Ensuring the Quality and Safety of Clinical Research in Children

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Over the past decade, there has been an explosion in clinical research, largely because society is demanding it. While most patient-based research occurs in adults, there is a need and an obligation to also conduct clinical research in children.

For one reason, children are not simply small adults. Their bodies are different depending on what stage of development they’re at, and they suffer from different diseases and conditions than do adults. Research into treatment for congenital heart disease, for example, is very different from research into heart disease in adults, where environmental factors like diet and stress often play a large role. It is also very important for children to be included in the development of new drug therapies because children react very differently to medications, such as with the level of toxicity.

“Clinical research is considered to be much more complex in children than adults. They are less able to give consent to participation in research, which is primarily done by parents as surrogates for the child. There is also a perceived vulnerability, in that children are perceived to be more susceptible to harm from new interventions during the growth period,” said Dr. Denis Daneman, associate chief of clinical research at The Hospital for Sick Children (HSC).

“Nevertheless, it is up to academic health science centres like The Hospital for Sick Children to initiate and conduct clinical research in children because it is through research that we are able to improve patient care and outcomes,” added Dr. Daneman.

Currently, there are more than 1,000 clinical research studies taking place at The Hospital for Sick Children, with most of these directly involving patients.

HSC’s Clinical Research Secretariat has developed a model for ensuring clinical research safety and excellence, which outlines the process and supports for conducting clinical research. It includes the scientific, ethical, operational, monitoring and dissemination phases of research. The Clinical Research Office at Sick Kids is available to assist researchers through the different parts of the process.

A scientific review of the proposed study ensures that the research question being asked is worth asking. HSC’s Clinical Research Support Unit provides expertise to investigators in terms of study design, biostatistics, and epidemiology.

For the ethical review of the research, the 18-member Research Ethics Board (REB) determines whether the research can be done safely and effectively without exposing the children to too much harm. The REB follows very strict principles such as those outlined by the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, NIH guidelines, and good clinical practice.

In tandem with the scientific and ethical reviews, HSC’s Intellectual Property and Commercial Development Office reviews any contracts related to the research study and makes sure the contract meets the institution’s guidelines (such as the right to publish results). Any possible conflicts of interest the principal investigator may have, such as a possible financial gain from the research, are also disclosed.

The clinical research review process further looks into whether there are the resources available to complete the study, and that the research will take place in the appropriate setting in the hospital, such as the Clinical Investigation Unit or the Exercise Physiology Unit.

Once a study has been approved and is underway, it then needs to be monitored to make sure it meets the ethical and scientific agenda that was established. HSC is currently putting in place a program for the monitoring and auditing of all clinical research. All studies will be assigned a level of monitoring, based on the type of research study, the type and invasiveness of research participants, the potential risk to research participants.

The final phase of the HSC clinical research process involves the dissemination of results. This includes the publication of results, and also informing the patients in the study of what was done on them, what the findings were, and what the implications of the findings are. Beyond the immediate patients in the study, there is also an obligation to inform the wider community of the implications of the research.

“Clinical research, particularly in children, should not be done on a whim. It needs to follow a process such as the one we have developed in order to ensure the quality and safety of the research,” said Dr. Daneman. “A system with the appropriate checks and balances is time consuming. But, it is up to the institution to provide the infrastructure necessary so the investigator is not over-burdened, or discouraged from engaging in necessary clinical research.”