1. Gunnar Alvan November 2002 Perspectives and Achievements with Rational Pharmacotherapy - Gunnar Alvan MD, Ph D, Prof Director General Medical Products Agency (MPA) The role of the authorities

2. Gunnar Alvan November 2002 Rational pharmacotherapy Rational or based on reason would mean science or evidence based

3. 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.)

4. Gunnar Alvan November 2002 What is rational pharmacotherapy? An ideal situation 1.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….

5. Gunnar Alvan November 2002 An ideal situation 3.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choice of dose, evaluation of effect, dose adjustment, therapy and adverse effect monitoring. 4.Therapy should be withdrawn when a defined and preset endpoint has been reached.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?

6. Gunnar Alvan November 2002 Great mission to fulfil Goal given in the official instruction Contribute on many levels Pharmacotherapy The role of authorities

7. 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

8. 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

9. Gunnar Alvan November 2002 Rationality - scientifically based work The guidelines are continuously developed and reflect the movement of the research front. Role of guidelines

10. Gunnar Alvan November 2002 Scientific domain Observation Description Analysis Cause-effect relationship Statistical perspective: reality/uncertainty Objectivity Reproducibility Hypothesis: confirmation/rejection Consistence Evolution

11. 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

12. Gunnar Alvan November 2002 Abbreviations SPC:Summary of Product Characteristics PIL:Package Insert Leaflet EPAR:European Public Assessment Report

13. 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

14. 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?

15. 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?

16. Gunnar Alvan November 2002 Number of published studies vs total number of clinical studies

17. Gunnar Alvan November 2002. Treatment guidelines Expert meetings (6-8/year) together with the Norwegian drug authority with reviews as basis Internet WS-books Information from the MPA bulletin Guidelines Information pharmacists Drug committees

18. 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

19. 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

20. 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

21. 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

22. 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?

23. 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

24. 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