Transcript WHO Essential Medicines List Concept/Process and Update on EML

WHO Essential Medicines List
Concept/Process and Update on EML 2015
WHO Technical Briefing Seminar
Nicola Magrini – WHO, EMP
November 4, 2014 – WHO Geneva
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Essential Medicines List: Concept and Procedures
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 costeffectiveness.
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Essential Medicines List: Concept and Procedures
… 38 years of EML
1977 1st Model list published, 208 active substances
- List is revised every two years by WHO Expert Committee
- 2002 Revised procedures approved by WHO (EB109/8)
- Last revision EML (April 2013) contains 374 medicines
The first list was a major breakthrough in the history of medicine,
pharmacy and public health
Médecins sans Frontières, 2000
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Essential Medicines List: Concept and Procedures
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Essential Medicines List: Concept and Procedures
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
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Essential Medicines List: Concept and Procedures
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
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Essential Medicines List: Concept and Procedures
18th WHO Model List of Essential Medicines 2013
Report of the WHO Expert Committee, 2013
N. = 208
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Essential Medicines List: Concept and Procedures
N. = 374
EML 2013 in numbers
 374 – total number of drugs/medicines
– Core list: 282 (FDC: 23)
– Complementary list: 68 (FDC: 1)
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Essential Medicines List: Concept and Procedures
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)
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Essential Medicines List: Concept and Procedures
Process
Evidence Based and Transparent
 Applications invited - 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 experts
– 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
– Report goes on line
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Essential Medicines List: Concept and Procedures
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”
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Essential Medicines List: Concept and Procedures
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)
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Essential Medicines List: Concept and Procedures
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
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Essential Medicines List: Concept and Procedures
A walk through the process
http://www.who.int/selection_medicines/committees/en/
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Essential Medicines List: Concept and Procedures
The application form/template
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Essential Medicines List: Concept and Procedures
EML Application: additional info posted
on how to prepare an applicatio
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Essential Medicines List: Concept and Procedures
EML criteria and GRADE … the basics
 A systematic review of the best available evidence
 A systematic review (synthesis and appraisal) is more
important than a metanalysis (pooled estimate)
 Importance of summary evidence table … with appraisal
of risk of bias (study defect/reliability) to evaluate
confidence in estimates (for both outcomes of efficacy
and safety) … this was once called quality of evidence
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Essential Medicines List: Concept and Procedures
EML and evidence table for benefits and harms
GRADE … example 1
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Essential Medicines List: Concept and Procedures
EML and evidence table for benefits and harms
GRADE … example 2
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Essential Medicines List: Concept and Procedures
EML and evidence table for benefits and harms
GRADE … example 2
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Essential Medicines List: Concept and Procedures
EML and evidence table for benefits and harms
GRADE … example 2
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Essential Medicines List: Concept and Procedures
EML and evidence table for benefits and harms
GRADE … example 2
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Essential Medicines List: Concept and Procedures
EML and evidence table for benefits and harms
GRADE … example 3
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Essential Medicines List: Concept and Procedures
EML and evidence table for benefits and harms
… example 4
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Essential Medicines List: Concept and Procedures
The application review process (EB109/8)
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Essential Medicines List: Concept and Procedures
EML: transparency and dialogue
 All applications - public
 Expert reviews – public
 Comments and clarifications letters – public
 Technical Report (summarising all the discussion) public
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Essential Medicines List: Concept and Procedures
EML transparency: web applications
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Essential Medicines List: Concept and Procedures
EML transparency: Expert Reviews
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Essential Medicines List: Concept and Procedures
EML transparency: Comments
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Essential Medicines List: Concept and Procedures
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”
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Essential Medicines List: Concept and Procedures
EML 2015
A few big challenges
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Essential Medicines List: Concept and Procedures
Opportunity to improve EML updating
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:
see next table, …
 New HCV drugs (new direct antiviral, single agents and
combinations, IFN free regimens)
 TB large update
 New anticoagulants: oral (NAC) and surely LMWH
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Essential Medicines List: Concept and Procedures
Opportunity to improve EML updating
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:
see next table, …
 New HCV drugs (new direct antiviral, single agents and
combinations, IFN free regimens)
 TB large update
 New anticoagulants: oral (NAC) and surely LMWH
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Essential Medicines List: Concept and Procedures
EML cancer update: first line treatment
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Essential Medicines List: Concept and Procedures
EML cancer drugs: candidates (15-20)
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Essential Medicines List: Concept and Procedures
Opportunity to improve EML updating
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:
see next table, …
 New HCV drugs (new direct antiviral, single agents and
combinations, IFN free regimens)
 TB large update
 New anticoagulants: oral (NAC) and surely LMWH
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Essential Medicines List: Concept and Procedures
EML and New HepC drugs
 Very effective oral drugs (IFN free regimens)
 A WHO GL with a strong recommendation
 Sofosbuvir and Ledipasvit/sofosbuvir combination (already IN the
applications)
 What to di with financial implications
 What to do with new drugs in the pipeline
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Essential Medicines List: Concept and Procedures
Opportunity to improve EML updating
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:
see next table, …
 New highly HCV drugs (new direct antiviral, single agents and
combinations, IFN free regimens)
 TB large update
 New anticoagulants: oral (NAC) and surely LMWH
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Essential Medicines List: Concept and Procedures
WHO guidance on the management
of drug-resistant TB, 1996-2014
The candidate drugs
1) New molecules
Bedaquiline, Delamanid
2) Repurposed for TB, in EML
Amoxicillin-clavulanate, Azithromycin,
Clarithromycin, Clofazimine, Imipenem/cilastatin,
Meropenem
3) Repurposed, not in EML
Linezolid, Gatifloxacin, Terizidone
Opportunity to improve EML updating
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).
 New highly HCV drugs (new direct antiviral, single agents and
combinations, IFN free regimens)
 TB drugs (12)
WHO could have a leadership role in improving access to
highly effective medicines (as was for HIV in 2002)
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Essential Medicines List: Concept and Procedures
EML timeline
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Essential Medicines List: Concept and Procedures
EML 2014 - 2015 timeline
Apr 2014
June-Dic 2014
Jan-March 2015
Apr 2015
EML TRS 2013
printed
• Preparation of a 6 month application period
(15th June – 1st 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
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Essential Medicines List: Concept and Procedures
EML 2014 - 2015 timeline
Apr 2014
June-Dic 2014
Jan-March 2015
Apr 2015
Application
period open
• 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 (10th – 15th): web publication of all applications
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Essential Medicines List: Concept and Procedures
EML 2014 - 2015 timeline
Apr 2014
June-Dic 2014
Jan-March 2015
Apr 2015
EML reviewing
and EC referees,
and comments
• 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
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Essential Medicines List: Concept and Procedures
EML 2014 - 2015 timeline
Apr 2014
June-Dic 2014
Jan-March 2015
Apr 2015
EML web publication
• EC meeting 20-25 April 2015
• EML published end of April and summary of
decisions taken
• TRS finalisation for publication (…)
• TBC: Availability of a EML database of decisions
taken and indications evaluated/approved/rejected
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Essential Medicines List: Concept and Procedures
WHAT ABOUT DEVICES IN EML?
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Essential Medicines List: Concept and Procedures
Where do we start from
 2006
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Essential Medicines List: Concept and Procedures
 2008
Just few devices are 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)
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Essential Medicines List: Concept and Procedures
Conclusions
 Application for EML will be opened soon and will remain
open for 6 months
 It is strongly encouraged to make an application
connected with a WHO technical department
 Frame your proposal within a WHO policy document/GL
 Send it early enough to be reviewed
 Expert Committee 2015 EML Meeting: April 2015
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Essential Medicines List: Concept and Procedures
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Essential Medicines List: Concept and Procedures
Rational drug therapy (RDT)
Quality use of medicines
Appropriate use of medicines
Responsible and evidence-based use
Access to essential medicines and
implementation at country level
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Essential Medicines List: Concept and Procedures
Selection process
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Essential Medicines List: Concept and Procedures
EML: why a model?
 A model for process and transparency
 Evidence-based rigorous process: high scrutiny on
quality of evidence AND on its applicability at a global
level
 Management of conflicts of interests
 Feed backs from country implementation
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Essential Medicines List: Concept and Procedures
Access and appropriate use of medicines:
issues and challenges – PUSH MODE
 How to give access to the best available evidence
– Full access to all available evidence
– Understanding: critically appraised, highly scrutinised with
multidisciplinary considerations
– How? Are TRS report enough? Probably NOT …
 Connection and good alignment with WHO guidelines
– Examples from: OC, TB, HIV, HepC, Mental Health, …
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Essential Medicines List: Concept and Procedures
Access and appropriate use of medicines:
issues and challenges – PULL MODE
New drugs are introduced different from EML
 EML in delay … important new drugs
– LMWH
– Cancer drugs
– …
 Drugs lacking good enough supporting evidence
– Drugs for memory
– …
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Essential Medicines List: Concept and Procedures
How to support good prescribing
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Essential Medicines List: Concept and Procedures
Two different level of action:
one supporting the other
1. Access to available evidence
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Retrieval, systematic review, critical appraisal, synthesis and
user-friendly presentation
Understanding, applicability and relevance,
2. Guidelines and recommendation
–
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Standard and conditional recommendation and indicators of use
Essential Medicines List: Concept and Procedures
The importance of the context
 Actual medicines use at local/national level
 Access to available evidence
 Guidelines and recommendations
 Drug utilization data: international comparison, small and large area
variability, …
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Essential Medicines List: Concept and Procedures
The importance of the context
 Actual medicines use at local/national level
 Access to available evidence
 Guidelines and recommendations
 Drug utilization data: international comparison, small
and large area variability, …
 The need for a comprehensive pharmaceutical
policy:
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Essential Medicines List: Concept and Procedures
Pharmaceutical policy
• By pharmaceutical policy we mean the conscious efforts of
national governments to influence the pharmaceutical system
Pharmaceutical policy
• By pharmaceutical policy we mean the conscious efforts of
national governments to influence the pharmaceutical system
… health system
• Equitable access
• Affordability
• Appropriate use
Functions of pharmaceutical sector
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Registration of medicines
Licensing of pharmaceutical business
Inspection of establishment
Medicine promotion
Clinical trials and independent confirmatory research
Indipendent drug information
Guidelines program and evidence-based recommendations
Selection of essential medicines
Procurement of medicines
Distribution of medicines
Drug utilization
There is a difference
• Independent drug
bulletins
• Cochrane reviews
• Clinical Evidence
• Uptodate
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Guidelines
Recommendations
Consensus conferences
Inappropriate uses