Antimicrobial resistance

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The selection of essential medicines
Hans V. Hogerzeil, MD, PhD, FRCP
Edin Department of Essential Drugs and
Medicines Policy World Health Organization,
October 2002
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Overview

• The concept of essential drugs
• New procedures to update the Model List of
  Essential Drugs
• A fly in the ointment
• Guidelines for guidelines
• The WHO Essential Medicines Library
• Conclusion

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Essential medicines

• The concept of essential medicines
• A limited range of carefully selected essential
  medicines leads to better health care, better
  drug management, and lower costs
• Definition of essential medicines
• Essential medicines are those that satisfy the
  priority health care needs of the population
• 
  (Report to WHO Executive Board, January
  2002)

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History of the WHO Model List of Essential Drugs

• 1977 First Model list published, 200 active
  substances
• List is revised every two years by WHO Expert
  Committee
• Last revision (April 2002) contains 325 active
  substances
• 2002 Revised procedures approved by WHO

The first list was a major breakthrough in the
history of medicine, pharmacy and public health

Médecins sans Frontières, 2000
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The Essential Medicines Target
National list of essential medicines
Registered medicines
All the drugs in the world
Levels of use
CHW
S
S
dispensary
Health center
Supplementary specialist medicines
Hospital
Referral hospital
Private sector
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Relation between treatment guidelines and a list
of essential medicines
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Number of countries with a national list of
essential medicines
156 countries with EDLS 1/3 within 2 years 3/4
within 5 years
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Use of the WHO Model List of Essential Drugs

• 156 countries have a national list of essential
  drugs, of which 81 have been updated in the last
  5 years
• Major international agencies (UNICEF, UNHCR, IDA)
  base their catalogue on the WHO Model List
• Sub-sets UN list of recommended essential drugs
  for emergency relief (85 drugs) interagency New
  Emergency Health Kit (55 drugs for 10,000
  consultations)
• Normative tools WHO Model Formulary,
  International Pharmacopoea, Basic Quality Tests,
  and development of reference standards follow the
  WHO Model List

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Example of challengeNew essential drugs are
expensive

• Antibiotics for gonorrhoea 50-90x price of
  penicillins
• Antimalarial drugs chloroquine 0.10 per
  treatment coartem 3/pp developing country
  (30x) malarone 40 per dose (400x)
• Antituberculosis 20 for DOTS vs 400 for MDR
  (20x)
• Antiretrovirals 300-600/year but 38 countries
  with a drug budget

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The WHO Model List of Essential Medicines is
amodel product, model process and public health
tool

• Model product list of essential drugs with
  information
• Core list minimum drug needs for a basic health
  care system, listing the most cost-effective
  drugs for priority conditions (selected on the
  basis of burden of disease and potential for safe
  and cost-effective treatment).
• Complementary list essential drugs for priority
  diseases for which specialised health care
  facilities may be needed and (?) which are
  cost-effective but not necessarily affordable

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The WHO Model List of Essential Medicines is
amodel product, model process and public health
tool

• Independent Membership of the Committee, careful
  consideration of conflict of interest,
• Transparent process, standard application, review
• Link to evidence-based treatment recommendations,
  in accordance with WHO Recommended Process for
  Developing Clinical Practice Guidelines
• Systematic review of comparative efficacy, safety
  and cost-effectiveness, and review of public
  health relevance
• Rapid dissemination, electronic access
• Regular review

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Model process (1)Steps in review of
applications to the Model List

• 1 Summary of application posted on WHO Medicines
  web site
• 2 Specialist assessment of comparative efficacy,
  safety and cost-effectiveness
• 3 Review of assessments by Expert Committee
  member (presenter) formulation of draft
  recommendation
• 4 Review of draft recommendation by relevant
  Expert Advisory Panel members and posted on WHO
  Medicines web site
• 5 Review by presenter, prepares final draft
  recommendation
• 6 Discussion of draft recommendation and proposed
  text for WHO Model Formulary by the Expert
  Committee

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Model process (2)Presentation of
recommendations, report

• Presentation of recommendations
• Summary of reasons for each recommendation
• Reference to underlying evidence and systematic
  reviews
• Reference to existing clinical guidelines
• Report, web site, translations
• Report of the meeting published on WHO Medicines
  web site
• Report issued in WHO Technical Report Series
• List and recommendations translated into other
  languages

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Seven steps to get a new medicine onthe WHO
Model List of Essential Drugs

• 1. Identification of public-health need for a
  medicine
• 2. Development of the medicine phase I - II -
  III trials
• 3. Regulatory approval in a number of countries
• Effective and safe medicine on the market
• 4. More experience under different field
  circumstances post-marketing surveillance
• 5. Price indication for public sector use
• 6. Review by WHO disease programme define
  comparative effectiveness and safety in real-life
  situations, comparative cost-effectiveness and
  public health relevance
• Medicine included in WHO treatment guideline
• 7. Submission to WHO Expert Committee on
  Essential Drugs
• Medicine included in WHO Model List

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The WHO Model List of Essential Medicines is
amodel product, model process and public health
tool

• Main public health advocacy messages
• Essential drugs are the most cost-effective drugs
  for a given condition
• A limited range of carefully selected medicines
  can cater for most health care needs
• There is much waste through irrational selection
  and use
• Access to health care is a human right - to be
  progressively realized - and includes access to
  life-saving medicines
• The essential medicines concept is globally
  applicable

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A fly in the ointmentWHO Model List of
Essential Drugs 1999 compared with drugs included
in WHO Treatment Guidelines

• 306 active substances on 405 drugs
• WHO Model List mentioned in WHO
• of Essential Drugs Treatment Guidelines

250
56
155
e.g. cytotoxics, hormones, diagnostic agents,
gastrointestinal drugs
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Example of a link chloramphenicol

• Chloramphenicol is recommended for the following
  indications
• Injectable Severe pneumonia in children, severe
  asthma-pneumonia, brain abscess, meningitis in
  children with ARI, epiglottitis, granuloma
  inguinale, mastoiditis, meningitis (various
  kinds), obstetrics, septicaemia
• Oral severe pneumonia in children, asthma
  pneumonia, meningitis in children, cholera,
  louse borne typhus, measles pneumonia,
  meningitis (empirical and meningococcal),
  abortion care, plague, relapsing fever,
  Rickettsia, typhoid fever
• recommended as alternative drug

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Analysis of WHO treatment guidelines (1)Overview
of 192 printed materials collected (Robin Gray)

• 71 Primary guidelines
• 12 Secondary materials
• 11 Teaching and training materials
• 5 Recommended drug lists in other documents
• 28 Public health publications
• 21 Limited distribution
• 6 Drafts
• 15 Status unclear
• 23 Obsolete or irrelevant

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Analysis of WHO treatment guidelines (2)First
analysis of 71 primary treatment guidelines

• 52 (73) published within last 6 years
• 36 (51) target audience clearly defined
• 27 (38) development process clearly described
• 31 (44) affiliations of contributors mentioned
• 39 (55) link recommendations to references
• ! NB Inherent unfairness in comparing treatment
  guidelines of yesterday with standards of today

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Analysis of WHO treatment guidelines (3)
Conclusions

• WHO treatment guidelines are difficult to collect
• Many treatment guidelines are not user-friendly
  (eg. no index)
• Primary treatment guidelines are not easily
  identified as such
• Some guidelines do not state target audience,
  target disease
• Development process is not always clearly
  described
• Affiliations of contributors are not always
  mentioned
• Lack of graded recommendations and linked
  references

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The way forwardGuidelines for Guidelines

• WHO Cabinet discussion and decision January 2000
• All WHO treatment guidelines should be
  evidence-based
• Intensive collaboration between WHO and
• Scottish Intercollegiate Guidelines Network
  (SIGN)
• Cochrane Collaboration
• Pharmaceutical Benefit Scheme (PBS),
  Australia
• Council of Europe (AGREE)
• WHO internal procedure for guideline development
• Development of WHO Practice Guidelines
  Recommended Process

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Model process (3)Link to Guidelines for
Guidelines(approved by WHO Cabinet in January
2001)
Systematic and transparent process

• Guideline development group with wide
  representation
• Careful consideration of conflict of interest
• Systematic computer search for evidence
• Evaluation of strength of evidence
• Systematic cost-effectiveness analysis
• for WHO evaluation of public health
  considerations
• Graded recommendations with linked references
• External review of draft recommendations
• If there is insufficient evidence consensus
  expert opinion

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WHO Essential Medicines LibraryCombining
information from various partners
WHO clusters
WHO/EDM
Summary of clinical guideline
Clinical guideline
BNF
WHO Model Formulary
WHO/EC, Cochrane
Reasons for inclusion Systematic reviews Key
references
WHO Model List
WHO/QSM
MSH UNICEF MSF
Cost - per unit - per treatment - per month -
per case prevented
Statistics - ATC - DDD
Quality information - Basic quality tests -
Intern. Pharmacopoea - Reference standards
WCCs Oslo/Uppsala
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Conclusion

• Evidence-based WHO clinical guidelines are the
  foundation for the Model List of Essential Drugs
• The Model List remains a strong public health
  tool
• The WHO Essential Medicines Library is a valuable
  information tool for countries and institutions

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www.who.int / medicines
Thank you