Use of and barriers to access to opioid analgesics: a ...€¦ · Interpretation Use of opioid analgesics has increased, but remains low in Africa, Asia, Central America, the Caribbean,

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1644 www.thelancet.com Vol 387 April 16, 2016

Use of and barriers to access to opioid analgesics: a worldwide, regional, and national studyStefano Berterame, Juliana Erthal, Johny Thomas, Sarah Fellner, Benjamin Vosse, Philip Clare, Wei Hao, David T Johnson, Alejandro Mohar, Jagjit Pavadia, Ahmed Kamal Eldin Samak, Werner Sipp, Viroj Sumyai, Sri Suryawati, Jallal Toufi q, Raymond Yans, Richard P Mattick

SummaryBackground Despite opioid analgesics being essential for pain relief, use has been inadequate in many countries. We aim to provide up-to-date worldwide, regional, and national data for changes in opioid analgesic use, and to analyse the relation of impediments to use of these medicines.

Methods We calculated defi ned daily doses for statistical purposes (S-DDD) per million inhabitants per day of opioid analgesics worldwide and for regions and countries from 2001 to 2013, and we used generalised estimating equation analysis to assess longitudinal change in use. We compared use data against the prevalence of some health disorders needing opioid use. We surveyed 214 countries or territories about impediments to availability of these medicines, and used regression analyses to establish the strength of associations between impediments and use.

Findings The S-DDD of opioid analgesic use more than doubled worldwide between 2001–03 and 2011–13, from 1417 S-DDD (95% CI –732 to 3565; totalling about 3·01 billion defi ned daily doses per annum) to 3027 S-DDD (–1162 to 7215; totalling about 7·35 billion defi ned daily doses per annum). Substantial increases occurred in North America (16 046 S-DDD [95% CI 4032–28 061] to 31 453 S-DDD [8121–54 785]), western and central Europe (3079 S-DDD [1274–4883] to 9320 S-DDD [3969–14 672]), and Oceania (2275 S-DDD [763–3787] to 9136 S-DDD [2508–15 765]). Countries in other regions have shown no substantial increase in use. Impediments to use included an absence of training and awareness in medical professionals, fear of dependence, restricted fi nancial resources, issues in sourcing, cultural attitudes, fear of diversion, international trade controls, and onerous regulation. Higher number of impediments reported was signifi cantly associated with lower use (unadjusted incidence rate ratio 0·39 [95% CI 0·29–0·52]; p<0·0001), but not when adjusted for gross domestic product and human development index (0·91 [0·73–1·14]; p=0·4271).

Interpretation Use of opioid analgesics has increased, but remains low in Africa, Asia, Central America, the Caribbean, South America, and eastern and southeastern Europe. Identifi ed impediments to use urgently need to be addressed by governments and international agencies.

Funding International Narcotics Control Board, UN.

IntroductionFor more than 50 years, a UN convention has maintained that certain medicines are “indispensable for the relief of pain and suff ering”, so that their availability “must be” ensured.1 This position is often affi rmed.2 Yet, more than 5 billion people worldwide had little or no access to essential analgesics, such as codeine or morphine, between 2011 and 2013.3 In 2009, more than 90% of worldwide use of opioid analgesics occurred in the USA, Canada, Australia, New Zealand, and several European countries.4 Use in that year was deemed low in 21 countries and very low in more than 100.4 Inadequate access is inconsistent with international agreements, such as the Universal Declaration of Human Rights,5 which includes the right to medical care and encompasses palliative care. Authors of UN reports have stressed the need to redress this inequity for 25 years.4,6,7

Calls to close the so-called pain divide reiterate the concerns,8,9 and country-level initiatives seem capable of improving availability.9–11 A descriptive study of use against need was published in 2011 using 2006 data,12 a study of

regional use published in 2014 analysed data from 1980 to 2011,13 and a study of country use for some but not all world regions was done in 2013.14 Yet, no analysis of changes in opioid analgesic use applying longitudinal statistical methods has been done, along with any study of the nature and eff ect of barriers to availability and use of these medicines. Contemporary infor mation about the signifi cance of change in use and the eff ects of impediments to use (along with factors such as gross domestic product [GDP] and country develop ment) are needed to inform decision making. This study provides an assessment of changes to opioid analgesic use worldwide, regionally, and nationally, from 2001 to 2013. We identify the nature and signi fi cance of impediments to an increase of the availability of these medicines.

These data are timely because the UN General Assembly will hold its Special Session on the World Drug Problem (UNGASS 2016) in New York, NY, USA, in April, 2016. Information about the changes in and impediments to use of opioid analgesics can help deliberations and assist in specifying of policies to improve availability.

Lancet 2016; 387: 1644–56

Published OnlineFebruary 3, 2016

http://dx.doi.org/10.1016/S0140-6736(16)00161-6

See Comment page 1597

Secretariat of the International Narcotics Control Board, Vienna

International Centre, Vienna, Austria (S Berterame PhD, J Erthal MA, J Thomas BSc,

S Fellner MA, B Vosse MSc); International Narcotics Control

Board, Vienna International Centre, Vienna, Austria

(Prof W Hao MD, D T Johnson BA [Econ],

Prof A Mohar ScD, J Pavadia LLB, A K E Samak, W Sipp LLM,

Prof V Sumyai PhD, Prof S Suryawati PhD,

Prof J Toufiq MD, R Yans MA, Prof R P Mattick PhD); National

Drug and Alcohol Research Centre, Faculty of Medicine,

University of New South Wales, Sydney, NSW, Australia

(P Clare MBiostats, Prof R P Mattick); Psychiatry,

Mental Health Institute, Central South University, Changsha,

China (Prof W Hao); Unidad de Epidemiología, Instituto

Nacional de Cancerología, Instituto de Biomédicas,

Universidad Nacional Autónoma de México, Tlalpan,

Distrito Federal, Mexico (Prof A Mohar); Association of

Southeast Asian Nations Institute for Health

Development, Mahidol University, Salaya,

Nakhonphathom, Thailand (Prof V Sumyai); Division of

Medicine Policy and Management, Department of

Pharmacology and Therapeutics, Faculty of

Medicine, GadjahMada University, Yogyakarta,

Indonesia (Prof S Suryawati); and Faculty of Medicine,

University Mohammed V, Rabat, Morocco, and Hôpital

Universitaire Psychiatrique Arrazi, Salé, Morocco

(Prof J Toufiq)

http://crossmark.crossref.org/dialog/?doi=10.1016/S0140-6736(16)00161-6&domain=pdf

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www.thelancet.com Vol 387 April 16, 2016 1645

Correspondence to:Dr Stefano Berterame, International Narcotics Control Board, Vienna International Centre, A-1400 Vienna, [email protected]

MethodsData sourcesCountries provided data to the International Narcotics Control Board (INCB) on one aspect of availability of opioid analgesic medicines, specifi cally the amounts that each country’s competent national authority estimates are needed and used annually, including reporting of medicines destroyed, losses during manufacture, and so on. This information was verifi ed by the INCB using data from export and import notifi cations. We assess these data in terms of defi ned daily doses for statistical purposes (S-DDD) to establish the extent of use (see appendix for conversion methods). The S-DDD is a technical unit of measurement. It is not a recommended prescription dose. It recognises that no internationally agreed standard doses exist for opioid medicines and therefore provides a rough measure to rank opioid use of countries. Levels of use, expressed in S-DDD per million inhabitants per day, are calculated with the following formula: annual use divided by 365 days, divided by the population in millions of the country or territory during the year, divided by the defi ned daily dose. We include codeine, dextro-propoxyphene, dihydrocodeine, fentanyl, hydro codone, hydromorphone, ketobemidone, mor phine, oxycodone, pethidine, tilidine, and tri meperidine; we exclude metha-done and buprenorphine from these analyses because their use for pain relief cannot be distinguished from their predominant use in treatment of dependence on illicit opioids.

The regions of the Americas, Asia, and Europe have been divided into America (North), America (Central and Caribbean), America (South), Asia (east and southeast), Asia (south), Asia (west), Europe (west and central), Europe (southeast), and Europe (east) because the patterns of use within these regions vary. GDP data are

from the World Bank15 and Human Development Index (HDI),16 and population data are from the UNDP.17

We sent a questionnaire about determinants of use (appendix) to 214 national authorities. We also gathered information about disorders for which opioid medicines are needed to compare reported use with the prevalence of specifi c health disorders. Prevalence of cancer18 and AIDS-related deaths were available from the Joint UN Programme on HIV/AIDS19 and the WHO Global Health Observatory20 (appendix). On the basis of these data, the INCB is publishing a full report on the availability of narcotic drugs and psychotropic substances.21

Statistical analysisWe analysed annual S-DDD data from 2001 to 2013 using generalised estimating equation (GEE) modelling, controlling for within-country correlations, and assuming that correlations between timepoints were autocorrelated. Because the data were skewed and overdispersed, we used negative binomial GEE. Because GEE does not directly estimate the dispersion parameter (α), we did GEE using an α modelled with a generalised linear model. The model included a time-by-subregion inter-action eff ect, allowing for the change with time to vary based on subregion, and controlled for country GDP and HDI.16 We analysed the relation between impediments and S-DDD use with negative binomial regression, controlling for the same covariates. Parametric (t tests) and non-parametric (Wilcoxon rank-sum) tests assessed diff erences between responding and non-responding countries. We calculated confi dence limits at the worldwide, regional, and national level. GDP used was in present US$ per person; however, because it displayed a non-linear relationship with S-DDD, we transformed it using a natural logarithm for inclusion in the models.

Research in context

Evidence before this studyEvidence considered before doing this study drew on International Narcotics Control Board data and reports plus a search of the literature. Between Jan 1, 2001, and Nov 19, 2015, we searched MEDLINE, with no language restrictions, identifying 1788 publications (after excluding 110 duplicate citations). A full list of search terms is given in the appendix. We identifi ed several other important eff orts to characterise the worldwide situation before our study, including estimates of use against need in 2006, use in 2011, and barriers to accessibility, but not for all regions. No previous research has established the extent of change in use or the association between impediments and use with appropriate longitudinal and multivariate statistical analytic approaches.

Added value of this studyOur fi ndings provide an up-to-date analysis of worldwide, regional, and national opioid analgesic medicine use compared with clinical need for management of cancer and

HIV, and we provide an analysis of impediments that are determinants of use. We show the extent of progress that has occurred during a decade worldwide in terms of a doubling of use, but while use has substantially increased in many regions, change in use in low-income and middle-income regions remains low, and use unbalanced. The number of impediments to availability reported by countries is signifi cantly associated with unadjusted use, as are country gross domestic product and country level of development as indexed by the Human Development Index after adjustment.

Implications of all the available evidenceMany low-income and middle-income countries continue to fail to provide adequate opioid analgesic medicine for pain. Attention should be paid to the impediments faced by countries, and international and national policies and action should support an agenda for change within the next decade.

See Online for appendix

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We included HDI as the country rank in each year. We used Stata 14.1 for all analyses.

Role of the funding sourceThe named INCB Secretariat staff and INCB members developed the methods, had full access to all of the

data, completed decisions on analysis, write-up, and interpretation of results, and had fi nal responsibility for the decision to submit for publication. Other parts of the UN had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Consumption inS-DDD per millioninhabitants per day <1 1–100 101–200 201–2000 2001–5000 5001–10 000 >10 000

Figure 1: Mean availability of opioids for pain management in 2001–03The boundaries shown and the designations used on this map do not imply offi cial endorsement or acceptance by the UN. Final boundary between Sudan and South Sudan has not yet been established. The dotted line represents roughly the Line of Control in Jammu and Kashmir agreed on by India and Pakistan. The fi nal status of Jammu and Kashmir has not yet been agreed on by the parties. A dispute exists between the Governments of Argentina and the UK concerning sovereignty over the Falkland Islands (Malvinas). S-DDD=defi ned daily doses for statistical purposes.

Consumption inS-DDD per millioninhabitants per day <1 1–100 101–200 201–2000 2001–5000 5001–10 000 >10 000

Figure 2: Mean availability of opioids for pain management in 2011–13The boundaries shown and the designations used on this map do not imply offi cial endorsement or acceptance by the UN. Final boundary between Sudan and South Sudan has not yet been established. The dotted line represents roughly the Line of Control in Jammu and Kashmir agreed on by India and Pakistan. The fi nal status of Jammu and Kashmir has not yet been agreed on by the parties. A dispute exists between the Governments of Argentina and the UK concerning sovereignty over the Falkland Islands (Malvinas). S-DDD=defi ned daily doses for statistical purposes.

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ResultsBy May 18, 2015, 106 countries or territories (appendix), equating to 75% of the world’s population, had responded to the questionnaire about determinants of use, a response rate consistent with previous exercises.14 Figures 1 and 2 show evidence of increased use of opioid analgesics between 2001–03 and 2011–13. Some increase in use is evident in the Middle East and Latin America. Small increases have occurred in Russia and in some countries in central Asia, but levels of use remain low (101–200 S-DDD per million inhabitants per day). Use is very low in most of Africa and in southeast Asia. Increases have occurred to more than 10 000 S-DDD per million inhabitants per day in North America, western Europe, and Australia.

The USA, Canada, Australia, and some western European countries report very high levels of use (table 1, appendix). During the 13 year period of this study, use in North America increased in absolute terms from about 2·4 billion DDD per annum to about 5·3 billion DDD per annum, and in western and central Europe, this fi gure increased from about 0·5 billion DDD per annum to about 1·6 billion DDD per annum. These two regions used 94·1% of the analgesic opioids examined in 2011–13. With Oceania

included, 95·7% of worldwide use occurred in these three regions, accounting for about 15% of the world’s population. The situation in the other regions has changed little. Use remains low in 22 countries or territories (101–200 S-DDD) and very low in 113 countries or territories (<100 S-DDD). This situation is similar to that noted in 2009.4

Consistent with the changes in worldwide use, GEE analysis showed signifi cant temporal changes in overall country S-DDD use worldwide (p=0·0025 for year-by-region interaction eff ects, controlling for GDP and HDI), and we also noted change in seven of the 11 regions (appendix). The regions without signifi cant change in the GEE analysis were west Asia, eastern Europe, southeastern Europe, and Oceania. Notably, North America, Oceania, and western and central Europe had higher unadjusted S-DDD use than did the other regions (table 1); however, when GDP and HDI were controlled for, these diff erences were no longer signifi cant, as shown by the overlap in CIs (appendix). GDP and HDI were both highly signifi cant (both p<0·0001; appendix), suggesting that GDP and HDI are important determinants of use, accounting for much of the between-country diff erences and changes with time in S-DDD use.

S-DDD use per million people per day DDD use in total (per annum)

2001–03 2011–13 Absolute change*


Worldwide 1417(–732 to 3565)

3027(–1162 to 7215)

1610 3 012 989 376(–1 493 464 896 to 7 519 443 840)

7 347 347 296(–2 651 445 636 to 17 346 140 228)

4 334 357 920(–1 174 784 777 to 9 843 500 451)

Africa 50(–3 to 104)

41(–3 to 86)

–9 13 370 654(–1 223 269 to 27 964 577)

11 665 395(–1 297 345 to 24 628 135)

–1 705 259(–10 715 932 to 7 305 375)

South Africa 405 338 –67 6 246 920 6 171 964 –74 956

Saint Helena 1215 305 –910 1212 557 –655

Seychelles 97 184† 87 2851 6230† 3379

Tunisia 94 180 86 324 701 682 098 357 397

Namibia 94 119† 25 58 887 99 415† 40 528

Botswana 66† 113† 47 38 224† 81 618† 43 394

Mauritius 50 87† 37 21 444 41 347† 19 903

Ascension Island 23 82 59 12 30 18

Egypt 46 75 29 1 118 079 2 262 811 1 144 732

Algeria 22 43 21 241 626 548 851 307 225

Zimbabwe 29 35 6 135 734 161 588 25 854

Libya 35 35† 0 67 736 81 678† 13 942

Zambia 23 32 9 80 461 149 801 69 340

Cape Verde 7 32 25 1076 5934 4858

Uganda 23 31 8 179 247 372 485 193 238

Malawi 0 26‡ 26 0 147 870‡ 147 870

Morocco 375 23† –352 3 835 384 268 295† –3 567 089

São Tomé and Príncipe 37 24‡ –13 1886 1750‡ –136

Ghana 42 20 –22 290 710 172 090 –118 620

Chad 0 8‡ 8 436 31 598‡ 31 162

Benin 3 9 6 5903 27 645 21 742

Angola 15† 7† –8 69 438† 48 683† –20 755

(Table 1 continues on next page)

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(Continued from previous page)

Gabon 0 5‡ 5 0 2748‡ 2748

Tanzania 9† 5 –4 100 788† 85 548 –15 240

Mozambique 7 5 –2 43 181 37 919 –5262

Cameroon 6† 7† 1 31 533† 52 787† 21 254

Senegal 3 4† 1 9487 18 645† 9158

Togo 1 2 1 1820 5571 3751

Republic of the Congo 1 1 0 21 777 34 171 12 394

Côte d’Ivoire 1 1 0 6531 10 414 3883

Madagascar 3 1‡ –2 17 570 8637‡ –8933

Mali 0† 1‡ 1 117† 5977‡ 5860

Burkina Faso 1† 1† 0 3512† 5741† 2229

Eritrea 2 1† –1 2623 1993† –630

Nigeria 0† 1 1 14 928† 30 920 15 992

Burundi 10 0 –10 23 026 0 –23 026

Central African Republic 61‡ 0 –61 77 000‡ 0 –77 000

Comoros 2‡ 0 –2 490‡ 0 –490

Congo 0 0 0 0 0 0

Djibouti 2‡ 0 –2 492‡ 0 –492

Equatorial Guinea 0 0 0 0 0 0

Ethiopia 0 0 0 7858 0 –7858

The Gambia 0 0 0 0 0 0

Guinea 0 0 0 849 0 –849

Guinea-Bissau 0‡ 0 0 23‡ 0 –23

Kenya 20 0 –20 217 076 0 –217 076

Lesotho 8† 0 –8 6510† 0 –6510

Liberia 0 0 0 0 0 0

Mauritania 0 0 0 0 0 0

Niger 0 0 0 0 0 0

Rwanda 1 0 –1 1874 0 –1874

Sierra Leone 21 0 –21 33 707 0 –33 707

Somalia 0 0 0 0 0 0

Sudan 2 0 –2 18 973 0 –18 973

Swaziland 20 0 –20 6842 0 –6842

Tristan da Cunha 240‡ 0 –240 88‡ 0 –88

America (Central and Caribbean)

50(21 to 79)

94(52 to 137)

44 1 213 152(424 176 to 2 002 128)

2 690 793(1 184 845 to 4 196 718)

1 477 641(–37 112 to 2 992 415)

Cayman Islands 1473 4315 2 842 19 924 61 429 41 505

Curaçao - 2490† - - 129 042† -

Sint Maarten - 894 - - 12 075 -

Bahamas 293 425 132 32 077 51 069 18 992

Barbados 438 409‡ –29 42 648 40 864‡ –1784

British Virgin Islands 534‡ 396† –138 4676‡ 4340† –336

Panama 77 309 232 79 444 389 044 309 600

Saint Vincent and the Grenadines

84† 254 170 3442† 9914 6472

Trinidad and Tobago 0 199† 199 0 95 487† 95 487

Costa Rica 115 195 80 152 880 329 034 176 154

Jamaica 58 133 75 54 711 132 751 78 040

Guatemala 4 115 111 17 011 592 148 575 137

Cuba 69 95‡ 26 279 484 388 268‡ 108 784


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Dominica 74‡ 76 2 1951‡ 2083 132

Belize 0 73 73 0 8325 8325

El Salvador 129 65 –64 292 796 146 449 –146 347

Grenada 72 53‡ –19 2530 1935‡ –595

Honduras 2† 49† 47 4500† 137 673† 133 173

Montserrat 137 53 –84 313 77 –236

Anguilla 237† 42† –195 970† 184† –786

Nicaragua 36 37 1 65 915 76 887 10 972

Dominican Republic 22 19 –3 69 880 68 702 –1178

Haiti 7 4† –3 20 261 13 003† –7258

Antigua and Barbuda 96 0 –96 2316 0 –2316

Aruba 0 0 0 0 0 0

Bermuda 0 0 0 0 0 0

Saint Kitts and Nevis 85† 0 –85 1204† 0 –1204

Saint Lucia 131† 0 –131 7167† 0 –7167

Turks and Caicos Islands 271 0 –271 1629 0 –1629

America (North) 16 046(4032 to 28 061)

31 453(8121 to 54 785)

15 407 2 367 674 568(–1 319 511 540 to 6 054 860 679)

5 301 718 536(–2 791 639 071 to 13 395 076 143)

2 934 043 968(–1 474 667 244 to 7 342 755 183)

USA 22 554 43 879 21 325 2 273 841 537 5 015 206 017 2 741 364 480

Canada 8310 22 941 14 631 92 647 530 282 085 324 189 437 794

Mexico 33 110 77 1 185 377 4 427 336 3 241 959

America (South) 152(102 to 201)

347(239 to 455)

195 18 695 456(–3 274 934 to 40 665 846)

48 788 740(1 119 987 to 96 457 482)

30 093 284(2 441 000 to 57 745 557)

Falkland Islands 5381 2670 –2711 3928 2923 –1005

Chile 216 747 531 1 185 950 4 652 598 3 466 648

Argentina 158 741 583 2 107 837 10 967 402 8 859 565

Brazil 193 342 149 11 638 322 24 311 791 12 673 469

Colombia 84 329 245 1 269 736 5 516 793 4 247 057

Uruguay 604 311 –293 728 731 380 693 –348 038

Venezuela 94 126 32 804 138 1 315 196 511 058

Guyana 27 123‡ 96 8024 33 808‡ 25 784

Peru 55 102 47 502 942 1 092 862 589 920

Ecuador 42 79 37 192 723 398 267 205 544

Bolivia 20 32† 12 59 353 116 404† 57 051

Paraguay 94 0 –94 184 523 0 –184 523

Suriname 61 0 –61 9249 0 –9249

Asia (east and southeast) 56(–6 to 119)

189(–13 to 391)

133 40 885 544(–4 336 870 to 86 107 958)

148 522 285(183 770 to 296 860 783)

107 636 741(75 463 to 215 198 019)

South Korea 263 2244 1981 4 501 781 39 571 421 35 069 640

Japan 432 1192 760 19 998 207 55 229 499 35 231 292

Singapore 112 435 323 161 866 770 203 608 337

Macau 35 221 186 5511 36 713 31 202

Brunei 41 219 178 4971 32 361 27 390

Malaysia 78 212 134 646 122 2 158 081 1 511 959

Hong Kong 159 175 16 390 153 450 146 59 993

China 29 91 62 13 208 276 44 682 861 31 474 585

Thailand 39 85 46 887 148 2 107 700 1 220 552

Vietnam 7 34 27 210 776 1 107 909 897 133

Mongolia 11† 29 18 9647† 28 352 18 705


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North Korea 13 26 13 157 292 226 667 69 375

Philippines 10 21 11 276 900 701 871 424 971

Indonesia 4 16 12 292 961 1 362 450 1 069 489

Laos 2 7 5 3872 16 747 12 875

Cambodia 28 6 –22 118 565 33 578 –84 987

Myanmar 1 0† –1 11 494 5 722† –5772

Timor-Leste - 0 - 0 0 0

Asia (south) 10(8 to 11)

11(10 to 12)

1 4 017 864(–2 324 292 to 10 360 014)

5 665 686(–2 675 376 to 14 006 748)

1 647 822(–385 595 to 3 681 233)

Bhutan 1‡ 844† 843 678‡ 218 003† 217 325

Sri Lanka 26 24 –2 182 089 180 276 –1813

Maldives 6 19 13 569 2203 1634

India 10 11 1 3 520 326 4 677 970 1 157 644

Nepal 11 11 0 89 461 116 911 27 450

Bangladesh 5 8 3 224 739 470 323 245 584

Asia (west) 71(–1 to 142)

202(–19 to 423)

131 11 093 500(1 027 796 to 21 159 182)

41 784 552(–1 986 216 to 85 555 320)

30 691 052(–3 519 324 to 64 901 428)

Israel 1857 4664 2807 4 096 440 12 377 943 8 281 503

Turkey 142 706 564 3 373 459 19 098 889 15 725 430

Bahrain 109 465 356 26 697 162 265 135 568

Kuwait 79 383 304 60 471 411 459 350 988

Jordan 88 286 198 181 013 650 325 469 312

Saudi Arabia 111 258 147 814 259 2 486 793 1 672 534

Lebanon 211 221 10 258 593 342 431 83 838

Qatar 147 188 41 30 404 102 520 72 116

United Arab Emirates 122 181 59 121 586 357 674 236 088

Oman 55 140 85 47 848 142 457 94 609

Syria 26 136 110 152 289 1 059 465 907 176

Kazakhstan 60 120 60 328 560 687 786 359 226

Iran 46 116 70 1 060 526 3 154 838 2 094 312

Georgia 66 101 35 125 819 158 762 32 943

Armenia 23 26† 3 30 711 29 840† –871

Kyrgyzstan 37 22 –15 63 139 43 480 –19 659

Uzbekistan 7 10 3 59 989 103 648 43 659

Azerbaijan 10 11 1 27 636 36 958 9322

Turkmenistan 5 12 7 8610 21 958 13 348

Yemen 2‡ 8† 6 11 810‡ 65 439† 53 629

Iraq 3† 4‡ 1 24 254† 45 050‡ 20 796

Pakistan 4† 3 –1 189 384† 233 005 43 621

Tajikistan 0 3† 3 0 7356† 7356

Afghanistan 0 0 0 0 4214 4 214

Europe (east) 89(87 to 92)

106(80 to 132)

17 6 836 204(–732 936 to 14 405 344)

7 778 888(–656 112 to 16 213 888)

942 684(–1 312 948 to 3 198 320)

Belarus 75 300 225 276 221 1 053 426 777 205

Russia 89 106 17 4 762 723 5 476 157 713 434

Moldova 79† 103 24 105 393† 135 099 29 706

Ukraine 93 67 –26 1 691 865 1 114 207 –577 658

Europe (southeast) 238(138 to 338)

1100(699 to 1501

862 4 421 766(1 837 314 to 7 006 218)

21 150 936(3 266 416 to 39 035 456)

16 729 170(–4 775 428 to 38 233 768)

Croatia 490 2733 2243 793 027 4 390 853 3 597 826


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Montenegro - 1498 - - 338 014 -

Serbia - 1384 - - 4 968 171 -

Romania 203 1200 997 1 668 604 9 341 718 7 673 114

Bosnia and Herzegovina 0 591 591 0 813 386 813 386

Bulgaria 348 426 78 1 030 354 1 167 966 137 612

Macedonia 714 91 –623 523 521 67 800 –455 721

Albania 33 55 22 39 322 63 028 23 706

Europe (west and central) 3079(1274 to 4883

9320(3969 to 14 672)

6241 519 637 860(64 008 690 to 975 267 000)

1 641 965 130(221 551 530 to 3 062 378 700)

1 122 327 270(150 295 080 to 2 094 359 490)

Germany 7465 23 352 15 887 223 556 688 700 442 541 476 885 853

Austria 5838 20 066 14 228 17 249 006 61 250 498 44 001 492

Belgium 8547 18 281 9734 31 861 768 71 179 768 39 318 000

Denmark 7088 15 055 7967 13 768 932 30 183 306 16 414 374

Gibraltar 1354 13 685 12 331 12 792 134 869 122 077

Switzerland 2979 11 186 8207 7 764 608 31 020 322 23 255 714

Netherlands 2430 10 821 8391 14 034 859 65 620 199 51 585 340

Spain 2310 9090 6780 33 246 176 150 334 739 117 088 563

Norway 3614 8669 5055 5 888 619 15 279 581 9 390 962

Luxembourg 4279 8371 4092 673 005 1 010 249 337 244

Sweden 3342 8343 5001 10 809 679 28 363 605 17 553 926

Iceland 3410 7921 4511 345 830 921 048 575 218

France 3216 7042 3826 69 184 601 160 628 817 91 444 216

Finland 2719 6147 3428 5 126 769 11 988 080 6 861 311

Ireland 2302 5708 3406 3 148 923 9 390 873 6 241 950

UK 1658 5227 3569 35 916 961 117 982 759 82 065 798

Slovenia 1567 5034 3467 1 135 973 3 717 757 2 581 784

Hungary 1012 3984 2972 3 717 751 14 512 493 10 794 742

Czech Republic 924 3953 3029 3 468 787 15 015 279 11 546 492

Italy 725 3953 3228 15 225 539 86 733 546 71 508 007

Greece 1327 5132† 3805 5 032 570 20 864 728† 15 832 158

Slovakia 660 3221 2561 1 300 009 6 379 288 5 079 279

Andorra 603 2514 1911 14 763 82 811 68 048

Portugal 1148 2302 1154 4 180 692 8 977 575 4 796 883

Poland 830 1916 1086 11 715 941 26 701 007 14 985 066

Cyprus 304 1458 1154 83 531 482 784 399 253

Lithuania 255 1237 982 344 364 1 498 797 1 154 433

Latvia 700 1122 422 622 035 926 235 304 200

Estonia 355 588 233 181 373 284 457 103 084

Malta 180 382 202 25 314 57 103 31 789

Oceania 2275(763 to 3787

9136(2508 to 15 765)

6861 25 142 920(–19 741 480 to 70 027 300)

115 616 337(–93 515 215 to 324 747 872)

90 473 417(–73 966 612 to 254 913 446)

Australia 3287 13 440 10 153 22 751 306 106 307 246 83 555 940

Norfolk Island 1199 5792 4593 875 4228 3353

New Zealand 1525 5505 3980 2 121 782 8 737 791 6 616 009

New Caledonia 1300 3075 1775 98 140 240 171 142 031

French Polynesia 964‡ 1904 940 82 008‡ 170 248 88 240

Wallis and Futuna Islands 385 1155‡ 770 1968 6323‡ 4355

Palau 268 488 220 1840 3633 1793

Christmas Island 3667 247 –3420 3657 270 –3387


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The relation between use and the prevalence of health disorders warranting use of opioids shows that the consumption in many of these countries is less than levels

suggested by need. Data from the International Agency for Research on Cancer18 show that more than half of all cancer cases (56·8%) and cancer deaths (64·9%) in 2012 occurred in low-income regions. In these regions, the disease is mostly discovered when it is at an advanced stage because of a low capacity to prevent and detect cancer early.22 By then, palliation is often needed and access to opioid analgesics essential. The relation between cancer incidence and consumption of opioid analgesics shows a marked variation, as would be expected in view of the disparities in use between countries worldwide (fi gure 3) and regionally (appendix). The same is true in the case of AIDS (appendix). Inadequate availability of opioid analgesics to manage AIDS-related pain is a major problem for a large number of people in low-income countries, particularly sub-Saharan Africa and Asia, where AIDS-related palliative care needs are not met by suffi cient availability.24

Impediments to the availability of opioid analgesics are presented in table 2. The barriers to opioid medicine use include absence of prescriber training, fear of producing dependence on opioid analgesics, fi nancial constraints, and problems sourcing or importing opioid medicines. Cultural attitudes toward pain management, fear of diversion, and fear of criminal prosecution were also frequent impediments. We identifi ed the expense and diffi culty of control measures, such as the need for





Cook Islands 144 78† –66 889 515† –374

Federated States of Micronesia

64† 72† 8 2784† 2817† 33

Papua New Guinea 28 54‡ 26 50 309 125 305‡ 74 996

Nauru 0 45‡ 45 0 165‡ 165

Tonga 137 42† –95 4934 1601† –3333

Fiji 27‡ 42‡ 15 7910‡ 12 144‡ 4234

Samoa 27‡ 29† 2 1683‡ 2139† 456

Tuvalu 1276† 27† –1249 5120† 97† –5023

Vanuatu 20 20 0 1350 1634 284

Cocos (Keeling) Islands 21† 0 –21 8† 0 –8

Kiribati 30‡ 0 –30 896‡ 0 –896

Marshall Islands 75† 0 –75 1530† 0 –1530

Solomon Islands 25 0 –25 3924 0 –3924

Data in parentheses are 95% CIs. 95% CIs are given around the worldwide and regional estimates. Country 95% CIs are presented in the appendix. The reporting of the mean of 3 years of use (2001–03 and 2011–13) removed annual variations and provided the most stable use data, and if data for a year were not reported by a country, we divided use data for the available years by the number of years for which data were available. If fewer than three observations were available, we denoted the number of observations with footnotes. Countries provided the International Narcotics Control Board with estimates of their needs 6 months before the beginning of the year. These estimates were revised as needed at any time during the year. 6 months after the end of the year, countries provided fi nal statistics for consumption, manufacturing, export, and import for the year before. These statistics included the amount of drugs that had been destroyed and not used. The data for consumption are only for the drugs that were actually used. This information was verifi ed by the International Narcotics Control Board, and we checked quantities reportedly consumed against the import and export information provided by governments. We followed up discrepancies and asked governments to clarify these discrepancies on a routine basis. S-DDD=defi ned daily doses for statistical purposes. DDD=defi ned daily dose. *Because S-DDD is based on the population (ie, total S-DDD for a region is a weighted average on the basis of country S-DDD and average population over 3 years), CIs for change in S-DDD could not be calculated because the S-DDD was based on two diff erent populations (one for each of the time periods), so we could not weight by a single population estimate and thus could not calculate CIs for change in S-DDD. †Two observations for time period. ‡One observation for time period.

Table 1: Mean per-annum S-DDD and DDD use worldwide, regionally, and at the country level in the years 2001–03 and 2011–13, ordered by 2011–13 S-DDD use, and absolute changes in use

0 50 100 150 200 300250 350

0

15 000

25 000

30 000

40 000

45 000

5000

10 000

20 000

35 000

S-DD

D pe

r mill

ion

inha

bita

nts p

er d

ay

Cancer ASR

AfricaAsiaEastern EuropeWestern EuropeOceaniaAmericasUSA

Figure 3: Cancer ASR and consumption of opioid analgesicsData from some countries are not available in GLOBOCAN and are registered as 0. ASR=age-standardised rate. S-DDD=defi ned daily doses for statistical purposes. Data taken with permission from WHO18 and from the International Narcotics Control Board.23

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import and export authorisations, as impediments. Specifi cs of the nature of impediments are beyond the scope of this report, but are discussed elsewhere.21 Figure 4 shows the change in impediments reported in 1995, 2010, and 2015. Reporting of fear of causing dependence and onerous regulations or legislative restrictions, which were frequently mentioned impedi-ments 20 years ago, decreased in frequency (fear of dependence 23 [64%] of 36 in 1995 vs 67 [47%] of 144 in 2010 vs 34 [32%] of 106 in 2015; onerous regulation 19 [53%] vs 37 [26%] vs 19 [18%]).4,6,21

Negative binomial regression analyses of the weighted count (appendix) of the number of impediments reported per country showed that a higher number of impediments was signifi cantly associated with lower S-DDD worldwide (unadjusted incidence rate ratio 0·39 [95% CI 0·29–0·52]; p<0·0001), but not when adjusted for GDP and HDI (incidence rate ratio 0·91 [0·73–1·14]; p=0·4271). Subregion, GDP, and HDI also predicted S-DDD use (appendix). Regression separately assessing the 11 impediments showed that action by the Board was associated with less use (p=0·0158) being reported by four (4%) of the 106 countries than with no action, with 267 impediments being mentioned in total (appendix).

As expected on the basis of other work,25 countries that did not respond to the survey had signifi cantly lower S-DDD (u=–4·24, p<0·0001; appendix) and DDD (u=–6·07; p<0·0001) use than did responding countries, and lower mean HDI category (not responding mean 2·26 [SD 1·13]; responding mean 2·86 [SD 1·03]; t183=3·77; p<0·0001).

DiscussionA doubling in worldwide use of opioid analgesic medicines occurred between 2001–03 and 2011–2013. Use remains unevenly spread across regions, as reported in descriptive studies previously.13,14 In this study, to our knowledge, we have shown for the fi rst time that high-income countries, particularly in North America, Oceania, and western and central Europe, account for the growth of use, with signifi cantly higher use than all other regions for every year after 2001 unadjusted, but without a signifi cant diff erence after adjustment for GDP and HDI,16 which were also signifi cantly associated with S-DDD use. The situation has changed so little in regions with low-income and middle-income countries that improvement remains unlikely in the absence of specifi c strategies to deal with the impediments to increased

Absence of awareness or training in use of opioid drugs in members of the medical profession

Fear of addiction*

Restricted fi nancial resources

Issues in sourcing from industry or imports

Cultural attitudes towards treatment of pain

Fear of diversion to illicit channels

Control measures applicable to international trade such as need for import or export authorisation

Fear of criminal prosecution or sanction

Onerous regulatory framework for prescription of narcotic drugs for medical use

Actions taken by the INCB

Other reasons†

Worldwide count (106 [50%] of 214)

36 (34%) 34 (32%) 32 (30%) 31 (29%) 30 (28%) 30 (28%) 22 (21%) 22 (21%) 19 (18%) 4 (4%) 7 (7%)

Africa (20 [36%] of 56)

8 (40%) 6 (30%) 9 (45%) 11 (55%) 6 (30%) 9 (45%) 9 (45%) 5 (25%) 3 (15%) 4 (20%) 1 (5%)

America (North; 3 [100%] of 3)

2 (67%) 0 0 0 1 (33%) 0 1 (33%) 1 (33%) 0 0 2 (67%)

America (South and Caribbean; 19 [44%] of 43)

7 (37%) 6 (32%) 8 (42%) 5 (26%) 7 (37%) 5 (26%) 3 (16%) 7 (37%) 5 (26%) 0 2 (11%)

Asia (east and southeast; 9 [50%] of 18)

3 (33%) 5 (56%) 1 (11%) 3 (33%) 2 (22%) 6 (67%) 1 (11%) 3 (33%) 1 (11%) 0 0

Asia (south and west; 21 [68%] of 31)

4 (19%) 5 (24%) 3 (14%) 6 (29%) 6 (29%) 6 (29%) 6 (29%) 3 (14%) 5 (24%) 0 1 (5%)

Europe (west and central; 20 [69%] of 29)

7 (35%) 7 (35%) 6 (30%) 3 (15%) 6 (30%) 2 (10%) 0 1 (5%) 4 (20%) 0 0

Europe (east and southeast; 8 [67%] of 12)

4 (50%) 4 (50%) 3 (38%) 1 (13%) 1 (13%) 2 (25%) 0 2 (25%) 1 (13%) 0 0

Oceania (6 [27%] of 22)

1 (17%) 1 (17%) 2 (33%) 2 (33%) 1 (17%) 0 2 (33%) 0 0 0 1 (17%)

INCB=International Narcotics Control Board. *The term addiction was used in the international survey as an easily translatable term, but we note that it is deemed a pejorative term. †Included manufacturing or safety issues; interruptions in delivery of medicines through supply chain and distribution network; unexpected increase in demand for specifi c drugs; business decision to stop producing a drug; scarcity of controlled substances, mainly due to diversion into illicit channels via the internet; absence of drug forms, especially for the paediatric population; inadequate reporting and forecasting of need; and absence of some pharmaceutical forms of narcotic drugs.

Table 2: Impediments in relation to availability of opioid analgesics

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availability. Much of increased usage that has occurred in high-income countries is probably partly due to long-term prescribing for non-cancer pain,26 but the absence of real growth in use in most of the world shows a continuing absence of provision of these essential medicines.

The impediments most frequently identifi ed by countries included an absence of training for or awareness of medical professionals, fear of addiction, restricted fi nancial resources, issues in sourcing, cultural attitudes, and fear of diversion. These barriers have also been reported at a country level by others using diff erent methods and drawing on clinicians rather than staff in the national competent authorities.27 The frequency of concern about two impediments—fear of creation of opioid dependence and onerous regu-lations—decreased substantially since 1995.6 Fear of causing dependence might be specifi cally related to an absence of awareness and training and to cultural attitudes, although such fear can arise because of leg-itimate public health concerns.28 Our results are consistent with other reports on barriers to use,14,29–32 and together, they suggest a more complex array of reasons for low use than some have asserted.33 Our study is the fi rst to assess the association between impediments and use, controlling for potential confounders of GDP and country-level development. Unadjusted, the weighted number of impediments reported at the country level was signifi cantly associated with use, but after adjust-ment for these confounders, the number of imped i-ments was no longer signifi cantly associated. The

impediments seem to be candidate causes for the absence of change in many regions, but might be secondary to GDP and HDI.

Access and use is established not only by physical availability and practical accessibility, but also by aff ordability,14,34 as evidenced by the signifi cant relation between GDP, HDI, and use. Restricted resources and infrastructure impair the capacity of governments to provide or subsidise medicines and limit the capacity of patients to aff ord them. Medicine prices might be infl ated because of costs of regulation, licensing, taxation, importation, ineffi cient distribution systems, and absence of public reimbursement and inexpensive formulations. Manufacturers and importers or export-ers might not produce or trade aff ordable formulations of medicines when they perceive such formulations to be insuffi ciently profi table. Additionally, shortages can also arise from inadequate estimates of need by countries, lengthy and burdensome regulatory require-ments, and delays in the supply chain. Access to internationally controlled substances might also be unduly restricted because of concern of diversion into illicit channels and prescribers’ fears of prosecution or sanction. Fear of prosecution or sanction will be exacerbated when legislation is unclear and stigmatising and where health professionals lack legal knowledge or are fearful of harsh penalties for violations. These penalties can exceed the provisions of the drug control treaties.14 Such regulation can comprise short pre-scription validities, special multiple-copy pres cription forms, onerous record-keeping requirements, overly restricted access to prescription forms, and other restrictions to pre scribing or dispensing drugs and opioid medicines (which are often especially scarce in rural areas). Additionally, most countries or territories restrict prescribing to medical staff and do not allow refi lls without a new prescription. Such regulations are not required by international conventions,1 and could be changed.

Ensuring of access does not necessarily mean increased misuse and diversion, but a balance between control on the one hand and overly liberal availability on the other does need to be maintained. Countries can review legislation and regulatory systems35 to remove unduly restrictive provisions while still preventing diversion. An adequate and well-resourced infra-structure is needed to ensure the provision and distribution of medicines, especially in rural areas. Public funding and reimbursement schemes, in addition to the supply of aff ordable formulations by pharmaceutical companies, could help overcome fi -nancial barriers. Improved training of health-care professionals can reduce fear, stigma, and prejudices while curbing diversion for non-medical use. The capacity of competent national authorities to adequately estimate and assess the need for these medicines has to be strengthened.

1995 2010 20150

30

20

10

40

50

60

70

80

90

100

Coun

trie

s rep

ortin

g im

pedi

men

ts (%

)

Time (years)

Issues in sourcingOnerous regulationsFear of addictionRestricted financial resourcesAbsence of training for orawareness of professionals

Figure 4: Impediments to the availability of opioid analgesicsA small number of categories are presented in this fi gure because the number of categories of impediments in previous surveys was less than in the 2015 survey, and only the commonly reported impediments are presented. Valid responses were provided by 36 countries in 1995,6 144 in 2010,4 and 106 in 2015.21 Data taken from the International Narcotics Control Board.4,6,21

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potential collaborations.3,41 Initiatives by governments and international agencies can bring about greater use than at present while balancing improved availability with risks of overprescribing and the pernicious reverse problem: overly cautious prescribing with consequent reduced use.ContributorsSB, JE, DTJ, AM, AKES, WS, VS, SS, and RY conceived the study, which was designed by SB and JE and approved by DTJ, AM, AKES, WS, VS, SS, and RY. Data were acquired by JT and analysed by JT, PC, SF, and BV, and all authors interpreted it. The report was drafted by SB, JE, BV, and RPM, and all authors critically revised it. All authors contributed to and approved the fi nal report, and SB is the study guarantor.

Declaration of interestsWe declare no competing interests.

AcknowledgmentsThis work was funded by the International Narcotics Control Board and the UN. Louisa Degenhardt and Michael Farrell of the University of New South Wales, Australia, Wayne Hall of the University of Queensland, Australia, and Francisco E Thoumi of the International Narcotics Control Board provided valuable comments on drafts of this report. Timothy Dobbins of the University of New South Wales provided additional statistical advice.

References1 UN Offi ce on Drugs and Crime. The international drug control

conventions. New York: United Nations, 2009.2 Hogerzeil HV, Liberman J, Wirtz VJ, et al. Promotion of access to

essential medicines for non-communicable diseases: practical implications of the UN political declaration. Lancet 2013; 381: 680–89.

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Our work has limitations. DDD do not represent clinical use exactly, but represent one proxy. Oral morphine equivalents are an alternative to DDD36 and could provide diff erent rankings of countries, especially if large diff erences between DDD and prescribed doses exist. However, the picture of use presented in this study seems unlikely to be markedly altered by such an alternative assessment method. Uncertainty currently exists around the estimates of use because population estimates have imprecision, especially in low-income countries, and because medicines could be stockpiled or unused; however, the repeated annual country reporting of stock-on-hand to the INCB, with annual estimates of need, reduce the likely eff ect of such issues. Detailed statistics of various opioid medicines are not presented in this study, but are available.37 In terms of opioid availability and need, the extent of disease burden is diffi cult to precisely estimate, as is the need for pain relief, and as others note, no objective standard exists for an adequate level of opioid consumption.12 Additionally, many disorders need treatment with opioid analgesics, other than cancer and AIDS, that are not covered in this study. The extent of use could be far lower than is needed, and targets for improvement in use should possibly be set even higher. In that respect, our specifi cation of low levels of use provide guidance; they are necessarily an objective standard and countries should not be constrained if greater levels of use are needed. Finally, we have not included all analgesic formulations, but the worldwide picture would be unlikely to be markedly diff erent.

Turning to limitations in our analysis of impediments, countries that did not respond to the survey of impediments could have resulted in an underestimate of the extent of the barriers. Notably, the non-responding countries had signifi cantly lower S-DDD use (appendix) and thus might have a greater number of impediments than the responding countries. Additionally, the nature of impediments at a country level will be more nuanced than can be captured here, but we provide a checklist of the types of issues to be considered at a country level. Regional or country historical, cultural, and policy factors will aff ect use, and country-specifi c solutions are needed.9 Responses to country-level surveys of impediments are not easily validated, but staff of countries’ national competent authorities are in contact with the INCB annually and understand the issues of availability, and the number of impediments reported was signifi cantly related to opioid use in regression analysis, suggesting a reliable relation. Although we surveyed national competent authorities, practitioners’ views could have provided valuable data. Finally, we do not address within-country disparities in access.38

Progress during the next decade must be made to ensure that these factors do not continue to impede opioid analgesic use.8,9,39 New approaches to deal with the imbalance are being identifi ed,9,40 and others have set out roles for international organisations, governments, and

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36 Svendsen K, Borchgrevink P, Fredheim O, Hamunen K, Mellbye A, Dale O. Choosing the unit of measurement counts: the use of oral morphine equivalents in studies of opioid consumption is a useful addition to defi ned daily doses. Palliat Med 2011; 25: 725–32.

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41 Cleary J, Radbruch L, Torode J, Cherny N. Next steps in access and availability of opioids for the treatment of cancer pain: reaching the tipping point? Ann Oncol 2013; 24 (suppl 11): xi60–64.