Transcript Medical Products Agency and Heads of human and veterinary

Clinical evidence for regulatory
decision making, THE SWEDISH EXPERIENCE
AIFA Spring Conference, 2007
Gunnar Alvan
MD, Ph D, Prof
Director General
Medical Products Agency
GA
The Regulatory network should
promote public health by protecting
from drug hazards but also help
enhance availability of effective
pharmacotherapy through its various
actions
GA
patients
prescribers pharmacies
media
other agencies
patients interest groups
public
Agency
government
Responsibility
parliament
industry
organisations
producers
providers
EU
importers
GA
"evidence of "dose-response" has always
constituted the strongest possible positive
evidence of a pharmacologic mechanism
of action."
Effect
Peck et al CPT 73;481,2003
Dose
GA
Overview of documentation
ADME
Mechanism of action
Application,
substance
Clinical effect
dose, dosage, pk-pd
Drug product
Safety assessment
toxicology, teratology
Application,
extract
Well established use
Herbal
GA
The assessor´s dilemma
• What effects are expected from different drug
exposition in certain patients (drug metabolic
polymorphisms, age, gender, disease, nutrition, drug
metabolic induction and inhibition etc.)?
• Solid PK/PD knowledge and reliable biomarkers
provide the answer to the question how dosing should
be managed in individuals.
GA
Sheiner´s concept of response area
GA
There is not only science to consider...
Religion/conviction
Medical science
Politics/society/economy
GA
Multiple standards
scientific
evidence
tradition,
conviction
GA
Scientific domain
Observation
Description
Analysis
Cause-effect relationship
Statistical perspective: reality/uncertainty
Objectivity
Reproducibility
Hypothesis: confirmation/rejection
Consistence
Evolution
GA
Humanistic domain
Desired by patients
Holistic view
Recommended by leaders
Culture
Tradition
Well established use
Spiritual background
GA
To find the balance...
Decision by patient
Need for a doctor
Variation from patient to patient
GA
To be documented
Ideally, the clinician should have a perception
of a rational dose range and what outliers there
might be. The distribution of doses,
concentrations and effects should be known.
Suggested doses are often not exhaustively
documented in application files. Question of
schedule dependency rarely addressed.
dose
concentration
effect relationship
GA
Major trends
• Biotech and molecular medicine
• The pharmacoeconomic approach
• Improved...
– drug developmental process
– clinical trials
– pre-clinical safety and efficacy evaluation
– approval processes
– post-marketing surveillance/pharmacovigilance
GA
Biomarkers
Biomarkers have a key role in the development
of drugs. Regulatory authorities consider
biomarkers as they are presented and evaluated
by the applicants.
GA
Pharmaceutical Benefits Board
In October, 2002, the new Pharmaceutical
Reimbursement system took effect in Sweden
Prices have decreased 15% since the
introduction (Oct 2002 – Dec 2005).
Accumulated savings €760 million.
(Swedish population ≈ 9 million)
GA
Pharmaceutical Benefits Board
The board decides whether a prescription drug
should be subsidized based on the following
principles:
•The human value principle
– underlines the respect for equality of all human beings and
the integrity of every individual.
•The need and solidarity principle
– those in greatest need take precedence when reimbursing
pharmaceuticals.
•The cost-effectiveness principle
– the cost for using a medicine should be reasonable from a
medical, humanitarian and social-economic perspective.
GA
Dose related pricing
20
18
Relative price
16
14
12
Carve dilo l
Citalo pram
S imvas tatin
10
8
6
4
2
0
0,0
0,5
1,0
1,5
2,0
2,5
3,0
DDD
GA
Challenges
•
•
•
•
•
•
•
•
Availability of important treatment
Difficult to develop drugs, unmet needs
Payer´s responsibilities (NICE etc.)
Pricing and reimbursement principles
Special groups (orphans, pediatrics etc.)
Individualisation and targeting
New valuable drugs, not for use (antibiotics)
Consortia
GA
The European
Regulatory will continue
as a network granting
safe and effective
medicines
*modified
from EMEA
GA