Antibiotic resistance in the tropics. 3. Medical responsibilities of the pharmaceutical industry with respect to use of antibiotics in the tropics

The pharmaceutical industry has three major medical responsibilities: the efficacy and safety of its products, the accuracy of the statements it makes about them, and the provision to governments and health workers of full and proper information concerning these products. The development of new antibiotics is very costly, and their provision to Third World countries alone can never be financially rewarding; furthermore, only about 20% of world-wide pharmaceutical sales are to Third World countries. The industry's interest in developing drugs for exclusive or major use in such countries is declining. However, support from industry for the World Health Organization's action programme on essential drugs is growing, and this should help to provide drugs more cheaply to the poorer countries of the world.     

Globalization, pharmaceutical pricing, and South African health policy: managing confrontation with U.S. firms and politicians.

Brewing since the advent of South African democracy in 1994 and promises of health sector transformation, an extraordinary drug war between President Nelson Mandela's African National Congress government and U.S. pharmaceutical manufacturers took on global proportions in 1998-1999. Within months of the passage of South African legislation aimed at lowering drug prices, the U.S. government quickly applied powerful pressure points to repeal a clause allowing potential importation of generic substitutes and imposition of compulsory licensing. At stake were not only local interpretations of patent law and World Trade Organization rules on Trade in Intellectual Property, but international power relations between developing countries and the pharmaceutical industry. In reviewing the ongoing debate, this article considers post-apartheid public health policy, U.S. government pressure to change the law, and pharmaceutical industry interests and links to the U.S. government, and evaluates various kinds of resistance to U.S. corporate and government behavior. The case thus raises--not for the first time--concerns about contemporary imperialism ("globalization"), the role of the profit motive as an incentive in vital pharmaceutical products, and indeed the depth of "democracy" in a country where high-bidding international drug firms have sufficient clout to embarrass Vice President Al Gore by pitting him against the life-and-death interests of millions of consumers of essential drugs in South Africa and other developing countries.     

The World Bank and pharmaceuticals

Within less than a decade the World Bank has become the largest single source of finance (loans) for health in low and middle income countries as well as a major player in the field of pharmaceuticals. Often 20-50% of the recurrent government health budget in developing countries is used to procure drugs. Drugs are among the most salient and cost-effective elements of health care and often a key factor for the success of a health sector reform. However, pharmaceuticals are frequently being used irrationally, mainly due to market imperfections in health care, such as information asymmetries, leading to serious health problems and a heavy financial burden on the health system. Lending priorities set by the World Bank could be used to promote public health sector reform, leading to the rational use of affordable and available drugs of good quality in developing countries. This report provides the first analysis of World Bank activity in the pharmaceutical sector worldwide. The analysis of 77 staff appraisal reports, describing the planning phase of World Bank country projects, shows that 16% of the total World Bank health, nutrition and population budget, or approximately US$1.3 billion, has been committed to loans or credits supporting pharmaceutical activities in the programme countries between 1989-95. Roughly US$1.05 billion has been committed to procurement of drugs and medical equipment. Only 5% of the total pharmaceutical sector lending is committed to software components such as drug policy work and rational use of drugs. No more than 45% of the projects were developed in collaboration with pharmaceutical expertise. The World Bank is recommended to improve its pharmaceutical sector involvement by promoting drug policy research and development including national and international dialogue on pharmaceutical issues to ensure rational use of both drugs and loans. In this, the World Bank has an advantage given its experience from working with both the private and the public sector, its in-house expertise in health economics, and lastly its ability to be listened to by governments through its power.     

Generic drugs: an alternative for the Brazilian market

The analysis of the main characteristics of the pharmaceutical industry worldwide and market aspects of that industry in Brazil leads us to consider a high share of external dependency and oligopolization. This situation is not peculiar to our country, but is rather a global trend. Recent Government initiatives in Brazil, aiming at reducing that dependency, associated with the critical aspects regarding the prices and costs of drugs as compared to international prices, are the background that support the proposal of evaluating generic drugs as an alternative for Brazilian market. One of the most striking aspect is the verification of overpricing of raw materials as demonstrated by "transfer prices", a practice that has been observed in several countries. Analysing international concepts dealing with generic drugs, generic names and pharmaceutical equivalence, based on World Health Organization recommendations and evaluating the experiences of different countries, several actions are proposed in order to gradually enforce a policy of generic drugs, bioequivalent and interchangeable, as a possible regulatory mechanisms for Brazil.     

Brands or generics: the dilemma of pharmaceutical marketing in a developing country

A significant issue in pharmaceutical marketing in many developing countries is whether drugs should be sold by generic or by brand names. In Pakistan, legislation prohibited the sale of brand name drugs in order to increase price competition, and strengthen the market position of indigenous manufacturers to compete against multinationals. However, the government's objectives were not achieved for reasons discussed in the article. The Pakistan case has implications for multinational firms and for other developing countries in similar situations.     

Pharmaceutical Pricing in Emerging Markets: Effects of Income,Competition, and Procurement

This paper analyzes determinants of ex‐manufacturer prices for originator and generic drugs across countries. We focus on drugs to treat HIV/AIDS, TB, and malaria in middle and low‐income countries (MLICs), with robustness checks to other therapeutic categories and the full income range of countries. We examine the effects of per capita income, income dispersion, competition from originator and generic substitutes, and whether the drugs are sold to retail pharmacies versus tendered procurement by non‐government organizations. The cross‐national income elasticity of prices is 0.27 across the full income range of countries but is 0.0–0.10 between MLICs, implying that drugs are least affordable relative to income in the lowest income countries. Within‐country income inequality contributes to relatively high prices in MLICs. Although generics are priced roughly 30% lower than originators on average, the variance is large. Additional generic competitors only weakly affect prices, plausibly because generic quality uncertainty leads to competition on brand rather than price. Tendered procurement that imposes quality standards attracts multinational generic suppliers and significantly reduces prices of originator and generic drugs, compared with their respective prices to retail pharmacies. ©2013 The Authors. Health Economics Published by John Wiley & Sons Ltd.     

Commercial drug compendium information: a First World/Third World comparison

The purpose of this study was to determine what differences exist in the content of commercial drug compendium monographs available in First World and Third World countries. A content model representing First World information was developed from monographs contained in the Physicians' Desk Reference, ABPI Data Sheet Compendium, and the Rote Liste. The content of the three First World compendia was found to be variable, with the Physicians' Desk Reference consistently more comprehensive than either the ABPI or Rote Liste. This result suggests that there is a lack of agreement among industrialized countries regarding what amount of information is necessary or appropriate for inclusion in a commercial drug compendium. A sample of 58 monographs was selected from four Third World compendia and evaluated in terms of comprehensiveness and accuracy. These monographs represented five commonly prescribed drugs from the World Health Organization's Essential Drugs List. The monographs were found to be less comprehensive than any of the three monographs contained in the First World compendia. Approximately 5 percent of the information contained in the sampled monographs was determined to be inaccurate. The sampled monographs for drugs supplied by multi-national pharmaceutical firms were found to contain the same amount of information as those for drugs supplied by domestic firms.     

The effect of Paragraph IV decisions and generic entry before patent expiration on brand pharmaceutical firms

This purpose of this paper is to investigate the impact of Paragraph IV patent infringement decisions on brand drug pharmaceutical firms. Paragraph IV decisions determine whether a generic firm can enter before the period of exclusivity ends. I construct a novel dataset of all Paragraph IV decisions and find that they disproportionately involve the highest revenue drugs, significant periods of patent protection, and a non-trivial portion of all brand drugs facing generic entry. I also estimate the impact of Paragraph IV decisions on brand firm profitability and find they have large value consequences.     

我国各省药品集中招标采购政策分析和思考

目的:为完善我国各省药品集中招标采购工作提供参考和建议。方法:检索收集2015年我国各省药品集中招标采购最新方案、细则、办法等文件,采用文献分析、对比分析和实地调研访谈等方法进行归纳总结。结果与结论:各省招标采购工作进度不一,在招标药品范围、质量层次划分、双信封评审体系和中标产品数量等方面存在较大差异。建议发挥市场机制在药品招标采购中的作用,落实带量采购,构建完备的质量评价体系,加快仿制药一致性评价。     

Do Higher-Priced Generic Medicines Enjoy a Competitive Advantage Under Reference Pricing?

Background: In many countries with generic reference pricing, generic producers and distributors compete by means of undisclosed discounts offered to pharmacies in order to reduce acquisition costs and to induce them to dispense their generic to patients in preference over others. Objective: The objective of this article is to test the hypothesis that under prevailing reference pricing systems for generic medicines, those medicines sold at a higher consumer price may enjoy a competitive advantage. Method: Real transaction prices for 179 generic medicines acquired by pharmacies in Spain have been used to calculate the discount rate on acquisition versus reimbursed costs to pharmacies. Two empirical hypotheses are tested: the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical presentations for which there are more generic competitors; and, the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical forms for which the consumer price has declined less in relation to the consumer price of the brand drug before generic entry (higher-priced generic medicines). Results: An average discount rate of 39.3% on acquisition versus reimbursed costs to pharmacies has been observed. The magnitude of the discount positively depends on the number of competitors in the market. The higher the ratio of the consumer price of the generic to that of the brand drug prior to generic entry (i.e. the smaller the price reduction of the generic in relation to the brand drug), the larger the discount rate. Conclusions: Under reference pricing there is intense price competition among generic firms in the form of unusually high discounts to pharmacies on official ex-factory prices reimbursed to pharmacies. However, this effect is highly distorting because it favours those medicines with a higher relative price in relation to the brand price before generic entry.     

Essential drugs programmes in Africa

The essential drugs concept encompasses national drug policy, selection, quantification, quality assurance, procurement, inventory control and distribution, financing, rational drug use, and training. People from all sectors and levels were involved in developing Tanzania's national drug policy which was approved in 1991. The process developing a policy in Kenya continues. The policy will allow Kenya's Ministry of Health to implement various operational changes (e.g., improvements in hospital drug management). 40 sub-Saharan African (SSA) countries have a national essential drug list (EDL). A synergistic effect results when EDLs are merged with standard treatment guidelines (STGs) (e.g., in Tanzania and Zimbabwe) or constructed with STGs and a national formulary. The Federal Ministry of Health in Nigeria designated 209 drugs as essential drugs, while Nigerian states determined their own EDLs based on these 209 drugs. Spreadsheet models use morbidity patterns, past consumption, and population to help countries quantify drug needs which are then used to determine drug procurement. Various problems with quality assurance in regional and national quality control laboratories in SSA include staff turnover, limited equipment maintenance, and lack of reagents and laboratory standard solutions. A database, structured, flexible drug registration system allows countries (e.g., Zimbabwe) to monitor drug suppliers and agents. Drug procurement has improved in countries with established procurement systems. Computers help control and manage drug inventories. Kenya, Mozambique, Tanzania, and Uganda distribute ration kits of prepackaged drug selections. Cash and carry in Ghana, hospital fees in Kenya, and community insurance schemes in Guinea Bissau are some financing schemes in SSA. The International Network for the Rational Use of Drugs is operating in Ghana, Nigeria, the Sudan, and Tanzania. Training courses in drug supply management are held in Ghana, Tanzania, and Zimbabwe.     

Analysis of the World Bank's pharmaceutical lending

This article analyzes the World Bank's lending activity on pharmaceuticals and medical products (PMP) during the fiscal years (FY) 1999-2001 by regions, borrower and supplier country, and procurement method. Data for the study derived from the World Bank Project and the Business Warehouse databases. The information included all Bank projects approved during the study period. Information for the PMP procurement contracts was extracted for the health sector components of all sector projects awarded. Contract dollar amount was aggregated by borrower and supplier countries. A total of 365 contracts of PMP for a value of US$ 364.5 million (2001 prices) were awarded. International competitive bidding was the most common procurement method used representing 46.0% of the total PMP contracts amount. Domestic providers supplied 52.5% of the PMP contracts managed by the borrower countries. Twenty-two countries accounted for 97.0% of the total PMP purchased during the period of analysis. Only a small fraction of the Bank activity was directed to the pharmaceutical sector. There is a need for more involvement of the World Bank to increase accessibility, affordability and rational use of pharmaceuticals and medical products. An evaluation of the different procurement methods and their implications on drug quality and prices should be performed.     

Prescription habits of dispensing and non-dispensing doctors in Zimbabwe

The number of dispensing doctors has increased in the last decade, but the implication of this trend on the quality of health care and drug use is unknown. We present a comparative drug utilization study of 29 dispensing doctors and 28 non-dispensing doctors in Zimbabwe based on standard indicators developed by the World Health Organization. Dispensing doctors prescribed significantly more drugs per patient than non-dispensing doctors (2.3 versus 1.7), injected more patients (28.4% versus 9.5%), and prescribed more antibiotics (0.72 versus 0.54) and mixtures (0.43 versus 0.25) per encounter. Dispensing doctors also spent significantly less time on each encounter (8.7 min versus 13.0 min) than their non-dispensing colleagues. The use of generic name, brand name and essential drugs did not differ significantly between the two groups of practitioners. Multivariate analyses controlling for gender, race, place of education, location of practice and patients seen per day showed that dispensing by doctors was associated with less clinically and economically appropriate prescribing. These findings suggest that the quality of health care--as related to drug use, patient safety and treatment cost--is lower with dispensing doctors than with non-dispensing doctors.     

中国东部某省儿童基本药物可获得性、价格及可负担性调查分析

目的：分析儿童用药政策实施以来儿童基本药物可获得性、价格及可负担性的现状,为后续制定和完善相关政策提供实证依据。方法：利用中国东部某省基本药物采购平台数据库中2012、2016年数据,依据世界卫生组织（WHO）和国际健康行动组织（HAI）推荐的标准药物调查方法,对49种儿童基本药物的可获得性、价格及可负担性现状进行分析。结果：儿童基本药物可获得性、价格及可负担性整体较好。（1）可获得性方面,2016年较2012年总体出现下降;且2016年、2012年三级医疗机构均高于二级医疗机构和一级医疗机构;仿制药高于原研药。（2）价格方面,2016年较2012年8种原研药价格下降;26种仿制药价格下降,16种仿制药价格上升。（3）可负担性方面,2016年较2012年总体可负担性提高;仿制药总体可负担性优于原研药。结论：（1）三级医疗机构总体可获得性高于一、二级医疗机构。低年龄段儿童基本药物可获得性较差,缺少适宜品种、剂型和规格的药品。（2）儿童基本药物原研药的价格高于国际参考价格,仿制药的价格相对较低。（3）儿童基本药物可负担性较好,2016年较2012年总体可负担性提高,仿制药总体可负担性优于原研药。     

The essential drugs concept is needed now more than ever

The debate on access to essential medicines, which was live in the late 1970s and 1980s when strong pressure from public health advocates led the pharmaceutical industry to accept the concept, is now back on the international health policy agenda. Currently, the Essential Drugs List (EDL) forms an integral part of national drug policies in 146 countries, guiding the selection of drugs on the basis of public health relevance, efficacy, safety and cost. The essential medicines debate is back on the agenda as part of the access to medicines debate. The Trade Related Aspects on Intellectual Property Rights agreement has caused concern among public health advocates in terms of its impact on access to essential medicines. This article reviews the concept of essential medicines in the light of the changing political context and recommends that the EDL is supported as a crucial public policy tool in all countries.     

Generic antibiotic drugs: Is effectiveness guaranteed?

There are recently published arguments suggesting all generic antibiotic drugs do not present the full reliability needed to claim therapeutic equivalence with branded drugs. The problem is especially crucial for generic intravenous drugs, which do not need any bioequivalence study before they can be marketed. The evaluation of generic antibiotic drug effectiveness yields an important dispersion of results according to antibiotic agents and for the same antibiotic agent all generic drugs are not equivalent. There are differences at all levels: drug components, levels of impurity, pharmacokinetics, pharmacokinetic/pharmacodynamic relationship, in vitro effectiveness, therapeutic effectiveness in experimental models, etc. So that finally, the specifications approved in the initial submission file of a brand name drugs are not always respected by a generic drug. There is also a specific problem of taste and treatment acceptability for pediatric oral antibiotic drugs. Available data on clinical effectiveness is excessively rare. The marketing of a great number of generic drugs of the same specialty is followed by a sometimes very important increase of their use, even in countries where consumption is low. The corollary of this increase in consumption is an increase of resistance, and this is especially true for oral fluoroquinolones. Even if most of this information needs to be verified, it seems necessary to review regulations for marketing authorization of generic antibiotic drugs.