Professional Documents
Culture Documents
Efficacy-
Effectiveness gap
3
Case study: Acomplia
(rimonabant 20 mg)
4
Case study: Acomplia
(rimonabant 20 mg)
• Mibefradil (Posicor)
• Cerivastatin (Lipobay, Baycol)
• Rimonabant (Acomplia)
• Varenicline (Champix/Chantix)
• Metoclopramide (Maxolon et al)
• ….
6
Can we conceptualise the
efficacy - effectiveness
gap?
A problem of variability
7
Sources of variability in drug response
Biology Behavior
Genomics Environment Physician Patient
prescribing adherence
Patient’s Co-morbidity, Inappropriate Poor adherence
genomic makeup baseline severity prescribing, to prescribed
of disease, prescr. to non- drug regimen,
altered responders, non-persistence;
physiological medication "drug holidays";
states, external errors overdosing
factors
PD: Trastuzumab PD: Insulin and Cerivastatin; Anti-
Abacavir stress /activity Gemfibrozil; hypertensive,
PK: Codeine: PK: increased Mibefradil; anti-infective
resistance / tox. absorption with drugs
(CYP2D6) fruit juice 8
When expectations (efficacy)
don’t match reality (effectiveness)…
…there are two ways to bridge the gap:
• (a) lower the expectations to the level of
reality:
9
“Clean”, explanatory or efficacy trial
10
“Clean”, explanatory or efficacy trial
11
When expectations (efficacy)
don’t match reality (effectiveness)…
…there are two ways to bridge the gap:
• (b) bring up reality to the level of
expectations
… a drug-problem or a
healthcare delivery problem?
12
Addressing the efficacy -
effectiveness gap:
An area for regulatory sciences
13
Which patient for this drug?
Biomarker-guided benefit-risk
stratification
• Guidance for co-development of
drugs and companion diagnostics
• Qualification procedure for
(stratification) biomarkers
• Staggered approval, progressive
authorisation ?
14
Which patient for this drug?
Biomarker-guided benefit-risk
stratification
• Focus on “optimised” treatment-eligible
population
• Departure from “last-line first”
development / regulatory approach?
• Needs alignment of regulators and
post-regulatory decision makers
(payers, prescribers) 15
Addressing the efficacy -
effectiveness gap:
An area for regulatory sciences
17
Information in a useful format
18
Patient adherence,
the regulators’ contribution?
Is technology available?
Lester RT. Effects of a mobile phone short Intelligent pill caps use light and sound,
message service on antiretroviral treatment phone calls or text messages to remind
adherence in Kenya. Lancet 2010; 376: 144 people to adhere to drug regimen 19
Patient adherence,
the regulators’ contribution?
Is technology available?
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