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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.

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.

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.

ABSTRACTSustainable 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.

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 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.

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.

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.

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.

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.

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.

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 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 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.

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.

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 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 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.

Abstract Background Under-reporting of adverse drug reactions (ADRs) is a major challenge for pharmacovigilance in Africa. This study sets out to assess the level of awareness of Ghanaian patients about ADRs and ADR-reporting and explores how different patients in Ghana recognize an ADR and the steps they take when they experience an ADR. Methods This was a two-part study consisting of a survey to quantify the awareness of Ghanaian patients on ADRs and ADR-reporting, and in-depth interviews to explore how patients recognize an ADR and the steps they take thereafter. Participants were selected from 28 health care facilities (HCF) in rural and urban areas in 4 out of the 10 administrative regions of Ghana. Chi-square tests were used to examine associations between demographic variables and i) awareness of ADRs and ADR-reporting, ii) ADR experience and iii) awareness of the Ghana Food and Drug Authority (Ghana-FDA) and its patient reporting system (PRS). Only participants that indicated they experienced an ADR were included for the in-depth interviews. Data was investigated for participants’ awareness of ADRs, ADR reporting and steps taken when they experience ADRs. Results Of the total 572 participants enrolled in the study, 14% indicated they were unaware of ADRs and were excluded. Of the remaining 491 participants, 38% had experienced an ADR, of which 67% reported the ADR, 68% of them reported it to a doctor. Only 3% of the 491 participants were aware of the Ghana-FDA’s PRS. The interview phase consisted of 33 patients who had experienced an ADR. Three key findings from the interview phase were; most participants recognized an ADR themselves, the symptoms of the ADR were the most mentioned reason for reporting and participants experienced a wide variety of obstacles in ADR-reporting. Conclusions Most Ghanaian patients appear unaware of or unable/unwilling to use formal national channels for ADR reporting like the Ghana-FDA PRS. Motivation for ADR reporting appeared mainly personal and not communal. These findings warrant further attention in order to increase patient reporting of ADRs.

Abstract Background European legislation prohibits direct-to-consumer advertising of prescription medicines, but allows drug manufacturers to provide information to the public on health and diseases. Our aim was to measure the frequency of disease awareness campaigns in Latvian media and assess their compliance with international and European standards. Methods Materials on health/disease and treatments were collected between April and September 2015 from 12 newspapers and magazines and six online portals. Disease awareness campaigns were assessed using a previously developed instrument based on the WHO Ethical Criteria for Medicinal Drug promotion and European standards (EU law and pharmaceutical industry self-regulatory guidelines). Collected materials were used to examine the information provided on medical conditions and their diagnosis and treatment. The inter-rater reliability was calculated. Results We collected 263 materials from print (n = 149) and online media (n = 114); 94 were news items and 169 were disease-awareness advertisements. Cancer, cardiovascular problems, allergies and respiratory diseases were common topics. Of the 157 campaigns assessed, non-compliance was identified in 149 cases (inter-rater reliability 90%), mainly due to misleading or incomplete information, lack of balance and the absence of a listed author/sponsor. Six disease awareness campaigns directly mentioned a pharmaceutical product by brand name and other four included the logo or name of a manufacturer, referred to a condition and indirectly mentioned a treatment, all in contravention with European law. Conclusions The compliance of disease awareness campaigns in Latvian media with international and European standards is low. This raises concerns about the nature of information being conveyed. Through lack of balance, missing sponsorship information, and misleading or incomplete information, these campaigns could contribute to inaccurate self-diagnosis and generate demand among those who might not need medical treatment.

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.

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.

Abstract Background There is limited information on patterns of treatment change among new initiators of highly active antiretroviral therapy (HAART) in the regions most affected by HIV/AIDS. This makes it difficult to identify the determinants of treatment change. In this retrospective cohort study, we examined treatment change patterns over a five-year period among initiators of HAART. Methods De-identified data were obtained from the Fevers’ Unit Database at the Korle-Bu Teaching Hospital. All adult treatment-naive patients who started treatment with first line HAART between 1st January, 2008 and 31st December, 2012 were followed over a minimum period of three months. The main outcome was the first treatment change, defined as the first substitution/switch in accordance with the standard treatment guidelines. Data were analyzed stratified by year of treatment initiation. Crude and adjusted hazard ratios were calculated. Results A total of 3933 patients were followed with almost equal numbers of initiators per year. The mean age (standard deviation) at treatment initiation was 39 (10.3) years. The most prescribed HAART combination was AZT/3TC/EFV and overall for initiators zidovudine combination therapy was about 60%. Utilization of stavudine containing HAART increased gradually until 2010 and then dropped to zero. Over the study period, 44.9% of recorded deaths were from those initiated with a stavudine backbone, 41.1% from a zidovudine backbone, and 11.5% from a tenofovir backbone. Females had a significantly higher rate of treatment change compared to males (p-value = 0.0002), and d4T/3TC/EFV and d4T/3TC/NVP recorded independent treatment change hazard ratios of 12.05 (CI 9.58 to 15.16) and 12.03 (CI 9.27 to 15.61) respectively.. Kaplan-Meier curves showed that treatment change was higher among those who started treatment later in the study period compared with those who started earlier. Conclusion A major treatment change in the utilization of antiretroviral medicines in Ghana occurred during the study period which was associated with type of treatment, year of treatment, gender and disease stage. The influence of a policy change during the period may have made a significant impact.. For diseases involving life-long treatment in particular, it is important to monitor and periodically evaluation treatment utilization patterns.

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: Drug shortages are a potential threat to public health. Reliable data on drug shortages is limited. The objective was to examine the extent and nature of potential drug shortages signaled by authorities and pharmacy practice in the NetherlandsMaterials and Methods: The primary working systems of Dutch authorities (Medicines Evaluation Board and Health and Youth Care Inspectorate) and the archives of pharmacy practice (Royal Dutch Pharmacists Association) from 2012 to 2015 were searched for number, characteristics, overlap, and date of signals on potential drug shortages. Also, the product characteristics of the potential drug shortages were analyzed from the two different sourcesResults: Authorities detected 2.6 times more signals on potential shortages than pharmacy practice. Only 438 (8%) out of 5,731 potential drug shortages were detected by both authorities and pharmacy practice. Signals were detected later by authorities than by pharmacy practice, especially on potential permanent shortages (median difference −180 days (IQR: −4 to −405 days)). Authorities detected by majority (72%) signals related to permanent shortages with relative overrepresentation of rectal products and anti-infectives for systemic use. In contrast, pharmacy practice detected by majority (71%) signals related to temporary shortages with relative overrepresentation of ocular and cutaneous products, anti-infectives for systemic use, products for sensory organs and dermatologicals.Conclusions: Authorities and pharmacy practice detected different signals on potential drug shortages with little overlap. Combining data from both authorities and pharmacy practice seems to be necessary in order to gain a more complete overview and maximum insight in potential drug shortages at a national level. Moreover, the finding that authorities were informed later than pharmacy practice causes concerns in terms of opportunities for authorities to assist pharmacy practice to find solutions for shortages.

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.