For Parents

Why Clinical Research Studies in Children are Important?

Clinical research studies yield important information on a medical product's safety, dosing, and effectiveness, which is the basis for FDA approval and product labeling. Health care providers use labeling information to prescribe the right product for their patients and to monitor them for potential side effects. This includes prescribing the right drug at the right dose.

Historically, only 20–30% of drugs approved by FDA have been labeled for use in children. So, by necessity, doctors routinely give drugs to children off label." We need to do clinical trials in children so that a child will not be an experiment of one every time a doctor prescribes a drug," says Murphy.

Children's responses to drugs can't always be predicted from data collected in adult studies, says FDA's Pediatric Bioethicist Robert Nelson, M.D., M.Div., Ph.D. A child grows and the metabolism changes as he or she gets older, he says. "These changes mean the child has a different susceptibility to side effects over time. We may think we can predict some of these differences, but we really can't without studying them."


Potential Benefit

Clinical research studies in children, by law, must provide the potential for at least a minimal benefit, and the child must have the disease or condition being studied or be at risk for it. For example, many children have had otitis media (middle ear infections), says William Rodriguez, M.D., FDA's Science Director for Pediatrics, and they have the potential to benefit from studies of a treatment for otitis media. But a child could not be in a study to test a diabetes drug or a glucose monitor unless the child has diabetes or is at risk for it.

Depending on the type of study and the product being tested, a child may get an experimental drug, a standard treatment, or an inactive pill (placebo).

If a placebo is used in a study, it is because either the period of time the child is on the placebo is short and doesn't pose risks or because the therapy being tested is being used to treat discomfort or symptoms of a disease but not the underlying disease.

A child should not be deprived of a treatment in a clinical research study that is necessary for the child's health. For example, if the child has seizures, an experimental drug may be added on to a medication the child is already taking to help control seizures, or added onto another treatment that is known to work.

People often think that a clinical research study that tests an experimental drug is riskier than being treated in your doctor's office with an already approved drug, says Nelson. "Some research is riskier, but some is safer than being prescribed a drug in an off-label environment where you don't know the implications. Monitoring for adverse events would be much more intensive in a research study than in an off-label practice."

Informed Consent

FDA works to protect people in clinical research studies and to ensure that they have reliable information as they decide whether to join a study. "A fundamental concept of research is that it cannot take place without informed consent," says Murphy. "Otherwise, it would be experimenting on people without their permission." Adult participants must sign an informed consent document before joining a clinical research study.

Children, however, cannot give informed consent because consent implies a full understanding of the potential risks and other considerations of a clinical research study. "Parents, as the child's advocates, must decide if they wish to give permission in place of informed consent," says Murphy. Then, depending on the child's age, maturity, psychological state, and other considerations, the child may be asked to "assent" or "dissent." This means the child can agree or disagree to participate in a study.

Depending on the child's health and the potential benefit of an experimental treatment, parents can override a child's dissent. For example, if the child has a life-threatening illness for which there is no effective approved treatment, the child's opinion is secondary to the parents' opinion, says Rodriguez. But if the child has a mild condition, such as otitis media, parents should not force the child to enroll in a clinical research study.

The basic parts of an informed consent document include:

  • purpose of the study and how long it's expected to last
  • description of the procedures and experiments
  • reasonably foreseen risks and benefits to the participant or to others
  • appropriate optional treatments if you decide not to participate
  • statement of confidentiality
  • statement that participation is voluntary
  • compensation, if paid, for participation and compensation for a research-related injury

Making a Decision

Nelson urges parents to use the child's pediatrician as an advisor before enrolling in, and during, a clinical trial. "A pediatrician can help a parent evaluate the risks and potential benefits, assess the qualifications of the research team, clarify a child's understanding of the research, and support the parent and child throughout the research study."

Parents should also ask if their child's doctor is participating in the trial, adds Murphy, and, if so, what role the doctor has and if he or she is being reimbursed for participating.

Parents who are considering enrolling a child will be invited to the research site to talk with the study investigator or other scientist or health care professional on the research team. FDA experts offer some suggestions for this discussion:

  • Write down a list of questions at home and take it with you when you meet with the investigator. Make sure you get all of your questions answered.
  • Take notes during the discussion. Read the notes back to the investigator to make sure you heard everything correctly. Ask the investigator, "Can I tell you what I think this is about and you tell me if I'm right or not?"
  • If you do not understand any part of the trial, ask more questions. You should feel that the study team is receptive to your questions and concerns.
  • Ask what information is already known about the medical product that your child may be given. Studies may be in progress elsewhere and some data may be available.
  • Ask for contact information if you would like to talk to other parents whose child is participating in the study. The study team can provide this information if they get permission from other parents to have you contact them.
  • After being presented with information and an informed consent document, you do not have to sign it right away. Go home and think about it, talk it over with your family, your child's pediatrician, and other trusted people.
  • Listen to your "gut." If you're not satisfied with the information given to you and the answers to your questions, don't enroll your child.

Withdrawing From a Clinical Research Study

Parents can take their child out of a clinical trial at any time, and may want to if the treatment is not working for their child or if the side effects are intolerable. Before withdrawing a child from a trial, you should:

  • Talk to the child's pediatrician, who can help you evaluate the consequences of leaving the trial.
  • Ask the trial doctors if it is safe to leave. Some drugs should be tapered, so you should not just stop giving your child a drug.
  • Let any other doctors the child sees know that the child is leaving the trial, in case he or she needs another medication in place of the one received in the study.

After withdrawing a child from a trial, parents should report to any new doctors who see the child, even years later, that the child was in a clinical trial and may have received a certain treatment.

FDA Encourages Studies in Children

FDA has taken a carrot-and-stick approach to encourage studies in children, says Rodriguez. The "carrot" is the Pediatric Exclusivity Provision of the FDA Modernization Act, passed initially in 1997 and becoming law under the Best Pharmaceuticals for Children Act (BPCA) in 2002. BPCA gives drug manufacturers a voluntary incentive of an additional six months of marketing exclusivity—the ability to sell their drug without competition from generic drugs—if they conduct pediatric studies of drugs that FDA determines may be useful to children.

The "stick" has been the Pediatric Rule, finalized in 1998 and basically passed as the Pediatric Research Equity Act (PREA) in 2003. PREA authorizes FDA to require manufacturers of new drug and biologics products to conduct pediatric studies in certain circumstances.

Together these two acts have encouraged the development of important new information for drugs used in children.

As of Feb. 20, 2009, labeling changes have been made to more than 260 products that were studied in children under BPCA or PREA. Of the more than 170 drugs studied just under the exclusivity incentive program within the BPCA, 159 have new pediatric labeling information including:

  • 45 drugs with new or enhanced pediatric safety data that hadn't been known before
  • 27 drugs with new dosing or dosing changes
  • 50 drugs with information stating that they were not found to be effective in children

"This means that before these drugs were studied in children, we were giving children the wrong dose for at least some part of the pediatric populations for one-sixth of these drugs," says Murphy. "In addition, we found that one-third of them didn't work in children and one-fourth of them raised a new pediatric safety issue."

One of the safety issues that arose during the studies was concerns with suicidal thinking for antidepressants called selective serotonin reuptake inhibitors (SSRIs). These antidepressants now carry a black box warning—FDA's strongest warning—on their labeling about increased risk of suicidal thinking and behavior in children, adolescents, and young adults. The warning does not mean that the product shouldn't be used if a depressed child needs treatment, but it gives parents, caretakers, and physicians signs to monitor when beginning or changing the treatment.

As required by the FDA Amendments Act of 2007, the agency posts information on drugs and biologics studied in children, including which drugs have received additional marketing exclusivity, full clinical and other reviews, and characteristics of pediatric studies conducted under the BPCA and PREA.

This article appears on FDA's Consumer Update page1, which features the latest on all FDA-regulated products.