WHO Essential Medicines List

Concept and Process

IPC Meeting
June 6, 2014 – WHO Geneva

Nicola Magrini – WHO, EMP

1| 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 cost-
effectiveness.

2| 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):

• 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

3| 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

4| 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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18th WHO Model List of Essential Medicines - 2013
Report of the WHO Expert Committee, 2013

N. = 208 N. = 374

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 EML 2013 in numbers

 374 – total number of drugs/medicines

– Core list: 282 (FDC: 23)
– Complementary list: 68 (FDC: 1)

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 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)

8| Essential Medicines List: Concept and Procedures

 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)

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 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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 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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 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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 A walk through the process
http://www.who.int/selection_medicines/committees/en/

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 The application form/template

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 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

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 GRADE evidence table for benefits and harms
example 1: single RCTs

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 EML and evidence: for benefits and harms
GRADE … example 2

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 GRADE evidence table for benefits and harms
example 2: RCTs and observational studies

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 GRADE evidence table for benefits and harms
example 3: systematic review (meta-analysis)

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 EML and evidence table for benefits and harms
GRADE … example 4

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 EML and evidence table for benefits and harms
… example 5 …

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 Simplifying (by commenting)
the application form

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 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)

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 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)

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 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), …

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 EML 2015 timeline

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 EML 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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 EML 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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 EML 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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 EML 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 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)

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 WHAT ABOUT DEVICES IN EML?

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 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)

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 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

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