Rational use of drugs:

an overview

Kathleen Holloway
Technical Briefing Seminar
November 2009

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Objectives

• Define rational use of medicines and identify the

magnitude of the problem

• Understand the reasons underlying irrational use

• Discuss strategies and interventions to promote

rational use of medicines

• Discuss the role of government, NGOs, donors and

WHO in solving drug use problems

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 The rational use of drugs requires that patients receive
medications appropriate to their clinical needs, in
doses that meet their own individual requirements for
an adequate period of time, and at the lowest cost to
them and their community.
WHO conference of experts Nairobi 1985
• correct drug
• appropriate indication
• appropriate drug considering efficacy, safety, suitability for the
patient, and cost
• appropriate dosage, administration, duration
• no contraindications
• correct dispensing, including appropriate information for patients
• patient adherence to treatment

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Adequacy of diagnostic process
Source: Thaver et al SSM 1998, Guyon et al WHO Bull 1994, Krause et al TMIH
1998, Bitran HPP 1995, Bjork et al HPP 1992, Kanji et al HPP 1995.

Pakistan

Bangladesh

Burkino Faso

Senegal

Angola

Tanzania

0 10 20 30 40 50 60
% observed consultations where the diagnostic process was adequate

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 5-55% of PHC patients receive injections -
90% may be medically unnecessary
Source: Quick et al, 1997, Managing Drug Supply
A F R IC A

G ha na

C a m e ro o n

N ige ria

S uda n

T a nza nia

Z im ba bwe

A S IA

Yemen

Indo ne s ia

N e pa l
 15 billion injections per year globally
L.A M E R . & C A R .

E c ua do r  half are with unsterilized needle/syringe

G ua t e m a la

E l S a lv a do r
 2.3-4.7 million infections of hepatitis B/C
J a m a ic a and up to 160,000 infections of HIV per
E a s t e rn C a ribe a n
year associated with injections

0% 10% 20% 30% 40% 50% 60%

% of primary care patients receiving injections

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Variation in outpatient antibiotic use
in 26 European countries in 2002
35

30
DDD per 1000 inh. per day

25

20

15

10

0
FR GR LU PT IT BE SK HR PL IS IE ES FI BG CZ SI SE HU NO UK DK DE LV AT EE NL

Source: Goosens et al, Lancet, 2005; 365: 579-587; ESAC project.

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Database on medicines use

• Database of all medicines use

surveys using standard indicators in
primary care in developing and
transitional countries
• Studies identified from INRUD
biliog, PUBMED, WHO archives
• Data on study setting, interventions,
methods and drug use extracted &
entered
• All data extraction and entry
checked by 2 persons
• Now > 900 studies entered
• Systematic quantitative review
• Evidence from analysis used for
WHA60.16 in 2007

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 % compliance with guidelines by WB region

60
50
40
30
20
10
0
1982-1994 1995-2000 2001-2006
Sub-Saharan Africa (n=29-48) Lat. America & Carrib (n=5-13)
Middle East & C. Asia (n=4-8) East Asia & Pacific (n=7-11)
South Asia (n=6-12)

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Public / private treatment of acute diarrhoea
by doctors, nurses, paramedical staff
80
70
60
50
40
30
20
10
0
% diarrhoea cases % diarrhoea cases % diarrhoea cases
prescribed antibiotic prescribed anti-diarrhoeals prescribed ORS

Public (n=54-90) Private-for-profit (n=5-10)

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Treatment of ARI by prescriber type
80
70
60
50
40
30
20
10
0
% viral URTI cases % pneumonia cases % ARI cases treated with
prescribed antibiotic prescribed antibiotic cough syrup

Doctor (n=26-62) Nurse/paramedic (n=12-86) Pharmacy staff (n=9-17)

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Overuse and misuse of antimicrobials
contributes to antimicrobial resistance
Source: WHO country data 2000-3
• Malaria
– choroquine resistance in 81/92 countries
• Tuberculosis
– 0-17 % primary multi-drug resistance
• HIV/AIDS
– 0-25 % primary resistance to at least one anti-retroviral
• Gonorrhoea
– 5-98 % penicillin resistance in N. gonorrhoeae
• Pneumonia and bacterial meningitis
– 0-70 % penicillin resistance in S. pneumoniae
• Diarrhoea: shigellosis
– 10-90% ampicillin resistance, 5-95% cotrimoxazole resistance
• Hospital infections
– 0-70% S. Aureus resistance to all penicillins & cephalosporins

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Community surveillance
of AMR and use (1)
• Developing & piloting method for
integrated surveillance of AMR & AB
use & collection of baseline data in 2
resource-constrained settings
• 3 sites in India & 2 in S. Africa
• AMR & AB use data collected
monthly for 1-2 years from same
communities
• 4 sites measured AMR in E.Coli & 1
in S.pneum & H.influenzae
• AB use by private GPs, retailers,
public & priv hospitals & PHCs by
exiting patient interview or
prescribing & dispensing records
• Qualitative study (FGDs) into
provider & consumer behaviour

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Community surveillance of AMR and use (2):
results
• Antimicrobial resistance
– pathogenic E.Coli in pregnant women's urine in India
• Cotrim 46-65%; Ampi 52-85%; Cipro 32-59%; Cefalex 16-50%
– S.Pneumoniae & H.influenzae in sputa in S. Africa
• Cotrim > 50% (both organisms); Ampi >70% (H.influenzae)
• Antibiotic use
– About ½ patients in India & ¼ or less of patients in S.Africa get ABs
– Much inappropriate AB use especially in India e.g. use of fluoroquinolones
for coughs and colds in private sector
• Motivation of providers & consumers
– Patient demand – looking for quick cure
– Lack of CME & unwillingness to attend for fear of losing custom
– Uncontrolled pharmaceutical promotion, involving financial gain

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Adverse drug events
Source: Review by White et al,
Pharmacoeconomics, 1999, 15(5):445-458

• 4-6th leading cause of death in the USA

• estimated costs from drug-related morbidity &
mortality 30 million-130 billion US$ in the USA
• 4-6% of hospitalisations in the USA & Australia
• commonest, costliest events include bleeding,
cardiac arrhythmia, confusion, diarrhoea, fever,
hypotension, itching, vomiting, rash, renal failure

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Changing a Drug Use Problem:
An Overview of the Process

1. EXAMINE
Measure Existing
Practices
(Descriptive
Quantitative Studies)
improve
4. FOLLOW UP 2. DIAGNOSE
Measure Changes diagnosis Identify Specific
in Outcomes Problems and Causes
(Quantitative and Qualitative (In-depth Quantitative
Evaluation) and Qualitative Studies)
improve
intervention

3. TREAT
Design and Implement
Interventions
(Collect Data to
Measure Outcomes)

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Many Factors Influence Use of Medicines
Intrinsic
Prior
Knowledge
Scientific
Habits
Information Information

Influence Social &

of Drug Cultural
Industry Factors
Treatment Societal
Workload &
Choices Economic &
Staffing Legal Factors

Workplace Infra- Authority &

structure Relationships Supervision
With Peers
Workgroup

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Strategies to Improve Use of Drugs

Educational: Managerial:
 Inform or persuade  Guide clinical practice
– Health providers – Information systems/STGs
– Consumers – Drug supply / lab capacity

Use of
Medicines

Economic: Regulatory:
 Offer incentives  Restrict choices
– Institutions – Market or practice controls
– Providers and patients – Enforcement

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Educational Strategies
Goal: to inform or persuade
• Training for Providers
– Undergraduate education
– Continuing in-service medical education (seminars, workshops)
– Face-to-face persuasive outreach e.g. academic detailing
– Clinical supervision or consultation
• Printed Materials
– Clinical literature and newsletters
– Formularies or therapeutics manuals
– Persuasive print materials
• Media-Based Approaches
– Posters
– Audio tapes, plays
– Radio, television

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Impact of Patient-Provider Discussion Groups
on Injection Use in Indonesian PHC Facilities
Source: Hadiyono et al, SSM, 1996, 42:1185

% Prescribing Injections

80

60

Pre
40 Post

20

0
Intervention Control

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Training for prescribers
The Guide to Good Prescribing

• WHO has produced a Guide for Good

Prescribing - a problem-based method
• Developed by Groningen University in
collaboration with 15 WHO offices and
professionals from 30 countries
• Field tested in 7 sites
• Suitable for medical students, post grads,
and nurses
• widely translated and available on the WHO
medicines website

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Managerial strategies
Goal: to structure or guide decisions

• Changes in selection, procurement, distribution to

ensure availability of essential drugs
– Essential Drug Lists, morbidity-based quantification, kit systems

• Strategies aimed at prescribers

– targeted face-to-face supervision with audit, peer group
monitoring, structured order forms, evidence-based standard
treatment guidelines

• Dispensing strategies
– course of treatment packaging, labelling, generic substitution

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 RCT in Uganda of the effects of STGs, training and
supervision on % of Px conforming to guidelines
Source: Kafuko et al, UNICEF, 1996.

Randomised No. health Pre- Post- Change

group facilities intervention intervention

Control group 42 24.8% 29.9% +5.1%

Dissemination of 42 24.8% 32.3% +7.5%

guidelines

Guidelines + on- 29 24.0% 52.0% +28.0%

site training

Guidelines + on-
site training + 4 14 21.4% 55.2% +33.8%
supervisory visits

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Economic strategies:
Goal: to offer incentives to providers an consumers

• Avoid perverse financial incentives

– prescribers’ salaries from drug sales
– insurance policies that reimburse non-essential
drugs or incorrect doses
– flat prescription fees that encourage polypharmacy
by charging the same amount irrespective of
number of drug items or quantity of each item

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Pre-post with control study of an economic
intervention (user fees) on prescribing quality in Nepal
Source: Holloway, Gautam & Reeves, HPP, 2001

Fees (complete control fee / Px 1-band item fee 2-band item fee
drug courses) n=12 n=10 n=11

Av. no. items 2.9 2.9 2.9 2.0 2.8 2.2

per prescription (+/- 0) (-0.9) (-0.6)

% prescriptions 23.5 26.3 31.5 45.0 31.2 47.7

conforming to (+2.7%) (+13.5%) (+16.5%)
STGs

Av.cost (NRs) 24.3 33.0 27.7 28.0 25.6 24.0

per prescription (+8.7) (+0.3) (-1.6)

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 PHC prescribing with and without Bamako
initiative in Nigeria
Source: Scuzochukwu et al, HPP, 2002

no.EDL drugs avail 15.3

35.4
% pres EDL drugs 21
93
% Px with antibiotics 25.6
64.7
% Px with injections 38
72.8
no.drug items/Px 2.1
5.3

0 20 40 60 80 100

21 Bamako PHCs 12 non-Bamako PHCs

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Regulatory strategies
Goal: to restrict or limit decisions

• Drug registration
• Banning unsafe drugs - but beware unexpected results
– substitution of a second inappropriate drug after banning a first
inappropriate or unsafe drug
• Regulating the use of different drugs to different
levels of the health sector e.g.
– licensing prescribers and drug outlets
– scheduling drugs into prescription-only & over-the-counter
• Regulating pharmaceutical promotional activities

Only work if the regulations are enforced

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Intervention impact: largest % change in any
medicines use outcome measured in each study
source: database on medicines use 2009
Intervention type No. studies Median impact 25,75th centiles
Printed materials 5 8% 7%, 18%
National policy 6 15% 14%, 24%
Economic strategies 7 15% 14%, 31%
Provider education 25 18% 11%, 24%
Consumer education 3 26% 13%, 27%
Provider+consumer education 12 18% 8%, 21%
Provider supervision 25 22% 16%, 40%
Provider group process 8 37% 21%, 59%
Essential drug program 5 28% 26%, 50%
Community case mgt 5 28% 28%, 37%
Providr+consumr ed & supervis 7 40% 18%, 54%

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Impact of multiple interventions on injection
use in Indonesia

100% Interactive group discussion (IGC group only)

Proportion of visits

Seminar (both groups)

with injection

80%
District-wide monitoring
60% (both groups)

40%

20%

0%
1 3 5 7 9 11 13 15 17 19 21 23 25
Months
Comparison group Interactive group discussion

Source: Long-term impact of small group interventions, Santoso et al., 1996

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
What national policies do countries have to promote rational use?
Source: MOH Pharmaceutical policy surveys 2003 and 2007

Drug use audit in last 2 years

National strategy to contain AMR
Antibiotic OTC non-availability
Public education on antibiotic use
DTCs in >half general hospitals
Drug Info Centre for prescribers
Obligatory CME for doctors
UG doctors trained on EML/STGs
STGs updated in last 2 years
EML updated in last 2 years

0 20 40 60 80 100
2007 (n>85) 2003 (n>90) % countries implementing policies

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Percent change in antibiotic consumption,
out-patient care in 25 European countries 1997-2003
Data from ESAC
25

20 Increase
15

10
Percent change

-5

-10 Decrease
-15

-20
d ia e d al rk rg ry ly ia el y n ia ia ia d in s y m d lic K ce
l an oat eec lan tug ma ou ga Ita vak sra rwa ede str en ton lan pa and an giu lan ub U
an
I v l m l
Po Cr Gr Ire Por en mb un
H S lo o
N Sw Au lo Es Fi
n S
er er Be
e
Ic Rep Fr
D x e S h G
et h
Lu e
N ec
z
Th C
For Iceland, total data (including hospitals) are used Slide courtesy of Otto Cars, STRAMA, Sweden

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Percent change in antibiotic consumption,
out-patient care in 25 European countries 1997-2003
Data from ESAC
25

20
Co-ordination programs and national campaigns

15

10
Percent change

-5

-10

-15

-20
d ia e d al rk rg ry ly ia el y n ia ia ia d in s y m d lic K e
l an oat eec lan tug ma ou ga Ita vak sra rwa ede str en ton lan pa and an giu lan ub U nc
a
I v rl rm e l
Po Cr Gr Ire Por en mb un
Sl
o o
N Sw Au lo Es Fi
n S e
Ic Rep Fr
D xe H S t he Ge B
e h
Lu e
N ec
z
Th C
For Iceland, total data (including hospitals) are used Slide courtesy of Otto Cars, STRAMA, Sweden

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Why does irrational use continue?

Very few countries regularly monitor drug

use and implement effective nation-wide
interventions - because…
• they have insufficient funds or personnel?
• they lack of awareness about the funds wasted
through irrational use?
• there is insufficient knowledge of concerning the cost-
effectiveness of interventions?

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 What are we spending to promote rational
use of medicines ?

• Global sales of medicines 2002-3 (IMS): US$ 867 billion

• Drug promotion costs in USA 2002-3: US$ >30 billion

• Global WHO expenditure in 2002-3: US$ 2.3 billion

– Essential Medicines expenditure 2% (of 2.3 billion)
– Essential Medicines expenditure on
promoting rational use of medicines 10% (of 2%)
– WHO expenditure on promoting
rational use of medicines 0.2% (of 2.3 billion)

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 2nd International Conference for Improving
Use of Medicines, Chiang Mai, Thailand, 2004
472 participants from 70 countries

http://www.icium.org

Recommendations for countries to:

• Implement national medicines programmes to
improve medicines use
• Scale up successful interventions
• Implement interventions to address community
medicines use

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 WHO priorities

• Resolution WHA60.16
– Urges Member States " to consider establishing and/or
strengthening…a full national programme and/or
multidisciplinary national body, involving civil society and
professional bodies, to monitor and promote the rational use
of medicines "
– WHO to support countries to implement resolution

• Continue to give technical advice to countries

– Model EML and formulary
– Training on promoting RUM in community, PHC, hospitals
– Research to identify cost-effective interventions
– Advocacy
Department of Essential Medicines and Pharmaceutical Policy
TBS 2009
 Health systems with no national programs:
•No coordinated action
•No monitoring of use of medicines

Situational analysis

WHO facilitating
multi-stakeholder Develop
Modify
action in countries national plans
action plans
of action

Implement & evaluate

national action plans using
govt & local donor funds

Health systems with national programs:

•Coordinated action
•Regular monitoring of use of medicine

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
Health system rapid appraisal tool (1): structure
for national stakeholders to rapidly appraise their own health systems in
order to develop evidence-based national plans of action
• Introduction
– How to use the tool (in workbook format) and carry out the assessment
(preparation, data collection, analysis)
– Systematic data collection using document review, key informant
interviews and observation with triangulation of results
• Key respondent questionnaires
– MOH senior dept managers (incl. dept pharmacy, DRA),
– national drug supply organisation, insurance organisation(s),
– health training institutions, health professional organisations,
– health facility staff and health facility survey
• Data collation and analysis by component
– Identify recommendations for each component
• Cross-cutting analysis & presentation to govt & donors
– Analysis across components, prioritisation and formulation of national
recommendations (to be completed)

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Health system rapid appraisal tool (2):
components

• Components
– Medicines use surveys and activities
– Medicines policy framework
– Health system factors
• Service delivery & human resources, insurance, drug supply,
regulation, financial (dis)incentives
– Specific technical areas for RUM
• National program coordination, MTCs, EMLs, STGs, monitoring,
provider & consumer education, independent medicines info, AMR
• Data for each component
– Taken from key informant questionnaires & health facility survey,
identifying relevant data from coding system of questions
• Analysis for each component
– Compares actual practice against best practice, choosing solutions from
a menu of interventions

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Creating the WHO Essential Drugs Library
to facilitate the work of national committees

Evidence- Summary of clinical

based clinical guideline
guideline
WHO Model
Formulary
Reasons for inclusion WHO
Systematic reviews Model List
Key references

Cost: Quality information:

- per unit
- per treatment - Basic quality tests
- per month - Internat. Pharmacopoea
- per case prevented - Reference standards

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 WHO-sponsored training programmes

• INRUD/MSH/WHO: Promoting the rational use of drugs

• MSH/WHO: Drug and therapeutic committees
• Groningen University, The Netherlands / WHO:
Problem-based pharmacotherapy
• Amsterdam University, The Netherlands / WHO:
Promoting rational use of drugs in the community
• Newcastle, Australia / WHO: Pharmaco-economics
• Boston University, USA / WHO: Drug Policy Issues

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Global monitoring and identifying effective
strategies to promote rational use of medicines

• WHO/EMP databases on drug use and policy

– quantitative data on medicines use and interventions to
improve medicines use from 1990 to present day
– data from MOHs on pharmaceutical policies every 4 years –
1999, 2003, 2007
• ICIUM3 in 2011
– 3rd international conference on improving the use of
medicines (ICIUM3)
• Surveillance of antimicrobial use & resistance
– method for community-based surveillance in poor settings
– interventional approach for improving use in private sector

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Conclusions

• Irrational use of medicines is a very serious global

public health problem.

• Much is known about how to improve rational use of

medicines but much more needs to be done
– policy implementation at the national level
– implementation and evaluation of more interventions,
particularly managerial, economic and regulatory interventions

• Rational use of medicines could be greatly improved if

a fraction of the resources spent on medicines were
spent on improving use.

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009
 Activity
Discuss in groups the following questions

• What should be the roles of:

• government,
• NGOs and donors,
• WHO,
in promoting the rational use of medicines?

Department of Essential Medicines and Pharmaceutical Policy

TBS 2009