A Comprehensive Review on Ethical Considerations in Biomarker Research and Application

Abstract

A Comprehensive Review on Ethical Considerations in Biomarker Research and Application

Keywords

Introduction

A clinical trial consists of many stages, including phase 0 (micro-dosing studies), phase 1, phase 2, phase 3, and phase 4.[6] The stages of a clinical trial are as follows: Phase 0 and Phase 2, known as exploratory trials; Phase 1, which is not therapeutic; Phase 3, which is therapeutic confirmatory; and Phase 4, which is post-approval or post-marketing monitoring. To understand the dosage tolerability (pharmacokinetics) before being delivered as part of the phase 1 trial among healthy persons, phase 0, also known as the micro-dosing phase, is now conducted in human volunteers. This phase was formerly done in animals[6]. Clinical trials that examine the effects of an experimental therapy on a disease and its results may be categorized into four main types: those that aim to treat, prevent, detect, or diagnose.[7] Various types of biomarkers its mechanism, example and regulatory bodies were explored in table .1.

1. Overview of the ethical landscape in biomarker research

Ensuring the privacy and anonymity of participants is a top ethical concern in biomarker research. Concerns around the storage, sharing, and use of sensitive health information are heightened by the revelation of biomarkers. Protecting the anonymity of research participants is of the utmost importance, particularly when dealing with sensitive medical information that can expose them to prejudice or stigma.[19],[20]  One of the primary ethical dilemmas in biomarker research is the need to guarantee informed consent. Participants must have a thorough understanding of the use, preservation, and dissemination of their biological data. The possibility of the study scope expanding over time, perhaps including future data applications not initially anticipated, presents a special challenge for longitudinal studies[21]. The issue of permission is further complicated by the use of biomarkers in biobanks, where extensive datasets are held and may be accessed by several researchers for various investigations[21]. Privacy is a major issue of concern. Stringent measures are required to ensure the confidentiality of participant information, especially when it incorporates genetic data, due to the sensitive nature of biomarker data[22]. The potential for re-identification, even from supposedly anonymised data, presents a danger to privacy and underscores the need for strong data protection measures. Moreover, the growing incorporation of biomarker data into electronic health records and other digital platforms intensifies the possibility of privacy breaches and highlights the need for robust data management systems. The ethical concerns stem from issues of equity and access in biomarker research. Unequal distribution of access to the advantages of biomarker research might worsen current health inequities[23].

2. Historical Context and Ethical Evolution

Following WWII, Nuremberg tried 23 Nazi medical professionals and scientists for the systematic killing of captives taken from concentration camps for scientific experiments. Only fifteen of the twenty-three defendants received guilty verdicts. Eight received sentences ranging from ten years to life in jail, while seven received death by hanging sentences. These regulations, commonly referred to as the Nuremberg Code, were established in 1947 to regulate research involving human subjects, following a trial that revealed the existence of torture. The code placed emphasis on obtaining informed permission, hiring scientists with animal experience, justifying risks based on their benefits, and preventing psychological and bodily harm, death, or permanent disability[24] But other researchers disregarded the rule and kept taking advantage of patients' trust. The Willow brook Hepatitis Study (1956) included infecting children with a mild strain of hepatitis on purpose, getting their parents' assent without warning them about the risks, and offering them the chance to attend a certain school if they participated[25] Researchers in the Jewish Chronic Disease Study implanted cancer cells into elderly people without adequately explaining the risks to them in 1963. Both trials relied on a group of patients who were too weak to make their own decisions[26] A set of standards meant to protect the rights and welfare of people taking part in clinical trials were established in the 1964 World Medical Association (WMA) General Assembly in Helsinki, Finland, in response to the new circumstances. The 64th World Medical Assembly in Brazil made the most recent revisions to this document, which is known as the Declaration of Helsinki, and it undergoes periodic revisions. While the International Code of Medical Ethics states that "A physician shall act in the patient's best interest when providing medical care," the World Medical Association's statement binds the physician with the words, "The health of my patient will be my first consideration." It is the explicit responsibility of physicians participating in medical research to ensure the safety, health, and rights of their patients, as stated in the statement[27]. In 1972, the United States Public Health Service (Tuskegee Syphilis Study) revealed unethical research that was undertaken, causing a great deal of outrage. The study was commenced in 1932 to investigate the untreated progression of syphilis in African-American participants. Despite the availability of penicillin, the trial subjects were deliberately denied treatment. When this information was revealed, it was discovered that 28 individuals had died and 100 subjects had suffered permanent disabilities as a result. Additionally, 40 wives were infected, leading to 19 cases of congenital syphilis. The research not only denied but also misled the participants, falsely claiming that spinal tapas were a unique method of therapy[28] Many nations issued their own GCP regulations in the years that followed; in 1980, India's Indian Council of Medical Research (ICMR) issued a policy statement outlining the ethical issues surrounding human subject research for the first time. In response to debates, the ICMR released "Ethical Guidelines for Biomedical Research on Human Subjects" in 2000 and made further revisions in 2006[29] Ethical norms and policies surrounding biomarker research have changed in light of these and other debates. Ethical research standards were established by the Nuremberg Code (1947) and the Declaration of Helsinki (1964), which stressed the need for informed consent and the protection of participants. On the other hand, new rules pertaining to genetics and biobanking have emerged to deal with the growing complexity of biomarker research. Examples of such comprehensive frameworks for the ethical use of genetic information and biobanking practices include the UNESCO Universal Declaration on Bioethics and Human Rights (2005) and the OECD Guidelines on Human Bio-banks and Genetic Research Databases (2009). These documents guarantee that research is carried out in a way that respects human dignity, privacy, and justice[30].

3. Key Ethical Principles in Biomarker Research

The notion of respect for humans is a fundamental ethical guideline in biomarker research, highlighting the need for obtaining informed permission. Participants must possess comprehensive knowledge on the objective, methodologies, possible hazards, and advantages of the study, as well as their entitlement to withdraw at any given moment. Obtaining informed permission is vital in biomarker research since sensitive biological data is routinely collected. This ensures that participants fully comprehend how their data will be used, maintained, and perhaps disclosed. In longitudinal studies, it is crucial to have continuous contact with participants due to the potential changes in the study scope over time[31]. In biomarker research, voluntary involvement is a necessary aspect of respecting individuals because it upholds the notion of autonomy. Participants should be granted autonomy to make well-informed choices about their participation, free from any type of force or undue influence. This includes the entitlement to decline involvement or to retract from the research at any juncture, including subsequent to the commencement of data collection. Preserving independence in biomarker research poses significant difficulties, especially when working with susceptible groups, necessitating extra measures to defend participants' rights[32].

4. Beneficence and non-malfeasance:

According to the ethical principles of beneficence and non-malfeasance, researchers must maximize the potential benefits of biomarker research while minimizing potential hazards. Maintaining this equilibrium is critical because biomarker research frequently involves novel and experimental methodologies that may include unforeseen hazards. Researchers need to carefully weigh the possible benefits of finding new biomarkers, like better disease diagnosis, treatment, or prevention, against the possible risks, which could include harm to people's bodies or minds, or invasions of privacy[33] The principle of non-malfeasance, which emphasizes the need to avoid causing damage, is especially relevant when considering the use of biomarker research results. It is essential to confirm and demonstrate the safety and efficacy of any identified biomarker before its use in clinical settings. Furthermore, it is crucial to exercise caution when sharing biomarker-related information to avoid any misunderstanding that may result in unwarranted distress or injury. It is crucial to safeguard participants and the general public by ensuring the ethical conduct and use of biomarker research[34]

5. Privacy and Confidentiality Concerns:

Data collected and analyzed via biomarker research may provide very personal information about people, such as their genetic makeup and illness risk. Improper handling of the data can pose serious privacy hazards. Sensitive biological data, such as DNA sequences, can link back to specific individuals even after anonymization, thereby increasing the risk of re-identification and abuse. In order to avoid damage, such as genetic prejudice or stigmatization, and to maintain study participants' confidence, it is crucial to manage this information safely[35]. The rapid development of genetic technology has enhanced the capacity to produce huge datasets rapidly and inexpensively, further compounding the ethical difficulties of dealing with such sensitive information. This means that institutions and researchers need to take strong precautions to protect their data, such as using encryption, using secure storage, and implementing access restrictions. Furthermore, ethical concerns should govern the use of this data, with the goal of obtaining participants' unambiguous and transparent agreement after providing them with comprehensive information about the data's intended use, storage, and sharing[30]. In order to validate results, replicate studies, and collaborate widely across institutions, data sharing is essential in biomarker research. But there are major privacy issues with exchanging genetic and biological data. Despite the frequent use of de-identification measures to protect participant privacy, the potential for re-identification persists, particularly with the progress of computational tools for dataset connectivity[36].

6. Informed Consent Challenges:

Biomarker research sometimes entails complex technology and procedures, which might provide challenges for participants in terms of comprehension. These investigations may include the study of genetic data, the long-term storage of biological samples, and the possibility of using the data for future research purposes. Providing thorough education to participants may pose challenges due to the intricacy of elucidating various aspects in a clear and comprehensible manner[37]. The possibility of using the data for future research or sharing it with other academics complicates matters. Participants must be provided with information on these potential outcomes, which may not be completely specified at the moment of consent, thereby adding complexity to the procedure. As a result, there is a risk that individuals may agree to take part in the study without understanding the full extent of their engagement or the long-term consequences of their consent[38],[39].

7. Issues with comprehension and voluntariness:

The complexity of the material presented throughout the consent procedure may cause participants to have difficulty understanding. Research indicates that individuals frequently struggle to understand specialized terminology and the potential future use of their data, leading to concerns about the completeness of their consent[40]. Informed consent and voluntariness are also significant considerations. Some participants may feel compelled to provide their agreement because of their personal relationships with the researchers or healthcare providers, while others may feel pressured because of the potential advantages, such as access to new therapies. An important component of keeping research ethical is making sure people know it's completely voluntary and can stop at any moment without any repercussions[41].

8. Dynamic consent models and ongoing participant engagement:

Dynamic consent models provide a more adaptable and participant-centred alternative to conventional informed consent procedures, which have their own set of problems. By keeping participants updated on the study's progress and the use of their data, dynamic consent enables them to modify their permission as needed[42]

Because the intended outcomes of data use cannot be entirely clear when permission is first granted, this concept is especially applicable to biomarker research. Dynamic consent enables continuous engagement, which helps keep participants informed and allows them to make participation choices based on the most up-to-date facts. In addition to improving the research's ethical integrity, it gives participants a feeling of control and builds trust[43][44].

9. Ethical Issues in Biomarker Application and Translation

Early detection and more precise diagnoses are two ways in which biomarkers have the potential to enhance patient outcomes when used in clinical practice. On the other hand, there are ethical concerns that arise from the possible abuse or over-reliance on biomarker data that are associated with biomarkers' clinical adoption. Premature use of biomarkers without adequate validation raises the possibility of erroneous diagnoses and treatment choices. Also, if some people can't get their hands on biomarkers, the healthcare gap might widen even more from its already substantial size[45],[46].

10. Predictive and diagnostic use of biomarkers and ethical implications:

Biomarkers greatly assist in predicting illness risk and making early diagnoses. Concerns about privacy, prejudice, and psychological effects are among the ethical issues brought up by predictive biomarkers. For instance, individuals with a high genetic risk for a particular illness may face discrimination when applying for jobs or health insurance. In addition, knowing that you could become sick in the future can be very stressful emotionally, especially if there aren't any ways to avoid or cure it[47][48]. Despite their usefulness, diagnostic biomarkers pose moral questions. False positives or negatives may increase the risk of unwarranted treatments or a delusion of safety. Not only does it take a lot of knowledge to understand biomarker data, but there's also a chance that doctors may exaggerate the usefulness or accuracy of these tests, which might cause ethical problems while caring for patients[49].

11. Ethical dilemmas in personalized medicine and pharmacogenomics:

Personalized medicine and pharmacogenomics are at the cutting edge of medical innovation, offering the promise to transform therapy by customizing medicines based on individual genetic profiles. Nevertheless, these advancements give rise to intricate ethical quandaries. An important issue to consider is the possibility of uneven access to personalized therapies, which would only be accessible to those who have the financial means to pay them. This might further exacerbate current health inequalities[45] One further ethical concern in pharmacogenomics is the potential for excessive dependence on genetic data when making treatment decisions. This might result in the neglect of other significant elements, such as environmental impacts and patient preferences. Moreover, there is a possible danger of genetic determinism when people are reduced to their genetic profiles, which might result in stigmatization or prejudice[50] The ethical dilemmas in personalized medicine also include concerns around permission and the protection of data privacy. Robust permission mechanisms are necessary when using genetic data to ensure that patients have a clear understanding of how their data will be used, preserved, and shared. It is crucial to effectively control the possibility for further utilization of genetic information, such as by other entities, in order to safeguard patient confidentiality and autonomy[45],[50].

12. Considerations for research involving children, elderly, and marginalized communities:

Children, the elderly and marginalized communities are among the most susceptible populations in medical research. Given their participation in biomarker research, it is essential to subject them to meticulous ethical examination in order to safeguard their rights and welfare. Children's principal ethical issue pertains to their capacity, both legally and cognitively, to provide informed permission. Typically, guardians or parents provide permission on behalf of children. However, it is equally important to observe the ethical concept of assent, which means considering the child's desire to participate in addition to parental approval. Under-represented in biomarker research, vulnerable communities often experience inequities in the advancement of diagnoses and therapies. Researchers should proactively seek out a wide range of volunteers and guarantee equitable inclusion of marginalized populations in their research[51]. The elderly, particularly those with cognitive impairments such as dementia, have comparable ethical dilemmas. The deterioration of cognitive function may hinder their comprehension of intricate study methods and potential hazards, making them more susceptible to coercion or excessive manipulation. Ethical standards include conducting comprehensive evaluations of decision-making ability and using legally authorized agents where needed to guarantee that permission is both well-informed and freely given[52].  Biomarker research typically fails to adequately represent marginalized populations, such as racial and ethnic minorities, economically disadvantaged groups, and those with restricted healthcare access. The lack of representation not only hinders the capacity to apply research results to a broader population but also contributes to health inequalities by excluding these groups from the advantages of medical progress. The Tuskegee Syphilis Study and other historical cases of exploitation have created a lasting sense of distrust, which makes the process of recruiting and involving participants much more challenging[53].

13. Ensuring fair representation and avoiding exploitation:

Fair inclusion of marginalized groups in biomarker research is essential to the moral conduct of science and the fair allocation of its advantages. Including a variety of populations allows for the collection of more thorough data, leading to conclusions applicable to a wide range of demographic groups. Careful handling is required to prevent exploitation. Particularly if they believe that participating would provide them with access to financial incentives or medical treatment that they would not otherwise have, vulnerable people may be especially vulnerable to coercion[54]. Recognizing and resolving the power disparities that often exist between academics and disadvantaged people is also crucial. Researchers need to be careful not to engage in any activities that might be seen as being exploitative, such as recruiting subjects without providing them with sufficient information about the risks and rewards or using technical terms that are difficult for participants to grasp[55].

14. Cultural sensitivity and ethical practices in diverse populations:

Ethical research involving vulnerable groups must priorities cultural sensitivity. The ways in which people in various groups understand health, disease, and medical research may vary due to differences in norms, assumptions, and practices. Ethical research practices and the treatment of participants with respect and dignity depend on taking these cultural considerations into account and incorporating them into the study process[56]. Furthermore, maintaining ethical standards in biomarker research necessitates continuous involvement with participants to guarantee the protection of their rights throughout the study. This entails providing transparent and easily understandable information on the research's progress, its results, and any potential hazards that may emerge. Researchers must also be ready to handle any concerns or enquiries that participants may have, promoting an atmosphere of openness and mutual regard[57].

15. Ethical issues in the commercialization of biomarker technologies

Scientists commercialize biomarker technologies by turning scientific findings into marketable products like diagnostic tools, treatment interventions, or screening procedures. Although this procedure may result in substantial improvements in public health, it also gives rise to several ethical considerations. An additional concern is the possibility for profit-driven interests to influence the allocation of research resources, perhaps shifting focus away from crucial but less financially lucrative fields of study. Researchers may priorities studying biomarkers for illnesses that are more common in affluent communities, since there is a higher possibility of financial gain, rather than focusing on ailments that disproportionately impact underserved or economically disadvantaged groups[58]. In addition, the act of seeking patents and developing private technology might establish obstacles to the sharing of data and cooperation, both of which are crucial for the progression of scientific understanding and the enhancement of public health results. The exclusive characteristics of commercialized biomarkers may result in the retention of vital data that might be advantageous to the wider research community or enhance patient care. This exclusive methodology contradicts the ethical concept of beneficence, which highlights the significance of maximizing advantages and minimizing damage in research .Furthermore, the act of commercializing biomarker technology without sufficient validation might result in premature promotion, which raises worries about the possible damage it may do to patients and the general public[59].

16. Managing conflicts of interest in biomarker research:

Biomarker studies are fraught with potential conflicts of interest, especially when academics or organizations involved have financial links to companies that stand to gain from the results. Companies with a financial interest in the commercialization of biomarker technology may have conflicts of interest (COIs) due to advisory fees, stock ownership, or research funding. If these financial ties influence the study's planning, execution, and reporting, it could jeopardize the objectivity and reliability of the research and its results[60]. In order to handle conflicts of interest, it is crucial to set up transparent protocols that demand the disclosure of any relevant financial ties. To reduce the dangers of COIs, disclosure alone is not enough. Also, academic institutions need to figure out how to lessen the effect these conflicts have on study results. Examples of such approaches include separating research from business decision-making processes, using blinded or independent data analysis, and implementing independent project monitoring[61]. Journals and funding organizations also have a duty to make sure researchers follow all applicable ethical guidelines and implement strict COI procedures[62].

17. Transparency and disclosure requirements:

When discussing commercialization and potential conflicts of interest, transparency is essential in ethical biomarker research. To keep the public's faith and guarantee that researchers are held responsible for their work, it is crucial that they disclose any financial interests and ties. When presenting or publishing their work, researchers have an ethical obligation to be transparent about any financial relationships that may be seen as impacting their study. This includes disclosing this information to their institutions[63]. Furthermore, it is essential for institutions and funding organizations to implement and uphold rules that encourage openness at every stage of the research process, in addition to requiring individual researchers to disclose their findings. This entails mandating the registration of clinical trials and the dissemination of all findings, irrespective of the outcome, to mitigate the risk of selective reporting or publication bias[64]. Journals should mandate authors to provide comprehensive disclosures of any possible conflicts of interest (COIs), including financial associations, intellectual property stakes, and any other elements that could potentially exert influence on the study. The public should have access to these disclosures for impartial examination and to ensure understanding of the study within the appropriate framework[65]. Transparency also applies to the wider scientific community and the public, who have a significant stake in the ethical behavior of biomarker research. Engaging with stakeholders, including patients, advocacy organizations, and legislators, aids in directing research towards public health needs and ensuring equitable distribution of the benefits of biomarker technology[66].

18. Overview of national and international regulatory bodies:

Regulatory agencies at both the national and international levels have a crucial responsibility in monitoring biomedical research to ensure compliance with ethical standards and legal obligations. Internationally, the World Health Organization (WHO) and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) establish recommendations that have a worldwide impact on research procedures. The World Health Organization (WHO) is in charge of guiding global health affairs and establishing global norms and standards. Meanwhile, the worldwide Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) ensures consistency in regulatory demands across various areas, namely in the realm of drug research and clinical trials. Transparency also applies to the wider scientific community and the public, who have a significant stake in the ethical behavior of biomarker research. Engaging with stakeholders, including patients, advocacy organizations, and legislators, ensures that research objectives align with public health standards and equitable distribution of the benefits of biomarker technologies[67]. Adherence to ethical guidelines and standards is crucial in biomedical research. These guidelines serve as a framework for making moral decisions and safeguarding the well-being of human subjects. The Declaration of Helsinki, created by the World Medical Association (WMA), is a crucial international ethical guideline. The Declaration of Helsinki, first adopted in 1964, provides a comprehensive framework of moral principles for medical research involving human subjects. It covers important aspects such as informed consent, risk-benefit assessment, and safeguarding vulnerable populations[68]. The International Ethical Guidelines for Health-Related Research Involving Humans, developed by the Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the WHO, are an important set of guidelines to consider. The CIOMS guidelines serve as a valuable addition to the Declaration of Helsinki, offering comprehensive guidance on various ethical concerns. These include the appropriate use of placebos, conducting research in low-resource settings, and outlining the responsibilities of sponsors and researchers[69]. The Belmont Report, released in 1979 by the U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, is a fundamental document in the field of research ethics. The Belmont Report outlines three fundamental principles: respect for autonomy, beneficence, and justice. These principles have had an impact on the development of research ethics rules in the United States and elsewhere. They provide the foundation for the Common Rule, which regulates research involving human beings in the United States[70]. Various countries have established regulatory agencies to oversee different aspects of their healthcare systems. For instance, the United Kingdom has the Medicines and Healthcare Products Regulatory Agency (MHRA), Japan has the Pharmaceuticals and Medical Devices Agency (PMDA), and India has the Central Drugs Standard Control Organisation (CDSCO). The bodies in question are tasked with the implementation of national regulations that are in line with international standards, taking into account local ethical, cultural, and legal contexts[71].

19. Ethical guidelines and standards:

Ethical guidelines and standards are crucial in biomedical research, as they establish a framework for ethical decision-making and safeguard the well-being of human subjects. The Declaration of Helsinki, created by the World Medical Association (WMA), is a crucial international ethical guideline. The Declaration of Helsinki, which was first adopted in 1964, establishes ethical guidelines for medical research involving human subjects. It covers important aspects such as informed consent, risk-benefit assessment, and safeguarding vulnerable populations[72]. The Council for International Organisations of Medical Sciences (CIOMS) collaborated with the World Health Organisation (WHO) to produce the International Ethical Rules for Health-Related Research Involving Humans, which is another important set of rules. The CIOMS recommendations serve as a supplement to the Declaration of Helsinki and provide more comprehensive instructions on certain ethical concerns, including the use of placebos, conducting research in resource-limited environments, and outlining the obligations of sponsors and researchers[69].

20. Role of Institutional Review Boards (IRBs) and ethics committees:

Institutional Review Boards (IRBs), also known as ethics committees, are crucial elements in research governance frameworks. The responsibility of IRBs is to review and approve research protocols, ensuring their compliance with ethical standards and regulatory requirements. An IRB's main role is to ensure the protection of human research participants by carefully evaluating the study's design, informed consent process, and risk-benefit ratio[73]. Research institutions such as universities, hospitals, and research organizations typically house IRBs. These committees usually consist of a wide range of individuals, such as scientists, ethicists, legal experts, and community representatives. Their purpose is to conduct a thorough evaluation of research proposals from various angles. IRBs are carefully structured to guarantee a thorough ethical review process and to safeguard the well-being of research participants[74]. IRBs have a broader scope than just granting initial approval for research protocols. Besides their primary responsibilities, they also oversee the continuous monitoring of research activities. This includes carefully reviewing any amendments to the study protocol, adverse events, and deviations from approved procedures. To ensure ethical compliance throughout the research, continuous oversight is critical[75]. Furthermore, certain countries have implemented centralized ethics review bodies to oversee research conducted on a national or regional scale, in addition to national and institutional IRBs. In the United Kingdom, the Health Research Authority (HRA) oversees the Research Ethics Committees (RECs) to ensure that research is ethically reviewed consistently across the country[76]. In India, the Central Ethics Committee on Human Research (CECHR) is responsible for overseeing the ethical conduct of research at the national level. It provides guidance to institutional ethics committees, ensuring that research is conducted in an ethical manner[29].

21. Public perception of biomarker research and its applications:

Several elements, including media portrayal, individual encounters and wider cultural principles, influence the public's perspective on biomarker research. While biomarker technologies significantly advance healthcare, they also raise concerns about privacy, discrimination, and the potential misuse of genetic information. The public's attitude towards biomarker research may be quite divergent, with some individuals perceiving it as a crucial advancement towards more efficient and tailored therapies, while others may have doubts or concerns about the potential consequences of these technologies[77]. An important issue is the possibility of genetic discrimination, which refers to the unequal treatment of persons based on their genetic information. The presence of this anxiety might result in public reluctance to engage in biomarker research or undertake genetic testing, despite the substantial potential advantages[78]. Additionally, the use of biomarkers in prognostic medicine, where people are categorised as having a heightened susceptibility to certain illnesses based on their genetic makeup, may result in feelings of unease and ambiguity about what lies ahead[79]. The ethical problems of data privacy can impact public opinion. Questions arise about the access and protection of sensitive biological and genetic information throughout its collection, storage, and use. The occurrence of prominent data breaches and the improper use of genetic data in previous instances have intensified public awareness and apprehension around these matters[80].

22. Engaging communities and stakeholders in ethical discourse:

To ensure that the development and use of these technologies are in line with society's values and goals, it is critical to include communities and stakeholders in the ethical discussion around biomarker research. Public engagement projects facilitate the connection between academics and the wider community, promoting a reciprocal conversation that enables the sharing of information, issues, and opinions[81]. An effective method for including the public is to include a wide range of individuals with different interests and perspectives at every stage of the research, including study design, execution, and the sharing of findings. This may include collaborating with patient advocacy groups, community organisations, and lawmakers to ensure that the perspectives of those most impacted by biomarker research are acknowledged and taken into account.[82]. Organizing public forums, seminars, and deliberative events that bring together academics, ethicists, patients, and members of the public to engage in discussions on the consequences of biomarker research can foster ethical discourse. These events may elucidate complex scientific ideas, provide a forum for varied perspectives, and foster a more comprehensive approach to ethical decision-making[83].

23. Education and communication strategies for public awareness:

Efficient educational and communicative tactics are essential for improving public knowledge and comprehension of biomarker research. Providing people with clear, precise, and easily understandable information may allow them to make well-informed decisions about their involvement in research and use of biomarker-based technology[84]. An essential approach is creating teaching resources that explain the fundamental principles of biomarker research, its possible advantages, and the corresponding hazards. It is important to customize these materials for various audiences, taking into account variables such as age, educational attainment, and cultural heritage. We can effectively engage a wide range of individuals using various mediums like interactive internet resources, pamphlets, and movies. However, to effectively communicate with healthcare professionals, patients, and policymakers, more targeted materials may be necessary[85]. Transparency and trust-building should also be the focal points of communication activities. The aims of biomarker research, the procedures employed to safeguard participants' privacy, and the possible consequences of the results must all be openly communicated by researchers and institutions. This has the potential to allay public fears and increase faith in scientific enquiry[86]. Biomarker technologies may be better understood and accepted. Social media, television, and community events are just a few of the many media outlets that these campaigns may employ to spread the word about the value of biomarker research in enhancing healthcare outcomes to a wide range of people[87].

24. Future Directions and Emerging Ethical Challenges

The use of artificial intelligence (AI) and machine learning techniques in biomarker research is revolutionizing the profession by facilitating the examination of extensive datasets, discovering new biomarkers, and tailoring medical interventions with unparalleled accuracy. Nevertheless, these technologies give rise to substantial ethical considerations, namely pertaining to data privacy, algorithmic bias, and the openness of judgments made by AI[88]. Artificial intelligence (AI) systems often depend on extensive datasets that include sensitive genetic and health data. This highlights the need for strong data security mechanisms to prevent unauthorized access and exploitation of the information[89]. Algorithmic bias is a significant challenge in AI. Training AI models on biased information could either perpetuate or exacerbate existing health inequalities, leading to uneven outcomes for different population groups[90]. Artificial intelligence (AI) also poses new questions about openness and accountability in biomarker research. Many see AI-driven judgments as "black boxes," as there is little information available about the reasoning behind them. This opacity makes it harder to monitor the ethical and responsible use of AI in healthcare and may erode confidence in these applications[91].

25. Ethical frameworks for evolving research methodologies:

Ethical frameworks that are flexible enough to accommodate new research procedures and technology are becoming more and more necessary as biomarker research approaches continue to change. Conventional moral principles, such as those described in the Belmont Report or the Declaration of Helsinki, provide a strong basis but may not completely address the particular difficulties presented by developing technology [27]. Adaptive ethical frameworks should include principles that specifically tackle the issues posed by new research methodology. These principles should address the need for dynamic consent models, which enable participants to modify their consent choices as time goes on[42]. Furthermore, these frameworks need to take into account the ethical ramifications of analyzing real-time data and the possibility of ongoing surveillance of persons via wearable devices and other digital health technology[89].

26. Preparing for future ethical dilemmas in biomarker research:

As biomarker research progresses, it is expected that new ethical dilemmas will arise. To effectively handle these challenges, researchers, ethicists, and policymakers must proactively anticipate and address them. An area of concern is the growing use of biomarkers in predictive medicine. This involves identifying individuals at high risk for certain diseases based on their genetic profiles. There may be ethical dilemmas arising from genetic discrimination, stigmatization, and the psychological consequences of being identified as "high risk."[92]. One additional ethical concern that is arising involves the possibility of companies exploiting biomarker data for commercial gain, using genetic information in ways that may not priorities the well-being of individuals or society. In the upcoming years, it will be crucial to priorities the ethical aspect of biomarker research, ensuring its alignment with public health and patient well-being, rather than being driven solely by commercial interests[93]. In order to adequately address existing and potential future ethical quandaries, it is imperative to cultivate continuous discourse among academics, ethicists, politicians, and the general public. The purpose of this discourse is to primarily detect and resolve any ethical difficulties at an early stage, as well as to ensure that ethical concerns keep up with technical progress. Ongoing education and training in research ethics will be essential for providing researchers and healthcare practitioners with the necessary skills to negotiate the complex ethical terrain of biomarker research[94].

CONCLUSION:

Emerging biomarker research has the potential to transform healthcare by enhancing the accuracy of diagnoses, optimizing treatment approaches, and tailoring medicine to individual patients. The ethical dimensions of biomarker research and its implementation are multifaceted and need careful consideration. These dimensions include issues of privacy, informed consent, equitable access, exploitation, and bias. Ethical considerations are safeguarding sensitive genetic and health data, implementing transparent and inclusive consent processes, and ensuring that advancements in biomarker research benefit all demographic groups without exacerbating existing imbalances.

Ethics play a vital role in the field of biomarker science. Ensuring public confidence, upholding research honesty, and safeguarding the rights and welfare of biomarker study participants necessitates adherence to ethical principles and frameworks. The emergence of new technologies, such as AI and machine learning, necessitates the adaptation of ethical considerations to address novel challenges and opportunities. This entails addressing algorithmic bias, advocating for openness in AI-based decision-making, and upholding fairness and equality in the use of biomarker technology. As we progress, it is crucial to maintain constant watchfulness and uphold ethical accountability in biomarker research. Collaboration among researchers, ethicists, politicians, and other stakeholders is necessary to proactively identify and resolve ethical challenges that arise with the progress of biomarker science. This will ensure that the field evolves in a way that is both scientifically sound and morally strong. By giving priority to ethics, the biomarker research community may optimize the advantages of these formidable instruments while reducing possible risks, eventually contributing to a fairer and more just healthcare system.

Conflict of Interest

The authors have no conflicts of interest regarding this investigation.

REFERENCES

1. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS 2010;5:463–6. https://doi.org/10.1097/COH.0b013e32833ed177.
2. Lesnock JL, Darcy KM, Tian C, Deloia JA, Thrall MM, Zahn C, et al. BRCA1 expression and improved survival in ovarian cancer patients treated with intraperitoneal cisplatin and paclitaxel: a Gynecologic Oncology Group Study. Br J Cancer 2013;108:1231–7. https://doi.org/10.1038/bjc.2013.70.
3. Lou E, Johnson M, Sima C, Gonzalez-Espinoza R, Fleisher M, Kris MG, et al. Serum biomarkers for assessing histology and outcomes in patients with metastatic lung cancer. Cancer Biomark 2014;14:207–14. https://doi.org/10.3233/CBM-140399.
4. Kandi V, Suvvari TK, Vadakedath S, Godishala V. Microbes, Clinical trials, Drug Discovery, and Vaccine Development: The Current Perspectives. Borneo J Pharm 2021;4:311–23. https://doi.org/10.33084/bjop.v4i4.2571.
5. Purna Singh A, Shahapur PR, Vadakedath S, Bharadwaj VG, Kumar DP, Pinnelli VB, et al. Research Question, Objectives, and Endpoints in Clinical and Oncological Research: A Comprehensive Review. Cureus 2022;14:e29575. https://doi.org/10.7759/cureus.29575.
6. Kandi V, Vadakedath S. Clinical Research: An Overview of Study Types, Designs, and Their Implications in the Public Health Perspective. Am J Clin Med Res 2021;9:36–42. https://doi.org/10.12691/ajcmr-9-2-1.
7. Kandi V, Vundecode A, Godalwar TR, Dasari S, Vadakedath S, Godishala V. The Current Perspectives in Clinical Research: Computer-Assisted Drug Designing, Ethics, and Good Clinical Practice. Borneo J Pharm 2022;5:161–78. https://doi.org/10.33084/bjop.v5i2.3013.
8. Balk SP, Ko Y-J, Bubley GJ. Biology of prostate-specific antigen. J Clin Oncol 2003;21:383–91. https://doi.org/10.1200/JCO.2003.02.083.
9. Omland T, de Lemos JA, Sabatine MS, Christophi CA, Rice MM, Jablonski KA, et al. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med 2009;361:2538–47. https://doi.org/10.1056/NEJMoa0805299.
10. Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark Insights 2016;11:95–104. https://doi.org/10.4137/BMI.S38440.
11. Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 2007;26:6469–87. https://doi.org/10.1038/sj.onc.1210477.
12. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949–54. https://doi.org/10.1038/nature00766.
13. Li LT, Jiang G, Chen Q, Zheng JN. Ki67 is a promising molecular target in the diagnosis of cancer (review). Mol Med Rep 2015;11:1566–72. https://doi.org/10.3892/mmr.2014.2914.
14. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–39. https://doi.org/10.1056/NEJMoa040938.
15. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:1626–34. https://doi.org/10.1200/JCO.2007.14.7116.
16. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443–54. https://doi.org/10.1056/NEJMoa1200690.
17. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task F. Hypertens (Dallas, Tex  1979) 2018;71:1269–324. https://doi.org/10.1161/HYP.0000000000000066
18. Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011;89:806–15. https://doi.org/10.1038/clpt.2011.58.
19. Schulte PA, Hunter D, Rothman N. Ethical and social issues in the use of biomarkers in epidemiological research. IARC Sci Publ 1997:313–8.
20. Pappas G, Hyder AA. Exploring ethical considerations for the use of biological and physiological markers in population-based surveys in less developed countries. Global Health 2005;1:16. https://doi.org/10.1186/1744-8603-1-16.
21. Haga SB, Beskow LM. Ethical, legal, and social implications of biobanks for genetics research. Adv Genet 2008;60:505–44. https://doi.org/10.1016/S0065-2660(07)00418-X.
22. Knoppers BM, Chadwick R. Human genetic research: emerging trends in ethics. Nat Rev Genet 2005;6:75–9. https://doi.org/10.1038/nrg1505.
23. Lavery J V. “Wicked problems”, community engagement and the need for an implementation science for research ethics. J Med Ethics 2018;44:163–4. https://doi.org/10.1136/medethics-2016-103573.
24. Nuremberg Military Tribunal. The Nuremberg Code. JAMA 1996;276:1691.
25. Krugman S. The Willowbrook hepatitis studies revisited: ethical aspects. Rev Infect Dis 1986;8:157–62. https://doi.org/10.1093/clinids/8.1.157.
26. Sanmukhani J, Tripathi CB. Ethics in clinical research: the Indian perspective. Indian J Pharm Sci 2011;73:125–30. https://doi.org/10.4103/0250-474x.91564.
27. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013;310:2191–4. https://doi.org/10.1001/jama.2013.281053.
28. Das NK, Sil A. Evolution of Ethics in Clinical Research and Ethics Committee. Indian J Dermatol 2017;62:373–9. https://doi.org/10.4103/ijd.IJD_271_17.
29. Behera SK, Das S, Xavier AS, Selvarajan S, Anandabaskar N. Indian Council of Medical Research’s National Ethical Guidelines for biomedical and health research involving human participants: The way forward from 2006 to 2017. Perspect Clin Res 2019;10:108–14. https://doi.org/10.4103/picr.PICR_10_18.
30. Knoppers BM. Framework for responsible sharing of genomic and health-related data. Hugo J 2014;8:3. https://doi.org/10.1186/s11568-014-0003-1.
31. Rothstein MA. Is deidentification sufficient to protect health privacy in research? Am J Bioeth 2010;10:3–11. https://doi.org/10.1080/15265161.2010.494215.
32. Varkey B. Principles of Clinical Ethics and Their Application to Practice. Med Princ Pract 2021;30:17–28. https://doi.org/10.1159/000509119.
33. Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA n.d.;283:2701–11. https://doi.org/10.1001/jama.283.20.2701.
34. Faden RR, Beauchamp TL, Kass NE. Informed consent, comparative effectiveness, and learning health care. N Engl J Med 2014;370:766–8. https://doi.org/10.1056/NEJMhle1313674.
35. Gymrek M, McGuire AL, Golan D, Halperin E, Erlich Y. Identifying personal genomes by surname inference. Science 2013;339:321–4. https://doi.org/10.1126/science.1229566.
36. Antonov AA. Ohm’s Law Refutes Current Version of the Special Theory of Relativity. J Mod Phys 2016;07:2299–313. https://doi.org/10.4236/jmp.2016.716198.
37. Ploug T, Holm S. Informed consent and routinisation. J Med Ethics 2013;39:214–8. https://doi.org/10.1136/medethics-2012-101056.
38. Beauchamp T, Childress J. Principles of Biomedical Ethics: Marking Its Fortieth Anniversary. Am J Bioeth 2019;19:9–12. https://doi.org/10.1080/15265161.2019.1665402.
39. Rego S, Grove ME, Cho MK, Ormond KE. Informed Consent in the Genomics Era. Cold Spring Harb Perspect Med 2020;10. https://doi.org/10.1101/cshperspect.a036582.
40. Hall DE, Prochazka A V, Fink AS. Informed consent for clinical treatment. CMAJ 2012;184:533–40. https://doi.org/10.1503/cmaj.112120.
41. Stunkel L, Benson M, McLellan L, Sinaii N, Bedarida G, Emanuel E, et al. Comprehension and informed consent: assessing the effect of a short consent form. IRB 2010;32:1–9.
42. Kaye J, Whitley EA, Lund D, Morrison M, Teare H, Melham K. Dynamic consent: a patient interface for twenty-first century research networks. Eur J Hum Genet 2015;23:141–6. https://doi.org/10.1038/ejhg.2014.71.
43. Budin-Ljøsne I, Teare HJA, Kaye J, Beck S, Bentzen HB, Caenazzo L, et al. Dynamic Consent: a potential solution to some of the challenges of modern biomedical research. BMC Med Ethics 2017;18:4. https://doi.org/10.1186/s12910-016-0162-9.
44. Williams H, Spencer K, Sanders C, Lund D, Whitley EA, Kaye J, et al. Dynamic consent: a possible solution to improve patient confidence and trust in how electronic patient records are used in medical research. JMIR Med Informatics 2015;3:e3. https://doi.org/10.2196/medinform.3525.
45. Ginsburg GS, Willard HF. Genomic and personalized medicine: foundations and applications. Transl Res 2009;154:277–87. https://doi.org/10.1016/j.trsl.2009.09.005.
46. Hodgson DR, Whittaker RD, Herath A, Amakye D, Clack G. Biomarkers in oncology drug development. Mol Oncol 2009;3:24–32. https://doi.org/10.1016/j.molonc.2008.12.002.
47. Prainsack B, Buyx A. Solidarity. Reflections on an Emerging Concept in Bioethics. Summary. Jfwe 2012;17:331–44. https://doi.org/10.1515/jfwe.2012.17.1.331.
48. McGuire AL, Burke W. An unwelcome side effect of direct-to-consumer personal genome testing: raiding the medical commons. JAMA 2008;300:2669–71. https://doi.org/10.1001/jama.2008.803.
49. Braverman G, Shapiro ZE, Bernstein JA. Ethical Issues in Contemporary Clinical Genetics. Mayo Clin Proceedings Innov Qual Outcomes 2018;2:81–90. https://doi.org/10.1016/j.mayocpiqo.2018.03.005.
50. Goetz LH, Schork NJ. Personalized medicine: motivation, challenges, and progress. Fertil Steril 2018;109:952–63. https://doi.org/10.1016/j.fertnstert.2018.05.006.
51. Karlawish J. Measuring decision-making capacity in cognitively impaired individuals. Neurosignals 2008;16:91–8. https://doi.org/10.1159/000109763.
52. Shamoo AE. Book Review Ethics and Research With Children: A Case-Based Approach Edited by Eric Kodish. 361 pp. New York, Oxford University Press, 2005. $59.50. 0-19-517178-0. N Engl J Med 2005;353:1078–1078. https://doi.org/10.1056/NEJMbkrev38633.
53. Brandt AM. Racism and research: the case of the Tuskegee Syphilis Study. Hastings Cent Rep 1978;8:21–9.
54. Emanuel EJ. Undue inducement: nonsense on stilts? Am J Bioeth 2005;5:9–13; discussion W8-11, W17. https://doi.org/10.1080/15265160500244959.
55. Meyer P, van Voorst Vader PC. Lack of effect of cyclosporin A in pityriasis rubra pilaris. Acta Derm Venereol 1989;69:272.
56. Gillam L, Guillemin M, Bolitho A, Rosenthal D. Human research ethics in practice: deliberative strategies, processes and perceptions. Monash Bioeth Rev 2009;28:7.1-17.
57. Wendler D, Miller FG. Deception in the pursuit of science. Arch Intern Med 2004;164:597–600. https://doi.org/10.1001/archinte.164.6.597.
58. Miller JE, Korn D, Ross JS. Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012. BMJ Open 2015;5:e009758. https://doi.org/10.1136/bmjopen-2015-009758.
59. Ransohoff DF. Rules of evidence for cancer molecular-marker discovery and validation. Nat Rev Cancer 2004;4:309–14. https://doi.org/10.1038/nrc1322.
60. Bekelman JE, Li Y, Gross CP. Scope and impact of financial conflicts of interest in biomedical research: a systematic review. JAMA n.d.;289:454–65. https://doi.org/10.1001/jama.289.4.454.
61. Conflict of Interest in Medical Research, Education, and Practice. Washington, D.C.: National Academies Press; 2009. https://doi.org/10.17226/12598.
62. Bero L. Addressing Bias and Conflict of Interest Among Biomedical Researchers. JAMA 2017;317:1723–4. https://doi.org/10.1001/jama.2017.3854.
63. Gulbrandsen M, Smeby J-C. Industry funding and university professors’ research performance. Res Policy 2005;34:932–50. https://doi.org/10.1016/j.respol.2005.05.004.
64. Dickersin K. The existence of publication bias and risk factors for its occurrence. JAMA 1990;263:1385–9.
65. Ioannidis JPA. The Reproducibility Wars: Successful, Unsuccessful, Uninterpretable, Exact, Conceptual, Triangulated, Contested Replication. Clin Chem 2017;63:943–5. https://doi.org/10.1373/clinchem.2017.271965.
66. Campbell EG, Rao SR, DesRoches CM, Iezzoni LI, Vogeli C, Bolcic-Jankovic D, et al. Physician professionalism and changes in physician-industry relationships from 2004 to 2009. Arch Intern Med 2010;170:1820–6. https://doi.org/10.1001/archinternmed.2010.383.
67. Salm M, Ali M, Minihane M, Conrad P. Defining global health: findings from a systematic review and thematic analysis of the literature. BMJ Glob Heal 2021;6. https://doi.org/10.1136/bmjgh-2021-005292.
68. Robson G, Gibson N, Thompson A, Benatar S, Denburg A. Global health ethics: critical reflections on the contours of an emerging field, 1977-2015. BMC Med Ethics 2019;20:53. https://doi.org/10.1186/s12910-019-0391-9.
69. van Delden JJM, van der Graaf R. Revised CIOMS International Ethical Guidelines for Health-Related Research Involving Humans. JAMA 2017;317:135–6. https://doi.org/10.1001/jama.2016.18977.
70. Department of Health, Education  and W, National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report. Ethical principles and guidelines for the protection of human subjects of research. J Am Coll Dent 2014;81:4–13.
71. Roderick P. Regulating new drugs in India needs to be improved. Lancet Reg Heal Southeast Asia 2023;10:100144. https://doi.org/10.1016/j.lansea.2023.100144.
72. General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent 2014;81:14–8.
73. Grady C. Institutional Review Boards: Purpose and Challenges. Chest 2015;148:1148–55. https://doi.org/10.1378/chest.15-0706.
74. Hess JR, Fadare SO, Tolentino LS, Bangal NR, Winslow RM. The intravascular persistence of crosslinked human hemoglobin. Prog Clin Biol Res 1989;319:351–7; discussion 358-60.
75. Lidz CW, Appelbaum PS, Arnold R, Candilis P, Gardner W, Myers S, et al. How closely do institutional review boards follow the common rule? Acad Med 2012;87:969–74. https://doi.org/10.1097/ACM.0b013e3182575e2
76. Law M, Couturier D-L, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, et al. Medicines and Healthcare products Regulatory Agency’s “Consultation on proposals for legislative changes for clinical trials”: a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing. Trials 2023;24:640. https://doi.org/10.1186/s13063-023-07576-7.
77. Warrier P, Ho CW-L, Bull S, Vaz M, Vaz M. Engaging publics in biobanking and genetic research governance - a literature review towards informing practice in India. Wellcome Open Res 2021;6:5. https://doi.org/10.12688/wellcomeopenres.16558.2.
78. Haga SB, O’Daniel J. Public perspectives regarding data-sharing practices in genomics research. Public Health Genomics 2011;14:319–24. https://doi.org/10.1159/000324705.
79. Henneman L, Timmermans DRM, Van Der Wal G. Public attitudes toward genetic testing: perceived benefits and objections. Genet Test 2006;10:139–45. https://doi.org/10.1089/gte.2006.10.139.
80. Aicardi C, Del Savio L, Dove ES, Lucivero F, Tempini N, Prainsack B. Emerging ethical issues regarding digital health data. On the World Medical Association Draft Declaration on Ethical Considerations Regarding Health Databases and Biobanks. Croat Med J 2016;57:207–13. https://doi.org/10.3325/cmj.2016.57.207.
81. Dorr Goold S, Lipkin M. The doctor-patient relationship: challenges, opportunities, and strategies. J Gen Intern Med 1999;14 Suppl 1:S26-33. https://doi.org/10.1046/j.1525-1497.1999.00267.x.
82. Rowe G, Frewer LJ. A Typology of Public Engagement Mechanisms. Sci Technol Hum Values 2005;30:251–90. https://doi.org/10.1177/0162243904271724.
83. O’Doherty KC, Burgess MM. Engaging the public on biobanks: outcomes of the BC biobank deliberation. Public Health Genomics 2009;12:203–15. https://doi.org/10.1159/000167801.
84. Molster CM, Bowman FL, Bilkey GA, Cho AS, Burns BL, Nowak KJ, et al. The Evolution of Public Health Genomics: Exploring Its Past, Present, and Future. Front Public Heal 2018;6:247. https://doi.org/10.3389/fpubh.2018.00247.
85. Shim HS, Choi Y-L, Kim L, Chang S, Kim W-S, Roh MS, et al. Molecular Testing of Lung Cancers. J Pathol Transl Med 2017;51:242–54. https://doi.org/10.4132/jptm.2017.04.10.
86. Meacham MC, Starks H, Burke W, Edwards K. Researcher perspectives on disclosure of incidental findings in genetic research. J Empir Res Hum Res Ethics 2010;5:31–41. https://doi.org/10.1525/jer.2010.5.3.31.
87. Resnik DB. Ethical dilemmas in communicating medical information to the public. Health Policy 2001;55:129–49. https://doi.org/10.1016/s0168-8510(00)00121-4.
88. Char DS, Shah NH, Magnus D. Implementing Machine Learning in Health Care - Addressing Ethical Challenges. N Engl J Med 2018;378:981–3. https://doi.org/10.1056/NEJMp1714229.
89. Vayena E, Blasimme A, Cohen IG. Machine learning in medicine: Addressing ethical challenges. PLoS Med 2018;15:e1002689. https://doi.org/10.1371/journal.pmed.1002689.
90. Obermeyer Z, Powers B, Vogeli C, Mullainathan S. Dissecting racial bias in an algorithm used to manage the health of populations. Science 2019;366:447–53. https://doi.org/10.1126/science.aax2342.
91. Floridi L, Cowls J, Beltrametti M, Chatila R, Chazerand P, Dignum V, et al. AI4People-An Ethical Framework for a Good AI Society: Opportunities, Risks, Principles, and Recommendations. Minds Mach 2018;28:689–707. https://doi.org/10.1007/s11023-018-9482-5.
92. Lang M, Zawati MH. Returning individual research results in international direct-to-participant genomic research: results from a 31-country study. Eur J Hum Genet 2022;30:1132–7. https://doi.org/10.1038/s41431-022-01103-z.
93. Juengst ET, Fishman JR, McGowan ML, Settersten RA. Serving epigenetics before its time. Trends Genet 2014;30:427–9. https://doi.org/10.1016/j.tig.2014.08.001.
94. Ienca M, Ferretti A, Hurst S, Puhan M, Lovis C, Vayena E. Considerations for ethics review of big data health research: A scoping review. PLoS One 2018;13:e0204937. https://doi.org/10.1371/journal.pone.0204937.