Your child’s physician provides state of the art care that, hopefully, is second to none. However, we should not be satisfied
with this as our long-term goal. Just consider for a moment what “state of the art” meant for computers even 10 years ago.
No-one would buy a 1995 computer for their child today! Similarly, we must develop new cures for existing diseases and better
strategies to maintain health and prevent illness. Having our children participate in properly conducted research studies
is the way to achieve this goal. History has proven this statement: for example, in the 1980s only 20% of children diagnosed
with cancer lived, whereas today, thanks to research, more than 70% survive.
Babies and children are not just small adults; they have different bodies with different physiology and often suffer from
different diseases. Consequently, research involving children is essential: studying adults cannot teach us about children’s
health, development, and health problems. It is equally important, of course, to protect children who participate in research.
If your child has an illness, you may already be familiar with some of the aspects of clinical research. This column will
discuss the nature of clinical research, some barriers to clinical research in children, and some reasons to get involved.
When research is lacking: The problem of off-label prescribing
One example of necessary research that involves children is clinical trials of drugs. Most drugs, including many that we give
children routinely, have not actually been studied or approved for use in children. Because many childhood diseases are rare,
it is difficult and expensive to find enough children to study a particular treatment and the market for drugs in children,
with a few exceptions, is small. Even with incentives, manufacturers do not do much work in this area.
As a result, many drugs are prescribed to children, and especially to babies, “off-label.” This does not mean that the drug
is known to be harmful or that it should not be used, but it does mean that we lack information about its safety and effectiveness
for a particular condition or a particular age group. Usually, there is no choice but to prescribe off-label. There simply
is no information available about what drugs and dosages will work in children, so doctors calculate what a child needs from
the adult dosage, or give the drug in a different format. However, off-label prescribing can be ineffective or even dangerous.
Children’s different physiology means that they may handle the same drug differently; it may work differently in their bodies
than in an adult’s. This can result in unexpected side effects, overdoses, or “least worst,” a lack of effect.
The American Academy of Pediatrics estimates that 75% of drugs are used off-label in children. The younger the child, the
more likely it is that he or she will receive an off-label prescription.
As Dr. Philip Walson of Cincinnati Children’s Hospital has said, “It’s an uncontrolled experiment every time we give a drug
to kids which hasn’t been tested in their age group.” Without clinical trials, doctors must continue to prescribe drugs without
enough information. Drug trials in children are urgently needed.
Types of clinical research
Of course, while it gets a lot of attention, drug research is not the only kind of clinical research involving children. A
lot of research is conducted to learn more about diseases that only happen in children, or that have a different course in
children than in adults. We also study children’s mental and physical development in research that can ultimately benefit
all children.
At The Hospital for Sick Children (Sick Kids), like other paediatric academic health science centres, one of our mandates
is to develop new cures for childhood diseases. At Sick Kids we presently have about 1,700 active research studies. Approximately:
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33% are “chart reviews;” these look at the patients’ existing hospital records to study the
epidemiology, course, or prognosis
of a disease, to look at
diagnostic methods, or to assist in planning a prospective
clinical trial or investigation.
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23% involve talking to patients and using questionnaires, interviews, or information collected for databases to study disease
outcomes, behaviour, opinions, quality of life, or patient satisfaction.
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28% involve actual direct contact with study participants. These studies may include physical examinations, imaging, and specimen
collection to study diseases or diagnostic methods.
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17% are intervention studies that look at a therapy such as a drug, natural health product, medical device,
surgery, or behavioural
therapy.
The process of clinical research: Consent and safety are paramount
Sick Kids and other paediatric academic health science centres also mandate that our patients’ best interests are safeguarded
by having strict review processes throughout the entire life of the study. In general, a researcher at Sick Kids must go through
these steps to conduct any study:
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Scientific review
The study design is reviewed to make sure that it is scientifically valid and will produce useful results.
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Ethics review
The Research Ethics Board, whose members include health care researchers, lay members of our society, and others, must be
satisfied that study participants will be treated ethically and not put at undue risk.
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Government review
For drug, medical device, or natural health product studies, Health Canada must also review the study to ensure that study
participants will be safe and that the study is scientifically sound. Similar government agencies in other countries, such
as the U.S. Food and Drug Administration, may also review the study.
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Recruitment and informed consent
Once the study is approved, it begins to recruit patients. If a child is eligible to participate, a researcher approaches
the child and his or her parents to ask if they would like to be part of a research study. The researcher must carefully explain
the study and what the child will be asked to do, answer any questions, and ask for the informed consent of the parents and
the consent or assent of the child. Often, especially if the study is more intensive or invasive, the family is encouraged
to go away and think about it for a day or so before deciding whether to participate. Parents should feel free to refuse to
participate in a study; their child’s care will not be affected, whether or not they agree to participate.
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Research study
Exactly what is asked of a study participant varies from study to study. In some studies, the child will be asked to talk
to a researcher for 15 minutes. In other studies, children are followed for years or even decades, and must give regular blood
or tissue samples or have regular imaging tests. Most studies fall somewhere in between. Consent must be maintained all through
the study, meaning that the child or the family have the right to withdraw from the study at any point.
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Oversight
Throughout the study, it is monitored to ensure that the participants are safe, the researchers are complying with all necessary
guidelines and laws, and the research is valid and of high quality. This may involve written status reports, audits, and observation
of the study. The level of oversight is based on the level of potential risk to participants.
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Publication
At the end of the study, the researchers write one or more papers describing the results and submit them to peer-reviewed
medical and scientific journals for others to read and learn from, so that children around the world benefit from the new
knowledge that has been created. Most researchers will also provide study participants with a summary of the results of the
study.
Why participate in clinical research?
For various reasons, it can sometimes be difficult to find enough children to participate in clinical studies. Most childhood
diseases are rare, so studies can take a long time to recruit participants. In addition, the parents of a child who is ill
have many demands on their time, energy, and emotions, and may not want to deal with another demand. When a study requires
follow-up over long periods, a certain number of families may drop out. And there is no guarantee, in a treatment study, that
the child will necessarily be helped by the treatment.
Families who do decide to participate in clinical research often say they want to “give something back” and contribute to
science. Participating in a study often helps families to learn more about their child’s illness and feel that a cure is one
step closer. In many cases, even if the study may not help their child directly, there is a good chance it will help others
in the future.
Even healthy children can participate in research, often as healthy or “typical” comparisons for learning or behaviour studies.
This can be a good way for interested children or teens to learn about research from the inside, and even to get high school
volunteer credits.
Sick Kids will soon be launching a website that lists studies that are recruiting patients, which will make it easier for
parents to find studies their child might join and for researchers to find potential study participants.
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Hugh O’Brodovich, MD, FRCP(C), was Paediatrician-in-Chief at The Hospital for Sick Children from 1996 to 2006.
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