Risk Factors: An Essential Element for DDI Software

Transcription

1 Risk Factors: An Essential Element for DDI Software 14 October 2009 Philip D. Hansten, PharmD Professor Emeritus School of Pharmacy University of Washington

2 Michel de Montaigne [ ]

3 Montaigne on Drug Interactions After describing the complex potions used to treat various diseases he said, who could suppose that in this liquid confusion these faculties would not corrupt, confuse, and alter one another?

4 Who Said This? Prediction is very difficult. Especially if it s about the future.

5 100% Precise Prediction of Drug Interaction Outcomes in Specific Patients The Unknowable You Are Here 0% YEAR

6 Drug Interaction Predictions Swiss Cheese Model

7 Drug A + Drug B Drug Interaction Defenses Defenses Prescriber s Knowledge Computer Screening Pharmacist s Knowledge Drug Administration Patient Risk Factors Pharmacogenetics Patient Education Monitoring Hansten PD, Horn JR. Modified from: James Reason, Human Error, 1990 ADR

8 Drug Interaction Defenses A + B Prescriber s Knowledge Computer Screening Pharmacist s Knowledge Drug Administration Patient Risk Factors Pharmacogenetics Patient Education Monitoring NO ADR Hansten PD, Horn JR. Modified from: James Reason, Human Error, 1990

9 When the Holes Line Up A + B Prescriber s Knowledge Computer Screening Pharmacist s Knowledge Drug Administration Patient Risk Factors Patient Education Defenses Monitoring Latent Failures ADR Hansten PD, Horn JR. Modified from: James Reason, Human Error, 1990

10 Three Simple Questions EXISTENTIAL: Should the interaction be on the decision support system or not? Yes MITIGATING FACTORS: Are the drugs given in a way that minimizes risk in this patient or are there other mitigating factors? No MANAGEMENT: What are the management options for this patient that can reduce the risk of an adverse outcome?

11 Pascal on Wine Consumption and Discovering Truth Under the Heading Too Much & Too Little Wine Pascal said: If you give someone none, he cannot discover the truth. It is the same if you give him too much.

12 Pascal s Curve Truth Amount of Wine

13 Pascal s Curve for DDIs O Prevention of Adverse Interaction Outcomes M N P Q Number of Interactions on Computer System

14 The Parachute Principle A drug known to be a strong P-glycoprotein inhibitor is prescribed for a patient on colchicine, BUT there are no clinical studies of the drug interaction

15 Three Simple Questions EXISTENTIAL: Should the interaction be on the decision support system or not? Yes MITIGATING FACTORS: Are the drugs given in a way that minimizes risk in this patient or are there other mitigating factors? No MANAGEMENT: What are the management options for this patient that can reduce the risk of an adverse outcome?

16 Mitigating Factors Mitigating Factors A patient on nadolol gets a local anesthetic + epinephrine at dentist A patient on chronic levothyroxine is started on warfarin therapy A patient on ciprofloxacin takes an antacid at HS (4 h after ciprofloxacin) A patient on simvastatin takes a CYP3A4 inhibitor for only 2 days A patient on digoxin starts propafenone but digoxin concentration monitored

17 Three Simple Questions EXISTENTIAL: Should the interaction be on the decision support system or not? Yes MITIGATING FACTORS: Are the drugs given in a way that minimizes risk in this patient or are there other mitigating factors? No MANAGEMENT: What are the management options for this patient that can reduce the risk of an adverse outcome?

18 Management Are both drugs actually necessary? Can one drug be stopped during the administration of the other drug? Can an equally efficacious drug be used in place of one of the interacting drugs? Can drug administration times be changed to avoid the interaction? Can monitoring for ADRs (by patient, clinician or both) allow early detection?

19 Management Strategy: Override and Ignore Since most DDIs only cause adverse outcomes in a small percentage of people, this usually works. BUT it breaks Clifford s Law.

20 Clifford s Law Clifford s Law William K. Clifford s 1877 classic essay entitled Ethics of Belief about a hypothetical ship owner One must make decisions based on the best evidence available at the time When an action is once done, it is right or wrong for ever; no accidental failure of its good or evil fruits can possibly alter that.

21 Fishing is Contraindicated in Patients Receiving Warfarin PROTHROMBIN TIME FISHING FISHING DAYS

22 Threshold for Action versus Definitive Answer Scientific Evidence Evidence Needed for Definitive Answer on Patient Outcome Threshold for Action

23 Threshold for Action versus Definitive Answer Scientific Evidence Evidence Needed for Definitive Answer on Patient Outcome Threshold for Action

24 Threshold for Action versus Definitive Answer Scientific Evidence Evidence Needed for Definitive Answer on Patient Outcome Threshold for Action Non-science (Ethics, Logic, Philosophy)

25 Knowledge versus Wisdom Knowledge and Wisdom, far from being one, Have oft times no connexion. Knowledge dwells In heads replete with thoughts of other men; Wisdom in minds attentive to their own. Knowledge, a rude unprofitable mass, The mere materials with which Wisdom builds, Till smooth'd, and squared, and fitted to its place, Does but encumber whom it seems to enrich. The Task, William Cowper