “extra cost” of €330,300 (95% CI 276,100; 383,800), whereas strictly switching to generic cetirizine resulted in savings of €7,700 (95% CI 4,100; 11,100). Overall we estimated that the RDF resulted in “extra costs” of €503,600 (95% CI 444,500; 563,100).
Conclusions
Evergreening strategies have been successful in maintaining market share in Geneva, offsetting competition by generics and cost containment policies. Hospitals may be contributing to increased overall healthcare costs by listing follow-on drugs in their RDF. Therefore, healthcare providers and policy makers should be aware of the impact of evergreening strategies.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The development of a new medical drug—from discovery of a new compound to regulatory approval for its use—can take many years and cost millions of dollars. In 1995 the World Trade Organization adopted an international law (Trade-Related Aspects of Intellectual Property Rights—TRIPS) by which pharmaceutical companies can protect their intellectual property through patents. Under TRIPS, pharmaceutical companies are granted exclusive manufacturing rights for up to 20 years for each new drug, generating large revenues that often exceed initial investments costs, thus providing an incentive for pharmaceutical companies to continue to invest in the research and development of new drugs. However, recent stricter regulatory procedures for drug approval, national price control policies, and increased competition from generic manufacturers (that produce drugs similar to the brand drug once the patent has expired) have meant that pharmaceutical company profits have increasingly come under pressure.
Why Was This Study Done?
One of the tactics that pharmaceutical companies currently use in response to this situation is to extend their market monopoly. This practice is known as “evergreening” and refers to the situation in which pharmaceutical companies slightly change the formulation of their brand drug into “follow on” drugs, for example, by combining formulations or producing slow-release forms, so that they can extend the patent. The impact of such follow-on drugs on overall healthcare costs in high-resource settings is unclear and has received little attention. In this study, the researchers assessed the overall costs associated with the prescribing of follow-on drugs in the Swiss canton of Geneva.
What Did the Researchers Do and Find?
The researchers identified prescriptions of eight follow-on drugs issued by hospital and community pharmacists in Geneva between 2000 and 2008. To analyze the impact of evergreening strategies on healthcare spending, they calculated the market share score (an indicator of market competitiveness) for all prescriptions of the originally patented (brand) drug, the follow-on drug, and generic versions of the drug. The researchers then used hospital and community databases to analyze the costs of replacing brand and/or follow-on drugs with a corresponding generic drug (when available) under three scenarios (1) replacing all brand drug prescriptions, (2) replacing all follow-on drug prescriptions, and (3) replacing both follow-on and brand prescriptions.
Using these methods, the researchers found that over the study period, the number of patients receiving either a brand or follow-on drug increased from 56,686 patients in 2001 to 131,193 patients in 2008. The total cost for all studied drugs was €171.5 million, of which €103.2 million was for brand drugs, €41.1 million was for follow-on drugs, and €27.2 million was for generic drugs. Based on scenario 1 (all brand drugs being replaced by generics) and scenario 2 (all follow-on drugs being replaced by generics), over the study period, the healthcare system could have saved €15.9 million and €14.4 million in extra costs, respectively. The researchers also found some evidence that hospital prescribing patterns (through a restrictive drug formulary) influenced prescribing in the community: over the study period, the influence of hospital prescription patterns on the community resulted in an extra cost of €503,600 (mainly attributable to two drugs, esomeprazole and escitalopram). However, this influence also resulted in some savings because of a generic drug listed in the hospital formulary: use of the generic version of the drug cetirizine resulted in savings of €7,700.
What Do These Findings Mean?
These findings show that in a high-income setting, evergreening strategies developed by pharmaceutical companies for follow-on drugs substantially contributed to an increase in overall healthcare costs. These findings also provide further evidence that policies encouraging prescribing of generic medicines could have substantial savings on healthcare expenditure and, if implemented in hospital formularies, could also influence prescribing outside of the hospital setting, resulting in further savings. However, in their analysis, the researchers assumed that the health outcomes of patients would be the same whatever type of drug they used (brand, generic, or follow-on), as they had no information on health outcomes. Nevertheless, this study provides useful information for healthcare providers and policy makers about the cost implications of the evergreening strategies used by the pharmaceutical industry, particularly for follow-on drugs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001460.
This study is further discussed in a PLOS Medicine Perspective by Aaron Kesselheim
Wikipedia provides an explanation of evergreening (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The World Trade Organization has detailed information on TRIPS
doi:10.1371/journal.pmed.1001460
PMCID: PMC3672218  PMID: 23750120
23.  Cost-utility of an 8-month aquatic training for women with fibromyalgia: a randomized controlled trial 
Introduction
Physical therapy in warm water has been effective and highly recommended for persons with fibromyalgia, but its efficiency remains largely unknown. Should patients or health care managers invest in this therapy? The aim of the current study was to assess the cost-utility of adding an aquatic exercise programme to the usual care of women with fibromyalgia.
Methods
Costs to the health care system and to society were considered in this study that included 33 participants, randomly assigned to the experimental group (n = 17) or a control group (n = 16). The intervention in the experimental group consisted of a 1-h, supervised, water-based exercise sessions, three times per week for 8 months. The main outcome measures were the health care costs and the number of quality-adjusted life-years (QALYs) using the time trade-off elicitation technique from the EuroQol EQ-5D instrument. Sensitivity analyses were performed for variations in staff salary, number of women attending sessions and time spent going to the pool. The cost effectiveness acceptability curves were created using a non-parametric bootstrap technique.
Results
The mean incremental treatment costs exceeded those for usual care per patient by € 517 for health care costs and € 1,032 for societal costs. The mean incremental QALY associated with the intervention was 0.131 (95% CI: 0.011 to 0.290). Each QALY gained in association with the exercise programme cost an additional € 3,947/QALY (95% CI: 1,782 to 47,000) for a health care perspective and € 7,878/QALY (3,559 to 93,818) from a societal perspective. The curves showed a 95% probability that the addition of the water-based programme is a cost-effective strategy if the ceiling of inversion is € 14,200/QALY from a health care perspective and € 28,300/QALY from a societal perspective.
Conclusion
The addition of an aquatic exercise programme to the usual care regime for fibromyalgia in women is cost effective in terms of both health care costs and societal costs. However, the characteristics of facilities (distance from the patients' homes and number of patients that can be accommodated per session) are major determinants to consider before investing in such a programme.
Trial registration
Current controlled trials ISRCTN53367487.
doi:10.1186/ar2377
PMCID: PMC2374450  PMID: 18294367
24.  The FEeding Support Team (FEST) randomised, controlled feasibility trial of proactive and reactive telephone support for breastfeeding women living in disadvantaged areas 
BMJ Open  2012;2(2):e000652.
Objective
To assess the feasibility of implementing a dedicated feeding support team on a postnatal ward and pilot the potential effectiveness and cost-effectiveness of team (proactive) and woman-initiated (reactive) telephone support after discharge.
Design
Randomised controlled trial embedded within a before-and-after study. Participatory approach and mixed-method process evaluation.
Setting
A postnatal ward in Scotland.
Sample
Women living in disadvantaged areas initiating breast feeding.
Methods
Eligible women were recruited to a before-and-after intervention study, a proportion of whom were independently randomised after hospital discharge to intervention: daily proactive and reactive telephone calls for ≤14 days or control: reactive telephone calls ≤ day 14. Intention-to-treat analysis compared the randomised groups on cases with complete outcomes at follow-up.
Main outcome measures
Primary outcome: any breast feeding at 6–8 weeks assessed by a telephone call from a researcher blind to group allocation. Secondary outcomes: exclusive breast feeding, satisfaction with care, NHS costs and cost per additional woman breast feeding.
Results
There was no difference in feeding outcomes for women initiating breast feeding before the intervention (n=413) and after (n=388). 69 women were randomised to telephone support: 35 intervention (32 complete cases) and 34 control (26 complete cases). 22 intervention women compared with 12 control women were giving their baby some breast milk (RR 1.49, 95% CI 0.92 to 2.40) and 17 intervention women compared with eight control women were exclusively breast feeding (RR 1.73, 95% CI 0.88 to 3.37) at 6–8 weeks after birth. The incremental cost of providing proactive calls was £87 per additional woman breast feeding and £91 per additional woman exclusively breast feeding at 6–8 weeks; costs were sensitive to service organisation.
Conclusions
Proactive telephone care delivered by a dedicated feeding team shows promise as a cost-effective intervention for improving breastfeeding outcomes. Integrating the FEeding Support Team (FEST) intervention into routine postnatal care was feasible.
Trial registration number
ISRCTN27207603. The study protocol and final report are available on request.
Article summary
Article focus
To pilot the potential effectiveness and cost-effectiveness of continuing proactive and reactive telephone support for breast feeding for up to 14 days after hospital discharge for women living in more disadvantaged areas.
To assess the feasibility of implementing a dedicated feeding team on a postnatal ward.
To design an effective health service intervention for infant feeding by re-organising how routine care is provided to inform a larger programme of research.
Key messages
Proactive telephone care delivered by a dedicated feeding team shows promise for increasing breastfeeding rates 6–8 weeks after birth.
Only having a dedicated feeding team on a postnatal ward did not appear to make any difference to feeding outcomes at 6–8 weeks after birth.
We have demonstrated the feasibility of (1) implementing the FEeding Support Team intervention as part of routine postnatal care and (2) the recruitment and data collection processes for a proposed definitive trial.
Strengths and limitations of this study
Using a participatory approach and embedding a rigorous randomised control trial within a before-and-after cohort study with mixed methods data to evaluate costs are strengths that will enable us to design a definitive trial.
It is likely that the effect sizes are overestimated as the sample size was small and no sample size calculation was performed prior to the study.
Our sample included women requiring longer hospital stays due to birth complications.
The reactive call service was only free to those who had the same mobile phone network provider.
The incremental cost-effectiveness ratios presented represent the most favourable set of assumptions for proactive telephone support and are sensitive to how the service is organised.
doi:10.1136/bmjopen-2011-000652
PMCID: PMC3341594  PMID: 22535790
25.  Programme costs in the economic evaluation of health interventions 
Estimating the costs of health interventions is important to policy-makers for a number of reasons including the fact that the results can be used as a component in the assessment and improvement of their health system performance. Costs can, for example, be used to assess if scarce resources are being used efficiently or whether there is scope to reallocate them in a way that would lead to improvements in population health. As part of its WHO-CHOICE project, WHO has been developing a database on the overall costs of health interventions in different parts of the world as an input to discussions about priority setting.
Programme costs, defined as costs incurred at the administrative levels outside the point of delivery of health care to beneficiaries, may comprise an important component of total costs. Cost-effectiveness analysis has sometimes omitted them if the main focus has been on personal curative interventions or on the costs of making small changes within the existing administrative set-up. However, this is not appropriate for non-personal interventions where programme costs are likely to comprise a substantial proportion of total costs, or for sectoral analysis where questions of how best to reallocate all existing health resources, including administrative resources, are being considered.
This paper presents a first effort to systematically estimate programme costs for many health interventions in different regions of the world. The approach includes the quantification of resource inputs, choice of resource prices, and accounts for different levels of population coverage. By using an ingredients approach, and making tools available on the World Wide Web, analysts can adapt the programme costs reported here to their local settings. We report results for a selected number of health interventions and show that programme costs vary considerably across interventions and across regions, and that they can contribute substantially to the overall costs of interventions.
doi:10.1186/1478-7547-1-1
PMCID: PMC156020  PMID: 12773220

Results 1-25 (1146740)