Ethical Concerns

The American Academy of Pediatrics formed a Committee on Drugs to examine ethical issues of pediatric studies for its members and for the guidance of IRBs dealing with pediatric studies. The Committee released its report in 1995. This report (Committee Drugs, American Academy of Pediatrics) is very comprehensive, but amongst its many recommendations the following areas are highlighted, as follows.

Vulnerability

In this special population, there is a special duty to avoid (unintended) coercion of the patient, parent or guardian. This coercion may arise because the investigator is usually also the treating physician. It would be better to have a colleague explain and obtain the informed consent. There are varying degrees of vulnerability. Patients handicapped either mentally, emotionally or physically are frequently institutionalized and may be supervised as Wards of Court or by a social welfare agency. These patients should be rarely used, unless the treatment is for serious disease specific to institutional settings and no other treatment is available.

Emergency situations can arise where it may be impossible to obtain written informed consent from a parent or guardian. Medications for this type of problem will require intense IRB review and overview; only in special circumstances will informed consent be waived, and then it must 'not adversely affect the rights and welfare of the subject'. (Abramson et al 1986). The last category is the use of a research medicine in a child close to dying who has either no response to standard therapy or where no alternative therapy exists. The agent to be considered must have some evidence of efficacy (animal proof of concept or clinical data and a good chance of a beneficial result). The risk of unintended coercion of desperate parents is especially to be guarded against.

IRBs' Special Emphasis

IRBs have a duty to make sure the study is of value to children in general and in most cases to the patient him/herself; is robust enough to give answers; and attempts to minimize risk and maximize benefit. In reviewing the protocol, the IRBs should involve health care specialists who are aware of the special medical, psychological, and social needs of the child, and the disease as special medical, psychological and social needs of the child, and the disease as might be impacted by the study.

In studies conducted on diseases mainly affecting pediatric patients, the development will be entirely in pediatric patients. However, in addition to the appropriate usual toxicology and neonate animal toxicology, the first-in-humans studies for toxicity and safety are usually done in healthy adult volunteers. Clearly, however, drugs such as the surfactants would yield no useful data from adult testing. For these unique pediatric situations, new measurements and endpoints may need to be developed and validated. Frequently the FDA will involve an advisory panel to help determine what these might be.

The Use of a Placebo Control

Placebo control is desired whenever possible if using a placebo does not place the pediatric patients at increased risk. The AAP Committee on Drugs (1995) outlined other circumstances:

• No other therapy exists or is of questionable efficacy, and the new agent might modify the disease.

• If the commonly used therapy has a high profile of adverse events and risk greater than benefits.

• When the disease fluctuates frequently from exacerbations to remissions thus the efficacy of the (new) treatment cannot be evaluated.

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