Which group would be considered a vulnerable population, according to traditional guidelines?

Strengthening Core Public Health Functions

Vulnerable populations need to be informed, educated, and protected from risks and damages. Public health laws and regulations need to be established and enforced. Infrastructure needs to be in place to detect early and reduce the impact of emergencies and disasters on health. All this action needs to be implemented through a public health system that is transparent and accountable. Governments in developing countries generally recognize that these public health functions are important, but they often lack the capacity and financial resources to implement them. Indeed, few low-income countries receive support for the core public health functions that should serve as the backbone of any well-functioning and sustained health system, including collection and dissemination of evidence for health policies, prevention and control of diseases, human resource development, and intersectoral action for better health.

14.5 Ethics in the Vulnerable Population

“Vulnerable population” refers to (but is not limited to) those who are incapable of protecting their own interests and hence pregnant women, neonates, children, fetuses, prisoners, physically handicapped, mentally challenged, economically disadvantaged, institutionalized and very sick patients, etc., can all come under this group. The ethical issues in involving the vulnerable population for research are still debatable. The justification for involving the vulnerable population in research is mainly when a particular problem affects that group. However, it is important to understand that participation in biomedical research not only poses risks, but also may provide benefit to participants and society. Moreover, in today’s world of evidence-based medicines, we must have evidence in the vulnerable population as well. One of the important points of concern in the vulnerable population is that some lack the ability to consent or understand. In that case, a legally acceptable representative (LAR) should be involved in the decision. Further, vulnerable persons may require significant and repeated education/information about the research, benefits and risks, and alternatives, if any. As per the ICMR National Ethical Guidelines for Biomedical and Health Research involving Human Participants, 2017 [30], research must be planned in vulnerable populations only if that population will benefit from research. Care should be taken that participants are not exploited. LAR shouldn’t be given any reward for encouraging the participation of their dependents. It is the duty of the IRBs/IECs and clinical investigators to give special attention to protecting the welfare of vulnerable subjects, and to ensure voluntariness and freedom from coercion, to review justification for inclusion of such subjects, and to suggest additional safeguards for them.

Children are one of the several classes under vulnerable population due to their lack of ability to understand, and the fact that they are under the authority of others. Though involving children in research raises serious ethical concerns, restricting children is also not appropriate as their participation is necessary to develop new treatments or prevention methods [45]. Other advantages include detection of pediatric-specific adverse events, variable pharmacokinetics, etc. It has been seen that sponsors are generally reluctant to carry out studies in pediatrics due to the small market and the high cost of the trial. There are other obvious problems like difficult recruitment, non-compliance, excessive liability, etc. To work in this direction, the “NIH policy and guidelines on the inclusion of children as participants in research involving human subjects” was published in 1998 (http://grants.nih.gov/grants/guide/notice-files/not98-024.html) [46], last updated on Oct 13, 2015 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-010.html) [47]. As per the national ethics guidelines for biomedical research involving children, 2017 [48], research in children can be carried out on diseases exclusively seen in childhood or in other conditions (of both adults and children) where the results are expected to be significantly different in children or where the risk-benefit ratio is low and there is minimal risk to the child. The US code of federal regulations on research involving children (sub-part D of 45CFR46) classify the trial into one of four risk categories to determine the rules: (1) minimal risk and no direct benefit to subjects; (2) greater than minimal risk, but with direct benefit to subjects; (3) greater than minimal risk and no direct benefit to subjects, but likely to yield generalizable knowledge about condition; and (4) research not otherwise approvable which represents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children [49]. Decisions about the participation of a child in research are expected to be taken by the parents/LAR, in the best interests of their children. The ethics committee must carefully assess if there are any other extraneous factors involved in giving such consent. In addition to consent from parents/LAR, an oral or written assent, as approved by the ethics committee, should be obtained from children of 7–18 years of age (except under certain circumstances). Parental permission and a child’s assent remain critically important protections for a child’s participation in clinical research, and it is the responsibility of the investigator and ethics committee to ensure the same. As per eCFR §50.55, in determining whether children are capable of providing assent, the IRB must take into account the ages, maturity, and psychological state of the children involved. However, the assent of the children is not a necessary condition for proceeding with the clinical investigation if the IRB determines that the capability of the child is so limited that they cannot reasonably be consulted, or the intervention or procedure involved in the clinical investigation holds out a prospect of direct benefit that is important to the health or wellbeing of the children. Even where the IRB determines that the subjects are capable of assenting, the IRB may still waive the assent requirement if it finds that the clinical investigation involves no more than minimal risk to the subjects and will not adversely affect their rights and welfare, or when the clinical investigation could not practicably be carried out without the waiver.

Similar to children, there should be proper justification for inclusion of pregnant and nursing women in clinical trials designed to address the health needs of such women or their fetuses or nursing infants. For instance, a trial may be designed to test the safety and efficacy of a drug for reducing perinatal transmission of HIV infection from mother to child, or a trial of a device for detecting fetal abnormalities, etc. [45]. Other than research directed towards the health of a pregnant women and/or her fetus, it is recommended that pregnant women be actively excluded from the clinical research that involves greater than minimal risk [46]. In the USA, research involving pregnant women, fetuses, and neonates is covered in sub-part B of 45CFR46 according to which such a research may be conducted if previous research has been done on non-pregnant women to assess potential risks, and there should be evidence of a direct benefit to women or fetuses, or there should be minimal risk. If there is benefit only to the fetus, then consent of both parents may be required.

Displaced Persons

Other vulnerable populations may be those who are already dislocated from familiar settings, for instance, refugees, new immigrants, or minority groups. They may lose their papers, documents of identification. Their links to their new community may still be fragile. They may not have the language, knowledge, or understanding needed to respond to the incident. Alternatively, they may have integrated these events in terms of earlier experiences of threat. They may experience intense fears for their safety because the chaos of the disaster is similar to the chaos they have known. Those who have suffered oppression in their home country may be fearful of government or law enforcement officials and emergency service workers. Displaced persons have been identified as vulnerable groups in many disaster responses and may need special attention to facilitate their recovery.

People with a history of mental illness are also a group that is vulnerable to the effects of disasters. The stressors associated with disasters are commonly recognized as risk factors that may exacerbate a range of preexisting conditions. Following traumatic events, individuals with prior or ongoing psychiatric conditions are more likely to experience a relapse or an exacerbation of these conditions, as well as the development of other forms of psychopathology, including PTSD. In addition to the stress effects associated with common exposures, specific elements of the event and its aftermath may trigger key vulnerabilities. For example, bereavement or the loss of a support network or job may result in a relapse of major depression. The intense activity and officialdom of the recovery may heighten paranoid ideation in those experiencing psychotic conditions.

Indigenous peoples may face particular difficulties. Their backgrounds may have already involved life threat through premature mortality and racist violence. Other losses may involve family disruptions, deaths, and loss of land, culture, identity, and meaning. Such losses may entail both literal and symbolic dislocation from place, tribe, or community. Socioeconomic, educational, and other disadvantages may all contribute further to this background of traumatization. Disaster stressors superimposed on this context further increase the likelihood of adverse outcomes for these individuals and communities.

24.6.3 Safety Aspects in Clinical Trials With MSCs

In the vulnerable population of kidney transplant recipients, patient safety and prevention of adverse (immune) reactions is essential. Since transplant recipients have already an increased risk of (opportunistic) infections and malignancies due to the concomitant immunotherapy, it is very difficult to determine the additional risk of MSC infusions. Clinical studies should be performed under ethically approved protocols and serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) should be carefully recorded and reported to the proper authorities. Important potential risks in renal transplant recipients include direct toxicity of the MSC infusion, malignancies, and risks for over immune suppression and immunogenicity, as also extensively reviewed elsewhere.12,78

Summary

For nutritionally vulnerable populations, including the poor, the very young, the very old, pregnant women, and those suffering from chronic diseases, eggs are an affordable nutrient-dense source of high-quality protein important for maintaining health and facilitating recovery. Pregnancy is an especially important time to optimize the intake of high-quality protein and other essential nutrients to reduce the risk of low birth weight and the associated development of chronic diseases and other health problems during the infant's adult life. Eggs also serve as an important dietary source of choline during pregnancy and lactation, providing the fetus and newborn with choline for brain development. In addition, eggs provide a satiety effect, which, in view of the global problem of obesity, can be a valuable addition to weight-loss and weight-maintenance programs. For various populations, from infants to the aged, there are a multitude of health reasons to include nutrient-dense eggs as part of the diet, and for many of these groups it is economically feasible.

The high-quality protein, many nutritional components, low caloric content, affordability, blandness, ease of digestibility, and satiety response all make eggs ideal for inclusion in the diet at all ages, from very young to very old, and in times of both health and convalescence.

Summary

For nutritionally vulnerable populations including the poor, the very young, the very old, pregnant women, and those suffering from chronic diseases, eggs are an affordable, nutrient-dense source of high-quality protein important for maintaining health and facilitating recovery. Pregnancy is an especially important time to optimize intake of high-quality protein as well as other essential nutrients to reduce the risk of low birth weight and the associated development of chronic diseases and other health problems during the future adult years of the infant. Eggs also serve as an important dietary source of choline during pregnancy and lactation to provide choline to the fetus and newborn for brain development. In addition, eggs provide a satiety effect which, in view of the global problem of obesity, can be a valuable addition to weight-loss and weight-maintenance programs. For these various populations, from infant to aged, there are a multitude of health reasons to include nutrient-dense eggs as part of the diet, and for many of these groups it can be economically feasible.

The high-quality protein, many nutritional components, low caloric content, affordability, blandness, ease of digestibility, and satiety response are all characteristics that make eggs ideal for inclusion in the diet across the lifespan, from very young to very old, and under all conditions, health or convalescence. As noted in the Dietary Guidelines 2010, “Independent of other dietary factors, evidence suggests that one egg (i.e., egg yolk) per day does not result in increased blood cholesterol levels, nor does it increase the risk of cardiovascular disease in healthy people.”

Abstract

Although people in vulnerable populations, such as children and elderly females, are at a greater risk of injury in automotive crashes than middle-aged and midsized occupants, automotive safety designs are based on current crash-test dummies of limited number of shapes and sizes that do not adequately represent such vulnerable populations. Computational models that represent age- and gender-dependent changes in impact responses are necessary. To close the gap between injuries for which current safety testing is aimed at and the actual injuries suffered by children and elderly females who have been insufficiently protected, CHARMs (The Collaborative Human Advanced Research Models) have been developed to represent a 10-year-old child and a 70-year-old female. In this chapter, we introduce the development of CHARM-10 and CHARM-70F models as examples to show the general procedures and specific challenges of developing FE models of vulnerable subjects.

First, anthropometric investigation is performed with geometric and compositional datasets to ensure the model is a good representative of the target population. Second, multiblock meshing strategies are adopted to obtain good mesh quality and flexibility for changing mesh densities. Finally, component and whole-body validations are performed against different loading conditions to finalize material constitutive parameters and to assess the biofidelity of the model.

CONCLUSION

Children are a vulnerable population and deserve protection from the potential risks posed by research. The federal government has codified many of these protections into law, but because a lot of the language is vague and terms are defined imprecisely, much of the responsibility for their interpretation and application falls to individual IRBs. Even the relatively well-defined term minimal risk lends itself to multiple interpretations. Although consensus on the meaning of some of these words is reached eventually, this is not true of all. Hospitalist researchers studying children should carefully consider the risks and benefits of any proposed research protocol and discuss these issues with their IRBs, even if the risk appears to be minimal.

I Declarative Memory in Abused and Neglected Infants

Children are a particularly vulnerable population. Unfortunately, according to the National Child Abuse and Neglect Data System (NCANDS) report (U.S. Department of Health & Human Services, 2010), in 2008 in the United States, there were 772,000 substantiated cases (out of 3.3 million reports involving over 6 million children) of child maltreatment. Of the substantiated cases, 70% suffered neglect, whereas 25% suffered physical or sexual abuse. Many children were the victims of both neglect and abuse. Shockingly, in general, 80% of the perpetrators are parents, and 33% of all the cases are children under 3 years of age. Children younger than 12 months had the highest rate of victimization of all age groups at 22%. Maltreatment of children is a deplorable failure in caregiving that continues to be an insidious social issue. In fact, maltreated children experience developmental delays at three times the typical rate (Scarborough, Lloyd, & Barth, 2009). In the research reported in this chapter, we explored the cognitive effect of abuse and neglect by investigating the effects of chronic stress on declarative memory at a time when the neural substrates underlying cognitive development are in the formative stages.

Summary and Future Challenges

Current nutritional regimens in the vulnerable population of very preterm ELBW neonates produce postnatal growth failure. In order to develop data-based feeding strategies to achieve normal in utero growth rates postnatally, much more information needs to be obtained. Important areas for research include, but are not limited to, safe upper limits of amino acid intake, improved markers for protein toxicity, side-effects and mechanisms of action of insulin when used as a nutritional adjuvant, characterization of the neonatal stress response and its effect on nutritional metabolism, effects of commonly used neonatal medications on specific nutrient metabolism, and incidence of NEC in various enteral feeding strategies. Once these issues have been addressed, then nutritionally related long-term growth and developmental outcomes can be prospectively studied.