Children in clinical research

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Regulation of therapeutic goods in the United States

Prescription drugs Over-the-counter drugs
Law Federal Food, Drug, and Cosmetic Act CDAPCA Controlled Substances Act Prescription Drug Marketing Act Hatch-Waxman Act exemptions Marihuana Tax Act of 1937
Government agencies Department of Health and Human Services Food and Drug Administration Department of Justice DEA
Process Drug discovery Drug design Drug development New Drug Application Investigational New Drug Clinical trial phases Randomized controlled trial Pharmacovigilance Abbreviated New Drug Application Fast track approval Off-label use
International coordination ICH Uppsala Monitoring Centre WHO CIOMS Single Convention on Narcotic Drugs
Non-governmental organizations National Academy of Medicine RADAR NORML
v t e

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-alike), other medications or devices, or the standard medical treatment for a patient's condition.

To be ethical, researchers must obtain the full and voluntary informed consent of participating human subjects. If the subject is unable to consent for him/herself, researchers can seek consent from the subject's legally authorized representative. For a minor child this is typically a parent or guardian since as under the age of 18 cannot legally give consent to participate in a clinical trial.

International standards

According to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use 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

U.S. Food and Drug Administration (FDA) and Office for Human Research Protections regulations require the IRB to make specific "Subpart D" determinations 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 Department of Health and Human Services 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, 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. 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.

A particular source of concern is the ethics of enrolling babies in clinical trials aimed to study new analgesic drugs and treatments: some researchers argue that babies should never be given only placebo when exposed to pain during such trials.

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 National Institutes of Health-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.

Trials in Irish institutions

During the 1960s and 1970s, a series of vaccine trials were undertaken on 123 young children at several residential institutions in Ireland. The trials were conducted under the auspices of researchers at University College Dublin. Subsequent investigations by the Irish government, including the Commission to Inquire into Child Abuse, revealed a broad lack of documentation pertaining to the conduct of the trials at the institutions and the nature of any informed consent, as well as a failure to follow up with the participants. The commission's investigations in this area were abruptly halted after legal action was taken by the researchers involved.

References

"Code of Federal Regulations Title 21 Part 50 - Protection of Human Subjects". Accessdata.fda.gov. Retrieved 2018-05-30.
Kaufmann, R.E. (2000). Clinical Trials in Children: Problems and Pitfalls. Paediatric Drugs. 2(6):411-418
Bellieni, CV; A Taddio; JS Linebarger; JD Lantos (September 2012). "Should an IRB approve a placebo-controlled randomized trial of analgesia for procedural pain in neonates?". Pediatrics. 130 (3): 550–3. doi:10.1542/peds.2011-2910. PMC 4074620. PMID 22891235.
Politis P (2005). "Transition From the Carrot to the Stick: The Evolution of Pharmaceutical Regulations Concerning Pediatric Drug Testing". Widener Law Review. 12: 271.
^ The Forgotten Children Irish Independent, 20 Aug 2010
Report of the Inter-Departmental Group on Mother and Baby Homes Archived 2014-08-09 at the Wayback Machine, Irish Government Department of Children and Youth Affairs, pp 17-20

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