International Drug Control Issues and Implications

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International Drug Control Issues and Implications
2006 NIDA International ForumScottsdale AZ, USA,
June 17, 2006

• Willem Scholten PharmD, MPA
• Quality Assurance and Safety Medicines
• Department of Medicines Policy and Standards

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Overview

• The drug control system
• Uses of controlled medications
• Impact of (no) access
• Reasons for bad access
• Improving access
• Research topics in drug control, including access
  to controlled medications

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1. Drug controlThe system
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Drug Control

• Single Convention on Narcotic Drugs (1961)
• Convention on Psychotropic Substances (1971)
• Convention against Illicit Traffic in Narcotic
  Drugs and Psychotropic Substances (1988)
• International control system
• See www.incb.org for conventions and lists

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Drug Control

• Single Convention on Narcotic Drugs (1961)
• Convention on Psychotropic Substances (1971)
• Convention against Illicit Traffic in Narcotic
  Drugs and Psychotropic Substances (1988)
• Substances liable for abuse

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Drug Control

• Single Convention on Narcotic Drugs (1961)
• Convention on Psychotropic Substances (1971)
• Convention against Illicit Traffic in Narcotic
  Drugs and Psychotropic Substances (1988)
• Precursors (starting materials)
• for producing drugs in the other two
  conventions

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Drug Control

• 1961 and 1971 Conventions
• Prohibition as general rule
• Recognition of medical use ("indispensable")
• Licenses possible for science, trade,
  manufacturing et cetera
• Estimations and statistics system
• Import/export permits

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Drug Control

• 1961 and 1971 Conventions (contd.)
• Healthcare professionals and patients don't need
  a licence
• However
• Countries may apply stricter measures

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Drug Control

• Other drug control regulations
• National law
• State law, provincial law et cetera
• (some countries)
• Bi-lateral treaties
• Not discussed in this presentation

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Schedulingfor Drug Control

• WHO substance evaluation (for 1961 and 1971)
• Can lead to recommendations
• Guidelines (contain procedure)
• Expert Committee on Drug Dependence (ECDD)
• On initiative of
• Participants of Expert Committee
• Member States (through UN Secretary Gen.)
• Commission on Narcotic Drugs (CND)
• Also if there is information that requires such

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Schedulingfor Drug Control

• WHO recommends
• Commission on Narcotic Drugs (CND) decides
• For Single Convention
• Just "Yes/No"
• For Psychotropic Substances Convention
• Other Schedule then recommended possible
• WHO scientific and medical aspects
• CND can take administrative, social, economic and
  other matters into account

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Balance

• Conventions have two goals
• Prevention of harm from drug dependence
• Availability for rational medical use
• Any control measure taken should aim at the
• optimum for availability and prevention

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Drug dependence

• compulsive use ( psychological dependence)
• harm
• Unequal to physical dependence and tolerance,
  very common for medicines, e.g.
• cardiac medication (nitrates and other)
• xylomethazoline nose drops
• concept of disease/medication is inherent to
  physical dependence on medication
• (e.g. diabetes/insulin)

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Global consumption of morphine1972-2002
Kilograms
Source International Narcotics Control Board By
Pain Policy Studies Group/WHO Collaborating
Center, 2005 Top 10 countries Australia,
Canada, Denmark, Iceland, Ireland, New Zealand,
Norway, Sweden, the United Kingdom, and the
United States
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2. Uses of medications The uses made of them
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Pain

• Cancer pain
• Surgery
• Traffic and other accidents
• Myocardial infarction
• Chronic pain
• neuropathies
• post-surgery pain

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Pain

• WHO Three step ladder on cancer pain (1986)
  still actual
• Non-opioid adjuvant e.g. paracetamol
• If pain persisting/increasing
• Weak acting opioid (e.g. codeine, tramadol)
• If pain persisting/increasing
• Strong acting opioid (e.g. morphine, methadone)
• Increase dosage until freedom of pain

If more severe start on higher step
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Pain

• Special issue on 20th Anniversary of
• 3 Step Ladder (Vol 19,No 1, 2006)
• Publication of the WHO Collaborating Center for
  Policy Communications in Cancer Care
• University of Wisconsin, Pain Policy Study
  Group, Madison WI
• http//www.whocancerpain.wisc.edu/

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Opioid dependence

• Complications of Injected Drug Use
• Use of Contaminated needles
• HIV
• HCV ? liver cirrhosis, liver cancer
• Doubtful opioid quality/content (adulteration!)
• overdosage
• Cost of drugs often leads
• malnutrition
• episodes of withdrawal symptoms
• Lowered socio-economic status

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Opioid dependence

• Methadone solution
• (not tablets)
• Buprenorphine sublingual tablets
• (not injections)
• Essential medicines (? human right!)
• However not yet allowed in many countries
• New programmes China, Iran

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Opioid dependence

• Opioid agonist therapy
• No needles needed (oral therapy)
• No transmission of blood-borne disease
• Pharmaceutical quality
• No overdosing
• At no or moderate cost
• Money for food
• Regular application no withdrawal episodes
• Social re-integration

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Opioid dependence and HIV

• Use of contaminated needles threatens health of
  IDU and public health
• IDU HIV epidemics link to sexually transmitted
  HIV epidemics

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Opioid dependence and HIV

• " Have halted by 2015 and begun to reverse the
  spread of HIV/AIDS "
• Millennium Development Goals, target 7

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Opioid dependence and HIV
The HIV prevention challenge Rapid increases in
HIV prevalence among IDU's 40 may be reached
within two years Uncontrolled epidemics
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and then, there are happy events too, where we
need controlled medications
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Delivery

Photo WHO/Antonio Suáres Weise
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Delivery

• Ergotamine
• stops excessive bleeding after giving birth
• Ephedrine
• if blood pressure falls during anaesthesia in
  giving birth
• Can be life saving
• Both on WHO Model List of Essential Medicines ?
  Human right

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Delivery

• " To reduce by three quarters maternal mortality
  ratio between 2006 and 2015 "
• Millennium Development Goals, target 6

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Precursors
Delivery

• Ergotamine
• stops excessive bleeding after giving birth
• used in LSD production
• Ephedrine
• if blood pressure falls during anaesthesia in
  giving birth
• used in methamphetamine production
• 1988 Convention controls chemicals used for the
  manufacture of drugs
• (Precursors are chemicals used for the
  manufacture of other substances)

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3. Impact of (no) accessThe figures
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Impact of (no) access

• Millions have a drug problem
• photo WHO/Marko Kokic
• They can't get any

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Drug conventions
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Impact of (no) access

• Maternal mortality
• 500 000 deaths (annually)
• Some of them avoidable with contr. medications

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Impact of (no) access

• Injected drug use
• 13,1 million IDUs
• 2 3 mortality rate
• 250 000 400 000 deaths (annually)
• Over 90 avoidable w/ controlled medications

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Impact of (no) accessIDU mortality in France
With acknowledgement to Patrizia Carrieri,
INSERM, Marseille, France
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Impact of (no) access

• HIV/AIDS and its transmission
• 5 of all people living with HIV/AIDS are IDU's
• 3 million people die from AIDS every year
• 10 of all new cases (globally) are IDU's
• 25 90 of all new cases in countries outside
  Africa (30 average)
• Treatment of dependence w/ contr. medications
  prevents most of these new HIV cases

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Impact of (no) access

• Cancer
• 12 of world pop. will die from cancer
• 7.5 mln cancer deaths annually
• 80 have no access to narcotic analgesics
• ? 10 of all people in the world will suffer from
  cancer pain that can be treated, but will not be
  treated

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Impact of (no) access

• Cancer pain
• 600 million untreated (lifetime)
• 6 million untreated (annually)
• Other moderate/severe pain
• ? million untreated
• All avoidable with controlled medications

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Impact of (no) access

• In total
• Up to around 1 billion (lifetime)
• Up to around 10 million (annually)

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Impact of (no) access

• Is there anybody who has NO interest in good
  access to controlled medications?

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4. Reasons for bad accessThe barriers
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Barriers for access

• Fear of diversion
• Fear of dependence

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Barriers for access

• Political regulatory
• Too much emphasis on abuse prevention
• Too difficult requirements prevent actual use
• Attitude knowledge
• I am afraid that my patient will be an addict
• How to prescribe and dose morphine?
• Economical procurement
• Infrastructure
• Money

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Barriers for access

• Politically and regulatory (2)
• Unnecessary licensing
• Requirements to make pharmacies "fortresses"
• Prosecution of physicians
• for prescribing high but appropriate dosage
• for possession of opioids
• Too much red tape
• no industry efforts for marketing

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Barriers for access

• Politically and regulatory (3)
• Special prescription forms
• Limitations on prescriptions
• time (e.g. 1 day max.)
• dosage (e.g. 100 mgs max.)
• morphine prohibited
• Good example nurse prescribing in Uganda

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Barriers for access

• Attitude and Knowledge (1)
• Physicians
• Fear for addiction
• Not prescribing
• Too low dosage ? not pain free ? patient asks for
  next dose ? doctor believes patient is addicted
• Unfamiliarity
• What should be initial dose?
• How and when to increase?
• How to stop medication?

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Barriers for access

• Attitude and Knowledge (2)
• Patient and family
• Association morphine ?? impending death
• Conviction that one should suffer from pain

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Barriers for access

• Economical and Procurement
• General issues as for other medicines
• Lack of health care professionals
• Limited means of transportation
• Lack of finance
• Too heavy administration burden from donor
  countries
• Et cetera

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Consequence of scheduling
Tramadol (INN) units in Egypt before, during and
after scheduling
Tramadol (INN) units in Jordan before and after
scheduling
Scheduled December 2002
De-scheduled May 2004
Scheduledin 2000
Source IMS
Source IMS
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Consequence of scheduling
Morphine in India
Kilograms
Source International Narcotics Control Board
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5. Improving accessThe Access to Controlled
Medications Programme
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Imperative for improved access

• Unquestioned need for pain relief
• Medical and scientific basis
• Pain is real, must be relieved
• Opioids are safe and effective
• Psychological dependence in medical treatment is
  very rare and fear for it is unjustified
• Policy imperative
• Single Convention obligation of governments

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Drug conventions

• Recognizing that the medical use of narcotic
  drugs continues to be indispensable for the
  relief of pain and suffering and that adequate
  provision must be made to ensure the availability
  of narcotic drugs for such purposes
• (Preamble Single Conv. on Narcotic Drugs)

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Imperative for improved access

• INCB
• WHA
• Commission on Narcotic Drugs
• ECOSOC
• Joint position paper UNODC/WHO/UNAIDS
• Millennium Development Goals
• ICDRA

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Viewpoint of INCB

• In many countries, consumption of opioid
  analgesics remains extremely low in comparison
  to medical need, and many national governments
  have yet to address this important deficit.
• (International Narcotics Control Board, 1996)

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Resolutions

• U.N. ECOSOC Resolution 2005/25Treatment of pain
  using opioids
• Medical use of narcotic drugs is indispensable
  for the relief of pain and suffering
• Morphine should be available at all times in
  adequate amounts and appropriate dosage forms for
  the relief of severe pain
• Low national consumption of opioids is a matter
  of great concern

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Resolutions

• ECOSOC 2005/25
• On treatment of pain using opioid analgesics
• World Health Assembly 58.22 (25-05-2005)
• on Cancer Prevention and Control
• "..to examine jointly with the International
  Narcotics Control Board the feasibility of a
  possible assistance mechanism that would
  facilitate the adequate treatment of pain using
  opioid analgesics"

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Access to ControlledMedications Programme

• Feasibility study of a possible assistance
  mechanism that would facilitate the adequate
  treatment of pain using opioid analgesics
• (ECOSOC and WHA, May 2005)
• Exploring different options for the organisation
  of a fund

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Access to ControlledMedications Programme

• Funding
• Contributions expected from
• opium producing countries
• opioid medicines producing industries
• some other countries
• charities?
• 1 of opioid turnover
• ? US 7 US 12 mln per annum

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Access to ControlledMedications Programme

• Plan of activities
• Workshops to analyse problem
• Health care professionals
• Legislators law enforcement officers
• Action plan (tailor made to countries' needs)
• Training and attitude of health care
  professionals
• Other
• after the model used by the University of
  Wisconsin, Pain Policies Study Group, WHO
  Collaborating Center for Policy and
  Communications in Cancer Care, Madison, WI,
  United States of America

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WHO/EDM/QSM/2000.4 ENGLISH ONLY DISTRIBUTION
GENERAL 
NARCOTIC PSYCHOTROPIC DRUGS  ACHIEVING BALANCE
IN NATIONAL OPIOIDS CONTROL POLICY    GUIDELINES
FOR ASSESSMENT
www.medsch.wisc.edu/painpolicy available in 22
languages
World Health Organization
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Access to ControlledMedications Programme
Proposal to WHO management
In-house consultation w/ some external parties
Establishing a fund new NGO? in existing NGO?
in WHO?
Decision
?
Approval of draft programme
Start of activities
Fund raising
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Access to ControlledMedications Programme

• improvement in

2015 2016 2017 2018 2019 2020?
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6. Researchers' contributions Research topics
in drug control, including access to controlled
medications
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Access

• Access to analgesics
• Dosage level and duration of opioid medication in
  adequately treated (pain free) patients in
  practice
• Relation between opioid needs and morbidity
  pattern per country
• Calculation of adequate country needs, given
  morbidity and average need per patient
• Relevance establishing country needs and
  adequate supply

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Access

• Access to obstetrics
• Impact of access to ephedrine and ergotamine
• Availability in delivery care
• In countries with good access
• How often used? How often life saving?
• In countries with bad access
• Analysis of maternal death cause

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Access

• Access to opioid agonist treatment in opioid
  dependence
• Assessment of structural factors for impairment
  of access to treatment programs
• Evaluation of programmes in different cultural
  and health care contexts
• Treatment models for opioid dependence with
  co-morbidity
• Minimum requirements for treatment programs

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Access

• Access to opioid agonist treatment in opioid
  dependence
• Ethnical differences in opioid kinetics
• Economics of treatment programmes
• Systematic statistical information of drug use
• Calculation of adequate country needs for
  medication, given number of IDU's
• WHO will publish treatment guidelines in 2007
• Report to what extent national practices are
  congruent to best practices in guidelines

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Access

• Risk analysis
• At which points are substances diverted?
• Which points are controlled?
• And hence
• Which controls can be lifted
• Where is more / other control needed

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Access

• Legal impairment of availability
• Evaluation of legislation at all levels
  (national, state/province, local) with regard to
  access barriers

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Substance evaluation

• Use of pharmacovigilance data in substance
  evaluation
• Which adverse drug reactions (ADRs) are relevant
  for evaluation of abuse liability?
• Which ADRs (if any) are predictive for abuse
  liability?
• Relevance of data collected in therapeutic use
  for evaluation of non-medical use and abuse
• Collection of denominator data

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Substance evaluation

• Substances for evaluation in 2008
• (as far as identified by 34th ECDD data needed
  by summer 2007)
• Gamma-hydroxybutyrate (GHB)
• Gamma-butyrolactone(GBL)
• 2,4-butanediol (2,4-BD)
• Need for animal data

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Summary

• Balance efforts for prevention of abuse and
  trafficking should not interfere with medical
  accessibility
• Balance is lost, but should be restored,
  adressing
• - unnecessary legal impediments
• - education of health care professionals and
  others
• Addiction from medical treatment is very rare and
  fear for it is unjustified
• Research can contribute to bring back the balance

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International Drug Control Issues and Implications

• Willem Scholten PharmD, MPA
• Quality Assurance and Safety Medicines
• Department of Medicines Policy and Standards
• scholtenw_at_who.int
• 41 22 79 15540