Children in clinical research

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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.

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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 [1] 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.

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. [2] 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. [3]

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. [4]

Trials in Irish institutions

During the 1960s and '70s, 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. [5] 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. [6] The Commission's investigations in this area were abruptly halted after legal action was taken by the researchers involved. [5]

See also

Related Research Articles

Informed consent Process for obtaining subject approval prior to treatment or research

Informed consent is a process for getting permission before conducting a healthcare intervention on a person, or for disclosing personal information. A health care provider may ask a patient to consent to receive therapy before providing it, or a clinical researcher may ask a research participant before enrolling that person into a clinical trial. Informed consent is collected according to guidelines from the fields of medical ethics and research ethics.

Clinical trial biomedical or behavioral experiments or observations done in clinical research, designed to answer specific safety and efficacy questions, especially about new treatments such as novel vaccines, drugs and medical devices

Clinical trials are experiments or observations done in clinical research. Such prospective biomedical or behavioral research studies on human participants are designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted.

Human subject research systematic, scientific investigation that involves human beings as research subjects

Human subject research is systematic, scientific investigation that can be either interventional or observational and involves human beings as research subjects. Human subject research can be either medical (clinical) research or non-medical research. Systematic investigation incorporates both the collection and analysis of data in order to answer a specific question. Medical human subject research often involves analysis of biological specimens, epidemiological and behavioral studies and medical chart review studies. On the other hand, human subject research in the social sciences often involves surveys which consist of questions to a particular group of people. Survey methodology includes questionnaires, interviews, and focus groups.

Investigational New Drug

The United States Food and Drug Administration's Investigational New Drug (IND) program is the means by which a pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug across state lines before a marketing application for the drug has been approved. Regulations are primarily at 21 C.F.R. 312. Similar procedures are followed in the European Union, Japan, and Canada.

An institutional review board (IRB), also known as an independent ethics committee (IEC), ethical review board (ERB), or research ethics board (REB), is a type of committee that applies research ethics by reviewing the methods proposed for research to ensure that they are ethical. Such boards are formally designated to approve, monitor, and review biomedical and behavioral research involving humans. They often conduct some form of risk-benefit analysis in an attempt to determine whether or not research should be conducted. The purpose of the IRB is to assure that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in a research study. Along with developed countries, many developing countries have established national, regional or local Institutional Review Boards in order to safeguard ethical conduct of research concerning both national and international norms, regulations or codes.

In a clinical trial, the investigators must specify inclusion and exclusion criteria for participation in the study.

An investigational device exemption (IDE) allows an investigational device to be used in order to collect safety and effectiveness data required to support a premarket approval (PMA) application or a premarket notification [510(k)] submission to Food and Drug Administration (FDA). Clinical studies are most often conducted to support a PMA. Only a small percentage of 510(k)'s require clinical data to support the application. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated.

Good clinical practice (GCP) is an international quality standard for conducting clinical trials that in some countries is provided by ICH, an international body that defines a set of standards, which governments can then transpose into regulations for clinical trials involving human subjects.

The Declaration of Helsinki is a set of ethical principles regarding human experimentation developed for the medical community by the World Medical Association (WMA). It is widely regarded as the cornerstone document on human research ethics.

Clinical research is a branch of healthcare science that determines the safety and effectiveness (efficacy) of medications, devices, diagnostic products and treatment regimens intended for human use. These may be used for prevention, treatment, diagnosis or for relieving symptoms of a disease. Clinical research is different from clinical practice. In clinical practice established treatments are used, while in clinical research evidence is collected to establish a treatment.

An ethics committee is a body responsible for ensuring that medical experimentation and human subject research are carried out in an ethical manner in accordance with national and international law.

A Clinical Research Coordinator (CRC) is a person responsible for conducting clinical trials using good clinical practice (GCP) under the auspices of a Principal Investigator (PI).

The Office for Human Research Protections (OHRP) is a small office within the United States Department of Health and Human Services (DHHS), specifically the Office of the Assistant Secretary for Health in the Office of the Secretary of DHHS, that deals with ethical oversights in clinical research conducted by the Department, mostly through the National Institutes of Health (NIH).

A glossary of terms used in clinical research.

The following outline is provided as an overview of and topical guide to clinical research:

Human subject research legislation in the United States can be traced to the early 20th century. Human subject research in the United States was mostly unregulated until the 20th century, as it was throughout the world, until the establishment of various governmental and professional regulations and codes of ethics. Notable – and in some cases, notorious – human subject experiments performed in the US include the Tuskegee syphilis experiment, human radiation experiments, the Milgram obedience experiment and Stanford prison experiments and Project MKULTRA. With growing public awareness of such experimentation, and the evolution of professional ethical standards, such research became regulated by various legislation, most notably, those that introduced and then empowered the institutional review boards.

African countries have been sites for clinical trials by large pharmaceutical companies, raising human rights concerns. Incidents of unethical experimentation, clinical trials lacking properly informed consent, and forced medical procedures have been claimed and prosecuted.

Brodalumab is a human monoclonal antibody designed for the treatment of inflammatory diseases.

The term informed assent describes the process whereby minors may agree to participate in clinical trials. It is similar to the process of informed consent in adults, however there remains some overlap between the terms.

Various organizations have created guidelines for human subject research for various kinds of research involving human subjects and for various situations.

References

  1. ↑ "Code of Federal Regulations Title 21 Part 50 - Protection of Human Subjects". Accessdata.fda.gov. Retrieved 2018-05-30.
  2. ↑ Kaufmann, R.E. (2000). Clinical Trials in Children: Problems and Pitfalls. Paediatric Drugs. 2(6):411-418
  3. ↑ 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.
  4. ↑ Politis P (2005). "Transition From the Carrot to the Stick: The Evolution of Pharmaceutical Regulations Concerning Pediatric Drug Testing". Widener Law Review. 12: 271.
  5. 1 2 The Forgotten Children Irish Independent, 20 Aug 2010
  6. ↑ 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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