Clinical trials

CREATED BY OLES VAKAROV

Today, new methods of diagnosis and treatment
of internal diseases are actively developing

That is why the

two main
research levels
are distinguished:

Primary Secondary
researches research
Categories of
primary studies :
u experimental animal studies
u Clinical trials in which
pharmaceutical, surgical,
radiation treatment methods are
used according to a special
method and protocol on
observation groups
u Research (Survey) that are carried
out in small groups of patients
Secondary research :

u Reviews of literature
u Metaanalysis of several randomized studies
u Clinical recommendations
u Economic analysis
u Described methods of diagnosis, treatment and prevention of
diseases, etc.
Clinical trials
Clinical trial

This is a controlled experimental study, where the tests receive

prophylactic, diagnostic or therapeutic agents for assessing their
efficiency and safety
Gold standard of
clinical trials
PROSPECTIVE RANDOMIZED DOUBLE-BLIND PLACEBO-
CONTROLLED EXPERIMENTAL TRIAL
Types of clinical trials

uncontrolled study
with simultaneous uncontrolled study
Randomized
control (a controlled with historical Cohort trial.
controlled trial.
study without control.
randomization).

Investigation of type Observations (open Description of a

Cross-examination.
- case-control. research). series of cases.

Description of
individual cases.
Randomized trials

In these studies, the

practical identity of Analyze and evaluate
groups of participants the effectiveness of a
in quantitative and particular kind of
qualitative indicators is medical intervention
achieved
Nonrandomized involve the distribution of patients to groups is not
accidentally in the impossibility of random
trials distribution for technical reasons or ethical
considerations
Cohort trial

Provide the formation of two or more groups (cohort)

of patients, of which only an assessment of the
appropriate medical or therapeutic intervention,
although the clinical result is recorded in all groups

Observations can take years (for example, the effect

of smoking to develop lung cancer)
 u Conducted by a survey method, examination,
gathering answers to a specific question
among doctors and patients

Transverse
u Survey and collection of patient information (or
group of patients) are carried out once

(or one- u This makes it possible to establish a picture of

the disease in one patient (or groups of

stage) patients), to clarify the symptoms, to determine

individual manifestations and degree of

research u
severity of the disease
The end result is a description of the disease in
a separate patient, and in a set of options is a
study of the connection of some signs with a
variant of the disease
 u perform in situations where the expected clinical effect is
recorded very rarely or develops slowly

Investigation u form a group of persons from individual cases of an

appropriate disease or clinical effect

of type u select a control group from persons without such a

disease or condition, but similar to important prognostic
"case- characteristics - age, article, concomitant pathologies
calculate in all groups the number of patients who have
control"
u
experienced certain adverse and undesirable influences
u correlation of results is carried out taking into account
known and measured prognostic factors
 Description
Short notices of successful treatment or
manifestation of threatening complications of
pharmacotherapy, which is extremely necessary
of the case for operational medical information

or a series of
cases
Recommendations for patients
should be systematized on the
principle of degree of reliability
of efficiency and expediency
of application
Hierarchy of evidence sources of
information
Systematic reviews
Randomized clinical trials
Cohort trial
Case-control trial
Studies of a series of cases
Research of individual cases
Editorial articles, ideas
Animal trials
In vitro study
Classes of evidence

u Class I - the presence of consensus and / or evidence of efficiency,

expediency of application and favorable procedure.
u Class II - contradictory evidence and lack of consensus on the
effectiveness and expediency of application of the procedure
o IIA - "Chops of Scales" evidence / consensus are inclined to the
effectiveness and expediency of the procedure;
o IIB - "Chops of Scales" evidence / consensus are inclined to
inefficiency and inappropriate application of the procedure;
u Class III - the presence of consensus and / or evidence for
inefficiency and inappropriate application of the procedure, and in
some cases - even its harmfulness.
Grading of evidence

u Ia – systematic review or meta-analysis of randomized controlled trials

u Ib – at least one randomized controlled trial
u IIa – at least one well-designed controlled study without randomization
u IIb – at least one well-designed quasi-experimental study, such as a
cohort study
u III – well-designed non-experimental descriptive studies, such as
comparative studies, correlation studies, case-control studies and case
series
u IV – expert committee report, opinions and/or clinical experience of
respected aothorities
Clinical recommendations

Are based on the levels of reliability

A - high reliability
B - moderate reliability
C - limited reliability
D - a minor reliability
Grading of recommendation

u A – based on hierarchy I evidence

u B – based on hierarchy II evidence or extrapolated from I evidence
u C – based on hierarchy III evidence or extrapolated from I or II
evidence
u D – based on hierarchy IV evidence or extrapolated from I, II or III
evidence
Randomization

This is the method of appointing investigated groups by

random sample

Is the basis of statistical comparison of groups

The goal is the minimum differences between groups,

in all the features are random, not a deliberate nature
Blinding

u Single Blind - when the patient does not

know what treatment it is intended, and the
researcher knows to which the group is a
patient
u Double-Blind - when the patient and the
researcher does not know what treatment is
intended
Placebo
u This is a dosage form that is devoid of an
active component, such as a tablet form
identical to the color and shape, but contains
only an indifferent substance - kaolin or starch,
for injectable forms - an isotonic solution of
sodium chloride
u The use of placebo is not always possible, and
sometimes unethical, for example, when
patients are unacceptable to deprive
effective treatment
"Placebo
u A phenomenon when a person feels better
after taking a drug that is devoid of
therapeutic properties
effect" u A beneficial placebo effect is associated with
his psychological action on a patient
u Placebo has a slight influence only on the
results reflecting the subjective condition of
the patient (sleep quality, pain intensity)
u On clinically important results, the reception of
placebo does not affect (life expectancy,
duration of remission, functional defect, etc.)
Inclusion criteria
NECESSARY TO DESCRIBE THE POPULATION (GENERAL POPULATION)
THAT CORRESPONDS TO PATIENTS IN STUDY
Planning the number of participants

The number of patients included in the

experiment (sample size) should be
substantiated, while exiting:
•predictable level of efficiency
•research structures
•pre-established threshold of statistical
significance of detection of effect
•the prevalence of the disease
Exception criteria

Necessary to create a homogeneous sample, that is, a

smaller variability variability in the initial state and in the
assessment of the effect of the effect of intervention

Among the participants of the clinical study exclude persons

with severe concomitant diseases, threatening conditions or
prevents the experimental conditions

As a result - the statistical sensitivity of the experiment is

increasing
The purpose of treatment of patients in clinical
studies is determined by surrogate endpoints

u Surrogate endpoints - the

parameters of the disease that
provide direct or remote result of the
factor
 u Primary endpoints are leading indicators that
indicate the possible extension of the patient's
life (reduction of mortality from the disease,
recovery, reduction of the term and number of
hospitalization)
u Secondary endpoints are characterized by
Types of improving the quality of life of the patient or
due to reduction of morbidity of non-elegant
endpoints forms of complications, or due to facilitating
clinical signs of the disease
u Tertiary endpoints are indicators that are not
relevant to improving the quality of life or
extension it, but may indicate the possibility of
preventing diseases through the elimination of
risk factors.