In this section you find information about Clinical Trials to Children, their Parents and the Public.
TEDDY, a European network of scientists and physicians collaborating to improve the availability, efficacy and safety of medicines for children has developed answers to frequently asked questions about clinical trials with children. This information is meant for parents, children and the general public and explains the key issues around clinical trials.
1. Why are clinical trials with children important?
2. What is a clinical trial?
3. What types of clinical trials do exist?
4. what is a clinical trial design?
5. What are the benefits and risk of participating in a clinical trial?
6. What are side effects and adverse reactions?
7. What is informed consent?
8. What if I want to withdraw my child from a clinical trial?
9. Who sponsors clinical trials?
Children are not small adults and have a specific age-related response to medicines. Instead, they very often are treated with drugs which were only studied in adults (off-label and/or unlicensed medicines) with many risks (we do not know what the drug’s best dose is, whether it works in the same way, whether it is safe in a growing up body). For this reason it is so important to perform clinical trials properly designed for children.
A clinical trial is a research study that uses volunteers to test new methods of screening, prevention, diagnosis or treatment of a disease. Here we deal only with treatment trials.
These studies are designed to ask questions such as:
- "Does a new drug cure a disease, or make some of the symptoms go away?" (Efficacy studies or Phase III Clinical trial)
- “What is a proper dose for a child?” (Pharmacokinetics/Pharmacodynamic studies or Phase I/II clinical trial)
- “Is this drug safe for a child?” (Safety studies or Phase III/IV clinical trial)
Clinical trials are usually classified according to their scope and grouped into four main categories.
- Phase I Studies
Represent the early use of the drug under evaluation in man. These studies try to evaluate drug safety, determine a safe dosage range, and identify side effects, extrapolating from animal trials.
They are the more risky ones and so they generally enrol few healthy adults or in some cases children affected by very serious diseases for which there are not treatment or those existing are ineffective, in the hope that a new and untried drug will work.
- Phase II studies
Once the initial safety of the study drug has been confirmed in Phase I trials, these studies are performed on a few more people and in different doses to see if it is effective and to further evaluate its safety.
- Phase III studies
The drug is given to large groups of children to confirm its efficacy, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug to be used safely.
Generally they continue while the regulatory submission is pending at the appropriate regulatory agency. This allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase.
Other reasons for performing trials at this stage include attempts by the sponsor at "label expansion" (to show the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), to obtain additional safety data, or to support marketing claims for the drug.
- Phase IV studies
These studies are called also Post Marketing Surveillance ones, because they are conducted after the drug is commercialized. They can last many years and involve many subjects/children. They give additional information including the drug's safety (pharmacovigilance), its benefits and optimal use.
The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials.
The simplest way to prove efficacy and safety of an experimental drug is to perform comparison based on three important characteristics:
- Randomization: Each study child is randomly assigned to be either in the investigational drug group or in the control group (a group that is treated with the standard of care for the disease). For effect of randomization the choice of the treatment is at random and this provide the most persuasive evidence that the study treatment causes the expected effect.
- A control group: A control is the standard by which experimental observations are evaluated. It can be either a standard treatment for the illness (active control) or a fake treatment (placebo). The use of a control group allows the researchers to isolate the effect of the study treatment.
- Blindness: The participants do not know which study treatment they receive. In the double-blind studies, the researchers also do not know which group a given child belong to. This allow to avoid any conditioning both for the children and their families and for the researches.
A clinical trial is always a balance between risks and benefits for the subjects/children enrolled in the trial. The ultimate goal is however to provide people with drugs whose effectiveness and safety is adequately proved.
- Play an active role in their own health care.
- Gain access to new research treatments before they are widely available.
- Obtain expert medical care at leading health care facilities during the trial.
- Help others by contributing to medical research.
- There may be unpleasant or sometimes serious side effects to experimental treatment.
- The experimental treatment may not be effective for the participant.
- The protocol may require more time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements.
Side effects are any undesired actions or effects of the experimental drug or treatment.
Informed consent is the process of learning the key facts about a clinical trial before deciding whether or not to participate. It is not a contract, and the participant may withdraw from the trial at any time.
The objective of the informed consent process is that the parents and child are comfortable with their choice and can comply with it. All questions should be answered clearly and there should be no pressure to enrol the child in the study.
The basic parts of an informed consent document include details about the study, such as its purpose, duration, required procedures, risks and potential benefits and key contacts. The parents then decides whether or not to sign the document.
Children cannot give informed consent because consent implies a full understanding of the potential risks and other considerations of a clinical trial, but they may be asked to "assent" or "dissent”.
Participation in clinical trials is completely voluntary. 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.
Clinical trials are sponsored or funded by a variety of organizations or individuals such as, medical institutions, foundations, pharmaceutical companies, physicians, voluntary groups. Trials can take place in a variety of locations, such as hospitals, universities, doctors' offices.
Throughout the clinical trial, the sponsor is responsible for collecting adverse event reports from all site investigators in the study accurately and for informing the local site investigators of the true historical safety record of the drug to be tested.
The sponsor is responsible for monitoring the results of the study as they come in from the various sites, as the trial proceeds.
Courtesy to Paola Baiardi et al, TEDDY