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1.  Data processing costs for three posture assessment methods 
Background
Data processing contributes a non-trivial proportion to total research costs, but documentation of these costs is rare. This paper employed a priori cost tracking for three posture assessment methods (self-report, observation of video, and inclinometry), developed a model describing the fixed and variable cost components, and simulated additional study scenarios to demonstrate the utility of the model.
Methods
Trunk and shoulder postures of aircraft baggage handlers were assessed for 80 working days using all three methods. A model was developed to estimate data processing phase costs, including fixed and variable components related to study planning and administration, custom software development, training of analysts, and processing time.
Results
Observation of video was the most costly data processing method with total cost of € 30,630, and was 1.2-fold more costly than inclinometry (€ 26,255), and 2.5-fold more costly than self-reported data (€ 12,491). Simulated scenarios showed altering design strategy could substantially impact processing costs. This was shown for both fixed parameters, such as software development and training costs, and variable parameters, such as the number of work-shift files processed, as well as the sampling frequency for video observation. When data collection and data processing costs were combined, the cost difference between video and inclinometer methods was reduced to 7%; simulated data showed this difference could be diminished and, even, reversed at larger study sample sizes. Self-report remained substantially less costly under all design strategies, but produced alternate exposure metrics.
Conclusions
These findings build on the previously published data collection phase cost model by reporting costs for post-collection data processing of the same data set. Together, these models permit empirically based study planning and identification of cost-efficient study designs.
doi:10.1186/1471-2288-13-124
PMCID: PMC4015999  PMID: 24118872
Cost-efficiency; Exposure; Shoulder; Back; Inclinometry; Observation; Questionnaire; Work related musculoskeletal disorders; Methods development
2.  Costs of Multidisciplinary Parenteral Nutrition Care Provided at a Distance via Mobile Tablets 
Background
Determining the costs of healthcare delivery is a key step for providing efficient nutrition-based care. This analysis tabulates the costs of delivering home parenteral nutrition (HPN) interventions and clinical assessments through encrypted mobile technologies to increase patients’ access to healthcare providers, reduce their travel expenses, and allow early detection of infection and other complications.
Methods
A traditional cost-accounting method was used to tabulate all expenses related to mobile distance HPN clinic appointments, including (1) personnel time of multidisciplinary healthcare professionals, (2) supply of HPN intervention materials, and (3) equipment, connection, and delivery expenses.
Results
A total of 20 mobile distance clinic appointments were conducted for an average of 56 minutes each with 45 patients who required HPN infusion care. The initial setup costs included mobile tablet devices, 4G data plans, and personnel's time as well as intervention materials. The initial costs were on average $916.64 per patient, while the follow-up clinic appointments required $361.63 a month, with these costs continuing to decline as the equipment was used by multiple patients more frequently over time. Patients reported high levels of satisfaction with cost savings in travel expenses and rated the quality of care comparable to traditional in-person examinations.
Conclusion
This study provides important aspects of the initial cost tabulation for visual assessment for HPN appointments. These findings will be used to generate a decision algorithm for scheduling mobile distance clinic appointments intermittent with in-person visits to determine how to lower costs of nutrition assessments. To maximize the cost benefits, clinical trials must continue to collect clinical outcomes.
doi:10.1177/0148607114550692
PMCID: PMC4231785  PMID: 25245253
parenteral nutrition; nutrition; home nutrition support; reimbursement; outcomes research/quality; nutrition support practice
3.  Voluntary Medical Male Circumcision: Logistics, Commodities, and Waste Management Requirements for Scale-Up of Services 
PLoS Medicine  2011;8(11):e1001128.
Dianna Edgil and colleagues evaluate the supply chain and waste management costs needed to deliver mobile medical male circumcision services to 152,000 men in Swaziland, finding that per-procedure costs almost double when these factors are taken into account.
Background
The global HIV prevention community is implementing voluntary medical male circumcision (VMMC) programs across eastern and southern Africa, with a goal of reaching 80% coverage in adult males by 2015. Successful implementation will depend on the accessibility of commodities essential for VMMC programming and the appropriate allocation of resources to support the VMMC supply chain. For this, the United States President’s Emergency Plan for AIDS Relief, in collaboration with the World Health Organization and the Joint United Nations Programme on HIV/AIDS, has developed a standard list of commodities for VMMC programs.
Methods and Findings
This list of commodities was used to inform program planning for a 1-y program to circumcise 152,000 adult men in Swaziland. During this process, additional key commodities were identified, expanding the standard list to include commodities for waste management, HIV counseling and testing, and the treatment of sexually transmitted infections.
The approximate costs for the procurement of commodities, management of a supply chain, and waste disposal, were determined for the VMMC program in Swaziland using current market prices of goods and services.
Previous costing studies of VMMC programs did not capture supply chain costs, nor the full range of commodities needed for VMMC program implementation or waste management. Our calculations indicate that depending upon the volume of services provided, supply chain and waste management, including commodities and associated labor, contribute between US$58.92 and US$73.57 to the cost of performing one adult male circumcision in Swaziland.
Conclusions
Experience with the VMMC program in Swaziland indicates that supply chain and waste management add approximately US$60 per circumcision, nearly doubling the total per procedure cost estimated previously; these additional costs are used to inform the estimate of per procedure costs modeled by Njeuhmeli et al. in “Voluntary Medical Male Circumcision: Modeling the Impact and Cost of Expanding Male Circumcision for HIV Prevention in Eastern and Southern Africa.” Program planners and policy makers should consider the significant contribution of supply chain and waste management to VMMC program costs as they determine future resource needs for VMMC programs.
Please see later in the article for the Editors' Summary
Editors’ Summary
Background
About 33 million people (including 22.5 million in sub-Saharan Africa) are currently infected with HIV, the virus that causes AIDS. Although antiretroviral drugs keep HIV in check, there is no cure for HIV/AIDS. Consequently, prevention of HIV transmission is extremely important. Because HIV is usually spread through unprotected sex with an infected partner, individuals can reduce their risk of becoming infected with HIV by abstaining from sex, by having only one or a few partners, and by always using male or female condoms. In addition, trials in sub-Saharan Africa have shown that male circumcision—the removal of the foreskin, the loose fold of skin that covers the head of the penis—reduces the risk of HIV infection in men by 60%. In 2007, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended that voluntary medical male circumcision (VMMC) should be part of HIV prevention programs in regions with a generalized HIV epidemic and a low level of male circumcision. Together with the United States President’s Emergency Plan for AIDS Relief (PEPFAR), WHO, and UNAIDS also prioritized 14 countries in eastern and southern Africa for VMMC program scale-up. Mathematical models suggest that, if 80% VMMC coverage is reached by 2015 (which will entail performing 20.33 million circumcisions between 2011 and 2015) and sustained thereafter, VMMC programs in these priority countries will avert more than 4 million HIV infections among adults between 2009 and 2025.
Why Was This Study Done?
Successful VMMC scale-up will depend on the commodities that are essential for VMMC services being accessible and on the appropriate allocation of resources to support VMMC programs (which, in addition to circumcision, include HIV testing and counseling, sexually transmitted infection screening and treatment, condom provision and promotion, and counseling on risk reduction and safer sex). To help program planners and policy makers, costing studies have been undertaken in several African countries. These studies considered the costs of a standard list of commodities prepared by PEPFAR, WHO, and UNAIDS and estimated that, on average, one male circumcision costs about US$53. However, these studies did not include the costs of the supply chain, waste management, HIV counseling and testing, treatment of sexually transmitted infections, or the temporary infrastructure needed to deliver mobile VMMC services. Here, the researchers estimate these hitherto ignored costs for the Accelerated Saturation Initiative (ASI; Soka Uncobe [Circumcise and Conquer] in SiSwati), a one-year program to circumcise 152,000 men in Swaziland.
What Did the Researchers Do and Find?
The researchers used current market prices of goods and services to calculate the fixed and variable costs of various aspects of the VMMC commodity supply chain such as procurement, international freight, in-country distribution to service delivery sites, and warehousing, and of various aspects of waste management, such as the transportation of waste to incinerators and the maintenance of incinerators. They also estimated the staffing costs of supply chain and waste management services. From these component costs, the researchers estimate that, overall, the costs of supply chain and waste management, including procurement of commodities and associated labor, add US$58.92 if 152,000 men are circumcised and US$73.57 if 75,000 men are circumcised to the previously estimated cost of performing one adult male circumcision through the Swaziland ASI VMMC program.
What Do These Findings Mean?
This study suggests that, for the Swaziland ASI VMMC program, procurement, supply chain, and waste management costs nearly double the previously estimated cost per VMMC procedure. That is, the supply chain and waste management costs for this program are nearly as high as the costs of the equipment and staff needed to do the circumcisions. Because these costs were not taken into account during the planning stages of Swaziland’s ASI VMMC program, the initial needs assessment for this program underestimated the actual costs by about US$8 million. Although the magnitude of this underestimate cannot be generalized to other settings, this analysis emphasizes the importance of considering the contribution of supply chain and waste management to costs when determining the future resource needs of VMMC programs. Moreover, it provides a framework to help program planners and policy makers estimate the costs involved in the scale-up of VMMC programs in other priority countries.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001128.
This study is part of a PLoS collection of articles on VMMC (http://www.ploscollections.org/VMMC2011) and is further discussed in a PLoS Medicine Review Article by Hankins et al. (http://dx.doi.org/10.1371/journal.pmed.1001127).
Information is available from WHO, UNAIDS, and PEPFAR on all aspects of HIV/AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and information on male circumcision for the prevention of HIV transmission
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on all aspects of HIV prevention, and on HIV/AIDS in Africa and in Swaziland (in English and Spanish)
The Clearinghouse on Male Circumcision, a resource provided by WHO, UNAIDS, and other international bodies, provides information and tools for VMMC policy development and program implementation
Personal stories about living with HIV/AIDS are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001128
PMCID: PMC3226460  PMID: 22140363
4.  Voluntary Medical Male Circumcision: Modeling the Impact and Cost of Expanding Male Circumcision for HIV Prevention in Eastern and Southern Africa 
PLoS Medicine  2011;8(11):e1001132.
Emmanuel Njeuhmeli and colleagues estimate the impact and cost of scaling up adult medical male circumcision in 13 priority countries in eastern and southern Africa, finding that reaching 80% coverage and maintaining it until 2025 would avert 3.36 million new HIV infections.
Background
There is strong evidence showing that voluntary medical male circumcision (VMMC) reduces HIV incidence in men. To inform the VMMC policies and goals of 13 priority countries in eastern and southern Africa, we estimate the impact and cost of scaling up adult VMMC using updated, country-specific data.
Methods and Findings
We use the Decision Makers' Program Planning Tool (DMPPT) to model the impact and cost of scaling up adult VMMC in Botswana, Lesotho, Malawi, Mozambique, Namibia, Rwanda, South Africa, Swaziland, Tanzania, Uganda, Zambia, Zimbabwe, and Nyanza Province in Kenya. We use epidemiologic and demographic data from recent household surveys for each country. The cost of VMMC ranges from US$65.85 to US$95.15 per VMMC performed, based on a cost assessment of VMMC services aligned with the World Health Organization's considerations of models for optimizing volume and efficiencies. Results from the DMPPT models suggest that scaling up adult VMMC to reach 80% coverage in the 13 countries by 2015 would entail performing 20.34 million circumcisions between 2011 and 2015 and an additional 8.42 million between 2016 and 2025 (to maintain the 80% coverage). Such a scale-up would result in averting 3.36 million new HIV infections through 2025. In addition, while the model shows that this scale-up would cost a total of US$2 billion between 2011 and 2025, it would result in net savings (due to averted treatment and care costs) amounting to US$16.51 billion.
Conclusions
This study suggests that rapid scale-up of VMMC in eastern and southern Africa is warranted based on the likely impact on the region's HIV epidemics and net savings. Scaling up of safe VMMC in eastern and southern Africa will lead to a substantial reduction in HIV infections in the countries and lower health system costs through averted HIV care costs.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Every year, about 2.5 million people (mainly in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. There is no cure for HIV/AIDS. Consequently, prevention of HIV transmission is very important. Because the most common HIV transmission route is through unprotected sex with an infected partner, individuals can reduce their risk of HIV infection by abstaining from sex, by having only one or a few partners, and by using male or female condoms. There is also strong evidence that voluntary medical male circumcision (VMMC)—the removal of the foreskin, the loose fold of skin that covers the head of the penis—reduces the heterosexual acquisition of HIV in men by about 60%. In 2007, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended that VMMC should be offered to men as part of comprehensive HIV risk reduction programs in settings with generalized HIV epidemics and low levels of male circumcision. They also prioritized 13 countries in eastern and southern Africa for VMMC program scale-up.
Why Was This Study Done?
The impact of VMMC scale-up in terms of HIV infections and AIDS deaths averted (epidemiologic impact) is expected to be large, and the intervention should also reduce the costs associated with the treatment, care, and support of infected individuals. However, VMMC scale-up will require substantial funding and considerable effort by countries—many of which have weak health systems and limited resources—to train personnel, equip facilities, and provide the necessary commodities. To support planning for VMMC scale-up, the United States Agency for International Development Health Policy Initiative has collaborated with UNAIDS to develop the Decision Makers' Program Planning Tool (DMPPT), a mathematical model that allows analysts and decision makers to estimate the epidemiologic impact and cost of alternative VMMC scale-up programs. In this study, the researchers use DMPPT to estimate the impact and cost of scaling up adult VMMC in the 13 priority countries in eastern and southern Africa.
What Did the Researchers Do and Find?
The researchers derived VMMC unit costs for each priority country based on a cost assessment undertaken in Zimbabwe, one of the first countries to scale up VMMC services using WHO's “Models for Optimizing Volume and Efficiencies” (MOVE) guidelines. They fed these costs and recent epidemiologic data (including HIV infection rates and the effectiveness of VMMC in preventing HIV transmission) and demographic data (including the adult population size and pre-scale-up male circumcision prevalence) collected in each country into the DMPPT, together with information on the lifetime costs of HIV treatment. Results from running the DMPPT model suggest that scaling up adult VMMC to reach 80% coverage in the 13 priority countries by 2015 would require 20.33 million circumcisions to be completed between 2011 and 2015. To maintain this coverage, a further 8.42 million circumcisions would be required between 2016 and 2025. Such a scale-up would avert 3.36 million new HIV infections through 2025 and would cost US$2,000,000,000 between 2011 and 2025. However, it would result in net savings (because of averted treatment and care costs) of US$16,510,000,000.
What Do These Findings Mean?
These findings suggest that rapid VMMC scale-up in eastern and southern Africa is warranted, given its likely impact on the region's HIV epidemics and the resultant cost savings. However, the accuracy of these findings depends on the assumptions built into the DMPPT and on the data fed into it. For example, there could be risk behavior changes after circumcision. That is, risky sexual behaviors may increase in men who have been circumcised. However, the researchers show that, except in Rwanda, post-circumcision risk behavior change is unlikely to completely reverse the benefits of VMMC. These modeling results also assume that men seeking out VMMC services are typical of the general male population, but if they are actually at unusually low risk of HIV infection, then the benefits of VMMC reported here are likely to be overestimated. Finally, these findings assume 80% VMMC coverage. This may be optimistic, although results from Kenya indicate that this target is achievable. Thus, countries and their international partners must allocate sufficient resources to VMMC scale-up to achieve high coverage rates if they are to take full advantage of the benefits predicted here for VMMC scale-up.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001132.
This study is part of a PLoS Collection of articles on http://www.ploscollections.org/VMMC2011 and is further discussed in a PLoS Medicine Review Article by Hankins et al. (http://dx.doi.org/10.1371/journal.pmed.1001127)
Information is available from WHO, UNAIDS, and PEPFAR on all aspects of HIV/AIDS; the 2011WHO/UNAIDS progress report on VMMC scale-up in the 13 priority countries is available
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and information on male circumcision for the prevention of HIV transmission
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on all aspects of HIV prevention, and on HIV/AIDS in Africa (in English and Spanish)
The Clearinghouse on Male Circumcision, a resource provided by WHO, UNAIDS, and other international bodies, provides information and tools for VMMC policy development and program implementation, including information on the DMPPT and the MOVE guidance
Personal stories about living with HIV/AIDS are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001132
PMCID: PMC3226464  PMID: 22140367
5.  Can Broader Diffusion of Value-Based Insurance Design Increase Benefits from US Health Care without Increasing Costs? Evidence from a Computer Simulation Model 
PLoS Medicine  2010;7(2):e1000234.
Using a computer simulation based on US data, R. Scott Braithwaite and colleagues calculate the benefits of value-based insurance design, in which patients pay less for highly cost-effective services.
Background
Evidence suggests that cost sharing (i.e.,copayments and deductibles) decreases health expenditures but also reduces essential care. Value-based insurance design (VBID) has been proposed to encourage essential care while controlling health expenditures. Our objective was to estimate the impact of broader diffusion of VBID on US health care benefits and costs.
Methods and Findings
We used a published computer simulation of costs and life expectancy gains from US health care to estimate the impact of broader diffusion of VBID. Two scenarios were analyzed: (1) applying VBID solely to pharmacy benefits and (2) applying VBID to both pharmacy benefits and other health care services (e.g., devices). We assumed that cost sharing would be eliminated for high-value services (<$100,000 per life-year), would remain unchanged for intermediate- or unknown-value services ($100,000–$300,000 per life-year or unknown), and would be increased for low-value services (>$300,000 per life-year). All costs are provided in 2003 US dollars. Our simulation estimated that approximately 60% of health expenditures in the US are spent on low-value services, 20% are spent on intermediate-value services, and 20% are spent on high-value services. Correspondingly, the vast majority (80%) of health expenditures would have cost sharing that is impacted by VBID. With prevailing patterns of cost sharing, health care conferred 4.70 life-years at a per-capita annual expenditure of US$5,688. Broader diffusion of VBID to pharmaceuticals increased the benefit conferred by health care by 0.03 to 0.05 additional life-years, without increasing costs and without increasing out-of-pocket payments. Broader diffusion of VBID to other health care services could increase the benefit conferred by health care by 0.24 to 0.44 additional life-years, also without increasing costs and without increasing overall out-of-pocket payments. Among those without health insurance, using cost saving from VBID to subsidize insurance coverage would increase the benefit conferred by health care by 1.21 life-years, a 31% increase.
Conclusion
Broader diffusion of VBID may amplify benefits from US health care without increasing health expenditures.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
More money is spent per person on health care in the US than in any other country. US health care expenditure accounts for 16.2% of the gross domestic product and this figure is rising. Indeed, the increase in health care costs is outstripping the economy's growth rate. Consequently, US policy makers and providers of health insurance—health care in the US is largely provided by the private sector and is paid for through private health insurance or through government programs such as Medicare and Medicaid—are looking for better ways to control health expenditures. Although some health care cost reductions can be achieved by increasing efficiency, controlling the quantity of health care consumed is an essential component of strategies designed to reduce health expenditures. These strategies can target health care providers (for example, by requiring primary care physicians to provide referrals before their patients' insurance provides cover for specialist care) or can target consumers, often through cost sharing. Nowadays, most insurance plans include several tiers of cost sharing in which patients pay a larger proportion of the costs of expensive interventions than of cheap interventions.
Why Was This Study Done?
Cost sharing decreases health expenditure but it can also reduce demand for essential care and thus reduce the quality of care. Consequently, some experts have proposed value-based insurance design (VBID), an approach in which the amount of cost sharing is set according to the “value” of an intervention rather than its cost. The value of an intervention is defined as the ratio of the additional benefits to the additional costs of the intervention when compared to the next best alternative intervention. Under VBID, cost sharing could be waived for office visits necessary to control blood pressure in people with diabetes, which deliver high-value care, but could be increased for high-tech scans for dementia, which deliver low-value care. VBID has been adopted by several private health insurance schemes and its core principal is endorsed by US policy makers. However, it is unclear whether wider use of VBID is warranted. In this study, the researchers use a computer simulation of the US health care system to estimate the impact of broader diffusion of VBID on US health care benefits and costs.
What Did the Researchers Do and Find?
The researchers used their computer simulation to estimate the impact of applying VBID to cost sharing for drugs alone and to cost sharing for drugs, procedures, and other health care services for one million hypothetical US patients. In their simulation, the researchers eliminated cost sharing for services that cost less than US$100,000 per life-year gained (high-value services) and increased cost-sharing for services that cost more than US$300,000 per life-year gained (low-value services); cost-sharing remained unchanged for intermediate- or unknown-value services. With the current pattern of cost sharing, 60% of health expenditure is spent on low-value services and health care increases life expectancy by 4.70 years for an annual per person expenditure of US$5,688, the researchers report. With widespread application of VBID to cost sharing for drugs alone, health care increased life expectancy by an additional 0.03 to 0.05 years without increasing costs. With widespread application of VBID to cost sharing for other health care services, health care increased life expectancy by a further 0.24 to 0.44 years without additional costs. Finally, if the costs saved by applying VBID were used to subsidize insurance for the 15% of the US population currently without health insurance, the benefit conferred by health care among these people would increase by 1.21 life-years.
What Do These Findings Mean?
The findings of this study depend on the many assumptions included in the computer simulation, which, although complex, is a greatly simplified representation of the US health care system. Nevertheless, these findings suggest that if VBID were used more widely within the US health care system to encourage the use of high-value services, it might be possible to amplify the benefits from US health care without increasing health expenditures. Importantly, the money saved by VBID could be used to help fund universal insurance, a central aim of US health care reform. More research is needed, however, to determine the value of various health care interventions and to investigate whether other ways of linking value to cost sharing might yield even better gains in life expectancy at little or no additional cost.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000234.
Wikipedia has a page on health care in the United States (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Families USA works to promote high-quality affordable health care for all Americans and provides information about all aspects of US health care and about US health care reforms
The US Centers for Medicare and Medicaid provides information on the major government health insurance programs and on US national health expenditure statistics
doi:10.1371/journal.pmed.1000234
PMCID: PMC2821897  PMID: 20169114
6.  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
7.  Costs of day hospital and community residential chemical dependency treatment 
Background
Evidence suggests that expensive hospital-based inpatient chemical dependency programs do not deliver outcomes that are superior to less costly day hospital programs, but patient placement criteria developed by the Addiction Society of Medicine (ASAM) nonetheless have identified a need for low-intensity residential treatment for patients with higher levels of severity. Community-based residential programs may represent a low-cost inpatient alternative that satisfies the ASAM criteria, but research is lacking in this area. A recent clinical trial has found similar outcomes at social model residential treatment and clinically-oriented day hospital programs, but did not report on the costs associated with treatment in that study.
Aims
This paper addresses whether the similar outcomes in the recent trial were delivered with comparable costs. It also studies costs separately for men and women, and for Whites and non-Whites, subgroups not included or identified in prior cost effectiveness work.
Method
This paper reports on clients who participated in a randomized trial conducted in three metropolitan areas served by a large pre-paid health plan. Clients were eligible if they met the first five dimensions of the ASAM criteria for low-intensity residential treatment and had not been mandated to residential treatment due to dangerous home environment (the sixth ASAM dimension). The five day hospital programs included here are typical of mainstream private chemical dependency programs that were developed as an alternative to inpatient treatment. The seven residential programs are typical of those historically developed by members of alcohol mutual-help programs. Cost data for the study sites were collected using the Drug Abuse Treatment Cost Analysis Program (DATCAP) which produces estimates of average costs per week per client treated at a particular treatment program. Lengths of stay were derived from program records. Costs per episode for each study subject were calculated by multiplying the DATCAP-based program-specific costs (per week) by the number of weeks the subject stayed in the program to which they had been randomly assigned. Differences in length of stay, and in per-episode costs, were compared between residential and day hospital subjects using the Brown-Forsythe robust test of the equality of means.
Results
Lengths of stay at residential treatment were significantly longer than at day hospital, in the sample overall and in the disaggregated analyses for both genders and for both Whites and non-Whites. This difference was especially marked among non-Whites, who had quite short stays in day hospital. The average cost per week was $575 per week at day hospital, versus $370 per week at the residential programs. However, because of the longer stays in residential programs, this lower cost per week did not always translate to lower per-episode costs. Instead, the per-episode costs were significantly higher for those treated in residential programs than in day hospital in the sample overall, and among non-Whites. Costs were comparable for Whites and for women treated in either setting, but were marginally higher for men randomized to residential programs.
Discussion
These cost results must be considered in light of the null findings comparing outcomes between subjects randomized to residential versus day hospital programs in this study, in the overall sample and by gender and race/ethnicity: That is, the longer stays in the sample overall and for non-White clients at residential programs came at higher costs but did not lead to better rates of abstinence. An important component of the cost differential arose from especially short stays in day hospital among non-Whites, calling into question the attractiveness of day hospital for minority clients.
Conclusion
Outcomes and costs at residential versus day hospital programs were similar for women and for Whites in a randomized trial of pre-paid health plan members who met ASAM criteria for low-intensity residential treatment but were not at environmental risk. For non-Whites, and marginally for men, a preference for residential care would appear to come at a higher cost.
Implications for health care provision and use
Lengths of stay in residential treatment are significantly longer than in day hospital, but costs per week are lower. Women and Whites appear to be equally well-served in residential and day hospital programs, with no significant cost differential. Provision of residential treatment for non-Whites may be more costly than day hospital, because their residential stays are likely to be 3 times longer than they would be if treated in day hospital. For men, residential care will be marginally more costly.
Implications for health policy formulation
Residential treatment appears to represent a cost-effective alternative to day hospital for female and White clients with severe alcohol and drug problems who are not at environmental risk, although it will be important that the current study be replicated with different samples and study programs.
Implications for further research
The much shorter stays in day hospital than at residential among non-Whites highlight the need for research to better understand how to best meet the needs and preferences of non-White clients when considering both costs and outcomes.
PMCID: PMC2744443  PMID: 18424874
8.  Cost-analysis of XELOX and FOLFOX4 for treatment of colorectal cancer to assist decision-making on reimbursement 
BMC Cancer  2011;11:288.
Background
XELOX (capecitabine + oxaliplatin) and FOLFOX 4 (5-FU + folinic acid + oxaliplatin) have shown similar improvements in survival in patients with metastatic colorectal cancer (MCRC). A US cost-minimization study found that the two regimens had similar costs from a healthcare provider perspective but XELOX had lower costs than FOLFOX4 from a societal perspective, while a Japanese cost-effectiveness study found XELOX had superior cost-effectiveness. This study compared the costs of XELOX and FOLFOX4 in patients with MCRC recently treated in two oncology departments in Hong Kong.
Methods
Cost data were collected from the medical records of 60 consecutive patients (30 received XELOX and 30 FOLFOX4) from two hospitals. Drug costs, outpatient visits, hospital days and investigations were recorded and expressed as cost per patient from the healthcare provider perspective. Estimated travel and time costs were included in a societal perspective analysis. All costs were classed as either scheduled (associated with planned chemotherapy and follow-up) or unscheduled (unplanned visits or admissions and associated tests and medicines). Costs were based on government and hospital sources and expressed in US dollars (US$).
Results
XELOX patients received an average of 7.3 chemotherapy cycles (of the 8 planned cycles) and FOLFOX4 patients received 9.2 cycles (of the 12 planned cycles). The scheduled cost per patient per cycle was $2,046 for XELOX and $2,152 for FOLFOX4, while the unscheduled cost was $240 and $421, respectively. Total treatment cost per patient was $16,609 for XELOX and $23,672 for FOLFOX4; the total cost for FOLFOX4 was 37% greater than that of XELOX. The addition of the societal costs increased the total treatment cost per patient to $17,836 for XELOX and $27,455 for FOLFOX4. Sensitivity analyses showed XELOX was still less costly than FOLFOX4 when using full drug regimen costs, incorporating data from a US model with costs and adverse event data from their clinical trial and with the removal of oxaliplatin from both treatment arms. Capecitabine would have to cost around four times its present price in Hong Kong for the total resource cost of treatment with XELOX to equal that of FOLFOX4.
Conclusion
XELOX costs less than FOLFOX4 for this patient group with MCRC from both the healthcare provider and societal perspectives.
doi:10.1186/1471-2407-11-288
PMCID: PMC3146941  PMID: 21740590
9.  A Comparison of Cost Effectiveness Using Data from Randomized Trials or Actual Clinical Practice: Selective Cox-2 Inhibitors as an Example 
PLoS Medicine  2009;6(12):e1000194.
Tjeerd-Pieter van Staa and colleagues estimate the likely cost effectiveness of selective Cox-2 inhibitors prescribed during routine clinical practice, as compared to the cost effectiveness predicted from randomized controlled trial data.
Background
Data on absolute risks of outcomes and patterns of drug use in cost-effectiveness analyses are often based on randomised clinical trials (RCTs). The objective of this study was to evaluate the external validity of published cost-effectiveness studies by comparing the data used in these studies (typically based on RCTs) to observational data from actual clinical practice. Selective Cox-2 inhibitors (coxibs) were used as an example.
Methods and Findings
The UK General Practice Research Database (GPRD) was used to estimate the exposure characteristics and individual probabilities of upper gastrointestinal (GI) events during current exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) or coxibs. A basic cost-effectiveness model was developed evaluating two alternative strategies: prescription of a conventional NSAID or coxib. Outcomes included upper GI events as recorded in GPRD and hospitalisation for upper GI events recorded in the national registry of hospitalisations (Hospital Episode Statistics) linked to GPRD. Prescription costs were based on the prescribed number of tables as recorded in GPRD and the 2006 cost data from the British National Formulary. The study population included over 1 million patients prescribed conventional NSAIDs or coxibs. Only a minority of patients used the drugs long-term and daily (34.5% of conventional NSAIDs and 44.2% of coxibs), whereas coxib RCTs required daily use for at least 6–9 months. The mean cost of preventing one upper GI event as recorded in GPRD was US$104k (ranging from US$64k with long-term daily use to US$182k with intermittent use) and US$298k for hospitalizations. The mean costs (for GPRD events) over calendar time were US$58k during 1990–1993 and US$174k during 2002–2005. Using RCT data rather than GPRD data for event probabilities, the mean cost was US$16k with the VIGOR RCT and US$20k with the CLASS RCT.
Conclusions
The published cost-effectiveness analyses of coxibs lacked external validity, did not represent patients in actual clinical practice, and should not have been used to inform prescribing policies. External validity should be an explicit requirement for cost-effectiveness analyses.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Before a new treatment for a specific disease becomes an established part of clinical practice, it goes through a long process of development and clinical testing. This process starts with extensive studies of the new treatment in the laboratory and in animals and then moves into clinical trials. The most important of these trials are randomized controlled trials (RCTs), studies in which the efficacy and safety of the new drug and an established drug are compared by giving the two drugs to randomized groups of patients with the disease. The final hurdle that a drug or any other healthcare technology often has to jump before being adopted for widespread clinical use is a health technology assessment, which aims to provide policymakers, clinicians, and patients with information about the balance between the clinical and financial costs of the drug and its benefits (its cost-effectiveness). In England and Wales, for example, the National Institute for Health and Clinical Excellence (NICE), which promotes clinical excellence and the effective use of resources within the National Health Service, routinely commissions such assessments.
Why Was This Study Done?
Data on the risks of various outcomes associated with a new treatment are needed for cost-effectiveness analyses. These data are usually obtained from RCTs, but although RCTs are the best way of determining a drug's potency in experienced hands under ideal conditions (its efficacy), they may not be a good way to determine a drug's success in an average clinical setting (its effectiveness). In this study, the researchers compare the data from RCTs that have been used in several published cost-effectiveness analyses of a class of drugs called selective cyclooxygenase-2 inhibitors (“coxibs”) with observational data from actual clinical practice. They then ask whether the published cost-effectiveness studies, which generally used RCT data, should have been used to inform coxib prescribing policies. Coxibs are nonsteroidal anti-inflammatory drugs (NSAIDs) that were developed in the 1990s to treat arthritis and other chronic inflammatory conditions. Conventional NSAIDs can cause gastric ulcers and bleeding from the gut (upper gastrointestinal events) if taken for a long time. The use of coxibs avoids this problem.
What Did the Researchers Do and Find?
The researchers extracted data on the real-life use of conventional NSAIDs and coxibs and on the incidence of upper gastrointestinal events from the UK General Practice Research Database (GPRD) and from the national registry of hospitalizations. Only a minority of the million patients who were prescribed conventional NSAIDs (average cost per prescription US$17.80) or coxibs (average cost per prescription US$47.04) for a variety of inflammatory conditions took them on a long-term daily basis, whereas in the RCTs of coxibs, patients with a few carefully defined conditions took NSAIDs daily for at least 6–9 months. The researchers then developed a cost-effectiveness model to evaluate the costs of the alternative strategies of prescribing a conventional NSAID or a coxib. The mean additional cost of preventing one gastrointestinal event recorded in the GPRD by using a coxib instead of a NSAID, they report, was US$104,000; the mean cost of preventing one hospitalization for such an event was US$298,000. By contrast, the mean cost of preventing one gastrointestinal event by using a coxib instead of a NSAID calculated from data obtained in RCTs was about US$20,000.
What Do These Findings Mean?
These findings suggest that the published cost-effectiveness analyses of coxibs greatly underestimate the cost of preventing gastrointestinal events by replacing prescriptions of conventional NSAIDs with prescriptions of coxibs. That is, if data from actual clinical practice had been used in cost-effectiveness analyses rather than data from RCTs, the conclusions of the published cost-effectiveness analyses of coxibs would have been radically different and may have led to different prescribing guidelines for this class of drug. More generally, these findings provide a good illustration of how important it is to ensure that cost-effectiveness analyses have “external” validity by using realistic estimates for event rates and costs rather than relying on data from RCTs that do not always reflect the real-world situation. The researchers suggest, therefore, that health technology assessments should move from evaluating cost-efficacy in ideal populations with ideal interventions to evaluating cost-effectiveness in real populations with real interventions.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000194.
The UK National Institute for Health Research provides information about health technology assessment
The National Institute for Health and Clinical Excellence Web site describes how this organization provides guidance on promoting good health within the England and Wales National Health Service
Information on the UK General Practice Research Database is available
Wikipedia has pages on health technology assessment and on selective cyclooxygenase-2 inhibitors (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1000194
PMCID: PMC2779340  PMID: 19997499
10.  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
11.  Alternative Strategies to Reduce Maternal Mortality in India: A Cost-Effectiveness Analysis 
PLoS Medicine  2010;7(4):e1000264.
A cost-effectiveness study by Sue Goldie and colleagues finds that better family planning, provision of safe abortion, and improved intrapartum and emergency obstetrical care could reduce maternal mortality in India by 75% in 5 years.
Background
Approximately one-quarter of all pregnancy- and delivery-related maternal deaths worldwide occur in India. Taking into account the costs, feasibility, and operational complexity of alternative interventions, we estimate the clinical and population-level benefits associated with strategies to improve the safety of pregnancy and childbirth in India.
Methods and Findings
Country- and region-specific data were synthesized using a computer-based model that simulates the natural history of pregnancy (both planned and unintended) and pregnancy- and childbirth-associated complications in individual women; and considers delivery location, attendant, and facility level. Model outcomes included clinical events, population measures, costs, and cost-effectiveness ratios. Separate models were adapted to urban and rural India using survey-based data (e.g., unmet need for birth spacing/limiting, facility births, skilled birth attendants). Model validation compared projected maternal indicators with empiric data. Strategies consisted of improving coverage of effective interventions that could be provided individually or packaged as integrated services, could reduce the incidence of a complication or its case fatality rate, and could include improved logistics such as reliable transport to an appropriate referral facility as well as recognition of referral need and quality of care. Increasing family planning was the most effective individual intervention to reduce pregnancy-related mortality. If over the next 5 y the unmet need for spacing and limiting births was met, more than 150,000 maternal deaths would be prevented; more than US$1 billion saved; and at least one of every two abortion-related deaths averted. Still, reductions in maternal mortality reached a threshold (∼23%–35%) without including strategies that ensured reliable access to intrapartum and emergency obstetrical care (EmOC). An integrated and stepwise approach was identified that would ultimately prevent four of five maternal deaths; this approach coupled stepwise improvements in family planning and safe abortion with consecutively implemented strategies that incrementally increased skilled attendants, improved antenatal/postpartum care, shifted births away from home, and improved recognition of referral need, transport, and availability/quality of EmOC. The strategies in this approach ranged from being cost-saving to having incremental cost-effectiveness ratios less than US$500 per year of life saved (YLS), well below India's per capita gross domestic product (GDP), a common benchmark for cost-effectiveness.
Conclusions
Early intensive efforts to improve family planning and control of fertility choices and to provide safe abortion, accompanied by a paced systematic and stepwise effort to scale up capacity for integrated maternal health services over several years, is as cost-effective as childhood immunization or treatment of malaria, tuberculosis, or HIV. In just 5 y, more than 150,000 maternal deaths would be averted through increasing contraception rates to meet women's needs for spacing and limiting births; nearly US$1.5 billion would be saved by coupling safe abortion to aggressive family planning efforts; and with stepwise investments to improve access to pregnancy-related health services and to high-quality facility-based intrapartum care, more than 75% of maternal deaths could be prevented. If accomplished over the next decade, the lives of more than one million women would be saved.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, more than half a million women—most of them living in developing countries—die from pregnancy- or childbirth-related complications. About a quarter of these “maternal” deaths occur in India. In 2005, a woman's lifetime risk of maternal death in India was 1 in 70; in the UK, it was only one in 8,200. Similarly, the maternal mortality ratio (MMR; number of maternal deaths per 100,000 live births) in India was 450, whereas in the UK it was eight. Faced with the enormous maternal death toll in India and other developing countries, in September 2000, the United Nations pledged, as its fifth Millennium Development Goal (MDG 5), that the global MMR would be reduced to a quarter of its 1990 level by 2015. Currently, it seems unlikely that this target will be met. Between 1990 and 2005, global maternal deaths decreased by only 1% per annum instead of the 5% needed to reach MDG 5; in India, the decrease in maternal deaths between 1990 and 2005 was about 1.8% per annum.
Why Was This Study Done?
Most maternal deaths in developing countries are caused by severe bleeding after childbirth, infections soon after delivery, blood pressure disorders during pregnancy, and obstructed (difficult) labors. Consequently, experts agree that universal access to high-quality routine care during labor (“obstetric” care) and to emergency obstetrical care is needed to reduce maternal deaths. However, there is less agreement about how to adapt these “ideal recommendations” to specific situations. In developing countries with weak health systems and predominantly rural populations, it is unlikely that all women will have access to emergency obstetric care in the near future—so would beginning with improved access to family planning and to safe abortions (unsafe abortion is another major cause of maternal death) be a more achievable, more cost-effective way of reducing maternal deaths? How would family planning and safe abortion be coupled efficiently and cost-effectively with improved access to intrapartum care? In this study, the researchers investigate these questions by estimating the health and economic outcomes of various strategies to reduce maternal mortality in India.
What Did the Researchers Do and Find?
The researchers used a computer-based model that simulates women through pregnancy and childbirth to estimate the effect of different strategies (for example, increased family planning or increased access to obstetric care) on clinical outcomes (pregnancies, live births, or deaths), costs, and cost-effectiveness (the cost of saving one year of life) in India. Increased family planning was the most effective single intervention for the reduction of pregnancy-related mortality. If the current unmet need for family planning in India could be fulfilled over the next 5 years, more than 150,000 maternal deaths would be prevented, more than US$1 billion saved, and at least half of abortion-related deaths averted. However, increased family planning alone would reduce maternal deaths by 35% at most, so the researchers also used their model to test the effect of combinations of strategies on maternal death. They found that an integrated and stepwise approach (increased family planning and safe abortion combined with consecutively increased skilled birth attendants, improved care before and after birth, reduced home births, and improved emergency obstetric care) could eventually prevent nearly 80% of maternal deaths. All the steps in this strategy either saved money or involved an additional cost per year of life saved of less than US$500; given one suggested threshold for cost-effectiveness in India of the per capita GDP (US$1,068) per year of life saved, these strategies would be considered very cost-effective.
What Do These Findings Mean?
The accuracy of these findings depends on the assumptions used to build the model and the quality of the data fed into it. Nevertheless, these findings suggest that early intensive efforts to improve family planning and to provide safe abortion accompanied by a systematic, stepwise effort to improve integrated maternal health services could reduce maternal deaths in India by more than 75% in less than a decade. Furthermore, such a strategy would be cost-effective. Indeed, note the researchers, the cost savings from an initial focus on family planning and safe abortion provision would partly offset the resources needed to assure that every woman had access to high quality routine and emergency obstetric care. Thus, overall, these findings suggest that MDG 5 may be within reach in India, a conclusion that should help to mobilize political support for this worthy goal.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000264.
UNICEF (the United Nations Children's Fund) provides information on maternal mortality, including the WHO/UNICEF/UNFPA/The World Bank 2005 country estimates of maternal mortality
The World Health Organization also provides information on maternal health and about MDG 5 (in several languages)
The United Nations Millennium Development Goals Web site provides detailed information about the Millennium Declaration, the MDGs, their targets and their indicators, and about MDG 5.
The Millennium Development Goals Report 2009 and its progress chart provide an up-to-date assessment of progress toward all the MDGs
Computer simulation modeling as applied to health is further discussed at the Center for Health Decision Science at Harvard University
doi:10.1371/journal.pmed.1000264
PMCID: PMC2857650  PMID: 20421922
12.  Cost-Effectiveness of Interventions to Promote Physical Activity: A Modelling Study 
PLoS Medicine  2009;6(7):e1000110.
Linda Cobiac and colleagues model the costs and health outcomes associated with interventions to improve physical activity in the population, and identify specific interventions that are likely to be cost-saving.
Background
Physical inactivity is a key risk factor for chronic disease, but a growing number of people are not achieving the recommended levels of physical activity necessary for good health. Australians are no exception; despite Australia's image as a sporting nation, with success at the elite level, the majority of Australians do not get enough physical activity. There are many options for intervention, from individually tailored advice, such as counselling from a general practitioner, to population-wide approaches, such as mass media campaigns, but the most cost-effective mix of interventions is unknown. In this study we evaluate the cost-effectiveness of interventions to promote physical activity.
Methods and Findings
From evidence of intervention efficacy in the physical activity literature and evaluation of the health sector costs of intervention and disease treatment, we model the cost impacts and health outcomes of six physical activity interventions, over the lifetime of the Australian population. We then determine cost-effectiveness of each intervention against current practice for physical activity intervention in Australia and derive the optimal pathway for implementation. Based on current evidence of intervention effectiveness, the intervention programs that encourage use of pedometers (Dominant) and mass media-based community campaigns (Dominant) are the most cost-effective strategies to implement and are very likely to be cost-saving. The internet-based intervention program (AUS$3,000/DALY), the GP physical activity prescription program (AUS$12,000/DALY), and the program to encourage more active transport (AUS$20,000/DALY), although less likely to be cost-saving, have a high probability of being under a AUS$50,000 per DALY threshold. GP referral to an exercise physiologist (AUS$79,000/DALY) is the least cost-effective option if high time and travel costs for patients in screening and consulting an exercise physiologist are considered.
Conclusions
Intervention to promote physical activity is recommended as a public health measure. Despite substantial variability in the quantity and quality of evidence on intervention effectiveness, and uncertainty about the long-term sustainability of behavioural changes, it is highly likely that as a package, all six interventions could lead to substantial improvement in population health at a cost saving to the health sector.
Please see later in the article for Editors' Summary
Editors' Summary
Background
The human body needs regular physical activity throughout life to stay healthy. Physical activity—any bodily movement produced by skeletal muscles that uses energy—helps to maintain a healthy body weight and to prevent or delay heart disease, stroke, type 2 diabetes, colon cancer, and breast cancer. In addition, physically active people feel better and live longer than physically inactive people. For an adult, 30 minutes of moderate physical activity—walking briskly, gardening, swimming, or cycling—at least five times a week is sufficient to promote and maintain health. But at least 60% of the world's population does not do even this modest amount of physical activity. The daily lives of people in both developed and developing countries are becoming increasingly sedentary. People are sitting at desks all day instead of doing manual labor; they are driving to work in cars instead of walking or cycling; and they are participating less in physical activities during their leisure time.
Why Was This Study Done?
In many countries, the chronic diseases that are associated with physical inactivity are now a major public-health problem; globally, physical inactivity causes 1.9 million deaths per year. Clearly, something has to be done about this situation. Luckily, there is no shortage of interventions designed to promote physical activity, ranging from individual counseling from general practitioners to mass-media campaigns. But which intervention or package of interventions will produce the optimal population health benefits relative to cost? Although some studies have examined the cost-effectiveness of individual interventions, different settings for analysis and use of different methods and assumptions make it difficult to compare results and identify which intervention approaches should be give priority by policy makers. Furthermore, little is known about the cost-effectiveness of packages of interventions. In this study, the researchers investigate the cost-effectiveness in Australia (where physical inactivity contributes to 10% of deaths) of a package of interventions designed to promote physical activity in adults using a standardized approach (ACE-Prevention) to the assessment of the cost-effectiveness of health-care interventions.
What Did the Researchers Do and Find?
The researchers selected six interventions for their study: general practitioner “prescription” of physical activity; general practitioner referral to an exercise physiologist; a mass-media campaign to promote physical activity; the TravelSmart car use reduction program; a campaign to encourage the use of pedometers to increase physical activity; and an internet-based program. Using published data on the effects of physical activity on the amount of illness and death caused by breast and colon cancer, heart disease, stroke, and type 2 diabetes and on the effectiveness of each intervention, the researchers calculated the health outcomes of each intervention in disability-adjusted life years (DALY; a year of healthy life lost because of premature death or disability) averted over the lifetime of the Australian population. They also calculated the costs associated with each intervention offset by the costs associated with the five conditions listed above. These analyses showed that the pedometer program and the mass-media campaign were likely to be the most cost-effective interventions. These interventions were also most likely to be cost-saving. Referral to an exercise physiologist was the least cost-effective intervention. The other three interventions, though unlikely to be cost-saving, were likely to be cost-effective. Finally, a package of all six interventions would be cost-effective and would avert 61,000 DALYs, a third of what could be achieved if every Australian did 30 minutes of physical activity five times a week.
What Do These Findings Mean?
As in all modeling studies, these findings depend on the quality of the data and on the assumptions included by the researchers in their calculations. Unfortunately, there was substantial variability in the quantity and quality of evidence on the effectiveness of each intervention and uncertainty about the long-term effects of each intervention. Nevertheless, the findings presented in this study suggest that the assessment of the cost-effectiveness of a combination of interventions designed to promote physical activity might provide policy makers with some guidance about the best way to reduce the burden of disease caused by physical inactivity. More specifically, for Australia, these findings suggest that the package of the six interventions considered here is likely to provide a cost-effective way to substantially improve the health of the nation.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000110.
The World Health Organization provides information about physical activity and health (in several languages); it also provides an explanation of DALYs
The US Centers for Disease Control and Prevention provides information on physical activity for different age groups and for health professionals
The UK National Health Service information source Choices also explains the benefits of regular physical activity
MedlinePlus has links to other resources about exercise and physical fitness (in English and Spanish)
The University of Queensland Web site has more information on ACE-Prevention (Assessing Cost-Effectiveness Prevention)
doi:10.1371/journal.pmed.1000110
PMCID: PMC2700960  PMID: 19597537
13.  Physician Awareness of Drug Cost: A Systematic Review 
PLoS Medicine  2007;4(9):e283.
Background
Pharmaceutical costs are the fastest-growing health-care expense in most developed countries. Higher drug costs have been shown to negatively impact patient outcomes. Studies suggest that doctors have a poor understanding of pharmaceutical costs, but the data are variable and there is no consistent pattern in awareness. We designed this systematic review to investigate doctors' knowledge of the relative and absolute costs of medications and to determine the factors that influence awareness.
Methods and Findings
Our search strategy included The Cochrane Library, EconoLit, EMBASE, and MEDLINE as well as reference lists and contact with authors who had published two or more articles on the topic or who had published within 10 y of the commencement of our review. Studies were included if: either doctors, trainees (interns or residents), or medical students were surveyed; there were more than ten survey respondents; cost of pharmaceuticals was estimated; results were expressed quantitatively; there was a clear description of how authors defined “accurate estimates”; and there was a description of how the true cost was determined. Two authors reviewed each article for eligibility and extracted data independently. Cost accuracy outcomes were summarized, but data were not combined in meta-analysis because of extensive heterogeneity. Qualitative data related to physicians and drug costs were also extracted. The final analysis included 24 articles. Cost accuracy was low; 31% of estimates were within 20% or 25% of the true cost, and fewer than 50% were accurate by any definition of cost accuracy. Methodological weaknesses were common, and studies of low methodological quality showed better cost awareness. The most important factor influencing the pattern and accuracy of estimation was the true cost of therapy. High-cost drugs were estimated more accurately than inexpensive ones (74% versus 31%, Chi-square p < 0.001). Doctors consistently overestimated the cost of inexpensive products and underestimated the cost of expensive ones (binomial test, 89/101, p < 0.001). When asked, doctors indicated that they want cost information and feel it would improve their prescribing but that it is not accessible.
Conclusions
Doctors' ignorance of costs, combined with their tendency to underestimate the price of expensive drugs and overestimate the price of inexpensive ones, demonstrate a lack of appreciation of the large difference in cost between inexpensive and expensive drugs. This discrepancy in turn could have profound implications for overall drug expenditures. Much more focus is required in the education of physicians about costs and the access to cost information. Future research should focus on the accessibility and reliability of medical cost information and whether the provision of this information is used by doctors and makes a difference to physician prescribing. Additionally, future work should strive for higher methodological standards to avoid the biases we found in the current literature, including attention to the method of assessing accuracy that allows larger absolute estimation ranges for expensive drugs.
From a review of data from 24 studies, Michael Allan and colleagues conclude that doctors often underestimate the price of expensive drugs and overestimate the price of those that are inexpensive.
Editors' Summary
Background.
Many medicines are extremely expensive, and the cost of buying them is a major (and increasing) proportion of the total cost of health care. Governments and health-care organizations try to find ways of keeping down costs without reducing the effectiveness of the health care they provide, but their efforts to control what is spent on medicines have not been very successful. There are often two or more equally effective drugs available for treating the same condition, and it would obviously help keep costs down if, when a doctor prescribes a medicine, he or she chose the cheapest of the effective drugs available. This choice could result in savings for whoever is paying for the drugs, be it the government, the patient, or a medical insurance organization.
Why Was This Study Done?
Doctors who prescribe drugs cannot be expected to know the exact cost of each drug on the market, but it would he helpful if they had some impression of the cost of a treatment and how the various alternatives compare in price. However, systems deciding how drugs are priced are often very complex. (This is particularly the case in the US.) The researchers wanted to find out how aware doctors are regarding drug costs and the difference between the alternatives. They also wanted to know what factors affected their awareness.
What Did the Researchers Do and Find?
They decided to do a systematic review of all the research already conducted that addressed this issue so that the evidence from all of them could be considered together. In order to do such a review they had to specify precise requirements for the type of study that they would include and then comprehensively search the medical literature for such studies. They found 24 studies that met their requirements. From these studies, they concluded that doctors were usually not accurate when asked to estimate the cost of drugs; doctors came up with estimates that were within 25% of the true cost less than one-third of the time. In particular doctors tended to underestimate the cost of expensive drugs and overestimate the cost of the cheaper alternatives. A further analysis of the studies showed that many doctors said they would appreciate more accurate information on costs to help them choose which drugs to prescribe but that such information was not readily available.
What Do These Findings Mean?
The researchers concluded that their systematic review demonstrates a lack of appreciation by prescribing doctors of the large difference in cost between inexpensive and expensive drugs, and that this finding has serious implications for overall spending on drugs. They call for more education and information to be provided to doctors on the cost of medicines together with better processes to help doctors in making such decisions.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040283.
A brief guide to systematic reviews has been published by the BMJ (British Medical Journal)
The Web site of the Cochrane Collaboration is a more detailed source of information on systematic reviews; in particular there is a newcomers' guide and information for health-care consumers
The Kaiser Family Foundation, a nonprofit, private operating foundation focusing on the major health care issues in the US, has a section on prescription drugs and their costs
doi:10.1371/journal.pmed.0040283
PMCID: PMC1989748  PMID: 17896856
14.  Cost-Effectiveness of Preventing Loss to Follow-up in HIV Treatment Programs: A Côte d'Ivoire Appraisal 
PLoS Medicine  2009;6(10):e1000173.
Based on data from West Africa, Elena Losina and colleagues predict that interventions to reduce dropout rates from HIV treatment programs (such as eliminating copayments) will be cost-effective.
Background
Data from HIV treatment programs in resource-limited settings show extensive rates of loss to follow-up (LTFU) ranging from 5% to 40% within 6 mo of antiretroviral therapy (ART) initiation. Our objective was to project the clinical impact and cost-effectiveness of interventions to prevent LTFU from HIV care in West Africa.
Methods and Findings
We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International model to project the clinical benefits and cost-effectiveness of LTFU-prevention programs from a payer perspective. These programs include components such as eliminating ART co-payments, eliminating charges to patients for opportunistic infection-related drugs, improving personnel training, and providing meals and reimbursing for transportation for participants. The efficacies and costs of these interventions were extensively varied in sensitivity analyses. We used World Health Organization criteria of <3× gross domestic product per capita (3× GDP per capita = US$2,823 for Côte d'Ivoire) as a plausible threshold for “cost-effectiveness.” The main results are based on a reported 18% 1-y LTFU rate. With full retention in care, projected per-person discounted life expectancy starting from age 37 y was 144.7 mo (12.1 y). Survival losses from LTFU within 1 y of ART initiation ranged from 73.9 to 80.7 mo. The intervention costing US$22/person/year (e.g., eliminating ART co-payment) would be cost-effective with an efficacy of at least 12%. An intervention costing US$77/person/year (inclusive of all the components described above) would be cost-effective with an efficacy of at least 41%.
Conclusions
Interventions that prevent LTFU in resource-limited settings would substantially improve survival and would be cost-effective by international criteria with efficacy of at least 12%–41%, depending on the cost of intervention, based on a reported 18% cumulative incidence of LTFU at 1 y after ART initiation. The commitment to start ART and treat HIV in these settings should include interventions to prevent LTFU.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since the first reported case in 1981. Currently, about 33 million people are infected with the human immunodeficiency virus (HIV), which causes AIDS. Two-thirds of people infected with HIV live in sub-Saharan Africa. HIV infects and destroys immune system cells, thereby weakening the immune system and rendering infected individuals susceptible to infection. There is no cure for HIV/AIDS. Combination antiretroviral therapy (ART), a mixture of antiretroviral drugs that suppress the replication of the virus in the body, is used to treat and prevent HIV infection. ART is expensive but major international efforts by governments, international organizations, and funding bodies have increased ART availability. According to World Health Organization (WHO) estimates, at least 9.7 million people in low- and middle-income countries need ART and as of 2007, 3 million of those people had reliable access to the drugs.
Why Was This Study Done?
Although ART is an effective treatment for HIV, a large number of individuals who initiate ART do not receive long-term follow-up care. These patients are generally sicker and have a worse long-term outcome than those who receive follow-up care. Loss to follow up (LTFU) is a significant problem that can undermine the benefits of expanding ART availability. Strategies to improve follow up concentrate on bringing lost patients back into the health care system, but such patients often die before they can be contacted. Prevention of LTFU might be a better strategy to improve HIV care after ART initiation, but there is little information available on which specific interventions might best accomplish this goal.
What Did the Researchers Do and Find?
Given the lack of reported data on the actual costs and effectiveness of LTFU prevention, the researchers used a model to estimate the clinical impact and cost-effectiveness of several possible strategies to prevent LTFU in HIV-infected persons receiving ART in Côte d'Ivoire, West Africa. The researchers used the previously developed Cost-Effectiveness of Preventing AIDS Complications (CEPAC) computer simulation model and combined it with data from a program of ART delivery in Abidjan, Côte d'Ivoire. They then projected the clinical benefits and the cost required to attain a given level of benefit (cost-effectiveness ratio) of different LTFU-prevention strategies from the perspective of the payer (the organization that pays all the medical costs to provide care). Several interventions were considered, including reducing costs to patients (eliminating patient co-payments and paying for transportation) and increasing services to patients at their visits (improving staff training in HIV care, and providing meals at clinic times). LTFU was predicted to cause a 54.3%–58.3% reduction in the estimated life expectancy beyond age 37; patients continuing HIV care were predicted to live a further 144.7 months whie those lost to follow up by 1 year after ART initiation were predicted to live only for a further 73.9–80.7 months. LTFU-prevention strategies in the Côte d'Ivoire were deemed to be cost-effective if they cost less than $2,823 (which is 3× gross domestic product per capita) per year of life saved. The efficacy and cost of the different LTFU-prevention strategies varied in the analyses; stopping ART co-payment alone would be cost-effective at a cost of $22/person/year if it reduced LTFU rates by 12%, while including all the LTFU-prevention strategies described would be cost-effective at $77/person/year if they reduced LTFU-rates by 41%.
What Do These Findings Mean?
The findings suggest that moderately effective strategies for preventing LTFU in resource-limited settings would improve survival, provide good value for money, and should be used to improve HIV treatment programs. Although modeling is valuable to explore the costs and effectiveness of LTFU-prevention strategies it cannot replace the need for more reported data to shed light on problems leading to LTFU and the prevention strategies required to combat it. Also, Côte d'Ivoire might not be representative of all West African countries or resource-limited settings. A similar analysis using data from other ART programs in different countries would be useful to provide better understanding of the impact of LTFU in HIV treatment programs. Finally, the research highlights the cost of second-line ART (a new antiretroviral drug combination for patients in whom first-line treatment fails) as a crucial issue. It is estimated that 5% of all people receiving ART in low- and middle-income countries receive second-line ART and these numbers are expected to increase. Second-line ART had major effects on cost-effectiveness, and a reduction in the cost of this treatment is critical in order to guarantee continued access to HIV treatment.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000173.
This study is further discussed in a PLoS Medicine Perspective by Gregory Bisson and Jeffrey Stringer
WHO provides information on disease prevention, treatment, and HIV/AIDS programs and projects
The UN Millennium Development Goals project site contains information on worldwide efforts to halt the spread of HIV/AIDS
aidsmap, a nonprofit, nongovernmental organization, provides information on HIV and supporting those living with HIV
doi:10.1371/journal.pmed.1000173
PMCID: PMC2762030  PMID: 19859538
15.  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
16.  Cost-Effectiveness of Pooled Nucleic Acid Amplification Testing for Acute HIV Infection after Third-Generation HIV Antibody Screening and Rapid Testing in the United States: A Comparison of Three Public Health Settings 
PLoS Medicine  2010;7(9):e1000342.
Angela Hutchinson and colleagues conducted a cost-effectiveness analysis of pooled nucleic acid amplification testing following HIV testing and show that it is not cost-effective at recommended antibody testing intervals for high-risk persons except in very high-incidence settings.
Background
Detection of acute HIV infection (AHI) with pooled nucleic acid amplification testing (NAAT) following HIV testing is feasible. However, cost-effectiveness analyses to guide policy around AHI screening are lacking; particularly after more sensitive third-generation antibody screening and rapid testing.
Methods and Findings
We conducted a cost-effectiveness analysis of pooled NAAT screening that assessed the prevention benefits of identification and notification of persons with AHI and cases averted compared with repeat antibody testing at different intervals. Effectiveness data were derived from a Centers for Disease Control and Prevention AHI study conducted in three settings: municipal sexually transmitted disease (STD) clinics, a community clinic serving a population of men who have sex with men, and HIV counseling and testing sites. Our analysis included a micro-costing study of NAAT and a mathematical model of HIV transmission. Cost-effectiveness ratios are reported as costs per quality-adjusted life year (QALY) gained in US dollars from the societal perspective. Sensitivity analyses were conducted on key variables, including AHI positivity rates, antibody testing frequency, symptomatic detection of AHI, and costs. Pooled NAAT for AHI screening following annual antibody testing had cost-effectiveness ratios exceeding US$200,000 per QALY gained for the municipal STD clinics and HIV counseling and testing sites and was cost saving for the community clinic. Cost-effectiveness ratios increased substantially if the antibody testing interval decreased to every 6 months and decreased to cost-saving if the testing interval increased to every 5 years. NAAT was cost saving in the community clinic in all situations. Results were particularly sensitive to AHI screening yield.
Conclusions
Pooled NAAT screening for AHI following negative third-generation antibody or rapid tests is not cost-effective at recommended antibody testing intervals for high-risk persons except in very high-incidence settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Since 1981, acquired immunodeficiency syndrome (AIDS) has killed about 25 million people and about 30 million people are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV, which is most often transmitted through unprotected sex with an infected partner or injection drug use, infects and kills immune system cells, leaving infected individuals susceptible to other infectious diseases. The first, often undiagnosed stage of HIV infection—acute HIV infection (AHI)—lasts a few weeks and sometimes involves a flu-like illness. During AHI, the immune system responds to HIV by beginning to make antibodies that recognize the virus but seroconversion—the appearance of detectable amounts of antibody in the blood—takes 6–12 weeks. During the second, symptom-free stage of HIV infection, which can last many years, the virus gradually destroys the immune system so that by the third stage of infection unusual infections (for example, persistent yeast infections) begin to occur. The final stage of infection (AIDS) is characterized by multiple severe infections and by the development of unusual cancers.
Why Was This Study Done?
Antiretroviral drugs control HIV infections but don't cure them. It is very important, therefore, to prevent HIV transmission by avoiding HIV risk behaviors that increase the risk of HIV infection such as having sex without a condom or with many partners. Individuals with AHI in particular need to avoid high-risk behaviors because these people are extremely infectious. However, routine tests for HIV infection that measure antibodies in the blood often give false-negative results in people with AHI because of the time lag between infection and seroconversion. Nucleic acid amplification testing (NAAT), which detects HIV genetic material in the blood, is a more accurate way to diagnose AHI but is expensive. In this study, the researchers investigate whether pooled NAAT screening (specimens are pooled before testing to reduce costs) for AHI in clinic settings after third-generation antibody testing is a cost-effective HIV prevention strategy. That is, does the gain in quality-adjusted life years (QALY, a measure of the quantity and quality of life generated by healthcare interventions) achieved by averting new HIV infections outweigh the costs of pooled NAAT screening?
What Did the Researchers Do and Find?
The researchers combined effectiveness data from a US study in which AHI was detected using pooled NAAT in three settings (sexually transmitted disease [STD] clinics, a community clinic serving men who have sex with men [MSM], and HIV counseling/testing sites) with a “micro-costing” study of NAAT and a mathematical model of HIV transmission. They then calculated the costs per QALY gained (the cost-effectiveness ratio) as a result of HIV prevention by identification and notification of people with AHI through pooled NAAT screening compared with repeat antibody testing. Pooled NAAT for AHI screening following annual antibody testing (the recommended testing interval for high-risk individuals), they estimate, would cost US$372,300 and US$484,400 per QALY gained for the counseling/testing sites and STD clinics, respectively, whereas pooled NAAT for AHI screening was cost-saving for the community clinic serving MSM. The cost-effectiveness ratio increased for the counseling/testing sites and STD clinics when the antibody testing interval was decreased to 6 months but remained cost-saving for the community clinic. With an antibody testing interval of 5 years, pooled NAAT was cost-saving in all three settings.
What Do These Findings Mean?
Cost-effectiveness ratios of US$100,000–US$200,000 are considered acceptable in the US. These results suggest therefore, that the cost of pooled NAAT screening for AHI following negative third-generation antibody testing is not acceptable at the recommended testing interval for high-risk individuals except in settings where HIV infection is very common such as clinics serving MSM. The researchers reach a similar conclusion in a separate cost-effectiveness analysis of pooled NAAT screening following a negative rapid HIV test. Although the accuracy of these results depends on numerous assumptions made in the cost-effectiveness analyses (for example, the degree to which awareness of HIV status affects the behavior of people with AHI), sensitivity analyses (investigations of the effect of altering key assumptions) show that these findings are not greatly affected by changes in many of these assumptions. Thus, the researchers conclude, NAAT screening should be reserved for settings that serve populations in which there are very high levels of new HIV infection.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000342.
The US Centers for Disease Control and Prevention provides information on HIV infection and AIDS and on HIV testing and diagnosis
HIV InSite has information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS nonprofit organization on many aspects of HIV/AIDS, including HIV testing (in English and Spanish)
MedlinePlus has links to further resources on AIDS (in English and Spanish)
The UK National Institute of Health and Clinical Excellence has a page on measuring effectiveness and cost-effectiveness
doi:10.1371/journal.pmed.1000342
PMCID: PMC2946951  PMID: 20927354
17.  Cost-Effectiveness of Rapid Syphilis Screening in Prenatal HIV Testing Programs in Haiti 
PLoS Medicine  2007;4(5):e183.
Background
New rapid syphilis tests permit simple and immediate diagnosis and treatment at a single clinic visit. We compared the cost-effectiveness, projected health outcomes, and annual cost of screening pregnant women using a rapid syphilis test as part of scaled-up prenatal testing to prevent mother-to-child HIV transmission in Haiti.
Methods and Findings
A decision analytic model simulated health outcomes and costs separately for pregnant women in rural and urban areas. We compared syphilis syndromic surveillance (rural standard of care), rapid plasma reagin test with results and treatment at 1-wk follow-up (urban standard of care), and a new rapid test with immediate results and treatment. Test performance data were from a World Health Organization–Special Programme for Research and Training in Tropical Diseases field trial conducted at the GHESKIO Center Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes in Port-au-Prince. Health outcomes were projected using historical data on prenatal syphilis treatment efficacy and included disability-adjusted life years (DALYs) of newborns, congenital syphilis cases, neonatal deaths, and stillbirths. Cost-effectiveness ratios are in US dollars/DALY from a societal perspective; annual costs are in US dollars from a payer perspective. Rapid testing with immediate treatment has a cost-effectiveness ratio of $6.83/DALY in rural settings and $9.95/DALY in urban settings. Results are sensitive to regional syphilis prevalence, rapid test sensitivity, and the return rate for follow-up visits. Integrating rapid syphilis testing into a scaled-up national HIV testing and prenatal care program would prevent 1,125 congenital syphilis cases and 1,223 stillbirths or neonatal deaths annually at a cost of $525,000.
Conclusions
In Haiti, integrating a new rapid syphilis test into prenatal care and HIV testing would prevent congenital syphilis cases and stillbirths, and is cost-effective. A similar approach may be beneficial in other resource-poor countries that are scaling up prenatal HIV testing.
Analyzing data from Haiti, Bruce Schackman and colleagues report that scale-up of prenatal HIV testing programs provides a cost-effective opportunity to prevent congenital syphilis through rapid testing.
Editors' Summary
Background.
Congenital syphilis (syphilis that is passed on from a woman infected with the disease to her unborn baby) is a major preventable public health problem. Around half of all pregnancies among women infected with syphilis result in stillbirth or death of the baby shortly after birth. However, it should be possible to reduce the health burden of congenital syphilis if infections among pregnant women could be quickly and accurately diagnosed. In resource-poor countries, many syphilis infections go undiagnosed, because the tests that are normally used involve sending samples away to a laboratory for processing. This means that the diagnosis can only be confirmed, and treatment started, at the next available visit. As a result, there is a delay in starting antibiotic treatment, and some women may never receive their intended treatment at all if they cannot return for their follow-up visit. However, new tests are available that don't involve cold storage of reagents or electrical equipment, and these can be used to give an immediate result about syphilis infection even in rural or resource-poor settings. Currently, global initiatives are underway to ensure many more pregnant women are tested for HIV and to reduce the risk of HIV being passed on from a woman to her baby. These initiatives could provide an important opportunity for carrying out widespread immediate screening for syphilis during pregnancy as well. Such screening might then help reduce infant deaths substantially.
Why Was This Study Done?
Field trials evaluating rapid syphilis tests have already been carried out by the World Health Organization's Special Programme for Research and Training in Tropical Diseases. One such trial, carried out in Port-au-Prince, Haiti, evaluated the success of three different rapid syphilis tests as compared to two “gold standard” tests (older tests that are generally considered reliable, but which don't give an immediate result). These researchers wanted to use data from these trials to compare costs and predicted health outcomes of including different types of syphilis screening as part of scaled-up prenatal care. Specifically, the researchers wanted to find out whether including rapid syphilis testing as part of universal prenatal care would be cost-effective and whether it would reduce the rate of stillbirths and congenital syphilis.
What Did the Researchers Do and Find?
This research was based on data from the field trials previously carried out in Haiti. The data from these trials were used to create a model comparing three different strategies for screening pregnant women for syphilis infections. The three strategies were as follows: checking for the symptoms of syphilis (assumed to be the standard of care in rural areas); standard testing for antibody response to the syphilis bacterium, after which treatment can be provided at follow-up a week later (assumed to be the standard of care in urban areas); and, finally, rapid testing that gives an immediate result. For each strategy, the researchers predicted what the health outcomes would be. These outcomes are summarized in “disability-adjusted life years” (DALYs) that reflect the number of years of healthy life lost due to congenital syphilis among newborn babies, the number of stillbirths, and the number of neonatal deaths. Cost-effectiveness of each strategy was also worked out by dividing the additional costs of testing and treatment for each strategy by the number of DALYs avoided using that screening method compared to the next most expensive alternative. Under the model, urban and rural settings were looked at separately. Immediate testing was more expensive than either standard testing or checking for symptoms, but emerged as more cost-effective than standard testing in rural settings; the immediate test would cost an additional $7–$10 per disability-adjusted life year compared to the current rural or urban standard of care. The researchers predicted that if immediate syphilis testing were provided to all pregnant women in Haiti who currently have access to prenatal care, over 1,000 congenital syphilis cases would be avoided, along with over 1,000 stillbirths and neonatal deaths, at a yearly cost of $525,000.
What Do These Findings Mean?
This model suggests that including rapid syphilis testing as part of current global initiatives for preventing mother-to-child transmission of HIV could substantially reduce infant deaths. The strategy is also likely to be cost-effective.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040183.
MedlinePlus encyclopedia entry on congenital syphilis
Information from the World Health Organization about congenital syphilis, including information about screening programs and new screening tests
A report is also available from the Special Programme for Research and Training in Tropical Diseases regarding rapid syphilis tests
AVERT, an international AIDS charity, provides information about preventing mother-to-child transmission of HIV
doi:10.1371/journal.pmed.0040183
PMCID: PMC1880854  PMID: 17535105
18.  Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study, Peru 
PLoS Medicine  2014;11(7):e1001675.
Tom Wingfield and colleagues investigate the relationship between catastrophic costs and tuberculosis outcomes for patients receiving free tuberculosis care in Peru.
Please see later in the article for the Editors' Summary
Background
Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed “catastrophic” but are poorly defined. We studied TB-affected households' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs.
Methods and Findings
From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household's annual income. In poorer households, costs were lower but constituted a higher proportion of the household's annual income: 27% (95% CI = 20%–43%) in the least-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%–61%] versus 38% [95% CI = 34%–41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7–15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1.7 [95% CI = 1.1–2.6], p = 0.01). The adjusted population attributable fraction of adverse outcomes explained by catastrophic costs was 18% (95% CI = 6.9%–28%), similar to that of MDR TB (20% [95% CI = 14%–25%]). Sensitivity analyses demonstrated that existing catastrophic costs thresholds (≥10% or ≥15% of household annual income) were not associated with adverse outcome in our setting. Study limitations included not measuring certain “dis-saving” variables (including selling household items) and gathering only 6 mo of costs-specific follow-up data for MDR TB patients.
Conclusions
Despite free TB care, having TB disease was expensive for impoverished TB patients in Peru. Incurring higher relative costs was associated with adverse TB outcome. The population attributable fraction indicated that catastrophic costs and MDR TB were associated with similar proportions of adverse outcomes. Thus TB is a socioeconomic as well as infectious problem, and TB control interventions should address both the economic and clinical aspects of this disease.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Caused by the infectious microbe Mycobacterium tuberculosis, tuberculosis (or TB) is a global health problem. In 2012, an estimated 8.6 million people fell ill with TB, and 1.3 million were estimated to have died because of the disease. Poverty is widely recognized as an important risk factor for TB, and developing nations shoulder a disproportionate burden of both poverty and TB disease. For example, in Lima (the capital of Peru), the incidence of TB follows the poverty map, sparing residents living in rich areas of the city while spreading among poorer residents that live in overcrowded households.
The Peruvian government, non-profit organizations, and the World Health Organization (WHO) have extended healthcare programs to provide free diagnosis and treatment for TB and drug-resistant strains of TB in Peru, but rates of new TB cases remain high. For example, in Ventanilla (an area of 16 shantytowns located in northern Lima), the rate of infection was higher during the study period, at 162 new cases per 100,000 people per year, than the national average. About one-third of the 277,895 residents of Ventanilla live on under US$1 per day.
Why Was This Study Done?
Poverty increases the risks associated with contracting TB infection, but the disease also affects the most economically productive age group, and the income of TB-affected households often decreases post-diagnosis, exacerbating poverty. A recent WHO consultation report proposed a target of eradicating catastrophic costs for TB-affected families by 2035, but hidden TB-related costs remain understudied, and there is no international consensus defining catastrophic costs incurred by patients and households affected by TB. Lost income and the cost of transport are among hidden costs associated with free treatment programs; these costs and their potential impact on patients and their households are not well defined. Here the researchers sought to clarify and characterize TB-related costs and explore whether there is a relationship between the hidden costs associated with free TB treatment programs and the likelihood of completing treatment and becoming cured of TB.
What Did the Researchers Do and Find?
Over a seven-year period (2002–2009), the researchers recruited 876 study participants with TB diagnosed at health posts located in Ventanilla. To provide a comparative control group, a sample of 487 healthy individuals was also recruited to participate. Participants were interviewed prior to treatment, and households' TB-related direct expenses and indirect expenses (lost income attributed to TB) were recorded every 2–4 wk. Data were collected during scheduled household visits.
TB patients were poorer than controls, and analysis of the data showed that accessing free TB care was expensive for TB patients, especially those with multi-drug-resistant (MDR) TB. Total expenses were similar pre-treatment compared to during treatment for TB patients, despite receiving free care (1.1 versus 1.2 times the same household's monthly income). Even though direct expenses (for example, costs of medical examinations and medicines other than anti-TB therapy) were lower in the poorest households, their total expenses (direct and indirect) made up a greater proportion of their household annual income: 48% for the poorest households compared to 27% in the least-poor households.
The researchers defined costs that were equal to or above one-fifth (20%) of household annual income as catastrophic because this threshold marked the greatest association with adverse treatment outcomes such as death, abandoning treatment, failing to respond to treatment, or TB recurrence. By calculating the population attributable fraction—the proportional reduction in population adverse treatment outcomes that could occur if a risk factor was reduced to zero—the authors estimate that adverse TB outcomes explained by catastrophic costs and MDR TB were similar: 18% for catastrophic costs and 20% for MDR TB.
What Do These Findings Mean?
The findings of this study indicate a potential role for social protection as a means to improve TB disease control and health, as well as defining a novel, evidence-based threshold for catastrophic costs for TB-affected households of 20% or more of annual income. Addressing the economic impact of diagnosis and treatment in impoverished communities may increase the odds of curing TB.
Study limitations included only six months of follow-up data being gathered on costs for each participant and not recording “dissavings,” such as selling of household items in response to financial shock. Because the study was observational, the authors aren't able to determine the direction of the association between catastrophic costs and TB outcome. Even so, the study indicates that TB is a socioeconomic as well as infectious problem, and that TB control interventions should address both the economic and clinical aspects of the disease.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001675.
The World Health Organization provides information on all aspects of tuberculosis, including the Global Tuberculosis Report 2013
The US Centers for Disease Control and Prevention has information about tuberculosis
Médecins Sans Frontières's TB&ME blog provides patients' stories of living with MDR TB
TB Alert, a UK-based charity that promotes TB awareness worldwide, has information on TB in several European, African, and Asian languages
More information is available about the Innovation For Health and Development (IFHAD) charity and its research team's work in Peru
doi:10.1371/journal.pmed.1001675
PMCID: PMC4098993  PMID: 25025331
19.  Baggage handler seniority and musculoskeletal symptoms: is heavy lifting in awkward positions associated with the risk of pain? 
BMJ Open  2013;3(11):e004055.
Objectives
Heavy lifting is associated with musculoskeletal disorders but it is unclear whether it is related to acute reversible effects or to chronic effects from cumulated exposure. The aim of this study was to examine whether musculoskeletal symptoms in Danish airport baggage handlers were associated with their seniority as baggage handler, indicating chronic effects from cumulated workload.
Methods
We established a group of baggage handlers employed at Copenhagen Airport during the period 1983–2012 (n=3092) and a reference group of men in other unskilled occupations with less heavy work (n=2478). Data regarding work history, lifestyle and musculoskeletal symptoms were collected using a self-administered questionnaire (response rate 70.1% among baggage handlers and 68.8% among the reference group).
Results
The ORs of self-reported musculoskeletal symptoms during the last 12 months in the neck/upper back, lower back, shoulders, elbows, wrists, hips and knees were significantly higher in baggage handlers than in the reference group. These differences were explained by significant linear effects of baggage handler seniority for six anatomical regions. Adjustment for age, body mass index, smoking and leisure-time physical activity did not change these results. The findings were stable over age strata and among present and former baggage handlers.
Conclusions
The risk of musculoskeletal symptoms in six anatomical regions increased with increasing seniority as a baggage handler. This is consistent with the assumption that cumulated heavy lifting may cause chronic or long-lasting musculoskeletal symptoms. However, we cannot exclude that other factors related to baggage handler seniority may explain some of the associations.
doi:10.1136/bmjopen-2013-004055
PMCID: PMC3845067  PMID: 24293209
Epidemiology; seniority
20.  Optimizing cost-efficiency in mean exposure assessment - cost functions reconsidered 
Background
Reliable exposure data is a vital concern in medical epidemiology and intervention studies. The present study addresses the needs of the medical researcher to spend monetary resources devoted to exposure assessment with an optimal cost-efficiency, i.e. obtain the best possible statistical performance at a specified budget. A few previous studies have suggested mathematical optimization procedures based on very simple cost models; this study extends the methodology to cover even non-linear cost scenarios.
Methods
Statistical performance, i.e. efficiency, was assessed in terms of the precision of an exposure mean value, as determined in a hierarchical, nested measurement model with three stages. Total costs were assessed using a corresponding three-stage cost model, allowing costs at each stage to vary non-linearly with the number of measurements according to a power function. Using these models, procedures for identifying the optimally cost-efficient allocation of measurements under a constrained budget were developed, and applied on 225 scenarios combining different sizes of unit costs, cost function exponents, and exposure variance components.
Results
Explicit mathematical rules for identifying optimal allocation could be developed when cost functions were linear, while non-linear cost functions implied that parts of or the entire optimization procedure had to be carried out using numerical methods.
For many of the 225 scenarios, the optimal strategy consisted in measuring on only one occasion from each of as many subjects as allowed by the budget. Significant deviations from this principle occurred if costs for recruiting subjects were large compared to costs for setting up measurement occasions, and, at the same time, the between-subjects to within-subject variance ratio was small. In these cases, non-linearities had a profound influence on the optimal allocation and on the eventual size of the exposure data set.
Conclusions
The analysis procedures developed in the present study can be used for informed design of exposure assessment strategies, provided that data are available on exposure variability and the costs of collecting and processing data. The present shortage of empirical evidence on costs and appropriate cost functions however impedes general conclusions on optimal exposure measurement strategies in different epidemiologic scenarios.
doi:10.1186/1471-2288-11-76
PMCID: PMC3125387  PMID: 21600023
21.  Acute myeloblastic leukaemia--a model for assessing value for money for new treatment programmes. 
BMJ : British Medical Journal  1991;302(6772):323-326.
OBJECTIVE--To measure the effects of changes in treatment of acute myeloblastic leukaemia that may give better value for money. DESIGN--Retrospective analysis of patients' notes to identify items of management costing money; prospective costing of these items. The Medical Research Council acute myeloblastic leukaemia 9 trial was used to identify the amount and distribution of these costs when either one or two courses of induction treatment were required to obtain complete remission. These findings were then extrapolated to four published international controlled trials using similarly intense treatment and in which the number of courses of treatment required for complete remission was stated, to compare British costs for treatment with idarubicin and daunorubicin, both in combination with cytarabine. SETTING--Leukaemia unit, Royal Marsden Hospital, London. SUBJECTS--Data on 10 patients receiving intensive induction treatment for acute myeloblastic leukaemia were used to identify 160 items of cost in four broad groups: general (including accommodation), diagnostic, supportive treatment, and cytotoxic chemotherapy. One newly treated patient was prospectively assessed over one month, including a time and motion study, to cost these items; then costs for 268 patients from the MRC trial receiving moderate induction chemotherapy including daunorubicin were assessed, and costs for treatment of 522 patients in the four international studies comparing daunorubicin with idarubicin were analysed. MAIN OUTCOME MEASURES--Cost effectiveness was measured as the overall cost to obtain complete remission in untreated patients with acute myeloblastic leukaemia after treatment with idarubicin or daunorubicin. RESULTS--The 160 costed items were measured for their sensitivity in varying the total cost of treatment, this being assessed within Britain in other district general and private hospitals to measure the extremes of cost of these items. Overall, idarubicin, although more expensive, showed a substantial saving (1477 pounds per patient) in total hospital costs, more than offsetting the increased cost (607 pounds) of the new treatment, an overall savings of 870 pounds per patient (5%). CONCLUSION--Approaches modelling cost effectiveness may be an essential part of planning new programmes of treatment in the future. This method can be used to estimate the cost effectiveness of the treatments in different environments and countries where costs may vary widely.
PMCID: PMC1669019  PMID: 1900453
22.  Hospital treatment -is it affordable? A structured cost analysis of vaginal deliveries and planned caesarean sections 
Introduction
The analysis of cost effectiveness in hospitals is as difficult as treating the patients properly. We are yet not able to answer the simple question of what costs are caused by a certain diagnosis and its treatment during an average hospital stay.
Methods
To answer some issues of the global problem of cost effectiveness during hospitalisation, we analysed the costs and the cost structure of a normal obstetrical hospital stay during an uncomplicated vaginal delivery and a planned caesarean section. Cost data was collected and summarized from the patients file, the hospital's computer system gathering all cost centres, known material expenses and expenses of non obstetrical medical services.
Results
For vaginal deliveries/planned caesareans we can calculate with a surplus of about 83 €/1432 €. About 45% of the summarized costs are calculated on a reliable database.
Discussion
The introduction of the DRG based clearing system in Germany has aggravated the discussion on cost effectiveness. Our meticulous work-up of expenses excluded personal precautionary costs and personnel costs of documentation because no tools are described to depict such costs. If we would add these costs to the known expenses of our study, we strongly suspect that hospital treatment of vaginal deliveries or planned caesarean sections is not cost effective.
doi:10.1186/2047-783X-14-11-502
PMCID: PMC3352292  PMID: 19948447
cost effectiveness; vaginal delivery; caesarean section; DRG
23.  The Clinical and Economic Impact of Point-of-Care CD4 Testing in Mozambique and Other Resource-Limited Settings: A Cost-Effectiveness Analysis 
PLoS Medicine  2014;11(9):e1001725.
Emily Hyle and colleagues conduct a cost-effectiveness analysis to estimate the clinical and economic impact of point-of-care CD4 testing compared to laboratory-based tests in Mozambique.
Please see later in the article for the Editors' Summary
Background
Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique.
Methods and Findings
We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%–61.0%), increasing to 65.0% (95% CI, 64.9%–65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6–9.6 y) and US$2,440 (95% CI, US$2,440–US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3–10.3 y) and US$2,800 (95% CI, US$2,790–US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480–US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4.
Conclusions
POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
AIDS has already killed about 36 million people, and a similar number of people (mostly living in low- and middle-income countries) are currently 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, HIV-infected individuals usually died within ten years of infection. After effective antiretroviral therapy (ART) became available in 1996, HIV infection became a chronic condition for people living in high-income countries, but because ART was expensive, HIV/AIDS remained a fatal disease in low- and middle-income countries. In 2003, the international community began to work towards achieving universal ART coverage, and by the end of 2012, 61% of HIV-positive people (nearly 10 million individuals) living low- and middle-income countries who were eligible for treatment—because their CD4 cell count had fallen below 350 cells/mm3 of blood or they had developed an AIDS-defining condition—were receiving treatment.
Why Was This Study Done?
In sub-Saharan Africa nearly 50% of HIV-infected people eligible for treatment remain untreated, in part because of poor linkage between HIV diagnosis and clinical care. After patients receive a diagnosis of HIV infection, their eligibility for ART initiation is determined by sending a blood sample away to a laboratory for a CD4 cell count (the current threshold for treatment is a CD4 count below 500/mm3, although low- and middle-income countries have yet to update their national guidelines from the threshold CD4 count below 350/mm3). Patients have to return to the clinic to receive their test results and to initiate ART if they are eligible for treatment. Unfortunately, many patients are “lost” during this multistep process in resource-limited settings. Point-of-care CD4 tests at HIV diagnosis—tests that are done on the spot and provide results the same day—might help to improve linkage to care in such settings. Here, the researchers use a mathematical model to assess the clinical outcomes and cost-effectiveness of point-of-care CD4 testing at the time of HIV diagnosis compared to laboratory-based testing in Mozambique, where about 1.5 million HIV-positive individuals live.
What Did the Researchers Do and Find?
The researchers used a validated model of HIV testing, linkage, and treatment called the Cost-Effectiveness of Preventing AIDS Complications–International (CEPAC-I) model to compare the clinical impact, costs, and cost-effectiveness of point-of-care and laboratory CD4 testing in newly diagnosed HIV-infected patients in Mozambique. They used published data to estimate realistic values for various model input parameters, including the probability of linkage to care following the use of each test, the accuracy of the tests, and the cost of each test. At a CD4 threshold for treatment of 250/mm3, the model predicted that 60.9% of newly diagnosed HIV-infected people would survive five years if their immunological status was assessed using the laboratory-based CD4 test, whereas 65% would survive five years if the point-of-care test was used. Predicted life expectancies were 9.6 and 10.3 years with the laboratory-based and point-of-care tests, respectively, and the per person lifetime costs (which mainly reflect treatment costs) associated with the two tests were US$2,440 and $US2,800, respectively. Finally, the incremental cost-effectiveness ratio—calculated as the incremental costs of one therapeutic intervention compared to another divided by the incremental benefits—was US$500 per year of life saved, when comparing use of the point-of-care test with a laboratory-based test.
What Do These Findings Mean?
These findings suggest that, compared to laboratory-based CD4 testing, point-of-care testing at HIV diagnosis could improve survival for HIV-infected individuals in Mozambique. Because the per capita gross domestic product in Mozambique is US$570, these findings also indicate that point-of-care testing would be very cost-effective compared to laboratory-based testing (an incremental cost-effectiveness ratio less than one times the per capita gross domestic product is regarded as very cost-effective). As with all modeling studies, the accuracy of these findings depends on the assumptions built into the model and on the accuracy of the input parameters. However, the point-of-care strategy averted deaths and was estimated to be cost-effective compared to the laboratory-based test over a wide range of input parameter values reflecting Mozambique and several other resource-limited settings that the researchers modeled. Importantly, these “sensitivity analyses” suggest that point-of-care CD4 testing is likely to have the greatest impact on HIV-related deaths and be economically efficient in settings in sub-Saharan Africa with the most limited health care resources, provided point-of-care CD4 testing improves the linkage to care for HIV-infected people.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001725.
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); its “Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infections: Recommendations for a Public Health Approach”, which highlights the potential of point-of-care tests to improve the linkage of newly diagnosed HIV-infected patients to care, is available
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, and summaries of recent research findings on HIV care and treatment; it has a fact sheet on CD4 testing
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on starting, monitoring, and switching treatment and on HIV and AIDS in sub-Saharan Africa (in English and Spanish)
The “UNAIDS Report on the Global AIDS Epidemic 2013” provides up-to-date information about the AIDS epidemic and efforts to halt it
Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001725
PMCID: PMC4165752  PMID: 25225800
24.  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
25.  Diagnostic Accuracy and Cost-Effectiveness of Alternative Methods for Detection of Soil-Transmitted Helminths in a Post-Treatment Setting in Western Kenya 
Objectives
This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths (STH) in a post-treatment setting in western Kenya. A cost analysis also explores the cost implications of collecting samples during school surveys when compared to household surveys.
Methods
Stool samples were collected from children (n = 652) attending 18 schools in Bungoma County and diagnosed by the Kato-Katz and Mini-FLOTAC coprological methods. Sensitivity and additional diagnostic performance measures were analyzed using Bayesian latent class modeling. Financial and economic costs were calculated for all survey and diagnostic activities, and cost per child tested, cost per case detected and cost per STH infection correctly classified were estimated. A sensitivity analysis was conducted to assess the impact of various survey parameters on cost estimates.
Results
Both diagnostic methods exhibited comparable sensitivity for detection of any STH species over single and consecutive day sampling: 52.0% for single day Kato-Katz; 49.1% for single-day Mini-FLOTAC; 76.9% for consecutive day Kato-Katz; and 74.1% for consecutive day Mini-FLOTAC. Diagnostic performance did not differ significantly between methods for the different STH species. Use of Kato-Katz with school-based sampling was the lowest cost scenario for cost per child tested ($10.14) and cost per case correctly classified ($12.84). Cost per case detected was lowest for Kato-Katz used in community-based sampling ($128.24). Sensitivity analysis revealed the cost of case detection for any STH decreased non-linearly as prevalence rates increased and was influenced by the number of samples collected.
Conclusions
The Kato-Katz method was comparable in diagnostic sensitivity to the Mini-FLOTAC method, but afforded greater cost-effectiveness. Future work is required to evaluate the cost-effectiveness of STH surveillance in different settings.
Author Summary
Accurate methods of diagnosis and optimal strategies to sample the population are essential for the reliable mapping and surveillance of infectious diseases. The current standard for detection of soil-transmitted helminths (STH) entails use of the Kato-Katz diagnostic method. Alternative diagnostic methods, such as flotation techniques like the Mini-FLOTAC, have been developed with hopes of achieving greater sensitivity and ease of use. Here, we evaluate the diagnostic accuracy of the Kato-Katz method and the Mini-FLOTAC method for detecting STH infection. We use Bayesian latent class modeling to calculate the diagnostic accuracy in the absence of a gold-standard method for STH detection. Stool samples were collected from school-age children using school-based and community-based sampling. We present cost estimates for use of the Kato-Katz and Mini-FLOTAC diagnostic methods in combination with both sampling methods, providing cost data for the various survey scenarios. Sensitivity was comparable between the Kato-Katz and Mini-FLOTAC methods for detection of any STH species over a single day (Kato Katz: 52.0%, Mini-FLOTAC: 49.1%) and consecutive days (Kato-Katz: 76.9%, Mini-FLOTAC: 74.1%). Costs were lowest in scenarios using the Kato-Katz method; cost per child tested and cost per case correctly classified for school-based sampling with the Kato-Katz diagnostic were $10.14 and $12.84 respectively. The lowest cost per case detected was $128.24 with community-based sampling and use of Kato-Katz. Further work is required on the cost-effectiveness of diagnostic and sampling methods for STH surveys and surveillance of other neglected tropical diseases (NTDs) in various settings. To this end, we provide the model code used in the diagnostic analysis and a costing template for STH surveys.
doi:10.1371/journal.pntd.0002843
PMCID: PMC4014443  PMID: 24810593

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