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

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

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

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.

% 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 2.3-4.7 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

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: 579-587; ESAC project.

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

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

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

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

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

Adverse drug events 4-6th leading cause of death in the USA 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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

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

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?

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

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

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

DTC training course results 2000-3 361 people trained from 56 countries 87 (24%) responded to follow-up e-mail 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

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

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

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

Monitoring community cotrimoxazole resistance and use in Durban, S Monitoring community cotrimoxazole resistance and use in Durban, S.Africa, 2002-3 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.

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

Recommendations for countries to: 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

What are we spending to promote rational use of medicines ? Global sales of Px medicines in 2000: US$ 282.5 billion Drug promotion costs in USA in 2000: US$ 15.7 billion Global WHO expenditure in 2002-3: US$ 2.3 billion Essential Medicines expenditure 2% Essential Medicines expenditure on promoting rational use of medicines 10% WHO expenditure on promoting rational use of medicines 0.2%

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.

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