The concept of essential drugs and the WHO Model List of Essential Medicines Hans V. Hogerzeil, MD, PhD, FRCP Edin Department of Essential Drugs and Medicines Policy World Health Organization, September 2003

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)

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 2002 Revised procedures approved by WHO Last revision (April 2003) contains 315 active substances The first list was a major breakthrough in the history of medicine, pharmacy and public health Médecins sans Frontières, 2000

Full description of essential drugs (Expert Committee Report, April 2002) Definition: Essential medicines are those that satisfy the priority health care needs of the population Selection criteria: Essential medicines are selected with due regard to disease prevalence, evidence on efficacy and safety, and comparative cost-effectiveness Purpose: Essential medicines are intended to be available within the context of functioning health systems at all times, in adequate amounts, in the appropriate dosage forms, with assured quality, and at a price the individual and the community can afford. Implementation: The implementation of the concept of essential medicines is intended to be flexible and adaptable to many different situations; exactly which medicines are regarded as essential remains a national responsibility.

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

List of common diseases and complaints Clinical guidelines and a list of essential medicines lead to better prevention and care List of common diseases and complaints Treatment choice Treatment guidelines Essential medicines list / National formulary Training and Supervision Financing and Supply of drugs Prevention and care

Number of countries with a national list of essential medicines 156 countries with EDLS 1/3 within 2 years 3/4 within 5 years National Essential Drugs List < 5 years (127) > 5 years (29) No NEDL (19) Unknown (16)

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

Example of challenge: New essential drugs are expensive (1) 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: $10 for DOTS vs $250 for MDR (25x) Antiretrovirals: $300-600/year; but 38 countries with a drug budget <$2 pp/year

New essential drugs are expensive (2) also in industrialized countries! Canada: 55% of prescription cost rise of 93% over 1987-1993 was due to introduction of new drugs USA: Pharmaceuticals market grew with 16% in 1999, 18% in 2000 and 17% in 2001; volume rise in 2000 only 5.5% Growth due to * elderly population * new therapies * increased prescriptions by managed care * direct-to- consumer advertising Australia: Annual increase in drug costs for Pharmaceutical Benefit Scheme could pay for two new teaching hospitals

Perceived problems with the WHO Model List prior to 2002 revision of procedures (Expert Committee, 1999) Range of diseases covered by the Model List is not clear Discrepancies between Model List and treatment guidelines Selection is more consensus-based than evidence-based Use of data on cost and cost-effectiveness unclear Reasons for selection insufficiently recorded Drugs included without pharmacopoeal standard or supplier Official report comes out too late, and in English only

*e.g. cytotoxics, hormones, diagnostic agents, gastrointestinal drugs WHO 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 56* 250 155 *e.g. cytotoxics, hormones, diagnostic agents, gastrointestinal drugs

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

Outcome of the revised procedures: The WHO Model List of Essential Medicines is a model process, model product 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

Model process (1): Seven steps to get a new medicine on the 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

Systematic and transparent process Model process (2): 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

Model process (3): 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

Model process (4): Role of treatment cost and global cost-effectiveness analyses High cost alone should not exclude an essential medicine Cost-effectiveness (C/E) comparisons will be made among alternative medicines within the same therapeutic group Price information from existing UN sources will be used; all information sources will be identified Simple indicators will be used: cost per unit, cost per treatment/month, cost per cure, cost per case prevented Emphasis on usual outcome measures, and use of existing and published comparative cost-effectiveness analyses New C/E calculations will be transparent and can be adapted

Model process (5): Presentation of recommendations, report Summary of reasons for each recommendation Reference to underlying evidence and systematic reviews Reference to existing clinical guidelines Inclusion in WHO Essential Medicines Library 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

Summary of clinical guideline The WHO Model List of Essential Medicines is a model process, model product and public health tool The WHO Essential Medicines Library WHO clusters WHO/EDM Clinical guideline Summary of 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

WHO Model Formulary First edition launched at FIP, Nice (September 2002) WHO priced publication (SFr 40, SFr 20) Web version as PDF file and searchable database First print run of 7000 exhausted; second print January 2003 CD-ROM (searchable and downloadable) available June 2003 Translations ongoing in Arabic, Chinese, French, Russian, Spanish; maybe electronic versions only (on CD) Revision in 2003 (follows 13th Model List) 5-year commitment to RPS and BMJ Manual “How to develop a national formulary” in preparation

The New Emergency Health Kit 1984, 1990, 1998 Essential medicines and supplies for 10,000 people for three months Consensus between WHO, UNICEF, UNHCR, UNFPA, Red Cross, MSF, OXFAM, missions, IDA

Selection of emergency relief items 325 WHO Model List 2002 UN List of Emergency Relief Items 88 UNDP WHO ICRC FRC MSF UNICEF UNHCR UNFPA IDA EPN OXFAM New Emergency Health Kit 1998 55 Adaptation needed: ORS, antimalarials, syringes, emergency contraception

Essential medicines for Reproductive Health: Discrepancies in international RH lists 75 on UNFPA List 6 325 on WHO Model List 6 194 63 150 on Interagency RH medical commodities 65 22

The WHO Model List of Essential Medicines is a model process, model product 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. This includes access to essential medicines The essential medicines concept is globally applicable

Conclusion The concept of essential medicines is a global concept 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 base for all Member States, international organisations, drugs and therapeutic committees and health insurance organisations

Essential Drugs and Medicines Policy WHO Department of Essential Drugs and Medicines Policy www.who.int / medicines Thank you