Transcript Clinical Studies in Russia

ANALYSIS OF THE ORGANIZATION
AND CONDUCTING OF CLINICAL
TRIALS IN HEALTHY VOLUNTEERS
IN THE RUSSIAN FEDERATION
Alexander Khokhlov
Professor, Head of the Department of Clinical
Pharmacology YMSU
Clinical Studies in Russia
Article №21 of the Constitution of the Russian Federation,
Federal law «On circulation of medicines» from 12.04.2010
No.61-FL,
National standard of the Russian Federation «Good clinical
practice»,
Helsinki Declaration of the world medical Association,
amended and supplemented in accordance with the latest
edition of Guidelines for bioequivalence study in the countries of
the European Union.
Development of expertise of
Ethic Council of Russia
Chair Alexander Chuchalin
New SOPs are working
out, harmonized with
international requirements
The patient attention to
phase I studies
Collaboration with Ethic
Committees from different
countries
Clinical trials in Russia today
High-qualified specialists (PI, SC, SI) of Russia
conduct daily medical and consultative help to patients
using modern medical and diagnostic equipment
The volume of clinical trials in Russia
(1 and 2 quarters of 2015)
Orange Paper, 2015
Distribution of clinical trials: international and
Russian sponsors (1-2 quarters of 2015)
The structure of clinical trials in Russia
depending on the phase (1 and 2 quarters of
2015)
АОКИ, 2015
Planning of the sample size
1.3 Quantity of patients
Sample size. Author of the protocol should
provide a number of subjects is required to
prove the initial hypothesis (the value of the
sample size is calculated on the basis of
mathematical laws of statistics). The
sample size is affected by the disease to
be studied, the purpose of research and
study endpoints. Statistical evaluation of
the typical sample size should be based on
the estimated result of the treatment, the
variability of the data specified (small)
probability of error (ICH E9) and the
expected information about subgroups and
secondary endpoints. Some studies may
need a large database to establish the
safety of the drug. In clinical studies of the
drug for new indications may be used a
minimum sample size for a registration
database to evaluate the safety (ICH E1
and ICH E7 ). These numbers should not
be construed as absolute and may be
insufficient in some cases (such as when to
expect the delayed effects of the drug)
How to plan the sample size in clinical
trials?
ICH E9 STATISTICAL PRINCIPLES FOR CLINICAL
TRIALS 3.5 SAMPLE SIZE
«The number of subjects in a clinical trial should always be
large enough to provide a reliable answer to the questions
addressed.»
Note for Guidance on Statistical Principles for Clinical Trials
(CPMP/ICH/363/96)
The risks of wrong planning of
bioequivalence studies
• For the manufacturer: the production of defective
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products.
For patients: receiving a generic drug with a risk of a
lack of effect (worsening of the disease), or side effects.
For society as a whole: reducing the effectiveness of
drug therapy and public health,
loss of confidence in generics,
Increasing the cost of drug therapy.
PHARMACOGENOMICS IN
CLINICAL TRIALS :
ATTITUDE OF FDA
PHARMACOGENOMICS IN
CLINICAL TRIALS :
ATTITUDE OF
EMEA
Example: lornoxicam
(exception genotypes
CYP2C9*2, CYP2C9*3)
3.7 Screening of volunteers before beginning of the studies
After signing the informed consent is conducted clinical and paraclinical examinations of
volunteers, including a medical examination in view of the expected pattern of action of the
drug being studied, and the following laboratory tests:
If it is known that the test drug biotransformation is controlled
genetically by polymorphic cytochrome isoenzymes, in order to
reduce the variability of pharmacokinetic parameters
genotyping volunteers advisable to avoid participation in the
study patients with genotypes of "slow" and "fast" metabolism
Vulnerable groups of patients
Patients who are not able for various reasons to fully
exercise their right to voluntary informed consent to
participate in a clinical trial
Clinical trials involving children
These trails are carrying out after completion of
the similar studies of efficacy and safety in
adults (with a few exceptions especially
pediatric drugs) in phase III clinical trials.
Legal representatives of minors:
• Parents
• Adopters
Only parents and adoptive parents, under current
legislation, may sign the informed consent
• Guardians (children under 14)
• Trustees (children from 14 to 18 years)
How to plan the number and participation of volunteers
in bioequivalence studies?
When studies have a
complex design (longterm, multi-day
hospitalization, drugs with
poor tolerance, hormonal
treatments for women), as
well as during the flu
epidemic the number of
doublers shall be
sufficient to provide 80%
of the power of the
statistical test (about 25%
of the total number of
volunteers)
Doublers have to
go through all the
stages of study
Difficulties with compliance
Careful monitoring of
drug receiving (the drug
from the beaker, using
a spatula, a flashlight)
Although all methods of
control in 0.4% of cases
occur sample with zero
concentration of the test
drug
COMPLIENCE
In the narrow
medical sense
COMPLIANCE- IS THE DEGREE OF APPROPRIATE OF
BEHAVIOR OF THE PATIENT TO
RECOMMENDATIONS RECEIVED FROM DOCTOR
my
recommendations
You must perform
voluntarily
BASIS OF COMPLIANCE - CORRECT LINE OF
PHYSICIAN BEHAVIOR
Adherence to the study protocol
Smoking control
Vehicle conducting control
In 35% of cases registered attempts to
bring and pass the forbidden foods and
drinks in the clinic
Creating the necessary conditions for the
volunteers to stay in hospital
Regular training sessions for medical
staff to work with volunteers
The problems associated with multiday hospitalization (2-7 days)
Procuring of conveniences and good quality of life to
volunteers while they are staying in hospital (WiFi, books,
newspapers, television, games, shower)
24-hour monitoring by clinic staff is needed
Additional complexity of design are an additional factor
withdrawal of informed consent (failure rate of 0 to 3.7%).
Sufficient level of compliance
Psychological portrait of the
patient.
The search of new manners
of treatment, the thirst for
more information about the
disease, methods treatment,
search
for
"authorities".
Overly expressed interest in
the objective data about the
disease (results of analyzes,
opinions
of
experts).
Imaginary dangers excite
more than real.
All the bioequivalence studies in Yaroslavl
Clinical hospital №2 are carried out on the basis
of Standard operating procedures
In clinic is constantly working team of
professionals, consisting of 9 doctors and 25
nurses, 4 SC .
Department of bioequivalence consists of a
wardrobe, 8 wards for volunteers, 2 offices of
physicians, 2 bathrooms, the laboratory room
and the dining room.
It is possible to hospitalize 45 patients.
Department is equipped with electronic clock,
fire sensors and alarm system
For the study highlighted staff with professional experience in
the field of bioequivalence and pharmacokinetics. In our clinic
is constantly working team of professionals, consisting of 9
doctors and 25 nurses, 4 SC .
Department of bioequivalence consists of a wardrobe, 8 wards
for volunteers, 2 treatment rooms, 2 offices of physicians, 2
bathrooms, room of the laboratory and the dining room.
It is possible to hospitalize 45 patients.
Department is equipped with electronic clock, fire sensors and
alarm system
State membership in solving
the problems of developing
Russian pharmaceutical and
medical industry
The federal goal-oriented program
“Development of the
pharmaceutical and medical
industry in Russian Federation up
to the year 2020 and following
perspective” was worked out for
development realization of
pharmaceutical and medical
industry
Development of
market of Russian
drugs
According to the expert's opinion
to the year 2020 the market's
volume of drugs in Russian
Federation should extend up to 3
times and should be 300
milliards of roubles per year, and
Russian medicines' market
should be 1,5 trillions of roubles
per year.
Thank you for attention!