Patient reported outcomes (PRO) data complements traditional clinical research with scale & accessibility, as well as patient-centricity. The Fox Insight (FI) study aims to gather the world’s largest dataset on the day-to-day experience of living with PD, from 125,00 participants across the globe. This comprehensive dataset holds the power to help researchers better understand patients’ unmet needs, redefine therapeutic priorities and optimize clinical trial design.
Speaker:
Lindsey Riley, MPH, Senior Associate Director, Research Partnerships, The Michael J. Fox Foundation for Parkinson’s Research
John Fremer:
We would like to welcome you to the Sanguine Speaker Series Webinar, Fox Insight: Driving Discovery with the Patient Voice. Today’s webinar is presented by Lindsey Riley, the Senior Associate Director of Research Partnerships at the Michael J. Fox Foundation for Parkinson’s Research. Lindsey.
Lindsey Riley:
Thanks for that introduction and good afternoon, everyone. I’m excited to be talking to you today about the Michael J. Fox Foundation and how we’re advancing the field of Parkinson’s disease research with the Patient Voice. So, at the end of this 40 or so minutes, I hope to leave you with three key takeaways, if nothing else. First and foremost, that improved therapies start with patient-centered research, and that Fox Insight, the study that I’ll be talking about today, provides an opportunity for people with and without Parkinson’s disease to advance research. And lastly, that multimodal real-world data is available to researchers through Fox DEN, the Data Exploration Network, which I’ll talk about in more detail.
Lindsey Riley:
So, how am I going to get us to those three key messages today? I’ll first start with a brief intro of the Michael J. Fox Foundation, and then dive into more detail about Fox Insight, including characteristics of the cohort and examples of how we’ve leveraged the study to design patient centered-research. I’ll then wrap up with details on how to access this real-world dataset and how we can potentially partner together.
Lindsey Riley:
So, to start, a little stage setting about the organization. The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson’s disease through an aggressively funded research agenda, and to ensuring the development of improved therapies for those living with Parkinson’s today. Increasingly, Michael J. Fox’s role in fulfilling this mission is evolving to also include stakeholder education as well as engagement activities. Formed in 2000, MJFF is a 501 (C)(3) and the world’s largest patient-centered, not-for-profit funder of Parkinson’s research. To date, we’ve funded over $900 million in Parkinson’s research. We are centrally organized, meaning there are no chapters, and we don’t hold in endowment, meaning we spend the money we’ve raised over the course of the calendar year until we reach back to zero again the following year. This organizational model allows us to act with urgency, flexibility, and to fund new research as quickly as possible. We’re also agnostic to the type of organizations we fund and support solid research ideas that originate from both industry and academic settings.
Lindsey Riley:
So, that’s our mission. And how do we plan to get there? Well, fundamental to our business model is getting the right science together with the right money. We invest more than just capital towards the success of research that we fund. The Fox Foundation has 12 on-staff neuroscientists and a team of strategists to manage portfolios and guide decisions. With experience on over 3,000 projects, our team can help researchers elect the right models and tools, and foster collaboration as well as the sharing of scientific ideas. We also work extensively with key opinion leaders and advisors who help assess the research landscape, identify gaps, and plan programs and investments to meet needs and seize opportunities. In this way, we think of ourselves as a unique convener or a hub, if you will, connecting potential collaborators, including scientists, physicians, and patients and caregivers.
Lindsey Riley:
Venture philanthropy, probably most accurately defines our early role in therapeutic development with the idea that, we can continue encouraging innovative and new ideas for Parkinson’s disease treatment by making strategic investments in research and development. We support research to understand the underlying cause of PD, validate emerging targets, and advance individual therapeutic programs. We also tackle common challenges that hinder the field at large, such as identifying biomarkers and facilitating patient participation in clinical research. This includes, as well, development of tools from bench to bedside, animal models, assays, development of cell lines to validating clinical skills and funding novel endpoints.
Lindsey Riley:
It’s important to note that we believe patients are key partners to achieving our organizational mission. Elevating the patient perspective helps to identify unmet needs and understand what matters most to patients. MJFF is uniquely positioned to facilitate patient engagement across all activities of the research landscape. We also have a patient council that I want to call out, meets frequently to advise us on organizational strategy, a larger network of patient ambassadors, as well as strong ties within the Parkinson’s disease community.
Lindsey Riley:
In keeping with our goal to de-risk the field, we’ve made many investments over the years in building and establishing cohorts within Parkinson’s disease to help generate tools and resources and improve disease understanding. At the highest level, we aim to establish cohorts, standardize data sets and tools, and ultimately make all of this information available to the research community with as little lag time as possible.
Lindsey Riley:
I likely don’t have to tell this audience that traditionally, real-world data has been used to satisfy monitoring, and post-approval requirements and has been met with much skepticism about its credibility. However, I think that most of us would now argue that the unstructured and less precise nature of real-world data is exactly what makes this type of evidence valuable as it, quite frankly, is a reflection of the real world. Additionally, real-world data is often one of the only ways to provide a more holistic view of disease and well-being, particularly evidence that reflects the patient perspective. The FDA has invested in the concept of patient-focused drug development and has acknowledged that patient’s chief complaints are not explicitly considered in drug development, nor are matters around quality of life, which can critically inform the potential drug benefit as well as have implications for reimbursement. So, patient reported outcomes, or PROs can provide valuable information on symptom and disease burden, including, but not limited to, physical function, dissatisfaction or satisfaction with current treatments, unmet needs, and I think, perhaps most importantly, quality of life.
Lindsey Riley:
So, with that stage setting, I’ll now switch gears a bit and tell you more about our decision to invest in the development of a specific cohort for the Fox Insight study. Part of our role as a connector that I mentioned in an earlier slide is actively engaging with patients, families, and caregivers. And the common theme that we often hear is, “I want to do more,” And, “How do I get involved in research?” However, as we all know, engagement in research is often easier said than done and can be wrought with challenges on many levels, especially in the current reality that we find ourselves in. So, I think the second bullet listed here is, quite frankly, the understatement of the century that recruiting and retaining participants in conventional studies is challenging.
Lindsey Riley:
For these reasons, the Michael J. Fox Foundation launched Fox Insight in 2017, an online clinical study of people with and without Parkinson’s disease. Since that time, the cohort has grown to just under 50,000 participants worldwide. Additionally, over 10,000 individuals have also contributed genetic data to the study. And I’ll get into more specifics regarding this element in more detail in just a few moments.
Lindsey Riley:
So, to give you a quick synopsis of the study design, the study aims to recruit up to 125,000 volunteers both with and without Parkinson’s disease. And that includes care partners as well. Individuals are followed over a five-year period, and eligibility includes anyone 18 or older worldwide with or without Parkinson’s disease that has internet access and the ability to read and write in English. Collected assessments include PD relevant instruments, as well as several novel patient reported outcomes, which I’ll go into more detail later. As I mentioned in a former slide, data collection is also multimodal and includes genetic information on a subgroup of the cohort. And perhaps one of the most interesting features of the study is also the ability to deploy cross-sectional or ancillary surveys on topics of interest in a time-sensitive manner.
Lindsey Riley:
Developed in coordination with a digital product agency, Fox Insight collects information through a web-based, mobile optimized platform. You’ll see on the slide featured here several screen grabs from the volunteer experience. Participants or volunteers are asked to complete virtual study visits four times per year in addition to periodic one time, or as I mentioned, ancillary data collection opportunities. We’ve leveraged a number of opportunities to enhance participant engagement by email, as well as study newsletters and building a community page as well as virtual and formerly in-person events.
Lindsey Riley:
I alluded to this in an earlier slide, but through a unique partnership with consumer genetics company 23andMe, a subgroup of Fox Insight participants with Parkinson’s disease in the U.S. are also offered the opportunity to receive genetic testing and remote counseling at no cost. The PD health reports provided to some study participants include testing and counseling on mutation status for specific LRRK2 and GBA variants. And to date more than 10,000 participants have provided genetic information to pair with their longitudinal health data in the Fox Insight study.
Lindsey Riley:
Now, I’ll switch gears and talk a little bit more specifically about some of the characteristics of the study cohort to date. Formal recruitment for the study began in October 2017, leveraging several different recruitment channels, the primary one being our own patient, family, and supporter email audience, as well as the MJFF website. We’ve also employed several other multipronged recruitment tactics such as social and paid media. Since this study’s inception, participants have completed over 145,000 study visits and over a million assessments. The cohort is predominantly comprised of people with Parkinson’s disease, and the average age of a participant is 65 years old.
Lindsey Riley:
Though the study platform, as I mentioned earlier, is currently available in English only, we have been able to, fairly organically recruit participants from across the globe with representation from 52 countries and counting at present, making Fox Insight the largest global Parkinson’s disease cohort. In the interest of time, I didn’t include a slide on the distribution of participants in the U.S. only, but I will make a quick note that the cohort is predominantly bi-coastal in the U.S.
Lindsey Riley:
One more important point I wanted to raise is that at study enrollment, 76% of participants report that this is their first time engaging in research. And I think this indicates that we have a real opportunity here to facilitate entree into clinical research by engaging this sort of population and community online first, wetting their whistle if you will, and then should the opportunity to arise, participants may feel less fear in regards to participating in traditional clinical research. And this, like I said, provides a real opportunity to prime that type of engagement and allows participants to play an active role in advancing the state of the science.
Lindsey Riley:
Now, I’ll shift gears and provide a few examples of how we’re leveraging the Fox Insight study to power patient-centered research. So, the first case study is an example of how we’ve leveraged Fox Insight to systematically characterize Parkinson’s disease as reported directly by patients. As I mentioned at the top of the presentation, the FDA is increasingly focused on functional outcomes, and in 2017, we collaborated with Ira Shoulson out of Georgetown to pilot a novel PRO instrument entitled the PD PROP also known as Patient Reports Of Problems survey. And the PROP was modeled after a scale initially developed for Huntington’s disease known as the HD PROP.
Lindsey Riley:
The instrument itself was really born out of an FDA meeting, as Ira tells it where someone said, “Well, why don’t you just ask patients what bothers them the most?” And so that’s in fact what they did. So Dr. Shoulson developed a survey with the two primary questions listed here, what bothers you the most about your Parkinson’s disease? And in what way does this problem bother you by affecting your daily function? So, responses are provided and the severity is rated on a zero to three categorical scale. And then Ira and his team, using natural language processing as well as expert clinical curation and machine learning processes apply these techniques to responses to characterize the natural history of Parkinson’s disease from the patient perspective.
Lindsey Riley:
And now with over 10,000 baseline responses and counting, this dataset represents the largest compilation of patient reporting verbatim problems for any neurological disorder. You’ll see pictured here, a brief word cloud, if you will, of some of the key themes that emerge. I’ll also show a snapshot of data in this way where you might be able to tell that tremor and gait and balance are some of the categories, listed on the left side, seem to be the most bothersome to most participants. However, there are a number of participants that cite pain and fatigue closer to the right side, highlighted in the dotted graph, as their most troublesome symptom. I think what we know and what we can learn and glean from these types of responses is that non-motor symptoms need more attention from drug developers in Parkinson’s disease. And this can also be factored into therapeutic impact as well.
Lindsey Riley:
The second example and case study I’d like to highlight is the AT-HOME PD sub-study. And this is a multi-institutional collaboration sponsored by the NINDS. The objective of this sub-study is to provide long-term follow-on for participants in two former interventional studies, the STEADY-PD3 and SURE-PD3 studies, which were looking at the efficacy of as well as measuring Urate Elevation respectively. So through annual remote tele-health visits, as well as engagement with the Empower smartphone app developed by Sage Bionetworks and quarterly study visits through Fox Insight, long-term follow on is provided for participants in these particular trials.
Lindsey Riley:
If successful, this subsidy could really provide a great model for virtual follow-on for PD clinical trials. I’ll also note here that all of the data collected through this step study is available in the NINDS data repository for researchers to access. And lastly, I’ll highlight the third example of how we’re using Fox Insight and leveraging a platform to gather just in time data on an emerging public health crisis, which is quite obviously the impact of COVID-19 on the Parkinson’s disease community.
Lindsey Riley:
So together with the study PI, Caroline Tanner, based at the UCSF, we launched the first-of-its kind study in late April to the Fox insight cohort, with the goal of identifying the effects of the global pandemic on Parkinson’s symptoms and disruptions in care. Over the course of a four-week period, 7,000 survey responses were collected, 5,000 of which were from people with Parkinson’s disease. Out of those respondents, 51 reported having received the COVID-19 diagnosis, and of those, 75% reported new or worsening non-motor symptoms, 55% reported worsening of existing symptoms, and 18% reported new motor symptoms.
Lindsey Riley:
Among all PD respondents, interruptions to exercise and social activities unsurprisingly were also associated with worsening of PD symptoms, indicating the toll that living through the pandemic has taken on the Parkinson’s disease community. Also, unsurprisingly is that the majority of respondents reported interruptions to healthcare, including [inaudible 00:16:10] PD medication. Participants with lower income and the BiPAP community were also disproportionately affected in this way. MJFF has subsequently leveraged this data and spurned it into action, developing strategies and tools to combat social isolation and communication with our community, as well as informing policy around drug access during this time. So now what I’m sure you’re all waiting for, the answer to the burning question. How do I get access to this dataset? So, launched in April 2019, the Fox Data Exploration Network or Fox DEN, as it’s lovingly known that provides investigators with a tool to explore, download, and apply statistical models on de-identified aggregated data collected in the Fox Insight study.
Lindsey Riley:
This highly interactive platform allows researchers to explore PRO and PD-related genetic data, create and compare user defined cohorts, choose guided statistical models, and download data and study-related materials. And since Fox DEN launched, over 500 researchers from 21 different countries have visualized 2000 analyses. The platform is well positioned for exploratory now that’s across Parkinson’s disease, health, lifestyle, and genetic data modalities. I’ve included the URL and QR code here for bookmarking, but a quick Google machine search of Fox DEN and MJFF keywords would also get you there. So I encourage anyone listening today and interested in this type of data and those modalities, please register for Fox DEN. So I’ll wrap up here and bring us back to our key takeaways, patients and care partners, we feel are the real experts on disease and incorporating the patient perspective should be standard operating procedure and not an after thought.
Lindsey Riley:
We need PROs to stand alongside other clinical outcomes assessments and provide a holistic picture of what happens outside of a clinical setting. Fox Insight MDS has online clinical study of the lived experience of PD, provides a novel opportunity for people with and without Parkinson’s disease to engage in research virtually, which all of us know are critical and important throughout this time. And lastly, I encourage those interested in real-world data to register for the Fox Data Expiration Network or Fox DEN, and explore all the study data has to offer. I’ll Wrap up here with a final call for your collaborations as Michael himself states, “When the cure is found, it will because of all of us and not one of us.” And so I’ll ask you to please be in touch with me if you’re interested in partnering in any way. And my contact information is listed here.
Lindsey Riley:
We would love to talk with you and have you join our precompetitive public-private consortia, attend scientific meetings, potentially be a reviewer or an assessor on one of our grant RFAs if that’s applicable, and generally mostly gain your perspective on research landscape, and targets and pathways of interest in Parkinson’s disease, many projects that you might want to talk to us about. So with that, I’ll stop there and take any questions that have come in through the chat.
Lindsey Riley:
So one question that has come in is regarding how we reach or recruit participants to be part of the Fox Insight study community. So predominantly to date, we have leveraged our patient and family supporter, email audience, which is quite substantial, as I mentioned, we’ve been around for 20 years now, and so we’ve been able to grow a strong community, in that sense we’ve also leveraged opportunities to recruit for the study through our website and social media presence, and then we have done some recruitment through social media, paid media, and some limited opportunities to engage clinical sites on the ground, or ambassadors, if you will, to do recruitment in that way.
Lindsey Riley:
Question here has come in about the Fox DEN platform and how many researchers we envisioned using the platform. Honestly, I think the more folks that are looking at this data and using it, the better, more shots on goal, as we say, I think the interesting opportunities that Fox Insight Data presents is the ability to, like I said, look at the longitudinal data and the different modalities available, but also leverage some of the existing cross-sectional data that we have collected on a number of topics of interest. So I highlighted one case study in the presentation regarding COVID-19. We have also launched and collected data on a number of other ancillary topics of interest, including cannabis use in Parkinson’s disease. Most recently we will be collecting or we have collected, excuse me, data on the use of mindfulness and meditation strategies in the P.D. Community, as well as among caregivers. We’ve also leveraged the ability to deploy cross-sectional data and collect information on patient preference information through a collaboration with FDA partners, so I think that’s also really exciting juicy data set for Fox DEN investigators as well.
Lindsey Riley:
A question here has come in regarding how many researchers are using Fox Den to date, it’s been about 500 across a number of countries, and we are looking to, and actually have also opened an RFA related to use of Fox DEN data. So I encourage all of you to check out our said opportunities page on the Michael J. Fox website, as well as logging in and registering for Fox DEN.
Lindsey Riley:
A question here has come in regarding whether we see caregivers and family members having interest in joining Fox Insight study, and the answer is yes, I think resoundingly, they are also part of that group that is always sort of anecdotally asking how to do more and how to help us advance the research cause in our organizational mission. So as I mentioned before, predominantly the cohort is comprised of, and you’ll see individuals with Parkinson’s disease, but about 25% are individuals that do not have Parkinson’s disease, and we know a lot of those to be individuals that are caregivers, family members, and just general supporters. All of you can participate in Fox Insight, I participate in Fox Insight, so on top side of registering for Fox DEN I also encourage folks to visit the foxinsight.org page and sign up if you’re interested in advancing PD research.
Lindsey Riley:
A question here about the MJFF portfolio and strategy and whether it will be… Have research grants once again, the answer is resoundingly, yes. And so again, I encourage folks on the webinar today to, check out our website and go to our funding opportunities page where you’ll find a lot of exciting information about what we’re funding, even in the current climate and how to potentially apply if that is applicable to you and or your organization.
Lindsey Riley:
There’s a question here about how I think we can get more patients engage in research outside of PD as well. I can say certainly through our experience funding Fox Insight that online and virtual study participation is not going away. And in fact, it’s growing each and every day, quite obviously, and so I think as we’ve learned through surveying practicing site participants and majority of people that participate in the study, haven’t engaged in research formerly, and so I think as I mentioned before, online research and virtual participation can really be a nice way to facilitate entree, and it’s also, I think, as I mentioned, more of a patient-centered approach. So to what extent possible we encourage our industry partners to consider how to incorporate PRO development, as well as PRO collection in clinical studies.
Lindsey Riley:
A question has come in about use of the platform, both for Fox Insight and potentially I think through the AT-HOME PD study and the tele-health aspect of that sub study, whether we see an older age group using the platform, and again, there, the answer is yes. So the average age of a Fox Insight participant is 65. So I think it’s a real proof of concept that if you build a patient-centered study and design the interface to be, I think commensurate with both the practices and health literacy, and design it in a way that is approachable to folks of all age groups, but is in fact feasible to recruit and retain individuals from 65 and older. Lots of great questions. Thanks for your interest and engagement today.
Lindsey Riley:
The question about genetic factors related to Parkinson’s disease. So, we know, much research has been done in this area, that there are genetic links related to Parkinson’s disease, and so, I think that one potential way that we can help advance this particular research question is, through the Fox Insight study and specifically the genetic sub study and partnership and collaboration that we have with 23andMe, as I mentioned. So, just to… Yet another plug for Fox DEN registration, but I encourage all of you today for whom this is relevant to go ahead and register, and in particular, take a look at that particular modality, that genetic data, because I think now, as I mentioned, having recruited and enrolled over 10,000 individuals in that sub study, that particular part of the data set is ripe with opportunity for researchers.
Lindsey Riley:
And there’s one final question regarding research into the human gut microbiome for possible connection, not necessarily research or topics that we’re exploring through Fox Insight, although, never say never, but through some of our other sponsored cohorts, including the Parkinson’s Progression Markers Initiative or the PPMI study, we are actively working with a number of investigators in this space to incorporate how to interrogate those questions through some of our longitudinal and sponsored cohorts.
Lindsey Riley:
So, I think that covers everything, and I thank you for your participation and active engagement in the webinar today. My contact information is listed on the slide, which I believe will be provided. So please get in touch with me should you have any follow-up or additional questions, and most importantly, any questions or interest in partnership.
John Fremer:
Thank you for joining Sanguine for our S3 webinar, Fox Insight, driving Discovery with the Patient Voice. For a list of upcoming webinars or to request patient samples, visit sanguinebio.com. Thank you, Lindsey, and thank you all again. Enjoy the rest of your day.