Transcript The Accelerating Pace of Medical Development and Challenges in

The Accelerating Pace of Medical
Development and Challenges in
Evaluating Benefit and Risk
Alasdair Breckenridge
Medicines and Healthcare products
Regulatory Agency

Food and Drugs Administration (FDA)

European Medicines Agency (EMEA)

International Conference on Harmonisation
(ICH)
Risk
Unacceptable
Acceptable
Benefits (relative value)
Responsibilities of the Medicines’
Regulator
To protect the public health by allowing only
medicines which have a satisfactory riskbenefit profile to be marketed and remain so

To provide information to prescribers and
patients so that these products can be used
safely and effectively

Not to put unnecessary regulatory hurdles
in the way of innovative products

Measures of Drug Efficacy
 Peak expiratory flow rate
 Standard BP measurement
 Joint size and temperature
 Rating scales for dementia
 Rating scales for depression
Biomarker
A biochemical or physiological change that is : Quantifiable
 Related to an actual or potential health impairment
 May be used for measuring the progress of disease
or the effects of treatment
Biomarkers
 Collagen telopeptide fragments
 PET imaging for tumours
 Inflammation - Acute protein CRP
- Cytokine IL6
- Metalloproteases
Improvement of Risk-benefit Profile
Define accurately the population of patients who will
respond to a medicine.
Causes of Variation in Drug
Response
 Genetic
 Environmental
Pharmacogenetics and
Clinical therapeutics

Genes confer disease susceptibility
Diseases can be genetically
heterogeneous

Efficacy, adverse drug reactions and
drug interactions are often
genotype-dependent

Genetic Polymorphisms
Pharmacokinetic
Pharmacodynamic
Receptors
Absorption
Ion Channels
Distribution
Metabolism
Enzymes
Excretion
Immune system
Promise of Pharmacogenetics
Pharmacogenetics
 Drug will be approved for patients with defined genotype
 Trials will be smaller and shorter
 Market for drug may be smaller
 Genotype testing before drug administration
 Standardization of genotype test
 Greater post marketing safety surveillance
Dialogue Between
Regulators and Sponsors

Briefing Meetings

Safe Harbours

Regulatory Exemption
New drugs come from molecular, biochemical and physiological
research, much of which stems from academic institutions. As it
quits the quiet waters of academia, a concept with a market
potential is exposed to the entrepreneurs of the biotechnology
sector, the credulous greed of the equity market, the well
groomed executives of the pharmaceutical industry and the
paper maze of the drug regulator before it lands in the broad
handshake of the marketing manager- all before it crosses the
horizon of the sceptical and budget- driven clinician who might
want to use the product.
Gale E and Clark A (2000)