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Shortages and Price Variability of Essential Cytotoxic Medicines for Treating Children with Cancers

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Shortages and Price Variability of Essential Cytotoxic Medicines for Treating Children with Cancers Original research BMJ Glob Health: first published as 10.1136/bmjgh-2020-003282 on 10 November 2020. Downloaded from Shortages and price variability of essential cytotoxic medicines for treating children with cancers Yehoda M Martei,1 Kotoji Iwamoto,2 Ronald D Barr,3 John T Wiernkowski,3 2,4 Jane Robertson To cite: Martei YM, Iwamoto K, ABSTRACT Key questions Barr RD, et al. Shortages Introduction Low- income and middle- income countries and price variability of (LMICs) face the largest burden of mortality from childhood What is already known? essential cytotoxic medicines cancers with limited access to curative therapies. Few for treating children with The Essential Medicines Working Group of the comparative analyses across all income groups and world ► cancers. BMJ Global Health International Society of Paediatric Oncology (SIOP) regions have examined the availability and acquisition costs of 2020;5:e003282. doi:10.1136/ proposed a list of essential (core) and ancillary anti- essential medicines for treating cancers in children. bmjgh-2020-003282 neoplastic drugs to guide selection and procurement Methods A cross- sectional survey involved countries in five of medicines, particularly in low- income and middle- income groups—low- income (LIC), lower- middle- income Handling editor Soumitra S income countries (LMICs) which have the highest (LMC), upper- middle- income (UMC), two high- income country Bhuyan mortality burden from childhood cancers. groups (HIC1, HIC2). Physicians and pharmacists reported There are limited data on the use, availability, short- ► Additional material is institutional use, availability, stock outs and prices (brand and ► published online only. To view ages, procurement prices of these essential medi- generic products) of 34 essential medicines. Price comparisons please visit the journal online cines and treatment costs for common, treatable used US$, applying foreign exchange rates (XR) and purchasing (http:// dx. doi. org/ 10. 1136/ cancers in children across low-income countries power parity (PPP) adjustments. Medicine costs for treating bmjgh- 2020- 003282). (LICs), lower- middle- income countries (LMCs), acute lymphoblastic leukaemia (ALL), Burkitt lymphoma (BL) upper- middle- income countries (UMCs) and high- and Wilms tumour (WT) were calculated (child 29 kg, body income countries (HICs). Received 29 June 2020 surface area 1 m2). Comparisons were conducted using non- Revised 14 August 2020 parametric Kruskal- Wallis tests. What are the new findings? Accepted 28 August 2020 Results Fifty-eight respondents (50 countries) provided ► Use, availability and stockouts of SIOP core and information on medicine use, availability and stock outs, ancillary medicines varied across income groups, with usable price data from 42 facilities (37 countries). The with LMC and LIC facilities using fewer medicines, extent of use of International Society of Paediatric Oncology whereas UMC and LMC facilities were more likely to http://gh.bmj.com/ core and ancillary medicines varied across income groups report medicines not available or stockouts. (p<0.0001 and p=0.0002 respectively). LMC and LIC facilities ► Medicine prices varied widely within and between © World Health Organization used fewer medicines than UMC and HIC facilities. UMC and income bands; generic products were not always 2020. Licensee BMJ. LMC facilities were more likely to report medicines not available cheaper than brand equivalents; purchasing power 1 Hematology – Oncology or stockouts. parity adjustment showed relatively higher prices in Division, University of Medicine prices varied widely within and between income UMC and LMC facilities for some medicines. on September 24, 2021 by guest. Protected copyright. Pennsylvania, Philadelphia, bands; generic products were not always cheaper than brand ► Medicine costs were highest in HICs but varied Pennsylvania, USA 2 equivalents. PPP adjustment showed relatively higher prices widely within and between income groups for acute Health Technology and in UMC and LMC facilities for some medicines. Medicine costs Pharmaceuticals Programme, lymphoblastic leukaemia, Burkitt lymphoma and were highest in HICs for ALL (p=0.0075 XR; p=0.0178 PPP- World Health Organization Wilms tumour. adjusted analyses) and WT (p =<0.0001 XR; p=0.0007 PPP- Regional Office for Europe, What do the new findings imply? Copenhagen, Denmark adjusted). Medicine costs for BL were not significantly different. 3Pediatric Haematology/ Conclusion Problems with the availability of essential ► Irregular medicine availability, unreliable supply Oncology, McMaster University medicines, dependable supply chains, confidential medicine chains, confidential medicine pricing and wide vari- and McMaster Children's prices and wide variability in treatment costs contribute to ability in treatment costs contribute to persistent dis- Hospital, Hamilton, Ontario, persistent challenges in the care of children with treatable advantages for children requiring care for treatable Canada cancers, especially in LMICs. cancers, especially in LMICs. 4 Clinical Pharmacology, ► Reluctance to provide medicine cost information University of Newcastle, and/or reliance on list prices limit the usefulness Waratah, New South Wales, of comparisons of medicine and treatment costs Australia and inhibit progress in ensuring equitable and af- INTRODUCTION Correspondence to fordable access to essential cancer medicines and Kotoji Iwamoto; Childhood cancers constitute only a small treatments. iwamotok@ who. int proportion of the global cancer burden, but Martei YM, et al. BMJ Global Health 2020;5:e003282. doi:10.1136/bmjgh-2020-003282 1 BMJ Global Health BMJ Glob Health: first published as 10.1136/bmjgh-2020-003282 on 10 November 2020. Downloaded from 84% of them occur in low-income and middle-income Management Sciences for Health Inc (MSH) provides countries (LMICs), where nearly 90% of the world’s global data on prices, the current data are outdated, children live and where access to care and to curative with the most recent information available being 2015.16 treatments with long-term event- free survival benefit While there have been a number of studies and reports is often limited or non-existent. 1 There are many chal- comparing availability and prices of cancer medicines lenges to providing access to essential cytotoxic medi- within and between jurisdictions,17–23 these studies have cines for children with cancer in low-resource settings, focused on list prices for 31 originator medicines in including affordability, government underfunding and 18 HICs17 and in 10 countries of the South East Asian, institutional weaknesses in the pharmaceutical sector for Western Pacific and East Mediterranean regions,18 drawn procuring and supplying drugs.2 3 The challenges have on limited data pricing sources within the MSH data- been compounded in recent years by shortages of key base,19 been restricted to a single country20 or focused cytotoxic medicines that are the cornerstone of effective on patient out- of- pocket costs for cancer medications.21 22 treatment of cancers in children.4 These medicines are There are limited data on price and availability of often older, out- of- patent products and, in some cases, essential medicines for treating cancers in children, there are newer and more expensive alternatives avail- particularly in LMICs24 25 which bear a disproportionate able, although these will be unaffordable in many LMICs.5 burden of mortality from childhood cancers.26 Studies For other medicines, there are no alternatives, so care have reviewed the costs and cost-effectiveness of treating is compromised.6 Such shortages of cytotoxic medicines cancers in children in LMICs,5 and assessed the avail- are now so commonplace that an ethical framework for ability and affordability of these medicines in India.27 dealing with the problem has been proposed.7 We found no studies assessing availability and comparing As defined by WHO, on the supply side: ‘shortage’ prices paid for medicines by institutions providing treat- occurs when the supply of medicines, health products ment for childhood cancers across all income groups. or vaccines identified as essential by the health system The aim of this study was to assess the use and avail- is considered to be insufficient to meet public health ability of essential medicines for treating cancers in chil- and patient needs.8 This definition refers only to prod- dren, and the nature and extent of shortages, including ucts that have already been approved and marketed, in stockouts, of these antineoplastic medicines in selected order to avoid conflicts with research and development LICs, MICs and HICs. In addition, we collected informa- agendas. On the demand side: a ‘shortage’ will occur tion on the cost of procuring these drugs for the institu- when demand exceeds supply at any point in the supply tions providing cancer care. chain and may ultimately create a ‘stockout’ at the point of appropriate service delivery to the patient if the cause of the shortage cannot be resolved in a timely manner METHODS relative to the clinical needs of the patient. These short- The study was cross-sectional, involving survey- based data ages affect all countries regardless of incomes and health- collection from a sample of health professionals at insti- care systems.9 In high- income countries (HICs) the US tutions providing cancer care to children across the six http://gh.bmj.com/ Food and Drug Administration and the European Medi- WHO geographical
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