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Conteúdo (article):

Ética em pesquisa com humanos vulneráveis: estudo de revisão
Ethics in research with vulnerable human subjects: a review study
Ética en la investigación con sujetos humanos vulnerables: un estudio de revisión


Stella R. Taquette
Full Professor at the Scholl of Medical Sciences at University of the State of Rio de Janeiro – FCM-UERJ
Address: Av. Professor Manoel de Abreu 444 - Vila Isabel, Rio de Janeiro – RJ. CEP 20.550-170.
E-mail: taquette@uerj.br
ORCID: 0000-0001-7388-3025
Acknowledgement
This study received the support of Faperj – Programa Cientista do Nosso Estado (Scientist of Our State Program) and UERJ – Programa Prociência ao apoio no desenvolvimento de pesquisas (Pro-science Program for Research Development Support).

Resumo
Indivíduos vulneráveis amiúde não têm seus direitos garantidos ao serem ou não recrutados para pesquisas. Este estudo de revisão tem por objetivo analisar o conhecimento produzido em investigações sobre ética em pesquisa com populações vulneráveis para contribuir com maior proteção e justiça a esse público. Foi feita busca de artigos nas bases de dados PubMed e BVS com os termos do mesh database “Ethics, research” AND “Vulnerable populations” nos últimos dez anos. Foram encontrados 240 estudos, sendo 104 duplicados. Após leitura dos títulos, resumos e textos completos foram eleitos 33 artigos para análise de conteúdo temática. Três temas principais emergiram: vulnerabilidade x justiça; coerção/exploração/dumping ético; e desafios/barreiras para garantia da eticidade da pesquisa. Concluiu-se que para condução ética de pesquisas com populações vulneráveis com garantia da devida proteção e oportunidade de participação nos estudos que as beneficiem é necessário: o aperfeiçoamento das normas éticas internacionais quanto às populações vulneráveis; levar em consideração as particularidades dos sujeitos assim como o contexto em que se encontram; garantir acesso ao melhor tratamento existente nos ensaios clínicos; e utilizar estratégias específicas e individualizadas para minimizar suas vulnerabilidades.
Palavras-chave: ética em pesquisa, populações vulneráveis, beneficência.

Abstract
Vulnerable individuals often do not have their rights guaranteed when they are recruited or not to researches. This review aims to analyze the knowledge produced in studies on ethics in research with vulnerable populations to contribute to greater protection and justice for this population. A search for articles in the PubMed and VHL databases was carried out using the mesh database terms “Ethics, research” AND “Vulnerable populations” over the past ten years. A total of 240 studies were found, of which 104 were duplicates. After reading the titles, abstracts and full texts, 33 articles were selected for thematic content analysis. Three main themes emerged: vulnerability x justice; coercion/exploitation/ethics dumping; and challenges/barriers to ensuring ethics in research. It was concluded that in order to conduct ethical research with vulnerable populations, ensuring due protection and opportunity to participate in studies that benefit them, it is necessary to: improve international ethical standards regarding vulnerable populations; take into account the particularities of subjects as well as the context in which they find themselves; ensure access to the best treatment available in clinical trials; and use specific and individualized strategies to minimize their vulnerabilities.
Keywords: Ethics, Research, Vulnerable Populations, Beneficence

Resumen
Las personas vulnerables a menudo no tienen garantizados sus derechos cuando son reclutados o no para investigaciones. Esta revisión tiene como objetivo analizar estudios sobre ética en investigación con vulnerables para contribuir a mayor protección y justicia para este público. Se realizó una búsqueda de artículos en PubMed y BVS utilizando los términos “Ética, investigación” y “Poblaciones vulnerables” en los últimos diez años. Se encontraron 240 estudios, 104 de los cuales eran duplicados. Luego de leer los títulos, resúmenes y textos completos, se seleccionaron 33 artículos para el análisis de contenido temático. Surgieron tres temas principales: vulnerabilidad versus justicia; coerción/explotación/dumping ético; y desafíos/barreras para garantizar la ética de la investigación. Se concluyó que para realizar investigaciones con poblaciones vulnerables, asegurando la debida protección y la oportunidad de participar en estudios que las beneficien, es necesario: mejorar los estándares éticos internacionales respecto a las poblaciones vulnerables; tener en cuenta las particularidades de los sujetos así como el contexto en el que se encuentran; garantizar el acceso al mejor tratamiento disponible en ensayos clínicos; y utilizar estrategias individualizadas para minimizar sus vulnerabilidades.
Palabras clave: ética de la investigación, poblaciones vulnerables, beneficencia.

Introduction
Research ethics codes are applicable to all human beings. Some populations, however, are in situation of greater vulnerability and lesser autonomy, therefore in need of a differentiated, broader and individualized protection. Vulnerabilities refer to disadvantage situations that reduce the capacities to defend their interests adequately. The nature of these vulnerabilities can be social and economic, deprivation of freedom, health condition, among others. The groups most often identified as vulnerable are children, adolescents, prisoners, persons with mental health problems, and certain ethnocultural minority groups1.
The reliability of scientific research depends among other aspects on the ethics with which it is conducted, especially in the case of vulnerable populations, from the viewpoint of protection as well as beneficence and justice2. These populations are often inhibited from participating in studies due to the absence of full autonomy. However, in specific cases, not being able to participate may be unfair, because it will prevent them from benefiting of the results3.
Given the diversity of situations of vulnerability to which human beings may be submitted, it is challenging to ensure ethics in research with vulnerable individuals. As much as they must be protected, their rights of participation cannot be eliminated. Some vulnerable persons have no autonomy and others have no opportunity. The aim of this study is to analyze and synthetize the knowledge produced in empirical researches on the theme ethics in research with vulnerable populations, with the aim of contributing to overcome hindrances as to ensure ethics in studies with these individuals.

Method
The study carried out the review of articles on ethics in research with vulnerable populations on two databases that comprise most of the scientific journals in the field of health, namely PubMed (National Library of Medicine) and VHL (Virtual Health Library). The search was made on May 2, 2024, and was repeated on August 5, 2024, using the following descriptors: “Ethics, research” AND “Vulnerable populations”. PubMed made available 107 articles and VHL 133, with 104 in duplicate. The inclusion criteria for the selection of the analyzed studies were: original articles resulting from empirical investigations on the theme ethics in research with vulnerable populations, published in the past ten years, and whose full text was available.
In the first reading of the 136 titles and abstracts, 97 were eliminated for not fulfilling the inclusion criteria. After the full reading of the remaining articles (39), six were eliminated for the same reason. Finally, 33 studies were elected for the analysis, according to the diagram shown on Figure 1.
The articles underwent thematic content analysis4 with the support of WebQDA qualitative data analysis software. Initially, the articles were read and reread to obtain the sense of the whole and of the particularities. Next, they were grouped according to the most prominent themes and classified into thematic categories. Finally, an interpretative synthesis was made in a dialogue with the literature.

Results and Discussion
The 33 studies analyzed originate from almost all continents. Most of the studies (18) were conducted in North America, with 13 by researchers from the United States of America (USA), three from Canada and two from Mexico. In second place comes Europe with seven studies, with four carried out in the United Kingdom, one in the Netherlands, one in Sweden and one in Belgium. Next comes Africa with four studies, with two conducted in South Africa, one in Kenya and one in Malawi. Two studies represented Asia, one in the Philippines and one in Indonesia. One study was conducted by a researcher in Australia and one in South America, namely in Brazil.
Following the exploratory reading of the articles, three categories emerged, which are: I - vulnerability x justice; II - coercion/exploitation/ethics dumping; III - challenges and barriers in ensuring ethics in research with vulnerable populations.

I - Vulnerability X Justice
In this category were classified the articles that discuss the balance between the protection to individuals who are in a situation of vulnerability and their right to participate in studies that benefit them. Among the articles analyzed, 12 were included in this category and are listed on Table 1.
Some of the studies included in this category show that vulnerable populations are prevented a priori from participating in experiments, because research ethics committees (RECs) often do not approve researches of this nature. In a study on experiments with individuals deprived of freedom, the authors interviewed members of RECs in the United Kingdom, where ethics regulations are very restrictive. The authors identified that there is a low participation of prisoners in researches (0.7% of the studies). It is an unfair situation, because many prisoners could benefit from the studies, either directly from the results, or indirectly through financial gain or other benefits such as the satisfaction of contributing for society and feeling useful5. The motivation of individuals deprived of freedom to participate in studies was shown also by Hanson et al. (2015)6. When participants were interviewed, they stated their interest in contributing to society, having access to health care, and receiving financial compensation. A similar situation of impediment of participation in research due to restrictions by ethics committees was found in a Brazilian study7. The author reports hindrances to approve a research project on violence against women with disabilities, due to ableism of the REC\'s members. Persons with disabilities are treated as unable, although Brazil is a signatory of the Convention on the Rights of Persons with Disabilities, which ensures the legal capacity of these persons to participate in all acts of civil life, including researches.
The radical position of RECs regarding researches with vulnerable persons may be due to the lack of consensus in the academic literature on the meaning of vulnerability and to the measures to be taken in relation to research participants who might be in greater risk situation. The application of this concept of vulnerable in the sphere of investigation is controversial, because for some it is excessively broad and for others too restricted. An in-depth analysis of 11 ethics policies and guidelines of countries/group of countries with similar legal norms (Canada, United Kingdom, USA, Australia and European Union) on the concept of vulnerability, found that only three documents explicitly define vulnerability. The authors argue that besides respecting the autonomy of individuals, the protection of vulnerable persons implies the opportunity to participate in researches that benefit them1.
Other studies included in this category emphasize the importance of highlighting the benefit that an experiment can provide to certain vulnerable social groups, whose participation, therefore, should not be prevented. In a study with orphan and fostered children, who are doubly vulnerable due to their young age and parents\' absence, the authors defend the fairness of their inclusion in research because these can benefit them directly8. Another population group with great vulnerability are drug users, due to the stigma, violence, legal problems and social disadvantages that contribute to susceptibility to diseases and privations. In order to implement public policies for this public, it is necessary to have scientific evidence. Therefore, these individuals should have the opportunity to participate in studies on their benefit9. Some authors consider ethically acceptable that children participate in low-risk researches, without perspectives of direct benefit to them, but rather to the community. Certain diseases need clinical trial in children, because mortality is higher in childhood and without this participation, it is impossible to produce vaccines or to know which are the appropriate dosage of medicaments10. The inclusion of children in this type of research would be a matter of justice.
In an ethnographic research with oncological patients, it was found that those who live in places with no public health service consider that participating in clinical trials is their chance to receive treatment. Some of them have no notion that they are participating in a research, which characterizes a therapeutic misconception, a coercion, an unethical conduct in the recruitment for the investigation. However, the author considers that the benefits they receive are more relevant than the therapeutic misconception in the context of the inequities in cancer treatment11. This benefit was also acknowledged by populations of migrants and pregnant women in conflict zones12. Besides the access to quality health care, they receive financial resources. They accept to participate in studies despite recognizing their exacerbated vulnerabilities.
Another aspect addressed in studies in this category was that the vulnerability of some social groups, such as children, for example, should not be examined from the individual point of view, but rather considering the participant\'s context. Authors advocate that the approach of research ethics should be relational. The autonomy and capacity to make choices are not individual traits, but rather result from, and are reproduced by means of, social interactions13. Furthermore, the community\'s involvement regarding the sociocultural context and the informed consent with a multifaceted approach may protect the potential participants with reduced capacity, as demonstrated in a case study in Kenya with children and adolescents in street situation14. The community\'s involvement was also seen as necessary in studies in places where there are disasters, especially devastating ones, in developing countries with high levels of poverty. By means of the significant participation of the community, it is possible to establish relationships with the victims, together with the promotion of safety, confidentiality and data protection15.
The studies mentioned above show that vulnerable populations should be protected, though not prevented a priori from participating in scientific studies. The super-protection might block the necessary research, whereas the investigation without support and adequate benefits may worsen their situation of vulnerability. Given the high morbidity and mortality among persons in settings with few resources, there is the need of experiments with these populations16. Every investigation is dynamic and vulnerabilities are inserted in a context17. When the focus of the ethical analysis is solely on the protection of the researched individual, it prevents the promotion of innovative changes18.
Authors list the conditions to be considered for researches with vulnerable persons, as follows: convincing scientific justification; limitation of restrictions imposed on participants; robust informed consent process; community\'s participation in the public trust of the study; guarantee that participants do not have expenses or losses related to the investigation; and provision of compensations for possible damages caused by the investigation19,10.
In general, there are two types of justification for the inclusion of vulnerable groups in research: direct benefits are significant and surpass the risks; and the inexistence of another way of obtaining data that influence efficient policies for that population. Direct benefits refer to the financial support and the possibility of having access to health care during the research, as well as those arising from the results of the research20.
Members of RECs occasionally do not approve research projects due to the denomination of vulnerable of the possible participants, without taking into consideration the principles of respect and justice in decision-making. Vulnerable persons also have the right to science, and in order to be direct beneficiaries of researches they should not be left outside: “nothing about us without us” (p. 3)3, as claimed by some vulnerable social strata21. On the other hand, in countries without a universal public health system, certain population groups in situation of precariousness find in the participation in clinical trials a way to obtain treatment for their diseases6.
In short, the studies in this category show that populations in situation of vulnerability should not be prevented a priori from participating in researches, because new interventions may improve their health22. The assessment of risks should be prima facie, with an approach based on the vulnerable person in the context in which she/he lives, with attention to the existing cultural differences, and the researches should be conducted only when it is in the best interest of the individual, with minimum risk23,24. In the analysis of research projects with this public, it is necessary to take into consideration factors as: clear justification, community\'s engagement, careful informed consent process, financial compensation, benefits to participants and community, minimization of risks, post-research follow-up, and access to the positive results of the research.

II - Coercion/exploitation/ethics dumping of vulnerable populations
In this category were included studies that show that vulnerable populations are submitted to researches without the due autonomy and/or do not receive the necessary care during and after the study. These are recruited persons who accept to participate without having a consistent understanding about the study, or are co-opted by means of payment, or have no adequate protection as to decide with autonomy. The co-opting for researches of persons with reduced voluntariness, in developing countries, by researchers from developed countries, is named “ethics dumping”. In these studies, ethic principles are ignored to fulfil the interests of those who conduct them and vulnerable participants do not benefit from them. Among the articles analyzed, 11 were included in this category and are listed on Table 2.
Most of the articles in this category demonstrate ethics dumping. In a historical analysis of researches conducted in the Philippines in the period of the North American occupation, there was evidence of clinical trials carried out to address epidemics such as cholera, tuberculosis, smallpox and typhoid fever, without adequate treatment for those who participated in the experiences and without consent25. A similar picture was found in a case study in Indonesia26. Japanese researchers conducted researches with vulnerable population without any special protection, without informed consent and with exposure to risks. In a study conducted in Mexico with members of RECs, ethics dumping was also verified in the reduced autonomy of participants, undue incentives and therapeutic misconception, in which those recruited for clinical trials think they are receiving treatment, instead of participating in a research27. An investigation on Sexually Transmitted Infections (STI) carried out by a North American team in Guatemala in the 1940s, only revealed in the XXI century, was conducted without the consent of participants, including institutionalized orphan children, prisoners and psychiatric patients. Blood and spinal fluid samples were collected and the recruited persons were exposed to STIs. Participants received no restitution or reparation for the harms they suffered28.
In a study with pregnant women in Ghana, Dutch researchers showed the lack of understanding about the participation in experiments. The researchers questioned the women about the factors that influenced them to participate in clinical trials and the aspects that became evident were the participants\' lack of knowledge about what a scientific study is, the influence of inequity in the decision-making power to participate, and the occurrence of therapeutic misconception29. In a study with Indian sex-worker women who were volunteers in a research on HIV, about their motivations to participate in the investigation, the researchers found that the women felt obliged to take part and prevented from leaving the study due to having signed the term of consent30. In South Africa, a research with oncological patients who participated in clinical trials phase 3, to explore their perceptions after the process of informed consent, showed that most of them did not have adequate knowledge of the risks to which they were being submitted and some believed that they would be cured from cancer. Others participated for financial reasons because they would have a gratuitous treatment, or because their own oncologist had recommended, thus in order not to cause disappointment31.
The co-optation of participants, whose main vulnerability is related to the unfavorable socio-economic condition, is facilitated by the practice of paying them, which is regular in some countries. This leads the impoverished population to have this activity as a source of income and to be voluntary in several clinical trials at the same time32. A North American research on the ethical concerns of clinical trials phase 1 with healthy subjects provides this understanding. The motivation of most volunteers is economic, because the majority is unemployed and they belong to the poorest extracts of the population. The collateral effects that occurred were not reported out of fear to be excluded from the essay, because the payment is made only upon conclusion33. In the Democratic Republic of Congo, Belgium researchers observed a similar situation in a study on the ethical challenges of a pediatric randomized clinical trial on malaria. The study found that in places where there is no free access to health, people accept to participate because they will have gratuitous medicaments and reimbursement of transport expenses, regardless of any risk factor34.
Patients with chronic diseases are in a situation of vulnerability and participate in clinical trials hopping to obtain clinical improvement, without evaluating with due autonomy the risks of these experiments. Pérez-Roman et al. (2018)35 followed participants in a clinical trial of a new treatment for rheumatoid arthritis. Most patients had their condition worsened after the discontinuation of the trial, which reveals the researchers\' disrespect for the ethical duty regarding the post-trial care of patients.
In this category, it became evident that the co-optation of vulnerable populations to participate in researches is a usual practice. Although the international ethics guidelines stipulate that these populations should be inscribed in researches only in case these cannot be conducted with non-vulnerable groups, the ethics review process regarding vulnerability is sometimes flawed, with the risks being underestimated or overestimated. North American researchers recommend that the ethical norms related to the vulnerable persons are revisited and improved, taking into consideration the lessons learnt36.
The various vulnerabilities of possible research volunteers facilitate their co-optation for researches without the consistent understanding of what they will experiment. In some cases, for a better protection of the vulnerable, the approaches for the consent should be relational and not individual, involving the community, and not isolated within the family37. Likewise, authors suggest special strategies for the consent process of certain vulnerable diseased populations, such as using ludic resources with the inclusion of patients\' associations38,39. Some accept to participate in clinical trials in order not to disappoint their doctors or are victims of therapeutic misconception, because they do not differ between the roles of physicians and researchers40.
It is noteworthy that ethics dumping was facilitated with the relaxation of the Declaration of Helsinki regarding the use of placebo in clinical trials occurred in the year 2000. It was maintained in the following revisions, despite the criticism from part of the world community, including Brazil, only with the reservation that funders, researchers and governments of the host countries should make provisions for the post-trial access to all participants who still need an intervention identified as beneficial in the study. Brazil recently approved the Law No. 14,874/2024 on research with human beings. This new law eased the norms of protection to participants, hence reducing their safety, which represents a setback in the guarantee of rights, especially of vulnerable populations41. It is not acceptable to relax ethical norms in countries where poverty makes their subjects susceptible to researches that can cause them harm42.
Another factor that facilitates ethics dumping and co-optation of vulnerable for researches is low education level, because it hinders the safe understanding of volunteers about the experience of participating in a study. This is one of the main ethical dilemmas faced in researches with vulnerable populations36.
The ethical guidelines vary between countries due to cultural and legal differences, as aforementioned. For some countries, the informed consent is a simplified bureaucratic procedure, for others it is detailed and rigorous. The ethical analysis by RECs also differs from one nation to another, because some are non-independent and are ultimately influenced by conflicts of interest. The concession of payment to participants, as occurs in countries as the USA and Canada, clearly attracts economically deprived populations. In these countries, the support to participate in clinical trials includes the reimbursement of expenses and a financial compensation for the time and effort dedicated to the study. European countries such as the United Kingdom, Germany, France and Italy allow a financial compensation of expenses and directly related loss of income in studies with healthy volunteers43. In Brazil, the Law No. 14,874/2024 made more flexible the participation of healthy individuals in clinical trials phase 1 and in studies of bioequivalence, by allowing the concession of financial advantages and the reimbursement of expenses with transport or food44.
The payment for the inclusion in scientific researches, especially clinical trials, has created a new category of occupation, that of being a participant in several studies at the same time. Especially vulnerable to this type of “job” are immigrants, persons with low education level, former incarcerated and Black persons. The death of a healthy recurrent volunteer in clinical trials has highlighted the need to discuss and improve the existing directives on the repeated use of healthy volunteers45.
Coercion and ethics dumping in biomedical researches provide benefits to those who are already privileged. Poor populations and/or those in developing countries are submitted to studies whose positive results serve the funding countries. Besides having no benefits, they submit themselves to risks. The Declaration of Helsinki provides no special protection to low- and middle-income vulnerable individuals and this facilitates their exploitation46,41.

III - Challenges and barriers to ethics in research with vulnerable populations
In this category are included the articles that point out, debate and suggest measures to solve the verified ethical dilemmas, overcome and surpass barriers and challenges, ensuring the protection of participants with equity and justice. Among the articles analyzed, 10 were included in this category and are listed on Table 3. The challenges revealed in the studies refer to cultural barriers, vulnerabilities regarding certain diseases and situations, and to ethics committees\' protectionism.
North American researchers found cultural barriers in investigations with women participating in studies on HIV. The authors explored the women\'s reactions to the research in which they participated. Many of them did not have the understanding that they could interrupt their participation at any moment and demonstrated concern regarding confidentiality, even though this information was in the form of consent that they had signed47. Another study, conducted in Africa, by means of interviews with participants in clinical trials, verified that few of them had the proper understanding of what they were being submitted to48. These data highlight the need to improve the informed consent process in clinical trials with vulnerable populations. The informed consent is utterly important to ensure the autonomy of the subject in participating or not in the study. In general, the forms are long and use a language that is adequate to the requirements of RECs, but are not necessarily adequate to research participants. A study conducted in Australia to identify the needs in relation to informed consent practices revealed the need to adapt the form to the type of research and target audience, because different groups of persons have diversified necessities, and the consent should not be mandatorily written49. Campbell et al. (2020)50 conducted a research with participants of studies on the experience of a careful and differentiated informed consent process. This occurred in a silent room, with privacy, and involved the transmission of information on the study in a dialogued manner, with a duration of around 30 minutes. The participants considered this process as informative and consistent, which suggests that the face-to-face discussion, combined with the written consent document is a good strategy.
Several challenges are present in researches with populations whose vulnerabilities are related to their own pathological conditions. Singleton et al. (2014)51 show the ethical challenges of research participation of persons with hearing impairment. This population is seen only through the lenses of this impairment, with no consideration to other needs and individual rights. The authors advocate the adoption of culturally appropriate research guidelines and the recognition of the heterogeneity of the deaf community.
Similar communication hindrances were pointed out in researches with patients with neurodegenerative diseases. The authors suggest that the consent should be processual, with a limited number of questions and the possibility of participation of relatives together with the patients52. A great challenge is also observed in carrying out researches with mental illness patients. Newman et al. (2017)53 conducted a study with patients and health professionals on the ethical challenges of interviewing persons with mental illness. The strategies used were the distribution of leaflets with information about the research, which enabled to clarify doubts before the consent process, the construction of a confidence bond before starting the interview, and the care as not to confound the roles of health professional and researcher. An ethnographic study, conducted by a USA-based researcher and native Indian woman, with socially vulnerable epileptic women in an Indian community, had great difficulty to recruit participants due to the disease\'s stigma and to living in isolation. It was necessary to establish a partnership with local researchers, who contributed to construct a trust relationship with the participants54. Another great challenge is to conduct researches with populations in emergency care, because in general it is not possible to obtain the informed consent of the patient or a relative. A study conducted in Sweden to investigate the legal protection to individuals in emergency care recruited for researches revealed that there are rules prohibiting their participation in case there is no substitute consent from someone responsible. Some norms allow the participation without the consent of a substitute, as long as the standard requirements of protection are fulfilled. Another rule is to allow the research only in case the investigated persons themselves will benefit from the investigation55.
The protectionism of RECs members represents a barrier to research with vulnerable populations. Peter and Friedland (2017)56 showed that at times the evaluators overestimate the risks for vulnerable persons. The authors suggest that the evaluation would be fairer if it would be possible to listen to vulnerable participants and if there would be closer relationship between researchers and RECs to understand better the vulnerabilities and potentialities.
The vulnerabilities are not equal and deserve an individualized approach. The articles in this category highlight that some individuals have difficulty to understand what will occur in the research, due to either low education level, cultural issues or fragilities related to patients\' pathologies. They indicate the need of adaptation of the consent process, which should be processual and at times with the participation of family or community members. In the scientific literature, there are proposals of various strategies to overcome these barriers. An Argentinian researcher proposes the notion of vulnerability in layers and the action in two stages to deal with it. In a first stage, the vulnerability is identified, and in the second, it is evaluated according to the risks or threats posed to individuals or groups. The author defends that this procedure facilitates a more ethical resolution, prevents a superficial and automatic analysis of the vulnerability, and provides a valuable guidance on what and how to prioritize57.
In a different perspective, Mollard et al. (2020)58 propose an approach of vulnerable populations based on their strong points rather than on their fragilities. For example, to focus on the capacities and wellbeing, promote hope using an optimistic language centered on the person, identify resources in the social and community context, show respect for the participants, enabling them to speak about their own experience. Another option is a comprehensive and pragmatic approach of vulnerability, analyzing its implications and the research\'s justifications and applications59.
Facing challenges and barriers in researches with vulnerable populations has led to the improvement of ethical norms in several countries. South Africa has since 2004 the National Health Act that provides a strong protectionism to research participants60. In Brazil, the 2024 law went on the opposite direction, having relaxed norms that indicate a decrease in the protection to research participants61.
The main international documents on research ethics do not give special emphasis to the issue of vulnerable persons. Westra and Beaufort (2015)62 argue that it is necessary that the next revision of the Declaration of Helsinki improves the items regarding research with vulnerable persons, in order not to be unnecessarily restrictive or permissive, without no ethical justification.
In an article published on the journal Science & Society, Weigman (2015)63 poses the question if clinical trials participation in developing countries is often the only way for people to have access to medical care and what can be done to prevent the exploitation of this vulnerable population. The author affirms that this is not necessarily an unethical practice, because it may provide considerable benefits to participants, such as advantages to the person and to the community, besides the health treatment. However, it is not morally acceptable to take advantage of the fragilities of those individuals, to impose a risk to their health in a clinical trial when there is no legislation to protect them. Each case should be individually evaluated, so that the benefits of participation are certain and consecutive to the trial.

Final considerations
The studies reviewed in this article show that vulnerable populations should have the opportunity to participate in researches that present a minimum risk and can bring them benefits. However, the studies highlight the need to ensure the rights of participants.
Coercion/exploitation/ethics dumping of vulnerable populations is a historically proven practice and continues to exist by means of payment and provision of other benefits, and by the relaxation of international ethical regulations.
In order to overcome the highlighted challenges, the studies indicate the following aspects: improvement of ethical norms regarding researches with vulnerable populations, as well as of the projects evaluation process in RECs, which, in general, is very protectionist and does not admit the mediation with researchers and the subjects under study; the individualization of procedures for consent, with adequate and consistent information to the target group; and the involvement of the community and/or independent witnesses/community leaders for the adaptation of the research to the individual\'s culture and adequate protection to ensure his/her participation rights.
This review was limited to two databases; therefore, it may have not included studies that show other aspects about ethics in research with vulnerable persons. However, I consider that the knowledge produced in this review is useful for a more effective protection of this population and the expansion of possibilities of participation in studies that provide benefits. It is noteworthy the responsibility of researchers who intend to conduct investigation with people in situation of vulnerability, in the sense of acting in accordance to the ethical norms and having empathy with these populations, acting in the first place on behalf of their interest. 
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