Illustrating the financial consequences of outcome-based payment models from a payers perspective- the case of autologous gene therapy atidarsagene autotemcel (Libmeldy®).

OBJECTIVE: To illustrate the financial consequences of implementing different managed entry agreements ((MEA) for the Dutch healthcare system for autologous gene therapy atidarsagene autotemcel (AA, Libmeldy®), while also providing a first systematic guidance on how to construct MEAs to aid future reimbursement decision-making and create patient access to high-cost, one-off potentially curative therapies. METHODS: Three payment models were compared: (1) an arbitrary 60% price discount, (2) an outcome-based spread payment with discounts, and (3) an outcome-based spread payment linked to a willingness to pay model with discounts. Financial consequences were estimated for full responders (A), patients responding according to the predicted clinical pathway presented in HTA reports (B), and unstable responders (C). The associated costs for an average patient during the timeframe of the payment agreement, the total budget impact, and associated benefits expressed in quality-adjusted life-years of the patient population were calculated. RESULTS: When patients responded according to the predicted clinical pathway presented in HTA reports (Scenario B), implementing outcome-based reimbursement models (models 2 and 3) had lower associated budget impacts while gaining similar benefits compared to the discount (Scenario 1, €8,9 million to €6,6 million vs. €9.2 million). In the case of unstable responders (Scenario C), costs for payers are lower in the outcome-based scenarios (€4.1 million and €3.0 million, Scenario 2.C and 3.C, respectively) compared to implementing the discount (€9.2 million, Scenario 1.C). CONCLUSION: Outcome-based models can mitigate the financial risk of reimbursing AA. This can be considerably beneficial over simple discounts when clinical performance was similar to or worse than predicted.

Innovations in pharmaceutical policies and learnings for sustainable access to affordable medicines.

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.

Healthcare decision-making for tumour-agnostic therapies in Europe: lessons learned.

The tumour-agnostic authorisations of larotrectinib and entrectinib shifted the paradigm for indication setting. European healthcare decision-makers agreed on their therapeutic potential but diverged primarily in identified uncertainties concerning basket trial designs and endpoints, prognostic value of neurotrophic tropomyosin receptor kinase (NTRK) gene fusions, and resistance mechanisms. In addition, assessments of relevant comparators, unmet medical needs (UMNs), and implementation of NTRK-testing strategies diverged. In particular, the tumour-specific reimbursement recommendations and guidelines do not reflect tumour-agnostic thinking. These differences indicate difficulties experienced in these assessments and provide valuable lessons for future disruptive therapies. As we discuss here, early multistakeholder dialogues concerning minimum evidence requirements and involving clinicians are essential.

The impact of scheduling ketamine as an internationally controlled substance on anaesthesia care in Sub-Saharan Africa: a case study and key informant interviews.

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.

Availability and stock-outs of paediatric antiretroviral treatment formulations at health facilities in Kenya and Uganda.

INTRODUCTION: The large number of deaths among children with HIV is driven by poor antiretroviral treatment (ART) coverage among this cohort. The aim of the study was to assess the availability and stock-outs of paediatric and adult ART formulations in Kenya and Uganda across various regions and types of health facilities. METHODS: A survey on availability and stock-outs of paediatric ART at health facilities was adapted from the standardized Health Action International-WHO Medicine Availability Monitoring Tool. All preferred and limited-use formulations, and three phased-out formulations according to the 2021 WHO optimal formulary list were included in the survey, as well as a selection of adult ART formulations suitable for older children, adolescents, and adults. Availability data were collected in June-July 2022 and stock-out data were obtained over the previous year from randomly selected public and private-not-for-profit (PNFP) facilities registered to dispense paediatric ART across six districts per country. All data were analysed descriptively. RESULTS: In total, 144 health facilities were included (72 per country); 110 were public and 34 PNFP facilities. Overall availabilities of preferred paediatric ART formulations were 52.2% and 63.5% in Kenya and Uganda, respectively, with dolutegravir (DTG) 10 mg dispersible tablets being available in 70.2% and 77.4% of facilities, respectively, and abacavir/lamivudine dispersible tablets in 89.8% and 98.2% of facilities. Of note, availability of both formulations was low (37.5% and 62.5%, respectively) in Kenyan PNFP facilities. Overall availabilities of paediatric limited-use products were 1.1% in Kenya and 1.9% in Uganda. At least one stock-out of a preferred paediatric ART formulation was reported in 40.0% of Kenyan and 74.7% of Ugandan facilities. Nevirapine solution stock-outs were reported in 43.1% of Ugandan facilities, while alternative formulations for postnatal HIV prophylaxis were not available. CONCLUSIONS: Recommended DTG-based first-line ART for children across all ages was reasonably available at health facilities in Kenya and Uganda, with the exception of Kenyan PNFP facilities. Availability of paediatric ART formulations on the limited-use list was extremely low across both countries. Stock-outs were reported regularly, with the high number of reported stock-outs of neonatal ART formulations in Uganda being most concerning.

Monitoring Access to Child Medicines: Introducing a Standardized Set of Age-Appropriate Medicines.

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.

Tools for assessing quality of studies investigating health interventions using real-world data: a literature review and content analysis.

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).

Added benefit and revenues of oncology drugs approved by the European Medicines Agency between 1995 and 2020: retrospective cohort study.

OBJECTIVES: To evaluate the added benefit and revenues of oncology drugs, explore their association, and investigate potential discrepancies between added benefit and revenues across different approval pathways of the European Medicines Agency (EMA). DESIGN: Retrospective cohort study. SETTING: Oncology drugs and their indications approved by the EMA between 1995 and 2020. MAIN OUTCOME MEASURES: Added benefit was evaluated using ratings published by seven organisations: health technology assessment agencies from the United States, France, Germany, and Italy, two medical oncology societies, and a drug bulletin. All retrieved ratings were recategorised using a four point ranking scale to indicate negative or non-quantifiable, minor, substantial, or major added benefit. Revenue data were extracted from publicly available financial reports and compared with published estimates of research and development (R&D) costs. Finally, the association between added benefit and revenue was evaluated. All analyses were performed within the overall study cohort, and within subgroups based on the EMA approval pathway: standard marketing authorisation, conditional marketing authorisation, and authorisation under exceptional circumstances. RESULTS: 131 oncology drugs with 166 indications were evaluated for their added benefit by at least one organisation within the required timeframe, yielding a total of 458 added benefit ratings; 189 (41%) were negative or non-quantifiable. The median time to offset the median R&D costs ($684m, £535m, €602m, adjusted to 2020 values) was three years; 50 of 55 (91%) drugs recovered these costs within eight years. Drugs with higher added benefit ratings generally had greater revenues. Negative or non-quantifiable added benefit ratings were more frequent for conditional marketing authorisations and authorisations under exceptional circumstances than for standard marketing authorisations (relative risk 1.53, 95% confidence interval 1.23 to 1.89). Conditional marketing authorisations generated lower revenues and took longer to offset R&D costs than standard marketing authorisations (four years compared with three years). CONCLUSIONS: While revenues seem to align with added benefit, most oncology drugs recover R&D costs within a few years despite providing little added benefit. This is particularly true for drugs approved through conditional marketing authorisations, which inherently appear to lack comprehensive evidence. Policy makers should evaluate whether current regulatory and reimbursement incentives effectively promote development of the most effective drugs for patients with the greatest needs.

A literature review of quality assessment and applicability to HTA of risk prediction models of coronary heart disease in patients with diabetes.

This literature review had two objectives: to identify models for predicting the risk of coronary heart diseases in patients with diabetes (DM); and to assess model quality in terms of risk of bias (RoB) and applicability for the purpose of health technology assessment (HTA). We undertook a targeted review of journal articles published in English, Dutch, Chinese, or Spanish in 5 databases from 1st January 2016 to 18th December 2022, and searched three systematic reviews for the models published after 2012. We used PROBAST (Prediction model Risk Of Bias Assessment Tool) to assess RoB, and used findings from Betts et al. 2019, which summarized recommendations and criticisms of HTA agencies on cardiovascular risk prediction models, to assess model applicability for the purpose of HTA. As a result, 71 % and 67 % models reporting C-index showed good discrimination abilities (C-index >= 0.7). Of the 26 model studies and 30 models identified, only one model study showed low RoB in all domains, and no model was fully applicable for HTA. Since the major cause of high RoB is inappropriate use of analysis method, we advise clinicians to carefully examine the model performance declared by model developers, and to trust a model if all PROBAST domains except analysis show low RoB and at least one validation study conducted in the same setting (e.g. country) is available. Moreover, since general model applicability is not informative for HTA, novel adapted tools may need to be developed.

Adoption of new medicines in primary care: A comparison between the uptake of new oral anticoagulants and diabetes medicines.

AIMS: To gain insight in the uptake and practice variation in the prescription of 2 new medicine groups for common conditions in primary care (direct-acting oral anticoagulants [DOACs] and incretin-based therapies) from introduction, around 2007, to 2019 and the correlation between the adoption of those medicines in primary care. METHODS: Prescription data from general practices in the Dutch Nivel Primary Care Database from 2007 to 2019 were used. The percentage of patients with prescriptions for DOACs of all patients with prescriptions for DOACs and vitamin K antagonists was calculated per practice per year, as was the percentage of patients prescribed incretin-based therapies as a proportion of all patients with diabetes medication. Multilevel models were used to estimate practice variation for DOACs and incretin-based therapies, expressed as intraclass correlation coefficients. Linear regression analysis was used to study the association between the prescription of DOACs and incretin-based therapies. RESULTS: Per year, 46-424 general practices and 179 933-1 654 376 patients were included. In 2019, the mean percentage of patients per practice using DOACs or incretin-based therapies was 54.9 and 9.7%, respectively. The intraclass correlation coefficient decreased from 0.75 to 0.024 for DOACs and from 0.33 to 0.074 for incretin-based medicines during the study period. No clear correlation was found between the prescription of DOACs and incretin-based therapies. CONCLUSION: DOACs and incretin-based therapies have different adoption profiles and practice variation is large, especially in the years before these medicines were introduced in guidelines. Early adopters of both medicine classes differ.

A systematic review of policies regulating or removing mark-ups in the pharmaceutical supply and distribution chain.

The regulation of mark-ups throughout the pharmaceutical supply and distribution chain may be a valuable approach to control prices of medicines and to achieve broader access to medicines. As part of a wider review, we aimed to systematically determine whether policies regulating mark-ups are effective in managing the prices of pharmaceutical products. We searched for studies published between January 1, 2004 and October 10, 2019, comparing policies on regulating mark-ups against other interventions or a counterfactual. Eligible study designs included randomized trials, and non-randomized or quasi-experimental studies such as interrupted time-series (ITS), repeated measures (RM), and controlled before-after studies. Studies were eligible if they included at least one of the following outcomes: price (or expenditure as a proxy for price and volume), volume, availability or affordability of pharmaceutical products. The quality of the evidence was assessed using the GRADE methodology. A total of 32,011 records were retrieved, seven of which were eligible for inclusion for this review. The limited body of evidence cautiously suggests that policies regulating mark-ups may be effective in reducing medicine prices and pharmaceutical expenditures. However, the design of mark-up regulations is a critical factor for their potential success. Additional research is required to confirm the effects of these policies on the availability, affordability or usage patterns of medicines and in low- and middle-income countries.

Alignment in the registration, selection, procurement and reimbursement of essential medicines for childhood cancers in South Africa.

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.

Barriers to accessing internationally controlled essential medicines in sub-saharan Africa: A scoping review.

BACKGROUND: Access to internationally controlled essential medicines (ICEMs), medicines that are listed on both the World Health Organization's Essential Medicines List and one of three international drug control conventions, remains problematic in Sub-Saharan Africa (SSA). Previous reviews have focused only on specific ICEMs or ICEM-related healthcare fields, but none have focused on all ICEMs as a distinct class. This scoping review therefore aims to identify the barriers to accessing ICEMs across all relevant healthcare fields in SSA. METHODS: A scoping review was conducted across indexing platforms Embase, PubMed, Scopus and Web of Science of studies published between January 1 2012 and February 1 2022. Articles were eligible if they mentioned barriers to accessing ICEMs and/or ICEM-related healthcare fields, if studies were conducted in SSA, or included data on an SSA country within a multi-country study. The review was guided by the Access to Medicines from a Health System Perspective framework. RESULTS: The search identified 5519 articles, of which 97 met the inclusion criteria. Many barriers to access were reported and were common across the ICEMs drug class. Main barriers were: at the individual level, the lack of knowledge about ICEMs; at the health service delivery level, low availability, stockouts, affordability, long distances to health facilities, insufficient infrastructure to store and distribute ICEMs, and lack of ICEM knowledge and training among healthcare workers; at the health sector level, lack of prioritisation of ICEM-related healthcare fields by governments and subsequent insufficient budget allocation. Cross-cutting, governance-related barriers pertained to lack of proper quantification systems, cumbersome procurement processes, and strict national laws controlling ICEMs, leading to overly restrictive prescription practices. CONCLUSION: This review showed that there are a multitude of barriers to accessing ICEMs in SSA across all health system levels. Many of the barriers identified are applicable to all ICEMs, highlighting the importance of tackling barriers for this entire class of drugs together.

Sustainable Development Goal indicator for measuring availability and affordability of medicines for children: a proof-of-concept study.

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.

Transforming pharmaceutical education: A needs-based global analysis for policy development.

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.

Synergy between health technology assessments and clinical guidelines for multiple sclerosis.

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.

Medicine shortages: impact behind numbers.

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.

Suspected adverse reactions reported for blood, blood components, and blood products in VigiBase.

INTRODUCTION: Since being designated as medicines by World Health Organization (WHO), blood components are subject to pharmacovigilance reporting. Using VigiBase, the WHO global database of individual case safety reports (ICSRs), we characterized reports of adverse reactions for all blood products. STUDY DESIGN AND METHODS: ICSRs involving blood products as the suspected medicine in VigiBase between 1968 and 2021 were extracted. MedDRA preferred terms and the International Society of Blood Transfusion haemovigilance definitions were used to stratify adverse reactions. Descriptive statistics were used to characterize ICSR demographics. RESULTS: A total of 111,033 ICSRs containing 577,577 suspected adverse reactions with 6152 MedDRA preferred terms were reported for 34 blood products. There were 12,153 (10.9%) reports for blood components, 98,135 (88.4%) reports for plasma-derived medicines, and 745 (0.7%) reports for recombinant products. The majority of reports (21.0% and 19.7%, respectively) were from patients aged 45-64 and over 65 years. The Americas contributed the most ICSRs (49.7%). Top reported suspected adverse reactions were for the following MedDRA preferred terms: headache (3.5%), pyrexia (2.8%), chills (2.8%), dyspnoea (1.8%), and nausea (1.8%). CONCLUSION: VigiBase already has a large number of reports on blood products. When compared to other existing haemovigilance databases, our study found reports from a broader range of countries and reporters. This may provide us with new perspectives, but for VigiBase to reach its full potential in haemovigilance some alterations in what is captured in reports are required.

Improved knowledge on substandard and falsified (SF) medical products through a dedicated course for pharmacy students at three universities in sub-Saharan Africa.

BACKGROUND: Too few pharmacists receive formal training on substandard and falsified (SF) medical products. Strengthening knowledge across pharmacists is considered a moral and ethical duty of academia, that is, to build the health systems' capacities to combat this global health threat these poor-quality products represent. This study therefore aimed to evaluate whether a dedicated educational course for undergraduate pharmacy students can improve their knowledge on these products. METHODS: A survey was conducted at three sub-Saharan universities. Knowledge was assessed through scores on a 20-point questionnaire with questions related to the course content. Scores were compared before and after the course, and a linear mixed-effects model analysis was used to analyse score differences. Students were furthermore asked for feedback and self-assessment. In addition, teachers were interviewed on the context of the course introduction. These data were analysed descriptively. RESULTS: Among 335 out of 355 students who completed the survey (n=41/53 in Cameroon, n=244/252 in Senegal and n=50/50 in Tanzania), knowledge of SF medical products was enhanced, with increase in all countries, overall, by 3.5 (95% CI 3.1 to 3.9) score points. Students improved in all offered modules in each country. Students confirmed their improvement through self-assessment.The course was well received among students and teachers. Barriers included time constraints and access to practical means (equipment availability, room allocation, internet accessibility and affordability). These barriers can be overcome by key enablers such as the support from university leadership and early involvement of the university in the course design. CONCLUSIONS: The course improved students' knowledge on SF medical products. These findings encourage further full implementation of this course in existing curricula beyond the pilot and can inform possible future scale-up. This has a potential for reinforcing the capacity of health systems to protect communities from SF medicines, by empowering all pharmacist across the health systems to intervene.