National Tender Research Articles

Enfortumab vedotin plus pembrolizumab as a first-line treatment for advanced urothelial carcinoma: a cost-effectiveness analysis from China based on the EV-302 trial.

The efficacy and safety of enfortumab vedotin combined with pembrolizumab (EV-PEMB) was investigated as a first-line treatment for advanced urothelial carcinoma (UC) in a phase III clinical trial (EV-302). The trial findings indicated significant prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy with a favorable safety profile. However, EV-PEMB is costly and it is unknown whether it is cost-effective compared to chemotherapy. This study aimed to conduct a cost-effectiveness analysis of EV-PEMB versus chemotherapy as a first-line treatment for advanced UC from the perspective of the Chinese healthcare system. A Markov model with three distinct health states was developed to assess the cost-effectiveness of EV-PEMB as a first-line treatment for advanced UC versus chemotherapy based on the EV-302 trial. Drug costs were obtained from national tender prices. Other expenses and utility values were sourced from the literature or expert advice. The findings of the study included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We conducted a one-way sensitivity analysis and probabilistic sensitivity analysis to ensure the model's robustness. The EV-PEMB regimen demonstrated a gain of 3.22 QALYs at $375,420.24, compared to the chemotherapy regimen with 1.70 QALYs at $23,369.67. ICER for EV-PEMB compared to chemotherapy was at $232,256.16 per QALY gained. In China, at a willingness-to-pay threshold of $38,133 per QALY, EV-PEMB has a 0% probability of being cost-effective as a first-line treatment for advanced UC compared to chemotherapy. From the perspective of the Chinese healthcare system, EV-PEMB is unlikely to be a cost-effective first-line treatment option for advanced UC compared to chemotherapy.

Cost-effectiveness analysis of transarterial chemoembolization combined with lenvatinib as the first-line treatment for advanced hepatocellular carcinoma.

Purpose: Results from the LAUNCH trial suggest transarterial chemoembolization (TACE) in combination with lenvatinib is significantly more effective than lenvatinib as a first-line treatment option for advanced hepatocellular carcinoma (HCC). However, the cost of TACE is substantial. This study compares the cost-effectiveness of TACE in combination with lenvatinib (TACE-LEN) with that of lenvatinib alone as the first-line treatment for advanced HCC from the perspective of the Chinese healthcare system. Methods: Markov models of different health states were constructed to simulate first-line treatment, disease progression, and survival in patients with advanced HCC. Clinical efficacy was obtained from the LAUNCH trial. The cost of drugs was sourced from national tender prices, and the treatment cost of weight-decreased was obtained from the Fujian Provincial Bureau of Prices. Other costs and utility values were based on the published literature. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) comprised the model output. One-way and probabilistic sensitivity analyses were performed to validate model robustness and subgroup analyses were also conducted. Results: Analysis of the model showed that compared to lenvatinib, TACE-LEN improved effectiveness by 1.60 QALYs at a total cost increase of $48,874.69, with an ICER value of $30,482.13/QALY. A one-way sensitivity analysis found that the progression-free survival utility value per year had the greatest impact on the model. A probabilistic sensitivity analysis showed that TACE-LEN had a 97.9% probability of being cost-effective as the first-line treatment option for advanced HCC compared to lenvatinib when the willingness-to-pay (WTP) value was $38,201/QALY (three times the Chinese GDP per capita in 2022). Subgroup analysis showed that all subgroups of patients preferred TACE-LEN. However, when the WTP threshold was below $30,300/QALY, TACE-LEN is no longer cost-effective. Conclusion: Our study found TACE-LEN to be a cost-effective treatment option for patients with advanced HCC compared to lenvatinib from a Chinese healthcare system perspective, but not so in low-income provinces in China.

Exploring the impact of the national tender system on the use of costly drugs treating rheumatoid arthritis patients in ten rheumatology centers in Norway (2010–2019)

BackgroundBiologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019.MethodThe data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described.ResultThe tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively.ConclusionBased on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks.

Cost-effectiveness analysis of dostarlimab plus carboplatin-paclitaxel as first-line treatment for advanced endometrial cancer.

A recent phase III clinical trial (NCT03981796) evaluated the efficacy and safety of dostarlimab combined with carboplatin-paclitaxel (DOS-CP) compared to placebo combined with carboplatin-paclitaxel (PLB-CP) as a first-line treatment for advanced endometrial cancer (EC). The NCT03981796 trial demonstrated that DOS-CP significantly improved progression-free survival and overall survival of patients with advanced EC while maintaining an acceptable safety profile. However, DOS-CP is expensive and its cost-effectiveness has not been evaluated. This study aims to evaluate the cost-effectiveness of DOS-CP compared to PLB-CP as a first-line treatment for advanced EC from the perspective of the Chinese healthcare system. A Markov model with three health states was developed to evaluate the cost-effectiveness of DOS-CP as a first-line treatment for advanced EC. Clinical efficacy data were derived from the NCT03981796 trial, and drug costs were determined based on national tender prices. Other costs and utility values were obtained from published literature. The outcomes assessed included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The robustness of the model was assessed through one-way sensitivity analysis and probabilistic sensitivity analysis. In comparison to PLB-CP, the ICER of DOS-CP was $98,276.61/QALY for the overall population, $53,063.61/QALY for the dMMR subgroup, and $124,088.56/QALY for the pMMR subgroup. All of these ICER values were higher than the willingness-to-pay threshold of $38,201 per QALY. The most important variable that affected the results of the model was the discount rate, the cost of dostarlimab, and the utility value for progressive disease. From the perspective of the Chinese healthcare system, DOS-CP is unlikely to be a cost-effective first-line treatment option for advanced EC.

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

IntroductionThe 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...

The cost-effectiveness of cemiplimab plus chemotherapy as the first-line treatment for advanced non-small cell lung cancer.

Background: The EMPOWER-LUNG 3 clinical trial has shown that cemiplimab plus chemotherapy (CCT) significantly extended overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell cancer (NSCLC) compared to placebo plus chemotherapy (PCT). However, the cost-effectiveness of this new treatment option remains unknown. Thus, we evaluated the cost-effectiveness of CCT versus (vs.) PCT as the first-line treatment for patients with advanced NSCLC from the perspective of the Chinese healthcare system. Methods: We constructed a Markov model to evaluate the cost-effectiveness of CCT as the first-line treatment for patients with advanced NSCLC. The transition probabilities were extracted from the survival data of the EMPOWER-LUNG 3 trial. The drugs' costs were referred from national tender prices, while other model input parameters were derived from the EMPOWER-LUNG 3 trial and published literature. The outcome parameters mainly included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model outcomes. Results: Compared to PCT, in the CCT regimen, an additional $79,667 was spent in terms of the total cost and with an additional 0.31 QALYs, resulting in an ICER value of $253,148/QALY. Sensitivity analysis indicated that the hazard ratio (HR) of OS, the cost of cemiplimab (100mg), and the HR of PFS, all significantly impacted the model's results. The probability of CCT (vs. PCT) being cost-effective was 0% at a willingness-to-pay threshold of $38,201/QALYs in China. The scenario analysis showed that when the price of cemiplimab was reduced to less than $184.09/100mg, the CCT regimen could be considered cost-effective as the first-line treatment for patients with advanced NSCLC compared to the PCT. Conclusion: In China, the CCT was not cost-effective as the first-line treatment for patients with advanced NSCLC.

P888 Evaluating patient access to infliximab subcutaneous in inflammatory bowel disease

Abstract Background Infliximab(IFX) subcutaneous(SC) was developed as a novel formulation biosimilar added to the intravenous(IV) infliximab. Infliximab is one of the most effective treatments in IBD and approval of subcutaneous formulation was expected to bring greater patient convenience, yet it had to overcome its hurdles in Health Technology Assessment (HTA) in the absent of the SC originator. This research aims to evaluate patient access to IFX SC based on time-to-reimbursement decision post market authorization in July of 2021. Methods The pricing database, IQVIA MIDAS® data and epidemiology data were combined to analyze patient access in 32 countries. We evaluated 1) status of the reimbursement 2) volume consumed in a country 3) average period from marketing authorisation to positive reimbursement decision 4) reason for delayed access. Results Since the market authorization, positive reimbursement decisions were made in 18 countries among 31 European countries including UK. Among them, patients who reside in 15 countries had records of utilization of IFX SC in the year of 2022. About 74.76% of IBD patients is eligible for reimbursement of CT-P13 SC among the assumed 1,023,765 IBD patients in Europe. Average time from market authorisation to positive reimbursement decision by health authorities were 9 months(2-17) in the case of IFX SC which suggests delayed reimbursement compared to biosimilars. Although most of the European countries offered shortened or simplified HTA pathways to biosimilars, most of the countries did not have clear guidance on pricing of the novel biosimilars. Several countries failed to provide IFX SC after a positive reimbursement decision because the procurement system failed to differentiate a novel biosimilar with different strength and form from the existing biosimilars in same molecule. This may have deterred the market entry; countries where adopted national tender grouped IFX SC with IFX IV(Norway, Hungary) or extended procurement basket to all available IBD treatment(Denmark and Lithuania). Figure: Reimbursement status of infliximab subcutaneous in European countries Conclusion There are apparent differences in patient access to IFX SC among European countries. Biosimilars promises to bring improved patient access to biologics, however, pricing of bio-betters or bio-innovators could be convoluted that efforts are still warranted in order to bring the drug into the market within shortest possible time. Although IBD treatment options are expanding, IFX is still widely used. Adding another SC treatment may improve patient convenience and quality of life and thus, overall improved access to the drug is imperative for equitable use.

Cost-effectiveness analysis of adebrelimab combined with chemotherapy for extensive-stage small cell lung cancer

Background: The findings of the CAPSTONE-1 trial showed that adebrelimab in combination with chemotherapy (etoposide-carboplatin) (ADCHM) is clinically beneficial as a first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), compared with placebo plus chemotherapy (PLCHM, etoposide-carboplatin). However, owing to the higher cost of adebrelimab, it is unclear whether ADCHM is cost-effective compared with PLCHM. This study aimed to evaluate the cost-effectiveness of ADCHM as a first-line treatment for patients with ES-SCLC from the perspective of the Chinese healthcare system. Methods: A Markov model with three health states was developed to assess the cost-effectiveness of ADCHM as a first-line treatment option with ES-SCLC. Clinical data were obtained from the CAPSTONE-1 trial. Costs of the drug were calculated at national tender prices, and other costs and utility values were obtained from published literature. The outcomes included life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were used to validate the robustness of the model. Results: The ADCHM group achieved 1.21 QALYs (2.47 LYs) for $25,312, whereas the PLCHM group achieved 0.81 QALYs (1.59 LYs) for $14,846. The ICER for ADCHM versus PLCHM was $25914 per QALY gained. The variables with the greatest impact on the model results were the utility value of progressive disease, the utility value of progression-free survival, and the price of adebrelimab (100mg). At a willingness-to-pay threshold of $37,653/QALY, ADCHM had an 89.1% probability of being cost-effective compared with PLCHM. Conclusion: ADCHM may be a cost-effective first-line treatment strategy for ES-SCLC from the perspective of the Chinese healthcare system.

A multi-criteria decision analysis (MCDA) tool for purchasing off-patent oncology medicines in Egypt

BackgroundMulti- criteria decision analysis (MCDA) can assist policymakers in objectively choosing between alternative therapeutic options based on multiple value attributes. Our aim was to create an MCDA tool for the national tenders of off-patent oncology medicines in Egypt.MethodsAn initial list of criteria was developed through a literature review complemented by local expert interviews. Price or cost-related criteria were excluded to abide by the national regulations of the tender process. Next, a workshop hosting diversified stakeholders representing different governmental bodies was held. Anonymous voting was used to rank and weigh the criteria as well as assigning scores. Price was added as a separate step to identify best option based on price per point. The tool was then tested on a national tender sample of off-patent oncology medicines to assess its performance, and it was readjusted accordingly in a second workshop.ResultsSeven non-price criteria were selected, including use in reference countries (23.49% weight), equivalence with the reference product (18.79%), manufacturing quality (15.53%), provision of pharmacovigilance services (12.94%), supply reliability (10.78%), previous use in local settings (9.8%) and macroeconomic benefit (8.67%).A medicine receives a score ranging from 0 to 100% of each criterion’s weight. The aggregated score is calculated on a hundred-point scale. Based on participants’ consensus, an overall score of 65 was set as a cut-off for passing the technical eligibility phase of the tendering process. Any product receiving a lower score would be disqualified from the tender. For qualified products, the lower price per point represents preferential option for the national tender.ConclusionsThe created MCDA tool is capable of objectively comparing similar off-patent oncology medicines by considering multiple value attributes and providing reliable scoring functions for each.

Exploring drug cost and disease outcome in rheumatoid arthritis patients treated with biologic and targeted synthetic DMARDs in Norway in 2010\u20132019 \u2013 a country with a national tender system for prescription of costly drugs

BackgroundIn Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system.MethodsRA patients monitored in ordinary clinical practice were recruited from 10 Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process.ResultsThe number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39% in 2010 and 45% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 42 to 67%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47%, from 13.1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75% (13.0 thousand EUR in 2010 and 3.2 thousand EUR in 2019).ConclusionsIn the period 2010–2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities’ intention to reduce treatment costs by implementing a tender system has been successful.

POSA259 A Multi-Criteria Decision Analysis (MCDA) Tool for Purchasing Off-Patent Oncology Drugs in Egypt

Multi-criteria decision analysis (MCDA) can assist policy makers in objectively choosing between alternative therapeutic options based on multiple value attributes. Our aim was to create an MCDA tool for the national tenders of off-patent oncology drugs in Egypt.

Exploring Drug Cost and Disease Outcome in Rheumatoid Arthritis Patients Treated With Biologic and Targeted Synthetic DMARDs in Norway from 2010 to 2019 – A Country With a National Tender System for Prescription of Costly Drugs

Exploring Drug Cost and Disease Outcome in Rheumatoid Arthritis Patients Treated With Biologic and Targeted Synthetic DMARDs in Norway from 2010 to 2019 – A Country With a National Tender System for Prescription of Costly Drugs

Switching factor products: nurses’ experience with NovoEight

Abstract Haemophilia nurses in the UK are instrumental in supporting people with haemophilia in self-management, including managing treatment options, recording treatment use and understanding the budgetary impact of prescribing practice. The widespread use of prophylaxis identified haemophilia as a high cost disorder to treat, resulting in a financially successful national tendering process with increased scrutiny of clotting factor use at both individual and haemophilia treatment centre level. The UK tenders, undertaken at a national level every three years, have ensured access to current and new therapies at the most cost-effective price through economies of scale in committing to purchase large volumes from suppliers. In the 2018 tendering round, NovoEight® (NovoNordisk) was added to the prescribing list and other recombinant factors were withdrawn, resulting in changes in prescribing for individual people with haemophilia. This ‘switching’ process is not uncommon in the UK, where national tenders have been in place since 2004. However, the unseen additional workload for nurses, driven by the demands of timely switching to meet product volumes and contracts, has never been captured. During the 2018 switch we interviewed 11 nurses and one operational manager from haemophilia centres across the UK to identify the barriers and facilitators to instigating this change. Ultimately the switching was completed in a timely manner, demonstrating significant cost reductions for factor concentrates. The unseen workload of the nurse – identifying which patients should have their product switched, discussion with and education of patients/families, adjusting prescriptions for home delivery of clotting factor concentrates and stock management and control to avoid waste, and organising the necessary additional clinic visits – was identified and costed based on salary per hour. Nurses remained positive that they were able to undertake this additional role but recognised that, with no specific national guidance regarding product choice, there may have inevitably been differences in approach between treatment centres.

Experience of switching to NovoEight: views of people with haemophilia

Abstract Management of haemophilia A requires administration of factor VIII therapy which, for those with severe haemophilia A in the UK, is predominantly self-administered at home in a prophylactic regimen to prevent or minimise bleeding. The UK undertakes a national tendering process every three years to ensure access to current and new therapies at a cost-effective price, through contracting for large volumes from individual suppliers. This means that some products may no longer be available and that new products can enter the UK market at any tendering stage. In the latest tendering round, in 2018, more than one product was withdrawn from the UK market and a new product (NovoEight®; Novo Nordisk) was added to the prescribing list. This meant people with haemophilia having to change products. The experience of 77 people with haemophilia or their carers who changed treatment products during this process was captured by questionnaires administered by haemophilia nurses from 12 treatment centres. Overall, although people with haemophilia felt that they had little influence in decision making about changing to NovoEight, they were confident with their new treatment including packaging and accessories for administration. This was seen more in those who switched from plasma-derived products where ease of infusion was rated highly. Users’ views of haemophilia treatment should be collected at times of change to identify facilitators and barriers experienced in self-management

Competition in the off-patent medicine market in Spain: The national reference pricing system versus the regional system of tendering for outpatient prescription medicines in Andalusia

Spain has a reference price system (RPS) for off-patent medicines since 1997. In addition, from 2012, Andalusia is running a series of tenders for procuring off-patent medicines dispensed by community pharmacies, for those medicines included in the system of homogenous clusters within the national reference price system. Such tenders offer additional savings to the regional payer – in the form of rebates (“economic improvements”) from companies winning the tender. This paper estimates that the regional savings were between €43 M to €54 M over the period of study (April – September 2015). The paper also estimates that Spain could have made between 14 and 17 times higher savings than the national reference pricing system savings, had the Andalusian-type tender been implemented at national level over the same period of study. Based on our analysis, we have four remarks. First, the national RPS in Spain is not generating enough price competition for off-patent products dispensed in primary care pharmacies. Second, tenders can be a useful way to generate competition and financial savings in the off-patent market. Third, tenders can lead to discounts offered by medicine providers being redistributed from pharmacies to payers. And fourth, before implementing a national tender in Spain, several key issues need to be addressed to ensure it provides the right incentives both in the short and long run.

The Developing Trajectory of the Marketization of Public Employment Services in Denmark—A New Way Forward or the End of Marketization?

This article addresses the market for employment services. It adopts a dynamic perspective on welfare markets and demonstrates how the institutional design of quasi‐markets in the Danish Public Employment service has been promoted, altered, and re‐regulated over a period of 10 years. It was in 2002 when quasi‐markets have been created by using the instrument of contracting‐out employment services to private providers. Seen from the perspective of policymakers at the national level, contracting‐out is attractive as it has a buffering function and allows adapting the amount of the public financed employment services comparatively easy to changing needs resulting from changing labor market conditions. However, contracting‐out makes accountability to public goods more difficult as the chain of accountability is stretched or may even be broken. Against the background of accountability scandals, which have revealed the poor quality of privately provided services, the market design was re‐modeled again by replacing standardized national tendering with a decentralized, partnership‐based and dialogue‐oriented approach, where services are developed in joint efforts between purchaser and provider. All in all, the development of quasi‐markets in the Danish Public Employment system can be described as a partial reversal from marketization. Paradoxically, elements of network governance, which were abolished initially, have been introduced again.

Playing in the Sandpit Together Alone.

The community services sector is the largest provider of non-profit human services in Australia. This sector has experienced considerable growth as a consequence of public policy and sector reforms introduced by successive governments over the past two decades. These reforms have seen the introduction of private sector managerialist agendas, outsourcing of government services and competitive tendering processes. As the community sector has grown governments have sought to consolidate program funding mechanisms, simplify contracting out arrangements and encourage collaboration and formal partnerships through national tender processes. In recent years there has been significant evidence of governments actively encouraging formal intrasectoral partnerships and consortia in program tenders. While there is a considerable body of overseas and national literature on partnerships and collaboration, the predominant focus is on intersectoral relationships such as public-private partnerships between government and the business sector or government contracted services to the community sector. This research responds to a call for more local research on partnerships and collaboration in the Australian community service sector. A case study approach was used to examine the key drivers of intrasectoral partnership and collaborative practice in the context of the literature within business, government and community sectors. The study found prior interactions between organisations significantly influenced whether these drivers were viewed as strong, weak or ambiguous. The findings contribute to the understanding of intrasectoral partnerships and collaboration in the community sector in that prior relationships understood as parallel (i.e. disengaged) or cooperative in nature, can be predictive of potential partnership relationships and outcomes.

Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®)

Previous studies have suggested that development of inhibitors in previously treated patients (PTPs) may be attributable to a switch in factor VIII (FVIII) therapeutic product. Consequently, it is widely recognized that inhibitor development must be assessed in PTPs following the introduction of any new FVIII product. Following a national tender process in 2006, all patients with haemophilia A in Ireland changed their FVIII treatment product en masse to a plasma and albumin-free recombinant full-length FVIII product (ADVATE(®)). In this study, we retrospectively reviewed the case records of Irish PTPs to evaluate risk of inhibitor formation following this treatment switch. One hundred and thirteen patients participated in the study. Most patients (89%) had severe haemophilia. Only one of 96 patients with no inhibitor history developed an inhibitor. Prior to the switch in his recombinant FVIII (rFVIII) treatment of choice, this child had only experienced three exposure days (EDs). Consequently, in total he had only received 6 EDs when his inhibitor was first diagnosed. In keeping with this lack of de novo inhibitor development, we observed no evidence of any recurrent inhibitor formation in any of 16 patients with previously documented inhibitors. Similarly, following a previous en masse switch, we have previously reported that changing from a Chinese hamster ovary cell-produced to a baby hamster kidney cell-produced rFVIII was also associated with a low risk of inhibitor formation in PTPs. Our cumulative findings from these two studies clearly emphasizes that the risk of inhibitor development for PTPs following changes in commercial rFVIII product is low, at least in the Irish population.

High HIV incidence or poor test performance?

We read with much interest the article by Moodley et al. [1] who reported an HIV incidence of 10.7 per 100 woman-years among pregnant women in three provinces of South Africa [95% confidence interval (CI) = 8.2–13.1]. This high incidence is particularly worrisome considering its implications for programmes to prevent mother-to-child transmission (PMTCT) of HIV [2]. With improvements in coverage of PMTCT programmes and implementation of more efficacious prophylactic regimens, a considerable proportion of HIV infections in infants can be attributed to incident maternal HIV. A Botswana study [3] estimated that this proportion was as high as 40%. Before drawing such definitive conclusions, however, critical methodological issues around HIV testing need to be addressed. Variability in the performance of test kits, category of staff and testing algorithms make it hard to make direct comparisons between incidence studies. Concerns about testing validity present quite different policy implications from those described above. Using different testing methodologies, reports of HIV incidence among pregnant women in South Africa have varied from 0% (0/524) in the Western Cape [4] and 5.2% per year in a national sample [5] to 10.7 per 100 woman-years in the study by Moodley et al. [1]. Differences in the sensitivity of tests and of testing algorithms in field conditions could, at least in part, explain these differences. This assertion is supported by our experiences at PMTCT sites in three provinces of South Africa. Rapid kits for HIV testing often vary across sites and change frequently, depending on national tender processes and available stock. Training of midwives and counsellors in the performance of these tests is not systematic and often not repeated each time a kit changes. Given these circumstances, it was not surprising that Moodley et al. [1] reported previously on the poor sensitivity of four HIV rapid tests in field settings in a PMTCT programme in KwaZulu Natal. Sensitivity of kits in that study ranged from 92.5% to 97.3%, with a serial testing algorithm as recommended by the National Department of Health [6]. Using these figures and the HIV prevalence among pregnant women in South Africa (28.0%, 95% CI = 26.9–29.1) [7], it is possible to estimate the number of women who had a false-negative test and were then enrolled in the HIV incidence study of Moodley et al. [1]. Of the 2377 women enrolled, between 25 and 70 may have had false-negative initial tests, comprising a substantial proportion of the 72 incident cases that they report. The authors do not specify which rapid HIV tests or the algorithm used in the field to determine inclusion in the HIV negative cohort nor whether quality control procedures were in place at these sites. Interestingly, women in their cohort were re-tested later in pregnancy using the Determine HIV-1/2 rapid HIV test (Abbott Laboratories, Abbott Park, Illinois, USA), which demonstrated the highest sensitivity in the previous study by Moodley and et al. [8], and has been previously validated in Africa [9]. Use of a more sensitive test during re-testing may also partly explain the high incidence. To improve comparisons between studies and more clearly separate new HIV infections from low negative predictive values of HIV tests or testing algorithms, future reports should fully describe the test kits, algorithms and quality control procedures used. More importantly, additional research is needed to determine whether parallel HIV testing (in which a negative HIV diagnosis is made after two concordant negative tests) is superior to serial algorithms in field conditions. Robust quality control procedures in all sites offering HIV rapid tests remain critical. Moreover, we argue that it is premature to implement re-testing for pregnant women before obtaining further clarity about the quality of actual testing procedures. Acknowledgements Vivian Black, Regina Osih, Helen Rees and Matthew Chersich contributed to the conception and writing of the paper. There are no conflicts of interest.

Is decentralization good for logistics systems? Evidence on essential medicine logistics in Ghana and Guatemala

Efficient logistics systems move essential medicines down the supply chain to the service delivery point, and then to the end user. Experts on logistics systems tend to see the supply chain as requiring centralized control to be most effective. However, many health reforms have involved decentralization, which experts fear has disrupted the supply chain and made systems less effective. There is no consensus on an appropriate methodology for assessing the effectiveness of decentralization in general, and only a few studies have attempted to address decentralization of logistics systems. This paper sets out a framework and methodology of a pioneering exploratory study that examines the experiences of decentralization in two countries, Guatemala and Ghana, and presents suggestive results of how decentralization affected the performance of their logistics systems. The analytical approach assessed decentralization using the principal author's 'decision space' approach, which defines decentralization as the degree of choice that local officials have over different health system functions. In this case the approach focused on 15 different logistics functions and measured the relationship between the degree of choice and indicators of performance for each of the functions. The results of both studies indicate that less choice (i.e. more centralized) was associated with better performance for two key functions (inventory control and information systems), while more choice (i.e. more decentralized) over planning and budgeting was associated with better performance. With different systems of procurement in Ghana and Guatemala, we found that a system with some elements of procurement that are centralized (selection of firms and prices fixed by national tender) was positively related in Guatemala but negatively related in Ghana, where a system of 'cash and carry' cost recovery allowed more local choice. The authors conclude that logistics systems can be effectively decentralized for some functions while others should remain centralized. These preliminary findings, however, should be subject to alternative methodologies to confirm the findings.