Research ethics in the Brazilian CEP-CONEP system : necessary reflections

Brazil counts with a well-known human research ethics evaluation system – the CEP-CONEP System, which has been in operation for 20 years. However, its efficacy and effectiveness have been questioned, criticized and put in check, especially in recent years. This work is based on the author’s experiences as faculty member in the field of bioethics, researcher and former coordinator of a CEP and aims to critically reflect on the role of ethics as a driving force of all the steps of the research process, and discuss some deadlocks, gaps, and challenging issues which must be urgently considered and addressed by the CEP-CONEP System. Issues that deserve to be permanently and critically reevaluated are discussed to cope with several challenges, providing a real scientific advance, linked to the social and ethical advance of science, such as the issue of social relevance of the study and its yield/contribution to society; the ethical and political aspects involved in research priorities; the advance of the basic initial appreciation and of the simple normative evaluation; the need for the valorization and recognition of the Ethics Committees’ work; the System’s discredit due to poor infrastructure, post-study care, among others.


Introduction
The discussion about ethics takes on a high significance in the current context, considering its importance in the face of a reality where an advanced technological and scientific development coexists with a diversity of issues in the model of society in which we live is observed, such as emerging and persistent diseases; hunger; misery; violence; racism; social exclusion; disrespect to human beings and the environment, among many others that tamper with life.It should be noted that this tension between scientific progress and social development brings ethics to the heart of debate.Thus, such reflection becomes indispensable to the formation, as well as to practice in research in any area.
It is well known that science has provided increased knowledge over time, which necessarily was not based on ethical/moral progress.This growing disparity has an adverse impact on the different spheres of life, and in this particular case, on research activity.
Thus, much abuse has been denounced in this area in the history of mankind.The concern shown for the cure of diseases and the advancement of science was not fully projected on the subjects who participated in the studies, since many of them were placed in situations of inequality, vulnerability and moral suffering 1 .The study entitled Ethics and Clinical Research 2 published in 1966 showed that a great number of studies published in the most respected international journals at the time were considered unethical by its author.
Currently, while ethical principles used to guide the research process, to a certain extent, are considered universal, ethical conflicts and abuse regarding participants are still evident.An example in the recent history of international and national research is a 1997 publication in the prestigious scientific journal New England Journal of Medicine, which revealed the results of studies on the mother-to-child transmission of HIV carried out with African women through placebo-controlled groups 3 .This conduct characterized the use of a double standard in performing the research, since it is believed that this type of procedure would never have been accepted in developed countries, depending on the place of its accomplishment and the vulnerability of the participants involved.
In Brazil, the press reports about a group of São Raimundo do Pirativa-Amapá riverine people who received R$ 12.00 (twelve reais) to receive 100 mosquito bites over a year stand out since, according to reports, many have contracted malaria 4 .
Valuation and care for research subjects are established in the post-WWII period and can be materialized in the various documents that regulate the matter, both at national and international levels [5][6][7][8][9] .The implementation of these regulatory guidelines contributed significantly to reflection, education, and regulation regarding human research-related ethical precepts in our country.However, these documents have not been fully effective instruments towards ensuring the safety, integrity and respect for the people involved in research 1 .
Brazil has a recognized system of ethical assessment of human research, linked to the National Health Council (CNS), composed of the National Commission for Research Ethics (CO-NEP) and the various Research Ethics Committees (CEP) distributed in all regions of the Country.This CEP-CONEP System was established by Resolution CNS 196/96, and has been in operation for 22 years.
However, with an increased number of studies in Brazil, especially in recent years, efficacy and effectiveness of the CEP-CONEP system have been questioned, criticized and put in check.Thus, this work aims to critically reflect on the role of ethics as the guiding thread for all stages of the research process and to point out deadlocks, gaps and challenging issues that must be considered and addressed as a matter of urgency by the CEP-CONEP System to ensure the social control and construction of a conscious science, as Edgar Morin warns 10 .
It is important to state that the text is based on the author's experience as a teacher-researcher in the field of bioethics and former CEP coordinator.It is also worth noting that although this text focuses on the CEP-CONEP System and, consequently, human research, some of the aspects discussed here are also adequate for other studies.

Ethics in the research process and the role of the CEP-CONEP system
It can be clearly observed that the CEP-CO-NEP System has faced and is still facing different "moments" in its twenty-two years of existence, namely: The moment of its foundation, which is related to the approval of CNS Resolution 196/96, establishing a social control system, to analyze and follow the ethical aspects of human research; the moment of expansion and of con-solidation, which are still in full swing (considering that an increased number of CEPs has been noted since 1996 in the various education and research institutions in the Country, totaling 833 Committees in January 2019 -according to CO-NEP 11 data).However, the System must urgently enter effectively the moment of permanent evaluation and critical review, so that in practice it may really take care of the countless challenges, providing a real scientific advance, combined with the ethical-social advance, thus ratifying, above all, respect for people's dignity (research participants).This text was conceived and structured to contribute with this last moment.
Ethics must be incorporated as an inseparable part of scientific knowledge.Thus, it is essential to be aware that it should be the cornerstone of the whole process for making decisions, choices and actions, of those involved in scientific activities.The aim is to strike a balance between the process of scientific investigation and the protection of the people who participate in it, seeking in this course to promote the exercise of respect and responsibility for a better quality of life and dignity for all.It would be an alliance between science and humanity, as Potter 12 proposed in the genesis of bioethics.
Thus, when talking about research ethics, one would have to have the clarity that this should permeate the whole research process.We shall address issues included in this research process, pointing out concrete ethical problems that must still be tackled by the CEP-CONEP System.For educational reasons, we decided to present them based on the following research steps: a) Design and elaboration of the research; b) Evaluation and monitoring by Research Ethics Committees; c) Conducting the research; d) Post-study stage; and e) Dissemination of its results.a) Design and elaboration of the research One rarely spoken of and debated aspect in scientific terms, but included in Resolution CNS 466/12 8 (currently in force), is the issue of the social relevance of the study and its yield/contribution to society.In other words, when planning a research, such planning cannot be dissociated from a reflection about the probability that the study will contribute to health, well-being, improvement of the living conditions of the population involved, or even with knowledge of the population involved, mainly when financed with public resources.
This way of thinking will cause reflection on the values and purposes involved in the process of researching and generating knowledge, thus confirming that it is an ethical issue.Therefore, the following questions arise: What to research?Why research a particular subject?Why prioritize certain areas to the detriment of others?And going further: Because public funding for research funding are limited, should we, therefore, establish priorities?We note that the answers to these questions also lead the debate to the political field, and so there is a need for greater societal engagement, which justifies and supports the fact that the CEP-CONEP System is linked to the CNS.However, in spite of this linkage with the CNS, it is important to emphasize that, in practice, this debate has not effectively reached the society in general, showing that the educational function and social control expected from said System have not yet materialized effectively.
We should emphasize that in the area of clinical research, the choice of what to research should be guided by the needs and priorities of society, especially when financed by the State, based on epidemiological and sociodemographic data.However, this is not the case most of the time.
At present, the largest sponsor of clinical trials for the development of new drugs is the pharmaceutical industry.This segment consists of companies that follow the market logic.In this rationale, one must see which activities provide the highest financial return, in order to invest and ensure profits; something which is mostly not in line with the priority needs of society.Angell 13 warns "about the prudence of entrusting the development of a medicine to an industry whose responsibility is fully geared toward investors, not the public (except in the narrow sense that medicines should be safe and effective)".
Another issue that deserves reflection is that, because the scientific production within the Higher Education Institutions (HEIs) is often more recognized and valued than teaching and extension actions, everyone wants, or is somehow "pressured" to investigate and show results.This has sometimes generated within academia a process based on an inverse and perverse rationale, where publication becomes the major reason to conduct research, and the quantity factor is the main parameter to measure the teaching work.It is observed that many studies lack a scientific and social justification that supports them (for example, they repeat substantially or totally results previously proven), or they do not follow scientific rigor, among other aspects, but they are performed.This is a challenging issue that must be faced by the Brazilian System in conjunction with other sectors of society.
It is worth emphasizing that, an evident, not uncommon example is the fact that students just entering the undergraduate course already want to publish.But publish what?Their will and focus should first be learning how to learn, learning how to be and learning how to research, and then publishing this new knowledge.However, they are compelled by this perverse logic of production (with an end in itself), as they will have to make an "excellent" resume so that they can have better future opportunities.
In this way, it is believed that CONEP and CEPs should approach these issues, exercising more properly their educational dimension and complex ethics management, aiming at a more responsible and less utilitarian research education and practice.

b) Evaluation and monitoring by Research Ethics Committees
When talking about a system of evaluation of research ethics, this cannot be limited to the initial evaluation of the research and normative evaluation by the CEP-CONEP System, since standards, while necessary, are incapable of covering the complex nature of emerging issues, and the exercise of an ethical culture is indispensable and urgent.As Rego 14 warns, rather than imposing rules on the stakeholders involved in the issue, we must encourage the development of a moral competence so that they can make judgments and act accordingly.Thus, the author points to the significant role of education, whether in undergraduate or postgraduate studies, to stimulate critical reasoning for future professionals and scientists.
However, it is salutary to point out that members of the Ethics Committees should be mainly found within this same perspective.These members should be chosen from an appropriate profile, where the guiding line of their work should be protection, respect for the dignity of the subjects and the promotion of an ethical culture.To this end, they should be willing to make a continuous exercise of criticism and reflection, seeking to escape the accommodations of uniform, easy and ready-made answers of standards since studies in the most diverse areas of knowledge bring about different questions and challenges, which cannot be analyzed from a single perspective.For example, a social research in humanities cannot be evaluated under the same parameters used in the analysis of a clinical trial, and vice versa; or even, in the case of two clinical trials, each will have ethical peculiarities that should be evaluated, based on their particular characteristics.
Currently, the issue of consolidation of the CEP-CONEP System also involves the need to enhance and recognize this work of ethics management in institutions.It is observed that the demand for the number of studies is increasing progressively, and that, for example, due to the lack of encouragement and support given to teachers of an HEI to participate in the CEP, most of the time, they refuse to do it.This has resulted in a shortage of skilled and well-qualified people willing to act as members.This important factor has led, therefore, to a lower quality or a delay in the progress of ethical judgments (since there will be a much greater demand than the actual work capacity of the Committee).This situation causes widespread dissatisfaction, which may affect (and is already affecting) the credibility of such an important System for the implementation of research ethics.
The issue of a beyond reasonable delay for an effective ethical evaluation because of lack of structure is in itself a serious ethical issue.Delaying the approval of the onset of a research, or even delaying the approval of a new version of an Informed Consent Form, for example, in the area of cancer, where the time factor is paramount, raises important ethical issues for the CEP-CO-NEP System itself, allowing criticism and attacks that could be avoided, or even that would never be there if the System worked in its structural fullness.
Hence, the infrastructure and working process of the CEP-CONEP system, in all areas, is a point that deserves to be reviewed urgently.There is a need to rethink and reevaluate such aspects.It is not sustainable to continue in an almost "amateurish" perspective, dependent on the goodwill of "volunteers" and Committees which often do not have a basic operating structure.The current demands signal and demand an inevitable "sector professionalization", with the full support of the institutions involved and all spheres related to the CEP-CONEP System.Many should ask themselves: what was meant by professionalization?It would at the very least allow the Committees to be staffed with qualified people to make the ethical judgment of research protocols, free of conflict of interest, acting freely, having their work recognized and, mainly, working with a structure appropriate to the size of the demand.c) Conducting the research Scientific rigor in the design and conduct of research should be a first imperative.Such a process should be free from conflict of interest, which may influence or manipulate data, leading to non-true results, especially when talking about science based on scientific evidence.
In 2005, a paper published in Nature 15 released a study, where 35% of American scientists reported having had at least questionable behaviors and practices over the last three years.Examples of what has been reported by them are plagiarism; use of other people's ideas without due permission; breach of confidentiality; lack of concern and disregard for the welfare of the participants; counterfeiting, creating and concealing data and modifying the design, methodology and results, abiding by the pressures of financiers.These diverse issues require a system prepared not only to evaluate the initial protocols, but also the partial and final reports, but fundamentally to be able to follow effectively the conduct of the research.Such a question poses a great challenge: the need to structure a system that is more "equipped" in all aspects and levels, as explained above.Today, the system can only meet the initial evaluation, and often fails to meet the deadlines.
A serious issue is accepting a double standard in research, when it comes to countries and/or populations mainly vulnerable at the socioeconomic level.This would be to support ethical relativism, which could allow cruelty and injustice, as was the case of the aforementioned study on HIV mother-to-child transmission, carried out with African women, through placebo-controlled groups 3 .This aspect is something important for reflection and debate in the Brazilian perspective, since a significant number of multicenter studies are being developed in the Country and in the world.
Therefore, when talking about multicenter studies, it is worth highlighting those related to drugs' clinical trials.It is sometimes observed that such research main proponents are pharmaceutical industries, based in other countries, where the Brazilian research center and its members (doctors, nurses, etc.) are often paid to simply recruit Brazilian patients (who, besides being vulnerable to the disease, are socioeconomically vulnerable), receiving per patient, and applying protocols.
Thus, these professionals are not usually allowed to participate in the elaboration and design of the research, the full dissemination of results and the appropriation of the knowledge and technology generated.You have to ask yourself: is there a partnership and cooperation?Who are the biggest benefits being generated for?These are issues foreseen in Resolution CNS 466/12 8 and must have control of the CEP-CONEP System, so that they can be fully respected.
Another point that also deserves to be debated and which also involves health professionals/ researchers is the conflict generated when, for example, the health professional assumes the dual relationship with the research subject, especially in clinical studies: to be a caregiver (responsible for the treatment of the patient) and a researcher at the same time.The emergence of conflict of interest in this case is cause for concern, which has led, for example, to the belief that the consent process and the ICF, for the participation of patients in the research, should or could be conducted and applied by another person with no direct relationship with the research, reducing the potential impact of these conflicts 16 .Or, in a more direct perspective, which for many may be radical, but which would be more correct and pertinent when it comes to ethics, the functions of researcher and caregiver should not be exercised by the same professional.Recommendations such as these should be promoted and debated by the CEP-CONEP System.
Necessary and urgent demand for the debate on public health and ethics in research is to investigate why subjects agree to participate in clinical research.Is it mainly due to a lack of treatment options, difficult access to medications and complementary tests of high complexity 17 since there is a problem in accessing the public health service in our country?Or due to a solidary and conscious feeling aiming to contribute to the progress of science?Or, still, due to the search for a possible cure?
The principle of autonomy is greatly exalted; however, in some situations it is necessary to question about this autonomy and the human being's dignity: is there autonomy, where the means to meet the most basic needs of being are lacking?In this setting, too, questions arise around the ICF: could it be that, in a state of socioeconomic vulnerability and illiteracy, a signed informed consent form, instead of a free and clarified one, be most often than not achieved at most?Studies, research and monitoring are lacking in this regard.CONEP and the local CEPs should study these and other issues daily, in a process of permanent evaluation and critical review of the practice.
d) Post-study stage This topic will bring to reflection a discussion that deserves to be analyzed by all those involved in the research: What care is given to the people who participate in the studies after its completion?What knowledge is passed on to them?In clinical trials with medicines (if their positive ef-fect has been proven), have patients been assured of continuity of treatment after study completion?We believe that answers to these questions will be mostly none or few.Public universities themselves, in general, have not given the proper feedback to the communities and the participants.We often have a true culture of utility with a one-way path, where data are collected for purely academic activities and goals, following the perverse quantitative logic of scientific production.Similar behaviors cause post-study care to become gaps to be addressed by the CEP-CO-NEP System, through continuous dialogues with the various sectors involved. e

) Dissemination of its results
According to current Brazilian ethical standards -Resolution CNS 466/12 8 , public disclosure of results is imperative.At this stage, ethical issues are also evident, either regarding authorship (where due credits are not established correctly), or by hiding data that were not satisfactory against the initial hypothesis; or, still, the lack of strategies for disseminating research results to the general public, which are not limited to scientific journals, so that the population can more easily have access to the knowledge produced, and so forth.
Thus, the question is a one, since which are the strata of society who read the best scientific journals (for example -QUALIS A)? Does society in general have access to this knowledge?What for and for whom do we do a research and publish?
Another important item is non-disclosure of data due to many factors, including that most scientific journals do not want to publish research with negative results.Such conduct puts in check the credibility of science, especially evidence-based, because negative research findings are part of knowledge and must be publicized and known.Depending on "hidden" data, damage can be generated to society, with the possibility of being considered a crime.
How do we address these issues?This is the challenge for a System that wants to consolidate itself as a manager of ethics.

Final considerations
The need to conduct human research in all areas of knowledge is indisputable and evident.However, one must have the lucidity that norms, while essential, alone, do not ensure ethical research.The issue involves complicated aspects and challenges, which require a cumbersome coping action, driven by a well-structured ethics management system, to properly manage them.
Thus, some of the issues that are currently being experienced in Brazilian research, if not confronted with some urgency, place the important and necessary CEP-CONEP System (thought and established to be a transparent social control system, for the sake of ethical science, which values the dignity of research participants) in disrepute.This discredit favors those who seek other primary interests, mainly economic, to seek their extinction, or, at least, propose changes that overly relativize the ethical rigor and care with the research participants.
Then, it is necessary to stimulate and promote an ethical culture in research, in which those involved can recognize the challenges related to this process and have the sensitivity to act with equity, justice and respect, with a responsibility for present and future generations.It is hoped that ethical intentions become ethical actions.However, in order to achieve this, it is imperative to study and evaluate the CEP-CONEP system, as well as to provide it with sufficient human and material resources to meet the complex challenges and also value and account for the work of the members of the Committees within the institutions.
Therefore, this work reflects on urgent challenges that must be faced by the Brazilian system and all those who want responsible scientific development that respects the dignity of human beings.It also contributes with the scarce academic production on the contemporary competences of the CEP-CONEP System.