1. The need for
scientific research in human beings and its ethical issues. 1.1. Brazilian laws
concerning scientific research in human beings and its validity before the
Brazilian Federal Constitution 2. Procedures of scientific research in human
beings. 2.1. The participant’s free and intelligible agreement. 2.2. The
research protocol. 2.3. The Scientific Research Ethical Committee (CEP). 2.4.
The National Scientific Research Ethical Committee of the Ministry of
Health (CONEP/MS). 3. Operating a
scientific research in human beings.
1. The
need for scientific research in human beings and its ethical issues
In order
to get a constant development in medicine and also to obtain the cure for most
of known diseases, it is necessary to do planned scientific researches.
The main
objectives of scientific researches in Human Beings are to turn better (i) the
diagnoses, therapeutic and prophylactic procedures and (ii) the ethnology
comprehension and the disease pathogen.
This kind
of scientific research must be guided by four main bioethical principles, which
are:
a)
autonomy
principle: the scientific research’s participants must agree freely (the
participants that are incapable of giving a valid agreement can participate in
it only with his/her legal representative’s agreement) after a clear
explanation of (i) all objectives and procedures that will be used during the
research, (ii) all possible risks involved, (iii) all benefits that are
expected from the research, (iv) the safety
of the research, (v) the guarantee to obtain all the clarifications at any time
during the research, (vi) the right to stop participating in the scientific
research, (vii) the guarantee of confidentiality about data collected by the
scientists that involve the participant’s privacy and image and (viii) the way
to indemnify the damages caused by the research to the participant;
b)
non-malevolence
principle: in accordance to this principle, all persons involved with the
scientific research have the obligation to avoid known damages to the
participants, by all possible ways;
c)
benevolence
principle: by this principle, the scientists must make an analysis of all the benefits
and all the real and potential risks, obliging the person responsible for the
scientific research to produce the most possible benefits at minimum risks and
damages to the participants, in such a way that any scientific researches in
Human Beings will only be permitted that: (i) provide the acquisition of knowledge
that helps to understand the disease and also to prevent and reduce it; (ii)
justify the scientific research by the great importance of the expected benefits
against the risks involved; or that (iii) can produce better benefits or at
least the same benefits produced by another existing way of diseases’
diagnosis, prevention and treatment. Thus, the scientific research legitimacy
can be assured with the maintenance of an equilibrium between the objective and
the risks involved in the scientific research;
d)
justice and
equity principles: the scientific research must bring relevant advantages to
the participants and also must reduce at the maximum all the onuses caused by
the research, so the social and humanity goals of the research can be
maintained and also can balance the participants’ interests and the researchers’
interests.
So, obeying all the above principles, the
scientific research will be able to assure the scientific community, the
participants and the State’s rights and obligations.
1.1.
Brazilian laws concerning scientific research in human beings and its
validity before the Brazilian Federal Constitution
The scientific research in human beings is subject
in Brazil to Federal Law # 6.360, of September 23rd, 1976, which
regulates, in a general way, what kinds of medicine, drugs, pharmaceutical raw
materials and other products need to be registered before the National Sanitary
Surveillance Agency previously to its production and selling and also provide
for the need of a previous authorization and license in order to initiate an
enterprise that has as its main activity the production or selling of products
listed at Federal Law # 6.360/76.
Besides that law, there is now the Federal Law #
11.105, of March 24th, 2005, that has rules concerning the security
and control mechanisms of all activities that involve genetically modified
organisms and its derivatives, including trunk cells from human embryo and its
usage in scientific researches.
We also have two Resolutions of the National
Committee of Health # 251, of August 7th, 1997 and # 196, of October
10th, 1996, that regulate in a specific way the scientific research
in human beings.
All the above mentioned Brazilian laws are in accordance
with the Resolution GMC # 129 of 1996, which establishes a common regulation of
scientific research in human beings in MERCOSUL (Commonwealth of Southern
Cone).
Recently the discussion concerning the validity
of Brazilian Federal Law # 11.105/2005 took place in the Brazilian Federal Supreme
Court.
On May 30th, 2005, the General
Attorney of the Republic, filed a lawsuit n.ş ADI – 3510, before the
Brazilian Federal Supreme Court, in order to obtain the recognition of the
invalidity of article 5th and its paragraphs, of Federal Law #
11.105 (which allows the usage of trunk cells of human embryo in scientific
research), of March 24th, 2005, before the Brazilian Federal
Constitution.
According to his allegations, such legal norm violates
the constitutional guarantee of life and human beings dignity, because life
exists since there is the union of a spermatozoon and ovum, i.e., since the fertilization, so the
usage of trunk cells of human embryo in scientific research should not be
allowed, because the human embryo already has life.
Besides that, the scientific research using trunk
cells of human adults is more beneficent than the one done with trunk cells of
human embryo.
In May, 2008, the Brazilian Federal Supreme Court
judged the lawsuit mentioned and has decided for the validity of article 5th
of Federal Law # 11.105, i.e., the
Supreme Court decided for the constitutionality of the usage of trunk cells of
human embryo in scientific researches, since this does not violate the
constitutional guarantee of life and human dignity, because the usage of trunk
cells of human embryo is limited to the ones that have been fertilized in vitro and which the couple decided
not to use for fertilization and consequently it can not generate a human life.
Besides that, the trunk cell must not be able to
generate a life, i.e., it must be not
suitable and also the researchers must have the authorization of the trunk cell
parents.
So, nowadays, according to Brazilian Federal
Constitution it is possible to use trunk cells of human embryo in scientific
researches. In Latin America, only Brazil and Mexico have laws allowing the
usage of trunk cells of human embryo in scientific research.
2.
Procedures of scientific research in human beings
2.1. The participants’ free and intelligible agreement
All the participants of a scientific research
must agree with all the terms of the research by a free and intelligible agreement,
in order to respect the human dignity principle that is assured by article 1st,
item III, of the Brazilian Federal Constitution.
Thus, to
obey such constitutional principle, the simple signature in an application form
by the participants is not enough, but it is necessary to do all the
clarifications about the scientific research in a simple and exact way to them.
According
to item # II.11, of Resolution # 196/96 of the Brazilian National Health
Committee (CNS), the participants’ free and intelligible agreement can be
defined as the patient or his/her legal representative’s assent, without (i)
defects (i.e., without simulation, fraud or error), (ii) dependence,
(iii) subordination or (iv) intimidation, after a complete explanation about
the research’s nature, objectives, methods, foreseen benefits, involved risks
and all annoyance that it can cause to the participants. And this assent also
must be in writing.
So, it is
this kind of free assent that gives legitimacy to the scientific research in
human beings, and has as main objective the protection of the researcher and the institution that
supports the research.
In order
to have legal validity, the assent application form must have these four
requisites:
a)
the assent
application form must be done by the responsible researcher and it must have
clarifications about the objectives, the procedures that will be used, the
possible risks, the benefits foreseen, the participants’ security and
accompaniment, the participants right to obtain all information required, the
participants right to stop participating in the scientific research, the secret
guarantee about all confidential data and the indemnity ways for the damages
caused to the participants;
b)
it must be
approved by the Scientific Research Ethical Committee, that gives the referendum
to the research;
c)
it must be
signed by the participants of the scientific research; and
d)
it must be
done in two copies; one belongs to the researcher and another, to the
participant.
Those requisites are imposed by item # I-9, in
fine, of the 4th Helsinki’s Declaration, which requires preferentially
a written assent.
2.2
. The
research protocol
According to item # II.3 of the National
Committee of Health’s Resolution # 196/96, the research protocol is a kind of
project of the scientific research that will be done, which must contain
documents that describes the main aspects of the research, information related
to the participants of the research, to the researchers qualities and all the responsible
people for it.
This research protocol must be submitted to an
ethical revision, what will occur only if it contains:
a)
the
qualifications of the responsible researcher, and the patrons of the
organization where the scientific research takes place;
b)
the
descriptive title of the project, mentioning the substances that will be used
in the research;
c)
the research
summary containing:
1.
the research
objectives;
2.
the
hypothesis that will be researched;
3.
the
antecedents and the scientific data that justify the experimentation;
4.
a detailed
and ordered description of the research project;
5.
the analysis
of the possible risks and the foreseen benefits;
6.
the total
duration of the scientific research;
7.
a detailed
characterization of (i) the researcher liability, (ii) the research
institution, (iii) the research promoter and (iv) the research patrons;
8.
the justifiable
criteria of the research suspension or of its end;
9.
a
description of the research location;
10.
a
demonstration of infrastructure existence needed for the research development
and also for solving all the problems caused by the scientific research;
11.
the detailed
budget of the scientific research;
12.
the
demonstration of agreement about the property of the information obtained by
the research;
13.
a
declaration that the scientific research results will be published, even if
they are unfavorable; and
14.
a
declaration about the material and the destination of it and of the data
obtained with the research.
d)
the
information and the description of the participants and of the community
participant of the scientific research, containing (i) a detailed description of the methods
that will be used, (ii) the identification of the research material, (iii) a
description of the participants’ recruitment plan, (iv) the model of the assent
application form, (v) a description of all risks involved and an evaluation of
its gravity, (vi) a description of all steps that will be taken during the
scientific research, in order to protect the participants and to minimize all
risks involved and (vii) a foresight of the reimbursement of all expenses
spared by the scientific research participants;
e)
the
scientific researches résumés, i.e., the résumé of the responsible
researcher and of all researchers involved in the scientific research; and
f)
the
compromise term of the responsible researcher and also of the institution to
accomplish all the scientific terms.
So, those are the requisites that a research
protocol must have in order to be submitted to an ethical revision, what is one
of the previous requests for the beginning of a scientific research in human
beings.
2.3.
The Scientific Research Ethical Committee (CEP)
According to item # II.14 of the National
Committee of Health’s Resolution # 196/96, the Scientific Research Ethical
Committee is a committee formed by independent members graduated in a variety
of areas, which has public function and has a consultative, deliberate and
educational character, and it is created to defend the participants interests,
integrity and dignity and also to contribute to the research development
according to all ethical rules.
The Scientific Research Ethical Committee has the
following main functions:
a)
review the
research protocols of all scientific researches in human beings to guarantee
and to maintain not only the participants’ integrity, but also their rights;
b)
give an
opinion identifying the essay, the documents analyzed and the dates of its
review and classifying the research protocol as (i) approved, (ii) pending
(when the research protocol is acceptable, but the Scientific Research Ethical
Committee has identified some problems in the research protocol, in the assent
application form or in both, and recommends a specific review or requires a
relevant information that must be accomplished in 60 days), (iii) retired (when
the specific review is not made between sixty days, in the case of the research
protocol being classified as pending), (iv) not approved or (v) approved and
sent to the analysis of the National Scientific Research Committee of the
Ministry of Health (CONEP/MS);
c)
accompany
the research project execution by annual reports made by the researchers;
d)
receive
denunciations from the research
participants or anybody else about abuses during the scientific research;
e)
receive
notifications about contrary facts that can change the normal schedule of the
study, when the Scientific Research Ethical Committee must decide for the
continuity, the modification or the suspension of the research, adjusting the
assent term, if it is necessary;
f)
require to
the institution board, where the scientific research takes place, an
investigation of any denounce received about ethical irregularities in the
research;
g)
notify the
National Scientific Research Ethical Committee of the Ministry of Health about
ethical irregularities in scientific researches, always when there are proofs.
Thus, all scientific research in human beings must
be appreciated by a Scientific Research Ethical Committee that is created by
the institution where the research will take place.
If it is
not possible to create a Scientific Research Ethical Committee, the research
protocol must be submitted under the appreciation of another Scientific
Research Ethical Committee created by another institution and indicated by the
National Scientific Research Ethical Committee of the Brazilian Ministry of
Health (CONEP/MS).
According
to Brazilian Laws, the Scientific Research Ethical Committee must keep a file
for five years after the end of the scientific research, the research project,
the research protocol and all reports, but it must maintain all information
about the research under seal.
2.4. The National Scientific
Research Ethical Committee of the Ministry of Health (CONEP/MS)
The
National Scientific Research Ethical Committee of the Ministry of Health is an
administrative court, which is subordinated to the National Committee of Health
(CNS) of the Ministry of Health.
That
administrative court has the following functions:
a)
analyze the
ethical aspects of the scientific research in human beings;
b)
register all
the Scientific Research Ethical Committees created to each scientific research;
c)
approve and
accompany the research protocols submitted under its analysis;
d)
create
ethical rules to be applied to scientific research in human beings;
e)
and act as
the last administrative court to analyze appeals against decisions of other
administrative organs.
So, as we can conclude from the main functions of
the National Scientific Research Ethical Committee, it is a kind of
administrative organ that controls all legal procedures and requisites of a
scientific research made in human beings, but as a final administrative court
that belongs to the Ministry of Health.
3. Operating a scientific research
in human beings
Since the group of work is formed, they must
prepare the research protocol, that must be signed by the responsible
researcher and all the other researchers.
Afterwards, it must be sent to the Scientific
Research Ethical Committee, which is previously created specifically to this
research and registered before the National Scientific Research Ethical
Committee of the Ministry of Health.
Thereafter, it is necessary to begin a study
diary, which will contain all information about the facts that will occur since
the beginning until the end of the research.
If the research protocol is approved by the
Scientific Ethical Committee, this organ also becomes responsible for the
ethical aspects of the research, but it is important to notice that the
researchers’ liability concerning the ethical and legal aspects of the
scientific research still exists.
It is important to know that there are some kinds
of research protocols that the Scientific Research Committee must send to the
National Scientific Research Ethical Committee of the Ministry of Health’s
approval.
It will always occur with all research protocols
that the Scientific Research Ethical Committee considers necessary the National
Scientific Research Ethical Committee of the Ministry of Health’s approval and
also with all the research protocols involving one of the following objects:
a)
human
genetic;
b)
human
reproduction;
c)
new or non
registered drugs, medicines, vaccines and diagnosis tests or that are not
registered in Brazil;
d)
scientific
researches related to new modality, indication, dose or administration way,
that are different to the normal standard, including the combined employment;
e)
new
equipments, raw materials and materials in general or even if they are not
registered in Brazil;
f)
new
procedures that are not approved by the medical literature;
g)
indians;
h)
biosecurity;
i)
scientific
research that is coordinated from a foreign country, that has foreigners
(researches, institutions or alike) involved or that involves the sending of
biological material abroad; or
j)
all projects
that the Scientific Research Ethical Committee understands that need the
National Scientific Research Ethical Committee of the Ministry of Health’s previous approval .
In all cases above, the research protocols will
be sent to the National Scientific Research Ethical Committee of the Ministry
of health approval. After that, the research protocol must be sent to the
National Sanitary Surveillance Agency
in order to obtain its approval. And only after its approval, the research
protocol will be able to be executed by the researchers.
If the research protocol does not have one of the
objects listed in item # VIII.4, letter ‘c’, of the National Committee Health’s
Resolution # 196/96, it will be able to be executed immediately after the
Scientific Research Ethical Committee’s approval.
During the research project execution, the
responsible researcher is obliged to suspend the scientific research always when
there is a risk or some damage to the participants’ health, which has not been
foreseen in the free and clear assent application form.
When it is discovered another research method
that is better than the one used in the scientific research, the responsible
researcher must offer to the participants the usage of this new method.
If any relevant fact or adverse effect changes
the normal course of the research that had been foreseen in the research
project, the responsible researcher must communicate it to the Scientific Research
Ethical Committee.
Finally, the researcher, the patrons and the
institution must assume the liability to give full assistance and indemnify all
participants who suffered damage or any kind of complication caused by the
foreseen risks, even if the damage and the complication were not foreseen in
the free and clear assent application form. It is important to notice that the
participant right to receive full assistance and indemnity is not renounceable.
