1. Rational use of drugs: an overview
Kathleen Holloway
Technical Briefing Seminar September 2005
Department of Medicines Policy and Standards TBS 2005

2. 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

3. 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

4. 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.

5. % of primary care patients receiving injections
5-55% of PHC patients receive injections - 90% may be medically unnecessary
Source: Quick et al, 1997, Managing Drug Supply
15 billion injections per year globally
half are with unsterilized needle/syringe
million infections of hepatitis B/C and up to 160,000 infections of HIV per year associated with injections
% of primary care patients receiving injections

6. Variation in outpatient antibiotic use in 26 European countries in 2002
Total outpatient antibiotic use in 26 European countries in 2002 (WHO ATC/DDD version 2003).
This are ESAC data to position Belgium among other European countries…
Source: Goosens et al, Lancet, 2005; 365: ; ESAC project.

7. Trends in the use of medicines 1990-2003
Source: WHO/PSM database 2004
n=average number of studies per year i.e. data point

8. Regional variation in prescribing 1990-2004
Source: WHO/PSM database August 2004
Baseline data covering all diseases and all ages

9. Treatment of ARI cases
Source: WHO/PSM database 2004.

10. Public/private acute diarrhoea treatment
Source: WHO/PSM database, 2004.

11. Overuse and misuse of antimicrobials contributes to antimicrobial resistance
Source: WHO country data
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

12. Adverse drug events 4-6th leading cause of death in the USA
Source: Review by White et al, Pharmacoeconomics, 1999, 15(5):
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

13. Changing a Drug Use Problem: An Overview of the Process
1. EXAMINE
Measure Existing
Practices
(Descriptive
Quantitative Studies)
2. DIAGNOSE
Identify Specific
Problems and Causes
(In-depth Quantitative
and Qualitative Studies)
3. TREAT
Design and Implement
Interventions
(Collect Data to
Measure Outcomes)
4. FOLLOW UP
Measure Changes
in Outcomes
(Quantitative and Qualitative
Evaluation)
improve
intervention
diagnosis

14. Many Factors Influence Use of Medicines
Treatment Choices
Prior Knowledge
Habits
Scientific Information
Relationships
With Peers
Influence of Drug
Industry
Workload & Staffing
Infra- structure
Authority & Supervision
Societal
Information
Intrinsic
Workplace
Workgroup
Social & Cultural
Factors
Economic &
Legal Factors

15. Strategies to Improve Use of Drugs
Economic:
Offer incentives
Institutions
Providers and patients
Managerial:
Guide clinical practice
Information systems/STGs
Drug supply / lab capacity
Regulatory:
Restrict choices
Market or practice controls
Enforcement
Educational:
Inform or persuade
Health providers
Consumers
Use of Medicines

16. 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

17. 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
Intervention
Control

18. Promotional materials are most used source of information Increased adverts result in increased prescribing

19. Managerial and economic 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
Avoidance of perverse financial incentives
prescribers’ salaries from drug sales, flat prescription fees,
insurance policies that reimburse non-essential drugs or incorrect doses

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

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

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

23. 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

24. Source: Bavestrello & Cabello, ICIUM 2004
DDD/1000 inhabitant-days
This is where a large graphic or chart can go.
Source: Bavestrello & Cabello, ICIUM 2004

25. Impact of multiple interventions on injection use in Indonesia
Interactive group discussion (IGC group only)
Seminar (both groups)
District-wide monitoring
(both groups)
Source: Long-term impact of small group interventions, Santoso et al., 1996

26. Review of 30 studies in developing countries
size of drug use improvements with various interventions
Minor
Moderate
Large
Large group training
Small group training
Diarr. community case mgt
ARI community case mgt
Info/guidelines
Group process
Supervision/audit
EDP/Drug supply
Economic strategies 10 20 30 40 50 60
Improvement in outcome measure (%)
Source: Ross-Degnan et al, Plenary presentation, ICIUM 1997, Chiang Mai, Thailand.

27. Interventions: 844 in 204 study sites 18% evaluated with adequate study design
Source: WHO/PSM database, ICIUM 2004

28. 10 national strategies to promote RUM needs sufficient govt
10 national strategies to promote RUM needs sufficient govt. investment for medicines & staff !
Source: WHO Policy Perspectives no.5
1. Evidence-based standard treatment guidelines
2. Essential Drug Lists based on treatments of choice
3. Drug & Therapeutic Committees in hospitals
4. Problem-based training in pharmacotherapy in UG training
5. Continuing medical education as a licensure requirement
6. Independent drug information e.g bulletins, formularies
7. Supervision, audit and feedback
8. Public education about drugs
9. Avoidance of perverse financial incentives
10. Appropriate and enforced drug regulation

29. What are countries doing to promote rational use of medicines ?
Source: TCM pharmaceutical database 2003
% countries implementing policies to promote rational use

30. 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?

31. WHO priorities
Developing a model formulary process, the WHO Essential Drugs Library
Training programmes
Promoting drug & therapeutic committees
Pilot projects to contain antimicrobial resistance
Intervention research to promote RUM
cost-effectiveness of interventions, policies
Advocacy for the rational use of medicines (RUM)
Essential Drug Monitor, effective drug information
WHO Resolution

32. Evidence-based clinical guideline Summary of clinical guideline
Creating the WHO Essential Drugs Library to facilitate the work of national committees
Evidence-based clinical guideline
Summary of clinical guideline
WHO Model
Formulary
Reasons for inclusion
Systematic reviews
Key references
WHO
Model List
Cost:
- per unit
- per treatment
- per month
- per case prevented
Quality information:
- Basic quality tests
- Internat. Pharmacopoea
- Reference standards

33. 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

34. DTC training course results 2000-3
361 people trained from 56 countries
87 (24%) responded to follow-up request
57 (16%) participants had undertaken 152 DTC related activities
24 (7%) participants from 10 countries attended the follow-up workshop for active participants
Requires more support from donors

35. Source: Sisounthone, WPRO-EDM, 1(1), March 2002
Promoting DTCs: monitoring, training & planning through hospital DTCs in Laos
Source: Sisounthone, WPRO-EDM, 1(1), March 2002
Injections
Antibiotics
No.drugs 0%
20%
40%
60%
80%
100% 1 2 3 4 5 6 7 8
Months
% Px with
Abs/Inj.
Av.no.drugs / Px

36. Local pilot projects to contain AMR
Objectives
develop, implement & evaluate interventions to contain AMR using surveillance data in local sites
to develop a new method for the integrated surveillance, at community level, of antimicrobial use and resistance that can be used in many different countries
to build local capacity in developing a multi-disciplinary approach to the containment of AMR
3 phases
(1) set up surveillance,
(2) develop, implement & evaluate interventions
(3) expand to other sites

37. Looking at trends in cotrimoxazole resistance and use in Mumbai, India, 2002
Source: Thatte et al, ICIUM 2004

38. Monitoring community cotrimoxazole resistance and use in Durban, S
Monitoring community cotrimoxazole resistance and use in Durban, S.Africa,
Source: Gray and Essack et al, ICIUM 2004 0% 5%
10%
15%
20%
25% 10 11 12 1 2 3 4 5 6 7
% patients
treated
with cotri
40%
60%
80%
100%
% resistant
sputum
isolates
PHC clinics
Pharmacies
Private Practitioners
H.influenzae resist.
S.pneumoniae resist.

39. Identifying effective strategies to promote more rational use of drugs
Joint research initiative between WHO/PSM, MSH, Harvard and Boston Universities, and ARCH
over 20 intervention research projects in developing countries
WHO/PSM database on drug use
quantitative data on drug use and interventions to improve drug use over the last decade

40. Recommendations for countries to:
2nd International Conference for Improving Use of Medicines, Chiang Mai, Thailand, participants from 70 countries
Recommendations for countries to:
Implement national medicines programmes to improve medicines use
Scale up successful interventions
Implement interventions to address community medicines use

41. What are we spending to promote rational use of medicines ?
Global sales of Px medicines in 2000: US$ billion
Drug promotion costs in USA in 2000: US$ billion
Global WHO expenditure in : US$ billion
Essential Medicines expenditure %
Essential Medicines expenditure on promoting rational use of medicines 10%
WHO expenditure on promoting rational use of medicines 0.2%

42. 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.

43. Activity Discuss in groups the following questions
How can we stimulate:
governments,
NGOs and donors,
WHO,
to promote the rational use of medicines?