David Coulter NZ Intensive Medicines Monitoring Programme 27 March 2003 Lusaka 1
Introduction 1 Medicines are an important cause of harm. In many western countries adverse reactions account for about 6% of hospital admissions and about another 6% of patients develop reactions in hospital. But they also do good and save lives! 27 March 2003 Lusaka 2
Introduction 2 How do we assess that they do more good than harm? How do we make an appropriate balance between benefit and harm? This needs to be assessed on a population basis. It also needs to be assessed for each individual patient. 27 March 2003 Lusaka 3
Introduction 3 Can we accept that a drug causes benefit in many at the cost of serious injury in some? The answer will change for each disease being treated and for each population or person being treated. 27 March 2003 Lusaka 4
Introduction 4 If a disease is fatal and there is a chance of cure, greater risk may be acceptable. If a disease has a good outcome without treatment, then little risk can be accepted. 27 March 2003 Lusaka 5
Introduction 5 On a population basis, this is a public health problem and the assessment is important to drug regulatory authorities. On an individual patient basis, a decision on the balance of benefit and harm needs to be made by the physician and patient. 27 March 2003 Lusaka 6
Introduction 6 Pharmacovigilance: Basic introduction and specifics for malaria programme Plane crash Missiles SARS (severe acute respiratory syndrome) Is it worth the risk of harm? 27 March 2003 Lusaka 7
Introduction 7 How does the drug score in terms of efficacy (benefit) and safety? 27 March 2003 Lusaka 8
Assessment 1 Benefit mean level of improvement in users duration of improvement proportion of users with improvement Harm seriousness of reaction(s) outcome frequency 27 March 2003 Lusaka 9
Assessment 2 Problem: there is usually insufficient knowledge to make a definitive, objective assessment Efficacy -clinical trials do not reflect what might happen in the real world. Harm-adverse reaction data are usually incomplete and imprecise and unmeasurable. 27 March 2003 Lusaka 10
Assessment 3 Principle of Threes 1 Disease 2 Improvement produced by the drug 3 Adverse effects of the drug 27 March 2003 Lusaka 11
Assessment 4 1 Seriousness 2 Duration 3 Incidence Principle of Threes -Disease 27 March 2003 Lusaka 12
Assessment 5 Principle of Threes -Improvement produced by the drug 1 Seriousness (level of improvement) 2 Duration 3 Incidence 27 March 2003 Lusaka 13
Assessment 6 1 Seriousness 2 Duration 3 Incidence Principle of Threes -Adverse effects of the drug 27 March 2003 Lusaka 14
Assessment 7 Score High=3 Medium=2 Low=1 Seriousness Fatal Disabling Inconvenient Duration Permanent Persistent Temporary Incidence Common Frequent Rare 27 March 2003 Lusaka 15
Assessment 8 RESOURCES CIOMS Working Group IV, Benefit-Risk Balance for Marketed Drugs: Evaluating Safety Signals, CIOMS 1998 Meyboom RHG, Egberts, ACG. Comparing therapeutic benefit & risk. Therapie 1999; 54:29-34 27 March 2003 Lusaka 16
Assessment 9 NEW SIGNAL Evidence for unfavourable change in benefit-harm relationship Options analysis / impact analysis Decision making Implement, communicate Monitor, follow-up 27 March 2003 Lusaka 17
Assessment 10 Assessments may change with new information Assessments may be made by comparing the drug with no treatment other available treatment 27 March 2003 Lusaka 18