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

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

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

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

A critical review of methodologies used in pharmaceutical pricing policy analyses

Robust evidence from health policy research has the potential to inform policy-making, but studies have suggested that methodological shortcomings are abundant. We aimed to identify common methodological weaknesses in pharmaceutical pricing policy analyses. A systematic review (SR) of studies examining pharmaceutical pricing policies served as basis for the present analysis. We selected all studies that were included in the SR (n = 56), and those that were excluded from the SR due to ineligible study designs only (n = 101). Risk of bias was assessed and specific study design issues were recorded to identify recurrent methodological issues. Sixty-one percent of studies with a study design eligible for the SR presented with a high risk of bias in at least one domain. Potential interference of co-interventions was a source of possible bias in 53% of interrupted time series studies. Failing to consider potential confounders was the primary cause for potential bias in difference-in-differences, regression, and panel data analyses. In 101 studies with a study design not eligible for the SR, 32% were uncontrolled before-after studies and 23% were studies without pre-intervention data. Some of the methodological issues encountered may be resolved during the design of a study. Awareness among researchers on methodological issues will help improve the rigor of health policy research in general

Evidence on the effectiveness of policies promoting price transparency -: A systematic review

Policies promoting price transparency may be an important approach to control medicine prices and achieve better access to medicines. As part of a wider review, we aimed to systematically determine whether policies promoting price transparency are effective in managing the prices of pharmaceutical products. We searched for studies published between January 1, 2004 and October 10, 2019, comparing policies promoting price transparency 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 32011 records were retrieved, two of which were eligible for inclusion. Although based on evidence from a single study, public disclosure of medicine prices may be effective in reducing prices of medicines short-term, with benefits possibly sustained long-term. Evidence on the impact of a cost-feedback approach to prescribers was inconclusive. No evidence was found for impact on the outcomes volume, availability or affordability. The overall lack of evidence on policies promoting price transparency is a clear call for further research

Quantitative High-Resolution Genomic Analysis of Single Cancer Cells

During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics

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

Missing data on accessibility of children's medicines

Child-appropriate medicines are essential for the safe and effective treatment of children, yet we have observed a large gap in the data required to adequately monitor access to these medicines. We have examined data on the availability and pricing of child-appropriate medicines across 50 surveys. Child-appropriate medicines for nine out of 12 priority diseases in children were infrequently surveyed or not at all. A similar data deficit on age-appropriate medicines is detectable in the broader scientific literature. We also note that existing instruments for collecting data on the availability or prices of medicines are limited in their ability to generate the required data for children. We have identified four priorities as key for improved monitoring of access to medicines for children: (i) dedicated child medicine surveys are needed on availability and prices of child-appropriate medicines; (ii) standardized survey instruments should include age-appropriate medicines and dosages; (iii) health facility service readiness survey tools should include the collection of data on the price of child-appropriate medicines in addition to the availability of medicines; and (iv) sustainable development goal indicator 3.b.3 should be modified to enable the monitoring of access to medicines for children. These deficiencies need to be addressed to ensure the monitoring of access to child medicines as part of the sustainable development goal agenda for 2030 and to implement appropriate interventions for improving access for this vulnerable population

Missing data on accessibility of children's medicines

Child-appropriate medicines are essential for the safe and effective treatment of children, yet we have observed a large gap in the data required to adequately monitor access to these medicines. We have examined data on the availability and pricing of child-appropriate medicines across 50 surveys. Child-appropriate medicines for nine out of 12 priority diseases in children were infrequently surveyed or not at all. A similar data deficit on age-appropriate medicines is detectable in the broader scientific literature. We also note that existing instruments for collecting data on the availability or prices of medicines are limited in their ability to generate the required data for children. We have identified four priorities as key for improved monitoring of access to medicines for children: (i) dedicated child medicine surveys are needed on availability and prices of child-appropriate medicines; (ii) standardized survey instruments should include age-appropriate medicines and dosages; (iii) health facility service readiness survey tools should include the collection of data on the price of child-appropriate medicines in addition to the availability of medicines; and (iv) sustainable development goal indicator 3.b.3 should be modified to enable the monitoring of access to medicines for children. These deficiencies need to be addressed to ensure the monitoring of access to child medicines as part of the sustainable development goal agenda for 2030 and to implement appropriate interventions for improving access for this vulnerable population