This document discusses evaluating the efficacy of drugs for treating venous disease. It notes that while some drugs have shown efficacy in clinical trials, health authorities found the medical utility to be insufficient. The document explores different tools for evaluating efficacy, including indirect evidence from studies on microcirculation and direct evidence from clinical studies measuring symptoms, edema, and quality of life. It argues that future evaluations should focus on long-term studies demonstrating prevention of complications and measuring patient satisfaction, as patients now pay for these drugs out-of-pocket.

1. Epidemiologie sociale de la maladie veineuse Pr Francois André ALLAERT Président de la Société Française d'Angiologie. Vice Président de la société Française de phlébologie Secrétaire général de la Société Française Des docteurs en pharmacie Pr CHRU Dijon & McGill University Montreal. Canada. Pr Francois André ALLAERT Président de la Société Française d'Angiologie. Vice Président de la société Française de phlébologie Titulaire de la Chaire d’Evaluation des allégations de santé Ceren ESC Dijon Evaluation tools for venoactive drug : Does the future lies in patients’ satisfaction evaluation ?

2. INTRODUCTION De-reimbursement has discredited the efficacy of the venoactive drugs For most of them their efficacy was not in question According to the evidence based standards, one of them was able to claim for a level A evidence of efficacy and some other a level B It was the medical utility which appeared insufficient to the French Health authorities

4. An evolution of the drug registration A new approach of the drug registration Where efficacy is a sine qua none condition But which is not sufficient by itself To allow its registration and its reimbursement by the social insurance system.

5. The added medical value : a flexible paradigme Its fuzzy definition lets the commissions to interpret it as they whish by associating depending on the circumstances : « Effectiveness » « Efficacy » « Efficiency » «Utility» « Safety »

6. An anglosaxon terminology « Efficacy » measures how well it works in clinical trials or laboratory studies. « Effectiveness » » relates to how well a treatment works in practice « Efficiency » » is doing things in the most economical way « Safety » is the security in use «Utility» is a measure of the relative satisfaction from, consumption of various goods and services

7. Efficacy evaluation tools Indirect evidences :  an explanatory approach Direct evidences :  a conclusive approach

8. Efficacy evaluation tools Explanatory approach in vitro studies or animal studies On microcirculation On N0 production On inflammatory marker On pain mediator Interest : to explain the effects on functional and physical symptoms Difficulty : to démonstrate the link with the venous disease

9. Conclusive approach Clinical studies 56 studies fulfilling the criteria to get a level A evidence were analysed in the cochrane 2005 review and that we complete with a personal bibliography review after 2005 using the same key words Frequencyof evaluation criteria 54/56 Symptoms evaluation 96,4% 28/56 ankle or calf circumference 50,0% 13/56 Pléthysmographies 23,2% 4/56 leg volume measure using water displacement 7,1% 4/56 Venous reflux with doppler 7,1% 4/56 Venous pressure measure 7,1% 3/56 PO2 et PCO2 measure 5,4% 2/56 Echodoppler measure of oedema 3,8%

10. Conclusive approach Functional symptoms Visual analogic scales are better than qualitative or semi quantitative scales Oedema measures : Measure with measuring tape must be conducted with constant force and attention must be paid to do the measure at the exact same level. Pléthysmography : The most valuable measure except the photoplethysmography. Plethysmography using mercury strain-gauge are forbidden in many countries do to the restriction of using mercury. The most frequent is now air Plethysmography. Volume measurement and venous refilling time. Water displacement: The best way to measure oedema but only oedema.

11. Conclusive approach Reflux measure with echodoppler Demonstrate the reflux and its duration But some studies shows that only 20% of patients with a chronic venous disease avec a deep venous reflux Deep venous reflux are not very sensitive to medical treatment.. Mesure of the venous pressure at the ankle . Lack of standard or definition of a pathological threshold. Not very sensitive to medical treatment.. PCO2 et PO2 Measure Reflect the tissular stress induced by the venous stase But what is the correlation with the clinical symptoms? Oedema measure with echodpoppler. Requires a mathematical 3 dimensional reconstruction of the oedema and only gives a measure of oedema.

12. Conclusive approach Quality of life scales Generic scale : SF12 Specific scales : CIVIQ Show a patients’ quality of life benefit Health authorities do no pay a great attention to their results May re-enforce the opinion of health authorities that venous disease is a comfort troubles It could have been more interesting to compare the quality of life decrease induced by venous disease and those induced by some more « recognized » pathology

13. A lack of recognition Its a disease without real pathological status till some complications appear. Trophic troubles Varicose Ulcer Even not recognised as a risk factor of complications as phlebitis

14. Venous disease status A painful heaviness Whose physiopathological mechanisms have been partially elucidated whose symptoms are relieved by venoactive drugs But its severity is not perceived by authorities in the same manner than arthritic pain or headache .

15. What should we do ? Studies must be targeted in two directions. Health authorities Patients

16. To convince health authorities Long term clinical trials Long term cohorts studies Targeting new indications Not making reference to the venous disease But to the prevention of its complication who are acknowledge as « real » pathologies Requires many years A willingness to pay of the health authorities But what happens in italy is interesting : After venoactive de-reimbursement : frequency of varicose and ulcer increases inducing heath costs increase

17. To convince patients Because patients become consummers When they are paying for their own health expenses To bring evidence of their venous disease relief Functional symptoms +++ Physical symptoms (oedema) Quality of life And in the next future Patients’ satisfaction

18. To evaluate patients’ satisfaction VAS or Lickert scales but Some specific questionnaire Already exist in some other disease and especially in rheumatology They concern The answer to the patients’ expectations Its posology Its safety The patients decision to buy it again Its satisfaction/price A questionnaire should be soon validated In the venous disease

19. CONCLUSION Perhaps are we faced to a turning point of the evaluation of venoactive drugs? Because patients are now paying the venoactive drugs, should we pay more attention to the patienst satisfaction? Perhaps the consumer patient will require a specific metrology for OTC drug in general and venoactive particularly ? Utility is a measure of the relative satisfaction from, consumption of various goods and services