Ensuring safe and high quality studies of new and existing interventions is an undertaking that transcends geographic boundaries. Around 250 pediatric clinical trials are registered to take place in Canada annually. Two thirds of these studies are investigator-initiated and sponsored by MICYRN member organizations.
Did you know?
- Most medications used to treat children and virtually all medications for neonates have not been adequately studied and are not approved for use in the pediatric population or for specific pediatric ailments. There is a rising demand for therapeutics for orphan diseases, where the “genomics revolution” has led to better diagnosis of rare diseases — 75% of over 7000 rare diseases present in childhood. These “orphan” therapies have a high cost, yet cannot be studied by traditional trials methods.
- New forms of trials such as behavioural interventions or community clusters are needed to study important conditions like developmental disorders, mental health and obesity.
- Clinical trials in children inherently involve multiple sites and are frequently multi- national because there are too few cases at any one centre to conduct quality studies in a timely fashion.
In 2012, the Minister of Health, on behalf of Health Canada, asked the Council of Canadian Academies (CCA) to convene an expert panel and provide an evidence-based and authoritative assessment on the state of therapeutic products for infants, children, and youth. MICYRN contributed to the development of the proposal, presented to the panel, assisted in the dissemination of the report findings, and used these to develop a business case for national trials infrastructure. The panel identified five key findings in their report published in September 2014:
- Children take medications many of which have not been proven safe and effective for their use.
- Children respond to medications differently from adults; thus medicines must be studied in children and formulated for children.
- Studying medicines in children is always possible and is in their best interests.
- In the United States and the European Union, pediatric medicines research is encouraged, required and monitored in ways that offer lessons for Canada.
- Pediatric medicines research is a Canadian strength, but it requires reinforcement and sustained capacity and infrastructure to realize its full potential.
A major barrier to conducting pediatric studies is the need to repeat the setting up of infrastructure for each new study at each site involved. Core infrastructure includes qualified and experienced staff that can act as a contact for sponsors, reduce the time to study start-up, and improve the quality of research. Major international pharmaceutical companies are joining together in an initiative to create a Global Pediatric Clinical Trials Network in response to U.S. and EU legislation that requires manufacturers to submit acceptable pediatric investigation plans before authorization of any new medicine. In July 2015, the Critical Path Institute launched a PreLaunch Consortium, which involves MICYRN, to establish the Network, create its organizational and operating framework, and identify its leadership team.
MICYRN is committed to improving data quality, reliability, reporting and sharing. The network’s working group in clinical research informatics (CRI) brings together a broad complement of research informatics experts from across MICYRN member institutions, to share knowledge, develop best practices and determine approaches to investigator needs.
Did you know?
- Data support tools, processes, personnel and training often pose a high cost to research studies.
- As data becomes increasingly electronic, requirements for data security and consensus on standards is paramount.
- There is an ever-evolving need to integrate data from research studies with information collected during routine clinical care.
- Multi-site studies and teams of investigators require support systems to ensure the uniform quality of data.
- There is a need to share data internationally in order to determine genomic associations with disease risk and pathogenesis.
REDCap® (Research Electronic Data Capture; Vanderbilt University) provides an affordable, safe, easy-to-use, web-accessible software that is validated and compliant with regulatory standards. REDCap® installations are now established at the majority of MICYRN member sites, linked through the MICYRN CRI working group. To support investigator-initiated clinical trials, MICYRN has established a version of REDCap® subjected to extensive validation and maintained in an environment that meets requirements for data management in regulated clinical trials. The shared-resource model allows both the distribution of work required to maintain the system, as well as collaboration that would otherwise be difficult and costly for a single site to run and maintain.
Increasingly, investigators and teams in our community want to share data between project collaborators and other teams, both nationally and internationally, as well as be able to link and integrate data in one system with others. Thus, there is a need for tools that can harmonize, link or integrate data across different informatics platforms, not only within the research world, but also with hospital and community clinical information systems and electronic health records. MICYRN is developing a number of tactics to provide support in these areas.
In furthering its contributions to research informatics, MICYRN is partnering with the following groups.
- Public Population Project in Genomics and Society (P3G): P3G’s International Paediatric Research Programme developed tools and resources on ethical, legal and social issues (ELSI), biobanking, and longitudinal studies.
- Maelstrom Research: Maelstrom Research provides a suite of methods, open-source software, and expert advice to support valid data comparison, integration, and harmonization across cohort studies. MICYRN has partnered with Maelstrom to develop a birth cohort registry to support research into the developmental origins of health and disease (DOHaD).
- Public Health Agency of Canada (PHAC): MICYRN now benefits from a secure web-based collective of applications with an innovative IT architecture that PHAC has developed and administers to support document management, real-time data sharing and communication for national research initiatives that include the Canadian Longitudinal Study on Aging.
MICYRN aims to advance the quality and consistency of ethics review of reproductive and child health research. Our collaborative working group is comprised of chairs from eight self-standing reproductive and child health research ethics boards (REBs) in Canada, and other experts in ethics and law.
Did you know?
- Multijurisdictional research is common in the Canadian reproductive and child health research community – network and research team studies often involve 17-22 sites across the country and each site currently conducts an ethics review of the same study.
- The ethics approval process for a multi-site study is inefficient and resource intensive: with the amount of paperwork and deliberation involved, it can take upwards of two years for a study to be approved at all sites.
- Existing and emerging ethics issues challenge the capacity of REB members at multiple institutions to stay up-to-date, and retain ethics expertise to perform high-quality reviews.
MICYRN catalyzed the creation of a coalition of birth cohort investigators participating in the development of a Canadian metadata registry with Maelstrom Research to support studies on the developmental origins of health and disease (DOHaD).
This builds on our national birth cohort inventory.
Networks and Research Teams
Collaborative groups of researchers are essential to advancing maternal and child health, as individual centres have too few patients with any given condition or adverse outcome to conduct adequately powered clinical studies over reasonable time periods. National networks of practice-based clinician investigators have formed in maternal-fetal-medicine and most specialty areas of pediatrics. In addition to conducting on-going studies, the networks as a whole, groups within, or newly formed teams of researchers regularly respond to new funding opportunities.
Did you know?
- Clinical research networks address knowledge gaps and promote national standards of care across the Canadian provinces and territories, which are each independently responsible for health care delivery.
- Perinatal and pediatric networks make substantive impacts on health care, but are impeded by limited support, system inefficiencies, and lack of infrastructure. Networks work in specialty silos with few opportunities to share experiences.
MICYRN has set formal affiliation agreements with 20 practice-based pediatric and perinatal specialty networks, and is partnered with the nationally funded NeuroDevNet Network of Centers of Excellence, the Rare Diseases: Models and Mechanisms Network, and CanShare. International liaisons included StarChild Health, the NIH-Sponsored Pediatric Trials Network (PTN), the European Network for Pediatric Research atthe European Medicines Agency (Enpr-EMA), and The Critical Path Institute which has initiatives for an International Neonatology Consortium, and a Global Pediatric Trials Network.
If you are interested in joining our growing network coalition or are a research team in need of support, please refer to the affiliation terms of reference and contact us.
There is a dire need to develop rapid, accurate and economic ways to diagnose rare diseases, which are defined as disorders affecting less than one in 2000 people. The “genetic revolution” means that as new genes and cellular pathways are discovered, the array of possible tests and diagnoses expands regularly, leading to long, costly (>$10,000), and often unnecessary and unproductive diagnostic odysseys for patients. Less than 6% of the 2500 rare disease genetic tests are performed in Canada, so millions of dollars are spent for out-of-country testing every year. Finding cures and effective therapies is critically important given that more than 90% of rare diseases are currently untreatable.
Did you know?
- An estimated 7,000 rare diseases collectively affect one in twelve or approximately 2.7 million Canadians and their families.
- Over 80% have a genetic basis and 75% present in childhood.
- Rare diseases cause chronic illness, disability, and often premature death while consuming a disproportionate share of spending in health care, education and social support.
- Causative genes for human genetic disease are now being discovered at a remarkable rate, and model organisms such as yeast, C. elegans, fruit flies, zebrafish, and mice provide powerful tools for study.
Engaging youths in research that is both about and for them helps ensure their unique perspectives provide relevant input to researchers. This can have a meaningful impact on work that will benefit children and youths.
A pilot project to develop a Canadian Young Persons’ Research Advisory Group (YPAG), modeled after a program established for the UK Medicines for Children Research Network (now Clinical Research Network, Children Specialty), was funded by a foundational grant from the Peter Wall Society.
In the project, hosted at the Child and Family Research Institute in Vancouver, youth advisors provide advice to investigators on aspects associated with research studies, such as the design of patient information leaflets; opinions about study websites; format of research ethics consent forms; establishment of participant registries; and, input into study protocols and definition of outcome measures. Young people are exposed to a wide range of research activities, and empowered to know they can ‘make a difference’.
A team of Canadian advisors contributed to an international effort, supported by the Global Research in Pediatrics (GRiP) network, to develop a start-up tool. This tool guides the development and operation of YPAGs that will work collaboratively with trialists so young peoples’ insights may be integrated into trial design. This will result in research that “promotes the wellbeing of pediatric participants, is scientifically sound, and has a significant impact on the population it targets.”
Towards these efforts, an international YPAG has also been created, and the first International Children’s Advisory Network (iCAN) Summit was held in July 2015 in Washington DC. And finally, an Enpr-EMA working group has been established to determine means by which to guide development of YPAGs in European national and specialty networks.
The Healthy Infants and Children’s Clinical Research Program (HICCUP) is developing a registry of healthy children and parents in Alberta who are willing to take part in pediatric health studies. Healthy controls play an important role in health research and the discovery of the causes and treatment of childhood illnesses. The program will provide researchers and investigators with ready, systematic access to healthy controls for their studies. Families who participate can take pride in knowing that they have positively contributed to child and community health in Alberta.
HICCUP is a collaboration between the Women and Children's Health Research Institute (WCHRI), Stollery Children's Hospital Foundation and University of Calgary's Department of Pediatrics.
Learn more about how to get involved!
Birth Cohort Inventory
The Canadian Birth Cohort Inventory is a unique collection of pregnancy and birth cohort studies in Canada. These cohorts are fundamental research tools to monitor children’s health and development and to link prenatal and early postnatal exposures to long-term outcomes. The longitudinal perspective of these studies allows firmer causal inferences about the relationship between environmental and genetic factors to which children have been exposed and their subsequent outcomes.
Search the Inventory
MICYRN is leveraging the power of “strength in numbers” through the creation of a coalition of networks to heighten attention to maternal and child health issues. This forum allows affiliated networks working in specialty silos to explore opportunities for cross-network collaboration, share experiences, and exchange strategies and best practices that promote efficient and effective network research. The link below provides an inventory of network activity across the country.
Clinical Trials Standards
The Standard Protocol Items: Recommendation for Interventional Trials (SPIRIT) and Consolidated Standard of Reporting Trials (CONSORT) statements provide a minimum set of recommendations to guide investigators in the development and reporting of clinical trials. The guidance improves the quality of research and reporting, as well as the ability to compare results from one study to the next. Yet, these statements lack specific elements important for trials with children, such as details about the intervention, drug dose and method of delivery, and outcomes measured. A CIHR-Planning grant allowed Martin Offringa, the head and senior scientist of the SickKids Research Institute Child Health Evaluation Sciences unit, to host an international meeting in September and develop consensus on child-friendly additions to these statement checklists. A plan is being developed to guide researchers on how to implement the checklists, and MICYRN is well positioned to disseminate results and facilitate endorsement.
Data Management Standards
The Clinical Research Informatics (CRI) working group, which joins 23 individuals from 17 sites, completed consensus recommendations for clinical research information system infrastructure standards and systems functionality, and proposed terms of reference for the use of the trials platform, all of which were endorsed by the MICYRN Board.
These quality standards are the starting point for the MICYRN informatics platform, but also serve as a reference for other systems within individual MICYRN member organizations.
MICYRN is partnered with the Center of Genomics and Policy (CGP) based at McGill University (Director, Bartha M. Knoppers) and the Care for Rare project (PI Kym Boycott, CHEO-RI) to support the IPRP, which brings together pediatric experts from around the world to regroup tools and resources on ethical, legal and societal issues in order to optimize pediatric research. Led by Ellen Wright Clayton (Vanderbilt University), coordinated by Minh Thu Nguyen (CGP) and assisted by the Public Population Project in Genomics and Society (P3G), the IPRP has produced policy recommendations related to genetic studies in children and return of results.
The Pediatric Platform of P3G, which was supported in its development through MICYRN funding, had similar mandates and objectives and was at the same stage of identifying next action items and deliverables as the Global Alliance for Genomics and Health (GA4GH) Paediatrics Task Team. Thus it was determined that the platform should dissolve and join GA4GH to unify efforts.
MICYRN has been partnering with the Puplic Populations Project in Genomics and Society (P3G), a not-for-profit international consortium dedicated to facilitating collaboration between researchers and biobanks working on human population genomics.
Visit P3G International Paediatric Research Programme for more information.
BC Children's Hospital BioBank — Superhero Video Advances in medical research have drastically improved the quality of life for millions of people and lead to effective treatments for conditions that were once life-threatening; view the Superhero Video about the BC Children's Hospital BioBank.
The Mount Sinai Hospital Biobank now includes over 9000 specimens. It is a non-profit biobank operated by researchers, for researchers. The cost recovery fees help reimburse the cost of collection and storage of samples but the biobank nevertheless rely on institutional support to operate.
The Royal College of Paediactrics and Child Health has a number of online resources for researchers looking to work with and involve children in research.
The Biobank Resource Centre is an excellent resource, providing document templates, education and certification, registration, and tools.