1. Essential Medicines List: Concept and Procedures 1 |1 | WHO Essential Medicines List Concept and Process WHO Essential Medicines List Concept and Process IPC Meeting June 6, 2014 – WHO Geneva Nicola Magrini – WHO, EMP

2. Essential Medicines List: Concept and Procedures 2 |2 | Essential Medicines Guiding principle: A limited range of carefully selected essential medicines leads to better health care, better medicines management, and lower costs Definition: Essential medicines are those that satisfy the priority health care needs of the population Selection: Selected with due regard to disease prevalence, evidence on efficacy and safety, and comparative cost- effectiveness.

3. Essential Medicines List: Concept and Procedures 3 |3 | … 38 years of EML 1977 1 st Model list published, 208 active substances List is revised every two years by WHO Expert Committee 2002 Revised procedures approved by WHO (EB109/8): more evidence-based, more transparent and participated process Last revision EML (April 2013): 374 medicines The first list was a major breakthrough in the history of medicine, pharmacy and public health Médecins sans Frontières, 2000

4. Essential Medicines List: Concept and Procedures 4 |4 | The Essential Medicines List and concept "The concept of essential medicines is one of the major public health achievements in the history of WHO. It is as relevant today as it was at it inception over 30 years ago." Dr Margaret Chan — Director-General, WHO

5. Essential Medicines List: Concept and Procedures 5 |5 | Why is it 'model' Model for its selection process (“one medicine per class” approach unless clinically relevant differences demonstrated ) Model to facilitate efforts to 'improve health' of population Regulation Quality (Rational) Responsible and evidence-based use Procurement and Supply Access : Availability, Affordability, Accessibility and Acceptability

6. Essential Medicines List: Concept and Procedures 6 |6 | 18th WHO Model List of Essential Medicines - 2013 Report of the WHO Expert Committee, 2013 N. = 208 N. = 374

7. Essential Medicines List: Concept and Procedures 7 |7 | EML 2013 in numbers 374 – total number of drugs/medicines –Core list: 282 (FDC: 23) –Complementary list: 68 (FDC: 1)

8. Essential Medicines List: Concept and Procedures 8 |8 | EML 2013 in numbers Adult List 374 – total number of drugs/medicines –Core list: 282 (FDC: 23) –Complementary list: 68 (FDC: 1) Pediatric List 278 in total –Core list: 206 (FDC: 11) –Complementary list: 60 (FDC: 1)

9. Essential Medicines List: Concept and Procedures 9 |9 | Process Evidence Based and Transparent Applications invited and received - addition/deletion/modification –Format proposed (see Applications) and WHO technical Dpt involved –Deadlines: a semester the year before next EC (…, 2013, 2015, … yearly?) –All applications go online Applications peer-reviewed by EC member (2 or 3 indipendent reviewers) –Peer reviews go online Comments invited from any one interested (WHO Depts., Professional Societies, International agencies, Academia) –Comments go on line Expert Committee makes final decisions (full report - TRS)

10. Essential Medicines List: Concept and Procedures 10 | EML criteria (EB 109/8, 2001) Disease burden and public health need Sound and adequate data on the efficacy, safety and comparative cost-effectiveness of available treatments –Need for special diagnostic or treatment facilities considered “Absolute cost of the treatment will not constitute a reason to exclude a medicine from the Model List that otherwise meets the stated selected criteria”

11. Essential Medicines List: Concept and Procedures 11 | Application period for EML 2015 (Expert Committee April 2015) Open for 6 months: 15 June 2014 – 30 November 2014 Applications evaluated for methodology: systematic review, evidence appraisal and synthesis (when needed, changes and new application requested) Application can be rejected (by EML secretariat) for lack of sufficient rigour in reporting available evidence Application sent to 2 or 3 Panel members (acting indipendently as blinded referees)

12. Essential Medicines List: Concept and Procedures 12 | EML: applications, referees and EC The opinions and evaluations expressed by the 2 (or 3) referees are brought to the attention of WHO Expert Committee (EC) EC has a plenary discussion and takes a decision Usually without voting

13. Essential Medicines List: Concept and Procedures 13 | A walk through the process http://www.who.int/selection_medicines/committees/en/ http://www.who.int/selection_medicines/committees/en/ A walk through the process http://www.who.int/selection_medicines/committees/en/ http://www.who.int/selection_medicines/committees/en/

14. Essential Medicines List: Concept and Procedures 14 | The application form/template

15. Essential Medicines List: Concept and Procedures 15 | EML criteria: evidence review is central A systematic review of the best available evidence Systematic review (synthesis and appraisal) more important than metanalysis Importance of evidence table presentation … and appraisal of risk of bias (study defect/reliability) to evaluate confidence in estimates (for both outcomes of efficacy and safety) … once called quality of evidence

16. Essential Medicines List: Concept and Procedures 16 | GRADE evidence table for benefits and harms example 1: single RCTs

17. Essential Medicines List: Concept and Procedures 17 | EML and evidence: for benefits and harms GRADE … example 2

18. Essential Medicines List: Concept and Procedures 18 | GRADE evidence table for benefits and harms example 2: RCTs and observational studies

19. Essential Medicines List: Concept and Procedures 19 | GRADE evidence table for benefits and harms example 3: systematic review (meta-analysis)

20. Essential Medicines List: Concept and Procedures 20 | EML and evidence table for benefits and harms GRADE … example 4

21. Essential Medicines List: Concept and Procedures 21 | EML and evidence table for benefits and harms … example 5 …

22. Essential Medicines List: Concept and Procedures 22 | Simplifying (by commenting) the application form

23. Essential Medicines List: Concept and Procedures 23 | Opportunity to improve EML updating (2015) When highly effective drugs are available Cancer drugs: how to choose the few highly effective (patented, high cost) medicines (2 discussed in EML 2013: trastuzumab in breast cancer and imatinib in chronic myeloid leukemia). Other medicines: rituximab, erlotinib/gefitinib, sunitinib/everolimus, … New highly HCV drugs (new direct antiviral, single agents and combinations, IFN free regimens)

24. Essential Medicines List: Concept and Procedures 24 | Opportunity to improve EML updating (2015) When highly effective drugs are available Cancer drugs: how to choose the few highly effective (patented, high cost) medicines (2 discussed in EML 2013: trastuzumab in breast cancer and imatinib in chronic myeloid leukeima). Other medicines: rituximab, erlotinib/gefitinib, … New highly HCV drugs (new direct antiviral, single agents and combinations, IFN free regimens) WHO could have a leadership role in improving access to highly effective medicines (as was for HIV in 2002)

25. Essential Medicines List: Concept and Procedures 25 | Opportunity to improve EML updating (2015) When highly effective drugs are available Cancer drugs: how to choose the few highly effective (patented, high cost) medicines (2 discussed in EML 2013: trastuzumab in breast cancer and imatinib in chronic myeloid leukemia). Other medicines: rituximab, erlotinib/gefitinib, sunitinib/everolimus, … New highly HCV drugs (new direct antiviral, single agents and combinations, IFN free regimens) New anticoagulants: oral (NAC) and surely LMWH Endocrinology medicines chapter, anti-TNF medicines (for rheumatoid arthritis and IBD), …

26. Essential Medicines List: Concept and Procedures 26 | EML 2015 timeline

27. Essential Medicines List: Concept and Procedures 27 | Apr 2014 EML TRS 2013 printed June-Dic 2014 Jan-March 2015 Apr 2015 Preparation of a 6 month application period (15 th June – 1 st December 2014) Contacts and exchanges with WHO technical Dpts and other UN agencies Reviewing application forms and criteria towards full systematic reviews and GRADE adoption EML 2015 timeline

28. Essential Medicines List: Concept and Procedures 28 | Apr 2014 Application period open June-Dic 2014 Jan-March 2015 Apr 2015 Commissioning and coordination of applications Alignment of WHO GL with EML timeline (HIV, TB, RH, MH Verify the full adoption of systematic reviews and GRADE approach Manage questions and feedbacks from countries on EML adoption and implementation December (10 th – 15 th ): web publication of all applications EML 2015 timeline

29. Essential Medicines List: Concept and Procedures 29 | Apr 2014 EML reviewing and EC referees, and comments June-Dic 2014 Jan-March 2015 Apr 2015 Verify applications (the early the better) for full adoption of systematic reviews and GRADE approach Answers to questions and feedbacks from Countries to be presented to Expert Committee (EC) Summarise a TRS text for EC and prepare the List Merging adult and pediatric Lists into one List to facilitate readability Increase usefulness of EML database EML 2015 timeline

30. Essential Medicines List: Concept and Procedures 30 | Apr 2014 EML web publication June-Dic 2014 Jan-March 2015 Apr 2015 EC meeting 20-25 April 2015 EML published end of April with a summary of decisions taken TRS finalisation for publication (…) In progress: Availability of a EML database of decisions taken and indications evaluated (history and summary of all decisions) EML 2015 timeline

31. Essential Medicines List: Concept and Procedures 31 | WHAT ABOUT DEVICES IN EML?

32. Essential Medicines List: Concept and Procedures 32 | Just a few devices in EML To strengthen a WHO policy (on contraception) To be consistent across various WHO GL/documents If apply, be supported by a WHO technical Dpt Suggestion: first be in a WHO policy document or GL and then apply to EML (rather than the other way round)

33. Essential Medicines List: Concept and Procedures 33 | Conclusions Application for EML will be opened soon and will remain open for 6 months It is strongly reccomended to make an application connected with a WHO technical department And to frame the proposal within a WHO policy document/GL Send it early enough to be reviewed Expert Committee 2015 EML Meeting: April 2015