Expect pediatric clinical trials to surge

How to help parents decide whether to participate

A new law goes into effect in December requiring that all new drugs and new formulations of existing drugs be tested for use in children. On a national level, roughly 80 pediatric drug trials run each year, according to the Food and Drug Administration (FDA). However, based on the number of drugs approved in the last five years with potential benefit for children, the FDA estimates that, under the new law, an additional 375 pediatric drug trials will run each year.

"Anytime a patient gets a drug, it’s an experiment to see if it works for that particular patient. But with children, we’re even more in the dark because we don’t have the same quality information as we do for adults. Currently, only about 20% of the drugs on the market are well-studied in children," says Mark S. Schreiner, MD, medical director of The Children’s Clinical Research Institute at The Children’s Hospital of Philadelphia.

That predicted dramatic increase in the number of pediatric clinical trials raises a number of issues for pediatric case managers and the parents of the children whose care they coordinate. "From my perspective, there is never a justification for any individual patient to take on undue risk to benefit the rest of society. On the other hand, if children do not participate in trials, then children as a group will not benefit," he says.

"One of the principles behind all research is the idea of distributive justice. That is, there must be a balance between the burdens of research and the benefits of research," he adds. "We have inadequate information regarding the safety and effectiveness of drugs for children. As a result, children have not been equal recipients of the great advances in medicine and drug research. If we want to see children partake of the benefits, then we, as parents and society, must accept a communal obligation to bear part of the burden."

Case managers can play an important role in helping parents decide whether to enroll their children in a clinical trial. Schreiner suggests you prepare for the questions parents are most likely to ask about the safety, potential benefits, and risks of participating in a pediatric clinical trial.

Parents must make decisions as trustees for their children because children are not legally or developmentally able to make those decisions on their own, he notes.

Questions and answers

The following are Schreiner’s answers to what are, in his experience, the most common questions parents raise about enrolling their children in clinical trials. His advice, based on his own pediatric clinical trials, should help case managers counsel families through what may be a difficult decision-making process.

  1. Why have we been approached to have our child participate in a clinical trial? A child’s pediatrician may ask parents to participate in a clinical trial based on personal knowledge of their child’s medical history, Schreiner says. "If your child is hospitalized or is being seen in a clinic, you may be approached directly by an investigator or a clinical coordinator. Some hospitals maintain a database of patients and diagnoses.

    The database may be searched if researchers are looking for a particular disease or condition. In a hospital setting, physicians meet at least once a week to review challenging cases, and your child’s case may be one of them. It’s very important that you do not feel pressured into making a decision, even if it is your child’s pediatrician asking you to participate."
  2. Does my child have the disease or problem that the study targets? A drug study should always be a match for the child. "Obviously, a child should not participate in the study of an epilepsy drug unless the child has epilepsy," notes Schreiner. "However, some conditions are so common that all children will benefit from having your child participate. For example, researchers may be investigating a new drug to treat fever or ear infections in children."
  3. Will my child be able to cope with a trial? No one understands a child’s temperament better than the child’s parents, he notes. "You know your own child better than anyone else. Does your child have the temperament and personality to cope with the disciplined regimen required by a clinical trial? Children have a great sense of altruism, and they will benefit by understanding that they’re helping others."
  4. What is a protocol? Case managers may need to explain to parents in clear, layman’s terms about clinical protocols, says Schreiner. "A clinical protocol is the document by which all research studies flow. It’s essentially the research bible’ that outlines the exact procedures for the investigator to follow. There must be no deviation. A protocol begins by explaining what is being studied and why. It also includes the name of the sponsor and names of the principal investigators. The protocol will explain the study design, how many people will be in the study, how many times each patient will be seen, what laboratory tests will be done, and how often. It will also explain the risks and potential benefits of the study."
  5. What is involved in the study? Parents should receive a verbal explanation of the study, and the details of the protocol should be included in a written consent form, Schreiner says. "Although the consent form should give you most of the details, there are a few extra items [parents should] ask about," he explains. "For example, will you be actively involved with collecting and reporting data? If your child is older, will your child be required to keep a diary or to phone in results? How many visits will there be? Will blood be drawn? What are the risks? What are the expected benefits?"
  6. What are the doctor’s hours? Parents should find out whether the investigator keeps evening and weekend hours, he suggests. "You’ll want to minimize disruptions to your work schedule and to your child’s school day. When you arrive at the doctor’s office, will you be seen promptly? When you are participating in a trial, you should be seen right away without waiting as you might for a routine office visit."
  7. Is it safe? "When we conduct clinical trials, the safety of the child is our utmost concern. All aspects of a clinical trial are preapproved by the FDA and by an institutional review board [IRB]," he says. "This means all of the investigators are performing the same procedures in the same way. And from an educational point of view, everyone involved in conducting the trial shares information and experiences and contributes to problem solving. The level of surveillance in terms of number of provider visits and attention to the individual child is usually much higher than during routine medical care. The result? A well-written clinical trial reflects the best care."

FDA helps ensure safety

In addition, drugs are usually tested in adults first, notes Schreiner. "So we do know more about the drug and its likely benefits before we start a pediatric clinical trial. An exception would be when the drug affects only children. For example, a clinical trial for a new vaccine may be tested only in babies."

Finally, the FDA has established strict guidelines for how clinical trials are to be conducted. It requires the sponsor of the trial to scrutinize the credentials of the clinical investigators who conduct the trial."

  1. Will we be compensated for participating? If there are no extra visits or procedures, parents should not expect to receive any compensation. However, if there are, parents should be compensated for the trouble they take to participate in a study, Schreiner notes. "This includes reimbursement for transportation, meals, and overnight accommodations. Your child may also be offered a small gift, such as a savings bond or a gift certificate for toys or books. However, be wary of expensive gifts as a lure to participate in a study."
  2. What if my child is a girl of childbearing age? "[Because] there is so little information about the effects of drugs on pregnant women and developing fetuses, drug companies and clinical investigators will want to be sure that your daughter is not pregnant and will not become pregnant during the course of the trial," says Schreiner. "This may be a difficult issue for parents of young girls who are capable of childbearing but are not yet sexually active. A pharmaceutical company may require your daughter to take a pregnancy test and may also require her to use some form of birth control. Some companies may accept abstinence as a means of birth control."
  3. Is the investigator experienced? Has the investigator conducted previous studies? You have a right to ask for the credentials of the principal investigator and of anyone else involved in the trial, he notes.
  4. Is there an experienced study coordinator, nurse, or other resource person who is going to be available to me? Schreiner recommends that parents ask to meet the principal investigator, the study coordinator, and anyone else who will work with them and their child during the trial. "It’s important for parents to be at ease with all of them and to be confident they will be available whenever you have questions or a problem."
  5. Has the protocol been reviewed by an IRB? The IRB is a committee within the organization or hospital that ensures the protection and ethical treatment of all participants in a clinical study, explains Schreiner. "The IRB is an impartial, independent group that has no relationship with the individual clinical trial."
  6. If my child is injured during the the trial, who is responsible for paying for the cost of treatment? "This issue is usually addressed in the consent form," notes Schreiner. Parents should discuss this issue with the investigator before signing the consent form, he recommends.
  7. Can we drop out at any time? Parents should understand that they can drop out of a trial at any time, for any reason, without a penalty, says Schreiner.
  8. Do I understand the consent form? Parents will get a detailed consent form to sign, written in the language the parents speak with words they understand. "Informed consent is not a single event. It is an ongoing process during which parents must have time to understand, to make an informed decision, and to continually re-evaluate their willingness to participate. Parents should be given a copy of the consent form so they can reread it to refresh their memory about the study details."
  9. What if I have trouble making a decision? Sometimes parents are overwhelmed, especially if they have just learned that their child has a serious illness, notes Schreiner. "Parents should listen to what their child’s physician and the principal investigator have to say. They should also read through all of the materials presented to them," he says, adding parents should be reassured that it’s OK to say no if they feel the study is not right for their child.

    Many more parents will be approached by physicians asking for permission to enroll their children in drug trials, cautions Schreiner. "We were all children, many of us will have children, and our children will have children. So we all have a stake in this. It’s ironic that, to date, by protecting children from risks, we have also denied them the benefits."