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A highly miniaturized limb sounder for the observation of the O2 A-band to derive temperatures in the mesosphere and lower thermosphere is presented. The instrument consists of a monolithic spatial heterodyne spectrometer (SHS), which is able to resolve the rotational structure of the R-branch of that band. The relative intensities of the emission lines follow a Boltzmann distribution and the ratio of the lines can be used to derive the kinetic temperature. The SHS operates at a Littrow wavelength of 761.8 nm and heterodynes a wavelength regime between 761.9 and 765.3 nm with a resolving power of about 8000 considering apodization effects. The size of the SHS is 38 × 38 × 27 mm3 and its acceptance angle is ±5°. It has an etendue of 0.01 cm2 sr. Complemented by front optics with an acceptance angle of ±0.65° and detector optics, the entire optical system fits into a volume of about 1.5 L. This allows us to fly this instrument on a 3- or 6-unit CubeSat. The vertical field of view of the instrument is about 60 km at the Earth's limb when operated in a typical low Earth orbit. Integration times to obtain an entire altitude profile of nighttime temperatures are on the order of 1 min for a vertical resolution of 1.5 km and a random noise level of about 1.5 K. Daytime integration times are 1 order of magnitude shorter. This work presents the design parameters of the optics and a radiometric assessment of the instrument. Furthermore, it gives an overview of the required characterization and calibration steps. This includes the characterization of image distortions in the different parts of the optics, visibility, and phase determination as well as flat fielding.

Background: The WHO Essential Medicine List for Children was released on the 30th anniversary of the general Essential Medicine List in 2007, to recognise special needs for medicines in children, and to promote the inclusion of paediatric medicines in national procurement programmes. This study aimed to investigate the alignment of the medicines included in the Albanian reimbursement medicines list of the Mandatory Healthcare Insurance Fund (AMHIF) and the Essential Medicine List for Children. Methods: A quantitative evaluation was performed to compare the paediatric medicines included in the 2022 list of the AMHIF and the 2021 WHO Essential Medicine List for Children. In addition, vaccines in the Albanian vaccination programmes for children were compared to the ones listed on the WHO Essential Medicine List for Children. Results: Both lists had a total of 284 active ingredients in common, whereas 14 of 24 vaccines were found to be in common in the Essential Medicine List for Children list and the Albanian vaccination programmes. Conclusions: This is the first study in Albania to investigate the alignment of the WHO EMLc and AMHIF list. In case of the same active ingredient there were many deviations in terms of dosage form, strength and indication.

ABSTRACTBackground This study explored the treatment-related, financial and psychological experiences of caregivers during cancer treatment of their children in South Africa’s (SA) public and private sectors.Methods In this exploratory study, three focus groups were conducted with caregivers of children undergoing cancer treatment in SA’s public healthcare sector. A fourth small focus group with two parents in the private sector was conducted online. A mixed-methods approach was employed using a combination of thematic analysis and grounded theory.Results Of the 20 public sector caregivers, many expressed frustration at the number of visits to primary healthcare clinics before being referred. Caregivers had difficulties coping with and accepting the diagnosis, alongside managing continued care for the child and other children at home. Support received by family and community members was varied. Financial strain was an important concern. The two private sector parents indicated greater levels of support and no financial hardship, but expressed similar levels of emotional stress.Conclusion These caregiver experiences indicate that improvements are urgently needed in the recognition of childhood cancer symptoms at primary healthcare level in SA. They also highlight a need for increased financial support from government through social grants, travel allowances and nutritional support.

Background We sought to identify what barriers and facilitators determine current perceived access to childhood cancer care in South Africa through in-depth interviews with stakeholders in South Africa’s public and private sectors.Methods Qualitative semi-structured interviews were conducted with 29 key health system stakeholders, including policy-makers and regulators, medical insurance scheme informants, medicine suppliers, healthcare providers and civil society stakeholders. Identified barriers and facilitators in access to medicines and broader care were structured according to the pharmaceutical value chain (PVC).Results Barriers and facilitators were identified across all components of the PVC. Key barriers included (1) a lack of political commitment to childhood cancers, (2) discontinuation of essential chemotherapeutics, (3) incomplete insurance coverage for childhood cancers, (4) stock-outs of essential medicines, (5) the inability to access care, including travel to healthcare facilities and (6) low awareness on childhood cancers among primary healthcare (PHC) workers. Proposed priority interventions included pricing flexibilities, increased transparency and consistency in decision-making and healthcare spending, and improved training of PHC staff, nurses and pharmacists on childhood cancers.Conclusion This first comprehensive study of determinants of access to medicines used in childhood cancer in South Africa provides context-specific evidence for targeted policy development.

Abstract Objective Despite global recognition that access to medicines is shaped by various interacting processes within a health system, a suitable analytical framework for identifying barriers and facilitators from a system’s perspective was needed. We propose a framework specifically designed to find drivers to access to medicines from a country’s health system perspective. This framework could enable the systematic evaluation of access across countries, disease areas and populations and facilitate targeted policy development. This framework is the byproduct of a larger study on the barriers and facilitators to childhood oncology medicines in South Africa. Results Eight core (pharmaceutical) functional processes were identified from existing frameworks: (I) medicine regulation, (II) public financing and pricing, (III) selection, (IV) reimbursement, (V) procurement and supply, (VI) healthcare delivery, (VII) dispensing and (VIII) use. National contextual components included policy and legislation and health information systems. To emphasize the interlinkage of processes, the proposed framework was structured as a pharmaceutical value chain. This framework focusses on national processes that are within a country’s control as opposed to global factors, and functional mechanisms versus a country’s performance or policy objectives. Further refinement and validation of the framework following application in other contexts is encouraged.

Abstract Background Access to anaesthesia and surgical care is a major problem for people living in Sub-Saharan Africa. In this region, ketamine is critical for the provision of anaesthesia care. However, efforts to control ketamine internationally as a controlled substance may significantly impact its accessibility. This research therefore aims to estimate the importance of ketamine for anaesthesia and surgical care in Sub-Saharan Africa and assess the potential impact on access to ketamine if it were to be scheduled. Methods This research is a mixed-methods study, comprising of a cross-sectional survey at the hospital level in Rwanda, and key informant interviews with experts on anaesthesia care in Sub-Saharan Africa. Data on availability of four anaesthetic agents were collected from hospitals (n = 54) in Rwanda. Semi-structured interviews with 10 key informants were conducted, collecting information on the importance of ketamine, the potential impact of scheduling ketamine internationally, and opinions on misuse of ketamine. Interviews were transcribed verbatim and analysed using a thematic analysis approach. Results The survey conducted in Rwanda found that availability of ketamine and propofol was comparable at around 80%, while thiopental and inhalational agents were available at only about half of the hospitals. Significant barriers impeding access to anaesthesia care were identified, including a general lack of attention given to the specialty by governments, a shortage of anaesthesiologists and migration of trained anaesthesiologists, and a scarcity of medicines and equipment. Ketamine was described as critical for the provision of anaesthesia care as a consequence of these barriers. Misuse of ketamine was not believed to be an issue by the informants. Conclusion Ketamine is critical for the provision of anaesthesia care in Sub-Saharan Africa, and its scheduling would have a significantly negative impact on its availability for anaesthesia care.

BackgroundEarly identification is critical for mitigating the impact of medicine shortages on patients. The internet, specifically social media, is an emerging source of health data. ObjectiveThis study aimed to explore whether a routine analysis of data from the Twitter social network can detect signals of a medicine shortage and serve as an early warning system and, if so, for which medicines or patient groups. MethodsMedicine shortages between January 31 and December 1, 2019, were collected from the Dutch pharmacists’ society’s national catalog Royal Dutch Pharmacists Association (KNMP) Farmanco. Posts on these shortages were collected by searching for the name, the active pharmaceutical ingredient, or the first word of the brand name of the medicines in shortage. Posts were then selected based on relevant keywords that potentially indicated a shortage and the percentage of shortages with at least 1 post was calculated. The first posts per shortage were analyzed for their timing (median number of days, including the IQR) versus the national catalog, also stratified by disease and medicine characteristics. The content of the first post per shortage was analyzed descriptively for its reporting stakeholder and the nature of the post. ResultsOf the 341 medicine shortages, 102 (29.9%) were mentioned on Twitter. Of these 102 shortages, 18 (5.3% of the total) were mentioned prior to or simultaneous to publication by KNMP Farmanco. Only 4 (1.2%) of these were mentioned on Twitter more than 14 days before. On average, posts were published with a median delay of 37 (IQR 7-81) days to publication by KNMP Farmanco. Shortages mentioned on Twitter affected a greater number of patients and lasted longer than those that were not mentioned. We could not conclusively relate either the presence or absence on Twitter to a disease area or route of administration of the medicine in shortage. The first posts on the 102 shortages were mainly published by patients (n=51, 50.0%) and health care professionals (n=46, 45.1%). We identified 8 categories of nature of content. Sharing personal experience (n=44, 43.1%) was the most common category. ConclusionsThe Twitter social network is not a suitable early warning system for medicine shortages. Twitter primarily echoes already-known information rather than spreads new information. However, Twitter or potentially any other social media platform provides the opportunity for future qualitative research in the increasingly important field of medicine shortages that investigates how a larger population of patients is affected by shortages.

Abstract Introduction The COVID-19 pandemic highlighted an urgent need for harmonised requirements for the regulation of medicines. To fully implement harmonised medicines regulations across Africa, common technical standards of medicine regulations are needed. One such technical standard is the labelling of medicines on outer packaging. In this study, we compared outer packaging labelling requirements and transition terms for harmonization for countries in the Southern African Development Community (SADC) region. Methods Data on legislation and/or regulatory guidelines for medicine outer packaging labelling from National Medicines Regulatory Authorities (NMRAs) were obtained for countries in the SADC region (n = 16) by February 2023. A detailed comparative content analysis was conducted to determine alignment with the requirements of the Southern African Development Community (SADC) harmonised labelling guidelines to assess readiness levels of each country to transition to the SADC harmonised labelling guideline for outer packaging of medicines. Results Content analysis showed at least 11 out of 16 countries require national legal reform to transition to the SADC harmonised labelling guideline. In all cases where countries specified labelling requirements for outer packaging of medicines, these were stipulated in national medicines legislation. Conclusion Even though there is a high level of alignment across the countries in terms of national labelling requirements, most countries in the SADC region would still require national legislative reform to transition to regional harmonised labelling requirements and then ultimately to continental requirements of the African Medicines Agency (AMA).

IntroductionAlthough drug repurposing holds great potential in addressing unmet needs, successful practical implementation is challenging and has been less widespread than anticipated. Regulators may play a critical role in addressing this, and recent years have seen the conception of regulator-initiated and publicly-funded repurposing initiatives, with significant regulator involvement.MethodsInternational regulators and public funders (n = 8) were interviewed to obtain insight in how repurposing can be advanced from a regulatory perspective. Transcripts were thematically analyzed.ResultsMost initiatives employed a broad concept of repurposing. While patient access was the main focus, label extension remained the gold standard. Commonly perceived barriers were a lack of regulatory expertise, limited downstream drug development, insufficient financial incentives, inadequate awareness of challenges, and poor collaboration. Ways for regulators to facilitate repurposing include early and accessible involvement fostering education, collaboration, and awareness. Increased stakeholder engagement, including internationally, was recommended. Legislative changes may enable the current repurposing ecosystem to evolve.DiscussionRegulators may play a central role in advancing repurposing by reconsidering their responsibilities within the current regulatory framework, both in mitigating repurposing pitfalls and actively encouraging repurposing initiatives by industry and non-traditional drug developers.

Objectives We aimed to identify existing appraisal tools for non-randomised studies of interventions (NRSIs) and to compare the criteria that the tools provide at the quality-item level.Design Literature review through three approaches: systematic search of journal articles, snowballing search of reviews on appraisal tools and grey literature search on websites of health technology assessment (HTA) agencies.Data sources Systematic search: Medline; Snowballing: starting from three articles (D’Andrea et al, Quigley et al and Faria et al); Grey literature: websites of European HTA agencies listed by the International Network of Agencies for Health Technology Assessment. Appraisal tools were searched through April 2022.Eligibility criteria for selecting studies We included a tool, if it addressed quality concerns of NRSIs and was published in English (unless from grey literature). A tool was excluded, if it was only for diagnostic, prognostic, qualitative or secondary studies.Data extraction and synthesis Two independent researchers searched, screened and reviewed all included studies and tools, summarised quality items and scored whether and to what extent a quality item was described by a tool, for either methodological quality or reporting.Results Forty-nine tools met inclusion criteria and were included for the content analysis. Concerns regarding the quality of NRSI were categorised into 4 domains and 26 items. The Research Triangle Institute Item Bank (RTI Item Bank) and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) were the most comprehensive tools for methodological quality and reporting, respectively, as they addressed (n=20; 17) and sufficiently described (n=18; 13) the highest number of items. However, none of the tools covered all items.Conclusion Most of the tools have their own strengths, but none of them could address all quality concerns relevant to NRSIs. Even the most comprehensive tools can be complemented by several items. We suggest decision-makers, researchers and tool developers consider the quality-item level heterogeneity, when selecting a tool or identifying a research gap.OSF registration number OSF registration DOI (https://doi.org/10.17605/OSF.IO/KCSGX).

Abstract Introduction Current research to assess the impact that medicine shortages have on patients is limited to general aspects, such as the prevalence of shortages and product characteristics. The aim of this study is to assess the overall impact that medicine shortages have on economic, clinical, and humanistic outcomes. Methods A cohort of all known products in shortage in the Netherlands between 2012 and 2015 were characterized by their route of administration, anatomical therapeutic chemical class, and whether they were originator or generic products. A representative sample of 324 shortages (18% of all shortages) was rated as having low, medium, or high impact on the five elements that determine the impact of shortages on patients: availability of an alternative product, underlying disease, susceptibility of the patient, costs (for patients and society at large), and number of patients affected. Ratings were converted into numerical scores per element and multiplied to obtain an overall impact score. Results Two elements were most frequently rated as having a high impact: disease (29%) and costs (20%). Nearly half of the shortages (47%) rated high on at least one element, while nearly 10% rated high on multiple elements. Thirty percent of the shortages rated high on direct impact, which is represented by these elements: alternative product and disease. An additional 17% of the shortages rated high on indirect impact, which is represented by these elements: costs, susceptibility, and number of patients. High impact scores could not significantly be attributed to characteristics of the products in shortage. Conclusions An assessment of the medicine shortages’ impact using a framework based on economic, clinical, and economic outcomes showed that all three outcomes affect the overall impact that medicine shortages have on patients.

Introduction The effectiveness of a health system in providing access to medicines is in part determined by the alignment of several core pharmaceutical processes. For South Africa’s public health sector, these include the registration of medicines, selection and subsequent procurement through national tenders. Registration, selection and reimbursement are key processes in the private sector. This study assessed the alignment of forementioned processes for essential paediatric oncology medicines in South Africa.Methods A selection of priority chemotherapeutics, antiemetics and analgesics in the treatment of five prevalent childhood cancers in South Africa was compared with those listed in 1) the WHO Essential Medicines List for Children (WHO EMLc) 2021, 2) the registered health products database of South Africa, 3) the relevant South African National Essential Medicines Lists (NEML), 4) bid packs and awarded tenders for oncology medicines for 2020 and 2022 and 5) oncology formularies from the leading Independent Clinical Oncology Network (ICON) and two private sector medical aid schemes. Consistency between these sources was assessed descriptively.Results There was full alignment for 25 priority chemotherapeutics for children between the NEML, the products registered in South Africa and those included on tender. Due to unsuccessful procurement, access to seven chemotherapeutics was potentially constrained. For antiemetics and analgesics, eight of nine active ingredients included on the WHO EMLc were also registered in South Africa and on its NEML. An exploratory assessment of private sector formularies showed many gaps in ICON’s formulary and two medical scheme formularies (listing 33% and 24% of the chemotherapeutics, respectively).Conclusion Despite good alignment in public sector pharmaceutical processes, access constraints to essential chemotherapeutics for children may stem from unsuccessful tenders. Private sector formularies show major gaps; however, it is unclear how this translates to access in clinical practice.

Monitoring access to pediatric medicines as part of the Sustainable Development Goal (SDG) agenda for 2030 requires surveying age-appropriate medicines. This study aimed to develop tracer sets of essential age-appropriate medicines for use in SDG indicator 3.b.3 or in conjunction with other methodologies for monitoring access to medicines. Two sets of medicines were developed, one for young children (1 month to 5 years) and one for school-aged children (5–12 years). Priority diseases were selected based on the global burden of disease and linked to active ingredients of first choice according to treatment guidelines and the World Health Organization (WHO) Model List of Essential Medicines for Children (EMLc). To ensure clinical relevance, the Delphi technique was employed to identify areas of (dis)agreement among clinical pediatric experts. During two consultation rounds, experts were invited to indicate (dis)agreement. Five experts per age group were largely in agreement with the initial selections, but various therapeutic alternatives were suggested for addition. A second consultation round with five experts did not lead to major adjustments. The final sets included 26 treatment options for both groups. Specific age-appropriate formulations were selected from the WHO EMLc 2023. These two globally representative tracer sets of medicines consider the particular needs of children and could aid countries in the critical monitoring of accessibility to pediatric medicines.

Objectives To complement Sustainable Development Goal (SDG) indicator 3.b.3 that monitors access to medicines for all, a corresponding child-specific methodology was developed tailored to the health needs of children. This methodology could aid countries in monitoring accessibility to paediatric medicines in a validated manner and on a longitudinal basis. We aimed to provide proof of concept of this adapted methodology by applying the method to historical datasets.Method A core set of child-appropriate medicines was selected for two groups of children: children aged 1–59 months and children aged 5–12 years. To enable calculation of affordability of medicines for children, the number of units needed for treatment was created, incorporating the recommended dosage and duration of treatment for the specific age group. The adapted methodology was applied to health facility survey data from Burundi (2013), China (2012) and Haiti (2011) for one age group. SDG indicator 3.b.3 scores and (mean) individual facility scores were calculated per country and sector.Results We were able to calculate SDG indicator 3.b.3 based on historical data from Burundi, China and Haiti with the adapted methodology. In this case study, all individual facilities failed to reach the 80% benchmark of accessible medicines, resulting in SDG indicator 3.b.3 scores of 0% for all 3 countries. Mean facility scores ranged from 22.2% in Haiti to 40.3% in Burundi for lowest-price generic medicines. Mean facility scores for originator brands were 0%, 16.5% and 9.9% for Burundi, China and Haiti, respectively. The low scores seemed to stem from the low availability of medicines.Conclusion The child-specific methodology was successfully applied to historical data from Burundi, China and Haiti, providing proof of concept of this methodology. The proposed validation steps and sensitivity analyses will help determine its robustness and could lead to further improvements.

Background Globally accepted roles of pharmacists are described in the Good Pharmacy Practice (GPP) standards, published by the World Health Organization (WHO) and the International Pharmaceutical Federation (FIP) in 2011. These standards provide a wide-ranging description of four main roles pharmacists fulfil. The global platform, where pertinent discussions around excellence and innovation in various pharmacy roles take place, is the annual congress of the pharmacy organisation representing the profession globally, FIP. Objectives Given the world pharmacy congresses present and reflect on the most topical and contemporary matters, this longitudinal study aimed at creating a historical overview of the frequency of appearance of the different GPP roles in the programmes of the past 17 congresses (2003–2019). This is to distinguish the dominance of different roles over time and thus their relevance for the profession. Methods The GPP standards served as a framework to create a set of keywords that were analysed for their frequencies of appearance in the programmes through text analysis. Trends in the four overarching GPP roles and at individual keyword level were analysed descriptively over time. Results The study found that all four GPP roles appeared in the programme each year and none of them was significantly missing, neither in the decade preceding the publication of the GPP standards nor in the decade thereafter. Role 3 “Maintain and improve professional performance” was most frequently represented, also demonstrating an upward trend in appearance, together with Role 4: “Contribute to improve effectiveness of the health-care system and public health”. Trends emerged towards patient-centred clinical focus and positioning pharmacy as an important player in the health-care system—observed also at individual keywords level in areas such as health promotion—away from the more traditional product-centred practice roles such as compounding. Conclusions GPP roles have been already covered by the FIP annual congresses (long) before 2011, when the GPP roles were formally adopted, and they stayed relevant in the decade after. The more pronounced dominance toward the roles related to improving professional performance and positioning pharmacy are in line with the trend that the rather technical topics in pharmacy are increasingly covered by specialised meetings and that the FIP annual congresses have moved toward more general, scholarly platforms for dialogue and conversation.

Background Sub-Saharan Africa is going through an epidemiological transition, including an impressive increase in non-communicable diseases. The introduction of medicines has not kept pace with the needs in developing countries. The objectives of this study were to (i) examine the correlation between the number of medicine approvals and disease burden and (ii) compare approval timelines of medicines with disease burden in South Africa in the period 2012–2017. Methods The dataset was compiled from publicly available data on medicines registered in South Africa between 2012 and 2017. A correlation analysis was conducted to determine the level of alignment between the number and nature of medicines registered, as determined by the WHO ATC Classification and the Lancet Global Burden of Disease data. Median registration timelines were determined to assess whether medicines for diseases of higher burden were registered faster. Results A total of 3059 registered medicines were included in the study, including 2779 generic medicines, 267 new chemical entities and 13 vaccines. There was a high level of alignment between the number of medicines registered to treat diseases with higher disease burden levels more effectively, except for lower respiratory tract infections and HIV/AIDS which showed less medicines registered as compared to expectations based on disease burden, respectively. HIV/AIDS showed a lower level of correlation with a much higher disease burden compared to number of medicines registered, but simultaneously also a much shorter median registration timeline (32 months) compared to the other disease areas. Conclusions There was generally a high level of alignment between disease burden and number of medicines authorised, except for HIV/AIDS and lower respiratory tract infections. Regulatory authorities should continue to consider burden of disease data to ensure that public health needs are met.

The 4th PPRI Conference, held in Vienna in October 2019, addressed issues related to equitable and affordable access to medicines. A multi-stakeholder audience from around the globe discussed solutions and best practice models for current challenges such as high-priced medicines, limitations of current pricing and reimbursement policies and tight budgets for health technologies. A multi-faceted approach (so-called balance, evidence, collaboration and transparency/BECT strategy) was also discussed. This includes an improved balance of different interests and policy areas, generation of relevant evidence, collaboration between countries and stakeholders, and transparency, and was considered as the most promising pathway for the future.

Background High prices of pharmaceutical products are an increasing challenge in high- and low-income countries. Governments in many countries have implemented pricing policies to ensure affordability of medicines to patients and healthcare systems. The World Health Organization published in 2015 the Guideline on Country Pharmaceutical Pricing Policies, which was based on a series of evidence reviews in the preceding years. As part of the ongoing update of this guideline, we present a protocol for 10 systematic literature reviews on pharmaceutical pricing policies to be covered by the updated guideline. Methods The systematic literature reviews will be undertaken according to the principles embodied in the Cochrane Handbook and Centre for Reviews and Dissemination. The interventions studied are pharmaceutical pricing policies implemented by public institutions or a group of purchasing organizations/individuals (e.g. health services). Studies reporting price, volume, availability and/or affordability as the primary outcomes will be eligible for inclusion. Studies in any country or jurisdiction, in any language and in any setting published in 2004 or later are eligible. Eligible study designs are randomized and non-randomized trials, and observational studies including cohort studies, panel data analyses, comparative time series design (including interrupted time-series and repeated measures studies), and controlled before-after studies. A list of 21 databases of peer-reviewed and grey literature will be searched, along with supplementary searches of relevant national and international organizational and governmental websites. Risk of bias will be assessed according to the Cochrane Effective Practice and Organisation of Care (EPOC) guidelines. A summary table according to the EPOC Worksheets for preparing a Summary of Findings table (SoF) using GRADE will be provided. Discussion The results of the review will be used as part of the update of the WHO Guideline on Country Pharmaceutical Pricing Policies. The current protocol may serve as an example for performing systematic literature reviews to inform policy makers.

To ensure the sustainability of pharmacy practice and provide health for all, pharmacy as a profession must embrace the digital transformation that has been changing healthcare at a rapid pace. The International Pharmaceutical Federation (FIP) has conducted a global study on digital health in pharmacy education to describe the readiness, adaptability, and responsiveness of pharmacy education programmes to train the current and future pharmaceutical workforce on digital health and to identify the knowledge and skill gaps of the existing pharmaceutical workforce with regard to digital health. An online survey was distributed to collect feedback from academics, pharmacy schools, pharmacists, and pharmacy students. The findings showed that a large proportion of pharmacy schools do not offer any digital health education, and the skillsets and knowledge of how to apply digital health technologies to solve existing clinical problems and improve care have been identified as a gap. The future of pharmacy and pharmaceutical sciences is digital and exciting. A digitally enabled and agile pharmaceutical workforce will capitalise on the benefits of digital health to serve the higher purpose of providing good health and wellbeing for all, leaving no one behind. Therefore, pharmacy and pharmaceutical sciences education should act now.

In this article the design of three master programs (MSc in Pharmacy) and two postgraduate specialization programs for community or hospital pharmacist is described. After a preceding BSc in Pharmacy, these programs cover the full pharmacy education capacity for pharmacists in primary and secondary health care in the Netherlands. All programs use the CanMEDS framework, adapted to pharmacy education and specialization, which facilitates the horizontal integration of pharmacists’ professional development with other health care professions in the country. Moreover, it is illustrated that crossing the boundary from formal (university) education to experiential (workplace) education is eased by a gradual change in time spent in these two educational environments and by the use of comparable monitoring, feedback, and authentic assessment instruments. A reflection on the curricula, based on the principles of the Integrative Pedagogy Model and the Self-determination Theory, suggests that the alignment of these educational programs facilitates the development of professional expertise and professional identity of Dutch pharmacists.

Background Uganda was one of seven countries in which the United Nations Commission on Life Saving Commodities (UNCoLSC) initiative was implemented starting from 2013. A nationwide survey was conducted in 2015 to determine availability, prices and affordability of essential UNCoLSC maternal and reproductive health (MRH) commodities. Methods The survey at health facilities in Uganda was conducted using an adapted version of the standardized methodology co-developed by World Health Organisation (WHO) and Health Action International (HAI). In this study, six maternal and reproductive health commodities, that were part of the UNCoLSC initiative, were studied in the public, private and mission health sectors. Median price ratios were calculated with Management Sciences for Health International Drug Price Indicator prices as reference. Maternal and reproductive health commodity stocks were reviewed from stock cards for their availability for a period of 6 months preceding the survey. Affordability was measured using wages of the lowest paid government worker. Results Overall none of the six maternal and reproductive commodities was found in the surveyed health facilities. Public sector had the highest availability (52%), followed by mission sector (36%) and then private sector had the least (30%). Stock outs ranged from 7 to 21 days in public sector; 2 to 23 days in private sector and 3 to 27 days in mission sector. During the survey, maternal health commodities were more available and had less number of stock out days than reproductive health commodities. Median price ratios (MPR) indicated that medicines and commodities were more expensive in Uganda compared to international reference prices. Furthermore, MRH medicines and commodities were more expensive and less affordable in private sector compared to mission sector. Conclusion Access to MRH commodities is inadequate in Uganda. Maternal health commodities were more available, cheaper and thus more affordable than reproductive health commodities in the current study. Efforts should be undertaken by the Ministry of Health and stakeholders to improve availability, prices and affordability of MRH commodities in Uganda to ensure that sustainable Development Goals are met.

Objective To identify pharmaceutical policy changes during the economic recession in eight European countries and to determine whether policy measures resulted in lower sales of, and less expenditure on, pharmaceuticals. Methods Information on pharmaceutical policy changes between 2008 and 2011 in eight European countries was obtained from publications and pharmaceutical policy databases. Data on the volume and value of the quarterly sales of products between 2006 and 2011 in the 10 highest-selling therapeutic classes in each country were obtained from a pharmaceutical market research database. We compared these indicators in economically stable countries; Austria, Estonia and Finland, to those in economically less stable countries, Greece, Ireland, Portugal, Slovakia and Spain. Findings Economically stable countries implemented two to seven policy changes each, whereas less stable countries implemented 10 to 22 each. Of the 88 policy changes identified, 33 occurred in 2010 and 40 in 2011. They involved changing out-of-pocket payments for patients in 16 cases, price mark-up schemes in 13 and price cuts in 11. Sales volumes increased moderately in all countries except Greece and Portugal, which experienced slight declines after 2009. Sales values decreased in both groups of countries, but fell more in less stable countries. Conclusion Less economically stable countries implemented more pharmaceutical policy changes during the recession than economically stable countries. Unexpectedly, pharmaceutical sales volumes increased in almost all countries, whereas sales values declined, especially in less stable countries.

OBJECTIVE: To investigate potential differences in the availability of medicines for chronic and acute conditions in low- and middle-income countries. METHODS: Data on the availability of 30 commonly-surveyed medicines - 15 for acute and 15 for chronic conditions - were obtained from facility-based surveys conducted in 40 developing countries. Results were aggregated by World Bank country income group and World Health Organization region. FINDINGS: The availability of medicines for both acute and chronic conditions was suboptimal across countries, particularly in the public sector. Generic medicines for chronic conditions were significantly less available than generic medicines for acute conditions in both the public sector (36.0% availability versus 53.5%; P=0.001) and the private sector (54.7% versus 66.2%; P=0.007). Antiasthmatics, antiepileptics and antidepressants, followed by antihypertensives, were the drivers of the observed differences. An inverse association was found between country income level and the availability gap between groups of medicines, particularly in the public sector. In low- and lower-middle income countries, drugs for acute conditions were 33.9% and 12.9% more available, respectively, in the public sector than medicines for chronic conditions. Differences in availability were smaller in the private sector than in the public sector in all country income groups. CONCLUSION: Current disease patterns do not explain the significant gaps observed in the availability of medicines for chronic and acute conditions. Measures are needed to better respond to the epidemiological transition towards chronic conditions in developing countries alongside current efforts to scale up treatment for communicable diseases.

On 25–26 April 2024, the 5th PPRI (Pharmaceutical Pricing and Reimbursement Information) Conference on ensuring equitable access to affordable medicines took place in Vienna (Austria). Twenty-four accepted contributions were presented either as oral presentations or posters, adding to invited keynote lectures, stakeholder debates and workshops. The global multi-stakeholder audience discussed a range of approaches in pharmaceutical policies, which have the potential to successfully and sustainably address current and future challenges in ensuring patient access to affordable medicines globally. These discussions benefited from the interaction between policy-makers, stakeholders in the private sector and researchers who provided evidence on implemented and piloted policies. Among the policy options that drew the most attention during the PPRI Conference were procurement with targeted instruments to achieve strategic objectives, innovative payment models such as different variants of managed-entry agreements, and new models to fund pharmaceutical research and development. Experiences on established policy options that are being newly introduced in several countries, such as price regulation, health technology assessment, evidence-based selection for reimbursement decisions and measures to enhance the uptake of biosimilar medicines were also shared. The PPRI Conference reaffirmed the relevance of pharmaceutical pricing, procurement and reimbursement policies aligned with policy actions in other areas and along the pharmaceutical life-cycle and emphasised the importance of developing needs-driven health systems. Innovation in policy-making is needed to work towards equitable patient access to affordable medicines. This requires transparency, alignment on evidence requirements, communication, coordination, intra-country and international collaboration, solidarity and trust.

Sustainable access to affordable medicines remains a public health issue globally, including for high-income countries. To foster the debate on avenues for the future, the fifth PPRI Conference held in Vienna on 25 and 26 April 2024 will offer a forum for the debate on innovating pharmaceutical policymaking to develop and implement futureproof policy options, which are able to address current and future challenges. The Conference invites a broad audience of stakeholders, including researchers, policymakers, payers, patients, industry and health professionals. The conference topics are organised in three strands: Strand 1 on ‘Local challenges, global learnings’ aims to contribute to lively discussions on the implementation of pharmaceutical policies across the globe. Best-practice examples will be presented, supplemented by case studies of less effective policies which can offer rich learnings. Strand 2 on ‘Strengthening the evidence base’ is the place for presentations and discussions on topics such as health technology assessments, managed entry agreements and real-world data. Strand 3 ‘Futureproofing pharmaceutical policies’ is particularly dedicated to explore innovation in policymaking to achieve sustainable access to affordable medicines.

In the title molecule, C20H17Cl2NO2, the pyrrole moiety makes dihedral angles of 63.42 (11) and 70.43 (12)° with the chlorobenzene rings. The ethoxycarbonyl unit is present in a synperiplanar conformation with respect to the pyrrole ring, as indicated by the dihedral angle of 14.5 (3)°. In the crystal, molecules are linked into chains parallel to the a-axis direction by weak C—H...O hydrogen bonds.

In the molecule of the title compound, C21H14N2O3, the quinazoline ring system [maximum deviation = 0.076 (1) Å] makes dihedral angles of 40.57 (9) and 42.31 (11)°, respectively, with the phenyl and 1,3-benzodioxole rings. The dihedral angle between the phenyl ring and the 1,3-benzodioxole ring is 4.34 (10)°. In the crystal, C—H...O hydrogen bonds link the molecules into infinite zigzag chains extending along [100].

Abstract Background Sustainable Development Goal (SDG) indicator 3.b.3 monitors progress in medicines’ accessibility for adults and has significant limitations when applying to medicines for children. An adapted indicator methodology was developed to fill this gap, but no proof of its robustness exists. We provide this evidence through sensitivity analyses. Methods Data on availability and prices of child medicines from ten historical datasets were combined to create datasets for analysis: Dataset 1 (medicines selected at random) and Dataset 2 (preference given to available medicines, to better capture affordability of medicines). A base case scenario and univariate sensitivity analyses were performed to test critical components of the methodology, including the new variable of number of units needed for treatment (NUNT), disease burden (DB) weighting, and the National Poverty Line (NPL) limits. Additional analyses were run on a continuously smaller basket of medicines to explore the minimum number of medicines required. Mean facility scores for access were calculated and compared. Results The mean facility score for Dataset 1 and Dataset 2 within the base case scenario was 35.5% (range 8.0–58.8%) and 76.3% (range 57.2–90.6%). Different NUNT scenarios led to limited variations in mean facility scores of + 0.1% and -0.2%, or differences of + 4.4% and -2.1% at the more critical NPL of $5.50 (Dataset 1). For Dataset 2, variations to the NUNT generated differences of + 0.0% and -0.6%, at an NPL of $5.50 the differences were + 5.0 and -2.0%. Different approaches for weighting for DB induced considerable fluctuations of 9.0% and 11.2% respectively. Stable outcomes with less than 5% change in mean facility score were observed for a medicine basket down to 12 medicines. For smaller baskets, scores increased more rapidly with a widening range. Conclusion This study has confirmed that the proposed adaptations to make SDG indicator 3.b.3 appropriate for children are robust, indicating that they could be an important addition to the official Global Indicator Framework. At least 12 child-appropriate medicines should be surveyed to obtain meaningful outcomes. General concerns that remain about the weighting of medicines for DB and the NPL should be considered at the 2025 planned review of this framework.

Abstract Decision‐making for reimbursement and clinical guidelines (CGs) serves different purposes although the decision‐criteria and required evidence largely overlap. This study aimed to assess similarities and discrepancies between health technology assessment (HTA) reports as compared to CGs for multiple sclerosis (MS) medicines. All HTA reports and corresponding CGs for MS from the UK, France, Germany, the Netherlands, Poland, Sweden, and the European Union were assessed to identify synergies in recommendations for MS medicines (approved 1995–2020). A content analysis of HTA reports and CGs was performed to identify similarities and discrepancies in wording of treatment recommendations across documents. We assessed 132 HTA reports and 9 CGs for 16 MS treatments. Final recommendations for reimbursement and inclusion in CGs were mostly similar (90%), albeit with considerable differences in treatment lines and subindications. Since 2010, HTA reports refer to the use of CGs in 42% (55/132) and to consultations with clinicians in 43% (57/132) of cases. Six of nine CGs referred to HTA reports and two referred to HTA consultations, in one case having a formal relation to the HTA organization. CGs referenced pharmacoeconomic studies (4/9) for costs and cost‐effectiveness. To date, not all new HTA recommendations for MS treatments are included in CGs. Some synergy exists between treatment recommendations in HTA reports and CGs, although discrepancies were seen in timelines and in recommended treatment lines and subindications. More stakeholder dialogue and/or consultation of each other's publications may further improve synergy, facilitate transparency, and enhance patient access.

Abstract Background Medicine shortages are often described in plain numbers, suggesting all shortages have a uniform impact. However, some shortages have a direct and serious effect on patients and need a prompt reaction from stakeholders. This study aims to create a broad framework to assess the impact of a shortage. Method We identified high impact shortages and selected exemplary shortages which we considered our learning cases. From five learning cases, we identified elements that had a potentially profound impact on one or more of these cases. We tested data saturation on the elements with another five test cases. Based on these elements, we created a framework to assess impact of shortages on patients and presented practical examples how to rate these different elements. Subsequently, we visualised the impact of these five learning cases on patients in radar charts. Results The five elements which we identified as potentially having a large impact were 1) alternative product, 2) disease, 3) susceptibility, 4) costs and 5) number of patients affected. The five learning cases rated high on different elements, leading to diverse and sometimes even opposite patterns of impact. Conclusion We created a framework for assessing the impact of a medicine shortage on patients by means of five key elements. By rating these elements, an indication of the impact can be obtained.

Abstract Background Access to sexual and reproductive health services remains a challenge for many in Kenya, Tanzania, Uganda and Zambia. Health service delivery in the four countries is decentralised and provided by the public, private and private not-for-profit sectors. When accessing sexual and reproductive health services, clients encounter numerous challenges, which might differ per sector. Healthcare workers have first-hand insight into what impediments to access exist at their health facility. The aim of this study was to identify differences and commonalities in barriers to access to sexual and reproductive health services across the public, private and private not-for-profit sectors. Methods A cross-sectional survey was conducted among healthcare workers working in health facilities offering sexual and reproductive health services in Kenya (n = 212), Tanzania (n = 371), Uganda (n = 145) and Zambia (n = 243). Data were collected in July 2019. Descriptive statistics were used to describe the data, while binary logistic regression analyses were used to test for significant differences in access barriers and recommendations between sectors. Results According to healthcare workers, the most common barrier to accessing sexual and reproductive health services was poor patient knowledge (37.1%). Following, issues with supply of commodities (42.5%) and frequent stockouts (36.0%) were most often raised in the public sector; in the other sectors these were also raised as an issue. Patient costs were a more significant barrier in the private (33.3%) and private not-for-profit sectors (21.1%) compared to the public sector (4.6%), and religious beliefs were a significant barrier in the private not-for-profit sector compared to the public sector (odds ratio = 2.46, 95% confidence interval = 1.69–3.56). In all sectors delays in the delivery of supplies (37.4-63.9%) was given as main stockout cause. Healthcare workers further believed that it was common that clients were reluctant to access sexual and reproductive health services, due to fear of stigmatisation, their lack of knowledge, myths/superstitions, religious beliefs, and fear of side effects. Healthcare workers recommended client education to tackle this. Conclusions Demand and supply side barriers were manifold across the public, private and private not-for-profit sectors, with some sector-specific, but mostly cross-cutting barriers. To improve access to sexual and reproductive health services, a multi-pronged approach is needed, targeting client knowledge, the weak supply chain system, high costs in the private and private not-for-profit sectors, and religious beliefs.

Abstract Background Guideline adherence is generally high in Dutch general practices. However, the prescription of insulins to type 2 diabetes mellitus patients is often not in line with the guideline, which recommends NPH insulin as first choice and discourages newer insulins. This qualitative study aimed to identify the reasons why primary care healthcare professionals prescribe insulins that are not recommended in guidelines. Methods Digital focus groups with primary care practitioners were organised. A topic list was developed, based on reasons for preferred insulins obtained from literature and a priori expert discussions. The discussions were video and audio-recorded, transcribed verbatim and coded with a combination of inductive and deductive codes. Codes were categorized into an existing knowledge, attitudes and behaviour model for guideline non-adherence. Results Four focus groups with eleven general practitioners, twelve practice nurses, six pharmacists, four diabetes nurses and two nurse practitioners were organised. The prescription of non-recommended insulins was largely driven by argumentation in the domain of attitudes. Lack of agreement with the guideline was the most prominent category. Most of those perspectives did not reflect disagreement with the guideline recommendations in general, but were about advantages of non-recommended insulins, which led, according to the healthcare professionals, to better applicability of those insulins to specific patients. The belief that guideline-recommended insulins were less effective, positive experience with other insulins and marketing from pharmaceutical companies were also identified as attitude-related barriers to prescribe guideline-recommended insulins. One additional category in the domain of attitudes was identified, namely the lack of uniformity in policy between healthcare professionals in the same practice. Only a small number of external barriers were identified, focusing on patient characteristics that prevented the use of recommended insulins, the availability of contradictory guidelines and other, mostly secondary care, healthcare providers initiating non-recommended insulins. No knowledge-related barriers were identified. Conclusions The prescription of non-recommended insulins in primary care is mostly driven by lack of agreement with the guideline recommendations and different interpretation of evidence. These insights can be used for the development of interventions to stimulate primary care practitioners to prescribe guideline-recommended insulins.

BackgroundThe European Medicines Agency (EMA) aims to resolve uncertainties associated with conditionally approved drugs by imposing post-approval studies. Results from these studies may be relevant for health technology assessment (HTA) organizations. This study investigated the role of regulator-imposed post-approval studies within HTA. MethodsFor all conditionally approved drugs up to December 2018, regulator-imposed post-approval studies were identified from EMA’s public assessment reports. The availability for and inclusion of study results in relative effectiveness (re)assessments were analyzed for 4 European HTA organizations: NICE (National Institute for Health and Care Excellence, England/Wales), HAS (Haute Autorité de Santé, France), ZIN (Zorginstituut Nederland, the Netherlands) and the European Network for Health Technology Assessment (EUnetHTA, Europe). When study results became available between an HTA organization’s initial assessment and reassessment, it was evaluated whether and how they affected the assessment and its outcome. ResultsFor 36 conditionally approved drugs, 98 post-approval studies were imposed. In total, 81 initial relative effectiveness assessments (REAs) and 13 reassessments were available, with numbers of drugs (re)assessed varying greatly between jurisdictions. Study results were available for 16 initial REAs (20%) and included in 14 (88%), and available for 10 reassessments (77%) and included in all (100%). Five reassessments had an outcome different from the initial REA, with 4 (2 positive and 2 negative changes) relating directly to the new study results. Reassessments often cited the inability of post-approval studies to resolve the concerns reported in the initial REA. ConclusionResults from regulator-imposed post-approval studies for conditionally approved drugs were not often used in REAs by HTA organizations, because they were often not yet available at the time of initial assessment and because reassessments were scarce. When available, results from post-approval studies were almost always used within HTA, and they have led to changes in conclusions about drugs’ relative effectiveness. Post-approval studies can be relevant within HTA but the current lack of alignment between regulators and HTA organizations limits their potential.

Background: A needs-based approach is desirable for the transformation of pharmaceutical education, and to link pharmaceutical education with the health needs of populations and national priorities. There are varying levels of data in the literature on the status of pharmaceutical education in all six World Health Organization (WHO) regions, especially in the context of needs identification and evidence-based policy interventions. The framework for this study was the FIP Development Goals. Objectives: The aim of the study was to develop evidence-based policies through a needs-based approach for pharmaceutical education transformation nationally, regionally and globally by addressing the following objectives: 1. Identify global and regional needs in pharmaceutical education, through a regional SWOT analysis and prioritization of FIP development goals; 2. Develop valid and credible regional roadmaps for pharmaceutical education advancement according to the identified prioritized goals and 3. Develop a global call to action as a policy intervention for advancing pharmaceutical education. Methods: This study was conducted between 2020 and 2021 using a mixed methods approach. Surveys of higher education institutions and a series of qualitative interviews were conducted with national professional leadership organizations, with further regional workshops having 284 participants recruited from the International Pharmaceutical Federation (FIP) membership base, spanning all six WHO regions. Results: Eleven out of 21 FIP DGs were identified as priorities for regional roadmaps and FIP DG 1 (Academic capacity) was identified as a priority in four regions. All regions had distinctive results with an area of commonality between them. There were common weaknesses in the adoption of competency-based education and inter-professional education. Conclusions: It is critical for every country and region to develop needs- and evidence-based policies for the transformation of pharmaceutical education, for which FIP DGs provide a systematic framework.

Plain language summary The unmet need for contraception among adolescents is high in Uganda and Kenya, and has many negative consequences, including unwanted pregnancy, exposure to unsafe abortion, and maternal morbidity and mortality. National laws and policies play an important role in determining adolescents’ access to contraception. For example, national laws and policies can shape the government programs that provide (or withhold) contraception, and the social norms influencing adolescents’ access to contraception. Therefore, this research compares national laws and policies that determine access to contraception services and information for adolescents in Uganda and Kenya with WHO’s recommendations for access to contraception. This is an analysis of the content of Ugandan and Kenyan laws and policies in force between 2010 and 2018. The content of these documents was analyzed using WHO’s nine recommendations for how contraception information and services should be provided: non-discrimination, availability, accessibility, acceptability, quality, informed decision-making, confidentiality, participation, accountability. Ninety-three documents were screened and 26 documents were included in the analysis: 13 policies from Uganda and 13 policies from Kenya. On average, Ugandan policies include one WHO recommendation for adolescent contraception per policy and Kenyan policies include two WHO recommendations. This recommendation most frequently mentioned in all policies is the accessibility of contraception (for example, for adolescents living remotely, integrated in adolescent HIV or pre-/post-natal care, etc.). Together, all Ugandan policies mentioned 6/9 WHO recommendations whereas all Kenyan policies cover 8/9 WHO recommendations. In conclusion, Ugandan and Kenyan policies are consistent with many of WHO’s recommendations for access to contraception, however, there is still room for improvement.

Abstract Background Haemovigilance is an important element of blood regulation. It includes collecting and evaluating the information on adverse events resulting from the use of blood and blood components with the aim to improve donor and patient safety. We describe the results of the pilot of the integrated GBT+ Blood for the haemovigilance function in 10 sub-Saharan African countries. Methods We piloted the integrated WHO Global Benchmarking Tool plus Blood (GBT+ Blood) to assess the haemovigilance function of national regulatory authorities (NRAs) in Ethiopia, Kenya, Malawi, Nigeria, Liberia, Rwanda, South Africa, Tanzania, Uganda, and Zimbabwe. Data obtained from documents and face to face interviews were used to determine the status of implementation and performance of the following six indicators; legal provisions regulations and guidelines, organisation and governance, human resources, regulatory processes, transparency and accountability and finally, monitoring progress and assessing impact, by estimating median scores across 20 sub-indicators. In addition, a cluster analysis was performed. Results The countries showed inter-organisation variability in implementation and performance of the haemovigilance function. The overall median score (all sub-indicators) was 44 % (range: 7.5 % - 70 %). The lowest average performance scores were for the arrangement for effective organisation and coordination (35 %) and human resources (35 %) indicators. The highest average scores were observed for the mechanism to promote transparency and mechanism to monitor regulatory performance indicators (50 % and 60 %, respectively). We identified clusters of best-implemented sub-indicators from the procedures for haemovigilance and poorly implemented sub-indicators from the legal provisions, regulations and guidelines for haemovigilance and human resources. Conclusions Implementation of sub-indicators and performance of haemovigilance systems varied greatly for all countries with a few countries performing reasonably well in the implementation of some sub-indicators under procedures for haemovigilance. Most countries were poorly implementing sub-indicators in the legal provisions, arrangement for effective organisation and human resources indicators. The legislative provisions in most countries were at a nascent stage. There is a need to set up targeted and customised technical support coupled with prioritised interventions to strengthen the capacities of NRAs.

Abstract We aimed to determine whether uncertainties identified by the European Medicines Agency (EMA) were associated with negative relative effectiveness assessments (REAs) and negative overall reimbursement recommendations by national health technology assessment (HTA) agencies. Therefore, we identified all HTA reports from Haute Autorité de Santé (HAS; France), National Institute for Health and Care Excellence (NICE; England/Wales), Scottish Medicine Consortium (SMC; Scotland), and Zorginstituut Nederland (ZIN; The Netherlands) for a cohort of innovative medicines that the EMA had approved in 2009 to 2010 (excluding vaccines). Uncertainty regarding pivotal trial methodology, clinical outcomes, and their clinical relevance were combined to reflect a low, medium, or high level of uncertainty. We assessed associations by calculating risk ratios (RRs) and 95% confidence intervals (CIs), and agreement between REA and overall reimbursement recommendation outcomes. We identified 36 medicines for which 121 reimbursement recommendations had been issued by the HTA agencies between September 2009 and July 2018. High versus low uncertainty was associated with an increased risk for negative REAs and negative overall reimbursement recommendations: RRs 1.9 (95% CI 0.9–3.9) and 1.6 (95% CI 0.7–3.5), respectively, which was supported by further sensitivity analyses. We identified a lack of agreement between 33 (27%) REA and overall reimbursement recommendation outcomes, which were mostly restricted recommendations that followed on negative REAs in case of low or medium uncertainty. In conclusion, high uncertainty identified by the EMA was associated with negative REAs and negative overall reimbursement recommendations. To reduce uncertainty and ultimately facilitate efficient patient access, regulators, HTA agencies, and other stakeholders should discuss how uncertainties should be weighed and addressed early in the drug life cycle of innovative treatments.

Abstract Background Malaria is the single largest cause of illness in Uganda. Since the year 2008, the Global Fund has rolled out several funding streams for malaria control in Uganda. Among these are mechanisms aimed at increasing the availability and affordability of artemisinin-based combination therapy (ACT). This paper examines the availability and affordability of first-line malaria treatment and diagnostics in the private sector, which is the preferred first point of contact for 61% of households in Uganda between 2007 and 2018. Methods Cross-sectional surveys were conducted between 2007 and 2018, based on a standardized World Health Organization/Health Action International (WHO/HAI) methodology adapted to assess availability, patient prices, and affordability of ACT medicines in private retail outlets. A minimum of 30 outlets were surveyed per year as prescribed by the standardized methodology co-developed by the WHO and Health Action International. Availability, patient prices, and affordability of malaria rapid diagnostic tests (RDTs) was also tracked from 2012 following the rollout of the test and treat policy in 2010. The median patient prices for the artemisinin-based combinations and RDTs was calculated in US dollars (USD). Affordability was assessed by computing the number of days’ wages the lowest-paid government worker (LPGW) had to pay to purchase a treatment course for acute malaria. Results Availability of artemether/lumefantrine (A/L), the first-line ACT medicine, increased from 85 to100% in the private sector facilities during the study period. However, there was low availability of diagnostic tests in private sector facilities ranging between 13% (2012) and 37% (2018). There was a large reduction in patient prices for an adult treatment course of A/L from USD 8.8 in 2007 to USD 1.1 in 2018, while the price of diagnostics remained mostly stagnant at USD 0.5. The affordability of ACT medicines and RDTs was below one day’s wages for LPGW. Conclusions Availability of ACT medicines in the private sector medicines retail outlets increased to 100% while the availability of diagnostics remained low. Although malaria treatment was affordable, the price of diagnostics remained stagnant and increased the cumulative cost of malaria management. Malaria stakeholders should consolidate the gains made and consider the inclusion of diagnostic kits in the subsidy programme.

Abstract Background Access to sexual and reproductive health services continues to be a public health concern in Kenya, Tanzania, Uganda and Zambia: use of modern contraceptives is low, and unmet family planning needs and maternal mortality remain high. This study is an assessment of the availability, affordability and stock-outs of essential sexual and reproductive health commodities (SRHC) in these countries to inform interventions to improve access. Methods The study consisted of an adaptation of the World Health Organization/Health Action International methodology, Measuring Medicine Prices, Availability, Affordability and Price Components. Price, availability and stock-out data was collected in July 2019 for over fifty lowest-priced SRHC from public, private and private not-for-profit health facilities in Kenya (n = 221), Tanzania (n = 373), Uganda (n = 146) and Zambia (n = 245). Affordability was calculated using the wage of a lowest-paid government worker. Accessibility was illustrated by combining the availability (≥ 80%) and affordability (less than 1 day’s wage) measures. Results Overall availability of SRHC was low at less than 50% in all sectors, areas and countries, with highest mean availability found in Kenyan public facilities (46.6%). Stock-outs were common; the average number of stock-out days per month ranged from 3 days in Kenya’s private and private not-for-profit sectors, to 12 days in Zambia’s public sector. In the public sectors of Kenya, Uganda and Zambia, as well as in Zambia’s private not-for-profit sector, all SRHC were free for the patient. In the other sectors unaffordability ranged from 2 to 9 SRHC being unaffordable, with magnesium sulphate being especially unaffordable in the countries. Accessibility was low across the countries, with Kenya’s and Zambia’s public sectors having six SRHC that met the accessibility threshold, while the private sector of Uganda had only one SRHC meeting the threshold. Conclusions Accessibility of SRHC remains a challenge. Low availability of SRHC in the public sector is compounded by regular stock-outs, forcing patients to seek care in other sectors where there are availability and affordability challenges. Health system strengthening is needed to ensure access, and these findings should be used by national governments to identify the gaps and shortcomings in their supply chains.

The available evidence on relative effectiveness and risks of new health technologies is often limited at the time of health technology assessment (HTA). Additionally, a wide variety in real-world data (RWD) policies exist among HTA organizations. This study assessed which challenges, related to the increasingly complex nature of new health technologies, make the acceptance of RWD most likely. A questionnaire was disseminated among 33 EUnetHTA member HTA organizations. The questions focused on accepted data sources, circumstances that allowed for RWD acceptance and barriers to acceptance. The questionnaire was validated and tested for reliability by an expert panel, and pilot-tested before dissemination via LimeSurvey. Twenty-two HTA organizations completed the questionnaire (67%). All reported accepting randomized clinical trials. The most accepted RWD source were patient registries (19/22, 86%), the least accepted were editorials and expert opinions (8/22, 36%). With orphan treatments or companion diagnostics, organizations tended to be most likely to accept RWD sources, 4.3–3.2 on a 5-point Likert scale, respectively. Additional circumstances were reported to accept RWD (e.g., a high disease burden). The two most important barriers to accepting RWD were lacking necessary RWD sources and existing policy structures. European HTA organizations seem positive toward the (wider) use of RWD in HTA of complex therapies. Expanding the use of patient registries could be potentially useful, as a large share of the organizations already accepts this source. However, many barriers still exist to the widespread use of RWD. Our results can be used to prioritize circumstances in which RWD might be accepted.

Abstract Objective Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue recommended in international HIV treatment guidelines. Purpose of this study was to estimate the long term effects of TDF on renal profile in a cohort of HIV patients in Ghana. Three hundred (300) consecutive HIV-positive patients who initiated TDF-based antiretroviral treatment in 2008 at the Korle-Bu Teaching Hospital were sampled. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault equation at baseline and renal impairment was defined as CrCl values of 30.0–49.9 mL/min (moderate renal impairment) and

Abstract Background Many low- and middle-income countries (LMIC) are moving towards enforcing prescription-only access to antibiotics. This systematic literature review aims to assess the interventions used to enforce existing legislation prohibiting over-the-counter (OTC) sales of antibiotics in LMICs, their impact and examine the methods chosen for impact measurement including their strengths and weaknesses. Methods Both PubMed and Embase were systematically searched for studies reporting on impact measurement in moving towards prescription only access to antibiotics in LMICs. The PRISMA methodological review framework was used to ensure systematic data collection and analysis of literature. Narrative data synthesis was used due to heterogeneity of study designs. Results In total, 15 studies were included that assessed policy impact in 10 different countries. Strategies employed to enforce regulations prohibiting OTC sales of systemic antibiotics included retention of prescriptions for antibiotics by pharmacies, government inspections, engaging pharmacists in the design of interventions, media campaigns for the general public and educational activities for health care workers. A variety of outcomes was used to assess the policy impact; changes in antimicrobial resistance rates, changes in levels of antibiotic use, changes in trends of antibiotic use, changes in OTC supply of antibiotics, and changes in reported practices and knowledge of pharmacists, medicine sellers and the general public. Differences in methodological approaches and outcome assessment made it difficult to compare the effectiveness of law enforcement activities. Most effective appeared to be multifaceted approaches that involved all stakeholders. Monitoring of the impact on total sales of antibiotics by means of an interrupted time series (ITS) analysis and analysis of pharmacies selling antibiotics OTC using mystery clients were the methodologically strongest designs used. Conclusions The published literature describing activities to enforce prescription-only access to antibiotics in LMICs is sparse and offers limited guidance. Most likely to be effective are comprehensive multifaceted interventions targeting all stakeholders with regular reinforcement of messages. Policy evaluation should be planned as part of implementation to assess the impact and effectiveness of intervention strategies and to identify targets for further activities. Robust study designs such as ITS analyses and mystery client surveys should be used to monitor policy impact.

Abstract Background The valuation of medicines as health needs vary depending on the stakeholders involved (users, prescribers, managers, etc.) and their expectations. These factors modulate the role of medicines as a health need and influence access to medicines, and could be useful to explain the rising of Judicialization of access to medicines. Aim To conduct a comparative analysis of the causes and consequences of judicialization of access to medicines in Argentina, Brazil, Colombia and Chile from the perspective of medicines as health needs. Methods A qualitative, cross-country study was carried out in these 4 countries. Semi-structured interviews were conducted with 50 representatives of the different stakeholders involved in the judicialization of access to medicines, including Executive branch, Judiciary, health system managers, patient organizations. The interviews were audio-recorded and transcribed verbatim. Thematic analysis used a framework approach based on the theoretical model for medicines as health needs. Findings Representatives from Argentina, Brazil and Colombia considered judicialization of access to medicines as a widespread phenomenon in their respective countries. Meanwhile in Chile, the respondents highlighted that most lawsuits related to the right to health were filed against private insurers because of unjustified increases in the insurance premiums. The comparative analysis showed that judicialization of access to medicines emerged in the four countries regardless of the constitutional protection or the health system population coverage. Among the causes were mentioned difficulties in guaranteeing access to covered medicines and the influence of pharmaceutical marketing on needs assessment and prescription behaviours. The interviewees highlighted the pressure to health system managers to fulfil their responsibilities as a positive impact of litigation. In contrast, the funding of medicines without evidence of efficacy or safety was considered a negative impact. Only in Brazil, judicialization has had impact on R&D policies. In Colombia, litigation also encouraged the recognition of the right to health as a fundamental right and the development of policies for controlling medicines prices. Conclusion The results suggest that applying the adopted theoretical model creates the possibility of identifying critical points to guide policy makers to improve the health systems performances and to control lawsuits for access to medicines.

BackgroundAnnually, about 2.7 million snakebite envenomings occur globally. Alongside antivenom, patients usually require additional care to treat envenoming symptoms and antivenom side effects. Efforts are underway to improve snakebite care, but evidence from the ground to inform this is scarce. This study, therefore, investigated the availability, affordability, and stock-outs of antivenom and commodities for supportive snakebite care in health facilities across Kenya.Methodology/principal findingsThis study used an adaptation of the standardised World Health Organization (WHO)/Health Action International methodology. Data on commodity availability, prices and stock-outs were collected in July-August 2020 from public (n = 85), private (n = 36), and private not-for-profit (n = 12) facilities in Kenya. Stock-outs were measured retrospectively for a twelve-month period, enabling a comparison of a pre-COVID-19 period to stock-outs during COVID-19. Affordability was calculated using the wage of a lowest-paid government worker (LPGW) and the impoverishment approach. Accessibility was assessed combining the WHO availability target (≥80%) and LPGW affordability (ConclusionsAccess to snakebite care is problematic in Kenya and seemed to have worsened during COVID-19. To improve access, efforts should focus on ensuring availability at both lower- and higher-level facilities, and improving the supply chain to reduce stock-outs. Including antivenom into Universal Health Coverage benefits packages would further facilitate accessibility.

Abstract To evaluate the clinical benefit of new medicines for type 2 diabetes mellitus (T2DM), the Dutch guideline committee T2DM in primary care established the importance of outcomes and minimal clinically important differences (MCIDs). The present study used an online questionnaire to investigate healthcare professionals’ opinions about the importance of outcomes and preferences for MCIDs. A total of 211 physicians, pharmacists, practice nurses, diabetes nurses, nurse practitioners and physician assistants evaluated the importance of mortality, macro‐ and microvascular morbidity, HbA1c, body weight, quality of life, (overall) hospital admissions and severe and other hypoglycemia on a 9‐point scale. All outcomes were considered critical (mean scores 7–9), except for body weight and other hypoglycemia (mean scores 4–6). Only HbA1c and hospital admissions were valued differently by the guideline committee (not critical). Other relevant outcomes according to the respondents were adverse events, ease of use and costs. Median MCIDs were 4 mmol/mol for HbA1c (guideline: 5 mmol/mol) and 3 kg for body weight (guideline: 5 kg weight gain and 2,5 kg weight loss). Healthcare professionals preferred relative risk reductions of 20% for mortality (guideline: 10%) and macrovascular morbidity (guideline: 25%) and 50% for other hypoglycaemia (guideline: 25%). The MCID of 25% for microvascular morbidity, hospital admissions and severe hypoglycaemia corresponded to the guideline‐MCID. Healthcare professionals’ preferences were thus comparable to the views of the guideline committee. However, healthcare professionals had a stricter view on the importance of HbA1c and hospital admissions and the MCIDs for mortality and other hypoglycemia.

Background: Sexual and Reproductive Health and Rights (SRHR) investments are critical to people's well-being. However, despite the demonstrated returns on investments, underfunding of SRHR still persists. The objective of this study was to characterize donor commitments and disbursements to SRH aid in four sub-Saharan countries of Kenya, Tanzania, Uganda and Zambia and to compare trends in donor aids with SRH outcome and impact indicators for each of these countries.Methods: The study is a secondary analysis of data from the Organization for Economic Co-operation and Development's Assistance creditor reporting system and SRH indicator data from the Global Health Observatory and country demographic health surveys for a 16-year period (2002–2017). We downloaded and compared commitments to disbursements of all donors for population policies, programs and reproductive health for the four African countries. SRH indicators were stratified into health facility level process/outcome indicators (modern contraceptive prevalence rate, unmet need for family planning, antenatal care coverage and skilled birth attendance) and health impact level indicators (maternal mortality ratio, newborn mortality rate, infant mortality rate and under five mortality rate).Results: Donor commitments for SRH aid grew on average by 20% while disbursements grew by 21% annually between 2002 and 2017. The overall disbursement rate was 93%. Development Assistance Cooperation (DAC) countries donated the largest proportion (79%) of aid. Kenya took 33% of total aid, followed by Tanzania 26%, Uganda 23% and then Zambia (18%). There was improvement in all SRH outcome and impact indicators, but not enough to meet targets.Conclusion: Donor aid to SRH grew over time and in the same period indicators improved, but improvement remained slow. Unpredictability and insufficiency of aid may be disruptive to recipient country planning. Donors and low- and middle-income countries should increase funding in order to meet global SRHR targets.