Transcript Risk Management Plan and the elderly Dolores Montero iPhVWP

Varsow, 7 October 2011
Risk Management
Plan and the elderly.Some thoughts
Dolores Montero
• 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,
Selected Years 1990-2000 and Projected 2010-2050
Chronic Disease
Age—A Major Risk Factor
Chronic Disease
The Number of People with Chronic Conditions
is Rapidly Increasing
Prevalence of Cardiovascular Disease: Heart Disease and Stroke
Age—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)
800
700
600
500
CT elderly
CT total
400
300
200
100
0
2000
2002
2004
2006
2008
Active substance
Therap indication
Patients above 65
years in clinical
development
RMP
SPC
Ambrisentan
PPH
21%
Nothing
nothing
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
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%
Nothing
Care advise due
to the small nr of
elderly pat
Eltrombopag
TIP
65-75y: 10%
>75y: 6%
Nothing
Limited data.
Greater sensitivity
of some older
indivd not ruled
out
Active substance
Therap indication
Patients above 65
years
RMP
SPC
Belimumab
Add-on SLE
>65y: 2%
nothing
Efficacy and
safety not
established. Not
recommended
unless benefits
outweight risks
Roflumilast
Maintenance 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
efficacy studies (PAES) in real
conditions. Specially for chronic
treatments in frail patients (common comorbidities). FIRST CRITERIA
IDENTIFIED FOR THESE STUDIES??
• Recent examples: cilostazol, dronedarone
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?
Thinking on the issue.- Some ideas
• After authorisation
– Different approach for assessing
spontaneous reports?
• cilostazol
– Other criteria for assessing seriousness
taking into account functional or
cognitive impact?
Conclusions
• Some attention has been paid, but
probably not enough
• A systematic approach during the
different phases of drug regulation
may be a step forward