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Pricing appraisal of anti-cancer drugs in the South East Asian, Western Pacific and East Mediterranean… Salmasi, Shahrzad; Lee, Kah S; Ming, Long C; Neoh, Chin F; Elrggal, Mahmoud E; Babar, Zaheer-Ud- D; Khan, Tahir M; Hadi, Muhammad A Dec 28, 2017

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RESEARCH ARTICLE Open AccessPricing appraisal of anti-cancer drugs in theSouth East Asian, Western Pacific and EastMediterranean RegionShahrzad Salmasi1, Kah Seng Lee2, Long Chiau Ming3, Chin Fen Neoh4, Mahmoud E. Elrggal5,Zaheer-Ud- Din Babar6, Tahir Mehmood Khan7 and Muhammad Abdul Hadi8*AbstractBackground: Globally, cancer is one of the leading causes of mortality. High treatment cost, partly owing to higherprices of anti-cancer drugs, presents a significant burden on patients and healthcare systems. The aim of thepresent study was to survey and compare retail prices of anti-cancer drugs between high, middle and low incomecountries in the South-East Asia, Western Pacific and Eastern Mediterranean regions.Methods: Cross-sectional survey design was used for the present study. Pricing data from ten counties includingone from South-East Asia, two from Western Pacific and seven from Eastern Mediterranean regions were used in thisstudy. Purchasing power parity (PPP)-adjusted mean unit prices for 26 anti-cancer drug presentations (similarpharmaceutical form, strength, and pack size) were used to compare prices of anti-cancer drugs across three regions. Astructured form was used to extract relevant data. Data were entered and analysed using Microsoft Excel®.Results: Overall, Taiwan had the lowest mean unit prices while Oman had the highest prices. Six (23.1%) and nine (34.6%) drug presentations had a mean unit price below US$100 and between US$100 and US$500 respectively. Eightdrug presentations (30.7%) had a mean unit price of more than US$1000 including cabazitaxel with a mean unit priceof $17,304.9/vial. There was a direct relationship between income category of the countries and their mean unit price;low-income countries had lower mean unit prices. The average PPP-adjusted unit prices for countries based on theirincome level were as follows: low middle-income countries (LMICs): US$814.07; high middle income countries (HMICs):US$1150.63; and high income countries (HICs): US$1148.19.Conclusions: There is a great variation in pricing of anticancer drugs in selected countires and within their respectiveregions. These findings will allow policy makers to compare prices of anti-cancer agents with neighbouring countriesand develop policies to ensure accessibility and affordability of anti-cancer drugs.Keywords: Anti-cancer drugs, Pricing, South-East Asia, Western Pacific, Eastern MediterraneanBackgroundEarlier diagnosis and longer treatment durations con-tribute to rising expenditure on medicine for cancercare. Access to cancer treatment can be a challenge,since it is significantly affected by cost, particularly inlow and middle-income countries. According to theGlobal Oncology Trend Report [1], global spending oncancer medications rose from $75 billion in 2010 to$100 billion in 2014, 10.3% rise in spending. Medicationcost is a strong predictor of adherence [2, 3] with therisk of cost-related non-adherence being higher for thosewith lower income and higher out-of-pocket (OOP) drugspending [3].These growing costs inevitably provokeconcern regarding the financial burden experienced bycancer patients [1]. This concern is even more promin-ent in Asia because it is home to half of the world’s ex-tremely poor population [4].Asia accounts for 60% of the world population and50% of the global burden of cancer [4]. The projected in-crease in cancer incidence is predicted to be most* Correspondence: muhammad.hadi@dmu.ac.uk8Leicester School of Pharmacy, De Montfort University, Leicester, UKFull list of author information is available at the end of the article© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Salmasi et al. BMC Cancer  (2017) 17:903 DOI 10.1186/s12885-017-3888-ysignificant in low and medium—income countries inAsia [4, 5].Asia is very heterogeneous in terms of healthcare sys-tems. With the exception of a few high-income countriessuch as Israel, Kuwait, Qatar, the Republic of Korea,Singapore, and the United Arab Emirates who enjoywell-developed health services, the vast majority of theAsian people face a substantial cancer burden becausecancer care remains a low priority in healthcare planningand expenditure [4]. In these countries, over 60% of thetotal healthcare expenditure comes from private re-sources, of which more than 80% is direct out of pocketpayments, with catastrophic results for most families inthese countries [4]. Similarly, in the Middle East, spend-ing per capita on cancer drugs is considerably less thanin Europe or the US [6]. The cancer drug expenditure asa percentage of total drug expenditure is very low inMiddle Eastern countries [6].In this study, we aim to build on the existing body ofwork by providing comparable cancer drug retail pricesacross countries in the South-East Asian [SEA], WesternPacific (WP) and Eastern Mediterranean (EM) regions.A review based approach utilising selective content ana-lysis has been adopted to achieve the objective of thispaper. A previous study on comparing cancer drugprices focused on 18 high-income countries, member ofeconomic co-operation and development (OECD) coun-tries, in Europe and Oceania [7]. To our knowledge, thisis one of the very first initiatives taken to compare theretail price of cancer drugs across countries in theSouth-East Asia, Western Pacific and Eastern Mediterra-nean regions. By analysing and comparing the unitprices across Asian countries with differing gross na-tional income (GNI) per capita, we are hoping to assistin improving procurements, price negotiations, and loca-tion of new supply sources, and ultimately to create anopportunity for patients in Asia to gain access to moreaffordable cancer treatments.MethodsCountry selectionThe following criteria were adopted for the inclusion ofcountries: Geographically located in the South-East Asian,Western Pacific or Eastern Mediterranean regions Availability of drug pricing data published byrespective pricing/health authorities.Based on the inclusion criteria, Thailand was the only eli-gible country from South-East Asia, Malaysia and Taiwanwere included from the Western Pacific, and Oman,Pakistan, the United Arab Emirates, Lebanon, Egypt, SaudiArabia and Bahrain from the Eastern Mediterraneanregion. Countries in the Asia Pacific [Australia and NewZealand] were excluded from this study, despite being partof the Western Pacific region, as they had already beencovered in previous studies [7]. The included countrieswere classified into Low income [LIC], low middle income[LMIC], high middle income [HMIC] and high income[HIC] countries based on their GNI per capita, using thecut off points provided by the world bank website [8]. TheUnited Nation’s 3-letter standard abbreviations [ISOALPHA-3 code] were used to represent country names inTables 1, 2 and 3. [9]Data sourcesThe price of the cancer drugs in the ten included coun-tries was retrieved from official pricing authorities or therespective Ministry of Health or equivalent websites[Table 1]. The authors ensured that the prices were re-trieved from the most recent price lists published by therespective countries. The prices retrieved for Bahrain,Lebanon, Oman and Taiwan were published in 2016 andthe prices for the remaining countries were published in2015. However, the exact publication date of the pricingdata was unclear.The GNI per capita [USD] of nine of the ten includedcountries was retrieved from the World Bank website.For Taiwan, however, the data had to be retrievedfrom Taiwan’s national statistics bureau [10] since thecountry is not a member of United Nations and wasnot listed on the World Bank website. The respectiveGNI per capita and country classifications are shownin Additional file 1: Table S2.Medicine selectionA cross–country comparison of 31 selected samples ofcancer drugs was made by Vogler et al. [7] whereby theselection of drugs was also dependent on the data avail-ability and availability of comparable products in themarket in at least ten countries. In this study, the same31 drug presentations were chosen initially as a guide.The inclusion criterion for selecting a drug presenta-tion was the availability its pricing data in at least fourout of the ten countries.Data analysisThe price data were reviewed by the six co-authors. As theunit of measurement, we selected retail price per unit [i.e.per tablet/capsule or per vial]. Retail prices were chosen inthis study because they represent the patients’ actual out ofpocket expenditure. Another advantage of using retailprices is that they include all the add-ons such as taxes,distribution and pharmacist fees; these add-ons sometimeslead to the final price costing more than double the actualcost of the drug [11, 12]. The other reason for the useof retail prices was that ex-factory prices are hard toSalmasi et al. BMC Cancer  (2017) 17:903 Page 2 of 11measure accurately, especially in countries that haveno publicly funded drug coverage. [12]Prices were only included if they referred to the samepresentation in terms of pack size, strength and pharma-ceutical form. Pricing data were originally extracted andpresented in national currencies but later converted toUSD using purchasing power parity (PPP) to allow faircomparison between different countries. Microsoft Excelwas used for PPP-related calculations. Purchasing powerparity rates were retrieved from the World Bank website[8]. The purchasing power parity conversion rates usedare presented in Additional file 1: Table S1. The meanunit prices were calculated for each drug presentation aswell as for each country. The high/low ratio for eachpresentation was calculated by dividing the highest unitprice of the presentation by the lowest unit price of thesame presentation to analyze the inter-country variabilityof the price for every presentation. A high/low ratio of10 implies that the highest unit price is ten times moreexpensive than the lowest unit price. All calculationswere performed in Microsoft Excel. All statistical ana-lyses were descriptive.In order to present the price comparison more effect-ively, the results have been arranged into the World Bankcategories and comparisons are made accordingly. Of theten included countries, one country [Pakistan] is classifiedas a low-income country, one [Egypt] as middle-income,three [Thailand, Malaysia and Lebanon] as higher-middleincome, and five [the United Arab Emirates, Bahrain, SaudiArabia, Oman and Taiwan] as high-income countries.ResultsUpon applying the selection criteria for presentations, thefollowing presentations that were originally in Vogler etal.’s study [7] were excluded from this study due to a lackof pricing information for at least four countries: benda-mustine [HCl], bevacizumab [16 ml vial], clofarabine, eri-bulin mesylate, lenalinomide, nelarabine, ofatumumab,plerixafor, sorafenib [112-tablet pack], temsirolimus andvemurafenib. On the other hand, five additional presenta-tions for which price data was available in the includedregions were added to the list: nilotinib 200 mg, suni-tinib 12·5 and 25 mg, trastuzumab 440 mg, and sorafenib[60-tablet pack].We were unable to find pricing data on sorafenib [the112-tablet box] so we replaced it with the 60-tablet boxfor which pricing data was available. Moreover, we foundadequate data for trastuzumab 440 mg in the regions ofinterest, therefore we added it to the list despite alreadyhaving a presentation for this drug [trastuzumab 150 mg].Although it was expected that the two would follow thesame pattern, the pricing data was included to providemore information for the readers. The same was true forsunitinib [12·5 mg, 25 mg and 50 mg] and nilotinib[150 mg and 200 mg].The final number of included presentations was 26.Table 2 provides an overview of the selected drugs withregards to their FDA-approved indications, selected pres-entation and country coverage. We only compared pricesfor the originator drugs because pricing policies for origin-ator drugs differ substantially from generic vials.Table 1 Data sources used in this studyCountries Data sources SpecificationUAE United Arab Emirates Ministry of Health Drug DepartmentURL:http://www.cpd-pharma.ae/downloads/Price-List-February/MoH-Price-List-as-on-07-Feb-2015.pdfThe data was retrieved from MOH, drug department.The Document includes both imported and genericdrugs and it was last updated on Feb 2015.Bahrain National Health Regulatory AuthorityURL: http://www.nhra.bh/SitePages/View.aspx?PageId=42The Drug Price List includes both innovator and genericmedicines prices. Last updated on 14 March 2016Taiwan National Health Insurance Administration, Ministry of Health and WelfareURL: http://www.nhi.gov.tw/query/Query1.aspxThe data was retrieved from Ministry of Health andWelfare of Taiwan. The Document includes both importedand generic drugs and it was last updated on June 2016.Thailand Drug And Medical Supply Information Center, Ministry of Public HealthURL: http://dmsic.moph.go.th/dmsic/index.php?p=1&type=3&s=3&id=p_drug_normal_en&lang=enThe Drug Reference Price list provides the medicalsupplies prices for commercial sector. Last updatedon March 2015.Malaysia Pharmaceutical Services Division, Ministry of HealthURL: http://www.pharmacy.gov.my/v2/en/apps/drug-priceThe Consumer Price Guide provides retail price list toserve as guidance to patients when purchasing medicines.Lebanon Ministry of Public HealthURL: http://www.moph.gov.lb/Drugs/Pages/Drugs.aspxThe data was retrieved from the MoPH Drugs PublicPrice List. Last updated on 16 February 2016Oman Ministry of Health https://www.moh.gov.om/en/web/dgpadc/resources The data was retrieved from the Ministry of Health,Sultanate of Oman website from the list of registereddrugs. Last updated on 17–05-2016.Pakistan PharmaGuide book, Pakistan edition, 24th edition. The pricing data was retrieved PharmaGuideBook. This handbook is published annually providingessential prescribing and trade information. The pricingdata was retrieved from the latest edition (24th) publishedon March 2016.Salmasi et al. BMC Cancer  (2017) 17:903 Page 3 of 11Table 2 Background information about drugs included in the analysisaGeneric drugnameProduct name FDA approved indications Selected presentation Country coverage Unit price isprice of:# Missing dataAbirateroneacetateZytiga Metastatic castration-resistantprostate cancer120 tablets 250 mg 7 PAK, MYS, LBN 1 TabBevacizumab Avastin NSCLCMetastatic Colorectal cancer,GlioblastomaMetastatic Renal cell carcinomaMetastatic Her2 negative breastcancerMetastatic cervical cancer.One 4 ml vial containing25 mg/mL concentrate forsolution for infusion.6 MYS, SAU, OMN, LBN 4 ml vialBortemozib Velcade One vial containing 3·5 mgpowder for solution for injection.7 EGY, PAK, SAU 1 vialCabazitaxel JEVTANA® Metastatic hormone refractoryprostate cancerOne vial containing 60 mgconcentrate and solvent forsolution for infusion.4 EGY, PAK,THA, SAU,BHR,TWN,1 vialCetuximab Erbitux K-ras wild-type, EGFR-expressingmetastatic colorectal cancer.Recurrent/metastatic head andneck cancerOne vial containing 5 mg/mLsolution for infusion.4 ARE, EGY, PAK,SAU,OMN, BHR1 vialDenosumab Prolia Unresectable giant cell tumor ofbone in adults and skeletallymature adolescentsOne pre-filled syringe containing60 mg solution for injection6 PAK, MYS, SAU, BHR One pre-filledsyringeErlotinib HCl Tarceva Non-small cell lung cancer.Pancreatic cancer.30 film-coated tablets 150 mg 7 MYS, SAU, LBN 1 film-coatedTabEverolimus Afinitor Subependymal giant cellastrocytoma.HER2-negative breast cancer.Progressive neuroendocrineTumors of Pancreatic origin.Advanced renal cell carcinoma.30 tablets 10 mg 8 PAK, MYS, 1 TabGefitinib Iressa Non-small cell lung cancer 30 film-coated tablets 250 mg 7 EGY, SAU,PAK 1 film coatedTabGemcitabine Gemita (Atco) Ovarian cancerBreast cancer.NSLCLCPancreatic cancer1 vial containing 1 g powderfor solution for infusion.9 SAU 1 vialImatinibMesylateGlivec (Novertis) Dermatofibrosarcoma protuberans.Gastrointestinal stromal tumor.Myelodysplastic/myeloproliferativeneoplasms.Systemic mastocytosis.Chronic Eosinophilic leukemia.Chronic Myelogenous Leukemia60 film-coated tablets 100 mg 9 BHR 1 film coatedTabInterferonAlpha - 2BInteron A(Schering PloughAIDS related Kaposi Sarcoma.Hairy cell leukemia.Melanoma.NHLOne multi-dose pen containing3 million IU/0·5 mL solution forinjection.6 THA, EGY, MYS,OMN One multi-dose penLapatinibditosylateTykerb FC HER2 positive breast cancer, 70 film-coated tablets 250 mg 7 MYS, BHR, TWN 1 film coatedTabNilotinib Tasigna CML 112 capsules 150 mg 8 PAK, MYS 1 Cap112 capsules 200 mg 6 THA,LBN, OMN, BHR 1 CapPaclitaxelAlbuminIntaxel 30 mg/5 ml injNSCLCBreast cancer pancreatic cancerOne vial containing 5 mg/mlpowder for suspension for infusion.6 ARE, EGY, SAU, BHR 1 VialPanitumumab Vectibix 400 mg/20 ml IVColorectal Cancer One vial containing 20 mg/mlconcentrate for solution for infusion6 THA, PAK, MYS, TWN 1 VialPazopanib votrient 30 film-coated tablets 200 mg 8 PAK, MYS 1 film coatedTabAlimta (Eli Lilly) non-squamous NSCLC 9 OMN 1 VialSalmasi et al. BMC Cancer  (2017) 17:903 Page 4 of 11Unit priceTable 3 represents prices per package as well as the cal-culated unit prices in USD using PPP. Upon estimatingthe PPP, cabazitaxel was the most expensive drug with aunit price of $17,304·9/vial [in Oman]. Nilotinib 150 mghad the lowest unit price in USD [$19·22/tab in Egypt].The PPP adjusted USD unit prices for each medicationare represented in Fig. 1. The different unit prices areconnected to illustrate variations between countries. Toensure that the variations among prices is easy to dis-cern for both low price and high price medications,the two have been presented in two different figures.Figure 1a represents cancer drugs with unit price be-tween $0–1000, while Fig. 1b represents cancer drugswith unit prices between $1000–20,000.Mean unit priceSix presentations [23·1%] had a mean unit price below$100.00 and nine drugs [34·6%] had a mean unit price be-tween $100·00 and $500·00. Eight drugs [30·7%] had a meanunit price of over $1000.00, of which, one [cabazitaxel] hada mean unit price of over $5000·00 [$11,832·9/vial]. Overall,Taiwan had the lowest mean unit prices[$492·61] andOman the highest [$2355·6]. So Overall, Taiwan had thelowest mean unit prices for all presentations.The average unit prices by country income categorywere as follows: LMICs $814.07, HMICs $1150·63, HICs:$1148·19. Using PPP-adjusted mean unit prices, thethree most expensive presentations were found to becabazitaxel [$11,832·93], trastuzumab 440 mg [$4779·35],and panitumumab [$4146·99]. The three cheapest oncol-ogy drugs were lapatinib ditosylate [$40·08], pazopanibdisodium heptahydrate [$52·20], and imatinib [$56·92].The high/low ratioThe high/ low ratio data included in Table 3 allowed us tolook at the price deviation between countries. The high/low unit price ratio was less than 3 for fourteen drugs[53·80% of the 26 total included products], between 3 and6 for eight drugs [30·77%] and more than 6 for four drugs[15·38%]. The smallest high/low ratio was 1·07, whichbelonged to sunitinib malate 25 mg, and the largest high/low ratio belonged to Interferon alpha-2B [13·68] [Table 3].The frequency of unit prices ranked in quartilesBox plots have been constructed based on the unit $price of the included drugs. The boxplot for low andhigh price cancer medicines have been presented separ-ately in Fig. 2a and b to ensure that the differences areeasy to discern. The box plot displays the inter-quartilerange [IQR] as calculated by Microsoft Excel; the bottomand top of the box are the 25th and 75th percentiles [the1st and the 3rd quartiles, respectively], and the band inthe middle of the box is the median. The extended linesdescribe the bottom and top whiskers.Drug prices varied significantly across the includedcountries. Figure 3 represents the frequency of unit prices,as of February 2016, ranked in quartiles [Note: quartile 1and 4 are not inclusive of the minimum and maximumvalues; these values have been categorized and representedTable 2 Background information about drugs included in the analysisa (Continued)Generic drugnameProduct name FDA approved indications Selected presentation Country coverage Unit price isprice of:# Missing dataPemetrexedDisodiumHeptahydrateMalignant pleural mesothelioma One vial containing 20 mg/mlsolution for injection.Sorafenib Nexavar (BayerSchering)Liver cancerKidney cancerThyroid cancer60 film-coated tablets 200 mg. 5 THA, MYS, OMN,BHR,LBN1 film coatedTabSunitinibmalateSUTENT (Pfizer) Kidney cancerGastointestinal stromal tumourPancreatic Neuroendocrinetumours28 capsules 12.5 mg 7 OMN, LBN, BHR 1 Cap28 capsules 25 mg 4 THA, LBN, MYS,OMN, BHR, TWN,1 Cap28 capsules 50 mg 6 THA, LBN, MYS,OMN,1 CapTrastuzumab Herceptin(Roche)Her2 over expressing breastcancerHer2 over expressive Gastricor Gastroesophageal junctionAdenocarcinomaOne vial containing 440 mgpowder for concentrate forsolution for infusion4 THA, LBN, MYS,SAU,OMN, BHR1 VialOne vial containing 150 mgpowder for concentrate forsolution for infusion4 ARE, EGYP, PAK, LBN,MYS, TWN,1 VialZolendronicacidZOLDIC Multiple Myeloma One vial containing 4 mg/5 mlconcentrate for solution forinfusion4 ARE, LBN, MYS, OMN,BHR, TWN1 VialaThe National Cancer Institute. A to Z List of Cancer Drugs. USA: The National Institutes of Health U.S. Department of Health and Human Services, 2015Salmasi et al. BMC Cancer  (2017) 17:903 Page 5 of 11Table3PPP-adjustedpricesoftheselectedcanceroriginatordrugsinthe10surveyedcountriesconvertedtoUSDLowmiddleincomeHighmiddleincomeHighincomeGenericnamePresentationPAK($)EGY($)MYS($)LBN($)THA($)TWN($)OMN($)BHR($)ARE($)SAU($)MeanunitpricefordrugsHigh/LowratioAbirateroneacetate250mg120tabNA9724·22NANANANANANA8470·088867·6170·171·731tabNA81·04NANA52·0259·1090·2164·3370·5873·90Bevacizumab25mg/mlInj.100mg(4ml)NA1233·18NANA1473·00602·104122·80767·001157·95NA1559·506·85Bortemozib3.5mg1vialNANA3622·222243·964630·122443·023878·902771·382560·04NA3164·222·06Cabazitaxel60mg1vialNANA11,492·57112·50NANA17,304·95NA11,421·76NA11,832·932·43Cetuximab5mg/ml1vialNANA1100·491850·55997·12456·25NANANANA1101·104·06Denosumab60mg/ml1mlprefilledsyringeNA798·21NA607·36934·69417·41757·00NA665·27NA696·662·24ErlotinibHCl150mg30filmcoatedtab7315.3411,659·19NANANANANANA6837·45NA194·844·931filmcoatedtab243.84388·64NANA160.5478.76152.5789111.62227.915NAEverolimus10mg30tabNA8565·02NANANANANANA8514·648697·73300·531·831tabNA285·50NA274·21404·60220·25338·68307·24283·82289·92Gefitinib250mg30film-coatedtabletsNANANANANANANANA3938.70NA144·332·401film-coatedtabNANA173·85123·84157·5282·79198·89142·14131·29NAGemcitabine1gVial295·81210·77496·53227·33179·04271·28359·10256·57281·60NA286·452·77ImatinibMesylate100mg60film-coatedtab2485·805156·95NANANANANANA2920·713571·0256·923·411film-coatedtab41·4385·9563.4925·2374·1441·4372·47NA48·6859·50InterferonAlpha-2B1mIU/injection1multidosepen208·81NANA21·02NA26·80NA72·7165·69287·50113·7613·68Lapatinibditosylate250mg70film-coatedtablets3341.731926·91NANANANANANA2526·364190·3440·082·681filmcoatedtab47.7427·53NA32·3922·30NA54·68NA36·0959·86Nilotinib150mg112capsNA2152·47NANANANANANA7906·289474·4366·075·561capNA19·22NA59·1670·7643·68106·9573·6270·5984·59Nilotinib200mg112caps15,113·642982·06NANANANANANA11,069·2512,631·8292·785·071cap134·9426·62116·07NANA67·44NANA98·83112·78PaclitaxelAlbumin5mg/ml1vial213·07NA125624·90242·7091·86348·21NANANA274·296·80Panitumumab20mg/ml1vialNA4932·74NANANANA7223·841291·005804·391482·964147·005·60Pazopanib200mg30tabNA762·33NANANANANANA1604.181994·8952·203·191tabNA25·411NA36.9251·5944·808157·9053·4766·496PemetrexedDisodiumHeptahydrate500mg1vial2485·803295·96694·44624·77795·70502·78NA2879·243200·213307·961976·326·58Sorafenib200mg6×10’stablets8267·055025·56NANANaNANANA4920·296620·4697·231·91Salmasi et al. BMC Cancer  (2017) 17:903 Page 6 of 11Table3PPP-adjustedpricesoftheselectedcanceroriginatordrugsinthe10surveyedcountriesconvertedtoUSD(Continued)LowmiddleincomeHighmiddleincomeHighincomeGenericnamePresentationPAK($)EGY($)MYS($)LBN($)THA($)TWN($)OMN($)BHR($)ARE($)SAU($)MeanunitpricefordrugsHigh/Lowratio1tab137·7883·76NANANA72·27NANA82·00110·34Sunitinibmalate12.5mg30caps3597·662578·48NANANANANANA3323·223425·57108·221·751cap119·9285·95150·47NA89·287·03NANA110·77114·19Sunitinibmalate25mg30caps7121·807134·08NANANANANANA6646·446851·71231·281·071cap237·39237·80NANANANANANA221·55228·39Sunitinibmalate50mg30caps13,943·1810,762·33NANANANANANA13,292·8913,703·98405·561·491cap464·77358·74NANANA312·31NA397·62443·096456·80Trastuzumab440mg1vial4616·484686·10NANANA3930·91NANANANA4779·351·50Transtuzumab1501vialNANANANA1240·85NA2599·531857·335883·892133·521957·812·09Zolendronicacid4mg/5ml1vial674·72605·38NANA268·79NANANANA845·45598·593·15Meanunitpriceforeverycountry708·75919·391803·51990·30658·09492·612355·60789·261496·34607·13Averageunitpricebyworldbankcategories814.071150.631148.19Salmasi et al. BMC Cancer  (2017) 17:903 Page 7 of 11separately using unique colours of their own]. Thailandand Taiwan had prices at the lower end, prices in Lebanonmainly fell in the first quartile, while prices in theUnited Arab Emirates and Bahrain fell in the secondand third quartiles. Prices in Oman and Saudi Arabiawere at the upper end [Fig. 3]. Prices in Oman wereranked the most expensive for eight presentations(Additional file 1: Table S3).Prices in high income countries are at the upper end,and are ranked as the maximum for 13 of the includedpresentations, while prices in low middle income coun-tries were ranked the most expensive for six presenta-tions only [Fig. 4].DiscussionThe aim of the present study was to survey and compareretail prices of anti-cancer drugs between high, middleand low-income countries in the South-East Asia, WesternPacific and Eastern Mediterranean regions. In the absenceof a systematic pricing system, pharmaceutical companiesdetermine the drug price according to what the society canafford, as people are ready to face a heavy financial burdenwhen it comes to treating fatal diseases [13]. In some devel-oped countries, price regulation measures such as externalreference pricing or international reference pricing havebeen widely used by policymakers to restrain drug costs.External reference pricing is defined by the WHO as: “Thepractice of using the price[s] of a medicine in one or severalcountries in order to derive a benchmark or reference pricefor the purposes of setting or negotiating the price of theproduct in a given country” [14].A list of 2010 cancer drug prices, has been publishedby the Management Sciences for Health based on theWHO’s 17th edition of the Essential Medicines List [15].This is the only procurement tool available to the pricingauthorities in LMICs, however, more support is neededsuch as an updated WHO essential medicine list sectionon oncology drugs along with cross-country pricing in-formation and procurement guidance. Although theWestern Pacific Region office of the WHO has devel-oped a Price Information Exchange that provides com-parative information on procurement prices for selectedmedicines across the Western Pacific region [15], it hasfaced many challenges such as lack of cooperation fromFig. 2 a Boxplots of incuded cancer drugs with mean USD unit price between 1 and 1000. b Boxplots of included cancer drugs with mean USDunit price between 1,000 and 20,0000Fig. 1 a Included cancer drugs with unit prices between 1-1000 USD stratified by country. b Included cancer drugs with unit prices between1000-20,000 USD stratified by countrySalmasi et al. BMC Cancer  (2017) 17:903 Page 8 of 11member countries. This is why we have attempted toundertake our own cross-country price comparison [13].Purchasing power parity conversion rates were usedinstead of exchanges rate in this review. Exchange ratesdetermine the producers’ actual profit from foreign salesin terms of domestic currencies [16], and can be usedwhen performing pharmaco-economic studies within acountry since the expected exchange rate fluctuationswould affect all drugs sourced from the same country,uniformly. In cross-country comparisons, however, toovercome the effect of large fluctuations in exchange rates,the PPP is used as an alternative sensitivity analysis [17].Purchasing power parity conversions are also argued to bemore apt for comparisons at final consumer level [16].Our review showed extreme variation between drugprices across countries; the high/low ratios were as highas 13·68 [PPP-adjusted]. While patents can explain theprice differences between drugs, they are not responsiblefor the price differences observed for the same medicine.Greater transparency of price information amongcountries may assist with in-country negotiations be-tween purchasers and suppliers. Information on theavailability of cheaper medicines in neighbouring coun-tries has the potential to encourage policy and manager-ial decisions at national levels in an effort to reduceprices [15]. Economic evidence on the impact of externalreference pricing is scarce. Only a few studies have expli-citly analysed the impact of external price referencing onmedicine prices. Stargardt et al., [18] using an analyticmodel to simulate the effect of a price reduction inGermany demonstrated that every 1 EURO reduction inprice in Germany would lead to a reduction of EURO0.15 to EURO 0.36 in 15 European countries that useexternal reference pricing. Similar results were reportedFig. 4 Frequency of PPP-adjusted unit prices ranked in quartiles for each income groupFig. 3 Frequency of PPP-adusted unit prices ranked in quartiles for each countrySalmasi et al. BMC Cancer  (2017) 17:903 Page 9 of 11by Windmeijer et al. [19] who investigated the result ofexternal reference pricing implementation on prices inNetherlands. Our study can hence be used by officials toimprove access to cancer treatment [13].LimitationsCross-country comparison of pharmaceutical prices ischallenging because of the differing level of sales, fre-quent changes in exchange rates and the differences inthe pharmaceutical presentations such as strength, packsize, dose and dosage form. Of the 57 countries in theSouth-East Asia, Eastern Mediterranean and WesternPacific regions (excluding Australia and New Zealand),we only managed to find reliable pricing information forten countries only due to: [i] under-developed/incom-plete/not-user-friendly websites of official pricing/heathauthorities; [ii] use of languages other than English in of-ficial websites; [iii] lack of public access to official drugprices; and [iv] absence of an official institution tosummarize/compare prices across Asia. However, wemanaged to include representative countries from differ-ent ranges of GNI per capita. The other key limitationsof this study are as follows: Firstly, the prices may notreflect the true cost of medications because the retrieveddata are the official prices as published by the pricingauthorities without consideration of [usually confiden-tial] discounts and rebates. Secondly, this study used re-tail prices, which include add-ons such as taxes anddistribution fees. Understanding of the amount andsources of add-ons would identify potential targets forprice reduction. Unfortunately, data on add-ons was lim-ited and hence we were unable to estimate them.Thirdly, the use of PPP calculations for price comparisonrequired the assumptions that the value of goods andservices are homogeneous across countries and thatinternational shipment of goods takes place instantan-eously, and with no cost. Unit prices were used to com-pare results in this study, when interpreting the resultsof this study, it should be kept in mind that one unitmay refer to the daily dose of a tablet, or monthly vialfor injection or a weight based two weekly injections.Future studies should use the data provided in this studyand perform a price comparison using monthly dose ortotal treatment cost, as a unit for measurement andcomparison. Finally, pricing revisions are done at irregu-lar intervals and the price lists may not be updated im-mediately. However, most recently available prices wereused for calculations.ConclusionThe significant price differences among Asian countriesis very evident. Taiwan had the lowest mean unit price[$492·61] and Oman the highest [$2355·60]. Significantvariation between drug prices across countries with thehighest high/low ratio was seen for Interferon alpha-2B:13.68. Cabazitaxel was ranked the most expensive drugin our sample with a mean unit price of $17,304·95.These discrepancies indicate that greater price transpar-ency is required. Our goal was to compare cancer drugprices and investigate whether the prices are significantlydifferent among countries. Significant differences werefound and reported accordingly, however, what this pricedifferences mean in terms of access to cancer medica-tions, government spending, and patient adherence, re-quires a much more in-depth analysis of each country’srespective health care system, which was beyond thescope of this paper.Our results can be used to help policy makers to com-pare the price of anti-cancer agents in their country withthat in neighbouring countries to decide if further policymeasures related to drug prices are required.Key issues Anti-cancer drug prices are highly variable in theSouth-East Asian, Western Pacific and EasternMediterranean regions. There is an association between price of anticancerdrugs and income category of the country. Almost one in three drugs assessed in this study hada mean unit price of more than US$ 1000. There is a need to review pricing policy in order toimprove accessibility and affordability of cancerdrugs in the selected countries.Additional fileAdditional file 1: Table S1. The purchasing power parity conversionrates used. Table S2. The respective GNI per capita and countryclassifications. Table S3. (XLSX 72 kb)AcknowledgementsThe authors are thankful to Mr. Allah Buksh, PhD Scholar at school ofPharmacy, Monash University Malaysia for his assistance in retrieving theprices of anticancer drugs from Pakistan.FundingNo funding from any public or private funding agency was obtained for thisstudy.Availability of data and materialsThe datasets used and/or analysed during the current study available fromthe corresponding author on reasonable request.Authors’ contributionsTMK, LCM and MAH conceived the idea. TMK, LCM, MAH, KSL, CFN and MEEextracted data. SS, KSL and TMK analysed data. SS, TMK, LCM drafted the initialversion of the manuscript. MAH, MEE, ZUD, CFN revised the manuscript withintellectual input. All authors have read and approved the final version of thepaper for publication.Ethics approval and consent to participateSince it was a pricing review, ethics approval was deemed not necessarytherefore not obtained.Salmasi et al. BMC Cancer  (2017) 17:903 Page 10 of 11Consent for publicationNot Applicable.Competing interestsThe authors declare that they have no competing interests.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.Author details1Collaboration for Outcomes Research and Evaluation, Faculty ofPharmaceutical Sciences, University of British Columbia (UBC), Vancouver,Canada. 2Pharmaceutical Services Division, Ministry of Health, Petaling Jaya,Selangor, Malaysia. 3Unit for Medication Outcomes Research and Education(UMORE), School of Medicine, University of Tasmania, Hobart, Australia.4Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor,Malaysia. 5College of Pharmacy, Umm-Al-Qura University, Makkah, SaudiArabia. 6Department of Pharmacy, School of Applied Sciences, University ofHuddersfield, Huddersfield, UK. 7School of Pharmacy, Monash UniversityMalaysia, Subang Jaya, Malaysia. 8Leicester School of Pharmacy, De MontfortUniversity, Leicester, UK.Received: 16 December 2016 Accepted: 8 December 2017References1. QuntilesIMS Institute. Developments in Cancer Treatments, MarketDynamics, Patient Access and Value: Global Oncology Trend Report 2015.Available at, https://morningconsult.com/wp-content/uploads/2016/06/IMS-Institute-Global-Oncology-Report-05.31.16.pdf. [Assessed June 10, 2016].2. Taira DA, Wong KS, Frech-Tamas F, Chung RS. Copayment level andcompliance with antihypertensive medication: analysis and policyimplications for managed care. Am J Manag Care. 2006;12(11):678–83.3. Mojtabai R, Olfson M. Medication costs, adherence, and health outcomesamong Medicare beneficiaries. Health Aff. 2003;22(4):220–9.4. Sankaranarayanan R, Ramadas K, Qiao YI. Managing the changing burden ofcancer in Asia. BMC Med. 2014;2(1):1–17.5. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancerstatistics. CA Cancer J Clin. 2011;61(2):69–90.6. Kasteng F, Wilking N, Jönsson B. 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[Assessed June 10, 2016].11. World Health Organisation, Pharmaceutical Pricing Policy: Financing andsustainability in Management sciences for Health. 2013. p. 9.12.12. Wagner JL, McCarthy E. International differences in drug prices. Annu RevPublic Health. 2004;25:475–95.13. Hoen E. Access to cancer treatment: A study of medicine pricing issues withrecommendations for improving access to cancer medication. 2014. Availableat https://www.oxfam.org/sites/www.oxfam.org/files/file_attachments/rr-access-cancer-treatment-inequality-040215-en.pdf. [Assessed June 10, 2016].14. Rémuzat C, Urbinati D, Mzoughi O, El-Hammi E, Belgaied W, Toumi M.Overview of external reference pricing systems in Europe. Journal of MarketAccess & Health Policy. 2015;3:27675. http://dx.doi.org/10.3402/jmahp.v3.27675.15. World Health Organization. Price information exchange for selectedmedicines in the Western Pacific Region. Available at https://www.piemeds.com/. [Assessed June 10, 2016].16. U.S. International Trade Commission. Pricing for prescription drugs. 2000.Available at https://www.usitc.gov/publications/docs/pubs/332/PUB3333.PDF. [Assessed June 10, 2016].17. Shi L, Hodges M, Drummond M, Ahn J, Li SC, Hu S, et al. Good researchpractices for measuring drug costs in cost-effectiveness analyses: aninternational perspective: the ISPOR drug cost task force report—part VI.Value Health. 2010;13(1):28–33.18. Stargardt T, Schreyogg J. Impact of cross-reference pricing on pharmaceuticalprices: manufacturers' pricing strategies and price regulation. Appl Health EconHealth Policy. 2006;5(4):235–47.19. Windmeijer F, de Laat E, Douven R, Mot E. Pharmaceutical promotion andGP prescription behaviour. Health Econ. 2006;15(1):5–18.•  We accept pre-submission inquiries •  Our selector tool helps you to find the most relevant journal•  We provide round the clock customer support •  Convenient online submission•  Thorough peer review•  Inclusion in PubMed and all major indexing services •  Maximum visibility for your researchSubmit your manuscript atwww.biomedcentral.com/submitSubmit your next manuscript to BioMed Central and we will help you at every step:Salmasi et al. BMC Cancer  (2017) 17:903 Page 11 of 11

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