Vol. 48 No. 4 October 2014 Journal of Pain and Symptom Management 649

Original Article

Cross-Sectional Pilot Study to Monitorthe Availability, Dispensed Prices, andAffordability of Opioids Around the GlobeLiliana De Lima, MHA, Tania Pastrana, MD, Lukas Radbruch, MD, andRoberto Wenk, MDInternational Association for Hospice and Palliative Care (L.D.L., L.R., R.W.), Houston, Texas, USA;

Department of Palliative Medicine (T.P.), RWTH Aachen University, Aachen, Germany; Department

of Palliative Medicine (L.R.), University Hospital Bonn, and Centre for Palliative Medicine (L.R.),

Malteser Hospital Seliger Gerhard Bonn / Rhein-Sieg, Bonn, Germany; and Fundacion FEMEBA

(PAMP-FF) (R.W.), La Plata, Argentina

Abstract

Context. Opioids are essential medicines. The World Health Organization and

Health Action International monitor the price of essential medicines. However,their surveys do not include opioids, and there is no information on theiraffordability.

Objectives. To provide information on access to pain treatment, as measured bythe availability and dispensed price of five opioids in 13 formulations, and theaffordability of oral immediate-release (IR) morphine.

Methods. The International Association for Hospice and Palliative Caremembers were distributed by their countries’ Gross National Income (GNI) levelusing the World Bank categories, i.e., high income country (HIC), upper middleincome country (UMIC), lower middle income country (LMIC), low incomecountry (LIC), and randomized. A total of 10 participants were selected from each(n¼ 40) domain. Participants were asked to identify a pharmacy located closest toa public facility that provides diagnosis/treatment for life-threatening conditionsand report the lowest dispensed price of the smallest selling unit and strength ofeach formulation. Availability and median (Me) price were calculated for each.Affordability and percentage of international buyer price (IBP) were calculatedfor morphine oral solid IR.

Results. A total of 30 participants from 26 countries (response rate¼ 75%)responded. Significant correlation was found between availability and GNI(range: 65e68% [HIC and LIC]; R¼ 0.781; P< 0.0001). Injectable andmorphine oral solid sustained release (SR) were the most available (59% and55%). Methadone (oral) was the least expensive (Me¼ 0.5) followed by fentanyl(transdermal; Me¼ 2.2). The Me price for morphine oral solid IR and ratiosbetween dispensed and IBP were lower in HIC than in LMIC (price¼ 0.03 vs.

Address correspondence to:LilianaDeLima,MHA, Inter-national Association for Hospice and Palliative Care,5535 Memorial Drive, Suite FdPMB 509, Houston,TX 77007, USA. E-mail: ldelima@iahpc.com

Accepted for publication: December 9, 2013.

� 2014 American Academy of Hospice and PalliativeMedicine. Published by Elsevier Inc. All rights reserved.

0885-3924/$ - see front matterhttp://dx.doi.org/10.1016/j.jpainsymman.2013.12.237

650 Vol. 48 No. 4 October 2014De Lima et al.

0.16; ratio¼ 2.23 vs. 0.03). Affordability for morphine oral solid IR was five days(Me¼ 0.1; range¼ 29e0.25).

Conclusion. Patients in LMIC and LIC have limited access to opioids, and thereare subsidies in place for more expensive medications and formulations in all GNIlevels, but not for morphine oral solid IR. Additional research is necessary toidentify the reasons behind these findings. J Pain Symptom Manage2014;48:649e659. � 2014 American Academy of Hospice and Palliative Medicine.Published by Elsevier Inc. All rights reserved.

Key Words

Essential medicines, opioids, availability, accessibility, affordability

14 15

IntroductionThe World Health Organization (WHO)

recognizes palliative care and pain relief ascritical public health issues.1e3 Strong opioidsare a cornerstone of pain treatment, of whichmorphine is considered essential by the WHO.4

In 2007, the International Association for Hos-pice and Palliative Care (IAHPC) developed alist of Essential Medicines (EMLs) in PalliativeCare,5 which includes opioids for the treatmentof pain and other symptoms. Still, inmany coun-tries, limited or no access is a significant prob-lem. Developing countries with about 80% ofthe world population account for 6% of theglobal morphine consumption3 resulting inmil-lions of patients suffering needlessly.

Access to opioids is limited owing to severalreasons, including restrictive drug control lawsand regulations, lack of education, and highprices.6,7 In developing countries, they havebeen reported to be more expensive than indeveloped nations,8e11 and prices in small citiesand rural areas are higher than in large cities.12

Opioid pricing is impacted by additional fac-tors, such as markups resulting from safetyand security measures required by the nationallaws on the manufacturing, importation, distri-bution, storage, and dispensation of controlledmedicines. Pricing is also affected by the type offormulation, namely complex delivery mecha-nisms, such as transdermal patches (TPs); trans-mucosal or SR formulations are costlier tomakethan immediate release (IR) oral formulations(solid or liquid).

The WHO and Health Action International(HAI) developed a method to monitor andreport the price of essential medicines asa measure of access,13 which has promptedsome governments to lower the cost of

medicines. However, with one exception,the WHO/HAI surveys do not include opioids,and there is limited information on their priceand affordability. In 2008, the IAHPC decidedto develop theOpioid PriceWatch (OPW) Proj-ect as a component of the agreement of work asa nongovernmental organization in formalrelations with the WHO. This article describesthe pilot study implemented to test the OPW.

ObjectivesThe objectives of the article are to:

1. Provide information on opioid availabilityglobally;

2. Show opioid price patterns among regionsand countries, as reflected in differencesin treatment costs, affordability, and dif-ferences in prices as a ratio of the interna-tional reference price; and

3. Allow further analysis of the difficultiesin availability and affordability of opioidanalgesics and suggest possible strategiesaddressing the identified problems.

MethodsThe study design was a cross-sectional study.16

The project proposal is available on the IAHPCweb site in http://hospicecare.com/resources/opioid-price-watch/. An ethics review boardfrom the Fundacion FederacionMedica de Bue-nos Aires in Argentina approved the study.The opioids were selected using the

following criteria:

1. Included in the 17th edition of the WHOModel EMLs4

2. Included in the IAHPC EML but notincluded in the WHO EML5

Vol. 48 No. 4 October 2014 651Access to Opioids Around the Globe

The following medications and formulationswere selected.

1. Fentanyl TPs2. Hydromorphone (injectable, oral liquid,

oral solid IR, and oral solid SR)3. Methadone (oral liquid and oral solid)4. Morphine (injectable, oral liquid, and

oral solid [IR and SR])5. Oxycodone (oral solid IR and SR)

All member states of the United Nationsreport consumption of these medications tothe International Narcotics Control Board.17

The study sample was selected using theIAHPC members’ list following a stratifiedrandom sampling:

1. The IAHPC members were listed by coun-try in alphabetical order.

2. Countries were stratified by their GrossNational Income (GNI) using the WorldBank categories: low income countries(LICs), low middle income countries(LMICs), upper middle income countries(UMICs), and high income countries(HICs).18

3. The IAHPC members were listed by theircorresponding country’s GNI and eachlist was randomized.19

4. The first 10 participants in each categorywere selected, resulting in 40 potentialparticipants.

Selected individuals were contacted bye-mail and invited to participate. Wheneverone declined the invitation or if he/she didnot reply, the next individual in the list wasinvited.

Participants were informed of the objectivesof the study, total estimated time to completethe survey, that their names would be acknowl-edged, and that the data presented would belinked to their countries. A signed informedconsent was submitted by all before completingthe survey. Participants were asked to select thepharmacy located closest to a public health fa-cility that provides diagnostic and treatmentservices for patients with life-threatening condi-tions. They were asked to speak to the chiefpharmacist. A letter describing the projectand identifying them as participants of thestudy was shown to the pharmacist. Participantswere instructed to inquire if at least one of theopioids included in the study was available and

dispensed for ambulatory patients. If opioidswere not available or the pharmacist was unwill-ing to cooperate, they were asked to go to thenext nearest pharmacy and to continue thisprocess until they located one pharmacy thathad at least one opioid available and wherethe chief pharmacist was willing to collaborate.Participants were asked to record in their localcurrency the lowest retail dispensed price of thesmallest selling dose and unit for the opioid for-mulations available on the day they completedthe survey. The address of the surveyed phar-macy was also recorded to avoid potential dupli-cation. The Appendix (available at jpsmjournal.com) includes a sample of the survey form.The completed survey was submitted viathe IAHPC server http://hospicecare.com/opioids/reports/add. Data were collectedfrom September 2012 to April 2013. Priceswere converted to U.S. Dollars (USD) usingGoogle Finance Converter.20 Survey resultswere exported to Microsoft Excel and IBMSPSS Statistics 21.

DefinitionsThe following definitions were applied in

the study:13

Accessibility: The extent that patientscan obtain the opioid medications they needfor pain reliefdpatient access is not possibleunless opioids are available and affordable.

Affordability: Total number of days requiredby a patient earning the minimum wage to pur-chase a 30-day treatment of medications at thedispensed price.21

Availability: Existence of the opioid medi-cation in stock at the pharmacy to bedispensed to patients arriving at the phar-macy with a legitimate medical prescription.It was calculated by the percentage of opioidsavailable at the moment the survey wascompleted, with 13 being the maximum num-ber of formulations. The amount of pharma-cies visited before finding one that had any ofthe opioids included in the study wasrecorded.

Dispensed Price: Pharmacy selling price plusany fees and any sales taxes. Dispensed pricefor a 30-day treatment for each medicationwas calculated by dividing the price of thepackage/bottle by the total milligrams ineach, and then multiplying the resulting priceper milligram by the corresponding monthly

652 Vol. 48 No. 4 October 2014De Lima et al.

treatment of the Defined Daily Dose (DDD;13

Table 1). The DDD is the average maintenancedose per day for a drug used for its main indi-cation in adults established by the WHOCollaborating Center for Drug Statistics Meth-odology.22,23 The DDD is a quantitative mea-sure for statistical purposes only and not tobe used as a treatment guideline.

Median (Me) Price: The middle value in adistribution, above and below which lie anequal number of the highest and lowest pricesrecorded for each medication.

Median Price Ratio (MPR): Differencebetween the reported dispensed price andthe international buyer reference price givenby the International Drug Price IndicatorGuide.24

Data AnalysisThis article presents results and analysis of

the following data:

1. For five opioids in 13 formulations: avail-ability, dispensed price of lowest dosageavailable, and Me price of each.

2. For morphine oral solid IR: In addition tothe Dispensed price, the MPR and Afford-ability were also calculated for this medica-tion and formulation. The reason is thatmorphine oral solid IR has been used asa reference for monitoring consumptionof opioids, and it is included as the goldstandard essential strong analgesic in theWHO Model EMLs.4

A descriptive analysis of the data and acomparative analysis by GNI region were

Table 1Amount Needed for a 30-Day Treatment for

Each Medication

MedicationdFormulation DDD (mg)

30-DayTreatment

(DDD� 30)21

Fentanyldtransdermal 0.0012 36Hydromorphonedoral 20 600Hydromorphonedinjectable 4 120Morphinedoral (IR and SR) 100 3000Morphinedinjectable 30 900Oxycodonedoral 75 2250Methadonedorala 20 600

DDD¼Defined Daily Dose; IR¼ immediate release; SR¼ sustainedrelease.aGiven that there is no identified DDD for pain treatment withmethadone, a morphine equivalent dose was defined as 1:5 basedon the published literature:22 (100 mg/5¼ 20 mg).

conducted. Given the sample size, Spearman’srank correlation coefficients (Rs) and Kruskal-Wallis tests were used when applicable.

ResultsData were submitted by 30 participants from

26 countries (75% response rate). Participantsare listed in the Acknowledgment section.Reports were submitted from two locations intwo countries, namely China (Beijing andChengdu) and the U.K. (Edinburgh andLeeds); whereas reports from three locationswere submitted from Tanzania (two in Arushaand one in Dar es Salaam). Reports from Aru-sha (Arusha 1 and 2) were the same for avail-ability and prices. In Chile and Poland, thesurvey was submitted by the invited participantand an additional collaborator, not included inthe response rate but listed in the Acknowledg-ment section.

AvailabilityThe average number of pharmacies visited

before finding the one that had at leastone of the opioids included in the study variedby GNI: HIC: 1 (range¼ 0e1, Me¼ 0.6),UMIC: 1 (range¼ 0e2, Me¼ 1), LMIC: 9(range¼ 1e40, Me¼ 2.5), and LIC: 4.5(range¼ 3e15, Me¼ 6.1). In Moldova, Nepal,and Sudan, opioids are available only in hospi-tal pharmacies allowed to dispense for nonhos-pitalized patients.Availability of opioid formulations ranged

from11 (85%) inNorway to 0 in Kenya,Nigeria,Tanzania (Dar es Salaam), and Uganda. In fivelocations (Bangladesh, Brazil, Ethiopia,Tanzania [Arusha 1 and 2], and Uruguay),only one opioid was available, followed by Mol-dova with two. Norway had the highest numberavailable,11 followed by Germany, New Zealand,and Spain.9

The mean percentage of medications avail-able is strongly related to GNI level, rangingfrom 65% to 8% (HIC and LIC, respectively;Table 2). A significant positive correlation be-tween the country’s GNI and the availabilityof opioids was found (Rs¼ 0.781;P< 0.0001). In all HIC, availability was higherthan 50%, with the exception of Poland(46%). Brazil and Uruguay had the lowestavailability in the UMIC group (8%), whereas

Vol. 48 No. 4 October 2014 653Access to Opioids Around the Globe

the highest availability was in China (Cheng-du) and Romania (almost 50%). The extremesof the LMIC groups were Guatemala andNigeria (62% and 0%, respectively). Nepalstands out in the LIC group with 31% of themedications available.

Injectablemorphine (ampoule) was themostavailable (58%, n¼ 17), followed by morphineoral solid SR (53%, n¼ 16), then by morphineoral solid IR, fentanyl TP, and oxycodone SR(47%, n¼ 14). Morphine ampoule was avail-able in three of the LIC (Bangladesh, Ethiopia,and Nepal), whereas morphine liquid was avail-able in Nepal and Tanzania (Arusha 1 and 2).No opioids were available in Kenya, Nigeria,Tanzania (Dar es Salaam), or Uganda, butnone reported that the opioids were never avail-able. Hydromorphone was the least available ofall: liquid (none), ampoule (China [Beijing]),IR solid (Norway and China [Beijing]), andSR solid (Germany, Norway, and Spain).

Dispensed PricesOpioids are dispensed free in Chile, Moldo-

va, Nepal, New Zealand, Russia, Sudan, and

Table 2Availability of Opioids by

Income Group (GNI) Mean Percenta C

HIC 64.8 NorwayGermanNew ZeaSpain (PU.K. (LeU.K. (EdPoland (

UMIC 29.1 China (CRomaniaChile (SIran (TeArgentinChina (BRussia (KBrazil (RUruguay

LMIC 28.2 GuatemaPhilippinIndia (NSudan (KMoldova

LIC 7.7 Nepal (BEthiopiaTanzaniaTanzaniaTanzaniaKenya (NUganda

GNI¼Gross National Income; HIC¼ high income country; UMIC¼ upperLIC¼ low income country.aSpearman’s rank correlation coefficient (Rs)¼ 0.781; P< 0.0001, Kruskal-Wa

Tanzania (Arusha 1 and 2). In Edinburgh, opi-oids are free, but not in Leeds (U.K.). In Ger-many, medications are dispensed at no cost tothe patients through a health insurance fund,but patients are required to pay a fixeddispensing fee.

The Me price for morphine oral solid IR10 mg ranged between USD 0.03 and 0.16 forHIC and LMIC, respectively, whereas the MPRranged between USD 0.06 and 0.33 in HICand LMIC, respectively (Table 3). Table 4describes the Me price comparison of a 30-daytreatment by GNI. The Me price of 30-day treat-ment of morphine oral solid IR 10 mg was lessin HIC (USD 4.6) than in lower GNI groups(UMC¼ 30.5 and LM¼ 46.8). Apart frommorphine liquid, which is free in seven of13 countries (Me¼ 0), methadone oral solidwas the lowest-priced medicine (Me¼ 0.5), fol-lowed by fentanyl TP (Me¼ 2.2). Synthetic opi-oids and in some cases opioids with morecomplex delivery mechanisms (TP and oralSR) were dispensed at lower prices thanmorphine oral solid IR. Fentanyl TP is free inChile, Iran, New Zealand, Romania, and Russia

Income Groups

ountry (City) % Of Opioids Available

(Bergen) 84.62y (Aachen) 69.23land (Wellington) 69.23amplona) 69.23eds) 61.54inburgh) 53.84Poznan) 46.15hengdu) 46.15(Brasov) 46.15

antiago) 38.46heran) 38.46a (San Nicolas) 30.77eijing) 23.08emerovo) 23.08io de Janeiro) 7.69(Montevideo) 7.69la (Guatemala City) 61.54es (Iloilo City) 38.46ew Delhi) 30.77hartoum) 23.08(Chisinau) 15.38 Nigeria (Ibadan)haratpur) 30.77 Bangladesh (Dhaka)(Hawassa) 7.69(Arusha 1) 7.69(Arusha 2) 7.69(Dar es Salaam) 0airobi) 0(Kampala) 0

middle income country; LMIC¼ lower middle income country;

llis tests P< 0.0001.

Table 3Morphine Oral Solid, IR 10 mg TabletdMedianPrice Per Unit and Median Price Ratio (MPR) by

Income Groups

GNI GroupMedian Price (10 mg),

USD MPR

HIC 0.03 0.06UMIC 0.10 0.22LMIC 0.16 0.33LIC d d

GNI¼Gross National Income; HIC¼ high income country;UMIC¼ upper middle income country; LMIC¼ lower middleincome country; LIC¼ low income country.MPR¼ difference between the reported dispensed price and theinternational buyer reference price. The 2011 international buyerreference price for morphine oral solid IR 10 mg tablet was USD0.47.24

Table4

Med

ianPrice

ComparisonofOne30-Day

Opioid

Treatmen

tByInco

meGroups

All(n

¼26

)LIC

(n¼8)

LMI(n

¼6)

UMI(n

¼9)

HIC

(n¼7)

Free

MeUSD

Free

MeUSD

Free

MeUSD

Free

MeUSD

Free

MeUSD

lidim

med

iate

release(tab

letan

dcapsule)

6/14

18.9

1/1

0.0

1/4

46.8

1/3

30.5

3/6

4.6

lidsustained

release(tab

letan

dcapsule)

7/16

7.5

1/1

0.0

2/5

44.6

2/3

0.0

2/7

7.9

quid)

7/13

0.0

3/3

0.0

1/2

35.1

1/2

114.1

2/6

21.9

ble

(ampoule)

6/17

16.8

1/3

1.8

1/3

31.7

3/6

8.4

1/5

64.4

rmal

patch

es)

5/14

2.2

dd

0/3

27.6

4/5

0.0

1/6

2.2

mmed

iate

release(tab

letan

dcapsule)

3/11

144.1

dd

0/2

525.4

0/3

200.5

3/6

70.9

lowrelease(tab

letan

dcapsule)

5/14

112.6

dd

0/2

734.8

2/5

334.0

3/7

10.5

olid(tab

letan

dcapsule)

5/10

0.5

dd

0/1

76.6

2/4

0.5

3/5

0.0

liquid)

3/8

8.9

dd

dd

0/1

1.3

3/7

16.6

oralim

med

iate

release(tab

letan

dcapsule)

0/2

228.5

dd

dd

0/1

10.5

0/1

446.5

oralslowrelease(tab

letan

dcapsule)

1/3

97.7

dd

dd

dd

1/3

97.7

oral(liquid)

dd

dd

dd

dd

dd

injectab

le(ampoule)

0/1

5.2

dd

dd

0/1

5.2

dd

leinco

meco

untry;

LIC

¼lowinco

meco

untry;

LMIC

¼lower

middle

inco

meco

untry;

HIC

¼highinco

meco

untry;

Me¼med

ian;USD

¼U.S.Dollars.

ee’’thenominatoreq

ualsnumber

ofco

untrieswheremed

icationisdispen

sedfree,den

ominatoreq

ualsnumber

ofco

untrieswheremed

icationisavailable.

654 Vol. 48 No. 4 October 2014De Lima et al.

and the least expensive in Germany, Guatemala,India, Norway, Philippines, Poland, Spain, andtheU.K. (Leeds). In general, it was found that ifavailable, patients in LMIC are likely to paymore for the medication than patients in theother two groups. Hydromorphone oral solidIR was the most expensive formulation(Me¼ 228.5) followed by oxycodone (IR:Me¼ 144.1; SR: Me¼ 112.6).

AffordabilityThe mean number of days’ wages required

by the lowest-paid worker to purchase a 30-day treatment of morphine oral solid IRamong the 14 countries that reported avail-ability was five days (Me¼ 0.1; SD¼ 9.1), butvaries greatly by country, ranging from:29.48 (Philippines) and 20.75 (India) to0.25 days (Spain). In five countries (Nepal,Sudan, Romania, New Zealand, and Poland),it is dispensed free to patients. The resultsindicate that morphine oral solid IR is lessaffordable in countries in lower incomegroups: LMIC (Me¼ 14.4; mean¼ 14.6[SD¼ 13.1]), UMIC (Me¼ 2.2; mean¼ 2.7[SD¼ 9.3]), and HIC (Me¼ 0.2 [SD¼ 0.36];Table 5). In general, a negative correlationbetween the days’ wages and the country in-come category (Rs¼ 0.544; not significant)was identified: the lower the income, themore working days required to pay for thetreatment.

Med

ication

Morphineoralso

Morphineoralso

Morphineoral(li

Morphineinjecta

Fen

tanyl

(transde

Oxyco

doneorali

Oxyco

doneorals

Methad

oneorals

Methad

oneoral(

Hydromorphone

Hydromorphone

Hydromorphone

Hydromorphone

UMIC

¼upper

midd

Note:In

column‘‘F

r

DiscussionThis is the first pilot study that presents

information on the differences among

Table 5Affordability for a 30 Day Treatment of

Morphine Oral Solid IR by Income Group

GNIGroup

Number ofDays’ Wages Country

Number ofDays’ Wages

All Me¼ 0.1IQR¼ 6.9x ¼ 5$0CI¼ 4.76

All countries

HIC Me¼ 0.0IQR¼ 0.5x ¼ 0.2

CI¼ 0.32

U.K. (Leeds) 0.8Spain 0.3New Zealand 0.0Poland 0.0Norway a

UMIC Me¼ 2.2IQR¼ 6.0x ¼ 2.7

CI¼ 3.19

Argentina 6.5China (Chengdu) 4.5Romania 0.0

LMIC Me¼ 14.4IQR¼ 25.3x ¼ 14.6

CI¼ 12.84

Philippines 29.5India 20.8Guatemala 8.1Sudan 0.0

LIC Me¼ 0.0IQR¼ 0.0x ¼ 0.0CI¼ 0.0

Nepal 0.0

GNI¼Gross National Income; Me¼median; IQR¼ interquartilerange; x ¼mean; CI¼ confidence interval; HIC¼ high incomecountry; UMIC¼ upper middle income country; LMIC¼ lowermiddle income country; LIC¼ low income country; IR¼ immedi-ate release.aMorphine oral solid IR was available in Norway; however, it wasnot possible to determine the affordability given that there is nominimum wage in the country.

Vol. 48 No. 4 October 2014 655Access to Opioids Around the Globe

availability, prices, and affordability of opioidsacross the World Bank GNI groups in pharma-cies close to a public health facility that pro-vides diagnostic and treatment services forpatients with life-threatening conditions suchas HIV and cancer.

AvailabilityThe information reflects opioid availability

in a specific pharmacy on any given day, sono inferences regarding availability in thewhole country are possible. Although resultsindicate that several opioids and formulationswere not available at the time of the survey, itdoes not imply that these opioids are neveravailable in such locations. None of the coun-tries included in the study reported not havingany opioids available at any time, which is anindication of progress.7 The possibility offinding an opioid at the pharmacy is directlycorrelated to the country’s GNI, which isconsistent with opioid consumption reportspublished by the International Narcotics Con-trol Board. The number of medications

available in Guatemala was high comparedwith countries within the middle and lowGNI, which may reflect recent efforts toimprove availability to pain treatment in thatcountry. Almost all the African countries regis-tered very limited availability, with either noneor one opioid available, with the exception ofSudan, which reported having three medica-tions/formulations available. The partici-pating African countries were LIC (Ethiopia,Kenya, Tanzania, and Uganda) or LMIC(Nigeria and Sudan). Recent efforts havebeen made to improve opioid availability inseveral African countries, so future OPW re-ports should reflect increased availability inthese countries as well. As suggested by theWHO,13 the availability of medications can beimproved through adequate managementand realistic assessment of local supply optionsand needs.

While this report was being prepared, theWHO published a new edition of the EML,which includes all the morphine formulationsand lists oxycodone and hydromorphone assubstitutes for morphine.25

The WHO Model List also includes a newsection of medications for pain and othersymptoms common in palliative care, whichwill hopefully result in increased awarenessabout the importance and relevance of hav-ing these medications available to relievesuffering of patients with life-threateningconditions.

Dispensed PricesIn regard to its international reference price

(USD 0.47), the Me price of morphine oralsolid IR (10 mg) is 5.8 times higher in LMICthan in HIC. In the former, the cost of addi-tional burdens and requirements resultingfrom stringent norms and regulations may betransferred on to the patients, whereas inHIC, the costs tend to be covered throughother funds and pooling of resources.26

Hydromorphone oral IR and oxycodone oralIR and SR were the highest dispensed pricemedications. However, in Iran and Norway,the dispensed price of oxycodone oral IR waslower thanmorphine injectable; and in Poland,the dispensed price of oxycodone oral SR waslower than methadone oral liquid. Resultsalso show an unexpected favorable price differ-ence for fentanyl TP: it is dispensed free in five

656 Vol. 48 No. 4 October 2014De Lima et al.

countries (1 HIC and 4 UMIC) and the cheap-est opioid in seven, indicating that there couldbe heavy subsidies in place at all GNI levels. Forexample, morphine oral solid IR tablet wasmore expensive than fentanyl TP in China(Chengdu), Germany, Guatemala, India, Iran,Norway, Poland, Spain, the Philippines, andthe U.K. It would be useful to find out the rea-sons why morphine is not included in subsidyprograms, even in LMIC. Artificially loweringthe dispensing price of the most expensivemedications and formulations results in an eco-nomic disadvantage for morphine oral solid IRand probably also in less demand for this medi-cation. Morphine oral IR is cheaper than otheropioids,10,27,28 so there may be insufficientmargin to generate profit incentive for phar-maceutical companies to commercialize it.Although availability of several opioids and for-mulations is desirable, it is also critical toensure access to morphine oral solid IR solid,which has been proven to be efficacious andsafe for treatment of severe pain.29

Methadone (in both formulations) waspriced lower than several morphine formula-tions in almost all the countries where availableand the most consumed in China, Iran, NewZealand, Tanzania, and the U.K.30 It is impor-tant to note that methadone is mostly used insubstitution therapy for dependence syndrome,but its use as an analgesic has been increasing inpalliative care.31e33

AffordabilityNew Zealand had the best affordability (nine

medications/formulations available for free).Monthly treatment costs of morphine oral solidIRmeasured in the number of days’ wages of thelowest-paid worker varies greatly (Philippines29, India 21, and Guatemala 8 days). Many peo-ple in these countries earn less than the mini-mum wages used for this study (USD: 2.18,4.85, and 8.16 per day respectively)23 and livebelow the international poverty line of USD1.25/day,34 indicating that the number of work-ing days needed to pay the cost of treatmentmaybe higher than the results in this study and thatpain treatment is accessible to only a few whocan afford it.

Governments and policy makers need to takethe necessary steps to ensure that the patientsare able to receive the treatment that theyneed. Prices can be reduced by strategies such

as manufacturing the oral morphine in thecountry, eliminating taxes and tariffs, regu-lating markup charges, and regularly moni-toring the distribution chain. However, thesemeasures are related to wider aspects in therespective country such as the Human Develop-ment Index.35

LimitationsAlthough the OPW follows a methodology

similar to the one used by HAI/WHO, thelatter does not include controlled medica-tions. Opioids are internationally controlled;thus, the availability and pricing are impactedby additional factors, such as markups re-sulting from safety and security measuresrequired by the national laws on themanufacturing, importation, distribution,storage, and dispensation. This survey is un-able to determine the extent of the impactof these measures on the dispensed price ofthe medication.This study is based on the data collected from

external collaborators, and it is not possibleto determine how rigidly they followed theinstructions.This study is a one day cross-sectional survey.

Out-of-stock situations occur frequently, espe-cially in LIC and MLIC, so the results on avail-ability might differ in a longitudinal survey.However, the results reflect the situation thatpatients in need of opioids may face in anygiven day.The study is based on a sample of data of a

local pharmacy in the selected countries,which is not representative of the whole coun-try. However, the fact that pharmacies werelocated to major treating centers may indicatethat other pharmacies distant from hospitalsmay have fewer medications in stock.The OPW indicates differences in opioid pri-

ces among different locations. With the excep-tion of morphine oral solid IR, it does nottake into account the differences in purchasingpower among countries. Future studies usingpurchasing power parity should be carried outtomeasure howpricesmay affect access to otheropioids.

ConclusionThe study indicates that patients in LIC and

MIC have less access to opioid medications

Vol. 48 No. 4 October 2014 657Access to Opioids Around the Globe

and highlights the need to continue efforts atimproving their availability and affordability.Efforts should be made by governments,health care administrators, and pharmaciststo ensure that opioids are available in localpharmacies near to the health care facilitiesthat provide care for life-threatening condi-tions. Results also show an unexpected favor-able price difference for fentanyl TPs over IRmorphine, indicating heavy subsidies for fen-tanyl. Additional studies are needed to iden-tify the reasons why morphine, which ischeaper than other medications, is notincluded in subsidy programs, even in coun-tries with limited resources. Although avail-ability of several opioids and formulations isdesirable, it is also critical to ensure access tomorphine, which has been proven to be effica-cious and safe for severe pain treatment andhas been classified as an essential medicinefor the treatment of pain by the WHO. Addi-tional studies are also needed to identify theextent that factors such as restrictive lawsand regulations have on the dispensed priceof opioid medications.

Disclosures and AcknowledgmentsThis study was partially funded by a seed

grant from the U.S. Cancer Pain ReliefCommittee. The funder did not play anydirect role in the study development, datacollection, data analysis or interpretation,the writing, or the submission of the manu-script. The authors declare no conflicts ofinterest.

Contributors: The following individualsmade comments to the project proposal andcontributed to Opioid Price Watch:

International Association for Hospice andPalliative Care (IAHPC) Board members:Eduardo Bruera (U.S.), James Cleary (U.S.),Arthur Lipman (U.S.), and M.R. Rajagopal(India)

IAHPCwebmaster:DaniloFritzler (Argentina)provided the technical support and guidancein the data collection and reporting processes.

WHO Department of Essential Medicinesand Health Products (Geneva): Willem Schol-ten, Dele Abegunde, Barbara Milani, andAnne Nguyen.

External contributors: Rosa Buitrago (Pan-ama) and David Joranson (U.S.)

Participants: Sofia Bunge (Argentina), Ma-riam Lubna (Bangladesh), Lilian Hennemann(Brazil), Natalie Rodriguez (Chile), LauraTupper (Chile), Jinxiang Li (China), Di Xiao(China), Aweke Yilma Dubi (Ethiopia),Heike Reineke-Bracke (Germany), Eva Duarte(Guatemala), Ann Thyle (India), MamakTahmasebi (Iran), Mildred Agnes Waka(Kenya), Natalia Carafizi (Moldova), MinaKumari Ranabhat (Nepal), Brian Ensor (NewZealand), Olaitan Soyannwo (Nigeria), DagnyFaksv�ag Haugen (Norway), Jesus Eugenio deJesus (Philippines), Aleksandra Kotlinska-Lemieszek (Poland), Iwona Zaporowska-Sta-chowiak (Poland), Daniela Mosoiu (Romania),Olga Usenko (Russia), Nahla Gafer (Sudan),Miriam Giraldez (Spain), Mark Jacobson(Tanzania), Alick Kayange (Tanzania), MichaelKing’ori (Tanzania), Zirimenya Ludoviko(Uganda), Scott Murray (U.K.), MoiraCookson (U.K.), and Maria Mercedes Bernada(Uruguay).

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___If NONE of the opioids listed in this study are available at ANY TIME in your country, check this box___If opioids are available in your country ONLY in hospital pharmacies (and NOT in street pharmacies) check this box

If your country has a tiered system in which medicines (including opioids) are priced according to the person’s income level, report the price that a patient earning the lowest minimum wage would have to pay.

The form will require providing information on the prices for the formulations below. To see samples on how to complete this table, click on http://hospicecare.com/opioids/uploads/examples.pdf

Opioid

Check this box if the medication is NOT available in the pharmacy on

the day of the survey

Check this box if the medications

is dispensed Free

(at no cost for the patient)

If patient has to pay, write in numbers the amount required to pay (in your local

currency)

Smallest selling dose (total units for dry formulations or

total volume for liquid formulations)

Fentanyl (transdermal patches)

Hydromorphone ampoule, injectable

Hydromorphone oral solid (tablet or capsule), immediate release

Hydromorphone oral solid (tablet o capsule), prolonged release

Hydromorphone oral liquid (oral solution)

Methadone oral solid (tablet or capsule)

Methadone oral liquid (oral solution)

Morphine ampoule, injectable

Morphine oral solid (tablet or capsule), immediate release

Morphine oral solid (tablet or capsule), sustained release

Morphine oral liquid (oral solution)

Oxycodone oral solid (tablet or capsule), immediate release

Oxycodone oral solid (tablet or capsule), sustained releaseNumber of pharmacies you visited before finding one which has AT LEAST ONE opioid in stock (if available in your country)____Pharmacy address: __________________________________________________________________________________________________________Select the appropriate category (select one): Licensed retail pharmacy ____ Licensed hospital pharmacy:___

Appendix

Sample Data Collection Form

659.e1

Vol.

48No.

4October

2014

DeLimaetal.