1. Rational use of drugs: an overview Kathleen Holloway Technical Briefing Seminar November 2009 Department of Essential Medicines and Pharmaceutical Policy TBS 2009

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. 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

4. 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.

5. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 5-55% of PHC patients receive injections - 90% may be medically unnecessary % of primary care patients receiving injections Source: Quick et al, 1997, Managing Drug Supply ä 15 billion injections per year globally ä half are with unsterilized needle/syringe ä 2.3-4.7 million infections of hepatitis B/C and up to 160,000 infections of HIV per year associated with injections

6. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Variation in outpatient antibiotic use in 26 European countries in 2002 Source: Goosens et al, Lancet, 2005; 365: 579-587; ESAC project.

7. 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

8. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 % compliance with guidelines by WB region

9. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Public / private treatment of acute diarrhoea by doctors, nurses, paramedical staff

10. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Treatment of ARI by prescriber type

11. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Overuse and misuse of antimicrobials contributes to antimicrobial resistance 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 Source: WHO country data 2000-3

12. 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

13. 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

14. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Adverse drug events 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 Source: Review by White et al, Pharmacoeconomics, 1999, 15(5):445-458

15. 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) 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 improve diagnosis

16. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 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 Many Factors Influence Use of Medicines

17. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 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

18. 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

19. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Impact of Patient-Provider Discussion Groups on Injection Use in Indonesian PHC Facilities InterventionControl 0 20 40 60 80 % Prescribing Injections Pre Post Source: Hadiyono et al, SSM, 1996, 42:1185

20. 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

21. 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

22. 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.

23. 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

24. 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

25. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 PHC prescribing with and without Bamako initiative in Nigeria Source: Scuzochukwu et al, HPP, 2002

26. 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

27. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Intervention impact: largest % change in any medicines use outcome measured in each study Intervention typeNo. studiesMedian impact25,75 th centiles Printed materials5 8% 7%, 18% National policy615%14%, 24% Economic strategies715%14%, 31% Provider education2518%11%, 24% Consumer education326%13%, 27% Provider+consumer education1218% 8%, 21% Provider supervision2522%16%, 40% Provider group process837%21%, 59% Essential drug program528%26%, 50% Community case mgt528%28%, 37% Providr+consumr ed & supervis740%18%, 54% source: database on medicines use 2009

28. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Impact of multiple interventions on injection use in Indonesia Source: Long-term impact of small group interventions, Santoso et al., 1996 Interactive group discussion (IGC group only) Seminar (both groups) District-wide monitoring (both groups)

29. 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

30. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 For Iceland, total data (including hospitals) are used Increase Decrease Slide courtesy of Otto Cars, STRAMA, Sweden

31. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 For Iceland, total data (including hospitals) are used Co-ordination programs and national campaigns Slide courtesy of Otto Cars, STRAMA, Sweden

32. 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?

33. 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 medicines10% (of 2%) –WHO expenditure on promoting rational use of medicines0.2% (of 2.3 billion)

34. 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 Recommendations for countries to: Implement national medicines programmes to improve medicines use Scale up successful interventions Implement interventions to address community medicines use http://www.icium.org

35. 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

36. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Health systems with no national programs: No coordinated action No monitoring of use of medicines Health systems with national programs: Coordinated action Regular monitoring of use of medicine Develop national plans of action Situational analysis Modify action plans Implement & evaluate national action plans using govt & local donor funds WHO facilitating multi-stakeholder action in countries

37. 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)

38. 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

39. Department of Essential Medicines and Pharmaceutical Policy TBS 2009 Creating the WHO Essential Drugs Library to facilitate the work of national committees WHO Model List Summary of clinical guideline Reasons for inclusion Systematic reviews Key references WHO Model Formulary Cost: - per unit - per treatment - per month - per case prevented Quality information: - Basic quality tests - Internat. Pharmacopoea - Reference standards Evidence- based clinical guideline

40. 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

41. 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 –3 rd 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

42. 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.

43. 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?