Why studies in children?
The younger and sicker children are, the fewer approved medicinal products are available for their treatment. The backlog of medicinal product studies in children is therefore large, and a large proportion of medicinal products currently used in children have never been tested in children and are not authorised for use in children.
However, pharmaceutical companies are now required by new European laws to test medicinal products specifically in children and to have them approved for children. And for good reason, because the organism of a developing child is different from that of an adult, which is why medicinal products can have different effects in children. Thus medicinal products in children need to be specifically tested to systematically determine correct doses, effects and adverse reactions. In the absence of such information, medicinal products may be unsafe for children with regard to effects and adverse reactions.
The need for medicinal product studies for children, in principle, concerns all child age groups.
Important for all age groups – especially for the very young
As a rule, active substances that are successfully used in adults are often also suitable for the treatment of children and adolescents. However, additional clinical studies are needed to evaluate the correct dosage for each age group. This ultimately leads to different dosage recommendations, either related to body weight or age group (infants, toddlers, school children or adolescents).
The need for medicinal product studies for children, in principle, concerns all child age groups. In the neonatal period however, this problem is particularly pronounced: more than 90% of all medicinal products used in neonatal intensive care units have never been tested on the specific patient group of premature and sick newborn infants. For this group of patients, clinical studies are thus a particularly important opportunity to render existing therapies safer and to make new therapies possible.
How is a medicinal product (for children) developed?
- Preclinical studies (laboratory, cell cultures, animal studies)
- Clinical medicinal product trials (human studies): Phase I study | Phase II study | Phase III study | Phase IV study
* After approval, a fourth study phase is conducted in which the medicinal product is further tested, monitored and frequently optimised.
In preclinical studies the first step is to search for active substances with potential therapeutic effects. This is followed by intensive testing in laboratory experiments, on cell cultures and subsequently on animals. Only if active substances have proven to be effective and safe in these series of tests is the active substance further developed and then finally tested in clinical medicinal product studies on humans.
A clinical medicinal product trial in humans consists of three phases, each usually lasting between 1.5 and 5+ years, up until final approval of the medicinal product. If an active substance is completely new, it is whenever possible first tested on adult volunteers. Only in exceptional cases and with highly specific replacement therapies for congenital diseases is initial testing also carried out in children, in close consultation with the parents.
In each phase, an increasing number of patients are tested in the study.
With common diseases and studies on vaccinations, high numbers of participants are aimed for. The largest of this kind was a phase III study of 65,000 children for testing a vaccine against rotaviruses which cause diarrhoea. To confirm the efficacy and also to systematically record adverse reactions, at least two parallel groups are compared. The control group receives the standard treatment and the second group receives the new medicinal product being tested.
Why should my child participate in a study?
By participating in a medicinal product study, children have early access to new treatment possibilities and receive the best possible adjunctive therapy. During studies the children are observed in a particularly detailed and systematic way, which in turn creates special conditions for high-quality care structures. Sick children are not subjected to excessive stress, and for this reason studies for children are specifically planned to take account of their particular needs.
Participating children and adolescents therefore experience excellent medical care during a study:
*Of course, participation in a study can be terminated prematurely at any time without needing to give reasons.
- Supplementary medical examinations are carried out at certain intervals, possibly with additional laboratory tests.
- The sick child may be treated earlier with a medication that complies with the latest medical findings.
- Treatment is either with a promising new medicinal product, usually already proven in adults, or with the best approved therapy (which is usually the result of previous studies).
- However, there are also rare diseases that begin in childhood and for which no specific treatment has yet been developed. In such cases, a novel medicinal product must also be tested on children for the first time.
Advice on the decision regarding study participation
Your attending doctor will inform you about the treatment options and also explain which unanswered questions remain concerning the current routine treatment. The doctor will also explain what the benefits and risks are for your child upon participation in the study as compared to routine treatment. Participation in the study is voluntary, and the decision is up to the legal guardians and children concerned, if these are old enough. Whatever treatment you choose, your child will be treated according to best knowledge and judgement.
How is a clinical study conducted?
Studies with children follow the same guidelines and usually last between a few weeks and a few months. First, you as parents are informed by the attending medical team that a suitable study exists for your child’s medical condition. If you are interested, first of all you are provided with information about all aspects of the study in an informed consent interview.
If you decide to participate, you then sign an appropriate informed consent form together with your doctor. According to Austrian law, the signature of one parent is sufficient. Only then can your child be included in the study. The information for and clarification of your child is always age appropriate. Children of pre-school age upwards also sign an age-appropriate information sheet, but this is not required for younger children.
You can withdraw the declaration of consent at any time without providing reasons.
During the so-called “screening examination” it is checked whether your child meets the criteria of the study and is able to participate in it.
... how the respective medicinal product is administered or the medical device to be tested (e.g. inhalers for asthma therapies) is used. The study team carefully monitors the course of treatment and tolerance to the medicinal product and documents the results. In some cases questionnaires must be completed, or it is necessary to keep a patient diary to document how your child is progressing with the study medication when not under hospital observation.
... will be invited to regular interim examinations. If the overall use of the medicinal product is satisfactory, your child remains in the study until its scheduled end.
At the end of the treatment phase your child will be examined again in detail at a final examination, and the state of health of the child will be compared with that before the start of treatment. Follow-up examinations may be carried out at a later date to determine the long-term results of the therapy.
How are children protected in clinical studies?
The clinical investigation plan is the detailed description of the study and its conduct. Prior to the start of the study, this is carefully checked by the responsible ethics committee and the responsible authority in Austria (Federal Office for Safety in Health Care), and only approved if all requirements are complied with. Here, special protective measures apply to children and adolescents.
An ethics committee for clinical research consists of physicians, scientists, lawyers, theologians and patient representatives
Medicinal product studies in children commissioned by the pharmaceutical industry for approval of a medicinal product are reviewed in advance by the Paediatric Committee of the European Medicines Agency. This committee determines whether there are good chances that the medicinal product is able to advance treatment in children.
The aim is to evaluate research projects from an ethical, legal and social point of view and to assess the potential risk in a study for children and adolescents. Furthermore, the ethics committee appraises whether the medical facility is suitable for conducting a study. The quality of study physicians is also evaluated.
The texts on the information sheets are examined for ease of understanding and completeness.
Studies involving minors must be planned in such a way as to minimise stress. Examinations must therefore not be conducted more frequently than is absolutely necessary.
The authorities and ethics committees monitor all ongoing authorised studies. These bodies will terminate a study if serious adverse reactions occur.
As part of a clinical study, insurance is provided for all participants. If, despite all precautions, health impairments occur during the treatment or during the follow-up phase, these are covered by the insurance.
If you have any concerns about the safety or effectiveness of the treatment, you may terminate participation in the study at any time. Treatment is then continued with the standard therapy.
What is OKIDS?
The advantage of this network is that paediatricians pool their experience – on the one hand this allows the best possible standard treatments for children in coordination between the centres, and on the other, enables the testing of new treatment options in close cooperation between the centres and international networks.
OKIDS has established a forum of experts consisting of Austrian paediatricians to ensure a focus on medicinal product trials in order to improve the most urgent treatment deficits for children. With support via public funding, OKIDS provides organisational structures that enable medicinal product trials to be conducted safely, efficiently and in an acceptable way for children as part of the requisite treatment.
Download our consultation brochure on paediatric medicinal product studies as a PDF: