decision making and communication in the face of uncertainty: the challenge of pharmacovigilance
DESCRIPTION
Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance. I Ralph Edwards WHO Foundation Collaborating Centre for International Drug Monitoring. A critique of pharmacovigilance. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/1.jpg)
Decision making and
communication in the face of
uncertainty: the challenge of
pharmacovigilance. I Ralph Edwards
WHO Foundation Collaborating Centre for
International Drug Monitoring
![Page 2: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/2.jpg)
A critique of pharmacovigilance
Current tools and resources are not used maximally to deliver useful outputs for patient care
• Current decision–making processes do not result in public confidence
• Current practice underplays several areas of safety importance
• Current gaze of regulation is on the control of drugs, not the safety of patients
![Page 3: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/3.jpg)
What issues I will cover
• Decision making in drug safety• Delays in action (examples)
– Outcome research?
• Prevention in drug safety– Effectiveness and risk
• Comparison between medicines– Risk assessment
• Communication and miscommunication– Communication of uncertainty
• Patient involvement– Patient, and not drug, safety
• An international Programme
![Page 4: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/4.jpg)
Decision making in drug safety
Items in red are key issues to be tackled
![Page 5: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/5.jpg)
Managing a signal ?
A first signal
Increasing information and knowledge
Public Information 1
Public Information 1
Public Information2
Public Information2
Media coverageMedia coverage
SCARESCARE
(also misinformation)
![Page 6: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/6.jpg)
Five broad activities essential to pharmacovigilance:
• Suspected ADR signal generation and formation of hypotheses
• Analysis of all issues around the signal, particularly confirmation (or refutation) of hypothesis, estimation of the size of the risk and whether susceptible patients exist
• Consideration of possible effectiveness-to-risk issues in therapy (comparative)– How to do it?– Economics
• Communication of information to health professionals and patients in a useful way. And possible regulatory action.
• Consequence evaluation.
Decisions
Decisions
Decisions
Decisions
![Page 7: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/7.jpg)
Do we really use our tools?
• Studies tell us about populations and not individuals– Most ADRs are rare (< 1/1000)
• Large numbers of patients and controls needed
• Case reports can tell us a huge amount about what concerns individual doctors/h.p’s/consumers– We could get much more information on what
happens to people, medication error, interactions, patients at risk, how to diagnose ADRs, etc.
![Page 8: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/8.jpg)
Frequently repeated myths?:• Case reports
– Cannot prove causality– Under-reporting is a big problem – Bias is unavoidable
• Epidemiological studies – Prove/disprove causality– Only, should be used for regulatory
action and information• Databases
– What actually happens (effectiveness and risk)?
![Page 9: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/9.jpg)
Delays in action (examples)Consequences - Outcomes research
needed
![Page 10: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/10.jpg)
Example of a decision problem to be solved [1] ...
Cisapride - heart rhythm disorders• 1986: double blind study “cisapride
produced tachycardia”• 1992 WHO Signal published in Br
Med J on serious arrhythmialetters to Br Med J “no epidemiological support”
• 1995 case report published, Lancet “QT prolongation and tachycardia”
Dear Doctor letter in USA by manufacturer
![Page 11: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/11.jpg)
Example of a decision problem to be solved [2] ...
• Piroxicam is the most GI toxic of the NSAIDS in several comparative studies– GI toxicity is a major cause of morbidity
• Why is it still available?
![Page 12: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/12.jpg)
Example of a decision problem to be solved ?? [3] ...
• . At the WHO Meeting,Tunis ( Oct, 2000) the Netherlands Monitoring Centre (Lareb) presented the first signal of cardiovascular disorders relating to rofecoxib, for 8 cardiovascular ADRs (of 62 total reports) with 4 fatalities and which occurred early in treatment. (ROR 12.4 (4.5-35), all drugs: 12.0 (3.8-38.2), NSAIDS
![Page 13: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/13.jpg)
Consequences
• Newspaper article showing extensive scars on the legs of a young woman following venous thrombectomy
• Cause for thromboses given as Diane (cyprotereone acetate : ethinyloestradiol) used for acne
![Page 14: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/14.jpg)
Consequences• Patient given wide media coverage• Many patients reported to stop taking
Diane• Dermatologist rings National
Monitoring Centre– ' Many patients taking Diane are also
taking Roaccutane. The logic is to provide both contraception and an additional (anti-androgenic) therapy for their acne'.
– 'They are at risk for malformed fetus, if they stop contraception'
![Page 15: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/15.jpg)
Consequences
• Since all prescriptions of Roaccutane must be prescribed by a dermatologist– And patients must give informed consent
• Notify all dermatologists• Call in patients on Roaccutane• Advise about contraception and relative
risks of Diane• Also make a media announcement on
the above
![Page 16: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/16.jpg)
Consequences
• No unwanted pregnancies reported!• By luck and rapid, complete and
appropriate action a disaster was anticipated and avoided
• But this was a special case!
![Page 17: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/17.jpg)
Consequences
• Letter:– The 'Dear Doctor' letter on cerivastatin, interaction and
rhabdomyolysis• ....do not co-prescribe with ....
• Intention:– To change prescribing, to reduce rhabdomyolysis
particularly linked with interaction with gemfibrosil• Result:
– After 3 letters and 2 years only a 2% reduction in co-prescription, BUT more reports sent to the authority
• Lesson:– Check response; modify approach; give guidance as
well as warning
![Page 18: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/18.jpg)
This is only part of the story!
• Vigilance• Signal• Hypothesis• Analysis• Probability• Frequency
• Epidemiology• Signal• Hypothesis• Analysis• Confirmation • Probability• Frequency
Decision
![Page 19: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/19.jpg)
Prevention in drug safetyEffectiveness and risk
Need for comparison between medicines
Risk assessment
![Page 20: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/20.jpg)
The true balanced concepts
• Efficacy (hard data)
• Effectiveness
• Benefit (what the patient
feels)
• Hazard
• Risk
• Harm (soft data)
NO!
Yes!Yes!
This does matter
![Page 21: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/21.jpg)
Size and severity of the ADR problem Meta-analysis
• 39 prospective studies from US hospitals
• Overall incidence of serious ADRs = 6.7%
• Overall incidence of fatal ADRs = 0.32% (106 000 individuals)
• 4th - 6th leading cause of deathLazarou et al JAMA 1998;279: 1200 - 1205
![Page 22: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/22.jpg)
6.7% of hospital patients have serious adverse drug reactions (medication error excluded)
Lazarou J. Pomeranz BH, Corey PN. JAMA 1998;279:1200-5
16.2% of hospital admissions are drug-related Therapeutic failure 54.8% Adverse reactions 32.9% Overdose 12.3%
Avoidable 49.3% Nelson KM, Talbert RL. Pharmacotherapy 1996;16:701-7
![Page 23: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/23.jpg)
Pirmohamed M JS, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK,
Breckenridge AM. Adverse drug reactions as cause of admission to hospital: prospective
analysis of 18 820 patients. BMJ
2004;329(7456):15-19.
• ….identifies the main drug culprits in a large hospital based study. They are old drug groups (low dose aspirin, diuretics, warfarin, and non-steroidal anti-inflammatory drugs other than aspirin: the most common reaction being gastrointestinal bleeding) on which we have much information……
![Page 24: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/24.jpg)
Proposed risk assessmentEliminating risk (not possible!)
• Risk specification • Risk plan
– Milestones
• Risk minimisation • Start early and
continue • High potency, high
risk products – Tripartite involvement:
• Prescriber• Dispenser • Patient
How do the new compare with the old?
![Page 25: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/25.jpg)
Some new challenges• Medication error• ADR diagnosis• Therapy adherence
– ‘Intelligent non-compliance’
• Lack of effect– Sub-standard and counterfeit
drugs
• Interactions• Herbals• Public health programmes
– incl. Vaccines
• Comparisons of therapies– UK NICE– Data mining
Patient safety
Patient safety
![Page 26: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/26.jpg)
Communication and miscommunication
Communication of uncertainty
![Page 27: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/27.jpg)
Effectiveness/risk communicationcommunication
• The correct message• To the right audience• By the right medium• Consequences
– Message received?– Message understood?– Followed up?– Acted upon appropriately?
![Page 28: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/28.jpg)
Warning and communication of risk -now
• SPC– Use of PSUR – Legal v. Communication– Which section of SPC
• Contra indication, warning
– When changed? – Design ?
• ‘Dear Health Professional‘ communication – Web – Design – Repeated
• Media • Bulletins
![Page 29: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/29.jpg)
Warning and communication of risk
• Players may have competing interests in communication even if public health is a common aim
• Media – Dramatic news a priority – Internet
• No control
• Wide range of issues possible – Difficult to predict response – Prepare for rapid and intense
communication
![Page 30: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/30.jpg)
Warning and communication of risk – the future
• Outcomes – Follow up?
• Questionnaires – General – Specific
– Need more information on outcomes
– Better public education– Less paternalism
• Better view of us!• Openness
– Constructive law & media interaction
![Page 31: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/31.jpg)
The Erice Declaration on Communicating Drug Safety
Information
• The following declaration was drawn up at the International Conference on Developing Effective Communications in Pharmacovigilance, Erice, Sicily, 24-27 September 1997. It was attended by health professionals, researchers, academics, media writers, representatives of the pharmaceutical industry, drug regulators, patients, lawyers, consumers and international health organisations.
![Page 32: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/32.jpg)
The Erice Declaration
• 1. Drug safety information must serve the health of the public. Such information should be ethically and effectively communicated in terms of both content and method. Facts, hypotheses and conclusions should be distinguished, uncertainty acknowledged, and information provided in ways that meet both general and individual needs.
![Page 33: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/33.jpg)
The Erice Declaration
• 2. Education in the appropriate use of drugs, including interpretation of safety information, is essential for the public at large, as well as for patients and health-care providers. Such education requires special commitment and resources. Drug information directed to the public in whatever form should be balanced with respect to risks and benefits.
![Page 34: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/34.jpg)
The Erice Declaration
• 3. All the evidence needed to assess and understand risks and benefits must be openly available. Constraints, on communication participants, which hinder their ability to meet this goal must be recognised and overcome.
![Page 35: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/35.jpg)
Managing a signal: the future
A first signal
Increasing information and knowledge
Public Information 1
Public Information 1
Public Public InformationInformation22
Public Public InformationInformation22
Media coverageMedia coverage(also misinformation)
Pre-marketing riskPre-marketing risk managementmanagement
![Page 36: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/36.jpg)
Patient involvementPatient, and not drug, safety
![Page 37: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/37.jpg)
Patient involvement
• Patients need more general information about drugs and their effectiveness and risk
• VERY IMPORTANT– We need much more information
about what risks patients are prepared to take for what benefit to them. Until we know this we will continue to ‘second-guess’ about what is acceptable or not
![Page 38: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/38.jpg)
![Page 39: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/39.jpg)
Measuring true effectiveness and risk
• Needs knowledge finding in patient care databases– E.g Data mining in
IMS Health database of 2 million patients
• Can show comparative effectiveness and risk– Data quality
(OneYear)
Fluoxetine
Amitrityline
Suicidality
![Page 40: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/40.jpg)
An international Programme
![Page 41: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/41.jpg)
WHO Programme for International Drug Monitoringplus Global Alliance for Patient
Safety
Associate member Official member
![Page 42: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/42.jpg)
Functions• Collection and processing of international ADR data
– > 3.5 million concerns about drugs from HPs and patients since 1968
• Signal detection and analysis– Available free
• Tools– WHO DD and terminologies are world standards
• Research– Data mining of patient care databases
• Information and feedback• Education and support• Harmonisation Please use it!
![Page 43: Decision making and communication in the face of uncertainty: the challenge of pharmacovigilance](https://reader035.vdocuments.mx/reader035/viewer/2022062801/56814462550346895db0f70d/html5/thumbnails/43.jpg)
Conclusions
• Think less about drug safety: more about patient safety
• Think less about regulating and automating data input: more about useful information output
• Think more about impact and consequences of decisions and non-decisions
• Think more about global cooperation: not competition