title: Symmetrical analysis of risk-benefit.
abstract: To quantify the value of a medical therapy the benefits are weighed against the risks. Effectiveness is defined by objective evidence from predefined endpoints. This benefit is offset against the disadvantage of adverse events. The safety assessment is usually a subjective summary of concerns that can often be neither confirmed nor dismissed. But sometimes a clinical database is so large that a parameter common to both efficacy and safety can be quantified with reasonable certainty: myocardial infarction (MI) is used here as an example. Recently the Food and Drug Administration (FDA) proposed set limits for the incidence of MI as a safety threshold for diabetes treatment. Setting a threshold before something is considered as a safety concern opens the possibility of setting a threshold for clinically important efficacy. When a parameter is common to both safety and efficacy, then logically a unit change in either direction should be of equal weight in the risk and benefit analysis. For example, a doubling in the incidence of myocardial infarction as a safety signal should be given equal weight to the halving of the incidence of myocardial infarction as an efficacy signal. Similarly, if FDA guidance suggests that a less than a 30% increase in the incidence of MI as a safety parameter is considered acceptable, for example for diabetes treatment, when there is no other major toxicity, this opens a debate about a possible inverse threshold for clinical benefit for drugs that reduce a risk factor, such as antihypertensives.
authors.affiliation: Medicines Assessment, 196 Rotherhithe Street, London, UK. info@medicinesassessment.com
authors.forename: John B
authors.initials: JB
authors.lastname: Warren
authors.forename: Simon
authors.initials: S
authors.lastname: Day
authors.forename: Peter
authors.initials: P
authors.lastname: Feldschreiber
mesh_terms: D016208:Databases, Factual; D003920:Diabetes Mellitus / Q000188:drug therapy*; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D007004:Hypoglycemic Agents; D004364:Pharmaceutical Preparations