Ethical problems using children in clinical trials
Encyclopedia
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 anyone under the age of 18 cannot legally give consent to participate in a clinical trial.
, 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.
regulations require the IRB to make specific "Subpart D" determinations regarding children. To approve the trial, it must meet all of the following conditions:
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:
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.
, 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.
Health care
Health care is the diagnosis, treatment, and prevention of disease, illness, injury, and other physical and mental impairments in humans. Health care is delivered by practitioners in medicine, chiropractic, dentistry, nursing, pharmacy, allied health, and other care providers...
, a clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
is a comparison test of a medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
or other medical treatment (such as a medical device
Medical device
A medical device is a product which is used for medical purposes in patients, in diagnosis, therapy or surgery . Whereas medicinal products achieve their principal action by pharmacological, metabolic or immunological means. Medical devices act by other means like physical, mechanical, thermal,...
), versus a placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
(inactive look-alike), other medications or devices, or the standard medical treatment for a patient's condition.
To be ethical
Medical ethics
Medical ethics is a system of moral principles that apply values and judgments to the practice of medicine. As a scholarly discipline, medical ethics encompasses its practical application in clinical settings as well as work on its history, philosophy, theology, and sociology.-History:Historically,...
, researchers must obtain the full and voluntary informed consent
Informed consent
Informed consent is a phrase often used in law to indicate that the consent a person gives meets certain minimum standards. As a literal matter, in the absence of fraud, it is redundant. An informed consent can be said to have been given based upon a clear appreciation and understanding of the...
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
Minor (law)
In law, a minor is a person under a certain age — the age of majority — which legally demarcates childhood from adulthood; the age depends upon jurisdiction and application, but is typically 18...
this is typically a parent or guardian since anyone 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 practiceGood clinical practice
Good Clinical Practice is an international quality standard that is provided by International Conference on Harmonisation , an international body that defines standards, which governments can transpose into regulations for clinical trials involving human subjects.Good Clinical Practice guidelines...
, 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
World Medical Association
The World Medical Association is an international and independent confederation of free professional Medical Associations, therefore representing physicians worldwide...
's Declaration of Helsinki
Declaration of Helsinki
The Declaration of Helsinki is a set of ethical principles regarding human experimentation developed for the medical community by the World Medical Association . It is widely regarded as the cornerstone document of human research ethics...
requires researchers to take special care with consent involving vulnerable subject populations which have barriers to informed consent. These groups include minors
Minor (law)
In law, a minor is a person under a certain age — the age of majority — which legally demarcates childhood from adulthood; the age depends upon jurisdiction and application, but is typically 18...
, prisoners, and the mentally ill.
In the United States
U.S. Food and Drug Administration (FDA) and Office for Human Research ProtectionsOffice for human research protections
The Office for Human Research Protections is a small office within the United States Department of Health and Human Services that deals with ethical oversight of clinical research conducted by the department, mostly through the National Institutes of Health.The office's primary duty is the...
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
United States Department of Health and Human Services
The United States Department of Health and Human Services is a Cabinet department of the United States government with the goal of protecting the health of all Americans and providing essential human services. Its motto is "Improving the health, safety, and well-being of America"...
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
Informed consent
Informed consent is a phrase often used in law to indicate that the consent a person gives meets certain minimum standards. As a literal matter, in the absence of fraud, it is redundant. An informed consent can be said to have been given based upon a clear appreciation and understanding of the...
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.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 syndromeReye's syndrome
Reye's syndrome is a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver, as well as causing a lower than usual level of blood sugar . The classic features are liver damage, aspirin use and a viral infection...
, for example, is a potentially fatal complication of aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
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
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
-sponsored testing for pediatric drug testing, although these requests are subject to NIH funding constraints. Patent
Patent
A patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....
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.
See also
- Clinical trials
- Human experimentation in the United StatesHuman experimentation in the United StatesThere have been numerous experiments performed on human test subjects in the United States that have been considered unethical, and were often performed illegally, without the knowledge, consent, or informed consent of the test subjects....
- Medical ethicsMedical ethicsMedical ethics is a system of moral principles that apply values and judgments to the practice of medicine. As a scholarly discipline, medical ethics encompasses its practical application in clinical settings as well as work on its history, philosophy, theology, and sociology.-History:Historically,...
- Informed consentInformed consentInformed consent is a phrase often used in law to indicate that the consent a person gives meets certain minimum standards. As a literal matter, in the absence of fraud, it is redundant. An informed consent can be said to have been given based upon a clear appreciation and understanding of the...
- Philosophy of HealthcarePhilosophy of healthcareThe philosophy of healthcare is the study of the ethics, processes, and people which constitute the maintenance of health for human beings. For the most part, however, the philosophy of healthcare is best approached as an indelible component...