Have we improved use of medicines in developing and transitional countries and do we know how to? Two decades of evidence.

OBJECTIVE: To assess progress in improving use of medicines in developing and transitional countries by reviewing empirical evidence, 1990-2009, concerning patterns of primary care medicine use and intervention effects. METHODS: We extracted data on medicines use, study setting, methodology and interventions from published and unpublished studies on primary care medicine use. We calculated the medians of six medicines use indicators by study year, country income level, geographic region, facility ownership and prescriber type. To estimate intervention impacts, we calculated greatest positive (GES) and median effect sizes (MES) from studies meeting accepted design criteria. RESULTS: Our review comprises 900 studies conducted in 104 countries, reporting data on 1033 study groups from public (62%), and private (mostly for profit) facilities (26%), and households. The proportion of treatment according to standard treatment guidelines was 40% in public and <30% in private-for-profit sector facilities. Most indicators showed suboptimal use and little progress over time: Average number of medicines prescribed per patient increased from 2.1 to 2.8 and the percentage of patients receiving antibiotics from 45% to 54%. Of 405 (39%) studies reporting on interventions, 110 (27%) used adequate study design and were further analysed. Multicomponent interventions had larger effects than single component ones. Median GES was 40% for provider and consumer education with supervision, 17% for provider education alone and 8% for distribution of printed education materials alone. Median MES showed more modest improvements. CONCLUSIONS: Inappropriate medicine use remains a serious global problem.

Predictors of antibiotic use in African communities: evidence from medicines household surveys in five countries.

OBJECTIVES: To investigate antibiotic use in five national household surveys conducted with the WHO methodology to identify key determinants of antibiotic use in the community. METHODS: Data from The Gambia, Ghana, Kenya, Nigeria and Uganda surveys were combined. We used logistic regression models that accounted for the clustered survey design to identify the determinants of care seeking outside the home and antibiotic use for 2914 cases of recent acute illness. RESULTS: Overall, 95% of individuals with acute illness took medicines, 90% sought care outside their homes and 36% took antibiotics. In multivariate analyses, illness severity was a strong predictor of seeking care outside the home. Among those who sought outside care, the strongest predictor of antibiotic use was the presence of upper respiratory symptoms (OR: 3.02, CI: 2.36-3.86, P<0.001), followed by gastrointestinal symptoms or difficulty breathing, and antibiotics use was less likely if they had fever. The odds of receiving antibiotics were higher when visiting a public hospital or more than one healthcare facility. CONCLUSIONS: The nature and severity of symptoms and patterns of care seeking had the greatest influence on decisions to take antibiotics. Antibiotics were widely available and inappropriately used in all settings. Policies to regulate antibiotics distribution as well as interventions to educate prescribers, dispensers and consumers are needed to improve antibiotic use.

Medicine prices, availability, and affordability in 36 developing and middle-income countries: a secondary analysis.

BACKGROUND: WHO and Health Action International (HAI) have developed a standardised method for surveying medicine prices, availability, affordability, and price components in low-income and middle-income countries. Here, we present a secondary analysis of medicine availability in 45 national and subnational surveys done using the WHO/HAI methodology. METHODS: Data from 45 WHO/HAI surveys in 36 countries were adjusted for inflation or deflation and purchasing power parity. International reference prices from open international procurements for generic products were used as comparators. Results are presented for 15 medicines included in at least 80% of surveys and four individual medicines. FINDINGS: Average public sector availability of generic medicines ranged from 29.4% to 54.4% across WHO regions. Median government procurement prices for 15 generic medicines were 1.11 times corresponding international reference prices, although purchasing efficiency ranged from 0.09 to 5.37 times international reference prices. Low procurement prices did not always translate into low patient prices. Private sector patients paid 9-25 times international reference prices for lowest-priced generic products and over 20 times international reference prices for originator products across WHO regions. Treatments for acute and chronic illness were largely unaffordable in many countries. In the private sector, wholesale mark-ups ranged from 2% to 380%, whereas retail mark-ups ranged from 10% to 552%. In countries where value added tax was applied to medicines, the amount charged varied from 4% to 15%. INTERPRETATION: Overall, public and private sector prices for originator and generic medicines were substantially higher than would be expected if purchasing and distribution were efficient and mark-ups were reasonable. Policy options such as promoting generic medicines and alternative financing mechanisms are needed to increase availability, reduce prices, and improve affordability.

Controlled trial of interventions to increase testing and treatment for Helicobacter pylori and reduce medication use in patients with chronic acid-related symptoms.

BACKGROUND: Many symptomatic patients take proton pump inhibitors or histamine-2 blockers for years and those without gastro-oesophageal reflux disease might benefit from Helicobacter pylori eradication. AIM: To increase testing and treatment of H. pylori and reduce chronic use of proton pump inhibitors and histamine-2 blockers. METHODS: We conducted a three-armed controlled trial in 14 managed care practices. We included adults who used proton pump inhibitors or histamine-2 blockers for >1 year and excluded those with gastro-oesophageal reflux disease or previous endoscopy. We compared usual care (n = 312 patients from 6 practices) to low-intensity (n = 147 from 3 practices) and high-intensity (n = 122 from 5 practices) interventions. Low-intensity intervention consisted of guidelines, patient-lists, and a "toolkit"; high-intensity intervention added academic group detailing by a gastroenterologist with reinforcement by pharmacists. RESULTS: Compared with usual care, the high-intensity intervention increased H. pylori test-ordering (29% versus 9% at 12 months, P = 0.02). About half (23 of 58) of patients tested positive and 22 received eradication treatments. The high-intensity intervention decreased proton pump inhibitor use by 9% per year (P = 0.028), but did not alter histamine-2 blocker use. The low intensity intervention was ineffective. CONCLUSIONS: Providing guidelines, patient-lists, and toolkits was no better than usual care. Adding group detailing and pharmacist reinforcements led to improvements in H. pylori management and decreases in proton pump inhibitor use.

Timeliness and quality of care for elderly patients with acute myocardial infarction under health maintenance organization vs fee-for-service insurance.

BACKGROUND: A commonly voiced concern is that health maintenance organizations (HMOs) may withhold or delay the provision of urgent, essential care, especially for vulnerable patients like the elderly. OBJECTIVE: To compare the quality of emergency care provided in Minnesota to elderly patients with acute myocardial infarction (AMI) who are covered by HMO vs fee-for-service (FFS) insurance. METHODS: We reviewed the medical records of 2304 elderly Medicare patients who were admitted with AMI to 20 urban community hospitals in Minnesota (representing 91% of beds in areas served by HMOs) from October 1992 through July 1993 and from July 1995 through April 1996. MAIN OUTCOME MEASURES: Use of emergency transportation and treatment delay (>6 hours from symptom onset); time to electrocardiogram; use of aspirin, thrombolytics, and beta-blockers among eligible patients; and time from hospital arrival to thrombolytic administration (door-to-needle time). RESULTS: Demographic characteristics, severity of symptoms, and comorbidity characteristics were almost identical among HMO (n = 612) and FFS (n = 1692) patients. A cardiologist was involved as a consultant or the attending physician in the care of 80% of HMO patients and 82% of FFS patients (P = .12). The treatment delay, time to electrocardiogram, use of thrombolytic agents, and door-to-needle times were almost identical. However, 56% of HMO patients and 51% of FFS patients used emergency transportation (P = .02); most of this difference was observed for patients with AMIs that occurred at night (60% vs 52%; P = .02). Health maintenance organization patients were somewhat more likely than FFS patients to receive aspirin therapy (88% vs 83%; P = .03) and beta-blocker therapy (73% vs 62%; P = .04); these differences were partly explained by a significantly larger proportion of younger physicians in HMOs who were more likely to order these drug therapies. All differences were consistent across the 3 largest HMOs (1 staff-group model and 2 network model HMOs). Logistic regression analyses controlling for demographic and clinical variables produced similar results, except that the differences in the use of beta-blockers became insignificant. CONCLUSIONS: No indicators of timeliness and quality of care for elderly patients with AMIs were lower under HMO vs FFS insurance coverage in Minnesota. However, two indicators of quality care were slightly but significantly higher in the HMO setting (use of emergency transportation and aspirin therapy). Further research is needed in other states, in different populations, and for different medical conditions.

Reducing infections among women undergoing cesarean section in Colombia by means of continuous quality improvement methods.

BACKGROUND: Improving obstetric care in resource-limited countries is a major international health priority. OBJECTIVE: To reduce infection rates after cesarean section by optimizing systems of obstetric care for low-income women in Colombia by means of quality improvement methods. METHODS: Multidisciplinary teams in 2 hospitals used simple methods to improve their systems for prescribing and administering perioperative antibiotic prophylaxis. Process indicators were the percentage of women in whom prophylaxis was administered and the percentage of these women in whom it was administered in a timely fashion. The outcome indicator was the surgical site infection rate. RESULTS: Before improvement, prophylaxis was administered to 71% of women in hospital A; 24% received prophylaxis in a timely fashion. Corresponding figures in hospital B were 36% and 50%. Systems improvements included implementing protocols to administer prophylaxis to all women and increasing the availability of the antibiotic in the operating room. These improvements were associated with increases in overall and timely administration of prophylaxis (P<.001) in both hospitals by time series analysis, with adjustment for volume and case mix. After improvement, overall and timely administration of prophylaxis was 95% and 96% in hospital A and 89% and 96% in hospital B. In hospital A, the surgical site infection rate decreased immediately after the improvements (P<.001). In hospital B, the infection rate began a downward trend before the improvements that continued after their implementation (P =.04). CONCLUSION: Simple quality improvement methods can be used to optimize obstetric services and improve outcomes of care in resource-limited settings.

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.

Changing behavior to maintain a healthy home.

Multidimensional strategies involving interpersonal interaction, strategic alliances and targeted use of the media have been shown experimentally to be the most effective behavioral change programs. Health providers need to communicate with schools and community groups, as well as work with product manufacturers and consumer and health organizations. Together these groups can collaborate with the media to communicate accurate information and guidance to the public. Planning effective public health and behavioral change campaigns involves diagnosis and identification of the target behavior. The intervention message must be focused, tested and refocused. Effective communication, crucial to public health campaigns, uses multiple channels and provides frequent repetition of the message.

Utilization of essential medications by vulnerable older people after a drug benefit cap: importance of mental disorders, chronic pain, and practice setting.

OBJECTIVE: To identify specific characteristics of patients, physicians, and treatment settings associated with decreased receipt of essential medications in a chronically ill, older population following a Medicaid three-prescription monthly reimbursement limit (cap). DESIGN: Quasi-experiment with bivariate and multivariate regression. SETTING: Patients in the New Hampshire Medicaid program and their regular prescribing physicians. PARTICIPANTS: Three hundred and forty-three chronically ill Medicaid enrollees with regular use of essential medications for heart disease, asthma/chronic obstructive pulmonary disease, diabetes mellitus, seizure, or coagulation disorders who received an average of three or more prescriptions per month during the baseline year. MEASUREMENTS: Postcap patient-level change in standard monthly dose of essential medications compared with the baseline period, presence of 11 comorbidities (defined by regular use of specific indicator drugs), practice setting, and location of regular prescribing physician. RESULTS: The mean percentage change in standard doses of essential medications following the cap was -34.4%. Larger changes were significantly associated with several baseline measures: greater numbers of precap medications, greater numbers of comorbidities, longer hospitalizations, and greater use of ambulatory services. The three comorbidities associated with the largest relative reduction in essential drug use were psychoses/bipolar disorders, anxiety/sleep problems, and chronic pain. Patients of physicians in group practices, clinics, or hospitals tended to have smaller dose reductions than those whose physicians were in solo or small-group practice. CONCLUSIONS: Patients most at risk of reduced access to essential medications because of a reimbursement cap include those with multiple chronic illnesses requiring drug therapy, especially illnesses with a mental health component. Physicians in clinics or large group practices may have maintained patient medication regimens more effectively.

Effects of long-acting versus short-acting calcium channel blockers among older survivors of acute myocardial infarction.

OBJECTIVE: Recent studies have highlighted the potentially harmful effects of short-acting calcium channel blockers, especially of the dihydropyridine type, in patients with coronary heart disease. Some have argued that long-acting calcium channel blockers are safer, but few outcome data exist. The objective of the study was to compare the occurrence of adverse outcomes among recipients of long-acting versus short-acting calcium channel blockers, with dihydropyridines and non-dihydropyridines compared separately. SETTING: The New Jersey Medicare population. DESIGN: A retrospective cohort study using linked Medicare and drug claims data. PARTICIPANTS: Older survivors of acute myocardial infarction (MI) occurring in 1989 and 1990. Eligible subjects had survived at least 30 days after the MI, participated in Medicare and a drug benefits program, and were prescribed a single type of either a long-acting or a short-acting calcium channel blocker within 90 days after the MI. MEASUREMENTS: The two outcome measures were rates of all-cause mortality and cardiac rehospitalization. Using separate Cox regression models for dihydropyridines (nifedipine, nicardipine) and non-dihydropyridines (diltiazem, verapamil), we examined these outcomes for recipients of long-acting compared with short-acting calcium channel blockers. RESULTS: Of the 833 patients eligible for the study, 160 were prescribed long-acting and 673 short-acting calcium channel blockers. Clinical characteristics of long-acting and short-acting users were comparable. During 2 years of follow-up, 221 deaths and 300 rehospitalizations occurred. Controlling for age, sex, race, and indicators of disease severity and comorbidity, the relative risk of dying for recipients of long-acting, compared with short-acting, dihydropyridines was .42 (95% confidence interval (CI), 0.21-0.86). For cardiac rehospitalization, the relative risk was 0.57 (95% CI, 0.34-0.94). For the long-acting versus short-acting nondihydropyridines, the adjusted relative risk of dying was 1.43 (95% CI, 0.88-2.32), and for cardiac rehospitalization, .65 (95% CI, 0.40-1.05). CONCLUSION: Use of long-acting dihydropyridine calcium channel blockers after acute MI was associated with substantially lower rates of cardiac rehospitalization and death compared with use of their short-acting counterparts. More data are needed to address the possibility that long-acting, compared with short-acting, non-dihydropyridines could decrease rehospitalization rates but increase mortality.

A population-based study of xerophthalmia in the extreme North Province of Cameroon, West Africa.

OBJECTIVE: To obtain cross-sectional data on clinical and nutritional vitamin A deficiency from which to design appropriate intervention strategies. DESIGN: A population-based survey using multistage, cluster sampling. SETTING: Extreme North Province of Cameroon, West Africa. PARTICIPANTS: Children aged 0 to 5 years. MAIN OUTCOME MEASURES: Clinical signs of active xerophthalmia and dietary vitamin A intake. RESULTS: Of 5352 children examined, signs of active xerophthalmia were noted in 0.62%. Bitot's spots, corneal xerosis, and corneal ulceration were noted in 0.47%, 0.06%, and 0.12% of the subjects, respectively. Children with xerophthalmia had lower vitamin A intake scores when compared with age-matched controls and with a 20% systematic subsample of children. CONCLUSION: Xerophthalmia is a major public health problem in this region.

Do open formularies increase access to clinically useful drugs?

Before 1990 many state Medicaid programs maintained "restrictive" formularies, which denied reimbursement for unlisted prescription drugs. This type of formulary has been criticized for denying important medications to poor, medically needy persons. As part of the Omnibus Budget Reconciliation Act of 1990, restrictive formularies in Medicaid programs were disallowed. Based on research into the 200 top-selling prescription drugs in the United States, we conclude that eliminating Medicaid restrictive formularies improved access to a subset of the 200 best sellers, but that the majority of these products offered only questionable or no additional therapeutic benefit.

Use of antihypertensive drugs by Medicare enrollees: does type of drug coverage matter?

Research has demonstrated that Medicare beneficiaries with drug coverage consume more clinically essential drugs. However, generosity of coverage varies considerably across beneficiaries. This study examines the association between types of drug coverage and the consumption and cost per tablet of essential antihypertensive medications among beneficiaries with hypertension. The findings indicate that while both state- and employer-sponsored drug coverage are associated with greater consumption of antihypertensive drugs and lower out-of-pocket costs per tablet, private supplemental coverage is not associated with greater use and is associated with only slightly lower out-of-pocket costs than among noncovered beneficiaries.

Blindness and eye disease in Kenya: ocular status survey results from the Kenya Rural Blindness Prevention Project.

A series of eight regional eye surveys were conducted in Kenya as part of the Kenya Rural Blindness Prevention Project. Each survey consisted of clinical examinations of about 1800 individuals selected by a random cluster sampling technique in geographically distinct and culturally homogeneous rural areas; 13,803 examinations were completed in all. Together these surveys provide the basis for national estimates of the prevalence and aetiology of visual loss and ocular pathology. The results showed that 0.7% of rural Kenyans are blind in the better eye by WHO standards, and another 2.5% suffer significant visual impairment. Rates of visual loss tend to increase five-fold in each 20-year age cohort. Females have higher prevalence of visual loss than males over age 20, and certain geographical areas have markedly higher rates. The commonest cause of both blindness and visual impairment is cataract, accounting for 38% of all visual loss. Trachoma (a localised problem), glaucoma, macular degeneration, and severe refractive errors follow cataract as leading causes of blindness in the better eye. Trauma, corneal scars of various causes, phthisis, and staphyloma are important causes of monocular blindness. Nutritional eye disease does not appear to be a problem of any magnitude in rural Kenya.

Prevalence and causes of low vision and blindness in the Extreme North Province of Cameroon, West Africa.

A survey to determine the prevalence and causes of blindness and visual impairment in the Extreme North Province of Cameroon was conducted in the Spring of 1992. A total of 10,647 people age 6 years and older was selected from a multi-stage, clustered sample stratified by ecological zone. The subjects were examined by ophthalmologist-led teams for visual acuity and ocular diseases. Approximately 1.2% of the sample was bilaterally blind by the World Health Organization classification (Category 3) of vision less than the ability to count fingers at 3 meters. Similarly to results found in other developing countries, senile cataract was the most common diagnosis encountered and the most frequent principal cause of low vision and blindness.

Field methodology for ocular surveys in rural Africa.

A series of nine on-site ocular surveys has been carried out in rural Kenya. This article summarizes the organizational and logistical experiences of these site surveys.

Retail pharmacies in developing countries: a behavior and intervention framework.

Retail pharmacies in developing countries are one of the most important sources of advice on pharmaceuticals. Among the reasons the clients give are ease of access; availability of medicines; quality of service (no waiting and convenient hours of operation); and cheaper products, availability of credit, or the option to buy drugs in small amounts. However, the appropriateness of prescribing by retail pharmacy staff has been found to be far from acceptable. In childhood diarrhea, for example, oral rehydration salts (ORS), the appropriate diarrhea treatment, are recommended much less than pharmaceuticals of limited value, such as antimotility agents, adsorbents, etc. Little information is available for reasons underlying such behaviors. In this paper, we present a conceptual framework in which to analyze factors that may affect retail pharmacy prescribing, and we suggest strategies for behavior change. We developed this framework after examining relevant literature on retail pharmacy prescribing. We propose that pharmacy factors, client factors, physician practice and regulatory factors are the four sets of important factors for understanding pharmacy prescribing behavior. For intervention, we present four types of interventions which could be used for changing the behavior of pharmacy staff: information alone, persuasion, incentives and coercion. The behavior and intervention frameworks presented in this paper should also help in guiding further research in this area. For example, new information on the effects of ownership type, availability vs actual role of professional staff and authority structure on pharmacy treatment behaviors would be useful areas for future research. Similarly, additional research is needed on the comparative effects of coercive, persuasive and incentive strategies on pharmacy treatment behaviors.

Undercover careseekers: simulated clients in the study of health provider behavior in developing countries.

The simulated client method (SCM) has been used for over 20 years to study health care provider behavior in a first-hand way while minimizing observation bias. In developing countries, it has proven useful in the study of physicians, drug retailers, and family planning services. In SCM, research assistants with fictitious case scenarios (or with stable conditions or a genuine interest in the services) visit providers and request their assistance. Providers are not aware that these clients are involved in research. Simulated clients later report on the events of their visit and these data are analyzed. This paper reviews 23 developing country studies of physician, drug retail, and family planning services in order to draw conclusions about (1) the advantages and limitations of the methods; (2) considerations for design and implementation of a simulated client study; (3) validity and reliability; and (4) ethical concerns. Examples are also drawn from industrialized countries, related methodologies, and non-health fields to illustrate the issues surrounding SCM. Based on this review, we conclude that the information gathered through the use of simulated clients is unique and valuable for managers, intervention planners and evaluators, social scientist, regulators, and others. Areas that need to be explored in future work with this method include: ways to ensure data validity and reliability; research on additional types of providers and health care needs; and adaptation of the technique for routine use.

A strategy for promoting improved pharmaceutical use: the International Network for Rational Use of Drugs.

Over the last decade, pharmaceutical selection, procurement, distribution, and financing have improved as a result of essential drugs programs. However, despite improved availability, pharmaceuticals are frequently used irrationally. The International Network for the Rational Use of Drugs (INRUD) has been established to help address this problem. The Network joins core groups of researchers from four African and three Asian countries with support groups in Boston, Sweden, WHO, and Australia. The activities of the Network are supported by multilateral, bilateral, foundation donors and by Management Sciences for Health. INRUD functions as a participatory organization in which members are involved in decision-making. The primary objective of the Network is to identify through a coordinated set of country-based research projects a set of effective interventions to recommend as policy options for the promotion of rational drug use. In developing these research projects, INRUD stresses the importance of a multi-disciplinary perspective for adequately understanding the reasons underlying inappropriate use of drugs. To better enable country groups to utilize strong research methodologies and to blend the strengths of multiple disciplines effectively, a major activity of the Network thus far has been the building of local research capacity.

Computerized reminders to monitor liver function to improve the use of etretinate.

OBJECTIVE: to determine whether computerized reminders during the process of prescribing can improve the use of drugs requiring prior laboratory testing according to the indications listed in the Drug Package Insert. MEASURES: Change in proportion of appropriate prescribing and frequency of severe hepatotoxicity between pre- and post-intervention. METHODS: etretinate, a medication indicated for psoriasis, was selected as a monitored drug because it was the most prescribed of all the identified drugs that require specific prior laboratory tests. Computerized reminders are designed to alert a physician who is about to prescribe etretinate either without the alanine aminotransferase (ALT) test or the aspartate aminotransferase (AST) test within 3 months or despite abnormality in ALT or AST. Data on alerts were gathered by using electronic mail whenever alerts occurred. RESULTS: prescriptions of etretinate with normal ALT or AST results within the previous three months increased suddenly from 25.9% (127/491) in the pre-intervention period to 66.2% (353/533) in the post-intervention period (P < 0.0001). Moreover, three patients who used etretinate had markedly abnormal tests in the pre-intervention period, but none of the patients were classified in this way in the post-intervention period. CONCLUSIONS: the computerized reminders appear to improve physicians' use of a drug requiring specific prior laboratory tests.