1. Dolores Montero Varsow, 7 October 2011 Risk Management Plan and the elderly.- Some thoughts

2. General considerations – Demographic data – Particularities of the elderly Current situation.- Some examples Thinking for the future.- Some ideas

3. Number of People Age 65 and Over, by Age Group, Selected Years 1990-2000 and Projected 2010-2050

4. Chronic Disease Age—A Major Risk Factor

5. Chronic Disease The Number of People with Chronic Conditions is Rapidly Increasing

6. Prevalence of Cardiovascular Disease: Heart Disease and Stroke Age—A Major Risk Factor Prevalence of Cardiovascular Disease: Heart Disease and Stroke Age—A Major Risk Factor

7. Particularities in the Elderly (drug oriented) PK – Higher distribution of liposoluble drugs – Decreased hepatic metabolism capacity – Progressive deterioration of renal function (not reflected by serum creatinine) PD: less studied and probably more relevant – Decrease hemostatic response (postural control, termoregulation, cognitive function). Altered by a number of drugs: psychopharm, anticoagulants

8. Some data SPC specific information on the 100 drugs most consumed by the elderly: – 52% specific PK info – 6% specific PD info – 81% specific posology – 46% specific warings – 16% specific interactions – 15% specific info on ADRs

9. Particularities in the elderly (Patient oriented) Functional status (calcium antagonists in patients with chronic constipation) Cognitive status (ASA above 100mg) Co-morbidities, which deals to polymedication and relevant drug interactions – 35% of patients above 65 with 3 or more concomitant illnesses – Integral review often lacking, dealing to duplications and cascade of drugs Specially relevant in frail patients

10. Is the elderly accurately represented in clinical trials? What about risk management plans? Does the SPC provides helpful information?

11. CT authorised by AEMPS (1993- 2009) Elderly population included in 30% of the trials The percentage has increased over time (14% of trials in 1993; 50% of trials in 2009)

13. Active substance Therap indication Patients above 65 years in clinical development RMPSPC Ambrisentan PPH 21%Nothingnothing Bivaluridin Prevention of thrombotic events in ACS 65-75y: 30% >75y:10% Nothing“caution in the elderly due to age-related decre. in renal F Ticagrelor Antiaggregant 65-75y: 25% >75y: 10% Nothing Pravast/fenofibr Mixed dislipem 65-75y: 20% >75y: 2.6% Nothing“limited safety data in>75y. Care to be exercise” Romiplostim TIP >65y: 25%NothingCare advise due to the small nr of elderly pat Eltrombopag TIP 65-75y: 10% >75y: 6% NothingLimited data. Greater sensitivity of some older indivd not ruled out

14. Active substance Therap indication Patients above 65 years RMPSPC Belimumab Add-on SLE >65y: 2%nothingEfficacy and safety not established. Not recommended unless benefits outweight risks Roflumilast Maintenance of severe COPD >65y: 22%nothing Duloxetine (somatic pain) 65-75y: 17% >75y: 22% nothingNA

15. Are we requiring useful data? Are we giving meaningful information?

16. Thinking on the issue.- Some ideas Before authorisation – Enough sample? (prevalence of illness, duration of treatment). Sufficiently analysed? BUT ALSO – Inclusion and exclusion criteria in CT – Posology – Easiness of administration

17. Thinking on the issue.- Some ideas At the time of authorisation – Requirement of post-authorisation efficacy studies (PAES) in real conditions. Specially for chronic treatments in frail patients (common co- morbidities). FIRST CRITERIA IDENTIFIED FOR THESE STUDIES?? Recent examples: cilostazol, dronedarone Recent examples: cilostazol, dronedarone

20. Thinking on the issue.- Some ideas At the time of authorisation – Specific informative material in case of potential cognitive/functional impairment or meaningful interactions? – Standard text in the SPC encouraging the periodic review of medication, in case of chronic treatments?

21. Thinking on the issue.- Some ideas After authorisation – Different approach for assessing spontaneous reports? cilostazol cilostazol – Other criteria for assessing seriousness taking into account functional or cognitive impact?

22. Conclusions Some attention has been paid, but probably not enough Some attention has been paid, but probably not enough A systematic approach during the different phases of drug regulation may be a step forward A systematic approach during the different phases of drug regulation may be a step forward