Introduction

Coinciding with the recent increase in the conduct of research involving human subjects in developing countries there has been the development of several guidelines, regulations, and recommendations regarding the ethics of health research [1]–[3]. Despite the existence of such documents, concern has been expressed regarding the presence and adequacy of ethics review systems in health research in developing countries, including those from the Eastern Mediterranean (EM) Region [4], 5. Another issue is the extent to which investigators are aware of the ethical considerations of their research. Little empirical research has been conducted on the research ethics practices of investigators in the developing world. Several papers have described in qualitative terms the status of ethics review systems and the awareness and practices of investigators regarding health research ethics in developing countries [6]–[8]. Two studies have explored the extent to which investigators obtain ethics review. One study involving researchers from Asia, Africa, and South America revealed that 25% of the investigators reported that their studies did not undergo ethics review [5]. The other study showed that among investigators who submitted research proposals funded by the Eastern Mediterranean Regional Office in 2003, 43% felt their research did not require ethical clearance [9]. A clearer picture regarding the extent to which investigators consider the ethical aspects of their research can help assess the ethics training needs of health researchers and provide further impetus to policymakers to strengthen ethical review systems in the EM Region. Accordingly, the purpose of this study was to analyze the ethical practices undertaken by health researchers from the EM Region who had submitted proposals for funding in 2006. We demonstrate in this larger study that the ethical practices of investigators in the EM Region regarding attaining ethical clearance, plans for obtaining informed consent, and ensuring confidentiality of sensitive data needs improvement.

Methods

Results

Health researchers from 12/22 (55%) countries within the EM Region submitted a total of 143 applications. These countries included: Iran, Egypt, Jordan, Lebanon, Morocco, Oman, Pakistan, Sudan, Syrian Arab Republic, Kuwait, Yemen, and Tunisia. Of these applications, 20/143 (14%) involved animal research and 15/143 (10%) involved literature review, analysis of health systems outcome data, or analysis of non-human specimens (e.g., water analysis or vector research). The remaining 108/143 (76%) proposals constituted the subject of our analysis.

Proposals were categorized as follows (see Table 1): analysis of prospectively collected biological samples; qualitative research involving a social behavioral intervention and the use of either questionnaires, interviews, or focus group discussions; qualitative research involving either questionnaires, interviews, or focus group discussions; exempt research (either qualitative research or analysis of archived data recorded without identifiers), and non-human subjects research (receipt of existing biological specimens that were de-identified). None of the qualitative studies involved normal educational practices. Seventeen qualitative research studies involving questionnaires, interviews, or focus groups discussions did not qualify for exempt status based on the following criteria: a) the obtainment of identifiable information that could be damaging to the subject's employability or reputation (n = 10), b) the inclusion of questions on surveys or interviews that might evoke greater than minimal risk emotional responses (n = 3), or c) involvement of children or adolescents less than 18 years of age (n = 9); several studies met more than one of these criteria. Twenty research studies involving qualitative methods qualified for exempt status.

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Table 1. Ethical considerations in submitted proposals (N = 108).

https://doi.org/10.1371/journal.pone.0002094.t001

Table 1 shows the extent to which investigators considered the various ethical safeguards categorized according to the type of research design. Results for the three research ethics practices (ethical clearance, informed consent, and confidentiality) were similar among the different non-exempt researches involving human subjects (p>0.05). These results were higher than those observed for proposals categorized as exempt or non-human subjects research (p<0.003). Regarding the 50 qualitative researches (both exempt and non-exempt), 29 investigators stated they would obtain informed consent, 15 stated they would not obtain informed consent, and 6 gave no answer. Of the 15 qualitative proposals in which investigators stated they would not obtain informed consent, 7 included interviews or focus groups discussions, while the other 8 involved only the use of questionnaires.

Table 2 shows the aggregate data for ethical practices for the four countries (shown anonymously) that submitted 5 or more proposals. For the non-exempt human subject researches, no significant differences were observed in the extent to which the ethical practices were considered between these four countries (p>0.05). Ethical clearance (obtained or pending) for proposals involving human subjects ranged between 62 and 100%; the plan to obtain informed consent ranged between 62 and 88%; and the plan to ensure the confidentiality of data ranged between 77–100%. Of these countries, only Country A has national regulations addressing the ethics of research practices. All four of these countries have national ethics committees. These results are similar to the overall aggregate data for all countries. Regarding the existence of national ethics committees for all 12 countries from where proposals were submitted, 10 have such committees and three are known to have national regulations/guidelines addressing the ethics of research.

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Table 2. Ethical considerations in proposals from countries that submitted five or more proposals.

https://doi.org/10.1371/journal.pone.0002094.t002

Table 3 shows a summary of the reasons given by investigators for not obtaining ethical clearance categorized according to the type of research. Several investigators felt that obtaining biological samples from patients seeking medical care did not require ethical clearance. Many investigators thought that research involving qualitative research does not require ethical clearance, because it does not involve an intervention, an invasive procedure, or the administration of drugs. Also, several investigators planning to do qualitative research involving children did not think ethical clearance was necessary. In all types of research studies, several investigators thought that approval from other entities (e.g., ministry of health, director of the hospital, and university internal review board) could substitute for a review by an independent ethics review committee.

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Table 3. Reasons given by investigators as to why ethical clearance was not obtained (n = 25).

https://doi.org/10.1371/journal.pone.0002094.t003

Discussion

Health research can play a crucial role in improving national and global health by developing and evaluating interventions and by exploring strategies that can empower individuals to alter unhealthy behaviors. However, health research involves human subjects and such individuals might be harmed by their participation in research. Accordingly, a strong system of ethical review is needed to enhance the protections of the rights and welfare of human subjects. Also, to enhance the public trust in research activities, investigators need to subscribe to a strict code of ethics that equals the highest standard of respect for human rights. This framework thus places ethics at the very core of a country's programs for health and development [11].

The present study shows that, in general, the extent to which investigators in the EM Region consider ethics safeguards in the conduct of their research requires improvement. Of the submitted proposals determined to involve “human subjects”, ethical clearance was not obtained in 29% of the proposals; investigators thought that informed consent was not needed in 29% of the submitted studies; and investigators did not mention any measures to ensure confidentiality of the obtained data in 8% of the studies. The magnitude of these deficiencies was similar regardless of study design type, i.e., prospective collection of biological samples and qualitative research methods. Our results are made more significant by the fact that the summary data regarding ethical practices excluded research that could be determined by a research ethics committee to be either exempt from their ongoing review or not to involve human subjects. Indeed, percentages for the ethical practices observed for these types of researches were lower compared to the non-exempt human subject research.

It is not clear why 15 of 50 investigators planning to do qualitative research (exempt and non-exempt research) stated they would not obtain informed consent. Obviously, subjects who complete questionnaires or participate in interviews or focus group discussions are giving their consent to a certain extent, even if they might not be fully informed. To account for these responses, investigators might have believed that informed consent was not practicable (six studies planned to enroll “hundreds” of subjects to complete questionnaires) or that they were not required to give subjects a full explanation of the research due to the setting of the research (e.g., six studies planned to involve students or staff of an organizations). Alternatively, investigators might have thought they were being asked if they planned to obtain written informed consent, as the one-page questionnaire of the grant application asked investigators to “please attach the consent letter”.

A review of the reasons given for not obtaining ethical clearance revealed that many researchers thought that research involving questionnaires, interview, or focus group discussions do not require ethical clearance, because such research does not involve an intervention or the administration of experimental drugs. This finding might reflect a lack of understanding of the psychological and social harms that can occur from obtaining private and sensitive data. Also, several investigators did not consider a need for additional ethical safeguards for research involving the participation of adolescents. Finally, a few investigators felt that ethical clearance and informed consent were not necessary when obtaining biological samples from patients seeking medical care. Such an attitude might be due to several perspectives; for example, investigators might believe that such patients, especially those in the public sector, might have an obligation to participate in research. Additionally, investigators might think that obtaining “left-over” samples of biological tissues involves no additional risk to the patients and hence, do not require informed consent or ethical clearance from an independent committee. However, regardless of the risk of the study, failure to obtain informed consent is not respectful of human subject rights. Also, all research ethics guidelines recommend independent review of all human subject research [2], [3], [10].

Two other studies have reported on the extent to which ethical review is obtained in developing countries. Hyder and colleagues reported the results of a self-administered survey that asked investigators from Asia, African, and South American questions regarding a previous research project [5]. This study observed that 25% of the investigators stated that their studies did not undergo some form of ethics review. Another study involving investigators from the Eastern Mediterranean Region who submitted proposals for funding to EMRO/WHO in 2003 revealed that 43% of the investigators did not believe that their proposals required ethical clearance [9]. This previous study did not indicate whether exempt and non-human subject researches were excluded from the analysis and hence, it is difficult to compare these results to those obtained in the present study.

Several factors might account for the present findings. First, failure to obtain ethical clearance might be indicative of the absence of a system of ethical review at the investigators' respective institutions. Second, investigators might be unaware of the need for independent ethical clearance, informed consent, and confidentiality protections. Lack of awareness might result from the failure of the undergraduate and post-graduate curriculum to include materials in the area of research ethics. Also, unawareness might result from the lack of support for research ethics practices at the national level. Indeed, of the 12 countries represented in this study, only three are known to have national regulations mandating the existence of research ethics committees and the need for informed consent. To be sure, 10 of the 12 countries represented in the present sample are known to have national ethics committees. National ethics committees might be involved in setting ethics standards, review of national research, or providing ethics education and any one of these activities could be expected to influence the practices of investigators. However, our findings might indicate the relative failure of national regulations or national ethics committees to have a downstream effect on the practices of the research staff. The lack of guidance at the national level might also lead to inconsistent approaches among investigators and academic officials regarding the types of researches that might be categorized as exempt or as non-human subject research.

Key limitations of the present study include the limited scope of the types of the research proposals reviewed and hence, the generalizability of the observed results might be limited. For example, the proposals analyzed in the present study represent the limited priority areas of public health and biotechnology and genomics and therefore, might underestimate the practices of investigators performing pharmaceutical-sponsored research that usually require ethical review, informed consent, and confidentiality assurances. On the other hand, the research proposals represent those submitted to a highly competitive WHO/COMSTECH grant scheme and therefore, reflect the practices of senior investigators who might be expected to be aware of ethical practices regarding research. Accordingly, our results might overestimate the practices of more junior investigators and those in training who submit research proposals for thesis projects. Also, our data regarding the obtainment of ethics review included the intent of investigators to obtain such review. Since we do not have information as to whether such review occurred, our results might overestimate the extent to which ethics review was obtained. Finally, scientific review committees in the absence of research ethics committees might have been involved in reviewing the ethical aspects of the submitted protocols. Accordingly, investigators might have indicated that ethical clearance was obtained if their proposals received review from such scientific review committees. However, the WHO states in their guidelines that ethics review should be separate from the scientific review of research [7]. Having said this, we are not aware as to whether local scientific review was a requirement in any of the countries in the EM region.

Another limitation of the study stems from the use of criteria in the U.S. federal regulations to categorize studies as being exempt or non-human subject research. The use of such criteria might not be relevant to the local context or might differ from those embraced by national authorities or international funders. In the absence of explicit, external guidelines, investigators might have taken upon themselves to determine the types of research that could be classified as exempt or non-human subject research and accordingly, decide by themselves which proposals require ethical clearance, informed consent, and the protection of confidential information. Finally, our data relied heavily on the self-report of investigators and therefore, bias might have been introduced by the motivation of the investigators to obtain funding.

Our results have several implications for research and research ethics in the Eastern Mediterranean Region. First, the lack of a firm foundation and affirmation for research ethics might impact negatively on the ability of investigators to obtain internationally funded research. Indeed, many funders (both private and governmental) from the U.S., Europe, and Canada have stringent research ethics requirements that might be met more readily if national regulations exist or if a national ethics committee conduct overview of such research. Furthermore, international journals require evidence of ethics review and informed consent and hence, the lack of attention to such research ethics practices might represent one reason to explain the under-representation of developing countries in the research literature [12].

Finally, our results might reflect investigators' lack of adequate or reinforced training in human subjects protection. It is unclear whether the results of this study demonstrate what might be an appropriate learning curve in investigators' awareness and educational capacity regarding research ethics practices, as this topic has only been introduced in developing countries during the last decade. We do not have data as to how our results compare with other WHO Regions. Nonetheless, the results emphasize the need to continue to raise the overall level of awareness and training among researchers regarding the importance of considering explicitly various ethical safeguards in the conduct of their research. Accordingly, we recommend that educational efforts be enhanced to emphasize the implications of research ethics on the value of protecting the welfare and rights of individuals who volunteer to participate in research studies. Presently, there are several existing programs that aim to help strengthen research ethics capacity in the EM Region. For example, the United Nations Educational, Scientific and Cultural Organization (UNESCO) has launched several recent programs aimed at strengthening research ethics in the Arab Region [13]. The Wellcome Trust in the United Kingdom provides support to build ethics capacity in resource-poor countries that have well-established research centers [14]. The Fogarty International Center of the U.S. National Institutes of Health has provided funding for the establishment of training programs in research ethics for individuals from the Middle East [15]. Based on the results of this study and other sources of data, the WHO is continuing national training initiatives for ethics in biomedical research in the different member countries of the EM Region. Finally, individual countries should adopt national research ethics regulations to ensure a consistent approach to the review of research. A robust human subject protection program that includes research ethics training and a strong system of ethics review can help ensure the public trust in research and enhance the research agenda in the developing world.