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1.  Evaluating Drug Prices, Availability, Affordability, and Price Components: Implications for Access to Drugs in Malaysia 
PLoS Medicine  2007;4(3):e82.
Background
Malaysia's stable health care system is facing challenges with increasing medicine costs. To investigate these issues a survey was carried out to evaluate medicine prices, availability, affordability, and the structure of price components.
Methods and Findings
The methodology developed by the World Health Organization (WHO) and Health Action International (HAI) was used. Price and availability data for 48 medicines was collected from 20 public sector facilities, 32 private sector retail pharmacies and 20 dispensing doctors in four geographical regions of West Malaysia. Medicine prices were compared with international reference prices (IRPs) to obtain a median price ratio. The daily wage of the lowest paid unskilled government worker was used to gauge the affordability of medicines. Price component data were collected throughout the supply chain, and markups, taxes, and other distribution costs were identified. In private pharmacies, innovator brand (IB) prices were 16 times higher than the IRPs, while generics were 6.6 times higher. In dispensing doctor clinics, the figures were 15 times higher for innovator brands and 7.5 for generics. Dispensing doctors applied high markups of 50%–76% for IBs, and up to 316% for generics. Retail pharmacy markups were also high—25%–38% and 100%–140% for IBs and generics, respectively. In the public sector, where medicines are free, availability was low even for medicines on the National Essential Drugs List. For a month's treatment for peptic ulcer disease and hypertension people have to pay about a week's wages in the private sector.
Conclusions
The free market by definition does not control medicine prices, necessitating price monitoring and control mechanisms. Markups for generic products are greater than for IBs. Reducing the base price without controlling markups may increase profits for retailers and dispensing doctors without reducing the price paid by end users. To increase access and affordability, promotion of generic medicines and improved availability of medicines in the public sector are required.
Drug price and availability data were collected from West Malaysian public sector facilities, private sector retail pharmacies, and dispensing doctors. Mark-ups were higher on generic drugs than on innovator brands.
Editors' Summary
Background.
The World Health Organization has said that one-third of the people of the world cannot access the medicines they need. An important reason for this problem is that prices are often too high for people or government-funded health systems to afford. In developing countries, most people who need medicines have to pay for them out of their own pockets. Where the cost of drugs is covered by health systems, spending on medicines is a major part of the total healthcare budget. Governments use a variety of approaches to try to control the cost of drugs and make sure that essential medicines are affordable and not overpriced. According to the theory of “free market economics,” the costs of goods and services are determined by interactions between buyers and sellers and not by government intervention. However, free market economics does not work well at containing the costs of medicines, particularly new medicines, because new medicines are protected by patent law, which legally prevents others from making, using, or selling the medicine for a particular period of time. Therefore, without government intervention, there is nothing to help to push down prices.
Why Was This Study Done?
Malaysia is a middle-income country with a relatively effective public health system, but it is facing a rapid rise in drug costs. In Malaysia, medicine prices are determined by free-market economics, without any control by government. Government hospitals are expected to provide drugs free, but a substantial proportion of medicines are paid for by patients who buy them directly from private pharmacies or prescribing doctors. There is evidence that Malaysian patients have difficulties accessing the drugs they need and that cost is an important factor. Therefore, the researchers who wrote this paper wanted to examine the cost of different medicines in Malaysia, and their availability and affordability from different sources.
What Did the Researchers Do and Find?
In this research project, 48 drugs were studied, of which 28 were part of a “core list” identified by the World Health Organization as “essential drugs” on the basis of the global burden of disease. The remaining 20 reflected health care needs in Malaysia itself. The costs of each medicine were collected from government hospitals, private pharmacies, and dispensing doctors in four different regions of Malaysia. Data were collected for the “innovator brand” (made by the original patent holder) and for “generic” brands (an equivalent drug to the innovator brand, produced by a different company once the innovator brand no longer has an exclusive patent). The medicine prices were compared against international reference prices (IRP), which are the average prices offered by not-for-profit drug companies to developing countries. Finally, the researchers also compared the cost of the drugs with daily wages, in order to work out their “affordability.”
The researchers found that, irrespective of the source of medicines, prices were on average very much higher than the international reference price, ranging from 2.4 times the IRP for innovator brands accessed through public hospitals, to 16 times the IRP for innovator brands accessed through private pharmacies. The availability of medicines was also very poor, with only 25% of generic medicines available on average through the public sector. The affordability of many of the medicines studied was again very poor. For example, one month's supply of ranitidine (a drug for stomach ulcers) was equivalent to around three days' wages for a low-paid government worker, and one month's supply of fluoxetine (an antidepressant) would cost around 26 days' wages.
What Do These Findings Mean?
These results show that essential drugs are very expensive in Malaysia and are not universally available. Many people would not be able to pay for essential medicines. The cost of medicines in Malaysia seems to be much higher than in areas of India and Sri Lanka, although the researchers did not attempt to collect data in order to carry out an international comparison. It is possible that the high cost and low availability in Malaysia are the result of a lack of government regulation. Overall, the findings suggest that the government should set up mechanisms to prevent drug manufacturers from increasing prices too much and thus ensure greater access to essential medicines.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040082.
Read a related PLoS Medicine Perspective article by Suzanne Hill
Information is available from the World Health Organization on Improving Access to Medicines
Information on medicine prices is available from Health Action International
Wikipedia has an entry on Patent (a type of intellectual property that is normally used to prevent other companies from selling a newly invented medicine). (Wikipedia is an internet encyclopedia anyone can edit.)
The Drugs for Neglected Diseases Initiative is an international collaboration between public organizations that aims to develop drugs for people suffering from neglected diseases
doi:10.1371/journal.pmed.0040082
PMCID: PMC1831730  PMID: 17388660
2.  Living Alone and Alcohol-Related Mortality: A Population-Based Cohort Study from Finland 
PLoS Medicine  2011;8(9):e1001094.
Kimmo Herttua and colleagues showed that living alone is associated with a substantially increased risk of alcohol-related mortality, irrespective of gender, socioeconomic status, or cause of death, and that this effect was exacerbated after a price reduction in alcohol in 2004.
Background
Social isolation and living alone are increasingly common in industrialised countries. However, few studies have investigated the potential public health implications of this trend. We estimated the relative risk of death from alcohol-related causes among individuals living alone and determined whether this risk changed after a large reduction in alcohol prices.
Methods and Findings
We conducted a population-based natural experimental study of a change in the price of alcohol that occurred because of new laws enacted in Finland in January and March of 2004, utilising national registers. The data are based on an 11% sample of the Finnish population aged 15–79 y supplemented with an oversample of deaths. The oversample covered 80% of all deaths during the periods January 1, 2000–December 31, 2003 (the four years immediately before the price reduction of alcohol), and January 1, 2004–December 31, 2007 (the four years immediately after the price reduction). Alcohol-related mortality was defined using both underlying and contributory causes of death. During the 8-y follow-up about 18,200 persons died due to alcohol-related causes. Among married or cohabiting people the increase in alcohol-related mortality was small or non-existing between the periods 2000–2003 and 2004–2007, whereas for those living alone, this increase was substantial, especially in men and women aged 50–69 y. For liver disease in men, the most common fatal alcohol-related disease, the age-adjusted risk ratio associated with living alone was 3.7 (95% confidence interval 3.3, 4.1) before and 4.9 (95% CI 4.4, 5.4) after the price reduction (p<0.001 for difference in risk ratios). In women, the corresponding risk ratios were 1.7 (95% CI 1.4, 2.1) and 2.4 (95% CI 2.0, 2.9), respectively (p ≤ 0.01). Living alone was also associated with other mortality from alcohol-related diseases (range of risk ratios 2.3 to 8.0) as well as deaths from accidents and violence with alcohol as a contributing cause (risk ratios between 2.1 and 4.7), both before and after the price reduction.
Conclusions
Living alone is associated with a substantially increased risk of alcohol-related mortality, irrespective of gender, socioeconomic status, or the specific cause of death. The greater availability of alcohol in Finland after legislation-instituted price reductions in the first three months of 2004 increased in particular the relative excess in fatal liver disease among individuals living alone.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Throughout most of human history, people have lived in tight-knit communities where there was likely to be someone to turn to for help, advice, or company. But the modern way of life in industrialized countries is greatly reducing the quantity and quality of social relationships. Instead of living in extended families, many people now live miles away from their relatives, often living and working alone. Others commute long distances to work, which leaves little time for socializing with friends or relatives. And many delay or forgo getting married and having children. Consequently, loneliness and social isolation are getting more common. In the UK, according to a recent survey by the Mental Health Foundation, 10% of people often feel lonely, a third have a close friend or relative who they think is very lonely, and half think people are getting lonelier in general. Similarly, over the past two decades, there has been a three-fold increase in the number of Americans who say they have no close confidants.
Why Was This Study Done?
Some experts think that loneliness is bad for human health. They point to studies that show that people with fewer social relationships die earlier on average than people with more social relationships. But does loneliness increase the risk of dying from specific causes? It is important to investigate the relationship between loneliness and cause-specific mortality (death) because, if for example, loneliness increases the risk of dying from alcohol-related causes (heavy drinking causes liver and heart damage, increases the risk of some cancers, contributes to depression, and increases the risk of death by violence or accident), doctors could advise their patients who live alone about safe drinking. But, although loneliness is recognized as both a contributor to and a consequence of alcohol abuse, there have been no large, population-based studies on the association between living alone and alcohol-related mortality. In this population-based study, the researchers estimate the association between living alone (an indicator of a lack of social relationships) and death from alcohol-related causes in Finland for four years before and four years after an alcohol price reduction in 2004 that increased alcohol consumption.
What Did the Researchers Do and Find?
The researchers obtained information on about 80% of all people who died in Finland between 2000 and 2007 from Statistics Finland, which collects official Finnish statistics. During this period, about 18,200 people (two-thirds of whom lived alone) died from underlying alcohol-related causes (for example, liver disease and alcoholic poisoning) or contributory alcohol-related causes (for example, accidents, violence, and cardiovascular disease, with alcohol as a contributing cause). Among married and cohabiting people, the rate of alcohol-related mortality was similar in 2000–2003 and 2004–2007 but for people living alone (particularly those aged 50–69 years) the 2004 alcohol price reduction substantially increased the alcohol-related mortality rate. For liver disease in men, the risk ratio associated with living alone was 3.7 before and 4.9 after the price reduction. That is, between 2000 and 2003, men living alone were 3.7 times more likely to die of liver disease than married or cohabiting men; between 2004 and 2007, they were 4.9 times more likely to die of liver disease. In women, the corresponding risk ratios for liver disease were 1.7 and 2.4, respectively. Living alone was also associated with an increased risk of dying from other alcohol-related diseases and accidents and violence both before and after the price reduction.
What Do These Findings Mean?
These findings indicate that, in Finland, living alone is associated with an increased risk of alcohol-related mortality. Because of the study design, it is impossible to say whether living alone is a cause or a consequence of alcohol abuse, but the greater increase in alcohol-related deaths (particularly fatal liver disease) among people living alone compared to married and cohabiting people after the alcohol price reduction suggests that people living alone are more vulnerable to the adverse effects of increased alcohol availability. Further research in other countries is now needed to identify whether living alone is a cause or effect of alcohol abuse and to extend these findings to cultures where the pattern of alcohol consumption is different. However, the findings of this natural experiment suggest that living alone should be regarded as a potential risk marker for death from alcohol-related causes.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001094.
The Mental Health America Live Your Life Well webpage includes information about how social relationships improve mental and physical health
The Mental Health Foundation (a UK charity) presents the report The Lonely Society?
The US National Institute on Alcohol Abuse and Alcoholism has information about alcohol and its effects on health
The US Centers for Disease Control and Prevention has a website on alcohol and public health that includes information on the health risks of excessive drinking
The UK National Health Service Choices website provides detailed information about drinking and alcohol, including information on the risks of drinking too much, and personal stories about alcohol problems, including stories from people living alone (My drinks diary shock and I used to drink all day)
MedlinePlus provides links to many other resources on alcohol
doi:10.1371/journal.pmed.1001094
PMCID: PMC3176753  PMID: 21949642
3.  Quantifying the Impoverishing Effects of Purchasing Medicines: A Cross-Country Comparison of the Affordability of Medicines in the Developing World 
PLoS Medicine  2010;7(8):e1000333.
Laurens Niëns and colleagues estimate the impoverishing effects of four medicines in 16 low- and middle-income countries using the impoverishment method as a metric of affordability and show that medicine purchases could impoverish large numbers of people.
Background
Increasing attention is being paid to the affordability of medicines in low- and middle-income countries (LICs and MICs) where medicines are often highly priced in relation to income levels. The impoverishing effect of medicine purchases can be estimated by determining pre- and postpayment incomes, which are then compared to a poverty line. Here we estimate the impoverishing effects of four medicines in 16 LICs and MICs using the impoverishment method as a metric of affordability.
Methods and Findings
Affordability was assessed in terms of the proportion of the population being pushed below US$1.25 or US$2 per day poverty levels because of the purchase of medicines. The prices of salbutamol 100 mcg/dose inhaler, glibenclamide 5 mg cap/tab, atenolol 50 mg cap/tab, and amoxicillin 250 mg cap/tab were obtained from facility-based surveys undertaken using a standard measurement methodology. The World Bank's World Development Indicators provided household expenditure data and information on income distributions. In the countries studied, purchasing these medicines would impoverish large portions of the population (up to 86%). Originator brand products were less affordable than the lowest-priced generic equivalents. In the Philippines, for example, originator brand atenolol would push an additional 22% of the population below US$1.25 per day, whereas for the lowest priced generic equivalent this demographic shift is 7%. Given related prevalence figures, substantial numbers of people are affected by the unaffordability of medicines.
Conclusions
Comparing medicine prices to available income in LICs and MICs shows that medicine purchases by individuals in those countries could lead to the impoverishment of large numbers of people. Action is needed to improve medicine affordability, such as promoting the use of quality assured, low-priced generics, and establishing health insurance systems.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In recent years, the international community has prioritized access to essential medicines, which has required focusing on the accessibility, availability, quality, and affordability of life-saving medicines and the development of appropriate data and research agendas to measure these components. Determining the degree of affordability of medicines, especially in low- and middle-income countries, is a complex process as the term affordability is vague. However, the cost of medicines is a major public health issue, especially as the majority of people in developing countries do not have health insurance and medicines freely provided through the public sector are often unavailable. Therefore, although countries have a legal obligation to make essential medicines available to those who need them at an affordable cost, poor people often have to pay for the medicines that they need when they are ill. Consequently, where medicine prices are high, people may have to forego treatment or they may go into debt if they decide to buy the necessary medicines.
Why Was This Study Done?
The researchers wanted to show the impact of the cost of medicines on poorer populations by undertaking an analysis that quantified the proportion of people who would be pushed into poverty (an income level of US$1.25 or US$2 a day) because their only option is to pay out-of-pocket expenses for the life-saving medicines they need. The researchers referred to this consequence as the “impoverishing effect of a medicine.”
What Did the Researchers Do and Find?
The researchers generated “impoverishment rates” of four medicines in 16 low- and middle-income countries by comparing households' daily per capita income before and after (the hypothetical) purchase of one of the following: a salbutamol 100 mcg/dose inhaler, glibenclamide 5 mg cap/tab, atenolol 50 mg cap/tab, and amoxicillin 250 mg cap/tab. This selection of drugs covers the treatment/management of three chronic diseases and one acute illness. The cost of each medicine was taken from standardized surveys, which report median patient prices for a selection of commonly used medicines in the private sector (the availability of essential medicines in the public sector is much lower so many people will depend on the private sector for their medicines) for both originator brand and lowest priced generic products. If the prepayment income was above the US$1.25 (or US$2) poverty line and the postpayment income fell below these lines, purchasing these medicines at current prices impoverishes people.
According to the results of this analysis, a substantial proportion (up to 86%) of the population in the countries studied would be pushed into poverty as a result of purchasing one of the four selected medicines. Furthermore, the lowest priced generic versions of each medicine were generally substantially more affordable than originator brand products. For example, in the Philippines, purchasing originator brand atenolol would push an additional 22% of the population below US$1.25 per day compared to 7% if the lowest priced generic equivalent was bought instead. In effect, purchasing essential medicines for both chronic and acute conditions could impoverish large numbers of people, especially if originator brand products are bought.
What Do These Findings Mean?
Although the purchasing of medicines represents only part of the costs associated with the management of an illness, it is clear that the high cost of medicines have catastrophic effects on poor people. In addition, as the treatment of chronic conditions often requires a combination of medicines, the cost of treating and managing a chronic condition such as asthma, diabetes, and cardiovascular disease is likely to be even more unaffordable than what is reported in this study. Therefore concerted action is urgently required to improve medicine affordability and prevent poor populations from being pushed further into poverty. Such action could include: governments, civil society organizations, and others making access to essential medicines more of a priority and to consider this strategy as an integral part of reducing poverty; the development, implementation, and enforcement of sound national and international price policies; actively promoting the use of quality assured, low-cost generic drugs; ensuring the availability of essential medicines in the public sector at little or no charge to poor people; establishing health insurance systems with outpatient medicine benefits; encouraging pharmaceutical companies to differentially price medicines that are still subject to patent restrictions.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000333.
For a comprehensive resource for medicine prices, availability, and affordability, see Health Action International
Guidelines about access to essential medicines and pharmaceutical policies can be found at WHO
Transparency Alliance provides more information about medicines
Access to essential medicines has become a key campaign topic; for more information see Médecins Sans Frontières (Doctors without Borders)
doi:10.1371/journal.pmed.1000333
PMCID: PMC2930876  PMID: 20824175
4.  The impact of generic substitution on the activities of pharmaceutical companies - a survey from the companies' perspective one year and five years after the introduction of generic substitution in finland 
Background
Mandatory generic substitution (GS) was introduced in Finland on 1 April 2003. The aim of this study was to explore and compare the impacts of GS on the activities of pharmaceutical companies representing mainly original or generic pharmaceutical products in Finland. The self-reported impact of GS from pharmaceutical companies' perspective was explored with a focus on the number of employees, the range of sales packages on the market, the marketing activities, the research and development of new pharmaceutical products and storage of pharmaceuticals.
Methods
A cross-sectional postal survey was conducted among pharmaceutical companies with an office in Finland and substitutable medicines in the Finnish pharmaceutical market one year (2004) and five years (2008) after the introduction of GS. Completed questionnaires were returned by 16 original and 7 generic product companies in 2004 (response rate 56%, n = 41) and by 16 original and 6 generic product companies in 2008 (response rate 56%, n = 39). Descriptive statistical analyses were performed.
Results
The number of employees (2004: n = 6/16, 2008: n = 7/16) and the amount of prescription medicine marketing (2004: n = 7/16, 2008: n = 8/16) decreased in many of the original product companies after the introduction of GS. GS resulted in problems related to the storage of pharmaceuticals in the original product companies shortly after GS was introduced (p = 0.032 between 2004 and 2008). In the generic product companies, the prescription medicine representatives' visits to pharmacies increased at the beginning of GS (p = 0.021 between 2004 and 2008). In addition, GS caused problems with the storage of pharmaceuticals one year and five years after the reform (2004: n = 4/7, 2008: n = 3/6). The differences between original and generic product companies regarding the impacts of GS were not, however, statistically significant. GS did not affect on the range of sales packages on the market or the research activities of the majority of companies.
Conclusions
The study suggests that GS has had impacts on the activities of pharmaceutical companies in Finland. There were also some differences, although not statistically significant, between the surveyed original and generic product companies regarding the self-reported impacts of GS. More investigations are needed in this field.
doi:10.1186/1472-6904-10-15
PMCID: PMC2974660  PMID: 20964869
5.  WHO Essential Medicines Policies and Use in Developing and Transitional Countries: An Analysis of Reported Policy Implementation and Medicines Use Surveys 
PLoS Medicine  2014;11(9):e1001724.
Kathleen Holloway and David Henry evaluate whether countries that report having implemented WHO essential medicines policies have higher quality use of medicines.
Please see later in the article for the Editors' Summary
Background
Suboptimal medicine use is a global public health problem. For 35 years the World Health Organization (WHO) has promoted essential medicines policies to improve quality use of medicines (QUM), but evidence of their effectiveness is lacking, and uptake by countries remains low. Our objective was to determine whether WHO essential medicines policies are associated with better QUM.
Methods and Findings
We compared results from independently conducted medicines use surveys in countries that did versus did not report implementation of WHO essential medicines policies. We extracted survey data on ten validated QUM indicators and 36 self-reported policy implementation variables from WHO databases for 2002–2008. We calculated the average difference (as percent) for the QUM indicators between countries reporting versus not reporting implementation of specific policies. Policies associated with positive effects were included in a regression of a composite QUM score on total numbers of implemented policies. Data were available for 56 countries. Twenty-seven policies were associated with better use of at least two percentage points. Eighteen policies were associated with significantly better use (unadjusted p<0.05), of which four were associated with positive differences of 10% or more: undergraduate training of doctors in standard treatment guidelines, undergraduate training of nurses in standard treatment guidelines, the ministry of health having a unit promoting rational use of medicines, and provision of essential medicines free at point of care to all patients. In regression analyses national wealth was positively associated with the composite QUM score and the number of policies reported as being implemented in that country. There was a positive correlation between the number of policies (out of the 27 policies with an effect size of 2% or more) that countries reported implementing and the composite QUM score (r = 0.39, 95% CI 0.14 to 0.59, p = 0.003). This correlation weakened but remained significant after inclusion of national wealth in multiple linear regression analyses. Multiple policies were more strongly associated with the QUM score in the 28 countries with gross national income per capita below the median value (US$2,333) (r = 0.43, 95% CI 0.06 to 0.69, p = 0.023) than in the 28 countries with values above the median (r = 0.22, 95% CI −0.15 to 0.56, p = 0.261). The main limitations of the study are the reliance on self-report of policy implementation and measures of medicine use from small surveys. While the data can be used to explore the association of essential medicines policies with medicine use, they cannot be used to compare or benchmark individual country performance.
Conclusions
WHO essential medicines policies are associated with improved QUM, particularly in low-income countries.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The widespread availability of effective medicines, particularly those used to treat infectious diseases, has been largely responsible for a doubling in the average global life expectancy over the past century. However, the suboptimal use (overuse and underuse) of medicines is an ongoing global public health problem. The unnecessary use of medicines (for example, the use of antibiotics for sore throats caused by viruses) needlessly consumes scarce resources and has undesirable effects such as encouraging the emergence of antibiotic resistance. Conversely, underuse deprives people of the undisputed benefits of many medicines. Since 1977, to help optimize medicine use, the World Health Organization (WHO) has advocated the concept of “essential medicines” and has developed policies to promote the quality use of medicines (QUM). Essential medicines are drugs that satisfy the priority needs of the human population and that should always be available to communities in adequate amounts of assured quality, in the appropriate dosage forms, and at an affordable price. Policies designed to promote QUM include recommendations that medicines should be free at the point of care and that all health care professionals should be educated about the WHO list of essential medicines (which is revised every two years) throughout their careers.
Why Was This Study Done?
Surveys of WHO member countries undertaken in 2003 and 2007 suggest that the implementation of WHO policies designed to promote QUM is patchy. Moreover, little is known about whether these policies are effective, particularly in middle- and low-income countries. For most of these countries, it is not known whether any of the policies affect validated QUM indicators such as the percentage of patients prescribed antibiotics (a lower percentage indicates better use of medicines) or the percentage of patients treated in compliance with national treatment guidelines (a higher percentage indicates better use of medicines). Here, the researchers analyze data from policy implementation questionnaires and medicine use surveys to determine whether implementation of WHO essential medicines policies is associated with improved QUM in low- and middle-income countries.
What Did the Researchers Do and Find?
The researchers extracted data on ten validated QUM indicators and on implementation of 36 policy variables from WHO databases for 2002–2008 and compared the average differences for the QUM indicators between low- and middle-income countries that did versus did not report implementation of specific WHO policies for QUM. Among 56 countries for which data were available, 27 policies were associated with improved QUM. Four policies were particularly effective, namely, doctors' undergraduate training in standard treatment guidelines, nurses' undergraduate training in standard treatment guidelines, the existence of a ministry of health department promoting the rational use of medicines, and the provision of essential medicines free to all patients at point of care. The researchers also analyzed correlations between how many of the 27 effective policies were implemented in a country and a composite QUM score. As national wealth increased, both the composite QUM score of a country and the reported number of policies implemented by the country increased. There was also a positive correlation between the numbers of policies that countries reported implementing and their composite QUM score. Finally, the implementation of multiple policies was more strongly associated with the composite QUM score in countries with a gross national income per capita below the average for the study countries than in countries with a gross national income above the average.
What Do These Findings Mean?
These findings show that between 2002 and 2008, the reported implementation of WHO essential medicines policies was associated with better QUM across low- and middle-income countries. These findings also reveal a positive correlation between the number of policies that countries report implementing and their QUM. Notably, this correlation was strongest in the countries with the lowest per capita national wealth levels, which underscores the importance of essential medicines policies in low-income countries. Because of the nature of the data available to the researchers, these findings do not show that the implementation of WHO policies actually causes improvements in QUM. Moreover, the age of the data, the reliance on self-report of policy implementation, and the small sample sizes of the medicine use surveys may all have introduced some inaccuracies into these findings. Nevertheless, overall, these findings suggest that WHO should continue to develop its medicine policies and to collect data on medicine use as part of its core functions.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001724.
The World Health Organization provides information about essential medicines; its latest lists of essential medicines are available on the Internet; information about WHO policies to improve the quality use of medicines is also available (in several languages)
The International Network for the Rational Use of Drugs designs, tests, and disseminates effective strategies to improve the way drugs are prescribed, dispensed, and used, particularly in resource-poor countries
The essentialdrugs.org website helps health care professionals, researchers, and policy makers obtain and discuss current information on essential drugs, policy, program activities, education, and training (available in several languages); the website is run by Satellife, which aims to use technology to connect health workers in resource-limited countries to each other and to up-to-date clinical and public health content
doi:10.1371/journal.pmed.1001724
PMCID: PMC4165598  PMID: 25226527
6.  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
7.  Evolution of Antiretroviral Drug Costs in Brazil in the Context of Free and Universal Access to AIDS Treatment  
PLoS Medicine  2007;4(11):e305.
Background
Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005.
Methods and Findings
We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir–ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs: patented lopinavir/r, efavirenz, tenofovir, atazanavir, enfuvirtide, and a locally produced generic, fixed-dose combination of zidovudine and lamivudine (AZT/3TC). Because prices declined for many of the patented drugs that constitute the largest share of drug costs, nearly the entire increase in overall drug expenditures between 2001 and 2005 is attributable to increases in drug quantities. Had all drug quantities been held constant from 2001 until 2005 (or for those drugs entering treatment guidelines after 2001, held constant between the year of introduction and 2005), total costs would have increased by only an estimated US$7 million. We estimate that in the absence of price declines for patented drugs, Brazil would have spent a cumulative total of US$2 billion on drugs for HAART between 2001 and 2005, implying a savings of US$1.2 billion from price declines. Finally, in comparing Brazilian prices for locally produced generic ARVs to the lowest international prices meeting global pharmaceutical quality standards, we find that current prices for Brazil's locally produced generics are generally much higher than corresponding global prices, and note that these prices have risen in Brazil while declining globally. We estimate the excess costs of Brazil's locally produced generics totaled US$110 million from 2001 to 2005.
Conclusions
Despite Brazil's more costly generic ARVs, the net result of ARV price changes has been a cost savings of approximately US$1 billion since 2001. HAART costs have nevertheless risen steeply as Brazil has scaled up treatment. These trends may foreshadow future AIDS treatment cost trends in other developing countries as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. The specific application of the Brazilian model to other countries will depend, however, on the strength of their health systems, intellectual property regulations, epidemiological profiles, AIDS treatment guidelines, and differing capacities to produce drugs locally.
Amy Nunn and colleagues analyze the cost of antiretroviral drugs in Brazil between 2001 and 2005 and discuss the implications for HIV treatment in other developing countries.
Editors' Summary
Background.
Acquired immunodeficiency syndrome (AIDS) has killed 29 million people since the first case occurred in 1981 and an estimated 40 million people live with HIV/AIDS today. AIDS is caused by the human immunodeficiency virus (HIV), which destroys the immune system. Infected individuals are consequently very susceptible to other infections. Early in the AIDS epidemic, most HIV-positive individuals died within a few years of becoming infected. Then, in 1996, highly active antiretroviral therapy (HAART)—a cocktail of antiretroviral drugs (ARVs)—was developed. For people who could afford HAART (which holds HIV infections in check), AIDS became a chronic disease. People who start HAART must keep taking it or their illness will progress.
Unfortunately, few people in low- and middle-income countries could afford these expensive drugs. In 2001, ARV prices fell in developing countries as AIDS activists and developing country governments challenged pharmaceutical companies about ARV prices, pharmaceutical companies set tiered prices for the low- and middle-income countries and more generic (inexpensive copies of brand-named drugs) ARVs became available. In 2003, the lack of access to HIV/AIDS treatment was declared a global health emergency. Governments, international organizations, and funding bodies began to set targets and provide funds to increase access to HAART in developing countries. By 2007, over 2 million people in low- and middle-income countries had access to HAART, but another 5 million remain in urgent need of drugs for treatment.
Why Was This Study Done?
In 1995, many countries in the world signed the World Trade Organization (WTO) Trade-Related Aspects of Intellectual Property (TRIPS) agreement, which requires countries to acknowledge intellectual property rights for many products, including pharmaceuticals. In 1996, Brazil became the first developing country to commit to and implement policies to provide free and universal access to HAART. Since then, Brazil's successful AIDS treatment program has become a model for the developing world, and 180,000 Brazilians were receiving HAART at the end of 2006. However, as a WTO member that signed on to the TRIPS agreement, Brazil was required to recognize the intellectual property rights of pharmaceutical companies' patented ARVs. As Brazil scaled up treatment in the late 1990s, the cost of treating AIDS patients rose quickly and the country took controversial public policy steps to reduce the cost of providing HAART to people living with HIV/AIDS. Brazil produces several non-patented ARVs locally, and since 2001 has challenged multinational pharmaceutical companies about the prices of patented ARVs. To induce price reductions for patented ARVs, Brazil has threatened to issue compulsory licenses (which under WTO terms allow countries facing a health emergency to produce patented drugs without consent of the company holding the patent). Brazil also recently issued a compulsory license for one ARV.
Although world leaders have set a target of universal access to HAART by 2010, little is known about the long-term costs of AIDS treatment in developing countries. In this study, the researchers have investigated how and why the costs of ARVs changed in Brazil between 2001 and 2005 and discuss the relevance of the Brazilian model for AIDS treatment for other resource-limited settings.
What Did the Researchers Do and Find?
The researchers analyzed the prices for each ARV recommended in Brazil's therapeutic guidelines for adults and estimated the changes in purchase quantities for each between 2001 and 2005. These changes likely stem from the growing number of options in Brazil's treatment guidelines, the steadily rising number of patients commencing treatment, and patients' shifts to second- and third-line treatments when their HIV infection became resistant to first-line drugs or they developed side effects. The researchers report that the generic drugs produced in Brazil were generally more expensive than similar drugs made elsewhere, but Brazil's negotiated drug prices for many patented ARVs were lower than elsewhere. Overall, total annual drug expenditure on ARVs doubled between 2001 and 2005, reaching US$414 million in 2005. Because many drug prices fell sharply as a result of declining patented drug prices over the study period, this increase was mainly attributable to increases in drug quantities purchased. If these quantities had stayed constant, the total annual cost would have increased by only $7 million, to $211 million. Conversely, without the decrease in the price of patented drugs, Brazil would have spent $952 million annually by 2005. If Brazil had enjoyed the lowest global prices for generic medicines, the total costs per year in 2005 would have been $367 million, or nearly $50 million less than the costs Brazil actually realized.
What Do These Findings Mean?
These findings tease out the many factors—clinical, commercial, and political—that affected the total costs of the Brazilian AIDS treatment program between 2001 and 2005.
Brazil's ability to produce generic drugs facilitated Brazil's price negotiations for patented drugs. Although Brazil saved approximately US$1 billion over the study period as a result of declining prices for patented medicines, the cost of producing generic drugs locally has risen while the prices for generic drugs have fallen elsewhere. Brazil's recent decision to import a generic ARV using a compulsory license suggests that the Brazilian model for AIDS treatment continues to evolve.
Questions remain about the precise causes of year-to-year cost trends in Brazil because, for example, the researchers did not have full data on when patients switched from first-line to second- or third-line drugs. The observed steep rise in costs from 2004 to 2005 in particular warrants further analysis. In addition, the findings may not be generalizable to countries with different policies on HIV/AIDS treatment, different access to generic drugs, or different bargaining power with multinational drug companies. Nevertheless, the trends this study highlights provide important information about how AIDS treatment costs are likely to evolve in other developing countries as efforts are made to provide universal access to life-saving ARVs.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040305.
Information from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information from the US Centers for Disease Control and Prevention on global HIV/AIDS topics (in English and Spanish)
HIV InSite, comprehensive and up-to-date information on all aspects of HIV/AIDS from the University of California San Francisco
Information from Avert, an international AIDS charity, on HIV and AIDS in Brazil and on HIV/AIDS treatment and care, including universal access to ARVs
Progress towards universal access to HIV/AIDS treatment, the latest report from the World Health Organization (available in several languages)
The National STD and AIDS Program of Brazil
doi:10.1371/journal.pmed.0040305
PMCID: PMC2071936  PMID: 18001145
8.  Impact of medicine-related information on medicine purchase and use by literate consumers 
Indian Journal of Pharmacology  2014;46(4):420-424.
Aims:
To measure impact of information, education, and communication intervention (IEC) on rational medicine use, purchase, and stocking behavior.
Materials and Methods:
This was a pre- and post-design, interventional study. Base data were collected in first visit, using pre tested questionnaire from 500 respondents, who were of either gender, English speaking, at least graduates, permanent residents, and willing to participate. IEC was framed based on problems identified from this data. First intervention was handouts distributed in the second visit, containing information on cost saving in medicine purchase. Second intervention was a lecture session on medicine prices, rational use of medicines, and tips on saving on medicine purchase. Five articles about medicine use and price differences were published in the local newspaper, over 10 days, formed third intervention. After 1 month, post-intervention data was collected using same instrument with some additional questions. Results were analyzed by Chi-square test using Graph Pad prism Version 3.0.
Results:
Awareness about price variation, self-medication, expiry period, generic and brand quality increased post-intervention. Attitudes toward new, costly, brands, injections, sharing and reusing old prescriptions changed post-intervention. Behavioral changes in stocking habits, adherence to doctors’ advice, getting cash memo, comparing prices, reading labels, were seen post-intervention.
Conclusion:
People carry false notions about medicines which influence their use and habits. This intervention successfully changed behavior and could bring awareness on many aspects of medicine use.
doi:10.4103/0253-7613.135956
PMCID: PMC4118537  PMID: 25097282
Compliance; cost comparison; generic verses brand; media influence; medicine storage
9.  The Role of Health Systems Factors in Facilitating Access to Psychotropic Medicines: A Cross-Sectional Analysis of the WHO-AIMS in 63 Low- and Middle-Income Countries 
PLoS Medicine  2012;9(1):e1001166.
In a cross-sectional analysis of WHO-AIMS data, Ryan McBain and colleagues investigate the associations between health system components and access to psychotropic drugs in 63 low and middle income countries.
Background
Neuropsychiatric conditions comprise 14% of the global burden of disease and 30% of all noncommunicable disease. Despite the existence of cost-effective interventions, including administration of psychotropic medicines, the number of persons who remain untreated is as high as 85% in low- and middle-income countries (LAMICs). While access to psychotropic medicines varies substantially across countries, no studies to date have empirically investigated potential health systems factors underlying this issue.
Methods and Findings
This study uses a cross-sectional sample of 63 LAMICs and country regions to identify key health systems components associated with access to psychotropic medicines. Data from countries that completed the World Health Organization Assessment Instrument for Mental Health Systems (WHO-AIMS) were included in multiple regression analyses to investigate the role of five major mental health systems domains in shaping medicine availability and affordability. These domains are: mental health legislation, human rights implementations, mental health care financing, human resources, and the role of advocacy groups. Availability of psychotropic medicines was associated with features of all five mental health systems domains. Most notably, within the domain of mental health legislation, a comprehensive national mental health plan was associated with 15% greater availability; and in terms of advocacy groups, the participation of family-based organizations in the development of mental health legislation was associated with 17% greater availability. Only three measures were related with affordability of medicines to consumers: level of human resources, percentage of countries' health budget dedicated to mental health, and availability of mental health care in prisons. Controlling for country development, as measured by the Human Development Index, health systems features were associated with medicine availability but not affordability.
Conclusions
Results suggest that strengthening particular facets of mental health systems might improve availability of psychotropic medicines and that overall country development is associated with affordability.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Mental disorders—conditions that involve impairment of thinking, emotions, and behavior—are extremely common. Worldwide, mental illness affects about 450 million people and accounts for 13.5% of the global burden of disease. About one in four people will have a mental health problem at some time in their life. For some people, this will be a short period of mild depression, anxiety, or stress. For others, it will be a serious, long-lasting condition such as schizophrenia, bipolar disorder, or major depression. People with mental health problems need help and support from professionals and from their friends and families to help them cope with their illness but are often discriminated against, which can make their illness worse. Treatments include counseling and psychotherapy (talking therapies), and psychotropic medicines—drugs that act mainly on the brain. Left untreated, many people with serious mental illnesses commit suicide.
Why Was This Study Done?
About 80% of people with mental illnesses live in low- and middle-income countries (LAMICs) where up to 85% of patients remain untreated. Access to psychotropic medicines, which constitute an essential and cost-effective component in the treatment of mental illnesses, is particularly poor in many LAMICs. To improve this situation, it is necessary to understand what health systems factors limit the availability and affordability of psychotropic drugs; a health system is the sum of all the organizations, institutions, and resources that act together to improve health. In this cross-sectional study, the researchers look for associations between specific health system components and access to psychotropic medicines by analyzing data collected from LAMICs using the World Health Organization's Assessment Instrument for Mental Health Systems (WHO-AIMS). A cross-sectional study analyzes data collected at a single time. WHO-AIMS, which was created to evaluate mental health systems primarily in LAMICs, is a 155-item survey that Ministries of Health and other country-based agencies can use to collect information on mental health indicators.
What Did the Researchers Do and Find?
The researchers used WHO-AIMS data from 63 countries/country regions and multiple regression analysis to evaluate the role of mental health legislation, human rights implementation, mental health care financing, human resources, and advocacy in shaping medicine availability and affordability. For each of these health systems domains, the researchers developed one or more summary measurements. For example, they measured financing as the percentage of government health expenditure directed toward mental health. Availability of psychotropic medicines was defined as the percentage of mental health facilities in which at least one psychotropic medication for each therapeutic category was always available. Affordability was measured by calculating the percentage of daily minimum wage needed to purchase medicine by the average consumer. The availability of psychotropic medicines was related to features of all five mental health systems domains, report the researchers. Notably, having a national mental health plan (part of the legislation domain) and the participation (advocacy) of family-based organizations in mental health legislation formulation were associated with 15% and 17% greater availability of medicines, respectively. By contrast, only the levels of human resources and financing, and the availability of mental health care in prisons (part of the human rights domain) were associated with the affordability of psychotropic medicines. Once overall country development was taken into account, most of the associations between health systems factors and medicine availability remained significant, while the associations between health systems factors and medicine affordability were no longer significant. In part, this was because country development was more strongly associated with affordability and explained most of the relationships: for example, countries with greater overall development have higher expenditures on mental health and greater medicine affordability compared to availability.
What Do These Findings Mean?
These findings indicate that access to psychotropic medicines in LAMICs is related to key components within the mental health systems of these countries but that availability and affordability are affected to different extents by these components. They also show that country development plays a strong role in determining affordability but has less effect on determining availability. Because cross-sectional data were used in this study, these findings only indicate associations; they do not imply causality. They are also limited by the relatively small number of observations included in this study, by the methods used to collect mental health systems data in many LAMICs, and by the possibility that some countries may have reported biased results. Despite these limitations, these findings suggest that strengthening specific mental health system features may be an important way to facilitate access to psychotropic medicines but also highlight the role that country wealth and development play in promoting the treatment of mental disorders.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1001166.
The US National Institute of Mental Health provides information on all aspects of mental health (in English and Spanish)
The UK National Health Service Choices website provides information on mental health; its Live Well feature provides practical advice on dealing with mental health problems and personal stories
The UK charity Mind provides further information about mental illness, including personal stories
MedlinePlus provides links to many other sources of information on mental health (in English and Spanish)
Information on WHO-AIMS, including versions of the instrument in several languages, and WHO-AIMS country reports are available
doi:10.1371/journal.pmed.1001166
PMCID: PMC3269418  PMID: 22303288
10.  Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries 
PLoS Medicine  2013;10(2):e1001388.
Patricia McGettigan and David Henry find that, although some non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac are known to increase cardiovascular risk, diclofenac is included on 74 countries' essential medicine lists and was the most commonly used NSAID in the 15 countries they evaluated.
Background
Certain non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib [Vioxx]) increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events. Rates of cardiovascular disease are high and rising in many low- and middle-income countries. We studied the extent to which evidence on cardiovascular risk with NSAIDs has translated into guidance and sales in 15 countries.
Methods and Findings
Data on the relative risk (RR) of cardiovascular events with individual NSAIDs were derived from meta-analyses of randomised trials and controlled observational studies. Listing of individual NSAIDs on Essential Medicines Lists (EMLs) was obtained from the World Health Organization. NSAID sales or prescription data for 15 low-, middle-, and high-income countries were obtained from Intercontinental Medical Statistics Health (IMS Health) or national prescription pricing audit (in the case of England and Canada). Three drugs (rofecoxib, diclofenac, etoricoxib) ranked consistently highest in terms of cardiovascular risk compared with nonuse. Naproxen was associated with a low risk. Diclofenac was listed on 74 national EMLs, naproxen on just 27. Rofecoxib use was not documented in any country. Diclofenac and etoricoxib accounted for one-third of total NSAID usage across the 15 countries (median 33.2%, range 14.7–58.7%). This proportion did not vary between low- and high-income countries. Diclofenac was by far the most commonly used NSAID, with a market share close to that of the next three most popular drugs combined. Naproxen had an average market share of less than 10%.
Conclusions
Listing of NSAIDs on national EMLs should take account of cardiovascular risk, with preference given to low risk drugs. Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. Diclofenac should be removed from EMLs.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs. Aspirin, the first NSAID, was developed in 1897 but there are now many different NSAIDs. Some can be bought over-the-counter but others are available only with prescription. NSAIDs can help relieve short- and long-term pain, reduce inflammation (redness and swelling), and reduce high fevers. Common conditions that are treated with NSAIDs include headaches, toothache, back ache, and arthritis. NSAIDs work by stopping a class of enzymes called cyclo-oxygenases (COXs) from making prostaglandins, some of which cause pain and inflammation. Like all drugs, NSAIDs have some unwanted side effects. Because certain prostaglandins protect the stomach lining from the stomach acid that helps to digest food, NSAID use can cause indigestion and stomach ulcers (gastrointestinal complications). In addition, NSAIDs increase the risk of heart attacks and stroke to varying degrees and therefore should be avoided by people at high risk of cardiovascular diseases—conditions that affect the heart and/or blood vessels.
Why Was This Study Done?
Different NSAIDs are associated with different levels of cardiovascular risk. Selective COX-2 inhibitors (e.g., rofecoxib, celecoxib, etoricoxib) generally have fewer stomach-related side effects than non-selective COX inhibitors (e.g., naproxen, ibuprofen, diclofenac). However, some NSAIDs (rofecoxib, diclofenac, etoricoxib) are more likely to cause cardiovascular events than others (e.g., naproxen). When doctors prescribe NSAIDs, they need to consider the patient's risk profile. Particularly for patients with higher risk of cardiovascular events, a doctor should either advise against NSAID use or recommend one that has a relatively low cardiovascular risk. Information on the cardiovascular risk associated with different NSAIDs has been available for several years, but have doctors changed their prescribing of NSAIDs based on the information? This question is of particular concern in low- and middle-income countries where cardiovascular disease is increasingly common. In this study, the researchers investigate the extent to which evidence on the cardiovascular risk associated with different NSAIDs has translated into guidance and sales in 15 low-, middle-, and high-income countries.
What Did the Researchers Do and Find?
The researchers derived data on the relative risk of cardiovascular events associated with individual NSAIDs compared to non-use of NSAIDs from published meta-analyses of randomized trials and observational studies. They obtained information on the NSAIDs recommended in 100 countries from national Essential Medicines Lists (EMLs; essential medicines are drugs that satisfy the priority health care needs of a population). Finally, they obtained information on NSAID sales for 13 countries in the South Asian, Southeast Asian, and Asian Pacific regions and NSAID prescription data for Canada and England. Rofecoxib, diclofenac, and etoricoxib consistently increased cardiovascular risk compared with no NSAIDs. All three had a higher relative risk of cardiovascular events than naproxen in pairwise analyses. Naproxen was associated with the lowest cardiovascular risk. No national EMLs recommended rofecoxib, which was withdrawn from world markets 8 years ago because of its cardiovascular risk. Seventy-four national EMLs listed diclofenac, but only 27 EMLs listed naproxen. Diclofenac was the most commonly used NSAID, with an average market share across the 15 countries of nearly 30%. By contrast, naproxen had an average market share of less than 10%. Finally, across both high- and low-/middle-income countries, diclofenac and etoricoxib accounted for one-third of total NSAID usage.
What Do These Findings Mean?
These findings show that NSAIDs with higher risk of cardiovascular events are widely used in low-/middle- as well as high-income countries. Diclofenac is the most popular NSAID, despite its higher relative risk of cardiovascular events, which is similar to that of rofecoxib. Diclofenac is also widely listed on EMLs even though information on its higher cardiovascular risk has been available since 2006. In contrast, naproxen, one of the safest in relative terms of the NSAIDs examined, was among the least popular and was listed on a minority of EMLs. Some aspects of the study's design may affect the accuracy of these findings. For example, the researchers did not look at the risk profiles of the patients actually taking NSAIDs. However, given the volume of use of high-risk NSAIDS, it is likely that these drugs are taken by many individuals at high risk of cardiovascular events. Overall, these findings have important implications for public health and, given the wide availability of safer alternatives, the researchers suggest that diclofenac should be removed from national EMLs and that its marketing authorizations should be revoked globally.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1001388.
This study is further discussed in a PLOS Medicine Perspective by K. Srinath Reddy and Ambuj Roy
The UK National Health Service Choices website provides detailed information on NSAIDS
MedlinePlus provides information about aspirin, ibuprofen, naproxen, and diclofenac; it also provides links to other information about pain relievers (in English and Spanish)
The American Heart Association has information on cardiovascular disease; Can Patients With Cardiovascular Disease Take Nonsteroidal Antiinflammatory Drugs? is a Cardiology Patient Page in the AHA journal Circulation
The British Heart Foundation also provides information about cardiovascular disease and has a factsheet on NSAIDs and cardiovascular disease
The World Health Organization has a fact sheet on essential medicines; the WHO Model List of Essential Medicines (in English and French), and national EMLs are available
doi:10.1371/journal.pmed.1001388
PMCID: PMC3570554  PMID: 23424288
11.  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
12.  The Effects of Mandatory Prescribing of Thiazides for Newly Treated, Uncomplicated Hypertension: Interrupted Time-Series Analysis 
PLoS Medicine  2007;4(7):e232.
Background
The purpose of our study was to evaluate the effects of a new reimbursement rule for antihypertensive medication that made thiazides mandatory first-line drugs for newly treated, uncomplicated hypertension. The objective of the new regulation was to reduce drug expenditures.
Methods and Findings
We conducted an interrupted time-series analysis on prescribing data before and after the new reimbursement rule for antihypertensive medication was put into effect. All patients started on antihypertensive medication in 61 general practices in Norway were included in the analysis. The new rule was put forward by the Ministry of Health and was approved by parliament. Adherence to the rule was monitored only minimally, and there were no penalties for non-adherence. Our primary outcome was the proportion of thiazide prescriptions among all prescriptions made for persons started on antihypertensive medication. Secondary outcomes included the proportion of patients who, within 4 mo, reached recommended blood-pressure goals and the proportion of patients who, within 4 mo, were not started on a second antihypertensive drug. We also compared drug costs before and after the intervention. During the baseline period, 10% of patients started on antihypertensive medication were given a thiazide prescription. This proportion rose steadily during the transition period, after which it remained stable at 25%. For other outcomes, no statistically significant differences were demonstrated. Achievement of treatment goals was slightly higher (56.6% versus 58.4%) after the new rule was introduced, and the prescribing of a second drug was slightly lower (24.0% versus 21.8%). Drug costs were reduced by an estimated Norwegian kroner 4.8 million (€0.58 million, US$0.72 million) in the first year, which is equivalent to Norwegian kroner 1.06 per inhabitant (€0.13, US$0.16).
Conclusions
Prescribing of thiazides in Norway for uncomplicated hypertension more than doubled after a reimbursement rule requiring the use of thiazides as the first-choice therapy was put into effect. However, the resulting savings on drug expenditures were modest. There were no significant changes in the achievement of treatment goals or in the prescribing of a second antihypertensive drug.
Atle Fretheim and colleagues found that the prescribing of thiazides in Norway for uncomplicated hypertension more than doubled after a rule requiring their use as first-choice therapy was put into effect.
Editors' Summary
Background.
High blood pressure (hypertension) is a common medical condition, especially among elderly people. It has no obvious symptoms but can lead to heart attacks, heart failure, strokes, or kidney failure. It is diagnosed by measuring blood pressure—the force that blood moving around the body exerts on the inside of arteries (large blood vessels). Many factors affect blood pressure (which depends on the amount of blood being pumped round the body and on the size and condition of the arteries), but overweight people and individuals who eat fatty or salty food are at high risk of developing hypertension. Mild hypertension can often be corrected by making lifestyle changes, but many patients also take one or more antihypertensive agents. These include thiazide diuretics and several types of non-thiazide drugs, many of which reduce heart rate or contractility and/or dilate blood vessels.
Why Was This Study Done?
Antihypertensive agents are a major part of national drug expenditure in developed countries, where as many as one person in ten is treated for hypertension. The different classes of drugs are all effective, but their cost varies widely. Thiazides, for example, are a tenth of the price of many non-thiazide drugs. In Norway, the low use of thiazides recently led the government to impose a new reimbursement rule aimed at reducing public expenditure on antihypertensive drugs. Since March 2004, family doctors have been reimbursed for drug costs only if they prescribe thiazides as first-line therapy for uncomplicated hypertension, unless there are medical reasons for selecting other drugs. Adherence to the rule has not been monitored, and there is no penalty for non-adherence, so has this intervention changed prescribing practices? To find out, the researchers in this study analyzed Norwegian prescribing data before and after the new rule came into effect.
What Did the Researchers Do and Find?
The researchers analyzed the monthly antihypertensive drug–prescribing records of 61 practices around Oslo, Norway, between January 2003 and November 2003 (pre-intervention period), between December 2003 and February 2004 (transition period), and between March 2004 and January 2005 (post-intervention period). This type of study is called an “interrupted time series”. During the pre-intervention period, one in ten patients starting antihypertensive medication was prescribed a thiazide drug. This proportion gradually increased during the transition period before stabilizing at one in four patients throughout the post-intervention period. A slightly higher proportion of patients reached their recommended blood-pressure goal after the rule was introduced than before, and a slightly lower proportion needed to switch to a second drug class, but both these small differences may have been due to chance. Finally, the researchers estimated that the observed change in prescribing practices reduced drug costs per Norwegian by US$0.16 (€0.13) in the first year.
What Do These Findings Mean?
Past attempts to change antihypertensive-prescribing practices by trying to influence family doctors (for example, through education) have largely failed. By contrast, these findings suggest that imposing a change on them (in this case, by introducing a new reimbursement rule) can be effective (at least over the short term and in the practices included in the study), even when compliance with the change is not monitored nor noncompliance penalized. However, despite a large shift towards prescribing thiazides, three-quarters of patients were still prescribed non-thiazide drugs (possibly because of doubts about the efficacy of thiazides as first-line drugs), which emphasizes how hard it is to change doctors' prescribing habits. Further studies are needed to investigate whether the approach examined in this study can effectively contain the costs of antihypertensive drugs (and of drugs used for other common medical conditions) in the long term and in other settings. Also, because the estimated reduction in drug costs produced by the intervention was relatively modest (although likely to increase over time as more patients start on thiazides), other ways to change prescribing practices and produce savings in national drug expenditures should be investigated.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040232.
MedlinePlus encyclopedia page on hypertension (in English and Spanish)
UK National Institute for Health and Clinical Excellence information on hypertension for patients, carers, and professionals
American Heart Association information for patients on high blood pressure
An open-access research article describing the potential savings of using thiazides as the first-choice antihypertensive drug
A previous study in Norway, published in PLoS Medicine, examined what happened when doctors were actively encouraged to make more use of thiazides. There was also an economic evaluation of what this achieved
doi:10.1371/journal.pmed.0040232
PMCID: PMC1904466  PMID: 17622192
13.  Norwegian Physicians’ Knowledge of the Prices of Pharmaceuticals: A Survey 
PLoS ONE  2013;8(9):e75218.
The objectives of this study are to measure physicians’ knowledge of the prices of pharmaceuticals, and investigate whether there are differences in knowledge of prices between groups of physicians. This article reports on a survey study of physicians’ knowledge of the prices of pharmaceuticals conducted on a representative sample of Norwegian physicians in the autumn of 2010. The importance of physicians’ knowledge of costs derives from their influence on total spending and allocation of limited health-care resources. Physicians are important drivers in the effort to contain costs in health care, but only if they have the knowledge needed to choose the most cost-effective treatment options. A survey was sent to 1 543 Norwegian physicians, asking them for price estimates and their opinions on the importance of considering the cost of treatment to society as a decision factor when treating their patients. This article deals with a subsection in which the physicians were asked to estimate the price of five pharmaceuticals: simvastatin, alendronate (Fosamax), infliximab (Remicade), natalizumab (Tysabri) and escitalopram (Cipralex). The response rate was 65%. For all the five pharmaceuticals, more than 50% and as many as 83% gave responses that differed more than 50% from the actual drug price. The price of more expensive pharmaceuticals was underestimated, while the opposite was the case for less expensive medicines. The data show that physicians in general have poor knowledge of the prices of the pharmaceuticals they offer their patients. However, the physicians who frequently deal with a drug have better knowledge of its price than those who do not handle a medication as often. The data also suggest that those physicians who agree that cost of care to society is an important decision factor have better knowledge of drug prices.
doi:10.1371/journal.pone.0075218
PMCID: PMC3770612  PMID: 24040402
14.  The role of discounts and loss leaders in medicine procurement in Austrian hospitals - a primary survey of official and actual medicine prices 
Background
Knowledge about the prices of medicines used in hospitals, particularly the actually achieved ones, is scant. There are indications of large discounts and the provision of medicines cost-free to Austrian hospitals. The study aims to survey the official and actual prices of medicines procured by Austrian hospitals and to compare them to the out-patient prices.
Methods
Primary price collection of the official hospital list prices and the actually achieved prices for 12 active ingredients as of the end of September 2009 in five general hospitals in Austria and analysis of the 15 most commonly used presentations.
Results
The official hospital list prices per unit differed considerably (from 1,500 Euro for an oncology medicine to 0.20 Euro for a generic cardiovascular medicine). For eight on-patent medicines (indications: oncology, anti-inflammatory, neurology-multiple sclerosis and blood) actual hospital medicine prices equaled the list prices (seven medicines) or were lower (one medicine) in four hospitals, whereas one hospital always reported higher actual prices due to the application of a wholesale mark-up. The actual hospital prices of seven medicines (cardiology and immunomodulation) were below the official hospital prices in all hospitals; of these all cardiovascular medicines were provided free-of-charge. Hospital prices were always lower than out-patient prices (pharmacy retail price net and reimbursement price).
Conclusion
The results suggest little headroom for hospitals to negotiate price reductions for “monopoly products”, i.e. medicines with no therapeutic alternative. Discounts and cost-free provision (loss leaders) appear to be granted for products of strategic importance for suppliers, e.g. cardiovascular medicines, whose treatment tends to be continued in primary care after discharge of the patient.
doi:10.1186/1478-7547-11-15
PMCID: PMC3708833  PMID: 23826758
Medicine prices; Pharmaceutical policy; Hospital; Discount; Cost-free medicines; Austria
15.  A national survey on availability, price and affordability of selected essential medicines for non communicable diseases in Sri Lanka 
BMC Public Health  2014;14(1):817.
Background
Access to medicines is a universal right. Low availability and low affordability of medicines are issues that deny this right to a significant proportion of the world population. The objective of this study was to determine the availability, price and affordability of essential medicines prescribed to treat non communicable diseases in Sri Lanka.
Methods
Methodology was based on the 2nd edition of the World Health Organization Health Action International Manual. A country survey was conducted and facilities representing both public and private pharmacies were selected. A total of 109 facilities was surveyed. At each facility data on the availability and prices of 50 essential medicines for non communicable diseases were collected. Percentage availability, median price of originator brand and lowest priced generic, median price ratio to the International Reference Price were calculated for surveyed medicines. Affordability was determined using the daily incomes of the lowest - paid unskilled government worker.
Results
Semi government community pharmacies had the highest (>80%) availability while outdoor pharmacies of public health care facilities, private pharmacies and outdoor pharmacies of private hospital showed a fairly high availability (50 - 80%) of surveyed medicines.
Unit price of 76% of selected individual medicines was less than ten Sri Lankan rupees. Out of these 28% of medicines cost less than one Sri Lanka rupee. For 21 of the surveyed medicines the median price ratio to the international reference price was less than one. The prices of originator brands for 14 surveyed medicines were more than five times that of the lowest price generics.
Less than a single day’s wages was adequate to purchase a month's supply of the lowest priced generic of more than 67% of surveyed medicines.
Conclusions
The availability of selected essential medicines was fairly high in both public and private sectors in Sri Lanka. Most medicines are affordable to the lowest income earners in the community. There were many generic brands and generics available for most of the medicines in private and semi government community pharmacies increasing both availability and affordability.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-817) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2458-14-817
PMCID: PMC4138405  PMID: 25103467
Availability; Affordability; Price; Essential medicines; Non communicable diseases
16.  The experiences of implementing generic medicine policy in eight countries: A review and recommendations for a successful promotion of generic medicine use 
Generic medicines are clinically interchangeable with original brand medicines and have the same quality, efficacy and safety profiles. They are, nevertheless, much cheaper in price. Thus, while providing the same therapeutic outcomes, generic medicines lead to substantial savings for healthcare systems. Therefore, the quality use of generic medicines is promoted in many countries. In this paper, we reviewed the role of generic medicines in healthcare systems and the experiences of promoting the use of generic medicines in eight selected countries, namely the United States (US), the United Kingdom (UK), Sweden, Finland, Australia, Japan, Malaysia and Thailand. The review showed that there are different main policies adopted to promote generic medicines such as generic substitution in the US, generic prescribing in the UK and mandatory generic substitution in Sweden and Finland. To effectively and successfully implement the main policy, different complementary policies and initiatives were necessarily introduced. Barriers to generic medicine use varied between countries from negative perceptions about generic medicines to lack of a coherent generic medicine policy, while facilitators included availability of information about generic medicines to both healthcare professionals and patients, brand interchangeability guidelines, regulations that support generic substitution by pharmacists, and incentives to both healthcare professionals and patients.
doi:10.1016/j.jsps.2013.12.017
PMCID: PMC4281627  PMID: 25561861
Generic medicines; Health system; Generic policy; Generic substitution; Pharmacists; Physicians
17.  Food Pricing Strategies, Population Diets, and Non-Communicable Disease: A Systematic Review of Simulation Studies 
PLoS Medicine  2012;9(12):e1001353.
A systematic review of simulation studies conducted by Helen Eyles and colleagues examines the association between food pricing strategies and food consumption and health and disease outcomes.
Background
Food pricing strategies have been proposed to encourage healthy eating habits, which may in turn help stem global increases in non-communicable diseases. This systematic review of simulation studies investigates the estimated association between food pricing strategies and changes in food purchases or intakes (consumption) (objective 1); Health and disease outcomes (objective 2), and whether there are any differences in these outcomes by socio-economic group (objective 3).
Methods and Findings
Electronic databases, Internet search engines, and bibliographies of included studies were searched for articles published in English between 1 January 1990 and 24 October 2011 for countries in the Organisation for Economic Co-operation and Development. Where ≥3 studies examined the same pricing strategy and consumption (purchases or intake) or health outcome, results were pooled, and a mean own-price elasticity (own-PE) estimated (the own-PE represents the change in demand with a 1% change in price of that good). Objective 1: pooled estimates were possible for the following: (1) taxes on carbonated soft drinks: own-PE (n = 4 studies), −0.93 (range, −0.06, −2.43), and a modelled −0.02% (−0.01%, −0.04%) reduction in energy (calorie) intake for each 1% price increase (n = 3 studies); (2) taxes on saturated fat: −0.02% (−0.01%, −0.04%) reduction in energy intake from saturated fat per 1% price increase (n = 5 studies); and (3) subsidies on fruits and vegetables: own-PE (n = 3 studies), −0.35 (−0.21, −0.77). Objectives 2 and 3: variability of food pricing strategies and outcomes prevented pooled analyses, although higher quality studies suggested unintended compensatory purchasing that could result in overall effects being counter to health. Eleven of 14 studies evaluating lower socio-economic groups estimated that food pricing strategies would be associated with pro-health outcomes. Food pricing strategies also have the potential to reduce disparities.
Conclusions
Based on modelling studies, taxes on carbonated drinks and saturated fat and subsidies on fruits and vegetables would be associated with beneficial dietary change, with the potential for improved health. Additional research into possible compensatory purchasing and population health outcomes is needed.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
For the first time in human history, non-communicable diseases (NCDs) are killing more people than infectious diseases. Every year, more than 35 million people die from NCDs—nearly two-thirds of the world's annual deaths. More than 80% of these deaths are in developing countries, where a third of NCD-related deaths occur in people younger than 60 years old. And NCDs are not just a growing global public health emergency. They are also financially costly because they reduce productivity and increase calls on health care systems worldwide. Cardiovascular diseases (conditions that affect the heart and circulation such as heart attacks and stroke), cancers, diabetes, and chronic respiratory diseases (long-term diseases that affect the lungs and airways) are responsible for most NCD-related illnesses and death. The main behavioral risk factors for all these diseases are tobacco use, harmful use of alcohol, physical inactivity, and unhealthy diets (diets that have a low fruit and vegetable intake and high saturated fat and salt intakes).
Why Was This Study Done?
Improvements in population diets and reductions in salt intake are crucial for the control and prevention of NCDs, but how can these behavioral changes be encouraged? One potential but poorly studied strategy is food pricing—the introduction of taxes on unhealthy foods (for example, foods containing high levels of saturated fat) and subsidies on healthy foods (for example, foods high in fiber). However, although a tax on soft drinks, for example, might decrease purchases of these high-sugar drinks, it might also increase purchases of fruit juices, which contain just as much sugar and energy as soft drinks (“compensatory purchasing”), and thus undermine the intended health impact of the tax. Because randomized controlled trials of the effects of food pricing strategies are difficult to undertake, many researchers have turned to mathematical models (sets of equations that quantify relationships between interventions and outcomes) to provide the evidence needed to inform policy decisions on food taxes and subsidies. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), Helen Eyles and colleagues investigate the association between food pricing strategies and food consumption and NCDs by analyzing the results of published mathematical modeling studies of food pricing interventions.
What Did the Researchers Do and Find?
The researchers identified 32 studies that met their predefined inclusion criteria, which included publication by researchers in a member country of the Organisation for Economic Co-operation and Development (a group of largely developed countries that promotes global development). Most of the studies were of low to moderate quality and provided uncertain and varying estimates of the impact of pricing on food consumption. Where three or more studies examined the same pricing strategy and consumption or health outcome, the researchers calculated the average change in demand for a food in response to changes in its price (“own-price elasticity”). For taxes on carbonated soft drinks, the average own-price elasticity was −0.93; that is, the models predicted that a 1% increase in the price of soft drinks would decrease consumption by 0.93%. The modeled reduction in the proportion of energy intake from saturated fat resulting from a 1% increase in the price of saturated fats was 0.02%. Finally, although the researchers' analysis suggested that for each 1% reduction in the price of fruits and vegetables, consumption would increase by 0.35%, they also found evidence that such a subsidy might result in compensatory purchasing, such as a reduction in fish purchases.
What Do These Findings Mean?
These findings suggest that pricing strategies have the potential to produce improvements in population diets, at least in developed countries, but also highlight the need for more research in this area. Notably, the researchers found insufficient data to allow them to quantify the effects of pricing strategies on health or to analyze whether the effect of pricing strategies is likely vary between socio-economic groups. Given their findings, the researchers suggest that future modeling studies should include better assessments of the unintended effects of compensatory purchasing and should examine the potential impact of food pricing strategies on long-term health and NCD-related deaths. Finally, they suggest that robust evaluations should be built into the implementation of food pricing policies to answer some of the outstanding questions about this potential strategy for reducing the global burden of NCDs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001353.
The US Centers for Disease Control and Prevention provides information on all aspects of healthy living, on chronic diseases and health promotion, and on non-communicable diseases around the world
The Global Noncommunicable Disease Network (NCDnet) aims to help low- and middle-income countries reduce NCD-related illnesses and death through implementation of the 2008-2013 Action Plan for the Global Strategy for the Prevention and Control of Noncommunicable Diseases (also available in French); NCDnet's Face to face with chronic disease webpage is a selection of personal stories from around the world about dealing with NCDs
The American Heart Association and the American Cancer Society provide information on many important risk factors for non-communicable diseases and include some personal stories about keeping healthy
doi:10.1371/journal.pmed.1001353
PMCID: PMC3519906  PMID: 23239943
18.  Where are we now: assessing the price, availability and affordability of essential medicines in Delhi as India plans free medicine for all 
Background
Inequitable access to medicines is a major weakness in the Indian health care system. Baseline data needed to develop effective public health policy and provide equitable access to essential medicines. The present survey was conducted to investigate the price, availability, and affordability of fifty essential medicines in the public and private sector in Delhi, India using standardized WHO/HAI methodology.
Methods
Data on procurement price and availability was collected (July-October 2011) from three public healthcare providers: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Data on price and availability of medicines was collected from private retail and chain pharmacies of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR).
Results
The procurement price of surveyed medicines was 0.53-0.82 times the international reference price-IRP. However, the overall mean availability of surveyed medicines in facilities under state government and MCD was 41.3% and 23.2%, respectively. The overall mean availability of medicines in three tertiary care facilities operated by the federal government was 49.3%. Availability of generic medicines was much higher in the private sector. Off-patented medicines, like diazepam, diclofenac, and doxycycline had the highest MPRs. The price ratio between procurement and retail was as high as 28 (range 11–28) for certain medicines. Seven-day treatment with a popular brand of amoxicillin+clavulanic acid or one inhaler each of budesonide and salbutamol cost 2.3 and 1.4 days’ wages for the lowest paid government worker. A majority of India’s population cannot afford these prices.
Conclusions
This study revealed that procurement prices of surveyed medicines were reasonable in comparison to IRP. However, variation in procurement prices of certain medicines by different public procurement agencies was noted. Availability of medicines was very poor in public sector facilities, which are the primary source of free medicines for a majority of India’s low-income population. Availability of medicines is better in private retail pharmacies but affordability remains a big challenge for a majority of the population. These data have significant policy implications that could help in amending policies to increase the access to essential medicines for India’s population.
doi:10.1186/1472-6963-13-285
PMCID: PMC3733775  PMID: 23885985
Access; Essential medicines; Generic medicines; Medicine price; Medicine availability; Affordability; Public sector; Private retail pharmacies; Procurement price
19.  Methods for the comparative evaluation of pharmaceuticals 
Political background
As a German novelty, the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen; IGWiG) was established in 2004 to, among other tasks, evaluate the benefit of pharmaceuticals. In this context it is of importance that patented pharmaceuticals are only excluded from the reference pricing system if they offer a therapeutic improvement.
The institute is commissioned by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) or by the Ministry of Health and Social Security. The German policy objective expressed by the latest health care reform (Gesetz zur Modernisierung der Gesetzlichen Krankenversicherung, GMG) is to base decisions on a scientific assessment of pharmaceuticals in comparison to already available treatments. However, procedures and methods are still to be established.
Research questions and methods
This health technology assessment (HTA) report was commissioned by the German Agency for HTA at the Institute for Medical Documentation and Information (DAHTA@DIMDI). It analysed criteria, procedures, and methods of comparative drug assessment in other EU-/OECD-countries. The research question was the following: How do national public institutions compare medicines in connection with pharmaceutical regulation, i.e. licensing, reimbursement and pricing of drugs?
Institutions as well as documents concerning comparative drug evaluation (e.g. regulations, guidelines) were identified through internet, systematic literature, and hand searches. Publications were selected according to pre-defined inclusion and exclusion criteria. Documents were analysed in a qualitative matter following an analytic framework that had been developed in advance. Results were summarised narratively and presented in evidence tables.
Results and discussion
Currently licensing agencies do not systematically assess a new drug's added value for patients and society. This is why many countries made post-licensing evaluation of pharmaceuticals a requirement for reimbursement or pricing decisions. Typically an explicitly designated drug review body is involved.
In all eleven countries included (Austria, Australia, Canada, Switzerland, Finland, France, the Netherlands, Norway, New Zealand, Sweden, and the United Kingdom) a drug's therapeutic benefit in comparison to treatment alternatives is leading the evaluation. A medicine is classified as a therapeutic improvement if it demonstrates an improved benefit-/risk-profile compared to treatment alternatives. However, evidence of superiority to a relevant degree is requested.
Health related quality of life is considered as the most appropriate criterion for a drug's added value from patients' perspective. Review bodies in Australia, New Zealand, and the United Kingdom have committed themselves to include this outcome measure whenever possible.
Pharmacological or innovative characteristics (e.g. administration route, dosage regime, new acting principle) and other advantages (e.g. taste, appearance) are considered in about half of the countries. However, in most cases these aspects rank as second line criteria for a drug's added value.
All countries except France and Switzerland perform a comparative pharmacoeconomic evaluation to analyse costs caused by a drug intervention in relation to its benefit (preferably by cost utility analysis). However, the question if a medicine is cost effective in relation to treatment alternatives is answered in a political and social context. A range of remarkably varying criteria are considered.
Countries agree that randomised controlled head-to-head trials (head-to-head RCT) with a high degree of internal and external validity provide the most reliable and least biased evidence of a drug's relative treatment effects (as do systematic reviews and meta-analyses of these RCT). Final outcome parameters reflecting long-term treatment objectives (mortality, morbidity, quality of life) are preferred to surrogate parameters. Following the concept of community effectiveness, drug review institutions also explicitly favour RCT in a "natural" design, i.e. in daily routine and country specific care settings.
The countries' requirements for pharmacoeconomic studies are similar despite some methodological inconsistencies, e.g. concerning cost calculation.
Outcomes of clinical and pharmacoeconomic analyses are largely determined by the choice of comparator. Selecting an appropriate comparative treatment is therefore crucial. In theory, the best or most cost effective therapy is regarded as appropriate comparator for clinical and economic studies. Pragmatically however, institutions accept that the drug is compared to the treatment of daily routine or to the least expensive therapy.
If a pharmaceutical offers several approved indications, in some countries all of them are assessed. Others only evaluate a drug's main indication. Canada is the only country which also considers a medicine's off-label use.
It is well known that clinical trials and pharmacoeconomic studies directly comparing a drug with adequate competitors are lacking - in quantitative as well as in qualitative terms. This is specifically the case before or shortly after marketing authorisation. Yet there is the need to support reimbursement or pricing decisions by scientific evidence. In this situation review bodies are often forced to rely on observational studies or on other internally less valid data (including expert and consensus opinions). As a second option they use statistical approaches like indirect adjusted comparisons (in Australia and the United Kingdom) and, commonly, economic modelling. However, there is consensus that results provided by these techniques need to be verified by valid head-to-head comparisons as soon as possible.
Conclusions
In the majority of countries reimbursement and pricing decisions are based on systematic and evidence-based evaluation comparing a drug's clinical and economic characteristics to daily treatment routine. However, further evaluation criteria, requirements and specific methodological issues still lack internationally consented standards.
PMCID: PMC3011319  PMID: 21289930
20.  Effective policy initiatives to constrain lipid-lowering drug expenditure growth in South Korea 
Background
The rapid growth of prescription drug expenditures is a major problem in South Korea. Accordingly, the South Korean government introduced a positive listing system in 2006. They also adopted various price reduction policies. Nevertheless, the total expenditure for lipid-lowering drugs have steadily increased throughout South Korea. The present study explores the factors that have influenced the increased expenditures of lipid-lowering drugs with a particular focus on the effects of statins in this process.
Methods
This paper investigates the National Health Insurance claims data for prescribed lipid-lowering drugs collected between January 1, 2005 and December 31, 2009. We specifically focused on statins and assessed the yearly variation of statin expenditure by calculating the increased rate of paired pharmaceutical expenditures over a 2 year period. Our study classified statins into three categories: new entrants, core medicines and exiting medicines. For core medicines, we further examined influencing factors such as price, amount of drugs consumed by volume, and prescription changes (substitutes for other drug).
Results
Statin expenditure showed an average annual increase of 25.7% between 2005 and 2009. Among the different statins, the expenditure of atorvastatin showed a 36.6% annual increase rate, which was the most dramatic among all statins. Also we divided expenditure for core medicines by the price factor, volume factor, and prescription change. The result showed that annual weighted average prices of individual drug decreased each year, which clearly showed that price influenced statin expenditure in a negative direction. The use of generic drugs containing the same active ingredient as name-brand drugs increased and negatively affected statin expenditure (Generic Mix effect). However, the use of relatively expensive ingredients within statin increase, Ingredient Mix effect contributed to increased statin expenditure (Ingredient Mix effect). In particular, the volume effect was found to be critical for increasing statin expenditure as the amount of statin consumed increased steadily throughout the study period.
Conclusions
The recent rapid increase in statin expenditure can largely be attributed to an increase in consumption volume. In order to check drug expenditures effectively in our current situation, in which chronic diseases remain steadily on the rise, it is necessary to not only have supply-side initiatives such as price reduction, but also demand-side initiatives that could control drug consumption volume, for example: educational programs for rational prescription, generic drug promotional policies, and policies providing prescription targets.
doi:10.1186/1472-6963-14-100
PMCID: PMC4015215  PMID: 24589172
21.  Associations between Stroke Mortality and Weekend Working by Stroke Specialist Physicians and Registered Nurses: Prospective Multicentre Cohort Study 
PLoS Medicine  2014;11(8):e1001705.
In a multicenter observational study, Benjamin Bray and colleagues evaluate whether weekend rounds by stroke specialist physicians, or the ratio of registered nurses to beds on weekends, is associated with patient mortality after stroke.
Please see later in the article for the Editors' Summary
Background
Observational studies have reported higher mortality for patients admitted on weekends. It is not known whether this “weekend effect” is modified by clinical staffing levels on weekends. We aimed to test the hypotheses that rounds by stroke specialist physicians 7 d per week and the ratio of registered nurses to beds on weekends are associated with mortality after stroke.
Methods and Findings
We conducted a prospective cohort study of 103 stroke units (SUs) in England. Data of 56,666 patients with stroke admitted between 1 June 2011 and 1 December 2012 were extracted from a national register of stroke care in England. SU characteristics and staffing levels were derived from cross-sectional survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) of 30-d post-admission mortality, adjusting for case mix, organisational, staffing, and care quality variables. After adjusting for confounders, there was no significant difference in mortality risk for patients admitted to a stroke service with stroke specialist physician rounds fewer than 7 d per week (adjusted HR [aHR] 1.04, 95% CI 0.91–1.18) compared to patients admitted to a service with rounds 7 d per week. There was a dose–response relationship between weekend nurse/bed ratios and mortality risk, with the highest risk of death observed in stroke services with the lowest nurse/bed ratios. In multivariable analysis, patients admitted on a weekend to a SU with 1.5 nurses/ten beds had an estimated adjusted 30-d mortality risk of 15.2% (aHR 1.18, 95% CI 1.07–1.29) compared to 11.2% for patients admitted to a unit with 3.0 nurses/ten beds (aHR 0.85, 95% CI 0.77–0.93), equivalent to one excess death per 25 admissions. The main limitation is the risk of confounding from unmeasured characteristics of stroke services.
Conclusions
Mortality outcomes after stroke are associated with the intensity of weekend staffing by registered nurses but not 7-d/wk ward rounds by stroke specialist physicians. The findings have implications for quality improvement and resource allocation in stroke care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In a perfect world, a patient admitted to hospital on a weekend or during the night should have as good an outcome as a patient admitted during regular working hours. But several observational studies (investigations that record patient outcomes without intervening in any way; clinical trials, by contrast, test potential healthcare interventions by comparing the outcomes of patients who are deliberately given different treatments) have reported that admission on weekends is associated with a higher mortality (death) rate than admission on weekdays. This “weekend effect” has led to calls for increased medical and nursing staff to be available in hospitals during the weekend and overnight to ensure that the healthcare provided at these times is of equal quality to that provided during regular working hours. In the UK, for example, “seven-day working” has been identified as a policy and service improvement priority for the National Health Service.
Why Was This Study Done?
Few studies have actually tested the relationship between patient outcomes and weekend physician or nurse staffing levels. It could be that patients who are admitted to hospital on the weekend have poor outcomes because they are generally more ill than those admitted on weekdays. Before any health system introduces potentially expensive increases in weekend staffing levels, better evidence that this intervention will improve patient outcomes is needed. In this prospective cohort study (a study that compares the outcomes of groups of people with different baseline characteristics), the researchers ask whether mortality after stroke is associated with weekend working by stroke specialist physicians and registered nurses. Stroke occurs when the brain's blood supply is interrupted by a blood vessel in the brain bursting (hemorrhagic stroke) or being blocked by a blood clot (ischemic stroke). Swift treatment can limit the damage to the brain caused by stroke, but of the 15 million people who have a stroke every year, about 6 million die within a few hours and another 5 million are left disabled.
What Did the Researchers Do and Find?
The researchers extracted clinical data on 56,666 patients who were admitted to stroke units in England over an 18-month period from a national stroke register. They obtained information on the characteristics and staffing levels of the stroke units from a biennial survey of hospitals admitting patients with stroke, and information on deaths among patients with stroke from the national register of deaths. A quarter of the patients were admitted on a weekend, almost half the stroke units provided stroke specialist physician rounds seven days per week, and the remainder provided rounds five days per week. After adjustment for factors that might have affected outcomes (“confounders”) such as stroke severity and the level of acute stroke care available in each stroke unit, there was no significant difference in mortality risk between patients admitted to a stroke unit with rounds seven days/week and patients admitted to a unit with rounds fewer than seven days/week. However, patients admitted on a weekend to a stroke unit with 1.5 nurses/ten beds had a 30-day mortality risk of 15.2%, whereas patients admitted to a unit with 3.0 nurses/ten beds had a mortality risk of 11.2%, a mortality risk difference equivalent to one excess death per 25 admissions.
What Do These Findings Mean?
These findings show that the provision of stroke specialist physician rounds seven days/week in stroke units in England did not influence the (weak) association between weekend admission for stroke and death recorded in this study, but mortality outcomes after stroke were associated with the intensity of weekend staffing by registered nurses. The accuracy of these findings may be affected by the measure used to judge the level of acute care available in each stroke unit and by residual confounding. For example, patients admitted to units with lower nursing levels may have shared other unknown characteristics that increased their risk of dying after stroke. Moreover, this study considered the impact of staffing levels on mortality only and did not consider other relevant outcomes such as long-term disability. Despite these limitations, these findings support the provision of higher weekend ratios of registered nurses to beds in stroke units, but given the high costs of increasing weekend staffing levels, it is important that controlled trials of different models of physician and nursing staffing are undertaken as soon as possible.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001705.
This study is further discussed in a PLOS Medicine Perspective by Meeta Kerlin
Information about plans to introduce seven-day working into the National Health Service in England is available; the 2013 publication “NHS Services—Open Seven Days a Week: Every Day Counts” provides examples of how hospitals across England are working together to provide routine healthcare services seven days a week; a “Behind the Headlines” article on the UK National Health Service Choices website describes a recent observational study that investigated the association between admission to hospital on the weekend and death, and newspaper coverage of the study's results; the Choices website also provides information about stroke for patients and their families, including personal stories
A US nurses' site includes information on the association of nurse staffing with patient safety
The US National Institute of Neurological Disorders and Stroke provides information about all aspects of stroke (in English and Spanish); its Know Stroke site provides educational materials about stroke prevention, treatment, and rehabilitation, including personal stories (in English and Spanish); the US National Institute of Health SeniorHealth website has additional information about stroke
The Internet Stroke Center provides detailed information about stroke for patients, families, and health professionals (in English and Spanish)
doi:10.1371/journal.pmed.1001705
PMCID: PMC4138029  PMID: 25137386
22.  Factors associated with self-care activities among adults in the United Kingdom: a systematic review 
BMC Public Health  2009;9:96.
Background
The Government has promoted self-care. Our aim was to review evidence about who uses self-tests and other self-care activities (over-the-counter medicine, private sector, complementary and alternative medicine (CAM), home blood pressure monitors).
Methods
During April 2007, relevant bibliographic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Applied Social Sciences Index and Abstracts, PsycINFO, British Nursing Index, Allied and Complementary Medicine Database, Sociological Abstracts, International Bibliography of the Social Sciences, Arthritis and Complementary Medicine Database, Complementary and Alternative Medicine and Pain Database) were searched, and potentially relevant studies were reviewed against eligibility criteria. Studies were included if they were published during the last 15 years and identified factors, reasons or characteristics associated with a relevant activity among UK adults. Two independent reviewers used proformas to assess the quality of eligible studies.
Results
206 potentially relevant papers were identified, 157 were excluded, and 49 papers related to 46 studies were included: 37 studies were, or used data from questionnaire surveys, 36 had quality scores of five or more out of 10, and 27 were about CAM. Available evidence suggests that users of CAM and over-the-counter medicine are female, middle-aged, affluent and/or educated with some measure of poor health, and that people who use the private sector are affluent and/or educated.
Conclusion
People who engage in these activities are likely to be affluent. Targeted promotion may, therefore, be needed to ensure that use is equitable. People who use some activities also appear to have poorer measures of health than non-users or people attending conventional services. It is, therefore, also important to ensure that self-care is not used as a second choice for people who have not had their needs met by conventional services.
doi:10.1186/1471-2458-9-96
PMCID: PMC2674604  PMID: 19344526
23.  Access to antibiotics in New Delhi, India: implications for antibiotic policy 
Objective
The present survey was conducted to investigate the price and availability of a basket of 24 essential antibiotics and eight high-end antibiotics at various levels of health care in public and private sector in National Capital Territory of Delhi, India using standardized WHO/HAI methodology.
Methods
Data on procurement price and availability was collected from three public healthcare providers in the state: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Overall a total of 83 public facilities, 68 primary care, 10 secondary cares and 5 tertiary care facilities were surveyed. Data was also collected from private retail (n = 40) and chain pharmacies (n = 40) of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR).
Results
Public sector: Delhi state government has its essential medicine list (Delhi state EML) and was using Delhi state EML 2007 for procurement; the other two agencies had their own procurement list. All the antibiotics procured including second and third generation antibiotics except for injections were available at primary care facilities. Antibiotic available were on the basis of supply rather than rationality or the Delhi state EML and none was 100% available. There was sub-optimal availability of some essential antibiotics while other non-essential ones were freely available. Availability of antibiotics at tertiary care facilities was also sub-optimal. Private sector: Availability of antibiotics was good. For most of the antibiotics the most expensive and popular trade names were often available. High-end antibiotics, meropenam, gemifloxacin, and moxifloxacin were commonly available. In retail pharmacies some newer generation non-essential antibiotics like gemifloxacin were priced lower than the highest-priced generic of amoxicillin + clavulanic acid, azithromycin, and cefuroxime aexitl.
Conclusions
Inappropriate availability and pricing of newer generation antibiotics, which may currently be bought without prescription, is likely to lead to their over-use and increased resistance. All providers should follow the EML of whichever of the three concerned Delhi public sector agencies that it is under and these EMLs should follow the essential medicine concept. The Indian regulatory authorities need to consider urgently, drug schedules and pricing policies that will curtail inappropriate access to new generation antibiotics.
doi:10.1186/2052-3211-6-6
PMCID: PMC3987069  PMID: 24764541
Access; Antibiotics; Antibiotic availability; Antibiotic price; Primary care; Public health sector; Private retail pharmacies; Procurement price
24.  Factors influencing medical students’ choice of family medicine 
Canadian Family Physician  2012;58(11):e649-e657.
Abstract
Objective
To identify factors that influence medical students’ choice of family medicine versus another specialty and to analyze influential factors by urban versus rural background of students.
Design
Cross-sectional questionnaire survey conducted in 2010.
Setting
University of Alberta in Edmonton.
Participants
A total of 118 first-, 120 second-, and 107 third-year medical students.
Main outcome measures
Twenty-two factors influencing preferred career choice, type of community lived in (rural vs urban), and student age and sex.
Results
Overall, 283 (82.0%) students responded to the survey. Those who preferred family medicine rather than another specialty as a career option were older (≥ 25 years) (69.6% vs 40.9%, P < .001), female (69.6% vs 39.3%, P < .001), and had previously lived in rural locations (< 25 000 population) (46.8% vs 23.9%, P < .001). Four factors were significantly associated with students preferring family medicine compared with any other specialty: emphasis on continuity of care (87.3 vs 45.3%, P < .001); length of residency (73.4% vs 25.9%, P < .001); influence of family, friends, or community (67.1% vs 50.2%, P = .011); and preference for working in a rural community (41.8% vs 10.9%, P < .001). For students with urban backgrounds, the preference for family medicine was more strongly influenced by the opportunity to deal with a variety of medical problems; current debt load; and family, friends, or community than for those with rural backgrounds. Practice location preferences also differed between students from rural and urban backgrounds.
Conclusion
Medical students who prefer family medicine as a career choice appear to be influenced by a different set of factors than those who prefer other specialties. Being female; being older; having previously lived in a rural location; placing importance on continuity of care; desire for a shorter residency; and influence of family, friends, or community are associated with medical students preferring family medicine. Some differences in factors influencing career choice exist between medical students from rural versus urban backgrounds. To increase the supply of family physicians, medical schools might consider introducing elements into the admissions process and the medical curriculum that encourage family medicine as a career choice.
PMCID: PMC3498039  PMID: 23152472
25.  A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia  
PLoS Medicine  2008;5(2):e32.
Background
Since 1998 the serious public health problem in South East Asia of counterfeit artesunate, containing no or subtherapeutic amounts of the active antimalarial ingredient, has led to deaths from untreated malaria, reduced confidence in this vital drug, large economic losses for the legitimate manufacturers, and concerns that artemisinin resistance might be engendered.
Methods and Findings
With evidence of a deteriorating situation, a group of police, criminal analysts, chemists, palynologists, and health workers collaborated to determine the source of these counterfeits under the auspices of the International Criminal Police Organization (INTERPOL) and the Western Pacific World Health Organization Regional Office. A total of 391 samples of genuine and counterfeit artesunate collected in Vietnam (75), Cambodia (48), Lao PDR (115), Myanmar (Burma) (137) and the Thai/Myanmar border (16), were available for analysis. Sixteen different fake hologram types were identified. High-performance liquid chromatography and/or mass spectrometry confirmed that all specimens thought to be counterfeit (195/391, 49.9%) on the basis of packaging contained no or small quantities of artesunate (up to 12 mg per tablet as opposed to ∼ 50 mg per genuine tablet). Chemical analysis demonstrated a wide diversity of wrong active ingredients, including banned pharmaceuticals, such as metamizole, and safrole, a carcinogen, and raw material for manufacture of methylenedioxymethamphetamine (‘ecstasy'). Evidence from chemical, mineralogical, biological, and packaging analysis suggested that at least some of the counterfeits were manufactured in southeast People's Republic of China. This evidence prompted the Chinese Government to act quickly against the criminal traders with arrests and seizures.
Conclusions
An international multi-disciplinary group obtained evidence that some of the counterfeit artesunate was manufactured in China, and this prompted a criminal investigation. International cross-disciplinary collaborations may be appropriate in the investigation of other serious counterfeit medicine public health problems elsewhere, but strengthening of international collaborations and forensic and drug regulatory authority capacity will be required.
Paul Newton and colleagues' international, collaborative study found evidence that counterfeit artesunate was being manufactured in China, which prompted a criminal investigation.
Editors' Summary
Background
Malaria is one of the world's largest public health problems, causing around 500 million cases of illness and at least one million deaths per year (the estimates vary widely). The most serious form of malaria is caused by the parasite Plasmodium falciparum, which has become resistant to multiple drugs that had previously been the cornerstones of antimalarial regimens. One group of drugs for treating malaria, the artemisinin therapies including artesunate, are based upon a Chinese herb called qinghaosu; these have now become vital to the treatment of P. falciparum malaria. But counterfeit artesunate, containing none or too little (“subtherapeutic levels”) of the active ingredient, is a growing problem especially in South and East Asia. Fake artesunate is devastating for malaria control: it causes avoidable death, reduces confidence in the drug, and takes away profit from legitimate manufacturers. Of major concern also is the potential for subtherapeutic counterfeit artesunate to fuel the parasite's resistance to the artemisinin group of drugs.
Previous estimates have suggested that between 33% and 53% of artesunate tablets in mainland South East Asia are counterfeit. In this paper the authors report on an unprecedented international collaboration and criminal investigation that attempted to quantify and source counterfeit artesunate among some of the most malarious countries in Asia.
Why Was This Study Done?
Previous reports have identified the problem of fake artesunate, but as of yet there have been few reports on the potential solutions. Concerned health workers and scientists, the regional World Health Organization (WHO) office and the International Criminal Police Organization (INTERPOL) got together to discuss what could be done in May 2005 when it became clear the counterfeit artesunate situation was worsening in the Greater Mekong Sub-Region of South East Asia (comprising Cambodia, Lao People's Democratic Republic, Myanmar, Thailand, Vietnam, and Yunnan Province in the People's Republic of China). Their subsequent investigation combined the goals and methods of a range of concerned parties—police, scientists, and health workers—to identify the source of counterfeit artesunate in South East Asia and to supply the evidence to help arrest and prosecute the perpetrators.
What Did the Researchers Do and Find?
The researchers conducted forensic analyses of samples of genuine and counterfeit artesunate. They selected these samples from larger surveys and investigations that had been conducted in the region beginning in the year 2000. Genuine samples were supplied by a manufacturer to provide a comparator. The authors examined the physical appearance of the packages and subjected the tablets to a wide range of chemical and biological tests that allowed an analysis of the components contained in the tablets.
When comparing the collected packages and tablets against the genuine samples, the researchers found considerable diversity of fake artesunate in SE Asia. Sixteen different fake hologram types (the stickers contained on packages meant to identify them as genuine) were found. Chemical analysis revealed that all tablets thought to be fake contained no or very small quantities of artesunate. Other ingredients found in the artesunate counterfeit tablets included paracetamol, antibiotics, older antimalarial drugs, and a range of minerals, and there were a variety of gases surrounding the tablets inside the packaging. Biological analyses of pollen grains inside the packaging suggested that the packages originated in the parts of South East Asia along the Chinese border.
What Do these Findings Mean?
The results were crucial in helping the authorities establish the origin of the fake artesunate. For example, the authors identified two regional clusters where the counterfeit tablets appeared to be coming from, thus flagging a potential manufacturing site or distribution network. The presence of wrong active pharmaceutical ingredients (such as the older antimalarial drugs) suggested the counterfeiters had access to a variety of active pharmaceutical ingredients. The presence of safrole, a precursor to the illicit drug ecstasy, suggested the counterfeits may be coming from factories that manufacture ecstasy. And the identification of minerals indigenous to certain regions also helped identify the counterfeits' origin. The researchers concluded that at least some of the counterfeit artesunate was coming from southern China. The Secretary General of INTERPOL presented the findings to the Chinese government, which then carried out a criminal investigation and arrested individuals alleged to have produced and distributed the counterfeit artesunate.
The collaboration between police, public health workers and scientists on combating fake artesunate is unique, and provides a model for others to follow. However, the authors note that substantial capacity in forensic analysis and the infrastructure to support collaborations between these different disciplines are needed.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050032.
The World Health Organization in 2006 created IMPACT—International Medical Products Anti-Counterfeiting Taskforce—with the aim of forging international collaboration to seek global solutions to this global challenge and in raising awareness of the dangers of counterfeit medical products. The task force membership includes international organizations, nongovernmental organizations, enforcement agencies, pharmaceutical manufacturers' associations, and drug and regulatory authorities. IMPACT's Web site notes that trade in counterfeit medicines is widespread and affects both developed and developing countries but is more prevalent in countries that have weak drug regulatory systems, poor supply of basic medicines, unregulated markets, high drug prices and/or significant price differentials. IMPACT holds international conferences and maintains a rapid alert system for counterfeit drugs.
The drug industry's anticounterfeit organization, Pharmaceutical Security Institute, works to develop improved systems to identify the extent of the counterfeiting problem and to assist in coordinating international inquiries. Its membership includes 21 large pharmaceutical companies.
The Web site of David Pizzanelli, a world expert on security holography, contains a PowerPoint presentation co-authored by Paul Newton that illustrates the different types of fake holograms found on fake artesunate packages, and their implications for artemisinin resistance (http://www.pizzanelli.co.uk/content/artesunate.html).
doi:10.1371/journal.pmed.0050032
PMCID: PMC2235893  PMID: 18271620

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