1. Introduction

Biomedical research on human subjects in Lower Middle-Income or Low-Income Countries (LMICs or LICs)¹ has raised interest in bioethics on how to achieve an equitable distribution of benefits, with the interaction of several agents with very different power, interests and needs: on the one hand there is the pharmaceutical industry, which sponsors much of the research in LMICs, seeking knowledge to improve therapeutics, but clouded by large commercial interests and, on the other, the reality of the localities where such research is carried out, generally conducted in public medicine, with a low research budget, with their health research programs and priorities that often do not coincide with those of industry, with a good research staff but with insufficient facilities and equipment, and with a large demand of patients in need of diagnosis and treatment.

The conflict of interest that exists in this briefly described reality has been characterized as a primary scientific interest, which is clouded by another commercial or secondary interest. The issues of justice inherent in such a conflict of interest have been addressed in bioethics under the concept of «reasonable availability» or «fair distribution of benefits», emphasizing a fair distribution of the benefits generated by the research among the participants ⁽¹⁾. However, the inadequacy of this approach lies in the fact that questions of a public nature have been dealt with from the standpoint of the ethics of the doctor-patient relationship -beneficence and non-maleficence-, or involving third parties -particularly distributive justice-. The subject has been dealt with from the point of view of social justice, but the approach to ethics referring to populations, or public ethics, is a pending subject for further exploration ⁽²⁾. An example of this is the use of data obtained in research, which has traditionally been limited to the personal sphere, as stated in the document of the World Medical Assembly in Taipei in 2016 ⁽³⁾. Today, it is requested that the data obtained be studied from the perspective of public ethics or, at least, from the collective, as indicated by the latest LMICs standards ⁽⁴⁾.

Research ethics has focused on informed consent and the protection of personal data, but public ethics is now questioning whether collective data can be disseminated because of a need so great as to justify making the data public ⁽⁵⁾. Consider the case of data that can be shared for the development of vaccines against SARSCoV-2, as well as mechanisms to take vaccines off patent for the duration of the emergency. Or to generate collateral research to help mitigate the effects of the pandemic ⁽⁶⁾.

Outside the field of public ethics, another related aspect that has been worked on is to evaluate the social value of the research; that is, whether it generates knowledge that avoids harm ⁽⁷⁾ and has an impact in favor of the local community ⁽⁸⁾. This is knowledge oriented to banish those injustices that make the population sick; for example, the social determinants of health that make the health burden of certain diseases much greater for LMICs. It has to do with what kind of knowledge will be generated and for whose benefit ⁽⁵⁾.

Finally, although there is some awareness of the duty to ensure social value, in the practice of Research Ethics Committees (RECs) it is not known what this is or how to measure it. Moreover, issues of justice are often far from the experience of IRBs, which are limited to aspects of informed consent or the risk-benefit balance ⁽⁹⁾.

This paper aims to highlight the importance of a complementary approach to the reasonable availability and fair benefit-sharing approaches, given that the issue of fair benefit-sharing in biomedical research has been widely addressed in the bioethics literature ⁽¹, ⁹-¹³⁾. The aim, from the perspective of public ethics, is to highlight the need to focus on the social value of the knowledge generated, and to offer some guiding criteria to be detected by RECs.

2. Social value of research

The term social value is very plural and ambiguous. In research ethics, it has been conceived as generating knowledge that leads to improvements in health. For E. Emmanuel, knowledge and social value are indistinguishable. Emmanuel, as well as the improvement it produces in health as the instrumental value of research ⁽¹³⁾.

The Declaration of Helsinki affirms the need to generate benefits in every research: The primary purpose of medical research on human subjects is to understand the causes, evolution and effects of diseases and to improve preventive, diagnostic and therapeutic interventions (methods, procedures and treatments)⁽¹⁴⁾. And the World Medical Association’s Manual of Medical Ethics devotes a subheading to the need to incorporate social value assessment into the ethical review process of human research protocols. It states that:

One of the most controversial requirements of a medical research project is that it contribute to the welfare of society at large. It was widely accepted that advances in scientific knowledge were of intrinsic value and needed no further justification. However, since the resources available for medical research are increasingly inappropriate, social value has emerged as an important criterion for deciding whether a project should be funded...The social value of a research project is more difficult to determine than its scientific merit, but it is not a good reason to ignore it ⁽¹⁵⁾.

The 2016 LMICs standards say of the social value of research:

The scientific and social value of research can be difficult to quantify, but is generally founded on three factors: the quality of the information produced, its relevance to significant health problems, and its contribution to the creation or evaluation of interventions, policies, or practices that promote individual or public health ⁽⁴⁾.

Some say that the social value of research lies in the knowledge generated or in the type of information produced, which can be of various forms; for example, progressive, translational ⁽¹⁶⁾, humanitarian, clinical, present or future information, and so on. It must benefit local populations, and not only those who resemble the clinical trial participants. However, what they all mean is that social value has to do with values shared by a set of individuals or held by a society, in contrast to individual conceptions. It gives the concept of benefit the notion of appreciation, esteem or importance. While confusing, it offers more than the concept of benefit. It presupposes that the IRB questions the research question of the clinical trial in the sense of whether it will benefit the population involved, or whether it subjects the research subjects to unacceptable risks or harms ⁽⁷, ¹⁷, ¹⁸⁾.

Other authors conceive it as the knowledge valued by a society, and for which research subjects may submit to certain risks of harm in scientific experiments. This eliminates ill-considered research or research that seeks superfluous or redundant knowledge. For knowledge to have social value, it must include an instrumental or applicable component, which will depend on the context of each place; for example, prevalence of a disease, public resources for health, local infrastructure, etcetera ⁽¹⁹⁾.

The social value has to operate on the basis of the intended or expected output of a clinical trial, and the anticipated value that can be placed on the knowledge that will be generated. Although there is no access to the knowledge that will be produced, it is possible to know what type of knowledge will be created and how robust the findings will be, which diseases are investigated and how relevant the results are for a given population, as well as how to obtain them ⁽²⁰⁾.

Offering immediate therapeutic benefits from a clinical trial is difficult to guarantee because of the uncertainty of obtaining them. A Phase I trial will take many years to progress to new stages, and may not reach completion, let alone success. But what can be asked of research in advance is that the social value generated be significant for the society in which it will be carried out.

For the same reason, in some cases, rather than evaluating the risk/benefit ratio, the risk/social value ratio must be considered, given that the damage to which the research subjects may be exposed must be offset by the value of the research in terms of its nature or significance; that is, by the knowledge generated for a given place, beyond the direct benefits.

This is evaluated in advance. It requires not only methodological rigor in the design, but also to see how the population will benefit. It also assumes that the research can evolve towards generating knowledge that translates into concrete clinical or therapeutic improvements for the people in the place where the research is being conducted or transferred. And, finally, the validity of a trial is evaluated by experts ⁽¹⁷⁾.

More recently, D. Wenner has argued that social value lies in subjecting research to the principles of social justice and going beyond the transaction between researchers, industry, health authorities and research subjects. Social value implies that the research has a clinical impact on the research community and, therefore, that the sponsors are in some way responsible for the health of the research community ⁽²⁰⁾. Other authors criticize this view for having unclear theoretical foundations, or because it is publicly funded research and because it has a minimal risk for withholding consent from participants. In other words, the social value is justified from a soft rationale, but not from a strong one ⁽²¹, ²²⁾. The issue needs more debate and a better social justice rationale. In Latin American countries it will have to do with the responsible use of limited resources and the avoidance of exploitation ⁽²³⁾.

When research is carried out in places where epistemic injustice is the main feature ⁽²⁴⁾,² the benefits must be designed not to reinforce the established order, for example, the creation of drugs as an extension of patents, but which are not an improvement over the gold standard and which will be marketed at prices inaccessible to the majority ⁽¹⁾, but to generate knowledge aimed at banishing those injustices that make the population sick. Therefore, it will have to do with existing resources, with health priorities, with the prevalence of diseases, with what type of knowledge will be generated and for the benefit of whom, etcetera.

Collaboration between researchers and community builds the principle of collaborative research, which assumes that the community where the research is conducted should favor and participate in the research effort. Collaborative research indicates to the community whether the scientific effort will help to solve their problems and to define whether it is acceptable to develop the research in their own environment ⁽²⁵⁾. It is clear, therefore, that this problem escapes from the field of research ethics to become part of the ethics of public health, health policies and health systems ⁽⁸⁾.

3. Some causes of the forgetting of social value in an investigation

4. A view from the perspective of public ethics

Public health ethics identifies, analyzes and resolves the ethical problems inherent to public health, beyond the individual. It is concerned with populations (race, gender, age, locality, etc.), governmental action, public or collective goods, prevention, and is intrinsically results-oriented. It is related to an essential dimension of well-being, health, to the avoidance of harm that threatens it and to those strategic determinants for its preservation, including those that belong to other non-health fields ⁽², ⁶⁾.

Public ethics is concerned with preventing or avoiding harm and promoting well-being. It is also concerned with social responsibility. Such ethical categories, when viewed from the social lens, are not considered from the individual but from the collective, and are therefore relational in nature. Non-maleficence, beneficence and responsibility have to do with concrete relationships of dependence that are not chosen, established between moral agents, individual or collective, but always with public repercussions. Also with the inequitable or repressive modes that are structured in a given society, causing groups of people or social sectors to be harmed or not to be granted the benefits to which they are entitled. For example, it is a matter of considering that research in a population that is vulnerable due to its poverty is much more likely to incur in therapeutic confusion, as the subjects believe that they are receiving treatment and are unable to assess the social benefit, given the magnitude of their need, as their right to health care is not satisfied; in other words, it is research under conditions of epistemic injustice.

Specifically, and analogous to the reasons for the crisis of the biomedical model, it is first and foremost a public ethics that focuses its attention not on individuals but on populations, with all that this implies. If populations with unmet primary needs are recruited, it will be very difficult for them to understand the meaning of the procedure to which they will be subjected, i.e. everything related to informed consent. Similarly, populations subjected to conditions with a greater burden of disease should see the knowledge generated reflected in a social benefit that others subjected to the same burden will possibly obtain ⁽³²⁾; for example, research on measures for the detection of pre-diabetes, before having already developed symptoms of the disease.

Secondly, public ethics is related not only to the immediate factors that impact the health of a population, but also to the prevention and removal of damage, as well as to the social determinants of health and to those factors that define the society in which one lives ⁽³³⁾.⁴ Such influences on health are best described in terms of probabilities and risks, and public ethics is thus motivated by a concern for uncertainty and precaution. Thus, in a population where diabetes is endemic, such as Mexico, research protocols should not be based on the search for the «best» therapeutic molecule, but on the probability of efficacy of preventive measures, or on the limitation of risk factors in society. Or based on cost/benefit studies of already marketed treatments that are cheaper and, therefore, more accessible.

In the light of public ethics, biomedical research must take into account the great variability of factors that can make a population dependent; for example, the economic situation, the purchasing power of wages, gender, race, social class, and so on. It must also be in tune with that which goes beyond the aggregate or distributive dimensions, such as the social or environmental determinants of health: the causes that are shared by many and the degree to which these causes are contained, controlled or excluded from a population. For example, investigating the social impact of advertising campaigns for various foods and how they do or do not affect diabetes prevention. Similarly, to study the beneficial impact of advertising campaigns in favor of healthier lifestyles and lower sugar consumption.

Thirdly, public ethics requires collective action, often undertaken by the State; for example, prevention and health care, inasmuch as many ends are impossible to achieve by individuals in isolation. It goes hand in hand with factors related to the lack of prevention or removal of harm, or with the absence of due health protection by the State ⁽³⁴⁾.

Health research is one of the most important inputs to forge a rational and fair response to the problems of backwardness and, above all, to the emerging challenges, which are more complex and more costly to address. Its contribution to the reduction of the burden of disease in our country can, moreover, be improved if it is directed at solving priority problems... ⁽³⁵⁾.

This is health research organized in a strategic, interdisciplinary and interinstitutional manner, beyond the individual, which is what characterizes our country, with the consequent dispersion of the objectives of such studies ...focused on the 21st century, we have in our country as many health research topics as active researchers⁽³⁶⁾.

In the bioethics literature, not only in Latin America, but also in the literature with a social perspective, vulnerable populations are those who suffer a greater burden of disease and, therefore, require extra attention or protection. They are identified as social groups that have a relative risk of susceptibility to adverse health outcomes ⁽³⁷⁾. Social vulnerability is the product of conditions of special fragility, in which certain environments or socio-economic situations place the people who suffer from them ⁽³⁸⁾.

The following Table 1 shows in a synoptic way some criteria to assess the adequacy between research and public ethics, and to determine their respective social value ⁽⁵, ³⁵, ³⁹⁾.

Thus, for example, in the case of research on non-communicable diseases:

5. Conclusion

International collaborative biomedical research needs to be thought out and regulated from the perspective of public ethics, so that the knowledge generated has an impact in favor of local communities. The classical approaches based on principles read from research bioethics are insufficient, such as reasonable availability or fair distribution of benefits. The public ethics approach focuses on the benefit generated or not for a given population, and not only for specific individuals, so it seems to be a complementary approach in multinational research.

The social value of research has been defined in several ways. One of its main characteristics is that it can be foreseen prior to the research, and that it can be seen in what way the population will benefit from the line of knowledge in order to translate it into concrete clinical or therapeutic improvements.

The social value of research has been forgotten for various reasons, such as explanatory individualism, the neglect of causal factors of the disease, the existing conflict of interest that is little evidenced, and the privatization of knowledge. Public ethics rescues the social value, focusing attention not on individuals but on populations in a given context. The explanatory factors are analyzed from the prevention and removal of harm, as well as the social determinants of health, and the causes that make a certain population dependent or exploited. And it places the State as a central agent in arbitrating the existing conflicts of interest between the public and private spheres.

Finally, the social value of research can be detected on the basis of guiding criteria that help RECs; for example, in the generation of knowledge that includes epidemiological aspects that apply the trial to the community or the relationship of the protocol with the major local health research priorities.