Dolores MonteroDolores Montero

Varsow, 7 October 2011

Risk ManagementPlan and the elderly.-Some thoughts

• General considerations– Demographic data– Particularities of the elderly

• Current situation.- Some examples

• Thinking for the future.- Some ideas

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

Chronic DiseaseAge—A Major Risk Factor

Chronic Disease The Number of People with Chronic Conditions

is Rapidly Increasing

Prevalence of Cardiovascular Disease: Heart Disease and StrokePrevalence of Cardiovascular Disease: Heart Disease and StrokeAge—A Major Risk FactorAge—A Major Risk Factor

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

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

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

• Is the elderly accurately represented in clinical trials?

• What about risk management plans?

• Does the SPC provides helpful information?

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)

0

100

200

300

400

500

600

700

800

2000 2002 2004 2006 2008

CT elderly

CT total

Active substanceActive substance

Therap indicationTherap indicationPatients above 65 Patients above 65 years in clinical years in clinical developmentdevelopment

RMPRMP SPCSPC

AmbrisentanPPH

21% Nothing nothing

BivaluridinPrevention of thrombotic events in ACS

65-75y: 30%>75y:10%

Nothing “caution in the elderly due to age-related decre. in renal F

TicagrelorAntiaggregant

65-75y: 25%>75y: 10%

Nothing Nothing

Pravast/fenofibrMixed dislipem

65-75y: 20%>75y: 2.6%

Nothing “limited safety data in>75y. Care to be exercise”

RomiplostimTIP

>65y: 25% Nothing Care advise due to the small nr of elderly pat

EltrombopagTIP

65-75y: 10%>75y: 6%

Nothing Limited data. Greater sensitivity of some older indivd not ruled out

Active substanceActive substance

Therap indicationTherap indicationPatients above 65 Patients above 65

yearsyearsRMPRMP SPCSPC

BelimumabAdd-on SLE

>65y: 2% nothing Efficacy and safety not established. Not recommended unless benefits outweight risks

RoflumilastMaintenance of severe COPD

>65y: 22% nothing nothing

Duloxetine(somatic pain)

65-75y: 17%>75y: 22%

nothing NA

• Are we requiring useful data?

• Are we giving meaningful information?

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

Thinking on the issue.- Some ideas

• At the time of authorisation– Requirement of post-authorisation Requirement of post-authorisation

efficacy studies (PAES) in real efficacy studies (PAES) in real conditions. conditions. Specially for chronic Specially for chronic treatments in frail patients (common co-treatments in frail patients (common co-morbidities). morbidities). FIRST CRITERIA IDENTIFIED FIRST CRITERIA IDENTIFIED FOR THESE STUDIES??FOR THESE STUDIES??• Recent examples: cilostazol, dronedaroneRecent examples: cilostazol, dronedarone

Thinking on the issue.- Some ideas

• At the time of authorisation– Specific informative material in case of Specific informative material in case of

potential cognitive/functional potential cognitive/functional impairment or meaningful interactions? impairment or meaningful interactions?

– Standard text in the SPC encouraging Standard text in the SPC encouraging the periodic review of medication, in the periodic review of medication, in case of chronic treatments? case of chronic treatments?

Thinking on the issue.- Some ideas

• After authorisation– Different approach for assessing Different approach for assessing

spontaneous reports?spontaneous reports?• cilostazol cilostazol

– Other criteria for assessing seriousness Other criteria for assessing seriousness taking into account functional or taking into account functional or cognitive impact?cognitive impact?

Conclusions

• Some attention has been paid, but Some attention has been paid, but probably not enoughprobably not enough

• A systematic approach during the A systematic approach during the different phases of drug regulation different phases of drug regulation may be a step forwardmay be a step forward