Ethical problems using children in clinical trials

In health care, a clinical trial is a comparison test of a medication or other medical treatment (such as a medical device), versus a placebo (inactive look-a-like), other medications or devices, or the standard medical treatment for a patient's condition.

To be ethical, researchers must obtain the full and informed consent of participating human subjects. If the patient is unable to consent for him/herself, researchers can seek consent from the patient's legally authorized representative. For a minor child this is typically a parent or guardian since the child cannot legally give consent.

International Standards

According to ICH Good clinical practice, all trials involving unapproved medical treatments are reviewed for ethics before the study begins. These approving groups are typically called Institutional Review Boards (IRB) in the United States, in Europe they are typically called Independent Ethics Committees (IEC). The IRB or IEC will review not only the protocol of the trial but also the way that subjects are recruited and the consent form that they sign. These groups also examine the incentives given for participation in the trial to ensure that they are not coercive.

The World Medical Association's Declaration of Helsinki requires researchers to take special care with consent involving vulnerable subject populations which have barriers to informed consent. These groups include minors, prisoners, and the mentally ill.

In the United States

FDA and OHRP regulations require the IRB to make specific "Subpart D" determinations [ [http://www.cfsan.fda.gov/~lrd/cfr50.html Code of Federal Regulations: 21 CFR 50 - Protection of Human Subjects ] ] regarding children. To approve the trial, it must meet all of the following conditions:

*The trial must involve no more than a minor increase over minimal risk.
*The treatments must be appropriate to the condition or to medical care that the child would otherwise receive.
*The treatment must either yield "generalizable knowledge" about the specific condition that is vital for understanding or treatment.

If not all of those criteria are met, the FDA commissioner or the Secretary of DHHS must then consult appropriate experts and can approve the trial if both:

*The study is a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem that specifically affects children.
*"Sound ethical principles" are used.

In either case, "adequate provisions" must be made to allow the child to decide if they want to participate in the trial. The IRB must ensure that the assent process is appropriate for children. A child cannot legally give Informed Consent but they must be given the opportunity to decline. A parent or guardian legally consents to the child's participation. Additional safeguards exist for "wards of the state" such as orphans.

Ethical concerns

Since parents often receive compensation for their children's participation in research, children, there are concerns that the payments received may be coercive and lead them to participate in trials which are not in their child's best interest. [Kaufmann, R.E. (2000). Clinical Trials in Children: Problems and Pitfalls. Paediatric Drugs. 2(6):411-418 ] . The IRB or IEC is expected to evaluate both the consent and assent process to ensure that children are not coerced into participation. They are also expected to evaluate the compensation given to ensure that participants are not coerced by the lure of payment.

Problems for the practice of medicine

Partially because of these issues many drugs that are used in children have never been formally studied in children. Many drugs work differently in children. Reye's syndrome, for example, is a potentially fatal complication of aspirin therapy in children that is very rare in adults.

The 2002 Best Pharmaceuticals for Children Act, allowed the FDA to request NIH-sponsored testing for pediatric drug testing, although these requests are subject to NIH funding constraints. Patent term extensions were offered to manufacturers that conducted trials of drugs that would be used in children. The Pediatric Research Equity Act of 2003, Congress codified the FDA's authority to mandate manufacturer-sponsored pediatric drug trials for certain drugs as a "last resort" if incentives and publicly funded mechanisms proved inadequate.cite journal |author=Politis P |year=2005 |title=Transitiion From the Carrot to the Stick: The Evolution of Pharmaceutical Regulations Concerning Pediatric Drug Testing |journal=Widener Law Review |volume=12 |pages=271]

ee also

*Clinical trials
*Medical ethics
*Informed consent
*Philosophy of Healthcare

References