Ethics in the Publication of Studies on Human Visceral Leishmaniasis in Brazilian Periodicals

OBJECTIVE: To analyze ethical aspects of Brazilian articles on human visceral leishmaniasis, published after Resolution CNS 196/1996, and to analyze the policy on Brazilian periodicals on research ethics. METHODS: An explanatory study with a bibliographical and documental nature was conducted. Selection of publications on research involving human beings since 1996 was performed in the SciELO Brazil database. Gaps associated with editorial policies on medical periodicals, based on information obtained from the " Instructions to authors " section of each periodical, were analyzed. RESULTS: While there were no articles on the compliance with ethical aspects in the fi rst four-year period (from 1997 to 2000), 75% fulfi lled at least one of the ethical requirements evaluated in the fi rst year (2009) of a subsequent four-year period (from 2009 to 2012). A total of six out of 11 periodicals indicated that the information about ethical aspects should be mentioned in the body of the article. There were three periodicals that required a letter or document, informing about compliance with these aspects and signed by the author(s), to be sent; two that requested a copy of the document used to obtain the free and informed consent; one that clarifi ed the need of a copy to authorize the approval by the Committee on Ethics in Research; and four in which no requirements of ethical aspects were found. CONCLUSIONS: There was an improvement in the description of compliance with ethical aspects found in articles. Standardization of ethical requirements for human research in Brazilian periodicals is suggested. This could promote compliance with the presuppositions of documents regulating human research.


INTRODUCTION
In recent years, the theme of "ethics in research on human beings" has been increasingly focused on by part of the academic-scientifi c community.In Brazil, one of the reasons for this increase is associated with the existence of specifi c legislation establishing the directives and norms that regulate research on human beings.The Brazilian Health Council Resolution (CNS) 196/1996 5 represents a regulatory landmark for Brazilian scientifi c research involving experiments on humans.Such resolution was designed with the purpose of protecting participants in studies and guaranteeing the rights and duties of scientists, sponsors, the organizations involved and the government.Despite the growing concern and studies in the area of bioethics, 4 there are still problems and confl icts that need to be overcome.Guilherm & Squinc 9 (2009) emphasize the use of impoverished countries as the locus of performance of studies, production of knowledge and development of products.According to Clotet 3 (2009), the adoption of a common moral standard to resolve controversies about biomedical sciences and high technologies applied to health is also a challenge to modern ethics.Garrafa et al 7 (1999) and Garrafa 8 (2008) emphasize that the democratic use of the benefi ts resulting from the scientifi c and technological development is far from being achieved and, consequently, poses a challenge for the 21 st century.On the other hand, according to what is pointed out by Sanches & Ruthes 16 (2009), new discussions arise as a challenge to bioethics, especially when it comes to biological sciences and the existing triad of religion, science and culture.
However, in addition to these confl icts, there are those associated with ethics in the dissemination of results of research on human beings.When the internationallyimposed concept of "publish or perish" is considered, the scientifi c community is forced to publish their studies.In this case, ethical questions and the directives on research on human beings stand out as safeguards that need to be taken into consideration, aiming to prevent confl icts in the fi eld of ethics and medicine.
Among the innumerable prevalent diseases that are neglected in Brazil, human visceral leishmaniasis (HVL) was selected as the focus of the present study, because it is a serious chronic disease, potentially fatal to human beings and whose lethality can be as high as 10% if the treatment is not adequately performed. 2,5,11,14 It is estimated that its worldwide incidence is higher than 500,000 new annual cases. 5Brazil has the highest number of endemic cases of HVL in the Americas (approximately 97% of cases in the continent), recorded in at least 19 states.a Since its discovery in the early 20 th century, research on HVL has been conducted in animals and human beings to better understand and control this disease.In many countries, the exploitation, coercion and manipulation of the informed consent, on behalf of "the science of their publications", can still coexist.In this context, the present study aimed to analyze the policy of Brazilian periodicals on research ethics and ethical aspects of articles on HVL, published in the years following Resolution CNS 196/1996.

METHODS
An explanatory study with a bibliographical and documental nature was conducted.Articles were selected from the SciELO Brazil database, using the terms a Ministério da Saúde.Secretaria de Vigilância em Saúde.Manual de Vigilância e controle da Leishmaniose visceral.Brasília; 2006."leishmaniose visceral", "visceral leishmaniasis" and "Leishmania chagasi", between 1997 and 2009.
Articles involving research conducted out of Brazil, even if they included authors connected to Brazilian universities, and those that mentioned visceral leishmaniasis without the human disease, such as studies on vectors and the biology of etiological agents, were excluded.
The evaluation of ethical aspects included in the body of articles was based on the following questions/instructions: 1) The article deals with the approval of a study by a Research Ethics Committee (REC); 2) It refers to the use of the Informed Consent Form (ICF); 3) It mentions that the study followed the ethical directives established in Resolution CNS 196/1996.;4) It mentions the date of approval of the study by the REC; 5) It includes the protocol number through which the REC approved the study; 6) It mentions the guarantee of anonymity of participants involved in the research; and 7) It clarifi es about the existence of confl icts of interest that could have infl uenced this study.
The period of time of this study (from 1997 on) is justifi ed by the fact that this is the fi rst year after the publication of Resolution CNS 196/1996.Analyses were made according to four-year periods.
The "Instructions to authors" section, present in the electronic pages of journals, was accessed on January 25 th , 2010, to evaluate whether scientifi c periodicals have guided authors to exclusively submit research manuscripts that meet the ethical standards.The following questions/instructions were established according to the content of Resolution CNS 196/1996: to have been the result of research approved by a REC registered with the Brazilian Ministry of Health Research Ethics Comittee (CONEP/MS); to have suggested that authors read the documents on ethical questions; to have recommended that authors read extracts or complete documents that regulate research on human beings; to have emphasized the need to use the ICF and to read the ethical instructions of common requirements for manuscripts submitted to biomedical periodicals.
The way editors require veracity of information about the ethical aspects shown by the authors, upon submission of their work, was analyzed according to the instructions described in Table 1.In this group, the questions/instructions sought to evaluate the periodical-authors dynamics associated with the requirement of proofs.

RESULTS
A total of 76 articles were found for "leishmaniose visceral", 113 for "visceral leishmaniasis", and 22 for "Leishmania chagasi", totaling 211 articles.When the criteria of exclusion were applied, 37 were selected for analysis.The number of articles annually published was not constant, but rather higher in 2002 (fi ve publications), 2004 (six publications) and 2008 (fi ve publications) (Figure 1).
Table 2 shows the periodicals evaluated and the number of articles published between 1997 and 2009.The Revista da Sociedade Brasileira de Medicina Tropical (RSBMT) was responsible for the publication of a third of the articles.The states of Maranhão (Northeastern Brazil), Mato Grosso do Sul (Central Western) and Minas Gerais (Southeastern) were those where the highest number of studies was conducted (seven publications in each).
There was a proportional increase in the number of articles published that mentioned the fact that ethical principles were met throughout the four-year periods analyzed.Whereas the fi rst four-year period (1997 to 2000) included no articles that mentioned this, 75% of articles met at least one of these aspects in 2009 (fouryear period from 2009 to 2012).
A total of 22 out of the 37 articles analyzed did not mention that ethical aspects of research on human beings had been met.In addition, eight reported the approval of the study by a REC and two included the date and protocol number of the approval by the REC, as well as the existence or not of confl icts of interest that could interfere with the work developed.
Although the majority (eight out of 11) of periodicals included, in their instructions, the need for approval of the research by the REC of the institution where the study was conducted, none of them emphasized the fact that this REC should have a valid registration with the CONEP/MS.A total of four periodicals recommended that the studies submitted should follow the ethical assumptions included in the declarations, resolutions or (national and/or international) ethical codes that regulate research on human beings.No periodicals had the summarized or complete extracts of the documents that regulate research on human beings or information about ethical instructions of the common requirements for manuscripts submitted to biomedical journals. 6A total of two periodicals included the need for an informed consent form (ICF), completed by the patient participating in the study.In addition, there were no records/ instructions on how the ethical aspects of research on human beings should be met in three periodicals.
A total of six out of 11 periodicals clearly indicated that the information about ethical aspects of research on human beings should be mentioned in the body of the article.There were three periodicals that required that a letter or document signed by author(s) be sent, informing Table 1.Guidance on the evaluation of the content of the "Instructions to authors" of the periodicals analyzed.

Investigative guidance
Does the periodical clearly indicate that the information about ethical aspects of research on human beings must be mentioned in the text of the article?Does it require a letter or document signed by author(s) that provides information about the fulfi llment of ethical aspects associated with research on human beings?Does it require a copy of the document that states that consent was obtained from all research participants?Does it clearly show the requirement that a copy of authorization from the REC that approved this study should be sent?
Is it implicit that the study was conducted according to ethical principles, standards or norms, without the requirement of any supporting document?Does it contain any information about how authors of manuscripts sent for publication must confi rm to editors whether ethical aspects of the study were met? about the fulfi llment of ethical aspects of research on human beings; two that required a copy of a document stating that the ICF was obtained from research participants; one that included the need to send a copy of authorization of the study by the REC; and four that did not include any requirements from the editors that ethical aspects of the study should be met.

DISCUSSION
In developing countries, where the predominance of infectious diseases is high and responsible for the mortality of a substantial part of the population, biomedical studies have received special attention in the sphere of bioethics in the development of research on human beings.b Although many results obtained by Brazilian or foreign researchers in national research institutes were published in international journals, there seems to be a growing number who have chosen and valued Brazilian periodicals.
In Brazil, the increase in the number of scientifi c publications on neglected diseases, such as HVL, is aimed at.This is probably due to the encouragement from research institutions and governmental institutions that promote such research, in addition to the growing quality of Brazilian periodicals.Cadernos de Saúde Pública, Memórias do Instituto Oswaldo Cruz and RSBMT are national periodicals that stand out as means of scientifi c research dissemination, which are responsible for the higher number of publications on HVL in Brazil, in recent years (Table 2).However, quantity does not always translate as quality.The quality of the scientifi c production includes aspects such as: 1) the factor of impact of the periodical in which studies are published; 2) measures of centrality of the factor of impact of the area, aiming to make comparisons; and 3) cited half-life of the means of communication.In this case, the number of articles may not guarantee their good technicalscientifi c quality or unquestioned relevance.
The results show an improvement in the dissemination of ethical aspects of the research on human beings, included in the body of the manuscripts on HVL.This improvement could suggest an advance in the bioethical thinking and approach of researchers, in terms of the fulfi llment of ethical assumptions in HVL research, and the importance of editorial directives of medical periodicals continuing to be in accordance with these ethical assumptions, established in Resolution CNS 196/1996. 12  There was an improvement in the description of the fulfi llment of ethical aspects in articles.The initial years when the new legislation was in effect were characterized as a period of transition, a stage of assimilation and   acceptance of new directives.This could be the reason why there were few articles in accordance with the ethical aspects, in the fi rst four-year periods (from 1997 to 2000 and from 2001 to 2004).On the other hand, the joint effort of research institutions to require the approval of studies by the RECs and that made by researchers, who showed higher assimilation and understanding about the importance of meeting ethical aspects, could have resulted in an increase in the number of studies that are in accordance with Resolution CNS 196/1996.
Recent studies indicate flaws in the reporting of information about the fulfi llment of ethical questions in the development of research on human beings in the international sphere.Karlawish et al 10 (1999)  observed that the majority of publications on elderly individuals living in homes (between 1993 and 1996) do not include the basic norms.Sumathipala et al 19  (2008) showed that one third of the medical publications in Sri Lanka, between 1994 and 2005, informed about the approval of research by a REC.The same was observed by Bavdekar et al 1 (2008) in 7.4% of the medical publications of two major periodicals of India, in 2006, which also reported the use of the ICF.Freeman et al 6 (2008) showed an improvement in the description of ethical aspects in the instructions to authors of medical journals published in English, between 1995 and 2008, although such authors reported the journals' diffi culty in checking the veracity of information they were provided.Rowan-Legg et al 15 (2009) pointed out, based on directives given to authors of 103 medical periodicals, the need for greater clarity and standardization of the requirements to meet the ethical aspects associated with research on human beings.
Gaps found in the fulfi llment of ethical principles of research on human beings are also present in Brazilian studies. 13,17,18,21  In the present study, articles on HVL found in Brazil have been conducted according to the ethical norms established by Resolution CNS 196/1996, although it is not possible to prove the information provided by the text.The number of periodicals that have few or no requirements for studies to be published, in terms of the fulfi llment of ethical aspects of research on human beings, is yet relevant.
These data suggest that there are irregularities between the ethical awareness in the institutions that develop research in accordance with the CONEP/MS system and the Brazilian medical periodicals that publish articles on parasitic diseases, especially HVL.Although not being inspection organizations, these periodicals could contribute to the exclusive publication of studies that meet ethical standards.Thus, it is suggested that periodicals should pay attention to aspects such as the instructions on the importance of the REC that approved the study being registered with the CONEP-CEP system, absent in 100% of the periodicals analyzed, and the requirement that a copy of the statement of approval issued by the institution's REC be sent, present in only one article.Rowan-Legg et al 15 (2009) affi rmed that adherence to ethical standards in the editorial policies of periodicals that publish research on human beings is important for the scientifi c community to follow such presuppositions more strictly.
Tavares-Neto & Azevêdo 20 (2009) showed fl aws and omissions in the "Instructions to authors" on ethical aspects of Brazilian medical periodicals.By analyzing 20 Brazilian medical periodicals qualifi ed as national level "A" or international level "I" for research on human beings, the authors showed that half of them required research approval from a REC, 35% recommended that such approval be recorded in the body of the manuscript and none required that the RECs be registered with CONEP.
In conclusion, there was an improvement in the description of the fulfi llment of ethical aspects in articles.It is suggested that the ethical instructions on research on human beings be standardized in Brazilian periodicals.This could promote the fulfi llment of presuppositions of documents that regulate human experimentation.

Figure .
Figure.Number of Brazilian publications on human visceral leishmaniasis indexed to SciELO Brazil, according to year (1997-2009).

Table 2 .
Number of articles published between 1997 and 2009 per periodical.