![Page 1: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/1.jpg)
Patients’ role in
post-marketing authorisation phase
in the 21st century
François HouÿezDirector of Health Policy
6th ECRD, 23-25 May 2012, Brussels
![Page 2: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/2.jpg)
Why does it matter?
Proof of concept studies
• A few tenths
Confirmation trials
• A few hundreds
Market
• A few more hundreds, thousands
F. Houÿez 25/05/2012 2
![Page 3: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/3.jpg)
Marketing
authorisation
Patient population & orphan drugs
F. Houÿez 25/05/2012 3
Proof of concept Confirmation
Target population
![Page 4: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/4.jpg)
Patients and off-label use
Authorised indication
Off-label uses
Often for rare diseases
F. Houÿez 25/05/2012 4
![Page 5: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/5.jpg)
20th century
Buffalo neck
Belly
Fat loss
Fat loss, prominent veins
5
1996 : highly active antiretroviral therapies to treat HIV/AIDS became available.
Very rapid intake in countries that made the products available. But:
Questions:
1) What was this?
2) Was it due to drugs? � Class of drugs?
� Individual drugs?
3) Was it due to
disease/increased
survival?
4) Could it change
benefit/risk?
F. Houÿez 25/05/2012
![Page 6: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/6.jpg)
� 2 March 1999: EMEA meeting
– The Oversight Committee for Metabolic Disorders of HAART (with industry, academic experts, patients’ representatives)
– 9 supportive MAH, budget: 5 746 056.3 € over 5 years
� A case definition study for “lipodystrophy” – Carr et al. Lancet. 2003 Mar 1;361(9359):726-35. An objective case definition of lipodystrophy in HIV-
infected adults: a case-control
� A retrospective cohort study/risk of cardiovascular events – Veterans Administration Database USA
� A multi-cohort prospective study / cardiovascular risk– The D.A.D. study (Data collection on Adverse events of anti-HIV Drugs). Lundgren et al., N Engl J Med
2003;349:1993-2003.
� Clinical trials meta-analysis (abandoned)– ACTG 384, INITIO, ATLANTIC, and FIRST
� Merging of 9 MAH safety databases (never started)6
Four studies started 1999
F. Houÿez 25/05/2012
![Page 7: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/7.jpg)
7
Risk of Myocardial Infarction According to Exposure to Protease Inhibitors and Non Nucleoside Reverse-
Transcriptase Inhibitors among Patients Unexposed to the Other Drug Class,
Lundgren et al., N Engl J Med 2003;349:1993-2003.
F. Houÿez 25/05/2012
Results
HAART was independently associated with an 26%
increased risk of myocardial infraction per year of exposure
![Page 8: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/8.jpg)
Lessons
� Patients’ rep. involved in each of the studies– design, conduct, analysis, communication
� Patients’ rep. in the oversight committee– Follow-up + reporting to EMEA and to patients’ community
� Total: increased transparency and trust in the
assessment/decisions
� Impact on pharmacovigilance legislation
– PASS and PAES, ADRs reporting by patients…
F. Houÿez 25/05/2012 8
![Page 9: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/9.jpg)
F. Houÿez 25/05/2012 9Peter Harlett, EMA, Implementation of the New Pharmacovigilance Legislation
![Page 10: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/10.jpg)
« Most important legislation on medicines
since 1995 » P.Harlett EMA
� 2003: EC decision to undertake an
assessment of the Community system of
pharmacovigilance
� Both Regulation (EC) 1235/2010 and
Directive 2010/84/EC have been published
on 31 December 2010
� July 2012: new legislation will apply
F. Houÿez 25/05/2012 10
![Page 11: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/11.jpg)
Watch out what’s (particularly) for us in
the Pharmacovigilance legislation
� Already active
– PhVWP, risk communication, some RMP
� With the legislation (selection)
– PRAC and national equivalents
– PASS/PAES studies
– Patient reporting and access to Eudravigilance data
(spontaneous reports)
• Visit: www.adrreports.eu
– RMP and their evaluation
– Public hearings
F. Houÿez 25/05/2012 11
![Page 12: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/12.jpg)
Drugs for children
Pharmacoepidemiology
European Reference Networks for
RD
To study
EMA network
MAHs
CNAs To assess
Trials
ADRs
Drugs
To inform
Healthcare
professionals
Patients
Many to
report
A role for everyone
F. Houÿez 25/05/2012 12
![Page 13: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/13.jpg)
ADR reporting tools as of May 2012
F. Houÿez 25/05/2012 13
On-line reporting form
Printed form
No information available
Non-EU/EEA
Q&A on suspected
adverse drug reactions
prepared by Eurordis DITA task force
![Page 14: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/14.jpg)
DAILY IMPACT OF ORPHAN
DRUGS IN PATIENTS’ LIVES
The DIOD project by Eurordis and partners
14F. Houÿez 25/05/2012
![Page 15: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/15.jpg)
F. Houÿez 25/05/2012 15
To provide patients with information on
the drugs they are taking
To collect their feedback on desired
effects of the drug
To collect their feedback on undesired
effects of the drug
Also useful
for CHMP
consultation
Objectives
![Page 16: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/16.jpg)
Constrains and ease of use
Constrains and ease of use
Frequency of side effects
Frequency of side effects
Efficacy including quality of life
Efficacy including quality of life
Severity of side effectsSeverity of side effects
Uncertainty what is known about the toxicity profile?
Uncertainty what is known about the toxicity profile?
F. Houÿez 25/05/2012 16
Benefit/risks is a matter of
![Page 17: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/17.jpg)
How?
F. Houÿez 25/05/2012 17
![Page 18: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/18.jpg)
Which OD to start with and how?
F. Houÿez 25/05/2012 18
![Page 19: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/19.jpg)
Longitudinal monitoring in outpatients:
feasibility
� 1373 first‐time users of pregabalin were approached
in Dutch pharmacies between 1 August 2006 and 31
January 2008.
� After online registration, patients received
questionnaires by email 2 weeks, 6 weeks, 3 months
and 6 months after the start of the drug use.
� Data on patient characteristics, drug use and ADRs
were collected and analysed.
F. Houÿez 25/05/2012 19
Longitudinal monitoring of the safety of drugs by using a web‐based system: the case of pregabalin
Pharmaco-epidemiology and Drug Safety 2011; 20: 591–597
![Page 20: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/20.jpg)
Some results
F. Houÿez 25/05/2012 20
Kaplain–Meier curves
illustrating the incidence
densities of the five most
frequently reported adverse
drug reactions. From the
top down to the first line
represents:
� increased weight
� Fatigue
� feeling drunk
� Somnolence
� dizziness ‘Survival’ pertains to those
patients who did not develop
particular adverse drug reaction
![Page 21: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/21.jpg)
Issues
� How do we get organise to deliver all this?
– Large scale patients’ involvement
• Role of EUPATI
– Large scale patients’ representatives involvement
• Training, EUPATI
• Time and support, cf Code du Travail
� Impact assessment: “Based on the feedback of stakeholders and in an
attempt to reduce costs, the final proposal for the committee structure has
been revised to include a small expert committee on PhV. This results in
an overall neutral effect of the committee structure changes compared to
the current situation”.
F. Houÿez 25/05/2012 21
![Page 22: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/22.jpg)
To conclude
� Each person taking a yet authorised product
for the first time does an experiment
– You never know for sure if the drug is going to
work for you
– You never know which toxic effects will occur
� We need to collect more information to
increase knowledge
� As patients, we need to be pharmaco-vigilant!
F. Houÿez 25/05/2012 22
![Page 23: Patients’ role in post-marketing authorisation phase in the 21 …download2.eurordis.org/ecrd2012/T5S0506_F_HOUŸEZ.pdf · 2018-03-28 · Patients’ role in post-marketing authorisation](https://reader034.vdocument.in/reader034/viewer/2022042113/5e8fe21f7744b84026414dd2/html5/thumbnails/23.jpg)
Thank you.
F. Houÿez 25/05/2012 23