essential medicines list: concept and procedures 1 |1 | who essential medicines list concept/process...

Essential Medicines List: Concept and Procedures1 |

WHO Essential Medicines ListConcept/Process and Update on EML 2015

WHO Essential Medicines ListConcept/Process and Update on EML 2015

WHO Technical Briefing Seminar

Nicola Magrini – WHO, EMP

November 4, 2014 – WHO Geneva


Essential MedicinesEssential 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.


… 38 years of EML… 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


The Essential Medicines List and concept

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


Why is it 'model'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 populationRegulation

Quality

(Rational) Responsible and evidence-based use

Procurement and Supply

Access: Availability, Affordability, Accessibility and Acceptability


18th WHO Model List of Essential Medicines - 2013

Report of the WHO Expert Committee, 2013

18th WHO Model List of Essential Medicines - 2013

Report of the WHO Expert Committee, 2013

N. = 208 N. = 374


EML 2013 in numbersEML 2013 in numbers

374 – total number of drugs/medicines– Core list: 282 (FDC: 23)– Complementary list: 68 (FDC: 1)


EML 2013 in numbersEML 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)


ProcessEvidence Based and Transparent

ProcessEvidence 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


EML criteria (EB 109/8, 2001)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”


Application period for EML 2015(Expert Committee April 2015)

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)


EML: applications, referees and ECEML: 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


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

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

http://www.who.int/selection_medicines/committees/en/

http://www.who.int/selection_medicines/committees/en/


The application form/templateThe application form/template


EML Application: additional info posted on how to prepare an applicatio

EML Application: additional info posted on how to prepare an applicatio


EML criteria and GRADE … the basicsEML 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


EML and evidence table for benefits and harms

GRADE … example 1EML and evidence table for benefits and harms

GRADE … example 1




GRADE … example 2




GRADE … example 3



… example 4EML and evidence table for benefits and harms

… example 4


The application review process (EB109/8)The application review process (EB109/8)


EML: transparency and dialogueEML: transparency and dialogue

All applications - public

Expert reviews – public

Comments and clarifications letters – public

Technical Report (summarising all the discussion) - public


EML transparency: web applicationsEML transparency: web applications


EML transparency: Expert ReviewsEML transparency: Expert Reviews


EML transparency: CommentsEML transparency: Comments


EML criteria (EB 109/8, 2001)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”


EML 2015EML 2015

A few big challenges


Opportunity to improve EML updatingOpportunity 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






TB large update



EML cancer update: first line treatmentEML cancer update: first line treatment


EML cancer drugs: candidates (15-20)EML cancer drugs: candidates (15-20)






TB large update



EML and New HepC drugsEML 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





New highly HCV drugs (new direct antiviral, single agents and combinations, IFN free regimens)

TB large update


WHO guidance on the management of drug-resistant TB, 1996-2014

The candidate drugs1) New moleculesBedaquiline, Delamanid

2) Repurposed for TB, in EMLAmoxicillin-clavulanate, Azithromycin, Clarithromycin, Clofazimine, Imipenem/cilastatin, Meropenem

3) Repurposed, not in EMLLinezolid, Gatifloxacin, Terizidone




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)


EML timelineEML timeline


Apr 2014

EML TRS 2013 printed

June-Dic 2014 Jan-March 2015 Apr 2015

• 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

EML 2014 - 2015 timeline


Apr 2014

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



Apr 2014

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



Apr 2014

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



WHAT ABOUT DEVICES IN EML?WHAT ABOUT DEVICES IN EML?


Where do we start from Where do we start from

2006 2008


Just few devices are in EML 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)


ConclusionsConclusions

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


Rational drug therapy (RDT)Quality use of medicines

Appropriate use of medicinesResponsible and evidence-based use

Rational drug therapy (RDT)Quality use of medicines

Appropriate use of medicinesResponsible and evidence-based use

Access to essential medicines and implementation at country level


Selection processSelection process


EML: why a model?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


Access and appropriate use of medicines:

issues and challenges – PUSH MODEAccess and appropriate use of medicines:

issues and challenges – PUSH MODEHow 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, …


Access and appropriate use of medicines:

issues and challenges – PULL MODEAccess 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– …


How to support good prescribingHow to support good prescribing


Two different level of action: one supporting the other

Two different level of action: one supporting the other

1. Access to available evidence– Retrieval, systematic review, critical appraisal, synthesis and

user-friendly presentation– Understanding, applicability and relevance,

2. Guidelines and recommendation– Standard and conditional recommendation and indicators of use


The importance of the contextThe 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 importance of the contextThe 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:

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

• 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

• Guidelines• Recommendations• Consensus conferences• Inappropriate uses

essential medicines list: concept and procedures 1 |1 | who essential medicines list concept/process...

Documents

list of essential medicines

concept of essential

model list

complementary list

pediatric list

total core list

numbers adult list

active substances list