# Presentation: 235020

## International Drug Control Issues and Implications

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

**2006 NIDA International Forum****Scottsdale AZ, USA, June 17, 2006**

## 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*

## 1. Drug controlThe system

## 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

## 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

## 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

## 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

## Drug Control

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

## Drug Control

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

## Schedulingfor 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

## 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

- 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

**Scheduling****for Drug Control**

## 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

## 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)

## Global consumption of morphine1972-2002

**Global consumption of morphine****1972-2002**

**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

## 2. Uses of medications The uses made of them

## Pain

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

## 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

## 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/

## 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

## 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

## 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

## Opioid dependence and HIV

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

## Opioid dependence and HIV

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

## Opioid dependence and HIV

**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

## ... and then, there are happy events too, where we need controlled medications...

**Delivery**

- Photo  WHO/Antonio Suáres Weise

## 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

- 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

**Delivery**

## 
" To reduce by three quarters maternal mortality ratio between 2006 and 2015 "

Millennium Development Goals, target 6

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

**Delivery**

## Precursors

- 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)

**Delivery**

## 3. Impact of (no) accessThe figures

## Impact of (no) access

**Impact of (no) access**

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

## Drug conventions

## Impact of (no) access

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

## 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*

## Impact of (no) accessIDU mortality in France

- With acknowledgement to Patrizia Carrieri, INSERM, Marseille, France

## 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*

## 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

- 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***

**Impact of (no) access**

## 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*

## Impact of (no) access

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

## Impact of (no) access

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

## 4. Reasons for bad accessThe barriers

## Barriers for access

- Fear of diversion
- Fear of dependence

## 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

## 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

## 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

## 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?

## Barriers for access

- Attitude and Knowledge (2)
- Patient and family
- Association morphine  impending death
- Conviction that one should suffer from pain

## 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

## Consequence of scheduling

- Scheduled
- December 2002

- De-scheduled
- May 2004

- Source: IMS

- Tramadol (INN) units in Egypt
- before, during and after scheduling

- Scheduledin 2000

- Source: IMS

- Tramadol (INN) units in Jordan
- before and after scheduling

## Consequence of scheduling

- Source: International Narcotics Control Board

- Kilograms

- Morphine in India

## 5. Improving accessThe Access to Controlled Medications Programme

## 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

## 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)*

## Imperative for improved access

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

## 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)*

## Resolutions

- U.N. ECOSOC Resolution 2005/25“Treatment 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** **

## 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"

## Access to ControlledMedications 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

## Access to ControlledMedications 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

## Access to ControlledMedications 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*

## www.medsch.wisc.edu/painpolicy

**World Health Organization**

**NARCOTIC & PSYCHOTROPIC DRUGS**
** **ACHIEVING  BALANCE IN  NATIONAL OPIOIDS CONTROL  POLICY
**GUIDELINES FOR ASSESSMENT**

**WHO/EDM/QSM/2000.4**
**ENGLISH ONLY**
**DISTRIBUTION: GENERAL **

_**www.med**__**sch.wisc.edu/painpolicy**_
_** **__**availa**__**ble in 22 languages**_

## Access to ControlledMedications Programme

- Approval of draft programme

- In-house consultation w/ some external parties

- Establishing a fund
- new NGO?
- in existing NGO?
- in WHO?

- Start of activities

**Access to Controlled****Medications Programme**

- Fund raising

- Decision

**?**

## Access to ControlledMedications Programme

- 										improvement in

- 2015
- 2016
- 2017
- 2018
- 2019
- 2020?

## 6. Researchers' contributions Research topics in drug control, including access to controlled medications

## 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

## 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

## 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

## 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

## 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

## Access

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

## 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

## 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

## 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

## Willem Scholten PharmD, MPA

Quality Assurance and Safety: Medicines
Department of Medicines Policy and Standards

scholtenw@who.int

+41 22 79 15540

- Willem Scholten PharmD, MPA
- Quality Assurance and Safety: Medicines
- Department of Medicines Policy and Standards
- scholtenw@who.int
- +41 22 79 15540

***International Drug Control Issues and Implications***