BY ALEXANDRA WHITE, MATT SMITH AND ERIKA LUTINS
IMPACTS ON JOUBERT SYNDROME AND OTHER RELATED DISORDERS
When scientists conduct clinical research, the traditional method is for the researcher to be the main contributor in the creation of the idea, the study, and the final publication of results. Patients and caregivers are typically only involved at the final stages: dissemination of results and the implementation of practice and policy changes. With this method, important stakeholders are excluded from the conversation at critical points. Many diverse ideas and perspectives are not being involved in the research process, which leaves a great amount of untapped potential for medical advancement. Researchers also tend to conduct their studies independently and quietly because of concerns regarding intellectual property and competition for funding. Data is kept private and things are done behind closed doors, which severely limits progress. What can be done to change this paradigm?
MAKING SURE EVERYONE IS INVITED TO THE TABLE
The answer to the traditional research limitation lies within open crowdsourcing forums aimed at involving diverse populations of people in the initiation, development, refinement, and finalization of research projects. The Community Engaged Network for All (CENA) and Mosaic recognize and capitalize on this opportunity for growth.
CENA is a network of disease advocacy organizations that engage their respective communities in the advancement of healthcare and health research by developing registries designed around the concerns of individuals and their communities. CENA is a key component of the Patient Powered Research Networks (PPRNs), which are all a part of a larger movement within the National Patient-Centered Clinical Research Network (PCORnet). This movement is aimed at working towards patient centricity in research by involving patients and caregivers at all points of the research process, especially at the critical points. CENA embodies the goals of PCORnet in a way that is unique from other PPRNs by using the Platform for Engaging Everyone Responsibly (PEER). PEER is a highly customizable system; groups create a survey that best serves their community and selects community leaders, known as guides, who help fellow participants choose the right options for sharing. Each guide gives suggestions to participants
with low, medium, and high privacy concerns pertaining to sharing their health information with other support groups, researchers, and data analysis platforms. Each participant can select one of the guide’s suggested privacy settings, modify a guide’s settings to better reflect their own privacy preferences, or create their preferences manually. The end result is a group-specific portal used to collect health information from patients, by patients themselves, or by their caregivers.
Mosaic is an online tool and crowdsourcing model designed to develop research studies to make use of the information collected in PEER in an open, collaborative research protocol development process. Mosaic was deployed and is managed by CENA’s Clinical Data Research Network (CDRN) partners at the University of California, San Francisco (UCSF) and the UCSF Clinical and Translational Science Institute (CTSI). Mosaic brings people together with many different perspectives on challenges specific to a condition or community and allows them to collaborate online in designing and conducting research studies. Mosaic is open to the public: anyone with interest in research on a condition or issue is welcome to participate. Mosaic allows participants to contribute to discussion threads related to a particular disease or community issue in hopes of discovering the common questions
and themes among all types of stakeholders— from patients and their families, to advocates, to researchers and healthcare providers—to draft a research plan. Researchers can then guide their studies using this information to ensure that they are focusing on what is important to everyone impacted by the disease. Mosaic participants can give suggestions, ask questions to researchers, and are updated regularly about the progress of the study. They are involved at every step. Once the study is finished, the results and conclusions are posted for all to see. Participants
can then like and comment on the results as a method of evaluation, so that future projects can be built from any outstanding questions or concerns.
CENA and Mosaic share the mutual goal of accelerating health research through the involvement of the too often forgotten patient populations. When patients, caregivers, researchers, scientists, policy makers, and advocates all come together to discuss ideas, share data, and design research studies, the impact is monumentally larger than those of traditional research methods. The fact that organizations such as these are making the shift to patient-powered and patient-centric research and data collections means that stakeholders have a heightened responsibility to participate in research. But with that comes many questions concerning the privacy and safety of themselves and their data.
DATA SHARING WITH THE PLATFORM FOR ENGAGING EVERYONE RESPONSIBLY
Sharing personal health data with broad audiences allows for analysis and contemplation about much larger samples of information, which in turn allows researchers to access larger samples for their projects. But many individuals have concerns about uploading their data. Thankfully, PEER has extensive privacy settings, which can be changed or updated at any time. Users can choose what they want to share and who to share with. There is also an “Ask Me” option, which prevents access until the participant decides if they want to share their data with the requesting party or not. This is effectively allowing the participant to say, “maybe, but ask me first.” Users will be notified when somebody is interested in accessing their data, and the individual can then decide to say yes or no on a situational basis. All organizations within CENA have their own customized PEER registry.
PATIENT-CENTERED RESEARCH FOR JOUBERT SYNDROME
Joubert Syndrome (JS) is a rare autosomal recessive genetic condition affecting one in every 80,000-100,000 people. JS has broad clinical and genetic overlap with other “ciliopathies”. Ciliopathies are biologically similar, yet complex, conditions whose root cause are due to defects of the cellular antenna known as the primary cilium, an extension of the cellular membrane found in nearly all cell types, or instability of the cilia anchoring structure, the
basal bodies, of the cell. In JS, dysfunction of the primary cilium during embryonic development leads to underdevelopment or malformation of the cerebellar vermis, the area connecting the two lobes of the cerebellum, which appears as a distinct feature on axial section of MRI called the molar tooth sign (MTS) because it resembles the roots of a molar or wisdom tooth. Among a broad spectrum of signs and symptoms, many individuals with JS experience decreased muscle tone (hypotonia), difficultly coordinating movements (ataxia), irregular breathing patterns, abnormal eye movements, and developmental delays of varying degrees. Disruption of cilium function can also lead to degenerative complications of the retina, kidney and liver later in life in some subsets of JS.
There are currently 25 gene mutations on multiple chromosomes known to be associated with JS. Alterations in these genes are not the cause of JS in many individuals, indicating that additional genetic causes remain to be identified. In order for JS to be inherited, both parents must usually be carriers of a particular gene mutation, and there is a 25 percent chance for them to have another child with JS with each pregnancy. There currently is genetic testing available for the detection of some gene mutations which cause subsets of JS. For more information, please visit www.jsrdf.org.
The Joubert Syndrome and Related Disorders Foundation (JSRDF) provides information about the condition and other related disorders to families all over the world. The JSRDF is a member of CENA and it has created a registry called the Joubert Syndrome Link to Information and Family Exchange (JS-LIFE), where patients and caregivers share their health information securely. The JSRDF, using information from JS-LIFE, is currently facilitating a research challenge on Mosaic, with the purpose of encouraging the participation of all stakeholders in the creation of research studies for JS. The research challenge is a series of discussion threads where caregivers, researchers, and anyone else involved in the JSRDF and rare disease communities can compile and discuss major questions, concerns, and ideas in order to guide research. Then, researchers can focus their studies and engage all stakeholders in the research process. The challenge has presented several emerging themes in very dynamic and interesting discussion threads: how to obtain an earlier and correct diagnosis, commonalities in the ways which children are diagnosed, shared medical complications and interventions, and the impact of the syndrome on daily activities and quality of life.
THE EFFECTS OF PATIENT DRIVEN RESEARCH
Patient-centered research allows for the formation of a community so that no individuals feel alone in their diagnosis. When children are facing rare genetic disorders like Joubert syndrome, ensuring that they do not feel isolated will help them to find normalcy in their daily lives. Moving from having symptoms to having an actual diagnosis can be a challenging transition for some, but having the community of people going through the same things can help to ease the process and make a child feel much more comfortable.
The movement behind JS-LIFE and all other members of CENA, PCORnet, and PPRNs is helping to move towards the involvement of everyone in the advancement of healthcare. When the diverse ideas from people of all different demographics, backgrounds, and lifestyles come together in a public arena, well-rounded research can be done that focuses on what is important to those who are most important – the patients.•
ABOUT THE AUTHORS:
Alexandra White is a rising junior at the George Washington University studying systems engineering with a minor in public health, hoping to be a healthcare systems engineer in her future career. She is currently an intern with the
BioTrust program at Genetic Alliance.
Matt Smith’s passion for this work arises from his desire to advance support and research for all individuals in the ‘Joubert family.’ He has a seven-year-old niece, Haley, affected by Joubert syndrome. Matt is the Principal Investigator of JS-LIFE and serves in leadership with the JSRDF. He is also a Program Manager at Genetic Alliance, managing technology aspects of the PEER platform.
Erika Lutins is a Translational Science Program Assistant at Genetic Alliance. She is passionate about furthering patient-centric health research and supplies individuals and organizations with the resources and guidance to succeed in this. She joined Genetic Alliance after graduating from the University of Michigan with a Bachelor of Science.
