The Accelerating Pace of Medical Development and Challenges in

Evaluating Benefit and Risk

Alasdair BreckenridgeMedicines and Healthcare products

Regulatory Agency

Food and Drugs Administration (FDA)

European Medicines Agency (EMEA)

International Conference on Harmonisation (ICH)

Unacceptable

Acceptable

Ris

k

Benefits (relative value)

To protect the public health by allowing only medicines which have a satisfactory risk-benefit 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

Responsibilities of the Medicines’ Responsibilities of the Medicines’ RegulatorRegulator

Measures of Drug EfficacyMeasures of Drug Efficacy

Peak expiratory flow rate

Standard BP measurement

Joint size and temperature

Rating scales for dementia

Rating scales for depression

BiomarkerBiomarker

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

BiomarkersBiomarkers

Collagen telopeptide fragments PET imaging for tumours Inflammation - Acute protein CRP

- Cytokine IL6

- Metalloproteases

Improvement of Risk-benefit ProfileImprovement of Risk-benefit Profile

Define accurately the population of patients who will

respond to a medicine.

Causes of Variation in Drug Causes of Variation in Drug ResponseResponse

Genetic

Environmental

Pharmacogenetics andPharmacogenetics andClinical therapeuticsClinical therapeutics

Genes confer disease susceptibility

Diseases can be genetically heterogeneous

Efficacy, adverse drug reactions and drug interactions are often genotype-dependent

Genetic PolymorphismsGenetic Polymorphisms

PharmacokineticPharmacokineticPharmacodynamicPharmacodynamic

Absorption

Distribution

Metabolism

Excretion

Receptors

Ion Channels

Enzymes

Immune system

Promise of PharmacogeneticsPromise of Pharmacogenetics

PharmacogeneticsPharmacogenetics

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 Dialogue Between Regulators and SponsorsRegulators 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)