Ομιλία-Παρουσίαση: Γιώτα Τουλούμη, Καθηγήτρια Βιοστατιστικής και Επιδημιολογίας, Εργαστήριο Υγιεινής, Επιδημιολογίας και Ιατρικής Στατιστικής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών

1. Clinical Conference 2017
Non commercial clinical studies: their
contribution and the main barriers in
their implementation
Giota Touloumi
Professor of Biostatistics and Epidemiology
Dept. Hygiene, Epidemiology & Medical Statistics
Medical School
National and Kapodistrian University of Athens (NKUA)
gtouloum@med.uoa.grDept. Hygiene, Epidemiology & Medical Statistics
Medical School, NKUA

2. Substantial contribution of non-
commercial or academic clinical
research
Dept. Hygiene, Epidemiology & Medical Statistics
Medical School, NKUA

3. Main Barriers
Dept. Hygiene, Epidemiology & Medical Statistics
Medical School, NKUA

4. Main Barriers
Dept. Hygiene, Epidemiology & Medical Statistics
Medical School, NKUA
 Luck of funding
 Increased costs (large-scale Clinical Trials)
 Insurance coverage
 Based on risk assessment
 Excessive Monitoring (ICH-GCP)
 FDA-EMA: risk based approach
 Complex and time costly regulatory requirements
 Harmonization and simplification
 Inadequate Infrastructure
 Background data
Registries, Health surveys, epidemiological studies


5. International Network for Strategic
Initiatives in Global HIV Trials
To develop strategies for the optimization of
treatment -- ART, immunomodulatory therapies,
and interventions to prevent and treat the
complications of HIV and ART – in order to
prolong disease-free survival in an
demographically, socio-economically, and
geographically diverse group of individuals with
HIV.

6. Strategies for Management of
Antiretroviral Therapy (SMART) Study
SMART study group. CD4+ count-guided interruption of antiretroviral therapy.
N Engl J Med 2006; 355:2283-96

7. Countries Participating in SMART
CPCRA
RCC
Brazil
Canada
Peru
South Africa
United States
Sydney
RCC
Argentina
Australia
Chile
Israel
Japan
New Zealand
Thailand
Uruguay
Copenhagen
RCC
Austria
Belgium
Denmark
Estonia
Finland
Germany
Lithuania
Luxembourg
Norway
Poland
Portugal
Russia
Spain
London
RCC
France
Greece
Ireland
Italy
Morocco
Switzerland
United Kingdom

8. SMART Study Design
Drug Conservation
(DC) Strategy
[Stop or defer ART until CD4+
< 250; then episodic ART
based on CD4+ cell count to
increase counts to > 350]
Virologic Suppression
(VS) Strategy
[Use ART to maintain viral
load as low as possible
throughout follow-up]
Participants with CD4+ > 350
n = 3000 n = 3000
Expected follow-up period: 7-8 years

9. Conclusion
Episodic use of ART based on CD4+ cell
count levels as per the SMART study
design is inferior to continuous ART for
the management of treatment experienced
patients and thus should not be routinely
recommended

10. Unexpected results in SMART led
to a new way of thinking about
non-AIDS events. The findings
from SMART motivate START

11. START design
HIV-infected individuals who are ART-naïve with
CD4+ count > 500 cells/mm3
Early ART Group
Initiate ART immediately
following randomization
N=450 in pilot phase and
estimated as N=2,000 for
definitive trial
Deferred ART Group
Defer ART until the CD4+ count
declines to < 350 cells/mm3 or
AIDS develops
N=450 in pilot phase and
estimated as N=2,000 for
definitive trial

12. Interin analysis results
START
Conclusion
cART should be offered to all individuals
diagnosed with HIV, irrespectively of the
CD4 cell count
NEJM 2015; 373: 795-807

13. START: Greek participation
 Approval: 10/2009
 Clinics: 6
 No of patients: 102
 Total money received so far: >1,500,000 euros
 Free cART for 8 years

14. Barriers in initiating and
implementing START (NOM)
 Patient’s Insurance
 total coverage: 60*200,000=12,000,000
Risk assessment
 Complex procedures
 Simplification, harmonization
 Time
1-2 months the approval letters to arrive

15. Barriers in initiating and
implementing START (SARGs)
 Hospitals’ Scientific council
 for years didn’t exist
 fees
 Contracts
Between Universities and clinics
 3-6 months
 University’s SARGS
 >2 months for the NOM fees
 >3 months to employ personnel
 Difficult to keep the trained personnel
 3-6 months to pay clinics

16. Background data
 Registries
Rare diseases? Cancer?
 Health Surveys

17. Hprolipsis
(prolipsis=prevention)
Health Examination Survey
(questionnaires and collection of biological samples)
General population
N=6,000
Roma
N=500
Migrants
N=600
Field survey:
3/2014 - 6/2016
Funded by EU structural funds and by National funds

18. Estimated Prevalence
General
population
Migrants Roma
HBsAg +
95% CI
1.74%
1.36-2.23
7.3%
5.35-9.96
7.5%
5.50-10.07
Anti-HCV +
95% CI
0.83%
0.57-1.19
3.0%
1.80-4.88
1.34%
0.64-2.79

19. EMENO preliminary results
Estimated
Prevalence
95% CI
Hypertension 38.3 36.8-39.8
Diabetes 10.6 9.7-11.5
Smoking 37.8 36.4 – 39.2
Dyslipidemia 44.7 43.1-46.4
Obesity 30.4 29,1-31.6

20. Background data
 Registries
Rare diseases? Cancer?
 Health Surveys
Luck of funding
 Epidemiological studies

21. Cascade of care in HIV + individuals
in Greece at the end 0f 2013
14147
[VALUE] (78.4%)
[VALUE] (67.5%)
[VALUE] (52.9%) [VALUE] (52.5%)
[VALUE] (43.4%)
[VALUE] (38.5%)
0
2000
4000
6000
8000
10000
12000
14000
16000
PLHIV Diagnosed Linked Ever Treated Retained on care On trt Suppressed
(200cps/ml)
78.4%
78.5%
77.9%
64.3%
57.1%
86.0%
AMACS: Athens Multicenter AIDS Cohort Study
Initiated: 1996; patients: >9,000

22. Conclusions
 There is potential for increase in the number
of non commercial clinical studies BUT
 simplification of regulatory procedures
 effective ways to reduce cost
 Reduce hospitals and Universities
bureaucracy; simplification; more effective
management
 Funding
 for non-commercial studies
 for epidemiological studies offering useful
public health data but also background data
for RCTs

23. Thank you