Quality assurance systems of pharmaceutical distributors in low-income and middle-income countries: weaknesses and ways forward.

INTRODUCTION: Access to quality-assured medicines is an essential prerequisite for universal health coverage, and pharmaceutical distributors play an important role to assure the quality of medicines along the supply chain. METHODS: We retrospectively assessed the compliance with WHO quality standards, that is, the Model Quality Assurance System for Procurement Agencies (MQAS) or the good distribution practices (GDP), of a convenience sample of 75 public, private-for-profit and non-for-profit distributors, audited by QUAMED in 14 low-income and middle-income countries (LMICs) between 2017 and 2019. We calculated the compliance per quality assurance activity, and we defined the percentage of compliant distributors, that is, the percentage (%) of distributors with MQAS or GDP levels of >2 for each activity. RESULTS: The distributors in our sample were mainly private for-profit (66/75). Only one MQAS-audited distributor out of 11 was found compliant with all MQAS-activities, while none out of 64 GDP-assessed distributors were found compliant with all GDP activities. The GDP-assessed distributors were generally less compliant with WHO standards than MQAS-audited distributors. Common weaknesses and strengths were observed. The activities with lowest compliance were quality control, and physical storage conditions, while those with highest compliance were warehouse organisation and stock control. CONCLUSIONS: The quality systems of pharmaceutical distributors in LMICs remain weak. For preventing harm caused by poor-quality medicines, a comprehensive and stringent regulatory oversight should be urgently implemented; the WHO MQAS-standards and GDP-standards should be incorporated in national regulations; and reliable information on the quality systems of distributors (and manufacturers from which they buy) should be publicly available.

Understanding acceptance of and adherence to a new formulation of paediatric antiretroviral treatment in the form of pellets (LPV/r)-A realist evaluation.

BACKGROUND: Improving access to paediatric HIV treatment requires large-scale antiretroviral treatment programmes and medication adapted to infants and children's needs. The World Health Organisation recommends lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors as first-line treatment for all HIV-infected children younger than three years, usually given as a syrup. A pellet formulation (i.e. tiny cylinders of compressed medication put in capsules) was developed to overcome the syrup formulation's disadvantages such as bitterness, toxicity and cold storage. This study assessed multi-level factors influencing caregivers' acceptance of and adherence to lopinavir/ritonavir pellets as well as their underlying mechanisms. METHODS: A realist evaluation (a theory-driven evaluation method considering the social context and mechanisms of change), embedded in a clinical trial was carried out in three hospital settings in Kenya. Data were collected through document review, observations (n = 34) in home and clinic settings and semi-structured interviews (n = 44) with caregivers and providers. Data analysis was based on realist principles. RESULTS: High levels of treatment initiation and adherence were observed. Taste masking, neutral packaging and easy storage made the new formulation highly acceptable. Caregivers developed individual strategies to deliver the treatment, particularly to overcome specific problems e.g. in case of just-weaned babies or food shortage. A refined program theory emerged from the triangulated findings showing that ease of administration combined with increased self-efficacy and competences of the caregivers, and effective provider support contributed to high levels of adherence. CONCLUSIONS: Formulating combined antiretroviral treatment in the form of pellets is clearly a more acceptable solution for infants and children and their caregivers compared to the syrup. Further research in non-trial settings may shed light on factors related to providers, services and the health system that contribute to better adherence of such formulations.

Pharmaceutical quality assurance of local private distributors: a secondary analysis in 13 low-income and middle-income countries.

INTRODUCTION: The rapid globalisation of the pharmaceutical production and distribution has not been supported by harmonisation of regulatory systems worldwide. Thus, the supply systems in low-income and middle-income countries (LMICs) remain exposed to the risk of poor-quality medicines. To contribute to estimating this risk in the private sector in LMICs, we assessed the quality assurance system of a convenient sample of local private pharmaceutical distributors. METHODS: This descriptive study uses secondary data derived from the audits conducted by the QUAMED group at 60 local private pharmaceutical distributors in 13 LMICs. We assessed the distributors' compliance with good distribution practices (GDP), general quality requirements (GQR) and cold chain management (CCM), based on an evaluation tool inspired by the WHO guidelines 'Model Quality Assurance System (MQAS) for procurement agencies'. Descriptive statistics describe the compliance for the whole sample, for distributors in sub-Saharan Africa (SSA) versus those in non-SSA, and for those in low-income countries (LICs) versus middle-income countries (MICs). RESULTS: Local private pharmaceutical distributors in our sample were non-compliant, very low-compliant or low-compliant for GQR (70%), GDP (60%) and CCM (41%). Only 7/60 showed good to full compliance for at least two criteria. Observed compliance varies by geographical region and by income group: maximum values are higher in non-SSA versus SSA and in MICs versus LICs, while minimum values are the same across different groups. CONCLUSION: The poor compliance with WHO quality standards observed in our sample indicates a concrete risk that patients in LMICs are exposed to poor-quality or degraded medicines. Significant investments are needed to strengthen the regulatory supervision, including on private pharmaceutical distributors. An adapted standardised evaluation tool inspired by the WHO MQAS would be helpful for self-evaluation, audit and inspection purposes.

Complex Leadership in Healthcare: A Scoping Review.

BACKGROUND: Nowadays, health systems are generally acknowledged to be complex social systems. Consequently, scholars, academics, practitioners, and policy-makers are exploring how to adopt a complexity perspective in health policy and system research. While leadership and complexity has been studied extensively outside health, the implications of complexity theories for the study of leadership in healthcare have received limited attention. We carried out a scoping review of complex leadership (CL) in healthcare to investigate how CL in healthcare has been defined, theorised and conceptualised and to explore how 'CL' has been applied in healthcare settings. METHODS: We followed the methodological steps proposed by (Arksey and O'Malley, 2005): (1) specifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting the data, (5) collating and summarizing the findings, and (6) reporting the results. We searched using Medline, Psychinfo, Wiley online library, and Google Scholar. Our inclusion criteria were: publication type (peer reviewed articles, theses, and book chapters); phenomenon of interest: complex leadership; context: healthcare and period of publication: between 2000 and 2016. RESULTS: Our search and selection resulted in 37 papers (16 conceptual papers, 14 empirical studies and 7 advocacy papers). We note that empirical studies on CL are few and almost all research reported by these papers was carried out in the North (mainly in USA and UK). We found that there is some variation in definitions of CL. Furthermore, the research papers adopt mostly an explorative or explanatory approach and do not focus on assessing effectiveness of CL approaches. Finally, we found that the majority of researchers seem to adhere to the mathematical complexity perspective. CONCLUSION: Complexity concepts derived from natural sciences may not automatically fit management of health services. Further research into how social complexity theories may offer researchers useful grounds to empirically test CL theories in health settings is warranted. Specific attention should be paid to the multi-layered nature of leadership.

Understanding the acceptability and adherence to paediatric antiretroviral treatment in the new formulation of pellets (LPV/r): the protocol of a realist evaluation.

BACKGROUND: Improving access to paediatric HIV treatment requires both large-scale treatment programmes and medication that is adapted to infants and children's needs. The WHO recommends lopinavir/ritonavir as first-line antiretroviral therapy for all HIV-infected children younger than 3 years. There is currently little evidence on the acceptability of, and adherence to, a formulation of this combination treatment if given in the form of pellets. This protocol presents how we will carry a realist evaluation to assess the factors that contribute to the acceptability and adherence to the new pellets formulation in 3 hospitals in Kenya. METHODS: We structured the protocol along the realist evaluation cycle following 4 steps: (1) the initial programme theory, (2) the study design, (3) the data collection methods and (4) the data analysis plan. Theories of behavioural sciences were reviewed for frames that could provide insights into how using such new formulations may contribute to better acceptability and adherence. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the Institute of Tropical Medicine, the Ethical Committee of the University Hospital Antwerp and the Kenyatta National Hospital/University of Nairobi Ethics and Research Committee. We aim to disseminate the findings through international conferences and peer-reviewed journals and to share them with Drugs for Neglected Diseases initiative's (DNDi) programme managers and with the Kenyan healthcare providers. DISCUSSION: In developing this study, we encountered some challenges. First, methods to measure the acceptability of any formulation and adherence to it are not standardised. The second challenge is common in realist evaluation and relates to how to choose from different potentially interesting theoretical frameworks. We identified relevant and empirically tested theories from behavioural science that may be helpful in our study. We will test them in 3 settings by exploring the multilevel factors that influence acceptability and adherence of this new paediatric Antiretroviral (ARV) formulation.