Amos Massele

Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future

Background: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIQs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new PIs vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes monitored in the future to provide additional guidance.

Outcome of the first Medicines Utilization Research in Africa group meeting to promote sustainable and rational medicine use in Africa

The first Medicines Utilization Research in Africa group workshop and symposium brought researchers together from across Africa to improve their knowledge on drug utilization methodologies as well as exchange ideas. As a result, progress was made on drug utilization research and formulating future strategies to enhance the rational use of medicines in Africa. Anti-infectives were the principal theme for the 1-day symposium following the workshops. This included presentations on the inappropriate use of antibiotics as well as ways to address this. Concerns with adverse drug reactions and adherence to anti-retroviral medicines were also discussed, with poor adherence remaining a challenge. There were also concerns with the underutilization of generics. These discussions resulted in a number of agreed activities before the next conference in 2016.

Initiative to progress research on medicine utilization in Africa: formation of the Medicines Utilization Research in Africa group

This two day meeting brought together drug utilisation researchers from across Africa. The purpose was to share current drug utilisation (DU) research findings to further DU research across Africa including the development of a medicines utilisation research group. This led to the formation of the MURIA (Medicine Utilisation Research in Africa) Group, with a tentative vision and mission as well as the first planned research methodology training course and a symposium in Botswana later in the year. Future research projects were also planned including studies on drug utilisation of ARVs in Botswana and across Africa as well as ways to enhance the appropriate use of antibiotics and increase generic utilisation.

Comparative chromatography-mass spectrometry studies on the antiretroviral drug nevirapine-Analytical performance characteristics in human plasma determination

A contrast between the analytical performance characteristics using gas chromatography-mass spectrometry (GC-MS) liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-ultraviolet (LC-UV) detection for the determination of the antiretroviral drug (ARV) nevirapine (NVP) in fortified human plasma after QuEChERS extraction has been made. Analytical performance characteristics, i.e. linearities, instrument detection limits (IDLs), limits of quantitation (LOQs), method detection limits (MDLs), % mean recoveries and the corresponding relative standard deviations (%RSDs) were estimated using techniques above. Using GC-MS, the correlation coefficients (r(2)) were ≥0.990, which were deemed acceptable linearities. The MDLs ranged between 11.1-29.8μg/L and 13.7-36.0μg/L using helium and hydrogen carrier gases respectively. The LOQs ranged between 16.5-66.7μg/L and 28.4-98.7μg/L using helium and hydrogen carrier gases respectively with a % mean recovery of 83% and %RSD of 4.6%. Using LC-MS and LC-UV, the correlation coefficients (r(2)) were ≥0.990. The MDLs were ranged between 3.14 and 47.1μg/L. The LOQs ranged between 2.85 and 90.0μg/L respectively. The MDLs using GC-MS, LC-MS and LC-UV were below the therapeutic range for NVP in human plasma is considered to be between 2300μg/L (Cmin) and 8000μg/L (Cmax). This study also demonstrated that helium can be substituted with hydrogen which is relatively cheaper and easily obtainable even by use of a generator.

Research activities to improve the utilization of antibiotics in Africa

ABSTRACT There is a need to improve the rational use of antibiotics across continents including Africa. This has resulted in initiatives in Botswana including treatment guidelines and the instigation of Antibiotic Stewardship Programs (ASPs). The next steps involve a greater understanding of current antibiotic utilization and resistance patterns (AMR). This resulted in a 2-day meeting involving key stakeholders principally from Botswana to discuss key issues including AMR rates as well as ASPs in both the public and private sectors. Following this, the findings will be used to plan future studies across Africa including point prevalence studies. The findings will be presented in July 2016 at the next Medicines Utilization Research in Africa meeting will ideally serve as a basis for planning future pertinent interventional studies to enhance the rational use of antibiotics in Botswana and wider.

Availability of guidelines and policy documents for enhancing performance of practitioners at the Primary Health Care (PHC) facilities in Gaborone, Tlokweng and Mogoditshane, Republic of Botswana

This study aimed to determine the profile and availability of policies and guidelines as reference documents at Primary Health Care (PHC) facilities in Gaborone and its surrounding in Botswana using the World Health Organisation/Drug Action programme (WHO/DAP) Questionnaire. The Questionnaire is a standard recommended by WHO and therefore was not piloted. All 20 PHC facilities were included in the study, however, data from 18 clinics was collected and analysed. The Matron from each PHC facility was asked to name and produce as evidence, guidelines and policy documents available as reference in his/her PHC facility. Data was entered in an Excel spread sheet and percentages, averages and frequencies were used to describe the profile and availability of the documents at each facility. Fifty two different documents were available at the facilities, 50% of them were on treatment and management of diseases. The remaining 50% were distributed between general information/policy, Ante-Natal Clinic, obstetrics and gynaecological care, and family planning. Except for guidelines for treating sexually transmitted diseases (86%), availability of the other guidelines and policy documents was low (56%) or less. Policy and guideline reference information for disease immunisation and prevention were available at 4 and 13% PHC, respectively. This low availability of such important instruments may be compromising patient care in the studied PHC facilities and should be addressed. While the Ministry of Health has produced many policy documents and guidelines as reference documents for PHC providers, none of the clinics had all the documents, raising questions on what is available at the facilities as reference and guide in the prescription practices. It is recommended that ministries of health and PHC workers should ensure that necessary reference documents are available at the facilities and staff should be trained and retrained on the use of such documents. Key words: Rational drug use, general policy documents, medical guidelines, benefits of the guidelines, health facilities.

Assessment of prescribing practices at the primary health care facilities in Botswana with an emphasis on antibiotics; findings and implications

Inappropriate drug prescribing has increased especially in developing countries where systems for monitoring medicine use are not well developed. This increases the rate of antimicrobial resistance. The study aim was to assess the prescribing patterns among urban primary health facilities in Botswana to provide future guidance including developing future quality indicators.

Outcome of the second Medicines Utilisation Research in Africa Group meeting to promote sustainable and appropriate medicine use in Africa

ABSTRACT The second Medicines Utilization Research in Africa (MURIA) group workshop and symposium again brought researchers together from across Africa to improve their knowledge of drug utilization (DU) methodologies and exchange ideas to further progress DU research in Africa. This built on extensive activities from the first conference including workshops and multiple publications. Anti-infectives were again the principal theme for the 2016 symposium following the workshops. This included presentations regarding strategies to improve antibiotic utilization among African countries, such as point-prevalence studies, as well as potential ways to reduce self-purchasing of antibiotics. There were also presentations on antiretrovirals including renal function and the impact of policy changes. Concerns with adherence in chronic treatments as well as drug-drug interactions and their implications were also discussed. The deliberations resulted in a number of agreed activities including joint publications before the next MURIA conference in Namibia in 2017.

Prescription patterns and adequacy of blood pressure control among adult hypertensive patients in Kenya; findings and implications

ABSTRACT Background: Hypertension is a major cause of global morbidity and mortality, with high prevalence rates in Africa including Kenya. Consequently, it is imperative to understand current treatment approaches and their effectiveness in practice. Currently, there is paucity of such data in Kenya, which is a concern. The aim is to describe prescribing patterns and adequacy of blood pressure (BP) control in adult hypertensive patients to guide future practice. Method: Retrospective study of patients attending a sub-county outpatient clinic combined with qualitative interviews. Results: 247 hypertensive patients, predominantly female, mean age 55.8 years on antihypertensive therapy for 1–5 years, were analyzed. ACEIs and thiazide diuretics were the most commonly prescribed drugs, mainly as combination therapy. Treatment typically complied with guidelines, mainly for stage 2 hypertension (75%). BP control was observed in 46% of patients, with a significant reduction in mean systolic (155 to 144 mmHg) and diastolic (91 to 83 mmHg) BP (P < 0.001). Patients on ≥2 antihypertensive drugs were more likely to have uncontrolled BP (OR:1.9, p = 0.021). Conclusion: Encouragingly good adherence to guidelines was helped by training. Poor blood pressure control in the majority needs to be addressed. Additional training of prescribers and follow-up of measures to improve BP control will be introduced and followed up.

A method employing SPE, MRM LC-MS/MS and a THF–water solvent system for the simultaneous determination of five antiretroviral drugs in human blood plasma

A multiple reaction monitoring liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for the simultaneous determination of five antiretroviral drugs i.e. emtricitabine, tenofovir, efavirenz, lopinavir and ritonavir using commercially sterilized human blood plasma as the matrix and a THF/water solvent system was developed for therapeutic drug monitoring purposes and partially validated using the United States Food and Drug Administration (US FDA) guidelines. The analytical performance characteristics that were examined were limits of detection (LODs), lower limits of quantification (LLOQs), upper limits of quantification (ULOQs), selectivity, percent mean recoveries, precision measured as percent relative standard deviations and accuracy. Optimized LC-MS/MS parameters were employed for this purpose. The percent mean recoveries were between 77.3 and 90.1% using solid phase extraction (SPE) for sample preparation. These recoveries were obtained at three spike levels i.e. the LOD, the LLOQ and the ULOQ. The precision of the SPE technique was within an acceptable range of <15% i.e. between 2.7 and 9.2% at the LLOQ. Accuracy was calculated as the percent deviation of the mean value from the true value and the values ranged between 9.9 and 22.7%. The SPE technique satisfied all the requirements of the US FDA guidelines except for efavirenz whose accuracy was slightly higher than recommended at the LLOQ i.e. 22.7% as opposed to 20%. The limits of detection using SPE also fell below the clinically relevant therapeutic range (3–8 mg L−1) for most of the drugs and therefore the method could be useful for therapeutic drug monitoring in HIV patients.