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
% observed consultations where the diagnostic process was adequate
Department of Essential Medicines and Pharmaceutical Policy
TBS 2009
60
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
 15
billion injections per year globally
 half are with unsterilized needle/syringe
 2.3-4.7 million infections of hepatitis B/C
and up to 160,000 infections of HIV per
year associated with injections
N e pa l
L.A M E R . & C A R .
E c ua do r
G ua t e m a la
E l S a lv a do r
J a m a ic a
E a s t e rn C a ribe a n
0%
10%
20%
30%
40%
50%
% of primary care patients receiving injections
Department of Essential Medicines and Pharmaceutical Policy
TBS 2009
60%
Variation in outpatient antibiotic use
in 26 European countries in 2002
35
DDD per 1000 inh. per day
30
25
20
15
10
5
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
Sub-Saharan Africa (n=29-48)
Middle East & C. Asia (n=4-8)
South Asia (n=6-12)
2001-2006
Lat. America & Carrib (n=5-13)
East Asia & Pacific (n=7-11)
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
prescribed antibiotic
% diarrhoea cases
prescribed anti-diarrhoeals
Public (n=54-90)
% diarrhoea cases
prescribed ORS
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
prescribed antibiotic
Doctor (n=26-62)
% pneumonia cases
prescribed antibiotic
Nurse/paramedic (n=12-86)
Department of Essential Medicines and Pharmaceutical Policy
TBS 2009
% ARI cases treated with
cough syrup
Pharmacy staff (n=9-17)
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)
4. FOLLOW UP
Measure Changes
in Outcomes
(Quantitative and Qualitative
Evaluation)
improve
diagnosis
improve
intervention
3. TREAT
Design and Implement
Interventions
(Collect Data to
Measure Outcomes)
Department of Essential Medicines and Pharmaceutical Policy
TBS 2009
2. DIAGNOSE
Identify Specific
Problems and Causes
(In-depth Quantitative
and Qualitative Studies)
Many Factors Influence Use of Medicines
Information
Scientific
Information
Influence
of Drug
Industry
Habits
Social &
Cultural
Factors
Treatment
Choices
Workload &
Staffing
Workplace
Intrinsic
Prior
Knowledge
Infrastructure
Relationships
With Peers
Societal
Economic &
Legal Factors
Authority &
Supervision
Workgroup
Department of Essential Medicines and Pharmaceutical Policy
TBS 2009
Strategies to Improve Use of Drugs
Educational:
 Inform or persuade
– Health providers
– Consumers
Managerial:
 Guide clinical practice
– Information systems/STGs
– Drug supply / lab capacity
Use of
Medicines
Economic:
 Offer incentives
– Institutions
– Providers and patients
Regulatory:
 Restrict choices
– Market or practice controls
– 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
Post
40
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
group
No. health
PrePostfacilities intervention intervention
Change
Control group
42
24.8%
29.9%
+5.1%
Dissemination of
guidelines
42
24.8%
32.3%
+7.5%
Guidelines + onsite training
29
24.0%
52.0%
+28.0%
14
21.4%
55.2%
+33.8%
Guidelines + onsite training + 4
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
drug courses)
control fee / Px 1-band item fee 2-band item fee
n=11
n=10
n=12
Av. no. items
per prescription
2.9 2.9
(+/- 0)
2.9 2.0
(-0.9)
2.8 2.2
(-0.6)
% prescriptions
conforming to
STGs
23.5 26.3
(+2.7%)
31.5 45.0
(+13.5%)
31.2 47.7
(+16.5%)
Av.cost (NRs)
per prescription
24.3 33.0
(+8.7)
27.7 28.0
(+0.3)
25.6 24.0
(-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
15.3
no.EDL drugs avail
35.4
21
% pres EDL drugs
93
25.6
% Px with antibiotics
64.7
38
% Px with injections
72.8
2.1
5.3
no.drug items/Px
0
20
21 Bamako PHCs
40
60
12 non-Bamako PHCs
Department of Essential Medicines and Pharmaceutical Policy
TBS 2009
80
100
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
Proportion of visits
with injection
Impact of multiple interventions on injection
use in Indonesia
Interactive group discussion (IGC group only)
100%
Seminar (both groups)
80%
District-wide monitoring
(both groups)
60%
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
2007 (n>85)
0
2003 (n>90)
20
40
60
80
% countries implementing policies
Department of Essential Medicines and Pharmaceutical Policy
TBS 2009
100
Percent change in antibiotic consumption,
out-patient care in 25 European countries 1997-2003
Data from ESAC
25
20
Increase
Percent change
15
10
5
0
-5
Decrease
-10
-15
For Iceland, total data (including hospitals) are used
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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
Percent change
15
10
5
0
-5
-10
-15
For Iceland, total data (including hospitals) are used
U
Fr K
an
ce
Po
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n
C d
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at
G ia
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H
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It
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Is
ra
N el
or
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Sw ay
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e
Au n
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Sl tria
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nl
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Th
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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 costeffectiveness 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
Modify
action plans
WHO facilitating
multi-stakeholder
action in countries
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
Develop
national plans
of action
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
Evidencebased clinical
guideline
Summary of clinical
guideline
Reasons for inclusion
Systematic reviews
Key references
WHO
Model List
Cost:
- per unit
- per treatment
- per month
- per case prevented
Department of Essential Medicines and Pharmaceutical Policy
TBS 2009
WHO Model
Formulary
Quality information:
- Basic quality tests
- Internat. Pharmacopoea
- Reference standards
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