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&Medicine =
Annals of = Oncology
Volume 21,=20 Issue 3
Pp. 615-626. =

Formulary availability and regulatory barriers = to=20 accessibility of opioids for cancer pain in Europe: a report from the = ESMO/EAPC=20 Opioid Policy Initiative

¹Cancer Pain and Palliative Medicine Unit, = Department of=20 Oncology, Shaare Zedek Medical Center, Jerusalem, Israel
²European Society for Medical Oncology
³Palliative Care Working Group
⁴Medical Oncology Service, Vall d'Hebron = University=20 Hospital, Barcelona, Spain
⁵European Society for Medical Oncology
⁶European Association for Palliative Care =
⁷Palliative Medicine, Aachen University, Aachen, = Germany=20

*Correspondence to: Dr N. I. = Cherny,=20 Cancer Pain and Palliative Medicine Service, Department of Medical = Oncology,=20 Shaare Zedek Medical Center, Jerusalem 91031, Israel. Tel: +972 = 508-685780;=20 Fax: +972-2-6666731; E-mail: nathancherny{at}yahoo.com

Received October 3, 2009.=20
Revision received November 25, 2009.=20
Accepted November 25, 2009. =

Next=20 Section

Abstract

Background: Many patients in Europe do not = receive=20 adequate relief of pain because of excessive regulatory restrictions on = the=20 availability and accessibility of opioids. This is a major public health = problem. The aim of the study is to evaluate and report on opioid = availability=20 and the legal and regulatory barriers to accessibility across the = countries of=20 Europe.

Methods: European Society for Medical = Oncology and=20 European Association for Palliative Care national representatives = reported data=20 regarding survey of opioid availability and accessibility. Formulary = adequacy is=20 evaluated relative to the World Health Organization (WHO) essential = drugs list=20 and the International Association for Hospice and Palliative Care list = of=20 essential medicines for palliative care. Overregulation is evaluated = according=20 to the guidelines for assessment of national opioid regulations of the = WHO.

Results: Data were reported on the = availability and=20 accessibility of opioids for the management of cancer pain in 21 Eastern = European countries and 20 Western European countries. Results are = presented=20 describing the availability and cost of opioids for cancer pain in each = surveyed=20 country and nine forms of regulatory restrictions.

Conclusions: Using standards derived from = the WHO and=20 International Narcotics Control Board, this survey has exposed formulary = deficiencies and excessive regulatory barriers that interfere with = appropriate=20 patient care in many European countries. There is an ethical and public = health=20 imperative to address these issues.

Key words

Previous=20 Section Next=20 Section

introduction

For patients with cancer, and especially those with advanced = and=20 incurable cancer, adequate relief of pain is the central goal of care = [1, 2].=20 Indeed, adequate relief of pain is now recognized as a patient right [3=E2=80=935]. This=20 right implies duties; the duties of clinicians to assess pain and to = treat it in=20 accordance with the best of contemporaneous practices (that prevailing = resources=20 will enable) and duties of governments and health care regulatory = systems to=20 ensure that patients can access the medications needed to relieve pain. =

Opioid analgesics are critical to the effective relief of = cancer pain.=20 Effective treatment is predicated on sound assessments, individually = tailored=20 analgesic therapy and the availability and accessibility of the required = medications. In some countries, pain relief is hampered by lack of = availability=20 or barriers to accessibility of opioid analgesics. In many countries,=20 excessively zealous or poorly considered laws and regulations to = restrict the=20 diversion of medicinal opioids into illicit markets profoundly interfere = with=20 the medical availability of opioids for the relief of pain. Often, the = logistics=20 of the treatment of pain with opioids is so burdensome or complex for=20 physicians, nurses and pharmacists as to be a major disincentive to = involvement.=20

These burdens are compounded for patients and their families = who, in=20 many situations, must cajole doctors, chase after permits, wait = excessively in=20 inconveniently located pharmacies and return for frequent refills of=20 prescriptions or any correction on a prescription that may not have been = written=20 with adequate attention to required details. In some countries, the = degree of=20 legal intimidation is such that fear of criminal prosecution contributes = to=20 deliberate undertreatment by clinicians to avoid risk of persecution or=20 prosecution.

The consequences for health care professionals, patients and = their=20 families are manifold and profound. Excessive regulatory restrictions = make it=20 near impossible for many Europeans to achieve relief of cancer pain that = undermines their quality of life. These issues are reflected in = substantial=20 differences in opioid consumption between European countries (Figure= 1)=20 and in profound differences in morphine consumption between Western and = Eastern=20 European countries (Figure= 2).=20 It is a public health travesty that many patients in Europe do not = receive=20 adequate relief of pain because of poorly considered regulations and=20 deficiencies in public policy. These issues have been highlighted in a = review of=20 the barriers to the development of palliative care in Eastern Europe [6].

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Figure 1.=20

European consumption of morphine, = 2006.

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Figure 2.=20

East versus West Europe: morphine = consumption,=20 average milligram per capita*, 1980=E2=80=932006. *Average milligram per = capita=20 calculated by adding milligram per capita statistic for each country and = dividing by the total number of countries.

The problem of overregulation has been highlighted by the = Open=20 Society Institute International Palliative Care Initiative (www.s= oros.org/initiatives/health/focus/access/about),=20 the International Observatory on End of Life Care (http://www.eolc-observatory.net= /),=20 the International Narcotics Control Board (INCB) [7=E2=80=9310= ],=20 the World Health Organization (WHO) [11= , 12= ],=20 the Council of Europe [13= ] and=20 most recently by Human Right Watch [3].

The largest bodies of cancer and palliative care clinicians = in=20 Europe, the European Society for Medical Oncology (ESMO) and the = European=20 Association for Palliative Care (EAPC), view this matter with utmost = gravity [14= ]. To=20 address this issue, they have developed a European Pain Policy = Initiative. The=20 first aim of this initiative is to evaluate and report on opioid = availability=20 and the legal and regulatory barriers to accessibility across the = countries of=20 Europe. This paper reports the findings of the ESMO/EAPC survey of = opioid=20 availability and accessibility across Europe. The adequacy of formulary=20 availability is evaluated relative to the WHO essential drugs list and = the=20 International Association for Hospice and Palliative Care (IAHPC) list = of=20 essential medicines for palliative care. Overregulation is evaluated = according=20 to the principles derived from the guidelines for assessment of national = opioid=20 regulations of the WHO [11= , 12= ].=20

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methods

On the basis of a review of the literature regarding opioid = availability and accessibility, a questionnaire was developed to survey = opioid=20 formularies across the countries of Europe, the cost of the medications = to=20 patients and the regulatory barriers that adversely effect = accessibility. The=20 questionnaire included items relating to formulary; cost to patients;=20 regulations relating to dose limits, prescribing, dispensing and = emergency=20 situations and the use of stigmatizing language in the opioid = regulations (Table = 1).=20

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Table 1.=20

Opioid analgesics on essential drug = lists

Both ESMO and EAPC distributed the questionnaires to = national=20 representatives in each of their European member countries in 2007 and = 2008,=20 respectively. These national representatives were all senior clinicians = holding=20 leadership positions in their respective countries in oncology or = palliative=20 care. The clinicians were requested to complete the questionnaire to the = best of=20 their knowledge and experience. In situations in which they lacked = specific=20 knowledge or information, they were instructed to seek advice from the = local=20 regulatory authorities in their country.

The questionnaires that were submitted by the national=20 representatives were collated by NC, tabulated, graphically presented = and=20 redistributed for corroborating comments or feedback and validation. In = January=20 2009, graphic presentations of the reports were recirculated to national = representatives of the two organizations for updating and verification = and to=20 all the members of the EAPC for open peer review and verification. = Amendments=20 were collated, cross-checked and incorporated into the final report, = which was=20 completed in June 2009.

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results

general

Data were reported on the availability and accessibility of = opioids=20 for the management of cancer pain in 41 countries in Europe: 21 = East-European=20 countries and 20 West-European countries (including Israel).

formulary availability and cost of opioids for cancer pain

The availability of opioids and their cost to consumer are = summarized=20 in Figure= s 3=20 and 4.= Except=20 for Greece and Turkey, the opioid formularies of most West-European = countries=20 avail a range of options with different opioids. In the majority of = Western=20 European countries, most opioids are available at no cost to patients = with=20 cancer pain. In Germany, Luxembourg, Spain, Switzerland, UK and Belgium, = the=20 opioid analgesics are subsidized >75% for cancer patients but are not = free.=20 In Iceland, opioid analgesics are not subsidized for any class of = patients.

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Figure 3.=20

Opioid availability in Western European = countries.=20 Propox, propoxyphene; NC, hydrocodone; DHC, dihydrocodeine; Bupr, = buprenorphine;=20 Mo, morphine; Oc, oxycodone; Methad, methadone; Fent, fentanyl; Hm,=20 hydromorphone; Peth, pethidine; PO, oral; Propox, propoxyphene; TD, = transdermal;=20 TM, transmucosal; Inj, injectable; IR, immediate release; CR, controlled = release.

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Figure 4.=20

Opioid availability in Eastern European = countries.=20 Propox, propoxyphene; NC, hydrocodone; DHC, dihydrocodeine; Bupr, = buprenorphine;=20 Mo, morphine; Oc, oxycodone; Methad, methadone; Fent, fentanyl; Hm,=20 hydromorphone; Peth, pethidine; PO, oral; TD, transdermal; TM, = transmucosal;=20 Inj, injectable; IR, immediate release; CR, controlled release.

In general, the opioid formularies of many East-European = countries=20 are substantially more limited. Some countries such as the Czech = Republic,=20 Croatia, Latvia, Rumania, the Slovak Republic, Hungary, Estonia and = Serbia avail=20 both essential medicines and other options with most either free for the = patient=20 or at >75% subsidy. Not all countries avail codeine and oral = morphine, which=20 are on the essential medicines list of the WHO [15= ].=20 Severe formulary deficiencies, characterized by unavailability of = essential=20 medicines, are present in Lithuania, Tajikistan, Belarus, Albania, = Georgia and=20 Ukraine.

regulatory restrictions to accessibility

Countries used a range of regulatory restrictions to limit=20 accessibility of opioids. Overall, regulatory restrictions were much = more common=20 in East-European countries than in West-European countries.

requirement for permission/registration of patient to render them = eligible=20 to receive opioid prescription.

Most of the East-European and a minority of the = West-European=20 countries require that patients, particularly outpatients, receive a = permit or=20 be registered to be eligible to receive opioid prescriptions for the = management=20 of cancer pain (Figure= 5).=20 In some countries, this is also true for hospice patients.

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Figure 5.=20

Requirement for authority to receive = and prescribe=20 opioids. *Only physicians who have applied for and received special = prescription=20 forms.

requirement for physicians to receive a special authority/license to = prescribe opioids.

Some countries restrict the authority to prescribe opioids = to=20 physicians with special permits or to practitioners of certain = subspecialties=20 (Figure= 5).=20 Greece is the only West-European country with such restrictions; they = are more=20 prevalent in East-European countries. In Montenegro and Ukraine, the = physicians=20 of some subspecialties do not have prescribing privileges and in Russian = Federation, Montenegro, Bosnia=E2=80=93Herzegovina and Ukraine, = privileges may be=20 extended to some nononcologic subspecialties in emergency situations = only.

requirement for duplicate prescriptions and special prescription = form.

All the East-European countries and most of the = West-European=20 countries require that opioids be prescribed using duplicate or = triplicate=20 prescriptions (Figure= 6).=20 In most of these countries, special forms must be used. Difficulty in = accessing=20 the required prescription forms was reported in Bulgaria, Moldova, = Russia,=20 Montenegro, Macedonia, Albania, Lithuania, Tajikistan and Ukraine. In = Latvia,=20 Estonia, Albania and Denmark, physicians need to purchase the = prescription=20 forms.

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Figure 6.=20

Requirement that opioids be prescribed = in multiple=20 copies or on special prescription. N/R, not relevant.

prescription limits.

Among the West-European countries, only Turkey and Greece = restrict=20 prescriptions to <21 days=E2=80=99 supply of medication (Figure= 7).=20 In contrast, many of the East-European countries restrict opioid = prescriptions=20 to <3 weeks=E2=80=99 supply and eight countries (Moldova, Russia, = Lithuania, Belarus,=20 Albania, Georgia and Ukraine) restrict supply to a week or less. In = Ukraine,=20 prescriptions are limited to 1-day supply at a time.

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Figure 7.=20

Prescription limits (days).

dose limits.

Several countries specify maximal daily doses for one or = more of the=20 opioids on formulary (other than over-the-counter codeine). Countries in = which=20 dose limits were reported include Germany (controlled release = oxycodone), Turkey=20 (controlled release and injectable morphine), Moldova (controlled = release and=20 injectable morphine), Rumania and Russia (morphine and immediate release = oxycodone).

limitations on dispensing privileges.

Representatives from Western European countries did not = report=20 restrictions of dispensing privileges (Figure= 8).=20 Restrictions were reported in most East-European countries. When = restrictions=20 exist, opioids were available from designated pharmacies, hospital = pharmacies or=20 regional pharmacies. In Georgia, dispensing privileges for outpatient = opioids=20 are restricted to special pharmacies in district police stations.

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Figure 8.=20

Limitations on dispensing privileges. = N/R, not=20 relevant.

provision for opioid prescribing in emergency situations.

An emergency situation is defined as the one when there is = an=20 immediate need to relieve strong cancer pain but the physician is not = able to=20 physically provide a prescription (Figure= 9).=20 Examples include a pain crisis at night, on a public holiday or in a = remote=20 region. Few countries allow physicians to prescribe by telephone or to = fax a=20 prescription to the pharmacist. In Lithuania and UK, both nurses and = pharmacists=20 may issue a limited emergency prescription.

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Figure 9.=20

Emergency provisions.

pharmacist privilege to correct technical error on a = prescription.

In the situation of a patient presenting with a = prescription that=20 contains a technical error (no address, misspelling, missing value, = etc.), few=20 countries allow the pharmacist to correct the error even at the = direction of the=20 prescribing physician (Figure= 9,=20 last column).

use of stigmatizing term for opioid analgesics in regulations.

Several countries in Europe continue to use pejorative or=20 stigmatizing terms for opioid analgesics in the regulations controlling = their=20 prescription and dispensation (Figur= e=20 10). Ten countries referred to them as drugs of addiction, four as = dangerous=20 drugs and two as poisons.

<= /A>

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Figure 10.=20

Stigmatizing language in regulations. = N/R, not=20 relevant.

cross-correlation of availability and accessibility

The countries with the most limited opioid formularies = tended also to=20 have the greatest number of regulatory barriers to accessibility. Among = the=20 Western European countries, Turkey and Greece had more limited = formularies and=20 more accessibility barriers compared with the other countries.

Among the East-European countries, there was much greater=20 heterogeneity. Some countries like the Czech Republic, Croatia and = Hungary had=20 formulary availability and accessibility that was as good as most of the = Western=20 European countries. In contrast, several countries including Russia, = Montenegro,=20 Macedonia, Bosnia=E2=80=93Herzegovina, Lithuania, Belarus, Albania, = Georgia and Ukraine=20 had very restricted formularies and multiple barriers to accessibility.=20

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discussion

There is a fundamental need to ensure that opioid = analgesics are=20 available to the patients who need them and to prevent these drugs from = becoming=20 a source of harm or abuse. Drug abuse is a significant global problem. = Although=20 most of the opioids abused on a worldwide scale are derived from illicit = channels [16= ], a=20 proportion are prescription medications which have been diverted through = fraud,=20 theft, forged prescriptions, illegal pharmacies [16= , 17= ] and=20 via unscrupulous health professionals or poor clinical = practice. These=20 considerations demand that the parties involved in the legal = manufacture,=20 distribution, prescription and dispensing of opioid medications for = medical=20 purposes be mindful of their substantial abuse potential.

Ideally, international and local regulations of opioid = manufacture,=20 distribution, storage, prescription and dispensing should aim to = maintain a=20 balance between good patient care and diversion prevention. Preventing = drug=20 abuse is important, but it should not hinder patients=E2=80=99 ability = to receive the=20 care they need and deserve. This is the approach of the WHO and the INCB = [8, 9, 12= , 16= , 18= ].=20 Both recommend that opioids should be available for cancer patients at = hospital=20 and community levels and that physicians should be able to prescribe = opioids=20 according to the individual needs of each patient.

While most governments allow physicians to prescribe = opioids for=20 patients, regulations vary among nations and in many countries, = regulations to=20 reduce substance abuse and to restrict the diversion of medicinal = opioids into=20 illicit markets unduly interfere with medical availability for the = relief of=20 pain. This is the basis for the internationally recognized public health = problem=20 of overregulation.

Bases on the findings of our survey we will address three = issues:

Are opioid formularies in European countries consistent = with the=20 essential medicines list of the WHO and the IAHPC?
How compliant are European countries with the guidelines = of the WHO=20 and the INCB regarding opioid regulations for cancer pain?
Do regulations make allowances for efficient emergency = prescribing=20 and dispensing of opioids for patients with strong pain in = out-of-hours=20 situations?

are opioid formularies in European countries consistent with the = essential=20 medicines list of the WHO and the IAHPC?

The WHO essential medicines list [15= ]=20 presents a minimal formulary for a basic health care system, listing the = most=20 efficacious, safe and cost-effective medicines for priority conditions. = In=20 addition to listing codeine and morphine (immediate release, controlled = release=20 and injectable) for pain in the most recent version, the WHO Expert = Committee=20 indicates that it has invited submission for specific medicines for = palliative=20 care to be considered for inclusion in the next version. Indeed, the WHO = requested that the IAHPC develop an expert-generated essential medicines = list=20 for palliative care on the basis of criteria of efficacy and safety. = This list=20 of recommendations, published in 2007 [19= =E2=80=9322= ], is=20 endorsed by the WHO Cancer Control Program [2]. The=20 IAHPC lists all the formulations on the WHO essential pain medications = along=20 with three others: transdermal fentanyl, oral methadone and oral = immediate=20 release oxycodone (Table = 1).=20

Most West-European countries in Europe provided broad = opioid=20 formularies with a range of drugs appropriate for different routes of = delivery.=20 Most are fully compliant with the formulary recommendations of the IAHPC = and the=20 WHO. Exceptions included the exclusion of oral immediate release = morphine in=20 Turkey; exclusion of immediate release oxycodone in Portugal, Greece, = Belgium=20 and Turkey and exclusion of oral methadone in Portugal, Cyprus, Greece = and=20 Turkey.

The situation is substantially different in the = East-European=20 countries where, in general, formularies are more restrictive. Of the 21 = East-European countries surveyed, only Croatia and Rumania carried all = the=20 IAHPC-recommended opioid formulations. Eleven countries (Czech Republic, = Latvia,=20 Slovak Republic, Hungary, Estonia, Serbia, Bulgaria, Poland and Russia) = provided=20 at least five of the seven IAHPC-recommended opioid formulations. The=20 formularies of seven countries (Bosnia=E2=80=93Herzegovina, Tajikistan, = Lithuania,=20 Belarus, Albania, Georgia and Ukraine) were particularly deficient, = excluding=20 four or more of the seven IAHPC essential opioid analgesics.

how compliant are European countries with the guidelines of the WHO = and the=20 INCB regarding opioid regulations for cancer pain?

In 2000, the WHO [11= ] in=20 cooperation with the INCB published a guideline =E2=80=98Achieving = balance in national=20 opioids control policy: guidelines for assessment=E2=80=99 to assist = policy makers to=20 assess the balance of laws and regulations. This document emphasizes the = concept=20 of balance that regulations should be sufficient to prevent diversion = and=20 trafficking but that they should not compromise access for genuine = medical need.=20 The document outlines criteria for fair and valid regulations that are=20 consistent with the aims of the INCB (Table = 2).=20 Important safeguards to prevent abuse, misuse and diversion include = health care=20 provider and pharmacist education, safe storage, documentation of = medication=20 dispensed, return of unused medications and sound clinical practice = consistent=20 with standards of care.

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Table 2.=20

Criteria for fair and valid regulations = that are=20 consistent with the aims of the International Narcotics Control = Board

Many of the regulations regarding opioid prescribing and = dispensing=20 identified in this survey are inconsistent with the WHO and INCB = recommendations=20 insofar as they seek to:

limit entitlement to receive opioid analgesics to relieve = severe=20 pain only to patients with special authorizations (requirements for = patient=20 permits),
limit the empowerment of some physicians to prescribe to = patients=20 with medical need (restrictions on prescriber privileges),
interfere with clinical decision making regarding drug = dosing (dose=20 limits),
preclude provision of an adequate supply of medication to = meet=20 individual clinical needs (limits on duration of prescription, i.e. 7 = days=E2=80=99=20 supply only),
reduce accessibility to patients (restriction on opioid=20 dispensing),
increase bureaucratic burden (complex prescription form=20 requirements, poorly accessible prescription forms, complex reporting=20 requirements) and
intimidate health care providers and pharmacists = (intimidatory=20 legal sanctions).

As problematic as each of these violations are alone, when = they are=20 sequential in the process of prescribing and dispensing, their affects = are=20 multiplied, and the impact on patient care is profound. This appears to = be the=20 situation in many East-European countries, particularly in Russia, = Montenegro,=20 Macedonia, Bosnia=E2=80=93Herzegovina, Lithuania, Belarus, Albania, = Georgia and Ukraine.=20

do regulations make allowances for efficient emergency prescribing = and=20 dispensing of opioids for patients with strong pain in out-of-hours = situations?=20

Problems of severe cancer pain do not respect = physicians=E2=80=99 working=20 hours. Indeed, situations arise when patients have urgent need for the = relief of=20 severe pain when a physician may not be able to attend to them. In such=20 circumstances, potential options for opioid prescription include (i) = presenting=20 to an emergency room, (ii) contacting the physician by phone or faxing = an=20 emergency prescription to a pharmacist, (iii) having the attending nurse = generate an emergency prescription or (iv) having the pharmacist = generate an=20 emergency prescription. Very few countries in Europe make regulatory = provision=20 for these circumstances.

disclaimers and limitations

The information presented in this survey was derived from = practicing=20 clinicians and not from state authorities or statutory bodies and this = may have=20 allowed for the introduction of some inaccuracies in the data. Several = steps=20 were undertaken to minimize the risk of inaccuracy. In circumstances in = which=20 the reporting physicians were unsure of a regulation or formulary issue, = they=20 were requested to consult with regulatory authorities. Veracity of the=20 information was strengthened by opening the data to peer review by = members of=20 the EAPC, the Open Society Institute, the International Observatory for=20 Palliative Care and the WHO Collaborating Center/Pain & Policy = Studies=20 Group.

The reported opioid availability refers only to formulary=20 availability. In situations in which national authorities have not = submitted=20 requests for adequate supply of the formulary medication from the INCB, = actual=20 availability may be restricted. There is strong evidence that requested=20 quantities of opioids are far below levels of actual need in many = countries,=20 particularly among the East-European countries.

The degree to which any one regulatory restriction on = opioid=20 accessibility actually reduces patient access is variable and is = influenced by=20 specific procedural requirements and logistic arrangements.

Other factors besides the regulatory issues highlighted in = this=20 report may contribute to the undertreatment of cancer pain. These = include the=20 attitudes of patients and their families toward opioid medications and = the=20 knowledge and attitudes of the prescribing physicians regarding the use = of=20 opioids; the management of strong pain and the availability and = accessibility of=20 other modalities of treatment of cancer pain (such as radiotherapy) may = also=20 effect the management of cancer pain.

facilitating regulatory review and reform

The Opioid Policy Group of the ESMO and the EAPC is = committed to=20 encouraging and catalyzing the regulatory reforms necessary to ensure = that all=20 cancer patients in Europe will have ready access to opioid medications = needed to=20 provide adequate relief of their pain. Our approach is supported by=20 international human rights law which requires that governments must = provide and=20 ensure accessibility of essential medicines including opioid = analgesics=E2=80=94as part=20 of their minimum core obligations under the right to health [23= ].=20

In many countries reported in this survey, the dominant = paradigm of=20 opioid regulations is most consistent with a =E2=80=98criminalization = model=E2=80=99 to mitigate=20 crime and addiction rather than a =E2=80=98public health model=E2=80=99 = to facilitate care and=20 reduce harms. Using standards derived from the WHO and the INCB, this = survey has=20 exposed formulary deficiencies and excessive regulatory barriers that = interfere=20 with appropriate patient care in many European countries. There is an = ethical=20 and public health imperative to address these issues vigorously and = urgently.=20

The experience of the University of Wisconsin Pain & = Policy=20 Studies Group, a WHO Collaborating Center, has demonstrated that policy=20 evaluation and collaboration between interested parties and regulators = can=20 facilitate constructive formulary and regulatory reforms. This process = has been=20 successfully initiated in Germany, Romania [24= , 25= ],=20 Italy [26= , 27= ],=20 India, including the state of Kerala [26= ],=20 Colombia [28= ] and=20 Uganda. Other countries have undertaken reforms without this assistance: = in the=20 UK, the Shipman tragedy precipitated a review of regulations [29= ] and=20 in Poland [30= ] and=20 Israel, reforms were initiated in response to intense lobbying by the = pain and=20 palliative care clinicians and patient advocacy groups.

The ESMO and the EAPC encourage an approach in which = regulatory=20 reform is combined with education initiatives to ensure clinically = appropriate=20 and responsible prescribing and dispensing. We emphasize the importance = of=20 maintaining the recommended safeguards of including health care provider = and=20 pharmacist education, safe storage, documentation of medication = dispensed,=20 return of unused medications and sound clinical practice consistent with = standards of care.

major recommendations

Formulary restrictions: We endorse the standards of the = WHO=20 essential medicines list as a minimal standard for opioid formulary. = This=20 minimal formulary should include oral codeine, immediate release = morphine,=20 controlled release morphine tablets and injectable morphine. We concur = with=20 the more expansive formulary described by the IAHPC as a preferred = minimal=20 standard but we view this as aspirational at this time. Furthermore, = we=20 endorse the policy of the IAHPC that governments should not approve = controlled=20 release morphine, fentanyl or oxycodone without first guaranteeing = widely=20 available immediate release oral morphine.
Regulatory restrictions: The ESMO and the EAPC echo the = WHO and the=20 INCB in calling for government examination of drug control policies = and repeal=20 of over vigilant or excessive restrictions that impede good clinical = care of=20 cancer pain. Examples of such restrictions include requirement for = patients to=20 have a special permit or restrictions on care settings where opioids = can be=20 prescribed, restrictions on prescribing privileges to limited = physician=20 specialties, arbitrary dose limits, excessive restrictions on the = number of=20 day's supply that can be prescribed at one time and severe = restrictions on the=20 sites of opioid dispensing.
Emergency prescribing: Regulatory provision should be = made for=20 emergency prescriptions of opioids for patients in severe pain who = cannot=20 obtain a physical prescription. The ESMO and the EAPC support the = approach of=20 the Drug Enforcement Administration of the United States which permits = emergency prescription by telephone or facsimile to the pharmacist. = The=20 pharmacist must ensure the veracity and validity of the prescription = before=20 dispensing the controlled substance and the prescriptions must be = transcribed=20 to hard copy by the pharmacist and retained (Title 21, Code of Federal = Regulations section 1306.21).
Special prescription forms: The requirement for special=20 prescription forms is not considered an excessive burden per = se. It=20 is essential, however, that forms be readily available to prescribers = and that=20 the process of procuring them not be excessively burdensome so as to = provide a=20 disincentive to do so.
Dispensing: Pharmacists must have the authority to = correct=20 technical errors in consultation with the prescribing = physician.

nonphysician prescribing

Nonphysician prescribing by specially trained nurses and = pharmacists=20 is advocated by some as a means of providing a backup system of = prescribing in=20 situations when there is no physician availability. Among European = countries,=20 regulations and procedures for nonphysician prescribing are best = developed in=20 the UK. The regulations, legislated in 2001 and initiated in 2003, = distinguish=20 between =E2=80=98independent nonmedical prescribers=E2=80=99 who have = prescribing privileges=20 within their area of professional competence and =E2=80=98supplementary = prescribers=E2=80=99 who=20 are not authorized to initiate courses of treatment but may extend or = modify=20 courses of treatment after initial diagnosis by a doctor or other = independent=20 prescribers [31= ].=20 The nurse and pharmacist prescribers program extends prescribing = privileges to=20 specially certified nurse prescribers with access to a defined formulary = of=20 prescription medicines including some opioid analgesics. Supplementary=20 prescribing enables qualified nurses and pharmacists to prescribe any = medicine=20 (including controlled drugs), within the framework of a patient-specific = clinical management plan, agreed with a doctor. Nurse prescribing has = also been=20 described in resource-poor settings to facilitate opioid accessibility = in rural=20 Africa [32= ].=20

Nonphysician prescribing remains contentious and is opposed = by many=20 medical authorities. The Opioid Policy Group of the ESMO and the EAPC = consider=20 that this may be a beneficial approach, especially in emergency = situations.=20 Further study of this experience is warranted.

conclusions

There is evidence that in many European countries, = particularly among=20 the East-European countries, patient access to the medication needed to = relieve=20 cancer pain is profoundly restricted by inadequate formulary = availability and=20 overregulation. The undertreatment of pain and the suffering that ensues = is a=20 public health catastrophe. Advocacy initiatives by stakeholder and = international=20 organizations partnering with authorities and regulators have = demonstrated that=20 regulatory reform is possible. Urgent and intensive efforts are needed = to expand=20 this process, particularly in the countries with the most severe = restrictions of=20 availability and accessibility. The ESMO and the EAPC have undertaken a = joint=20 program to lead these initiatives.

Previous=20 Section Next=20 Section

funding

ESMO; EAPC.

Previous=20 Section Next=20 Section

Acknowledgments

The authors declare no conflicts of interest.

The authors wish to acknowledge the contributions of the = members of=20 the ESMO Executive comittee, national representatives and the members of = the=20 Palliative Care Working Group who initiated this project; the board of = the EAPC=20 and the administrators of both organizations who collected the data; the = corresponding representatives listed in app= endix=20 1 who supplied the critical data, and the many members of the = organizations=20 who reviewed the data for verification. We wish to acknowledge the = members of=20 the Pain and Policy Studies Group of the WHO Collaborating Center for = Policy and=20 Communications in Cancer Care who provided feedback on earlier versions = of the=20 manuscript.

Previous=20 Section Next=20 Section

appendix 1

Vigjilenca Demiraj, Irena Laska, Alketa = Ymeri	Albania
Richard Greil, Franz Zdrahal, Gabriela = Kornek	Austria
Svetlana Petrovich	Belarus
Dirk Schrijvers, Simon Van Belle, Trudie = van=20 Iersel	Belgium
Semir Beslija	Bosnia=E2=80=93Herzegovina
Konstanta Timcheva, Irena Jivkova = Hadjiiska=20 Bildireva, Nikolay Yordanov	Bulgaria
Zrinka Mrsic-Krmpotic	Croatia
George Marcoullis, Barbara = Pitsillides	Cyprus
Lubos Petruzelka, Ondrej Slama	Czech Republic
Gedske Daugaard, Bodil Abild = Jespersen	Denmark
Simon Van Belle, Dirk Schriver, Trudie van = Iersel	Belgium
Eva Saliminen, Tarja Korhonen, Tarja = Heiskanen,=20 Tiina Saarto	Finland
Jean-Yves Blay, Maril=C3=A8ne Filbet	France
Nino Sharikadze	Georgia
Joachim Schmoll Hans, Christof = M=C3=BCller-Busch,=20 Marianne Kloke	Germany
Dimitrios Bafaloukos, Kyriaki Mystakidou, = Ioanna=20 Siafaka, Vadalouca Athina	Greece
Janos Szanto, Csaba Simk=C3=B3	Hungary
Sigurdur Bj=C3=B6rnsson, Valgerdur = Sigurdardottir	Iceland
Oscar S. Breathnach, Regina McQuillan	Ireland
Aaron Sulkes, Yoram Zinger	Israel
Giovanni Rosti, Giovanni Zaninetta, Carla=20 Rippamonti	Italy
Zanete Zvirbule, Vilnis Sosars	Latvia
Cesas Alvydas, Arvydas Seskevicius	Lithuania
Stefan Rauh, Jacqueline Genoux-Hames, = Liefgen=20 Marie-France	Luxembourg
Petar Stefanovski, Mirjana Adzic	Macedonia
Vasile Musteata, Natalia Carafizi	Moldova
Jadranka Lakicevic	Montenegro
Johan W. R. Nortier, Frans van Soest, = Manon=20 Boddaert	The Netherlands
Roy Bremnes, Dagny F. Haugen	Norway
Maciej Krzakowski, Jacek Luczak	Poland
Joao Oliveira, Jos=C3=A9 Ant=C3=B3nio = Ferraz Gon=C3=A7alves, Edna=20 Gon=C3=A7alves	Portugal
Mircea Dediu, Constantin Bogdan	Romania
Dmitry Nosov, Anonymous	Russian Federation
Svetislav Jelic, Natasa Milicevic	Serbia
Maria Wagnerova, Hedviga Jakubikova	Slovakia
Bojana Pajk, Branko Zakotnik, Slavica = Lahajnar,=20 Andreja Peternelj, Josipina Cervek	Slovenia
Felip Enriqueta, Maria Nabal	Spain
Bo Nordenskjoeld, Carl-Johan Furst	Sweden
Reto Obrist, Roland Kunz, Florian = Strasser, Esther=20 Schmidlin	Switzerland
Bakhtiyor Turaev, Nigora Abidjanova	Tajikistan
Fikri Icli, Ozgur Ozyilkan	Turkey
Alexander Dudnitchenko, Viktoriia = Tymoshevska	Ukraine
Johann De Bono, Nigel Sykes	UK

Table A1.=20

National representatives from ESMO and = EAPC who=20 contributed data

=C2=A9 The = Author 2010.=20 Published by Oxford University Press on behalf of the European Society = for=20 Medical Oncology. All rights reserved. For permissions, please email:=20 journals.permissions@oxfordjournals.org

Previous=20 Section

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in this=20 issue: = in this issue Ann Oncol (2010) = 21(3): 435=20 doi:10.1093/annonc/mdq040

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Formulary availability and regulatory barriers = to=20 accessibility of opioids for cancer pain in Europe: a report from the = ESMO/EAPC=20 Opioid Policy Initiative

Abstract

Key words

introduction

methods

results

general

formulary availability and cost of opioids for cancer pain

regulatory restrictions to accessibility

requirement for permission/registration of patient to render them = eligible=20 to receive opioid prescription.

requirement for physicians to receive a special authority/license to = prescribe opioids.

requirement for duplicate prescriptions and special prescription = form.

prescription limits.

dose limits.

limitations on dispensing privileges.

provision for opioid prescribing in emergency situations.

pharmacist privilege to correct technical error on a = prescription.

use of stigmatizing term for opioid analgesics in regulations.

cross-correlation of availability and accessibility

discussion

are opioid formularies in European countries consistent with the = essential=20 medicines list of the WHO and the IAHPC?

how compliant are European countries with the guidelines of the WHO = and the=20 INCB regarding opioid regulations for cancer pain?

do regulations make allowances for efficient emergency prescribing = and=20 dispensing of opioids for patients with strong pain in out-of-hours = situations?=20

disclaimers and limitations

facilitating regulatory review and reform

major recommendations

nonphysician prescribing

conclusions

funding

Acknowledgments

appendix 1

References

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