Ethical Issues in Conducting Cross-Cultural Research in Low-Income Countries: A Pakistani Perspective

Abstract

The rapid growth of pharmaceutical markets in the 20th century has increased the demand for human research participants in clinical trials. However, with the globalization of clinical research, most clinical trials are conducted in low-income countries (LICs) with political and economic instability, and lack of basic healthcare, but easy access to human subjects. This paper explores the unique ethical challenges faced during the pre-enrollment phase of cross-cultural research in a country like Pakistan, and how these challenges make the Pakistani population vulnerable to exploitation. It also outlines recommendations regarding conducting research in Pakistan within ethical parameters adopted according to local culture. This discussion is important because researchers must focus on the pre-enrollment phase of the research process for it’s cultural suitability and acceptability so that the research conducted is credible and valid and has social value for the research population.

Introduction

Low-income (LIC) and middle-income countries (MIC) represent the majority of the world’s population (UN Department of Economic and Social Affairs 2019). These countries bear nearly 90% of the worldwide burden of disease, mostly consisted of preventable infections (Alemayehu et al. 2018). Even though LICs carry the most substantial disease burden globally, there is a lack of significant research and development activity to address this inequity. Cultures and perceptions are significantly different globally; what is considered appropriate in one place might be unacceptable in another (Epstein 2007). With the globalization of clinical research, most clinical trials are conducted in LICs (da Silva et al. 2016). However, there is an underrepresentation of research addressing priority issues for LICs (Ahmad et al. 2011). Diseases relevant to high-income countries (HICs) are investigated in clinical trials more often (seven to eight times) than diseases whose burden lies mainly in LICs and MICs (Røttingen et al. 2013). Additionally, some of the trials being conducted in LICs seek to answer the HICs questions. A recent review of clinical trials showed that from 1995 to 2005, around one-third of 509 clinical trials sponsored by companies based in the US were conducted outside the country, many in LICs (Glickman et al. 2009). Another study indicated that out of the 1556 new drugs manufactured from 1975 and 2004, only 10 targeted the diseases prevalent in LICs (Chirac and Torreele 2006). According to Alemayehu et al. (2018), only 1% of the recently discovered drugs aim to manage tropical diseases. There is no doubt that clinical trials that use vulnerable populations for testing drugs solely for use in developed countries violate the principles of research ethics (CIOMS 2016). Many studies conducted in LICs could not be done in the countries sponsoring them due to strict regulations around research (da Silva et al. 2016). Therefore, drug companies are accessing LICs like Pakistan because research in these areas is less expensive, and the research subjects are readily available (da Silva et al. 2016; Drain et al. 2014).

The research population of LICs is vulnerable for various reasons. First, the population of these countries is striving for basic necessities like food, water, and shelter; most of the population lives below the poverty line and has no access to necessities of living, for example, safe drinking water (World Health Organization 2019). Second, economic instability, the burden of endemic disease, and poor healthcare system facilitate conducting research trials in these LICs (Glickman et al. 2009; Khowaja-Punjwani 2015). Third, most of the population in LICs like Pakistan is educationally disadvantaged. Additionally, religious beliefs, variation in cultural perspective, language barrier, and scarcity of formally trained research staff make enrollment of research participants challenging (Fatima 2021). Researchers have the best intentions when initiating a research study. However, due to a lack of understanding of social determinants of health and unique cultural factors of the community, they are unable to attain successful outcomes. Due to these factors, conducting research in LICs becomes substantially challenging (Khowaja-Punjwani 2015). These challenges can be divided into pre-enrollment, enrollment, and post-enrollment phases of biomedical research (Amerson and Strang 2015).

In the pre-enrollment phase, how the purpose of research can be conveyed to the research populations is explored. Additionally, the potential issues in the community that may impact the research study are identified, and ways to express respect for the potential research participants are explored (Woodsong and Karim 2005). Finally, the most significant ethical challenge researchers face in cross-cultural research with vulnerable population is how to ensure a fully informed and truly voluntary informed consent is taken before the enrollment in research study (Woodsong and Karim 2005). As per Igoumenidis and Zyga (2011), “informed consent is the cornerstone of modern ethics, but it tends to lose its true meaning when put in the context of a developing country.” Montalvo and Larson (2014) mentioned the results of a systematic review of 27 studies that were conducted to improve patient knowledge of informed consent. That study revealed comprehension issues with the meaning of “randomization, placebo, benefits, and risks.” Out of those 27 studies, three were conducted in low literacy counties and those three studies showed lack of understanding of the terminologies mentioned above. Hence, it becomes increasingly important for the researchers to take careful measures to prevent the LICs population from exploitation resulting from induction in the research study. Therefore, the pre-enrollment phase should be of special consideration in research to maintain the integrity of vulnerable populations and prevent exploitation.

Ethical Challenges in the Pre-Enrollment Phase of Cross-Cultural Research: A Pakistani Perspective.

There are multiple cultural and contextual issues in conducting cross-cultural research in a country like Pakistan. The principles of bioethics practiced in HICs focus on autonomy of person and individual’s right to consent. There is no concept of collective, cultural norm of the role of family in seeking informed consent and shared decision making that is intertwined in some cultures. The other issue is justice in addressing the question of the standard of care in LICs. If the standard of care is locally available best treatment instead of the treatment available in HICs, it is against the principle of justice. The Declaration of Helsinki by the World Medical Association (2013), and the Council for International Organization of Medical Scientist (CIOMS) guidelines revised in 2016 (CIOMS 2016) are well-known documents guiding conducting research on human subjects especially in LICs. However, they have inadequately addressed the issues faced in LICs, for example, CIOMS (2016) guideline 5 states “As a general rule, the research ethics committee must ensure that research participants in the control group of a trial of a diagnostic, therapeutic, or preventive intervention receive an established effective intervention,” but it does not say locally or globally established effective treatment because these could be different, mainly if we are referring to LICs versus HICs. In the Declaration of Helsinki (World Medical Association 2013), paragraph 32 states that: “The benefits, risks, burdens, and effectiveness of a new intervention must be tested against those of the best current proven intervention.” The question here is: is it a local or global therapeutic model because they differ. The other issue is the value of research (Khowaja-Punjwani 2015). The social value of research for the particular community where the research will be conducted should be determined before the initiation of research and should be deliberated by the population (World Medical Association 2013). Researchers from HICs, most of the time, are unsure of the customs, beliefs, and values of local communities. Usually, the researchers select the research subjects according to their needs and select the locality according to their understating, which may result in selecting a research area different from the need of the locality. This way, the social value of the research cannot be determined if someone else who is not a part of the culture or society is making the decisions on behalf of the people. This type of selection violates the principle of beneficence. Research conducted respectfully has maximum social value. To work in a culturally diverse community, the researcher must fully understand the community’s cultural, religious, social, and political background and family structure to be researched. In addition, they must show “cultural sensitivity” and “competency” by learning about key values and stakeholders and behave and communicate in a culturally appropriate manner (Eide et al. 2009). However, despite the codes and guidelines on research involving human subjects, there have been issues of exploitation and misconduct in clinical trials, mainly in LICs (Fatima 2021). In the next part of the paper, different ethical issues in doing cross-cultural research on human subjects in Pakistan will be discussed.

The Issues with Informed Consent

Informed consent is a key prerequisite for conducting research according to ethical standards. It is highlighted in all the international codes of ethics like the “Nuremberg Code” (1949, 181–182), the Declaration of Helsinki (World Medical Association 2013), the Belmont Report (Beauchamp 2008), and CIOMS (2016). Informed consent is based on the “autonomy of a person,” i.e., to choose the best course of action after learning about all the available options (Beauchamp and Childress 2001). Therefore, the fulfillment of specific components is crucial for well-comprehended consent. For consent to be voluntary and informed, it is required that consent is given freely. There is no coercion. The person giving consent has the capacity and can comprehend the possible harms, risks, and benefits to them and the community in general. Therefore, they should provide explicit permission for participation in the research study.

For informed consent, conventionally, a research participant is required to sign a consent form with the understanding that their privacy and anonymity will be kept confidential. The participant always chooses to withdraw from the research study without consequences (Aguila et al. 2016). A copy of the signed consent form is given to the research participant. However, the traditional protocol of seeking consent is not always adaptable in Pakistan (Khan 2008). A substantial population of Pakistan is educationally disadvantaged. Additionally, there is a variety of regional languages that are spoken in different parts of the country (Khowaja-Punjwani 2015). Even though people from different regions in Pakistan who speak regional languages have the capacity to make reasonable decisions for themselves, the above-mentioned factors make obtaining informed consent extremely challenging for the researchers as it is difficult to determine comprehension and understanding of informed consent in the presence of language barrier. The specific issues in commencing the process of informed consent are as follows:

Exploitation and Coercion

The international ethical guidelines and codes have provided guidance on conducting research on human subjects in LICs (World Medical Association 2013; CIOMS 2016). However, despite the codes and guidelines, there have been issues of exploitation and misconduct in clinical trials (Fatima 2021).

Obtaining informed consent in LICs raises questions about voluntariness. For people in the LICs in general and Pakistan in particular, independent decision-making may be influenced by familial, societal, and traditional practices of their families and communities (Fatima 2021). According to a study conducted by Dickens and Cook (2003), research in LICs means enrollment of vulnerable people who do not fully understand the concept of research. As mentioned above, several factors make people from LICs, like Pakistan, vulnerable to exploitation. The region has a low adult literacy rate (World Bank 2017); sometimes, participation in the research study is the only way to access some form of healthcare (Cho et al. 2018). Additionally, potential research risks are under-described, with an emphasis on keeping a positive approach to ensure maximum enrollment (Fatima 2021; Hutton 2000).

In a patriarchal and hierarchical society like Pakistan, the authority is in the hands of men, either government officials, community members, or the men of the family (Memon et al. 2021). This power imbalance makes individuals and communities vulnerable to exploitation when these gatekeepers prioritize their agendas above the benefit of the people they represent. Extensive poverty exposes these communities to more exploitation as individuals cannot decide if they want to participate in the study or not. Their decisions are often influenced by socioeconomic determinants like illiteracy, poverty, and the oppressive mentality of the people in power. This influence coerces people to participate in research studies. In such situations, the difference between compensation and reimbursement becomes indistinct. In some instances, financial compensation for research participants may surpass their annual salary. Additionally, participation in a clinical trial may be the only way to access treatment for the person affected with the condition under study (Glickman et al. 2009).

Security in LICs like Pakistan is a big issue. There can be instances where a local government health official will escort investigators to rural areas for safety concerns. Sometimes, assistance from the police may be required to ensure foreign researchers’ safety in Pakistani rural areas. The presence of the local health official known to the participants and police presence can influence the process of informed consent.

The perception of mandatory ethical review of research involving human subjects is gaining popularity in Pakistan. In January 2004, the National Bioethics Committee (NBC) was established in Pakistan (Khan et al. 2012). The purpose of NBC is to promote and enable ethical health care delivery, health care research, and to provide a platform that links all the IRBs of various organizations. However, even with gradually increasing numbers of IRBs and availability of bioethics trained personnel, the registration and accreditation of research are lacking, and the general guidelines for conducting ethical research locally are nonexistent (Jafarey et al. 2012). In the Code of Ethics of the Pakistan Medical and Dental Council (2011), there is a section on research ethics where it recommends the Declaration of Helsinki, making it “binding on all medical practitioners”. However, the Pakistan Medical and Dental Council is not authorized to regulate human subjects research in Pakistan. In addition to this, not all research involving human participants gets submitted to IRB for ethical review (Jafarey et al. 2012). In addition, the quality and integrity of IRB reviews are also questionable. Conflict of interest arising from the financial relationship between IRB members and sponsors, especially from pharmaceutical companies, and also non-financial interest make ethical IRB review questionable (Khan et al. 2012). Lack of inconsistent review process and accountability makes the job of influential people in authority easier by avoiding the IRB and approaching head of the institutions directly for approval of their research proposal without going through ethical review. Sometimes these people request expedite review of the study without credible reason (Jafarey et al. 2012).

Power Dynamics

The problem of power dynamics is a very apparent concern in research ethics in LICs. There are several gatekeepers like Physicians, Field workers (FWs), Community leaders, IRBs, and politicians whose conflicting interests could jeopardize the rights of the study participants in LICs like Pakistan.

In LICs, like Pakistan, physicians are considered instruments of God, are well respected, and people do not question their authority (Jafarey 2002). People think doctors from HICs have miraculous powers and outstanding expertise (Memon et al. 2021). In physician-deprived areas, the only local doctor serving the area may be involved in the research project to recruit subjects or may even be the principal investigator himself. Respect of physicians prohibits people from asking questions regarding the purpose and benefits of research. Also, with the high esteem given to the physician in the region, it may be difficult for the potential study participants to refuse their physician’s request to “voluntarily” enroll in the trial. There could also be a fear of reprisals from the only doctor in the area if the participants decide not to enroll (Upvall and Hashwani 2001).

Within this highly complex process, the staff employed to undertake consent is the junior-most and often the least trained member of the team (Jafarey 2002). They are called field workers (FWs). In addition to taking consent in the first language of potential participants (regional or local), fieldworkers conduct relatively simple research procedures like surveys and health checks (Madiega et al. 2013; Simon and Mosavel 2010). They provide access to the out-of-reach population (stigmatized, hidden population) (Abdul-Quader et al. 2006), and inform researchers about culturally appropriate conduct of research, including the process of taking a consent (Kamuya et al. 2011). FWs role is filled with different and continuously changing ethical challenges, with significant consequences for the consent process (Kamuya et al. 2011; Kingori 2013). For example, some FWs are motivated to help their communities (Mosavel et al. 2011; Simon and Mosavel 2010), which can have both positive and negative impacts on the process of informed consent, like excessive undue encouragement of research participants in the context of a resource-limited healthcare system (Chantler et al. 2013). The primary objective of FWs is to get consent forms filled; they may be get paid on the number of consents forms they get signed, also known as “a finder’s fee” (Jafarey 2002). This incentive could distort their objectivity in honestly explaining the benefits and risks of the research study to the potential participants. Issues regarding possible compensation to these FWs and volunteers must be clear for the FWs to deliver all the information about the scientific merit of the project, possible benefits, and risks, rights of the participants like the right to withdrawal without any repercussion, faithfully to the participants at the time of recruitment.

In Pakistan, there are tightly knitted communities that are isolated from outside influence. The views of local politicians, religious leaders, elders of the community, or heads of the tribe, are generally considered superior. Pakistan’s rural and some urban areas are intertwined well in the Biradari system (Usman et al. 2020). The Biradari system has a very hands-on role in all kinds of community and local matters including issues varying from minor conflicts to substantial social disagreements (Chaudhry et al. 2014). The matters varying from arranging a marriage to issuing justice are mainly dealt with by a group of elders named “Panchayat” in Pakistan’s rural areas (Shahid 2012). The panchayat is the “gatekeeper of the community” and regulates outsiders’ access to community members, especially when accessing women (Upvall and Hashwani 2001). Refusal to conduct a study comes from these gatekeepers rather than the proposed research participants because they are less powerful (Khowaja-Punjwani 2015).

On the other hand, if the community leader has provided consent, it is difficult for an individual to say no against it. Their refusal to participate may sometimes also lead to denunciation by the tribe or community they live in (Khowaja-Punjwani 2015). These gatekeepers use the process of obtaining informed consent as a play of power and block access to the communities they control. They do this to protect themselves in the disguise of protecting their community members (Upvall and Hashwani 2001). This hierarchical system makes women study participants more vulnerable when considered, along with low levels of education, poverty, and the high prevalence of corruption in this part of the developing world.

Additionally, due to being educationally disadvantaged, there is a therapeutic misconception. The research participants believe the reason for conducting a particular research in the local community is to provide benefit to the study participants and if they disagree to participate in research, they will be harming themselves as they will not benefit from the research study (Khowaja-Punjwani 2015).

Providing a copy of the signed informed consent form to the research participant is an integral part of the pre-enrollment phase of research. Due to being educationally disadvantaged, people in LICs like Pakistan are not aware of their rights. As a result, gatekeepers did not allow the distribution of letters based on their power (Upvall and Hashwani 2001). Thus, informed consent can be used as a power play of the gatekeepers and elite to deny access to the social settings they control.

Family Structure: Male Dominance

Pakistani culture is family-centered and based on the community. Extended families live together for many generations. The system is patriarchal and based on hierarchy (Khan 2008). Male members in general and those who earn, are the decision-makers, and the women and other family members are expected to respect them (Memon et al. 2021). This way of life has been prevailing for generations and is generally well respected and remains unchallenged primarily from within. People fear authority (Khan 2008; Memon et al. 2021). Shared decision-making is intertwined in Pakistani culture. The male member is considered the power figure in the family structure.

From the Western world’s perspective, an ethical dilemma will arise if a male family member is used to approve the female member’s participation in the research. However, it seemed culturally appropriate in a Pakistani household, as elders and men are the decision-makers (Memon et al. 2021). A man has the authority to make all the decisions for the family and is not required to ask the opinions of other members. Due to the respect for the elders and the family, husband in particular, surrogate decision-making is the norm (Memon et al. 2021). The place of family is above all other social associations (Fatima 2021). In the research context, husbands and mother-in-law decide if the women will participate in the study (Jafarey 2002).

According to a survey conducted by Jafarey (2006) in Karachi, Pakistan, for recruiting women, a total of 60% of the participants expressed that it is essential to sort father’s or husband’s permission before reaching out to the woman. In situations where there was a conflict of opinions between the family members, it was apparent that the male participants’ opinion has more value than the female participants. A male-dominated family structure of Pakistan can disadvantage women regarding the process of informed, voluntary consent (Jafarey 2002). Unwilling inclusion and unnecessary exclusion from participating in the research is a realistic possibility when the women’s opinion is wholly disregarded. Moreover, expectations of men of the household and their extended family can pressure women not to exercise their right to self-governance (Nyika et al. 2009).

Illiteracy and Language Barriers

HICs have a literacy rate of almost 100%; even then, the research participants do not completely understand the research methods and the issues of consent. In international collaborative research, language differences and cultural distinctions make earning genuinely informed consent exceptionally challenging (Dawson and Kass 2005). In Pakistan, the literacy rate is 59% (World Bank 2017). The high prevalence of illiteracy hinders the ability to read and understand the informed consent forms. Not all people in Pakistan understand the national language (Urdu). Only those who have received education in English medium schools understand the English language. In general, people follow regional dialects (Fatima 2021). The usefulness of the consent form becomes questionable when the participants cannot read it.

Another problematic area is in the signing of the document. Participants may wholeheartedly agree to enroll, but there may be reluctance in signing a document that they cannot read or understand. Its content can be frightening as they may have only signed or used thumbprints for marriage certificates or other significant life events. They may fear that they may be signing away the little property they own on which they depend upon for their livelihood (Upvall and Hashwani 2001). Language barriers also make communication with the researcher unsatisfactory even with translators’ help (Jafarey 2002). Even if the form is translated into the national or regional languages, all the words cannot be completely translatable (Amerson and Strang 2015). Words such as “randomization” or “Placebo” may not be translated if there is no substitution in the local language (Woodsong and Karim 2005). The form may be lengthy. It may have complicated concepts alien to the culture and are not practical (Woodsong and Karim 2005). These language problems can lead to the refusal to participate in the study.

In LICs, patients do not like doctors to break the bad news. Therefore, in clinical practice, many physicians prefer to keep the description simple. This practice continues in research as well. However, this prevents the physician from giving the necessary details of the clinical trials to the prospective participant, which is a pre-requisite of informed consent (Fatima 2021). Generally, risks involved either related to the clinical practice or in a research study are under described to keep an optimistic approach. A survey was conducted on general practitioners in Pakistan to gain their insight about bioethics. The results of the survey showed that even though these physicians felt that a patient has a right to know about the treatment being offered, a good proportion of these physicians did not think it was necessary to explain the details of the treatment (Qidwai et al. 2002).

Silent Refusal of the Research Participants

The act of “silent refusals” highlights complex power interactions rooted in the process of decision-making for research participation in the Pakistani context, with significant consequences for the consent process. Due to the hierarchical society, people in less power and women use silent refusal instead of openly saying no to participate in the study or withdraw from it. This silent refusal is the approach to escape conflicts and safeguard relationships within the household and appear to obey the wishes of the family’s elders and men (Kamuya et al. 2015).

Lack of Training of Local Researchers

Most of the local researchers trained within the country have no idea of research ethics. Most of the IRB members do not get formal research ethics training. They lack the proficiency in dealing with specific protocols, especially those submitted by experienced researchers (Jafarey et al. 2012). Bioethics is not taught to undergraduate medical students (Khan et al. 2012), neither it is a part of mandatory postgraduate training. Where there is a component of bioethics in postgraduate curriculum, it consists of some basic introductory lectures. While the doctors trained by these institutions do get involved in conducting research, they have a very basic understanding of research ethics. Many of them are unaware of the intricate details of informed consent, and some of them do not even know the fundamental principles of informed consent.

Physicians and researchers in Pakistan are also a part of the patriarchal and hierarchical society. They are used to getting consent form signed by the head of the family on the behalf of the participant in the research or clinical treatment (Khan 2008). Additionally, medical personnel in rural regions do not have enough background knowledge and education to completely inform the study participants about the research. Also, it is a common trend in rural areas of Pakistan to get treated from people without proper medical qualifications such as local health workers and quacks (Khan 2008).

Confidentiality

Just like autonomy, confidentiality is also collective in Pakistani culture. There may be an ethical dilemma when relatives, friends, and neighbors arrive at the interview and join the research participants (Shaibu 2007). Elderly females of the household or the husband accompany a young woman during an interview. A woman cannot keep anything confidential from her husband and may face severe consequences if she does. Also, there is a potential for confidentiality breach if the FW is well known within the community (Simon and Mosavel 2010).

Tackling the Issues of Informed Consent in a Low-Income Country like Pakistan

There is a consensus that research should be done based on the country’s culture where it is taking place (Amerson and Strang 2015; CIOMS 2016). Researchers from HICs are often not aware of the cultural norms, values, and beliefs of the local community. The importance of community leaders and families in the context of decision-making, and community engagement or community consultation is gaining support and appreciation. Community involvement has become a requirement for ethical research in global arena (Provenzano et al. 2010). Obtaining consent from persons by giving adequate information to potential participants and local, familial, and religious advisors is ethically acceptable. This enables potential research subjects to participate (Alaei et al. 2013). Going through community gatekeepers by no means undermines the value of the individual’s understanding of the research and willingness to cooperate in the research. It provides a layer of safety and security for traditional communities where collective consciousness and living are the customs. During the process of seeking consent, trust is a vital part of communication and impacts the decisions about participation (Syse 2000). In research involving communities, a successful partnership between researchers and research participants aids to generate trust and collaboration (Coombe et al. 2020). There may be considerable variations in the level of trust. Level of trust may depend upon an individual’s or community’s prior experience with research and other contextual factors such as social status and power. Individuals can develop a trusting relationship when the person who is responsible for taking consent shows respect for their cultural beliefs, language, understanding of risks, and sociopolitical history (Calman et al. 2002).

To tackle the issues of informed consent in LICs like Pakistan, researchers should adopt consent-seeking procedures that are acceptable to the local community while ensuring that the voluntary participation of the individual is confirmed by an independent observer. It is important to have the consent form in the participant’s language, worded simply enough to facilitate understanding. The person taking the consent must also know the local language because the form would often have to be read out to an educationally disadvantaged participant. The participant must have enough time to discuss the implications with the research team and other community or family members. There also needs to be a mechanism devised to check the comprehension of the participants before the enrol. Innovative methods are required to gain informed consent in low literacy areas. The Food and Drug Administration suggested videotaping the consent process in LICs like Pakistan (Fatima 2021). This way educationally disadvantaged participants who are able to understand spoken English or national language but are unable to converse or write in the language in which informed consent is written will be protected (Hyder and Wali 2006). In a survey conducted by Hyder and Wali (2006), in LICs, various innovative methods were used to inform the participants about the research projects, such as explanation with Q&A sessions, community meetings, pictorial descriptions, and video messaging. Social gatherings and events can be used for mass sensitization. At such events, videos, animations, or charts can be used to introduce the community to the study project and highlight its importance to them and science. Raising general awareness in such a manner will facilitate a meaningful two-way discussion between the field worker and study participants when approached individually for recruitment. In the above mentioned study, for informed consent, in addition to written consent, several other methods were used like approval from village /community leaders, oral consent with witness signature, approval from a family member in research with adults, and test of participation understanding. Additionally, 63% of the survey respondents agree that US IRBs should require the community leaders’ approval and acquire individual consent (Hyder and Wali 2006).

Community is a key stakeholder in the research process. Community engagement involves approaching the host community directly and accumulating community knowledge to identify the issues, concerns, and the needs of the community. This approach provides insight into the cultural and social context of the community which will assist in achieving the goals of the research. The concept of community approval and individual consent is critical in research in the developing world and is consistent with the sociocultural tradition. Evidence from previous studies shows the importance of involving religious leaders in creating awareness and community engagement (Ruark et al. 2019). Therefore, engaging with the religious leaders can be an essential component of community engagement. Developing a cultural protocol for a specific community will inform and prime researchers from HICs about the local culture of their prospective research community before they approach the community engagement process (Memon et al. 2021).

Mostly in community-based research projects, the consent process is supervised by FWs or community workers who are relatively less experienced. Getting together teams of researchers and communication specialists to work can meaningfully enhance the legitimacy and utility of the informed consent process (Fatima 2021). The consent process must be given the due importance and should be monitored by senior research staff. Additionally, it should also involve communication specialists who are specifically selected to work on the consent process. Also, the junior staff should be given adequate training. All of these steps like field workers’ training, community presentations, use of innovative methods for dissemination of information, and video or audiotaped consents will require money to implement. Therefore, more budgetary resources from the research fund will have to be allocated for this essential process to ensure its success.

IRBs play a critical role in research conducted in LICs because an effective ethical review of research provides necessary protections and establishes scientific validity and ethical acceptability. As most of the IRBs in Pakistan are in educational institutions, for a meaningful ethical review process, the institution’s leadership should be proactive in constituting independent review boards that can function without interference (Jafarey et al. 2012). Additionally, researchers, reviewers, and administrators should be trained in basics of research ethics. In LICs like Pakistan, IRBs should have people with proficiency in scientific and methodological components of research under review. These institutions should specify the regulations or ethical guidelines they use and must ensure that any international research or externally sponsored research must go through local IRBs approval to protect the LIC’s populations (Khowaja-Punjwani 2015). A robust centralized regulatory body should be established to guide quality research with good understanding of the risks involved and awareness of ethical implications of the research.

Perception of scientific misconduct is different among different people. Therefore, young researchers must be fully trained in research ethics and responsible research. IRBs have a critical role in ensuring that the research meets international standards and norms. Continuous preparation of young researchers and graduate students through workshops and short courses is necessary for their sensitization to ethical aspects of research. They must be fully aware of the research misconduct, including fabrication, falsification, or plagiarism in the design and conduct of the study and results (Iqbal 2015).

The Way Ahead

LICs like Pakistan are vulnerable, and if cross-cultural research is being done in developing countries, then special consideration should be given to protect the people from further exploitation. Informed consent remains an ethical and practical issue in countries like Pakistan. Gaining truly informed and culturally appropriate consent is central to the ethical conduct of research and is particularly important in LICs like Pakistan. Taking informed consent is a mutual responsibility of the local IRBs and the research sponsors.

Recommendations

Informed Consent

• While conducting cross-cultural research, the researchers should consider language barriers, literacy problems, and cultural and family dynamics. Special consideration should be given to the family dynamics and community culture of the research place. If the research participants can only be approached through elders, community leaders, and tribal chiefs, this should be respected and honored (Amerson and Strang 2015).

• Due to different cultural setups and limited education, people will be less likely familiar with the objectives of conducting research (Benatar and Fleischer 2007). Under these circumstances, the researcher needs to modify the communication style that is suitable and acceptable to the local community. Information should be conveyed in a way that is accepted locally. It should be done in the local language using culturally appropriate idioms and analogies (Crigger et al. 2001).

• Innovative measures are needed to deliver information to a generally uneducated population to facilitate the understanding of the research objectives in a better way. One way is to use social gatherings for information delivery. The use of videos and charts can facilitate understanding of the research project and initiate meaningful discussion in interviews.

• A mechanism should be in place to evaluate the research participants’ comprehension of the protocol before authorizing their participation in a clinical study. For example, to ensure understanding, a questionnaire could be used. Additionally, the potential participant can be interviewed once they have received the information about the research and before consent is obtained.

• In places where the research participants cannot read and write, signing the consent form may be problematic. It would be appropriate to read the consent form and take verbal consent. This form of consent can be done by recording a video before the interview. Additionally, asking the participant to put a cross on the dotted line on the consent form in the presence of a witness can also suffice (Barata et al. 2006; Meadows et al. 2003).

• Researchers should be mindful of disclosing the information and must ensure that the disclosure is sensitive to the local context (Emanuel et al. 2004).

• More emphasis should be placed on the actual process of obtaining consent rather than the procedure of getting a thumb imprint or a signature on the consent form. Special consideration should be given to ensure that potential study participants are fully informed about their right to consent or refuse to participate in the research study.

• The process of informed consent should not be rushed. Participants should have enough time to discuss the research’s consequences with the team, family members, or the community.

• Role of Fieldworkers/ research coordinators: The role of fieldworkers/research coordinators is crucial in the enrollment and retention of participants in the study. Using clinical research coordinators instead of principle investigator to simplify the informed consent form and clarify misconception regarding the study will facilitate better understanding of the consent process resulting in improved enrollment (Nijhawan et al. 2013). They should be adequately trained to guarantee that their provided information is suitable for original approval and should know how to safeguard confidentiality.

• The gatekeepers should be made clear that their permission to approach the individuals in the community is limited and does not substitute for an individual’s right to give an informed and voluntary consent to participate in the research (Jafarey 2002).

• Prevent undue inducement: To avoid coercion or retribution from the family, allocation of compensation and other benefits related to the research should be done (Denny and Grady 2007).

Developing a Cultural Protocol

• Developing a cultural protocol for researchers from HICs would be an appropriate step in developing relationships between researchers from HICs and the communities in the LICs they are planning to recruit in the research study. A cultural protocol is another way of showing respect to different cultural values and beliefs. A protocol would become an integral part of the community and participatory engagement process (Memon et al. 2021).

The Process of Ethical Review

• IRBs should be responsible for ensuring transparency of the informed consent process and protecting the rights of human subjects.

• Steps should be taken to construct and support effective ethical review of research that is independent of any influencers like government and sponsors.

Independent Body

• In universities and institutions, where large volumes of research take place, an independent institutional consent-taking body or group could be formed. This institutional group could be engaged by the researchers only for the impartial dissemination of information to the community and enrolling individuals as study subjects. This mechanism would ensure that the sanctity of this vital process is maintained.

Mandatory Bioethics Education

• Bioethics education should be compulsory in undergraduate and postgraduate medical education, including a specific curriculum on research ethics. This step is a much-needed measure as it will abolish the unethical practices among researchers due to the lack of proper knowledge.

The Social Value of Research

• It should be ensured that the research participants and communities involved in research collect benefits from the conduct and results of research.

• The feasibility of research study within the social, political, and cultural context should be assessed.

• Relevance of the research should be justified to appropriate IRB, especially when the research is externally sponsored.

• LICs should only support clinical research that predominantly advantage their local population.

Conclusion

Research participants in Pakistan are vulnerable to exploitation at different levels due to a myriad of reasons discussed above. People make decisions according to their cultural and social context. Therefore, informed consent parameters in LICs like Pakistan should be culturally relevant. The research world should appreciate a plurality of standards of ethical research. Therefore, in blending Western and Eastern ideas of decision making, we need to respond to the Pakistani context while respecting the universal standards for conducting ethical research.

Data Availability

Not applicable.

Declaration

Competing Interest

The author declares no competing interests.