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International Children’s Advisory Network: A Multifaceted Approach to Patient Engagement in Pediatric Clinical Research

Published:September 21, 2017DOI:https://doi.org/10.1016/j.clinthera.2017.09.002

      Abstract

      Pediatric youth advisory groups were created to provide insight and guidance to the clinical research community. Such efforts have become a priority and parallel the demand for patient-centered health care. While steps are being made to integrate the patient voice into research, there remains a lack of pediatric-specific engagement in the development of pharmaceuticals and in clinical research. For example, a significant number of children are still treated with medications that are not approved for use in this age group, due to a lack of clinical trials involving younger children and neonates. The American Academy of Pediatrics noted that physicians are faced with an ethical dilemma, as they must frequently either not treat children with potentially beneficial medications or treat them with medications based on adult studies or anecdotal empirical experience in children. By improving the approach to pediatric study design, indications for pediatric-specific therapies can be developed. We describe a structured organization with empowered youth and parents who are beginning to play a key role in the research process that suggests ways to improve pediatric research and for innovative medical products to be more “child friendly” and usable. We will also describe how investigators can engage the International Children’s Advisory Network to obtain valuable youth perspectives on many aspects of clinical research and health care advocacy.

      Key words

      Introduction

      Pediatric youth advisory groups were created to provide insight and guidance to the clinical research community. Such efforts have become a priority and parallel the demand for patient centered health care. While steps are being made to integrate the patient voice in research, there remains a lack of pediatric specific engagement in the development of pharmaceuticals and in clinical research. For example, a significant number of children are still treated with medications that are not approved for use in this age group, due to a lack of clinical trials involving younger children and neonates.
      • Choonara I.
      • Conroy S.
      Unlicensed and off-label drug use in children: Implications for safety.
      The American Academy of Pediatrics (AAP) noted that physicians are faced with an ethical dilemma, as they “must frequently either not treat children with potentially beneficial medications or treat them with medications based on adult studies or anecdotal empirical experience in children.”
      American Academy of Pediatrics
      Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations.
      By improving the approach to pediatric study design, indications for pediatric-specific therapies can be developed. The International Children’s Advisory Network (iCAN) addresses these focus areas through a multifaceted approach.
      iCAN is a worldwide consortium of youth and family advisory groups collaborating to provide a voice for children in pediatric clinical research, medicine, and innovation.
      • Thompson H.
      • Frederico N.
      • Smith S.R.
      • et al.
      iCAN: Providing a Voice for Children and Families in Pediatric Research.
      Having access to a structured engagement system provides young patients and their families a platform on which they can share their voice in a meaningful way. This novel organization offers medical and research professionals the opportunity to collect feedback from youth advisory groups and their families about all aspects of pediatric clinical research. Engaging patients and caregivers in the clinical research process not only provides valuable insight, but may allow researchers to improve their clinical studies through increased enrollment, better participant retention, and ultimately generate more significant outcomes.
      At the center of iCAN’s mission are four integral components: Education, Innovation, Advocacy, and Youth and Family Engagement. Together, these four pieces allow the iCAN network to collectively provide valuable and insightful feedback that may have a significant impact on the future of pediatric clinical research and medicine. Individual iCAN chapters or teams interact with local universities and researchers on a regular basis. Most local chapters meet monthly and review and discuss submitted materials, listen and interact with investigators in person, or connect online to provide feedback and advice.

      iCAN Research and Advocacy Summit

      iCAN officially commenced in 2015 at the iCAN Launch and Research Summit. This event took place in Washington, DC, and united 130 of iCAN’s inaugural youth advisors, parents, politicians, pharmaceutical organizations, and other stakeholders. For the very first time, young people from across the globe had the opportunity to come together and interact face to face with researchers, industry, regulatory, and government leaders to learn from one another and advocate for pediatric clinical research and health care. This successful event marked the beginning of this new international organization, and inspired youth advisory groups to build on their local and global agendas so children could have a voice in pediatric medicine.
      • Gwara M.
      iCAN Update - International Children’s Advisory Network.
      In June 2016, the second-annual iCAN Research and Advocacy Summit took place in Barcelona, Spain. The size of the Summit increased to 160 attendees, and focused on rare diseases, innovation, and pediatric health and well-being. At this event, “children and families had the opportunity to engage with world leaders in science, while learning about different innovative treatments, personal health, regulation, the clinical research design and process, and patient advocacy.”
      • Gwara M.
      iCAN Update - International Children’s Advisory Network.
      A poster session gave youth the opportunity to present the many projects that each local team had worked on since iCAN’s launch. Projects included revising a multitude of assent forms and clinical trial subject information sheets, a visit to a motion analysis laboratory to provide feedback, and working with Child Life Specialists to develop new strategies. The Summit also included other educational and cultural activities, such as tours of the Sagrada Familia de Gaudi, FC Barcelona’s Camp Nou, CosmoCaixa Museum of Science, and Fundació Alícia, a research center focused on healthy lifestyles.
      • Gwara M.
      iCAN Update - International Children’s Advisory Network.
      iCAN saw a tremendous growth this year, resulting in a 50% increase in attendance at the 2017 iCAN Research and Advocacy Summit in Orlando, Florida. Approximately 250 youth advisors, families, and stakeholders came together to once again learn about pediatric research, medicine, and innovation. The recent heartbreaking loss of a beloved youth advisor sparked a wave of strength and inspiration throughout the network to ensure that we do our part to decrease future cancer deaths. The event commenced with a keynote address from Raymond Rodriguez-Torres, Chair and Founder of the childhood cancer foundation, Live Like Bella. Mr. Rodriguez-Torres’ message resonated deeply with attendees, as he shared the story of his late daughter’s unwavering optimism and commitment to leading a happy and fulfilling life, despite being faced with a very rare and aggressive form of childhood cancer. He has dedicated his life to making childhood cancer a curable disease, founding Live Like Bella, and raising awareness and funding for pediatric cancer research. This set the tone for the rest of the week, as attendees participated in more than 30 hours of programming. Specific sessions included a nutrition workshop; an advocacy activity during which caregivers wrote letters to policy makers; a workshop teaching basic medical skills; and presentations on research ethics, STEM (science, technology, engineering or mathematics) careers, injury prevention, patient safety in drug development, pharmacogenomics, and the role of regulatory agencies. Attendees also visited the Give Kids the World Village, a resort where “children with life-threatening illnesses and their families are treated to week long, cost-free vacations.”

      Give Kids the World Village. Who We Are and What We Do. http://www.gktw.org/about/. Accessed July 16, 2017

      There, attendees received an informative tour of the facility and participated in a community service activity making celebration props for guests at the resort. The 5-day Summit ended with a keynote address by Florida Senator Marco Rubio, who discussed ways children and families can best advocate for pediatric clinical research, specifically for childhood cancer.

      An Expanding Network

      iCAN currently consists of 20 active chapters globally, with children from many different backgrounds (Figure 1). Diversity is part of what makes this consortium such a valuable resource for clinical researchers and regulators. A large portion of the youth members are former or current patients, many of whom live with a chronic condition. A small percentage of those youth members also have personal experience as participants in one or more clinical trials. Many youth members have a family member or friend affected by a chronic or acute condition, are interested in pursuing a STEM career, or simply want to help others. Children with varied backgrounds provide stakeholders the opportunity to obtain feedback applicable to a generalizable group of children and, when requested, children with specific medical conditions, such as diabetes.
      Figure 1
      Figure 1List of current International Children’s Advisory Network chapters (iCAN). iCAN introduced 3 new chapters to its consortium in 2017: KIDS Bari, KIDS Tokyo, and KIDS Childhood Cancer, the first-ever special interest chapter focusing on disease-specific initiatives. KIDS = Kids Impacting Disease through Science; YPAG = young persons’ advisory group.
      In 2017, iCAN also partnered with Live Like Bella to launch iCAN’s first special interest chapter, Kids Impacting Disease through Science−Childhood Cancer (KIDS CC). Unlike the other active chapters, KIDS CC connects childhood cancer patients, survivors, and caregivers on an international level to focus on disease-specific initiatives and studies. This new chapter will meet virtually once per month in collaboration with Live Like Bella and other organizations to provide youth advisors with resources and opportunities to lend input to clinical trials specifically for pediatric oncology patients. This chapter will also allow youth advisors with personal experience with childhood cancer to share experiences and provide support and advice to other children with cancer. iCAN plans to establish additional special interest or disease-specific chapters in the near future.
      This year, iCAN also announced the development of KIDS Bari, which will join the strong framework of young persons’ advisory groups (YPAGs) in Europe, and KIDS Tokyo, which marks iCAN’s first chapter in Asia. As iCAN continues to grow, youth from many regions of the world with unique ethnic and cultural backgrounds are able to contribute to the development of pediatric research and medical innovations.

      Fortifying the Organization’s Structure

      At the 2017 Summit, iCAN also introduced the formation of the European Young Persons’ Advisory Group Network. This sub-network is accredited by the European Network of Pediatric Research at the European Medicines Agency and operates under the iCAN umbrella to focus efforts in Europe, working at a national level as well as internationally with the overall iCAN consortium. This sub-network was established at a time when the rapidly expanding iCAN network experienced a need for further organization to ensure a consistent framework and improved collaboration capacity.
      The European Young Persons’ Advisory Group Network consists of the following iCAN chapters:
      • KIDS Barcelona
      • KIDS France
      • ScotCRN
      • Generation R
      In the near future, iCAN will work to establish a similar sub-network in North America, and eventually on other continents, as the network continues to expand quickly. The iCAN consortium will fortify the growing network and allow for more productive and collaborative work among chapters.

      Education

      iCAN members receive education in many aspects of pediatric health care, medicine, advocacy, innovation, and research on both a local and international level. In addition to sessions attended at the annual iCAN Summit, individual chapters frequently host presentations from leaders in research, engineering, and science. Chapters also provide youth advisors with opportunities to explore different career paths in these areas, and offer support and guidance to those interested in pursuing these professional careers.
      Frequent involvement in the clinical research process, as well as contact with patients from different backgrounds, provides youth advisors with an experiential understanding unlike anything that could be taught in a traditional classroom setting. iCAN members then apply their knowledge and experiences by contributing to the production of educational and research materials for other children in terms that they can understand.
      iCAN’s network-wide project for 2017 was an educational video series to teach and educate children and parents about clinical trials. The videos were scripted, designed, and acted out by youth advisors from each of iCAN’s 20 chapters. These videos will be shared publically on the iCAN website, social media, and with children’s hospitals. The video series will also be utilized as a fundamental training module for new iCAN youth members to ensure that all members have the same basic understanding of the clinical trial process. By educating younger generations about the complexities and benefits of clinical research, iCAN hopes to destigmatize participation in studies, as well as to allow young patients and caregivers the opportunity to make well-informed decisions regarding their medical care and participation in clinical research.
      Youth advisors are provided with numerous opportunities to not only attend, but participate in presentations, roundtable discussions, conferences, professional meetings, panel discussions, and more. In the past year, iCAN youth advisors have spoken at numerous pediatric, research, and innovation conferences across the globe. Through these opportunities, youth advisors have a public platform on which to share their personal anecdotes and speak from experience to weigh in on topics that have, in the past, been considered too complex due to their age. In October 2016, youth advisors from Generation R and KIDS Barcelona participated in a panel titled “How Can Children, Careers, and Families Contribute to Drug Development?” at the European Medicines Agency’s “Better Medicines for Children” event, during which they advocated for youth involvement in clinical research. In January 2017 at the 2017 Peds2040 conference, a youth advisor from KIDS CC sat on a panel of adults titled “Patient and Family Perspectives on Pediatric Innovation,” which highlighted the unmet needs of pediatric patients and new innovations that have benefitted patients everywhere. Youth advisors from YPAG London also gave a presentation about the importance of involving young people in research at the “Patients as Partners” event in February 2017. These are just a few examples of speaking opportunities that iCAN youth advisors have participated in over the last year.
      By being part of the discussion, iCAN youth have the opportunity to influence a change in perspective among key stakeholders and policy makers. The skills they gain from such experiences inspire and empower them to become confident advocates, which prepares a new generation of innovative trailblazers in STEM.

      Innovation and Advocacy

      The iCAN consortium is often reminded of the need for increased advocacy in pediatric clinical research when we hear stories from our youth advisors. A KIDS Georgia youth advisor, Hampton Woods, recently celebrated his 16th birthday, thanks to innovative research in organ transplantation decades ago. As Hampton has grown into a young adult, he has gained the confidence to advocate not only for himself, but for other children like him. Hampton participated in a 4-year study evaluating the need for ongoing immunosuppressive medications to determine whether some transplantation patients can safely discontinue these medications. While the outcome was not what he hoped for, Hampton considers his experience “invaluable” and knows that he contributed to a body of data that will one day help another child. Hampton has also turned his personal experiences into an opportunity to “leave the world better than he found it,” by collaborating with a close friend to create a patent-pending medical device, which earned them the title of “Best By Popular Vote” at a think-tank competition they attended at Peds2040 on behalf of iCAN. As an active member of iCAN, Hampton continues to share his valuable insights.
      Elizabeth Sheeren is a 17-year-old youth advisor from iCAN’s KIDS Michigan chapter who developed her first autoimmune disease at the age of 4 years. By age 15 years, she had accumulated a total of 6 autoimmune diseases. In fact, Elizabeth is currently the only known child with this particular combination of autoimmune diseases in the world. At this point, she has exhausted all known treatment options and is waiting for a research breakthrough to determine her future. Elizabeth lives each day uncertain of what may happen when her current treatments are no longer effective. The only thing that she does know for certain is that her disease will continue to progress beyond the reach of today’s medicine. Currently, Elizabeth is unable to participate in clinical trials because she does not meet the stringent criteria. Historically, there has also been very little focus on rare diseases because it is not financially feasible for most companies to invest in rare disease research. Advocacy from patients like Elizabeth is imperative to ensure that attention is brought to these uncommon diseases so that additional lifesaving treatment options may become available. Elizabeth’s participation in iCAN and sharing her story demonstrate the potential impact patients and families can have in medicine.
      Hampton and Elizabeth’s stories highlight both the strengths and weaknesses of current pediatric clinical research. Their dedication to patient advocacy and improving pediatric health care and research is mirrored by the hundreds of youth advisors and families of the iCAN consortium, and is a propelling force of this organization. Advocacy remains at the core of patient and public engagement, as it provides a platform on which patients and caregivers may collaborate for a common cause. For this reason, advocacy is well-integrated into iCAN’s mission.

      Youth and Family Engagement

      iCAN provides researchers with the ability to engage its entire network of educated and experienced youth advisors and families in order to gather feedback about their trial designs and logistics, feasibility, consent and assent forms, recruitment materials, applications, gamification, and medical products designed for children. Researchers or companies can contact iCAN at [email protected] to submit a proposal for a consultation with the iCAN Coordinator. After establishing a timeline and plan of action for feedback collection, the iCAN network can be engaged in the following ways:
      • 1.
        Researchers prepare a brief presentation to provide youth advisors with any relevant background information that may be necessary for them to provide well-informed, quality feedback. This may include information about a particular disease or condition, testimonials from young patients (or parents of young patients) with the referenced disease or condition, an overview of the proposed study detailing the possible treatments, the risks and benefits of the study, the requirements of the study, and more. This presentation can either take place in person with a single iCAN chapter (if only local feedback is requested), at the annual iCAN Summit, or virtually, using a teleconference platform.
      • 2.
        An open-ended discussion will take place, allowing the youth advisors to steer the conversation, ask questions, and discuss talking points that are most important to them, based on their impression of the information in the presentation.
      • 3.
        Researchers may ask the youth advisors and parents specific questions that they may have regarding the content of the presentation and the design of the study.
      • 4.
        A supplemental survey may be conducted to gather youth feedback in a measurable way. In some cases, surveys may be disseminated to the iCAN network without the accompaniment of a presentation.
      All iCAN youth advisors are educated about confidentiality and understand the parameters of such at the beginning of each engagement initiative. Presentations and surveys are blinded so that youth advisors and families are not informed of the company name or the particular drug or device that the proposed trial is studying.
      Once feedback has been collected and reviewed, it is disseminated directly to researchers to advise them on suggested changes that are well-suited for children and families, and may improve the quality and outcome of the study. Researchers are expected to follow-up with iCAN to highlight how the received feedback has been utilized, as well as whether or not it is believed to have had a positive impact on the outcome of the study. As iCAN begins to learn of the outcomes of studies on which it has collaborated, the results will be shared with the youth advisors and families, and data trends will be shared with stakeholders to measure the impact of the organization.

      Improving the Informed Consent and Assent Process

      One of the most common focus areas for iCAN is improving the informed consent and assent process in pediatric clinical research. It has been suggested that assent forms for all pediatric patients are not age-appropriate for all children, as the cognitive development of an 8-year-old is different than that of a 17-year-old. The Institute of Medicine Committee on Clinical Research Involving Children has specified that younger children have a better concept of the practical aspects of research than abstract dimensions, while children as young as 14 or 15 years can comprehend the research process much like an adult.
      Institute of Medicine Committee on Clinical Research Involving Children.
      For this reason, iCAN has frequently explored how researchers may be able to improve how they design and create content for assent forms for various developmental stages. Through teleconferences, roundtable discussions, webinars, and surveys, the same few suggestions are consistently brought up by iCAN youth advisors:
      • 1.
        Children younger than 12 years of age prefer shorter sentences and words, as well as the use of figures and images to demonstrate points.
      • 2.
        Older children prefer to be treated more like adults and some prefer to have assent forms designed at a higher reading level.
      • 3.
        All children prefer shorter assent documents, as many are often quite lengthy and verbose overall.

      Looking Ahead

      iCAN’s approach to engaging researchers of pediatric clinical trials has quickly become deeply rooted in a number of leading pharmaceutical companies’ protocols. The rapid expansion of the network and increased demand has quickly necessitated a more streamlined system for requests. In just 2 years, iCAN has grown to more than 20 chapters, spanning 8 countries on 3 continents. In the near future, iCAN aims to expand to South America; to develop additional chapters in the United States, Canada, and Europe; and to develop new virtual special interest chapters focusing on specific therapeutic areas. By increasing the reach to new countries, iCAN will be able to provide more useful feedback with representation from a greater number of geographic, cultural, religious, and socioeconomic backgrounds. More inclusive representation in consultations and engagement initiatives will allow pediatric researchers to receive much more comprehensive youth input, which will result in stronger studies overall and, ultimately, a greater number of treatment options for children. For more information, please contact iCAN at [email protected] or visit www.icanresearch.org.

      Conflicts of Interest

      The authors have indicated that they have no conflicts of interest regarding the content of this article.

      Acknowledgments

      No other individuals helped write or revise this manuscript.

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