Pharmaceutical industry-led partnerships focused on addressing the global burden of non-communicable diseases: a review of Access Accelerated.

OBJECTIVE: In spite of the increasing number of global health partnerships led by biopharmaceutical companies, there is a paucity of information on the number, type, and role of partners. This paper aims to analyze partnerships carrying out company programs included in Access Accelerated, a new industry initiative, focused on addressing the global non-communicable disease burden. STUDY DESIGN: Document review and content analysis. METHODS: We extracted data on the number, type, and role of partners from 63 company programs reported into the Access Observatory, a public platform for reporting on access-to-medicines programs, in 2017. We did a descriptive analysis of the proportion of partners by sector, institution, and location. We used the Fischer's exact test to analyze the relationship between the program strategies, disease focus, and countries with the type of program partners. Based on our empirical findings, we developed a typology of program partnerships, according to which we categorized each of the 63 programs. RESULTS: Programs worked with three partners on average, the majority of which were local governmental or non-governmental organizations (70%). Most programs focused on health service strengthening (83%), community awareness and linkage to care (81%), and health service delivery (60%). Twenty-six of the 63 programs (41%) worked with the local Ministries of Health while 25 (40%) partnered with disease-specific organizations, 21 (33%) with hospitals, and 16 (25%) with academic institutions. Partnering with the Ministries of Health was significantly associated with the use of a health service strengthening program strategy (P = 0.02). Partnering with a hospital (P = 0.004) or private sector partner (P = 0.0009) was significantly associated with a program disease focus on cancer. Seventy-nine percent of the programs were solely funded by pharmaceutical companies. According to our program typology, 40 (63%) programs partnered directly or indirectly with multiple implementing organizations, which delivered the program directly to beneficiaries. CONCLUSION: Pharmaceutical companies play a leading role in funding Access Accelerated programs with local governmental or non-governmental organizations mainly involved in program implementation. A detailed and transparent reporting of the role of local stakeholders in agenda setting, planning, and coordination of programs is needed to ensure public trust and accountability of programs led by pharmaceutical companies. More research is needed to identify the partnerships that are particularly suitable to promote efficient implementation, evaluation, and reporting depending on the nature of the program and context.

A perspective on global access to insulin: a descriptive study of the market, trade flows and prices.

AIM: To describe the global insulin market. METHODS: Market intelligence data, United Nations Commodity Trade Statistics for insulin trade, the International Medical Products Price Guide for prices of human insulin and additional web searches were used as data sources. These sources were combined to gain further insight into possible links among market, trade flows and prices. Descriptive statistics and Spearman's rank order correlation were used for the analysis. RESULTS: A total of 34 insulin manufacturers were identified. Most countries and territories are reliant on a limited number of supplying countries. The overall median (interquartile range) government procurement price for a 10-ml, 100-IU/ml vial during the period 1996-2013 equivalent was US$4.3 (US$ 3.8-4.8), with median prices in Africa (US$ 4.7) and low- (US$ 6.9) and low- to middle- (US$ 4.7) income countries being higher over this period. The relationships between price and quantity of insulin (Spearman's r=0.046; P>0.1) and number of import links (Spearman's r=0.032; P>0.1) were weak. The links between price and percentage of total insulin from a country where a 'big three' manufacturer produces insulin (Spearman's r=0.294; P<0.05) and total insulin from the main import link (Spearman's r=-0.392; P<0.05) were stronger. CONCLUSIONS: This research shows the high variability of insulin prices and the reliance on a few sources, both companies and countries, for global supply. In addressing access to insulin, countries need to use existing price data to negotiate prices, and mechanisms need to be developed to foster competition and security of supply of insulin, given the limited number of truly global producers.

Access to asthma medicines at the household level in eight counties of Kenya.

BACKGROUND: It is estimated that about 4 million Kenyans, i.e., 10% of the country's population, have asthma. We aimed to evaluate access to asthma medicines at the household level in eight counties of Kenya, including factors associated with location of purchase. METHODS: Individuals with a diagnosis and prescription of asthma medicines were asked about the location of diagnosis, purchase of medicines, availability of medicines at home and costs of medicines per month. A logistic regression model explored the relationship between patient characteristics and the probability that the patient purchased asthma medicines at a public facility. RESULTS: Of 128 (15.2%) individuals with a diagnosis of asthma who were receiving treatment, only 57.0% had asthma medicines at home. The most frequently purchased asthma medicine was salbutamol, with one third of individuals taking it orally instead of by inhalation. The majority (55.4%) purchased asthma medicines at private pharmacies. Female patients and lower socio-economic status were predictors of purchasing asthma medicines at public facilities. CONCLUSIONS: The availability and affordability of asthma medicines remain significant barriers to access to care. Improving the availability and affordability of all asthma medicines in the public sector, including inhaled corticosteroids, offers the opportunity to reach vulnerable populations.

How do the EMA and FDA decide which anticancer drugs make it to the market? A comparative qualitative study on decision makers' views.

BACKGROUND: The process leading to a regulatory outcome is guided by factors both related and unrelated to the data package, defined in this analysis as 'formal and informal factors', respectively. The aim of this qualitative study was to analyse which formal and informal factors drive the decision-making process of the European Medicines Agency (EMA) and Food and Drug Administration (FDA) regulators with regard to anticancer drugs, using in-depth semi-structured interviews with regulators of the two agencies. METHODS: In line with the theory and practice of qualitative research, no set sample size was defined a priori. Respondent enrolment continued until saturation and redundancy were reached. Data were collected through means of in-depth semi-structured interviews conducted either in a face-to-face setting or via Skype(®) with each regulator. The interviews were audio-recorded and verbatim transcribed. The analysis was manually carried out on the transcribed text. Data were independently coded and categorized by two researchers. Interpretation of the findings emerged through a process of triangulation between the two. RESULTS: Seven EMA and six FDA regulators, who had extensive experience with making decisions about anticancer medicines, were interviewed between April and June 2012. There is an open dialogue between the FDA and EMA, with the two moving closer and exchanging information, not opinions. Differences in decision-making between the agencies may be due to a different evaluation of end points. Different interaction modalities with industry and patients represent an additional source of divergence with a potential impact on decision-making. The key message of our respondents was that the agencies manage uncertainty in a different way: unlike the EMA, the FDA has a prevailing attitude to take risks in order to guarantee quicker access to new treatments. CONCLUSIONS: Although formal factors are the main drivers for regulatory decisions, the influence of informal factors plays an important role in the drug evaluation process.

Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.

Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.

Field tests for rational drug use in twelve developing countries.

Increasing efforts are being made to improve drug-use practices and prescribing behaviour in developing countries. An essential tool for such work is an objective and standard method of assessment. We present here a set of drug-use indicators produced and tested in twelve developing countries. We describe practical applications, which include the use of indicators to increase awareness among prescribers in Malawi and Bangladesh, to identify priorities for action (eg, polypharmacy in Indonesia and Nigeria, overuse of injections in Uganda, Sudan, and Nigeria, and low percentage of patients who understood the dosage schedule in Malawi), and to quantify the impact of interventions in Yemen, Uganda, Sudan, and Zimbabwe.

PIP: A set of drug-use indicators produced and tested in 12 developing countries and the recommended method for data collection are presented to improve drug use and prescribing behavior. The International Network for the Rational Use of Drugs in collaboration with the WHO Action Program on Essential Drugs undertook a project to develop and field-test a set of basic drug-use indicators. The method for collecting the data was first tested in Indonesia, Bangladesh, and Nepal; other tests took place in Guatemala, Malawi, Nigeria, Tanzania, and well as in Ecuador, Sudan, and Zimbabwe. In results from 12 developing countries, drug-use patterns were ascertained. The average numbers of drugs per encounter were high in Indonesia and Nigeria (3.3 and 3.8); the prescriptions of 1 or more antibiotics were also high in Uganda and Sudan (56% and 63%), similar to injectable drugs in Uganda, Sudan, and Nigeria (36-48%); and the availability of essential drugs was low in Ecuador (38%). 94% of drugs were prescribed by generic name in Zimbabwe, whereas only 37% were in Ecuador. In Yemen the comparison of an essential drugs project area to a control area demonstrated 1.5 and 2.4 drugs per encounter, 46% and 67% of them antibiotics and 22% and 45% of them injections, respectively. In Uganda, a study on the effect of training showed decline in the use of injections (50% to 41%), improvement in the use of oral rehydration treatment for diarrhea (52% to 89%), and reduction in antidiarrheal drug use (60% to 39%). In rural health facilities in Sudan the drugs prescribed by generic name increased from 17% to 70% between 1989 and 1991. In 10 developing countries the average number of drugs per prescription for general outpatient encounters ranges from 1.3 to 2.2., but in Indonesia and Nigeria it is 3.3 and 3.8. The median of 41% of antibiotics prescribed in the 12 countries reflects actual prescribing, not optimum values.

Knowledge and management of malaria in Dar es Salaam, Tanzania.

A study of knowledge and management of malaria was undertaken prospectively in 20 dispensaries, 20 drug stores, 120 patients attending dispensaries and 120 customers at drug stores in Dar es Salaam, Tanzania. This was a descriptive study where two different questionnaires were developed and administered to the target groups in oral interview. All the respondents were aged 14 years and above. The results of the interview showed that the knowledge of rural medical aides (RMA's) on signs and symptoms of malaria and which drugs cure malaria was satisfactory. However, only 65% of the RMA's could remember the correct dose of chloroquine for an adult. Although the knowledge of drug sellers on signs and symptoms of malaria was adequate, 45% of them did not know the correct dose of chloroquine. In view of the fact that only 30% of patients and 20% of shoppers knew the correct dose of chloroquine for adults, it appears that their management of malaria is inadequate. To improve the management of malaria at dispensary and drug store level, there is a need to introduce treatment charts and/or guidelines and the Ministry of Health should promote health education to the public.

PIP: In early 1992 in Tanzania, trained research assistants interviewed 20 rural medical aides (RMAs), 20 drug sellers, 120 patients at 20 dispensaries, and 120 customers of drug stores, all in Dar es Salaam, to examine knowledge and practices of health workers, drug sellers, and patients concerning malaria. The RMAs had adequate knowledge of the signs and symptoms of malaria (e.g., 90% for fever, 85% for headache, and 80% for painful joints). The drug sellers also had adequate knowledge of signs and symptoms (e.g., 80% for fever, 45% for headache, and 50% for painful joints). Even though chloroquine-resistant strains of Plasmodium falciparum malaria exist in Tanzania, all RMAs and most drug sellers (85%) believed that chloroquine could cure malaria. Further, it is the only antimalarial that the Ministry of Health provides its dispensaries. Just 65% of RMAs knew the correct dosage of chloroquine for people 14 years old and older. An even lower percentage of drug sellers knew the correct dosage (50%). Just 33.7% of patients and 22.5% of customers knew the correct dosage of chloroquine. An inadequate supply of chloroquine was available at 15% of dispensaries and 30% of drug stores. RMAs sometimes gave patients too few chloroquine tablets for a full course of therapy. Other drugs mentioned by RMAs to treat malaria were quinine, amodiaquine, cotrimoxazole, halofantrine, pyrimethamine/sulphalene, and pyrimethamine/sulphadoxine. Those mentioned by drug sellers included aspirin plus chloroquine, cotrimoxazole, pyrimethamine/sulphadoxine, and traditional medicines. These findings suggest that irrational drug therapy of malaria promotes resistant strains and prolongs the duration of illness. Introduction of treatment charts and health education promotion to the public are needed to improve malaria management at dispensaries and drug stores.

A study of prescribing patterns with special reference to drug use indicators in Dar es Salaam Region, Tanzania.

Drug prescribing patterns were studied in 720 retrospective and 779 prospective outpatient prescriptions from 20 dispensaries in Dar es Salaam region, and these revealed a mean drug exposure of 2.0 and 2.3, respectively. The percentage of patients leaving the dispensaries with no prescribed drugs was 1.3% and 0.7%, respectively. Prescriptions containing antibiotics were 36.8% (retrospective) and 39.8% (prospective), while injections accounted for 24.6% and 34% of the total encounters, respectively. Over 70% of prescriptions conformed to the Tanzania essential drug list (EDP) and/or standard treatment guidelines and consisted of 83.9% and 79.1% generic prescriptions, respectively. Interestingly, only 15% of the surveyed dispensaries had an EDP book and/or calendar. Despite the consulting and dispensing times being short (2.98 min and 77.7 s, respectively), 70% of the patients could remember the dosing instructions. Only 64% of the patients had a minimum physical examination.

Changes in the World Health Organisation essential drug list.

The World Health Organisation Model List of Essential Drugs is an attempt to provide guidelines for selection of essential pharmaceuticals. Analysis of the six lists produced between 1977 and 1990 shows an increase in the number of items from 205 to 268. 120 drugs have been added and 57 deleted; however, only 16 of the additional drugs can be considered new clinical entities or to have new indications. The original purpose of the essential drug list was to itemise the minimum number of essential drugs. Many additions were due to a change in perception about the usefulness of a particular drug, not scientific advances. Nevertheless, the list remains a useful guide for countries selecting their own national lists.

Changes in the World Health Organization essential drug list

The World Health Organization model list of essential drugs is an attempt to provide guidelines for selection of essential pharmaceuticals. Analysis of the six lists produced between 1977 and 1990 shows an increase in the number of items from 205 to 268. 120 drugs have been added and 57 deleted; howevwe, only 16 of the additional drugs can be considered new clinical entities or to have new indications. The original purpose of the essential drug list was to itemise the minimum number of the essential drugs. Many additions were due to a change in perception about the usefulness of a particular drug, not scientific advances. Nevertheless, the list remains a useful guide for countries selecting their own national lists (AU)

Intervention research to promote clinically effective and economically efficient use of pharmaceuticals: the International Network for Rational Use of Drugs.

Despite acceptance of the essential drug concept by over 100 countries, current drug use patterns frequently result in unsafe use, waste of scarce resources, non-compliance, excess adverse drug reactions and disease resistance. Even in countries where resources for research are available, most efforts to improve drug prescribing have never been properly evaluated. Proposed interventions should reflect the behavioral basis for current drug use, target priority public health areas, and be feasible in developing country contexts. Most importantly, they must be critically assessed for cost and effectiveness in well-controlled field trials. The International Network for Rational Use of Drugs (INRUD) is a cooperative organization of health professionals and researchers in developing countries whose aim is to promote improved quality of care through more clinically effective and economically efficient use of pharmaceuticals. To accomplish this, INRUD will strengthen regional and national capacities to develop and scientifically evaluate programs to improve drug use and disseminate information on practical strategies shown to be cost-effective.