A simplified checklist for the visual inspection of finished pharmaceutical products: a way to empower frontline health workers in the fight against poor-quality medicines.

BACKGROUND: Substandard and falsified medicines, mainly prevalent in low and middle-income countries (LMICs), cause avoidable morbidity and mortality, and put at stake the performance of health systems. They may be prevented by an adequate implementation of pharmaceutical Quality Assurance (QA) guidelines, but unfortunately, most guidelines address upstream stakeholders and specialized staff in the supply chain. A multi-layered approach is needed, in order to empower the health workers at the point-of-care to proactively contribute to the fight against poor-quality medicines.Visual inspection is a simple technique, suitable for field screening. The findings of a survey conducted in the Democratic Republic of the Congo (DRC) suggested that it might be a fairly good (yet partial) predictor of poor-quality, when compared to full laboratory tests. METHODS AND RESULTS: Starting from the 68-questions checklist originally used in the survey in the DRC, we developed a simplified checklist, specifically designed to guide health workers at the point of care to rapidly identify suspect poor-quality medicines. We selected those medicines' attributes the assessment of which does not require technical expertise, or access to regulatory information. Attributes were categorized according to a 3-level risk scale, to guide decision-making on suspect poor-quality medicines, based on an informed risk assessment.The simplified checklist contains 26 binary questions (YES/NO), grouped into four themes: packaging, identification, traceability, and physical appearance. Each non-conformity corresponds to a level of risk for patients. The user is guided towards three possible actions: A) reasonably safe for dispensing; B) dispense with explanation; C) quarantine and make a risk-benefit evaluation before dispensing. CONCLUSION: The simplified checklist should now be implemented in real-life setting in LMICs. If proven useful in guiding health workers at the point-of-care to take rapid, transparent, patient-centred actions when facing a suspect poor-quality medicine, it could be further extended to address specific formulations. Digitalization for linkage with pharmacovigilance programs could also be considered.

Quality assurance of medicines supplied to low-income and middle-income countries: poor products in shiny boxes?

OBJECTIVE: In today's context of globalisation of pharmaceutical production and distribution, international and national procurement agencies play a de facto key role in defining the quality of medicines available in sub-Saharan Africa. We evaluated the compliance of a sample of pharmaceutical distributors active in sub-Saharan Africa with the standards of the WHO guideline 'Model Quality Assurance System (WHO MQAS) for procurement agencies', and we investigated factors favouring or hindering the adequate implementation of the guideline. METHODS: We used mixed-methods methodology to analyse quantitative and qualitative data. The quantitative study consisted of a retrospective secondary analysis of data collected by QUAMED (Quality Medicines for all), a partnership that pleads for universal access to quality-assured medicines. The qualitative survey consisted of formal and informal interviews with key informants. We adopted an embedded multiple-case study design. FINDINGS: Our analysis suggests that international distributors based in Europe perform, on average, better than sub-Saharan African distributors. However, some weaknesses are ubiquitous and concern critical processes, such as the initial selection of the products and the ongoing reassessment of their quality. This is due to several different factors: weak regulatory oversight, insufficient human/financial resources, weak negotiating power, limited judicial autonomy and/or lack of institutional commitment to quality. CONCLUSIONS: Our findings suggest that pharmaceutical distributors active in sub-Saharan Africa generally do not apply stringent criteria for selecting products and suppliers. Therefore, product quality is not consistently assured but depends on the requirements of purchasers. While long-term solutions are awaited, the WHO MQAS guideline should be used as an evaluation and training tool to upgrade current standards.

Treatment outcomes for human African Trypanosomiasis in the Democratic Republic of the Congo: analysis of routine program data from the world's largest sleeping sickness control program.

OBJECTIVE: To enable the human African trypanosomiasis (HAT) control program of the Democratic Republic of the Congo to generate data on treatment outcomes, an electronic database was developed. The database was piloted in two provinces, Bandundu and Kasai Oriental. In this study, we analysed routine data from the two provinces for the period 2006-2008. METHODS: Data were extracted from case declaration cards and monthly reports available at national and provincial HAT coordination units and entered into the database. RESULTS: Data were retrieved for 15 086 of 15 741 cases reported in the two provinces for the period (96%). Compliance with post-treatment follow-up was very poor in both provinces; only 25% had undergone at least one post-treatment follow-up examination, <1% had undergone the required four follow-up examinations. Relapse rates among those presenting for follow-up were high in Kasai (18%) but low in Bandundu (0.3%). CONCLUSIONS: High relapse rates in Kasai and poor compliance with post-treatment follow-up in both provinces are important problems that the HAT control program urgently needs to address. Moreover, in analogy to tuberculosis control programs, HAT control programs need to adopt a recording and reporting routine that includes reporting on treatment outcomes.

Baseline reproducibility of B-mode ultrasonic measurement of carotid artery intima-media thickness: the European Lacidipine Study on Atherosclerosis (ELSA).

BACKGROUND AND OBJECTIVE: The European Lacidipine Study of Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multi-national interventional trial to determine the effect of four-year treatment using the calcium antagonist lacidipine versus the beta-blocker atenolol on the progression of carotid atherosclerosis in 2259 asymptomatic hypertensive patients. B-mode ultrasound is used to measure the primary and secondary endpoints including the mean maximum intima-media thickness (IMT) of the carotid bifurcations and the common carotid arteries (CBM(max)), the mean maximum IMT of 12 standard carotid sites (M(max)) and the overall maximum IMT (T(max)). This paper reports the cross-sectional reproducibility of ultrasound measurements at baseline. METHOD: To evaluate measurement reliability, each patient is scanned twice at baseline and again at four annual visits, with 80% of the replicate scans performed by the same sonographer and 20% by a different sonographer; 50% of the replicate scans are read by the same reader and the other 50% by different readers. RESULTS: The overall coefficient of reliability (R) was 0.859 for CBM(max), 0.872 for M(max) and 0.794 for T(max). The reliability for CBM(max) was stable during the 1 3/4-year baseline period (R = 0.848 to 0.953) and was uniform among the 23 field centres (R = 0.798 to 0.926). Intra- and inter-reader reliability were 0.915 and 0.872 respectively, and intra-sonographer reliability was 0.866. CONCLUSION: The results demonstrate that by implementing standardized protocols and strict quality control procedures, highly reliable ultrasonic measurements of carotid artery IMT can be achieved in large multi-national trials.

Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis.

BACKGROUND: The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN: The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment. METHODS: Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universität München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. RESULTS: Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. CONCLUSIONS: Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.