Prsentation PowerPoint

1
CLINICAL RESEARCH PUBLIC vs PRIVATE Loïc
Guillevin Paris, 10 May 2007
2
PUBLIC VS PRIVATE
THE OBJECTIVES OF PUBLIC RESEARCH

• A larger number of topics, not only based on
  drugs
• Supports studies on therapeutic strategies, with
   old drugs 
• Supports studies on new indications of already
  marketed drugs
• Organizes epidemiologic and public health
  research
• The objectives of public research is also to
  organize research around  public health
  objectives 
• Organizes research on orphan diseases and drugs

3
PUBLIC VS PRIVATE
THE ADVANTAGES OF PUBLIC RESEARCH

• More freedom and independance
• Public money
• Independance from the pharmaceuticals companies
• The choice of topics for clinical research
• Publications free choice and publication of
  negative results

4
PUBLIC VS PRIVATE

• INSTITUTIONAL PARTNERS
• UK The Welcome trust
• Provides funds, equivalent to public research
• USA Microsoft foundation (Bill Gates)
• Budget 30 billions dollars
• 2004 funding 6 billions dollars

5
PUBLIC VS PRIVATE

• INSTITUTIONAL PARTNERS
• France INSERM
• 2005 475 millions ( 7)

• UK MRC
• 2004/2005 512 millions (743 millions )

6
PUBLIC VS PRIVATE
ONE EXAMPLE

• Treatment of HBV-related PAN with lamivudine and
  plasma exchanges
• PAN is a rare disease
• HBV-PAN is extremily rare
• Plasma exchange is an expensive treatment
• The market for this new indication of lamivudine
  is too small to stimulate the interest of the
  company

7
PUBLIC VS PRIVATE
CS
LAMIVUDINE 100 mg/d
7 - 14 days
1 to 6 months
8
PUBLIC VS PRIVATE
LAMIVUDINE (LAMIPAN) PROTOCOL

• 1 death (septicemia)
• 9 patients recovered, 1 is dialysed
• 6 seroconversions Hbe/anti-Hbe
• No replication in 2 patients
• 1 active replication

9
PUBLIC VS PRIVATE
PRIVATE RESEARCH ADVANTAGES ?

• Good research despite the absence of market
• The risk to observe side effects which could be
  a disadvantage for the company
• Difficulties to attribute the positive results
  of the treatment to the drug or to PE or both

10
PUBLIC VS PRIVATE
THE DISADVANTAGES OF PUBLIC RESEARCH

• Slow.., sometimes very slow!
• In France, at least one year for expertises,
  funding, ethic committee etc
• Difficulties to obtain drugs from the companies
  (even if drugs are purchased)
• Daily organisation is difficult

11
PUBLIC VS PRIVATE
THE DISADVANTAGES OF PUBLIC RESEARCH

• Daily organisation is difficult
• Recruitment of patients
• Monitoring
• Meetings (for multicenter studies)

12
PUBLIC VS PRIVATE
THE DISADVANTAGES OF PUBLIC RESEARCH

• Not enough money
• Less than for private research
• Not enough for monitoring
• Not enough for meetings

13
PUBLIC VS PRIVATE
THE DISADVANTAGES OF PUBLIC RESEARCH

• Research should be organised by
   professionnals 
• clinicians
• but also administrators
• In our institutions, you have to give 50 of
  your time for patients care, 50 for teaching
  and 50 for research!!

14
PUBLIC VS PRIVATE
PRIVATE CLINICAL RESEARCH

• The objectives are clear
• New drugs
• New indications for already marketed drugs

15
PUBLIC VS PRIVATE
ADVANTAGES OF PRIVATE CLINICAL RESEARCH

• Research is largely funded
• Very well organized
• Perfect monitoring
• Money to organize the study
• Money for clinicians contributing to the project

16
PUBLIC VS PRIVATE
INCONVENIENCES OF PRIVATE CLINICAL RESEARCH

• A research organised for financial purposes
• Daily management is difficult for clinicians
• Selected population
• Short follow up
• No therapeutic strategy
• The quality of the protocol is sometimes better
  than the objective of the study!

17
PUBLIC VS PRIVATE
IS IT POSSIBLE TO COMBINE BOTH ?

• YES
• Private research provides funds
• The  know how  comes sometimes from private
  research
• Pharmaceutical companies are often prepared to
  support long term follow-up of their own studies

18
PUBLIC VS PRIVATE
IS IT POSSIBLE TO COMBINE BOTH ?

• YES
• Private foundations (often linked to
  pharmaceutical companies) are prepared to fund
  public clinical research
• Pharmaceutical companies could provide free
  drugs for public research
• Companies can also fund public research,
  especially for orphan drugs or orphan diseases

19
PUBLIC VS PRIVATE
IS IT POSSIBLE TO COMBINE BOTH ?

• YES
• Epidemiologic studies
• example the CORPUS study. A long follow-up
  study of patients treated by anti-TNF in France
• The study has been organized by the Direction
  Générale de la Santé.
• Funds are provided by Schering, Abbott and
  Wyeth.

20
PUBLIC VS PRIVATE
PROJECTS FOR THE FUTURE

• Cooperate with private foundations
• Ask to the companies to support large projects
  on epidemiology and surveys of drugs already
  marketed
• Such policy could serve each partner
• ex Cox 2
• ex Estrogens replacement
• ex antileukotriens and vasculitis

21
PUBLIC VS PRIVATE
CLARIFY DRUG SUPPORT IN  PUBLIC  TRIALS

• In institutional trials (mainly on rare
  diseases) the cost of drugs is so high that
  institutions cannot afford them
• Who should pay?
• The company which has not sponsored the study
  but could take advantage of a positive results?
• The public service ? The only advantage is
  sometimes a publication!

22
PUBLIC VS PRIVATE
EXAMPLE THE WGET STUDY

• An american group (NIH, Mayo, Mass Gen Hospital)
  has decided to organize a trial evaluating
  etanercept as the maintenance treatment of
  Wegeners granulomatosis
• The trial was designed by the authors
• The drug was provided free by Wyeth USA

23
TREATMENT OF VASCULITIDES WITH ETANERCEPT. THE
WGET STUDY

• Objective to maintain rémission
• Obtained in 72.4 patients, but 49 relapses
• No significant reference
• High rate of malignancies in the etanercept group

24
PUBLIC VS PRIVATE
EXAMPLE THE IGANCA STUDY

• Our group has proposed IV Ig as a treatment of
  relapses of ANCA-associated vasculitides
• The study was sponsored by the Assistance
  Publique-Hôpitaux de Paris
• Drug was provided free by the LFB (gt 1,000,000 )

25
ANCA VASCULITIDES
IGANCA

• Open, prospective, non randomized study in
  patients with relapses of ANCA vasculitides
• Monthly infusions of IV Ig for 6 months then
   free treatment 
• Objective 20 CR or 50 PR
• 21 patients included.

26
ANCA VASCULITIDES

• RESULTS
• 21 patients have been included
• 20/21 initial responses
• at 9 mois 13 CR, 1 PR, 7 relapses
• at 24 months
• 7 CR 10 CR with treatment modification
• 2 PR
• 2 relapses

27
22 patients (19 WG, 3 MPA)
21 (18 WG, 3 MPA) remission
Failure 1 WG
First 6 months
16 CR (15 WG, 1 MPA)
2 PR (1 WG, 1 MPA)
3 relapses after CR or PR (2 WG, 1 MPA)
6 months
4 relapses (4 WG)
9 months
13 CR (12 WG, 1 MPA)
7 relapses (6 WG,1 MPA)
1 PR (1 MPA)
Treatment change
4 relapses (3WG, 1 MPA) between M1518 monhs
4 CR (after changing regimen)
5 CR 2 PR
7 CR
1 CR
24 months
2 relapses
28
RESULTS

• Because of the good results, the company has
  decided, according to a contract between the
  Paris hospital and LFB, to buy the results and to
  ask an official approval for this new indication
  of this IV Ig

29
REFERAL CENTERS FOR RARE DISEASES

• Centre which is expert for rare diseases
• A secondary or tertiary referral center for
  patients with severe disease or therapeutic
  difficulties

30
REFERAL CENTERS FOR RARE DISEASES

• 1) Facilitate treatment care for patients
• Improve the quality of diagnosis and
  communication
• Organise the therapeutic strategy
• Inform patients ans family
• 2) Coordination of patients care with GP and
  other specialists
• Teaching of physicians in charge of rare diseases

31
REFERAL CENTERS FOR RARE DISEASES

• 3) Participation in
• Epidemiological studies
• Therapeutic trials
• Guidelines
• (Basic research)

32
REFERAL CENTERS FOR RARE DISEASES

• 4) Coordination with other centers in France and
  other european countries
• 5) A referral for
• Administration
• Other physicians
• Patients associations

33
REFERAL CENTERS FOR RARE DISEASES

• The French government has identified 120 referral
  centers in France (30/year)
• Each center has received grants to recruit
  physicians and organize networks
• Each referral center plays a role in identifying
   competence centers  which will play a role in
  treating patients at a local level.

34
COLLABORATION BETWEEN PUBLIC AND PRIVATE RESEARCH
IN RARE DISEASES

• Step 1 a company has a new drug which is
  effective in rare diseases
• Is it a rare disease?
• Step 2 the pharmaceutical company sponsors an
  epidemiologic study to prove that the disease is
  rare
• Step 3 Based on a scientific publication, the
  company obtains the orphan drug status for its
  drug

35
COLLABORATION BETWEEN PUBLIC AND PRIVATE RESEARCH
IN RARE DISEASES

• One example Actelion pharma and the development
  of bosentan
• Bosentan is an anti-endothelin drug
• The drug is effective for PHT treatment, primary
  or secondary to scleroderma and other CTD

36
COLLABORATION BETWEEN PUBLIC AND PRIVATE RESEARCH
IN RARE DISEASES

• In scleroderma, PHT is underestimated
• Actelion has sponsored many studies to establish
  the prevalence of PHT in scleroderma, and has
  also organized cohort studies and teaching
  programs with the objective to increase the
  detection of patients with PHT

37
COLLABORATION BETWEEN PUBLIC AND PRIVATE RESEARCH
IN RARE DISEASES

• Analysis of this program
• Advances and publications for the clinical
  researchers
• The better detection of PHT has increased the
  number of patients who are candidates to receive
  the drug
•  GAGNANT GAGNANT