Gunnar Alvan November 2002
Perspectives and Achievements with Rational Pharmacotherapy
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Gunnar Alvan MD, Ph D, Prof
Director General
Medical Products Agency (MPA)
The role of the authorities
Gunnar Alvan November 2002
Rational pharmacotherapy
Rational or based on reason
would mean
science or evidence based
Gunnar Alvan November 2002
Science The gold standard for regulatory work
T. Sjöstrand 1907-1987
"Science is a social process through which man, by making observations and experiments is providing factual data to found a system of concepts which will approximately describe reality as we experience it and which should be tested by further observations and experiments."
(translation by G.A.)
Gunnar Alvan November 2002
What is rational pharmacotherapy?
An ideal situation1. Indication for drug therapy in relation to all prevailing
circumstances: age, disease, abuse, pregnancy, sex, nutrition, concomitant drug use or other strategy….
2. Choice of drug according to factual criteria: pathophysiology, mechanism of action, the above conditions, characteristics of drug product….
Gunnar Alvan November 2002
An ideal situation3. Drug treatment should be carried out according to
knowledge based principles: choice of dose, evaluation of effect, dose adjustment, therapy and adverse effect monitoring.
4. Therapy should be withdrawn when a defined and preset endpoint has been reached.
What is rational pharmacotherapy?
Gunnar Alvan November 2002
• Great mission to fulfil
• Goal given in the official instruction
• Contribute on many levels
Pharmacotherapy The role of authorities
Gunnar Alvan November 2002
Post approval laboratory control
Scientific evaluation of documents
Information (SPC, PIL)
Pharmacovigilance
Therapeutic advice
Media
Environment
The emphasis for authorities has shifted
Gunnar Alvan November 2002
• Preregistration– Clinical trials, compassionate use
• Registration– Evaluation and approvals
• Post registration– Information, follow-up studies– ADR monitoring, evaluation, actions– Control laboratories– Inspections– Legal actions (advertisements, illegal claims etc)
The role of the authorities
Gunnar Alvan November 2002
• Rationality - scientifically based work
• The guidelines are continuously developed and reflect the movement of the research front.
Role of guidelines
Gunnar Alvan November 2002
Scientific domain
Observation
Description
Analysis
Cause-effect relationship
Statistical perspective: reality/uncertainty
Objectivity
Reproducibility
Hypothesis: confirmation/rejection
Consistence
Evolution
Gunnar Alvan November 2002
Adopted Guidelines 2002 (Efficacy, Safety and Quality)
Note For Guidance on:
• Clinical Investigation of Medicinal Products in the Treatment of Diabetes Mellitus
• Clinical Investigation of Medicinal Products in the Treatment of Depression
• Clinical Investigation of Medicinal Products in the Treatment of Peripheral Arterial Occlusive Disease
• Carcinogenic potential
• Photosafety Testing
• Quality of Water for Pharmaceutical Use
• Requirements for Pharmaceutical Documentation for Pressurised Metered Dose Inhalation Products
Gunnar Alvan November 2002
Abbreviations
• SPC:Summary of Product Characteristics
• PIL: Package Insert Leaflet
• EPAR: European Public Assessment Report
Gunnar Alvan November 2002
SPC and PIL
• Products description documents with instructions for use
• Founded on evaluated facts presented in registration file
• Anyone can view
• Problems: update, translation, disharmony, no reference list
Gunnar Alvan November 2002
Aim of PIL
• Patients can be aware of and correctly use the product
• Communication task, should be easy to read
• Problem: neglected? negativity?
Gunnar Alvan November 2002
At the time of approval….
• Is it possible for the professionals in the health care system to evaluate new drugs?
• To which extent is it possible to find clinical studies in PubMed at the time of approval of new drugs?
Gunnar Alvan November 2002
Number of published studies vs total number of clinical studies
0 10 20 30 40 50
Avandia
Celebra
Nexium
Relenza
Reminyl
Sonata
Subutex
Synagis
Vioxx
Zyban
Cipralex
Number
Published studies Clinical studies
Gunnar Alvan November 2002
.
Treatment guidelines
Expert meetings (6-8/year) together with the Norwegian drug authority with reviews as basis
InternetInternet
WS-booksWS-books
Information from Information from the MPA bulletinthe MPA bulletin
GuidelinesGuidelines
Information Information pharmacistspharmacists
Drug committeesDrug committees
Gunnar Alvan November 2002
• New drugs
• New knowledge about old
drugs
• How to use the drug-
treatment guidelines
Continuous drug communication is the basis for rational drug use
Gunnar Alvan November 2002
• Drug committees and Public drug information centres
• Drug regulatory agencies
• Pharmacies
• Independant drug bulletins i.e. La Revue Prescrire and The International Prescriber
• Medical technology assessment and research organisations
Non commercial drug information actors
Gunnar Alvan November 2002
From darkness into light
• Drug monographs on NCE:s and new indications
– Presentation of all, including unpublished, clinical trials
– Safety assessment
– Comments on the value of the drug
Gunnar Alvan November 2002
Distribution of the information
• Information from the MPA ”Bulletin”
• Internet - www.mpa.se
• A workshop book series
• Drug committees
• Information propagated from doctors and pharmacists
Gunnar Alvan November 2002
• NO!
• However, the file is under business secrecy.
• The approval, SPC and monographs is the outcome of the total file submitted.
• There is no crucial information ”hidden” in the files, but there will be bias in publication and citation.
Is the drug information role hampered by legal requirements?
Gunnar Alvan November 2002
• The European Parliament voted against the Commissions proposal to allow companies to communicate directly with consumers about some prescription medicines.
A personal view:• No inhibition of Internet sites that discuss drug treatment.• Advertising in public media for Rx is not in the interest of public
health. The public sector will have to pay for the advertising and also receive information without tools to evaluate its reliability.
DTC - direct to consumer advertising
Gunnar Alvan November 2002
Slogans we will not see in the underground
• Got cystitis? Get Uricure®!
• No more morning anxiety with Gloomy®!
• When it comes to high blood pressure use A-stop®, turns off your A-II receptors better than any other drug!
• Erected on Niagara®!
• Get high on Himalaya®!
Made up DTC examples