1. National Institute for Public Health and the Environment Risk assessment guidelines Leon van Aerts Scientific Committee meeting November 2008 Lisbon

2. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 2 Overview Need for redrafting the risk assessment guidelines Structure of the current draft guidelines Defining risk Use of categories and criteria in risk assessment Delphi method Ranking of risks

3. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 3 Need for redrafting the risk assessment guidelines (1) 97/396/JHA Joint Action replaced by Council Decision 2005/387/JHA Aim: information exchange, risk assessment, measures of control More transparancy needed Change of scope: 97/396/JHA Joint ActionCouncil Decision 2005/387/JHA 1971 UN Convention on psychotropic substances Schedules I and II 1971 UN Convention on psychotropic substances Schedules I, II, III and IV 1961 UN Convention on narcotic drugs Schedules I and III and IV

4. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 4 Need for redrafting the risk assessment guidelines (2) Conservatively revised version produced in 2007 -Recommendation from previous Sci.Comm. review the risk assessment items related to the involvement of organised crime with an input from Europol numerical scoring system should not constitute a formal part of the risk assessment, but could be used as a trigger to focus the discussion; only items where severe or moderate risk ratings are discussed by the full risk assessment Committee risk assessment meetings could explore the viability of using small working groups and rapporteurs for each assessed domain

5. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 5 Need for redrafting the risk assessment guidelines (3) Comments from current Sci.Comm. -Criminal involvement aspects -Some inconsistencies between headings for risk assessment, technical annexes and risk assessement categories -Further detailed remarks

6. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 6 Need for redrafting the risk assessment guidelines (4) Current revision: -Introductory chapter addressing the need for the guidelines and explaining their scope -Appropriate references to the legal framework -Clarify further the principles of risk assessment, also including prevalence as a factor contributing to the risk at the level of the population (i.e. public health risks). -Clarify further the headings for risk assessment. -Restructure the proposed scoring system in line with aforementioned adaptations and clarification of it as a tool for risk assessment.

7. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 7 Introduction: Aim The principle aim of a risk assessment as described in these guidelines is to provide a scientifically sound basis for a decision whether or not a new psychoactive substance should be subjected to measures of control at the level of the European Union. -Other options for control need to be considered as well. -The risk assessment has regard to the health and social risks of the use of, manufacture of, and traffic in the new psychoactive substance, and the involvement of organised crime and the possible consequences of control measures.

8. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 8 Introduction: Legal basis (1) Council Decision 2005/387/JHA of 10 May 2005 on the information exchange, risk-assessment and control of new psychoactive substances Has regard to the Treaty of the European Union, in particular Articles 29, 31(1)(e) and 34. These articles are provisions on police and judicial cooperation in criminal matters (Title VI of the Treaty of Amsterdam) – Third pillar. Risk assessment described in Article 6 of the Decision

9. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 9 Introduction: Legal basis (2) Council Decision also clearly refers to the 1961 United Nations Single Convention on Narcotic Drugs and the 1971 United Nations Convention on Psychotropic Substances. -definition of new psychoactive substances (article 3) -defining the scope (article 2) -affect the nature of the risk assessment (article 6) -can provide a basis for exclusion of a new psychoactive substance from risk assessment (article 7) -affect the measures of control to be taken by the Members States (article 8). The relevance of the UN Conventions for the risk assessment lies predominantly in indicating the factors that should be taken into account when a risk assessment is carried out.

10. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 10 Factors that need to be assessed Article 6(3): The risk assessment shall be carried out on the basis of information to be provided to the scientific Committee by the Member States, the EMCDDA, Europol, the EMEA, taking into account all factors which, according to the 1961 United Nations Single Convention on Narcotic Drugs or the 1971 United Nations Convention on Psychotropic Substances, would warrant the placing of a substance under international control.

11. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 11 Factors to be taken into account (1) Narcotic drugs: UN 1961 conv. Art 3.3.iii and 3.5): -Abuse liability and producing ill effects similar to substances already scheduled (I and II resp. IV), or is convertible to such a substance Psychotropic substances UN 1971 conv. Art 2.4.a): -Able to produce a state of dependence, and CNS stimulation or depression, resulting in hallucinations or disturbances in motor function, behaviour, thinking, perception or mood or -Similar abuse and ill effects as substances already scheduled

12. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 12 Factors to be taken into account (2) Psychotropic substances UN 1971 conv. Art 2.4.b): -sufficient evidence that the substance is being or is likely to be abused so as to constitute a public health and social problem -assessment of the substance, including the extent or likelihood of abuse, the degree of seriousness of the public health and social problem and the degree of usefulness of the substance in medical therapy, together with recommendations on control measures, if any, that would be appropriate in the light of its assessment.

13. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 13 Principles of risk assessment -Definition of risk -Prevalence of use -Benefits of use -Independent of legal status -Wide range of options for control -Comparison with better known substances -Quality of data -Reliability and relevance of data

14. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 14 Defining risk (1) Seriousness of an adverse effect. Often referred to as HAZARD Factors that increase Hazard -Extent of personal suffering -Mortality -Irreversibility -Impact on the social environment -Impact on society as a whole

15. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 15 Defining risk (2) PROBABILITY (chance) an adverse effect (Hazard) may occur in a single user Aspects that determine Probability -Weight of evidence Theoretical vs. Actual observations Animal data vs. Human data Case reports vs. Epidemiological studies -Actual figure that can be derived from observations

16. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 16 Defining risk (3) PREVALENCE of use of the substance The larger the population that uses a substance the greater the chance that an adverse effect may occur

17. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 17 Defining risk (4) RISK = HAZARD X PROBABILITY X PREVALENCE RISK at POPULATION LEVEL = (HAZARD X PROBABILITY) X PREVALENCE RISK at INDIVIDUAL LEVEL = (HAZARD X PROBABILITY)

18. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 18 Criminal involvement Definition: "Organised crime" is understood to be the large- scale and complex criminal activity carried on by groups of persons, however loosely or tightly organised, for the enrichment of those participating and at the expense of the community and its members. It is frequently accomplished through ruthless disregard of any law, including offences against the person, and frequently in connexion with political corruption.

19. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 19 Criminal involvement Main characteristics: A)It is an activity of groups of people primarily aimed at financial gain. B)Criminal offences are committed by these groups in a systematic way with serious consequences for society. C)These groups are prepared to protect themselves from law enforcement, especially by means of intimidation, violence or by corruption.

20. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 20 Risks to be assessed – comparison with other substances Health risks Social risks Involvement of organised crime Possible consequences of control measures

21. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 21 Risks to be assessed CAM (The Netherlands) Health: -Individual health Acute toxicity Chronic toxicity Dependence potential -Public health Extent and frequency of use Vulnerable groups Quality of information Availability of substance Quality of substance Quality of distribution system Reporting of incidents

22. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 22 Risks to be assessed CAM (The Netherlands) Social -Civil order and safety Public nuisance Violence Impaired reaction (traffic) Organised crime -Regarding final product -Regarding raw materials

23. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 23 CAM assessments until 2007 Substance Health individual Public health Civil order and safety Involvement crime Total score Recommendation khatsmall none-smallnone7,1Education; research Magic mushrooms none-smallmoderatesmall 8,5 Improvement quality product and trade; education ketamine small- moderate none-small8,8monitoring MBDB moderate- large moderatesmall 10,3 monitoring GHB small- moderate moderate small- moderate 10,9monitoring PMMAmoderate moderate- large small moderate- large 11,8Control measures 4-MTAmoderate moderate- large 12,1Control measures

24. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 24 Categories to be assessed Nutt et al., 2006 (ACMD, UK)

25. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 25 Categories to be assessed in Draft guidelines B Dependence and abuse potential C Prevalence of use D Health risks E Social risks F Involvement of organised crime

26. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 26 Delphi method 1 st round: Individual scoring by experts on each criterion 2 nd round: Discussion of outlyers -Difference of opinion? -Reaching consensus? -New score if needed Suitable for complex social and medical problems were multiple criteria are relevant

27. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 27 Advantages of using multiple risk scales Comprehensive Standardized Transparant Rational and scientific basis Facilitates drug-drug comparisons Can be repeated -as knowledge advances -or pattern of drug use develops Suitable for Delphi approach

28. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 28 Pitfalls of using numerical scores Extreme risks on a single criterion are not visible in average scores Average or total scores can be overemphasized

29. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 29 Conclusion The risk assessment of new psychoactive substances is a complex process in which many facets need to be considered and weighed and compared with other situations. It is the task of the Scientific Committee to do this in a multidisciplinary way. The result of this process should be a scientifically sound basis for a decision on control measures.

30. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 30 Thank you!

31. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 31 Backup slides

32. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 32 WHO assessment According to UN Conventions WHO is responsible for the assessment. Draft Proposal for the revision of the Guidelines for the WHO review of psychoactive substances for international control [vs. 15 April 2008] Par. 46-60 consider the assessment process. Reference to article 3 of 1961 Convention and article 2 of 1971 Convention Deliberations based on critical review document, report on the questionnaire, comments received, and information meeting

33. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 33 WHO critical review document (1) As thorough as possible Include adequate and relevant data from medical and abuse studies Balanced in its presentation Should facilitate evidence-based assessment

34. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 34 WHO critical review document (2) 1.substance identification by International Nonproprietary Name (INN), chemical or other common name and trade names, other identifying characteristics, Chemical Abstracts Service (CAS) registry number; 2.chemistry, including general information on synthesis, preparation and properties; 3.ease of convertibility into controlled substances; 4.general pharmacology, including pharmacokinetics and pharmacodynamics; 5.toxicology, including adverse reactions in humans; 6.dependence potential; 7.abuse potential; 8.therapeutic applications and extent of therapeutic use; 9.listing on the WHO Model List of Essential Medicines;

35. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 35 WHO critical review document (3) 10. marketing authorizations (as a medicine); 11. industrial use; 12. epidemiology of medical and non-medical use, abuse and dependence; 13. nature and magnitude of public health problems related to abuse and dependence; 14. licit production, consumption and international trade; 15. illicit manufacture and traffic, and related information; 16. current international controls and their impact; 17. current and past national controls; 18. other medical and scientific matters relevant for a recommendation on the scheduling of the substance.

36. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 36 Conclusion: What needs to be assessed? (1) Health risks, social risks, involvement of organised crime and possible consequences of control measures Abuse liability and ill effects similar to UN 1961 Convention schedule I, II or IV or, (a) ((1) Able to produce a state of dependence, and (2) CNS stimulation or depression, resulting in hallucinations or disturbances in motor function, behaviour, thinking, perception or mood) or, similar abuse and ill effects as substances already scheduled under UN 1971 Convention and (b) sufficient evidence that the substance is being or is likely to be abused so as to constitute a public health and social problem and

37. National Institute for Public Health and the Environment 18 November 2008Risk Assessment guidelines Leon van Aerts ׀ Lisbon 37 Conclusion: What needs to be assessed? (2) the extent or likelihood of abuse, the degree of seriousness of the public health and social problem