Context

The clinical trial of COVAXIN on children aged 2-18 years is approved by the Drugs Controller General of India. This will be the first Covid vaccine to be tested over children in India.

Background

• Covaxin, developed by Bharat Biotech in association with the Indian Council of Medical Research and the National Institute of Virology, is launched as the only Made-in-India Covid inoculation.
• Oxford-AstraZeneca’s Covishield produced by the Serum Institute, is the second vaccine being used in India.
• Last year, covaxin was cleared for emergency use meanwhile was also in clinical trial stage, which raised questions and was also seen to spur vaccine hesitancy in the early stages of India's vaccination programme.
• Due to the vulnerabilities of physical frailty and mental immaturity, rights of children and interest need to be protected from the risks correlated with any kind of research.

Analysis

What is bioethics?

• Bioethics is the study and analysis of ethical implications of the health-related life sciences and related technologies.
• Bioethics is also the discipline dealing with moral problems arising in the practice/research of medicine and other techniques.

What are the concerns regarding biomedical research on children?

• Children lack autonomy, due to their cognitive and emotional level of maturity and the legal status to consent to research participation on their own behalf (not on their own).
• Any examination on children must focus on the level of their cognitive, emotional, physical, and psychosocial development.
• A vulnerable set of patients (such as children from poor socio-economic strata being treated in government hospitals) should not be unduly exposed to research risks, just because they are easily obtainable.
• There are also special challenges regarding biomedical research in developing and third world countries. In resource-constrained settings where the guardians of children have poor levels of literacy, and meanwhile children are even more vulnerable.
• The concept of research is not well understood by most parents and research is often confused with treatment (therapeutic misconception), or seen as a way of accessing new therapies or better clinical care.
• The parents may also be unduly susceptible to financial inducements to participate in research because of their poor socio-economic status.
• Overuse of these vulnerable groups is a special concern when they are unlikely to benefit from the knowledge gained from research.
• Research in resource-poor countries has been found unjust when it does not consider the needs of those societies and countries. For instance, a survey being organized on the children of a developing country with potential beneficiaries of the intervention being children from rich nations is bound to raise concerns.
• India faces additional challenges given the multicultural society and diversity of health-care systems of considerably varying standards.

Why is biomedical research necessary in children?

• The disease may affect only children, for example, hyaline membrane disease, birth asphyxia, neonatal hyperbilirubinemia, extrahepatic biliary atresia, infantile spasms, infantile tremor syndrome, Kawasaki disease, etc.
• Such diseases do not have adult equivalents and therefore, it is significant to conduct an analysis in children to enhance our knowledge regarding such diseases.
• Moreover, if the same disease affects both adults and children, the pathophysiological processes and responses to treatment in children may differ from those in adults, therefore, we cannot conclude the aid approved for adults to children.
• Some diseases such as nephrotic syndrome, hypertension and rheumatoid arthritis affect both adults and children, but the pathophysiological basis and clinical approach varies in both.
• The physiology of children is different from that of adults, and the pharmacokinetics of many drugs is age-dependent based on the maturation of the drug metabolism pathways.
  • For example, children can metabolize many drugs much more rapidly as compared to adults; hence, the dosage of the drug (per kg of body weight) that needs to be given is much higher in children.
• The absorption of drugs also varies with age. Pharmacokinetics and toxicity profile varies with growth and maturation from infancy to adulthood.
• The adverse effects of many drugs may also be different in children as compared to adults. For illustration, tetracyclines causes teeth discoloration in young children and use of aspirin is associated with Reye’s syndrome in children
• Age-appropriate delivery vehicles and formulations (such as syrups) are needed for accurate, safe and palatable administration of medicines to infants and children.
• The pathophysiology of many disorders is dependent on a child’s growth, development and adaptive plasticity. For instance, adaptive changes in the motor system following a perinatal stroke.
• Research in children is also one of the ways to understand some adult diseases that are thought to have their origins in early life. The natural history of the disease may be understood better and it may lead to potential preventive interventions in early life.

Conclusion

Children are an exceptional population with specific ethical and clinical concerns. Clinical research is of paramount importance in developing safe medications, paediatric formulations, clinical interventions and best practice guidelines. The vulnerable nature of this population must be considered when balancing the risks of research with the need for safe and validated therapies. Indian Council of Medical Research, the nodal agency in the country for biomedical research has developed ethical guidelines for biomedical research involving children. These guidelines are based on scientific and ethical principles, and balanced in providing guiding principles and processes and practices for achieving compliance. Adherence to these guidelines is a sine qua non for the development of robust child-friendly biomedical research environment.