The Costs of Drugs in Infectious Diseases: Branded, Generics, and Why We Should Care.

While health care providers have largely turned a blind eye, the cost of health care in the US has been skyrocketing, in part as a result of rising drug prices. Patent protections and market exclusivity, while serving to incentivize targeted new drug development, have exacerbated inequitable outcomes and reduced access, sometimes fueling national epidemics. Branded drug manufacturers face few barriers to exorbitant pricing of drugs with exclusivity-as in the cases of Sovaldi, Zyvox, and Truvada. Furthermore, albendazole, pyrimethamine, and penicillin demonstrate that generic medications without patent exclusivity are not guaranteed to have durably low costs, especially where manufacturer competition is lacking. There is a way forward: through education and awareness, cost-conscious guideline development, government regulation, and market-level incentives, health care providers can collaborate to contain drug prices, curbing expenditures overall while expanding health care access to patients.

Production responses and cost-benefit of long-acting pre-lambing anthelmintic treatment of yearling ewes in two commercial flocks in New Zealand.

AIMS: To investigate the production responses and cost-benefit of administering a controlled-release anthelmintic capsule (CRC) to pregnant yearling ewes prior to lambing. METHODS: Yearling ewes from two commercial sheep flocks (A, n=489; B, n=248) in the North Island of New Zealand were enrolled in the study. Prior to lambing, CRC containing albendazole and abamectin were administered to half the ewes while the other half remained untreated. Ewe liveweights and body condition scores were measured prior to lambing, at weaning and, for Flock B, prior to subsequent mating. Lambs were matched to dams shortly after birth and the weight and number of lamb weaned per ewe were determined. A cost-benefit analysis was undertaken for Flock B considering the increased weight of lamb weaned per ewe, and the weight of ewes at the next mating and the benefit in terms of lambs born. RESULTS: The mean weight at weaning of treated ewes was greater for treated than untreated ewes by 2.76 (95% CI 0.64-4.88) kg in Flock A (p<0.001) and 2.35 (95% CI -0.41-5.12) kg in Flock B (p=0.003); the weight of lamb weaned per ewe was greater for treated than untreated ewes by 1.43 (95% CI -0.71 to -3.49) kg in Flock A (p=0.041) and 3.97 (95% CI 1.59-6.37) kg in Flock B (p<0.001), and ewe liveweight prior to subsequent mating was greater for treated than untreated ewes in Flock B by 4.60 (95% CI 3.6-5.6) kg (p<0.001). There was no difference in the percentage of lambs reared to weaning between treated and untreated ewes in either flock (p>0.8). The overall cost-benefit of treatment for Flock B was NZ$9.44 per treated ewe. CONCLUSIONS AND CLINICAL RELEVANCE: Pre-lambing CRC administration to yearling ewes resulted in increased ewe weaning weights and weight of lamb weaned in both the flocks studied. There was an economic benefit in the one flock where this was assessed.

High-cost generic drugs--implications for patients and policymakers.

Some older generic drugs have become very expensive, owing to factors including drug shortages, supply disruptions, and consolidations in the generic-drug industry. But generics manufacturers that legally obtain a market monopoly can also unilaterally raise prices.

Cost-effectiveness of triple drug administration (TDA) with praziquantel, ivermectin and albendazole for the prevention of neglected tropical diseases in Nigeria.

Onchocerciasis, lymphatic filariasis (LF), schistosomiasis and soil transmitted, helminthiasis (STH) are all co-endemic in Nigeria. Annual mass drug administration (MDA) with ivermectin (for onchocerciasis), albendazole (for STH and with ivermectin for LF) and praziquantel (for schistosomiasis) is the WHO-recommended treatment strategy for preventive chemotherapy. Separate delivery rounds for distribution of these drugs have been the usual approach to MDA. All three drugs, however, have now been shown to be clinically and programmatically safe for co-administration with what has come to be known as triple drug administration (TDA). We examined the cost savings of converting from separate delivery rounds to TDA in two states in Nigeria. In 2008, eight local government areas received a single round of ivermectin with albendazole followed at least 1 week later by a single round of praziquantel to school-aged children. The following year, a single round was administered with TDA. The number of treated individuals was essentially unchanged during both years (1,301,864 in 2008 and 1,297,509 in 2009) and no change in adverse events was reported. The total programmatic costs for the MDA, not including drug and overhead costs, reduced by 41% from $123,624 to $72,870. Cost savings were limited in larger populations due to economies of scale. TDA is recommended for mature MDA.

The Effect of Drug Pricing on Outpatient Payments and Treatment for Three Soil-Transmitted Helminth Infections in the United States, 2010-2017.

The price of certain antiparasitic drugs (e.g., albendazole and mebendazole) has dramatically increased since 2010. The effect of these rising prices on treatment costs and use of standard of care (SOC) drugs is unknown. To measure the impact of drug prices on overall outpatient cost and quality of care, we identified outpatient visits associated with ascariasis, hookworm, and trichuriasis infections from the 2010 to 2017 MarketScan Commercial Claims and Encounters and Multi-state Medicaid databases using Truven Health MarketScan Treatment Pathways. Evaluation was limited to members with continuous enrollment in non-capitated plans 30 days prior, and 90 days following, the first diagnosis. The utilization of SOC prescriptions was considered a marker for quality of care. The impact of drug price on the outpatient expenses was measured by comparing the changes in drug and nondrug outpatient payments per patient through Welch's two sample t-tests. The total outpatient payments per patient (drug and nondrug), for the three parasitic infections, increased between 2010 and 2017. The increase was driven primarily by prescription drug payments, which increased 20.6-137.0 times, as compared with nondrug outpatient payments, which increased 0.3-2.2 times. As prices of mebendazole and albendazole increased, a shift to alternative SOC and non-SOC drug utilization was observed. Using parasitic infection treatment as a model, increases in prescription drug prices can act as the primary driver of increasing outpatient care costs. Simultaneously, there was a shift to alternative SOC, but also to non-SOC drug treatment, suggesting a decrease in quality of care.

Evaluation of Treatment Coverage and Enhanced Mass Drug Administration for Onchocerciasis and Lymphatic Filariasis in Five Local Government Areas Treating Twice Per Year in Edo State, Nigeria.

The western region of Edo state in southern Nigeria is highly endemic for onchocerciasis. Despite years of mass drug administration (MDA) with ivermectin (IVM), reports suggest persistently high prevalence of onchocerciasis, presumably because of poor coverage. In 2016, twice-per-year treatment with IVM (combined with albendazole for lymphatic filariasis in the first round where needed) began in five local government areas (LGAs) of Edo state. We undertook a multistage cluster survey within 3 months after each round of MDA to assess coverage. First-round coverage was poor: among 4,942 people of all ages interviewed from 145 clusters, coverage was 31.1% (95% confidence intervals [CI]: 24.1-38.0%). Most respondents were not offered medicines. To improve coverage in the second round, three LGAs were randomized to receive MDA through a "modified campaign" approach focused on improved supervision and monitoring. The other two LGAs continued with standard MDA as before. A similar survey was conducted after the second round, interviewing 3,362 people in 87 clusters across the five LGAs. Coverage was not statistically different from the first round (40.0% [95% CI: 31.0-49.0%]) and there was no significant difference between the groups (P = 0.7), although the standard MDA group showed improvement over round 1 (P < 0.01). The additional cost per treatment in the modified MDA was 1.6 times that of standard MDA. Compliance was excellent among those offered treatment. We concluded that poor mobilization, medicine distribution, and program penetration led to low coverage. These must be addressed to improve treatment coverage in Edo state.

Shortage of Albendazole and Its Consequences for Patients with Cystic Echinococcosis Treated at a Referral Center in Italy.

Albendazole (ABZ) is the best drug available to treat cystic echinococcosis (CE), a neglected tropical disease. Cystic echinococcosis patients often receive a continuous course of the drug for 6-12 months. In Italy, ABZ shortages occur almost on a yearly basis. We searched clinical records at the World Health Organization Collaborating Center for the Clinical Management of CE in Pavia, Italy, to estimate the amount of ABZ prescribed to patients between January 2012 and February 2017. The cost of ABZ was estimated at €2.25 per tablet based on the current market price in Italy. Patients to whom ABZ had been prescribed were contacted to determine if they had experienced difficulties in purchasing the drug and to assess how such problems affected their treatment. Of 348 identified CE patients, 127 (36.5%) were treated with ABZ for a total of 20,576 days. This led to an estimated cost of €92,592. Seventy-five patients were available for follow-up, 42 (56%) reported difficulties in obtaining ABZ. Of these patients, four (9.5%) had to search out of their region and 10 (23.8%) had to go out of the country. A total of 27 patients (64%) had to visit more than five pharmacies to locate the drug and 10 patients (23.8%) interrupted treatment because of ABZ nonavailability. Shortages in ABZ distribution can disrupt CE treatment schedules and jeopardize patient health.

Sustainable access to deworming drugs in a changing landscape.

The global effort to control and eliminate soil-transmitted helminthiasis (STH) currently depends on donations of albendazole and mebendazole, which reached more than 530 million children in 2016. As we approach 2020, the WHO goal of eliminating STH as a public health problem will not be met in most endemic countries, and ongoing treatment will be necessary. Additionally, the volume of drugs required might increase because global strategies for STH aim to interrupt transmission. Under the 2012 London Declaration on Neglected Tropical Diseases, pharmaceutical company commitments to donate drugs to control or eliminate neglected tropical diseases extend to 2020. We are approaching a period of uncertainty regarding different strategies for control and elimination of STH, the size and target populations for future donations, and optimum drugs and drug combinations. Long-term reliance on large-scale donation of deworming drugs is not sustainable. The global STH community need to develop a strategy to secure a sustainable global supply of affordable and effective anthelmintic drugs. This strategy should include improvement of the quality of generic drugs through innovative technical partnerships.

Anthelmintic Drugs: Their Efficacy and Cost-Effectiveness in Different Parity Cattle.

Gastrointestinal nematodes are responsible for economic losses in bovines and are characterized by reduced milk production, decreased working efficiency, and even death. In our study, the effect of different anthelmintic treatments on nematode control in different parity cattle (Friesian crossbreds) at calving and their effect on milk yield were evaluated. The economics of anthelmintics and farm benefits in terms of increased milk production after deworming was also calculated. We screened cattle of first and second parity for nematodes. Animals were randomly selected in each group. In first parity animals, there were 23 positive cattle found, which were divided into 3 different groups, while in second parity animals there were 20 positive cattle which were also divided into 3 groups. For treatment of gastrointestinal nematodes, we used albendazole (velbazine) at 10 mg/kg body weight and levamisole (Nilverm®) at 7.5 mg/kg. In this study, both drugs were found effective in controlling nematode infections in cattle. Percentage reduction of eggs per gram (EPG) by albendazole was 48.20, 85.34, and 93.90% and 51.54, 81.43, 91.74% on day 7, 14, and 21 in first and second parity animals, respectively. Percentage reduction of EPG by levamisole was 44.45, 76.92, and 88.03% and 46.60, 73.78, 85.43% on day 7, 14, and 21 in first and second parity animals, respectively. The average increase in milk production in albendazole-treated groups was 0.39 and 0.92 L per day while increases in levamisole treated groups were 0.27 and 0.55 L per day in first and second parity cattle, respectively. After treatment, albendazole increased the milk fat by 0.07 and 0.1% while levamisole decreased by 0.02 and 0.05% in first and second parity cattle, respectively. It is concluded that anthelmintic treatments of recently calved cattle have a significant effect on milk production due to the nematode control. Milk production increased significantly in second parity cattle following anthelmintic treatment as compared to first parity animals. Levamisole had a negative effect on fat concentration in cattle while albendazole-treated cattle showed a positive effect. Albendazole has been found more efficient in reducing EPG of helminths in both parity animals as compared to levamisole-treated animals while the cost-benefit ratio of levamisole was greater than albendazole.

Progress towards countrywide control of schistosomiasis and soil-transmitted helminthiasis in Uganda.

Schistosomiasis caused by infection with Schistosoma mansoni is a serious public health burden in 38 of the 56 districts of Uganda. This article reviews the initial experience of the national control programme. Launched in 2003, this started with a pilot phase with the main aim of utilizing the experience to formulate feasible and appropriate methods of drug delivery. Overall, 432,746 people were treated and coverage was 91.4% in schools and 64.7% in communities. The issues raised by independent evaluators included that most communities did not participate in the selection of community drug distributors (CDD) and that teachers and CDDs needed refresher training mainly on health education and the management of side effects. As a way forward, it is suggested that the Ministry of Health should integrate deworming into the existing health infrastructure so that every time a child is reached for any health service, the child is also de-wormed.

A combined school- and community-based campaign targeting all school-age children of Burkina Faso against schistosomiasis and soil-transmitted helminthiasis: performance, financial costs and implications for sustainability.

A combined school- and community-based campaign targeting the entire school-age population of Burkina Faso with drugs against schistosomiasis (praziquantel) and soil-transmitted helminthiasis (albendazole) was implemented in 2004-2005. In total, 3,322,564 children from 5 to 15 years of age were treated, equivalent to a 90.8% coverage of the total school-age population of the country. The total costs of the campaign were estimated to be US 1,067,284 dollars, of which 69.4% was spent on the drugs. Delivery costs per child treated were US 0.098 dollar, in the same range as school-based only interventions implemented in other countries; total costs per child treated (including drugs) were US 0.32 dollar. We conclude that a combined school- and community-based strategy is effective in attaining a high coverage among school-age children in countries where school enrolment is low and where primary schools cannot serve as the exclusive drug distribution points. The challenge for Burkina Faso will now be to ensure the sustainability of these disease control activities.

The Leogane, Haiti demonstration project: decreased microfilaremia and program costs after three years of mass drug administration.

To support the global program to eliminate lymphatic filariasis (LF), well-monitored demonstration projects are important for defining the relationship between coverage and reductions in microfilaremia. We are using mass treatment with diethylcarbamazine (DEC) and albendazole in an effort to eliminate LF from Leogane, Haiti. Wuchereria bancrofti microfilaremia prevalence at baseline ranged from 0.8% to 15.9% in four sentinel sites. After three rounds of DEC-albendazole mass drug administration (MDA), both microfilaremia prevalence and intensity decreased dramatically. Mild and moderate adverse reactions after treatment were common, especially after the first MDA, but decreased after subsequent MDAs. Drug coverage for the first year was estimated to be 72%, but concerns about adverse reactions appeared to decrease drug coverage in the second MDA. As a result of community education efforts that focused on providing a greater understanding of adverse reactions, coverage increased dramatically for the third round. Program efficiency increased substantially; the costs per person treated for three rounds of MDA were 2.23 US dollars, 1.96 US dollars, and 1.30 US dollars per person, respectively. The Leogane experience highlights the importance of adapting community education and mobilization campaigns to achieve and maintain good coverage.

Frequency, severity, and costs of adverse reactions following mass treatment for lymphatic filariasis using diethylcarbamazine and albendazole in Leogane, Haiti, 2000.

In October 2000, 71,187 persons were treated for lymphatic filariasis using albendazole and diethylcarbamazine (DEC) or DEC alone in Leogane, Haiti. We documented the frequency of adverse reactions, severity and cost of treatment. Adverse reactions were classified as minor, moderate, or severe. Overall, 24% (17,421) of the treated persons reported one or more adverse reactions. There were 15,916 (91%) minor and 1502 (9%) moderate adverse reaction reports. Men outnumbered women 2:1 in reporting moderate problems. Three patients, representing roughly one in 25,000 persons treated, were hospitalized with severe adverse reactions judged to be treatment-associated by physician review. The cost per person treated for adverse reactions was more than twice the cost per person treated for lymphatic filariasis (dollar 1.60 versus dollar 0.71). Severe adverse reactions to lymphatic filariasis treatment using DEC with or without albendazole are uncommon. Minor and moderate reactions are more commonly reported and their management represents a challenge to lymphatic filariasis elimination programs.

Comparison of methods for estimating drug coverage for filariasis elimination, Leogane Commune, Haiti.

In the global effort to eliminate lymphatic filariasis, annual mass treatments are conducted with diethylcarbamazine (DEC) or ivermectin, combined with albendazole. The success of this strategy depends on achieving high levels of drug coverage, which reduces the number of persons with circulating microfilariae so that transmission of the parasite is interrupted. Because resources are often limited, a simple, inexpensive, and reliable method to estimate drug coverage is needed. During the period December 2000 to February 2001, three methods were used to assess drug coverage in Leogane Commune, Haiti: a probability survey using a cluster sample design (n = 1421 persons); a distribution-point survey based on a convenience sample of houses near the distribution points (n = 4341 persons); and a survey based on a convenience sample of primary schools (n = 5036 children). The coverage estimations were 71.3% (95% CI 66.7-75.9), 73.6% (95% CI 70.1-77.0), and 77.8% (95% CI 73.5-82.1), respectively. Survey costs for the probability, distribution point, and school surveys were US$2217, US$979, and US$312, respectively. The 2 convenience sampling methods provided point estimates of drug coverage that were similar to those of the probability survey. These methods may have a role for monitoring drug treatment coverage between less frequent, but more costly, probability sample surveys.

The cost of delivering and sustaining a control programme for schistosomiasis and soil-transmitted helminthiasis.

Large-scale chemotherapy programmes for helminth control continue to rely heavily on donor support. This is despite more than a 10-fold reduction in delivery costs from integrating drug distribution through the school system rather than using mobile teams and a marked decline in the price of albendazole and praziquantel. Even at these low prices (

The cost of large-scale school health programmes which deliver anthelmintics to children in Ghana and Tanzania. The Partnership for Child Development.

It has been argued that the delivery of anthelmintics to school-children through existing education infrastructure can be one of the most cost-effective approaches to controlling parasitic worm infection. This paper examines the actual costs of a combination of mass and selective treatment for schistosomiasis using praziquantel and mass treatment for intestinal nematodes using albendazole, as an integral part of school health programmes reaching 80442 pupils in 577 schools in Volta Region, Ghana, and reaching 109099 pupils in 350 schools in Tanga Region, Tanzania. The analysis shows that financial delivery costs per child treated using praziquantel, which involved a dose related to body mass and a prior screening at the school level, were US$ 0.67 in Ghana and US$ 0.21 in Tanzania, while the delivery costs for albendazole, which was given as a fixed dose to all children, were US$ 0.04 in Ghana and US$ 0.03 in Tanzania. The higher unit costs in Ghana reflect the epidemiology of infection; overall, fixed costs were similar in both countries, but fewer children required treatment in Ghana. Analysis of economic costs-which includes the cost of unpaid days of labour--indicates that the financial costs are increased in Ghana by 78% and in Tanzania by 44%. It is these additional costs which are avoided by integration into an existing infrastructure. It is concluded that: the base cost of delivering a universal, standard, school-based health intervention can be as low as US$ 0.03 per child treated; that even a slight increase in the complexity of delivery can have a significant impact on the cost of intervention; and that the use of the education infrastructure does indeed offer significant savings in delivery costs.

A study of the cost effectiveness of selective health interventions for the control of intestinal parasites in rural Bangladesh.

The study examined the cost effectiveness of 4 different regimens in reducing the prevalence and intensity of infection of Ascaris lumbricoides, Trichuris trichiura, and hookworm over an 18-mo period in randomized community samples of children aged 2-8 yr living in rural Bangladesh. The household was the unit of randomization in each community. The 4 regimens were (1) only chemotherapy to all household members at the commencement of the study (i.e., at an interval of 18 mo), (2) same as group (1) and regular health education throughout the study period, (3) chemotherapy to all household members at the commencement of the study and subsequent chemotherapy to all children at intervals of 6 mo, and (4) same as group 3 with the addition of regular health education throughout the study period. Health education (through home and school visits and focus group discussions) was aimed at increasing awareness of worm transmission and the disabilities caused by intestinal helminths. Simple ways of improving personal hygiene and sanitation through hand washing, nail trimming, wearing of shoes, and use of a latrine and clean water supplies were encouraged. Because albendazole is a broad spectrum anthelmintic, the cost effectiveness of the 4 interventions were compared by the weighted percentage reduction in prevalence and the weighted percentage reduction in intensities of infection as measured by geometric mean egg loads of all 3 worms combined. The most cost-effective strategy was the single albendazole mass chemotherapy at an interval of 18 mo. The 2 regimens involving health education were the least cost effective.

Production losses in Merino ewes and financial penalties caused by trichostrongylid infections during winter and spring.

The productivity of Merino ewes treated with ivermectin and a controlled-release capsule containing albendazole was compared with untreated ewes grazing the same pastures on each of 3 farms. Treated breeding ewes had significantly increased greasy fleece weights (GFW, 6.5% and 7.1%) compared with untreated breeding ewes, on 2 of 3 farms but treatment caused no significant increase in the GFW of non-breeding ewes. Other benefits of treatment on all farms were a significant increase in body weight gain (from 1.7 to 3.7 kg) and a significant decrease in the weight of dag removed at crutching (from 42 to 622 g). These benefits occurred despite the presence on each farm of worms resistant to benzimidazoles. One disadvantage of treatment was an increase in mean fibre diameter of wool from treated ewes of from 0.12 to 0.41 microns. This increase reduces the value of the wool. Partial budgets indicated a net loss of from 8 to 62 cents per ewe for treatment. However, potential benefits such as increased growth rate and wool production from lambs of treated ewes were not included in the analysis. On one farm ewes were classified as 'susceptible' to severe dag if they had a dag score > or = 4 at the time of capsule treatment. Ewes classified as 'susceptible' were about 7 times more likely to develop severe dag than were other ewes. There was no significant difference between the GFW of untreated 'susceptible' ewes and untreated ewes not classified as 'susceptible'.(ABSTRACT TRUNCATED AT 250 WORDS)