Pluri

The term zebra refers to an exotic medical diagnosis, or patients with such rare disease. Due to relatively small number of patients affected by such rare diseases, their voices often go unheard, their needs un-addressed, their meds not in the lab under development. This affects physicians too. These are the patients that one may have read in the book, but one that would never meet in the office. And when they do show up to one’s office, a lot of clinical management is dictated by “anecdotal expert opinions” instead of statistically-sound, scientifically-proven clinical guidelines from case-series or randomized clinical trials. And when the physician realize that it may be beyond one’s expertise, they are referred to quaternary referral centers, waiting months after months to see the world-renowned expert, who earned the title of being an “expert” from having seen 60 or so of such patients in one’s career. While some patients would self-describe themselves as having had the bad luck of the draw, a lot of these “one-off” conditions, to clinical scientists, are considered gift of nature, that are so unique in their presentation and pathophysiology that allow human minds to obtain better understanding of our bodies and disease processes.

Here’s how things are done today. A zebra shows up to one’s local endocrinologist. Further workup reveals that it is a rare genetic condition. His twin brother now tests positive for the same condition. But that twin brother will be on a different surveillance regimen such as routine MRI, blood draw, and endoscopy because there are no clinical guidelines that have been proven to decrease one’s mortality. For a second opinion and chance to enroll in a clinical trial/ experimental treatment, that patient is now referred to an expert many states away. This will take months, IF there happens to be the right trial on clinicaltrials.gov. As a physician, one may not know to whom to refer this patient to. Even when a physician peruses clinicaltrials.gov, most of them have nothing to do with one’s patient. A clinical scientist may want to reach out to more of these patients. A clinical scientist would need more patients for greater statistical power that will prove that one method or treatment will improve one’s outcome thus forming a clinical guideline. Currently, the system relies on these sporadic referrals from out of state, or select zealous and well-informed patients who find their way into trials. We need help in coming up with statistically sound medical practices, and in order to do so, we need help connecting zebras to scientists. We need to gather more zebras and hear what they have to say.

With technological advances, de-centralized enrollment and role-reversal have brought positive disruption of existing system, and bettered human lives. To address the problem, Pluri took a page out of existing solutions such as LinkedIN and Uber. The days of job-seekers’ shot-gun submitting their resume to every company in town is over. The same goes for travelers drenched in rain waving hand by the sidewalk trying to catch a cab. Pluri offers patient-doctor pairing to enter our platform, by creating a so-called disease-resume. It will highlight relevant disease manifestation, lab values, and your clinical characteristics that the disease-expert or clinical scientist are searching for. Instead of refreshing clinicaltrials.gov every week hoping to find the fitting trial, the trial finds the patient, just like how the companies filter LinkedIN resume and reach out to potential employees. By instituting what we call a “reverse clinical trial enrollment process”, we hope to connect only the patients who meet the inclusion criteria for each specific trials. In doing so, we hope to accelerate scientific advances by (1) increasing number of participants and statistical power subsequently, (2) eliminating faulty patient recruitment, which on average result in 30% of initial enrollees falling off the trial in the initial stage as they no longer meet the inclusion criteria, and resultant improvement in participant retention, (3) expediting patient-to-expert referral process.

Pluri is a digital platform in which rare disease patients can upload and share their verified medical/health data to be made visible to other physician experts or clinical trial scientists. Consider it "LinkedIN for rare disease patients". By facilitating data sharing, patient data visibility by rare disease patients themselves, our goal is to allow increased number of rare disease patients who are enrolled in clinical trials. Clinical trial experts currently rely on outside referrals to gain access and meet rare disease patients. With Pluri, we believe that the experts can reach out to rare disease patients with data set and abnormalities of interest thus increasing patient access to leading experts, and trials. With more patients within a trial, statistical power of trials will improve, leading to greater discoveries and breakthrough therapies for often neglected rare disease population. As the researchers are initiating the first contact, with initial data set at hand, this allows enrolling only the patients who meet the inclusion criteria of a study, thus accelerating the enrollment process, reducing confounders and patients who are likely to be excluded midway. In doing so, we expect to accelerate scientific discovery, improve patient access to leading experts and reduced cost associated with each clinical trial. Registration to Pluri involves a patient-physician pair to ensure that imported patient data is valid and un-modified. With physician-vetted, HIPAA compliant system, Pluri also strives to maintain a healthy community of rare disease patients who can openly discuss and share their experiences, knowing that others on Pluri are verified rare disease patients without external motives in a safe, protected environment of Pluri. Pluri also allows patients to determine what specific data is made visible and to what degree of detail. Once an outside physician or clinical trial scientist identifies patient's data to be of interest, Pluri allows matching of patient-scientist pair upon which the research scientists can reach out to patients to obtain further data or further medical evaluation along with invitation for a specific clinical trial that may benefit the patient. Additional features include patients to place a time-restriction on their data visibility, and ability to assign monetary values it will cost to access detailed data. Pluri aims to give full ownership of one's biological data to respective patients themselves.

Jun Park: (Internal medicine physician, endocrinology fellow at UC Davis Medical Center. Bioengineering major with research on solid-binding peptide, biosensors and peptide-on-graphene semiconductor research. Previous Mary Gates Foundation Award, and Washington Research Foundation Scholar at University of Washington Seattle.)  Jun Park experienced challenges faced by physicians while working as an internal medicine resident physician, especially when faced with diagnosing and providing medical care for rare disease patients. In particular, he had first-hand experience while caring for a MEN1 patient (multiple endocrine neoplasia type 1) who required multiple referral and potential enrollment in clinical trials. He took lessons from such encounters, recognized that these challenges affect many other rare disease patients and physicians who provide care for them, and has joined multiple experts by presenting such challenges in national meetings. 

Vinay Pai: (PhD in mechanical engineering with a focus on biomedical engineering. Was first division director of the Division of Health Informatics at National Institute of Biomedical Imaging and Bioengineering, a National Institute of Health. Has a NLP startup called Data Collaboratory, and is a general engineer within the Digital Health Center of Excellence at the US Food & Drug Administration’s Center for Devices and Radiological Health (CDRH). Has several patents on biomedical products from magnetic separation of blood components to rapid imaging techniques in magnetic resonance imaging.) Vinay Pai joins Pluri with his expertise in working with regulatory agencies at a national level. He is deeply involved in determining which projects and entities are funded by federal grants, and has witnessed challenges, costs and failures that affect large clinical trials. Some of them include ever increasing cost of running a trial, failure to approach target number of clinical trial participants, and extended length of such trial. His expertise and previous experiences allow Pluri to envision large-scale adoption that will one day allow Pluri to reach out to many zebras regardless of their location or healthcare system. 

John Metzcar: (Is a graduate fellow at Indiana University in the Complex Networks and Systems National Research Trainee NSF program. He is in both the Intelligent Systems Engineering and Informatics departments, working in bioengineering with Dr. Paul Macklin and complex networks and systems with Dr. Luis Rocha, studying the cell-cell and cell-environment interactions and signaling networks that lead to cancer or inhibit its treatment. He also has a masters degree in medical physics focused on radiation oncology. Prior to beginning his graduate career, he worked in food manufacturing (wine and beer making) on both production and quality. John is a patient advocate in the rare disease community, specifically for the multiple endocrine neoplasia (MEN) community. In this role, he serves as president of the Association of Multiple Endocrine Neoplasia Disorders (AMEND) USA.) John Metzcar joins us as a patient advocate who interacts with MEN patients on a daily basis as president of AMEND USA, which facilitates patient-to-patient interaction, provide education for the newly-diagnosed patients, and provide large-scale advocacy activities at national meetings such as International workshop on Multiple Endocrine Neoplasia, and American Society of Clinical Oncology (ASCO). His expertise and personal relations to rare disease patients, along with their family members who provide care have been a tremendous driver for Pluri as this allows sampling of targeted audience, receiving user feedback from the patients themselves, and subsequently improving Pluri’s implementation. 

Dhruv Pai: (is a senior in the gifted and talented program at Montgomery Blair High School, Silver Spring, Maryland. He recently represented the state of Maryland at the prestigious Research Science Institute (RSI) organized by Center for Excellence in Education and Massachusetts Institute of Technology (CEE-MIT). He has a single-author publication in mapping the genealogy of medical devices in the US and has won several national awards for his STEM and volunteering activities. He is an incoming freshman at Stanford.) Dhruv Pai joins Pluri with his expertise in computer science and project development. He plays pivotal role in providing technical expertise in designing and implementing Pluri’s minimum viable product demo, as well as serving as a boot-on-the-ground by presenting our cause, project, and vision to leading experts and patient advocacy groups in national conferences such as NIH Rare Disease Day.

With generous funding from MIT SOLVE,, we plan to achieve the following: maintain our minimum viable product (MVP) by paying for its server hosting fees, increase patient traffic by rolling out the 2nd prototype to larger group of early-adaptors within the MEN 1 community. Additional funding will be used to ensure that our data hosting and transmission are in compliance with HIPAA. Should there be any remaining funds after investing in our infrastructure, we hope to utilize the funds to allow our members to travel to various tech competitions and startup incubator meetings to enlarge our footprint and strengthen our product. 

Meaningful traction for Pluri would mean patients, doctors and researchers freely engaging in communication, information exchange and clinical trial enrollment. This would require high patient enrollment and maintenance of daily traffic and user retention. Thus, we would like to not only introduce our working product to select patients, but also begin enrolling physicians, and university-based clinical researchers to better observe, accommodate, and enhance their experience within Pluri. Our very initial goal is to achieve the critical number, which would be enrolling 60 MEN 1 patients. This is the number of patients previously involved in the largest clinical trial/ retrospective review thus far, and by proving that we can promote and facilitate the largest patient pool to ever exist, we hope to start recognizing patterns, gain statistical power, and yield clinically significant, practice-changing guidelines that are much needed in the MEN 1 research. In doing so, we hope to prove to our research community that Pluri is a powerful research tool, the one that can amass a larger patient pool, greater statistical power, all the while reducing incorrect patient enrollment that no longer meet inclusion criteria, medical waste, and prolonged trial enrollment period. 

The immediate challenges we are facing include providing incentives to physicians to take part in our noble cause. By participating in Pluri along with their own patients, Pluri is expected to facilitate communication between local physicians and the world-renowned clinical researchers at tertiary care centers. We are hoping to design a physician compensation model, under which physicians can bill patient’s insurers for providing clinical guidance online. Additional foreseeable challenges include verifying the integrity of patients’ self-reported laboratory values and uploading each data to our Pluri service. We are currently trialing multiple modes of data import mechanism, including but not limited to, utilizing existing physician’s ancillary staff for data entry, and optical character recognition (OCR) for automated data submission via each patient-physician pair. Additional guidance on reaching the self-sustainable phase with novel profit model is much needed to advance our Pluri model to incorporate not-so-rare disease patient population and clinical trial acceleration.

Match-making algorithms have transformed our lives in the recent past. These include finding jobs (Linkedin), finding relationships (Tinder), or selling products of various use. Such breakthrough has not been widely used in healthcare settings, especially one that connects rare disease patients to one another, or more importantly, such patients to clinical experts or clinical trials that they would benefit from. Such technology allows interaction between those who look for specific outcome, those who are few and far between, or those who have limited means of voicing their concern as a larger group. 

We believe that Pluri will be catalytic in 3 fronts. 

1) Connecting patients who suffer from rare diseases to each other. Many of these conditions occur sporadically, and only few patients exists in a given region/state. Because their experiences, treatments, and outcomes are unique, and also because only limited resources are available online, these patients would benefit greatly by interacting with one another. Such function is currently served by online community boards which are often un-protected from those malignant users who pretend to be suffering from specific disease condition, those who attempt to sell specific products to a group of people, and privacy infringement. 

2) Connecting patients with experts. A real-life referral process, as of today, is rather archaic. One would go online to look for previously known experts in this field, or via words of mouth. Because of how rare such cases are, such clinical experts are limited to certain tertiary or quaternary medical centers or universities that are many states over, with no means of directly communicating results and concerns to such experts. By making patient's disease resume visible to those who might be of help, Pluri aims to accelerate the referral process from their local system to clinical experts in national level. 

3) Empowering clinical trials. By increasing visibility of such rare patients and their notable data, Pluri expects to augment recruitment efforts by clinical trials. Involving greater number of rare disease subjects are crucial to achieving statistical power, sample collection, and robust analysis. Pluri aims to enable clinical trial scientist to reach out to such patients proactively, instead of waiting for potential referral in a passive manner which is the current process. By only enrolling those who are eligible, and targeting specific patients, Pluri anticipates that clinical trial scientists will be able to expedite the recruitment process, reduce funding associated with subject search, all the while enrolling more subjects per each study.  

Patient-centric) Pluri aims to facilitate communication between rare disease patients who suffer from identical conditions. In doing so, we anticipate increased communications between patients who are not just regionally close, but also between those who are far apart. 

Medicine-centric) Pluri anticipates that data visibility and match-making via the platform/algorithm would allow expedited referral process. Patients would spend less time waiting to hear back from clinical experts who practices in different healthcare system or in different state. 

Research-centric) Pluri aims to enroll greater number of rare disease patients to clinical trials of interest to specific patient population. We believe that it will result in statistically robust, more generalizable scientific findings. 

Patient-centric) Pluri will investigate if our system allows for greater interaction between the patients. Certain metrics that can be used to verify this is to look for number of nodes, messages, or posts shared by the members of specific disease group. Such metrics can be compared to that of existing platforms such as online message board, Facebook, or reddit disease community. 

Medicine-centric) Pluri will investigate if the time it takes between the initial referral and the first encounter of the patient to clinical experts/specialists. This is a measurable outcome, that can be compared against the current standard of practice, where a referral is generated by a local doctor or a specialist, it is faxed to a national expert, the expert's health system evaluates for appropriateness of the referral, then reaches out to the patient to schedule a new patient appointment, and then the patient flies out to meet the expert for the first time. Ideally Pluri will shorten that referral time. 

Research-centric) As an initial goal, Pluri aims to enroll the greater number of participants than that of recent clinical trial involving the same group of patients with identical medical condition. For example, if the latest clinical trial involving MEN 1 patients was able to recruit 50 patients, Pluri aims to exceed that, by enrolling 100 patients. Another metric would be to open a clinical trial of the same design but with more subjects involved, which will increase statistical power (measured as smaller P value, or narrower variance interval). 

Patient-centric) 
#activity: patient A is a newly diagnosed MEN 1 patient, who knows no one else in the family or community about expected outcomes or experiences of suffering from MEN 1. patient A joins Pluri to seek others like him, and to learn more from other patient's first-hand experience

#output: patient A is matched with patient B who is of similar age, background and interest. Patient B is able to provide personal guidance as an experienced patient, providing expertise to patient A that no other physicians or experts can provide

#outcomes: patient A is then able to avoid pitfalls or surprises that come with suffering, and managing MEN 1 that only 1 in billions of patients suffer each year. Patient A is able to make anticipatory moves and plans ahead, thanks to the forbearer and a colleague met on Pluri. 

 Medicine-centric)
#activity: A patient-physician pair joins Pluri to seek best options for sending out referrals to clinical experts outside of their region or healthcare system. 

#output: Patient A is able to meet the new clinical expert. 

#outcomes: Patient A is able to reduce the time between the onset of the referral transmission to the first encounter with the clinical experts. By seeing an expert early on, patient A is able to reduce healthcare cost, avoid unnecessary interventions, and reduce anxiety.  

Research-centric)
#activity: Patient A uploads his disease resume, detailing one's lab abnormalities and biometric findings. Clinical trial scientist notices patient A's interesting lab abnormality that is pertinent to upcoming clinical trial. 

#outcome: Patient A is contacted by a clinical trial scientist through Pluri system. Patient A is invited and is enrolled in the trial that he was not aware of. 

#outcomes: Patient A receives previously un-available medical therapy and intervention via clinical trial. A clinical trial scientist is able to reach out to greater number of rare disease patients, and recruit more patients. This results in statistically sound scientific findings, applicable to patients who suffer from such conditions. New scientific discovery is made, at a faster rate, with a greater certainty. 

The software-based platform proposed in this application (henceforth referred to as the “Pluri” platform) is an invention to address these concerns, in order to facilitate rare disease and

general patients to overcome such challenges in very unique ways: patient-centered, physician- coupled and guided, and algorithmically-driven information exchange between patients, their

care team, and the clinical research teams. For example, the current process of clinical trial enrollment primarily consists of two distinct approaches: a). The patient is guided by their specialist or primary care physician who, upon
shared decision-making with the patient, searches for open clinical trials on sites on the internet (e.g. clinicaltrials.gov) and reaches out to the recruiters during an enrollment period, or b). The clinical trial investigators reach out to a subset of patients who have been referred or seen by them in the past, by parsing through their existing patient roster, in order to determine the select few that might meet inclusion criteria for a clinical trial. While the former process relies on the patient and the physician pair to correctly identify potentially appropriate trial, and a luck-of-the draw for such trials to be actively enrolling patients at the time of discovery by the patient, the
latter process is limited and inherently biased (“selection bias”) as the trial will never have more than the number of patients previously seen by the researcher, which may potentially fail to capture greater number of study subjects (who had not been in the particular facility or the researcher’s database). The software-based platform proposed in this application is an invention that addresses this concern. In the proposed application, the patient and the clinician pair are stored in the platform’s internal database, and the clinical researchers are also having accounts on the platform. The medical history information is provided by the patient on an as-needed basis (and certified by their physician). The clinical researcher provides to the platform the various criteria that they are looking for in the patient population they intend to study. The platform’s algorithm then matches the patients with the most matches to the listed criteria, contacts the patients and asks them if they are interested in having their name put forward for the clinical trial. Upon consent from the patient, the patient's limited information (as decided by the patient) is provided to the clinical trial researcher. Additionally, the patients can also decide which of their clinical
team members are added to the sign-up/enrollment process. The enrollment decision is then made by the combination of the patient-their clinical team-and the clinical trial researchers. This approach improves upon current processes by reducing both the luck-of-the-draw and the potential biases that are present. Since both the patients and the clinical trials teams are on the same platform, the selection bias is somewhat minimized (obviously, the patients who are not on the platform are still going to be missed from the selection pool), and since the patients and their physicians are seeing all the clinical trials that align for their needs as they show up, and are being matched by the platform algorithmically, the luck-of-the-draw is now eliminated.

Patients want control over their data and medical data privacy is an important aspect of this control. When patients are being enrolled in clinical trials or when their data is being used for medical research, current healthcare solutions do not provide patients the ability to control the
level of data sharing that can be done: they cannot control the level of detail of sharing, they cannot control the type of data that can be shared, and they have limited control over who gets to see which portion of their data.
The software-based platform proposed in this application improves upon current processes by introducing the ability of the patients to control the level of data sharing that can be done, to whom it can be shared, which components of the data can be shared and till what duration, and
the resolution of the pertinent data that is shared.

For example, the current process of health-related data sharing for patients is usually all-or-nothing as far as data access when patients release their data. When a patient signs an authorization to release medical records, all their medical records are released to the requesting party, with rare exceptions pertaining to mental health records and transmittable disease states.

The software-based platform proposed in this application improves upon this current process by allowing the patient to select which portions of their data are shared and at what level of resolution. For example, if their TSH (thyroid stimulating hormone) level is 500 mIU/L (reference range: 0.5-4.5 mIU/L), then the patient can control whether the information that is shared with
the requesting party is the exact value, the value within a certain range, or just that the value exists. Thus, they could share that the value is 500 mIU/L, or that it is between 100-1000 mIU/L (or a range more relevant to the patient/requestor), or that the laboratory variable is being tracked. This example is just a view into how the patient can control the level of blurring of their data as shown to a data requestor; any one skilled in the art would realize that the blurring can be customized as per the patient’s need. By this approach, the software-based platform proposed in this application improves upon current patient data sharing processes by allowing the patient to control access to their data. The software-based platform proposed in this application improves upon current processes by introducing the ability of the patients to own their data and get revenue for their data. Current
processes have the data owned by the hospital systems or companies who buy the health care data from hospitals, and do not allow a voice for the patients. The proposed application allows the patient to sell their own data through the auction marketplace of the software-based platform proposed in this application; they can decide the level of blurring (resolution) in the data they want to sell, they can sell their data in a longitudinal basis (i.e. selling particular laboratory value that may change over time), they can sell as a bundled package with other similar patients, etc. Any one skilled in the art would realize that the patient can customize the carve out of their data
in approaches that allow the patient to increase the value of their data. Besides giving ownership of patient data back to the patients, this platform also incentivizes patients to get regular medical check-ups (as these act as individual data points) and increase the quality of healthcare. The system places emphasis on aspects of personal clinical data that often goes under-utilized: (1) it costs each patient their time, money, and physical pain to obtain such clinical data (such as laboratory values, X-ray/CT/MRI/echo images, data from smart devices worn by the patients), thus inherently assigning quasi-monetary value to these numbers, (2) such values can be used multiple times by multiple parties, with usages going beyond benefiting the patients themselves (i.e. fellow patients of similar disease state, or researchers), (3) being able to store, capture, and trend historical clinical values that well-predates one’s enrollment in a clinical trial, outside of the trial setting, thus potentially providing insights to early stages of disease manifestation from a larger population database.

We are group of 4 individuals, consisting of a physician, PhD scientist, PhD candidate and patient himself, and a high school student. We come from a very diverse background, with each living in different states in the US. Pluri has an open door policy where we welcome anyone who shows interest in working on this project. We have worked with industry experts from various universities, laboratory, hospitals, of various gender identities, ethnicity, and political views. As Pluri aims to empower those rare disease patients (zebras) whose voice went unheard for the past decades in terms of garnering research interest, public funding, and standardization of care, Pluri aims to be inclusive of those who come from various backgrounds which subsequently allows for innovative interactions and breakthroughs. 

Pluri will provide the following services:

-secure storage or medical information that is portable and transmittable
-imported patient data can be securely transmitted to clinical experts or clinical trial scientists
-Pluri serves as a messaging platform where clinical experts and clinical trial scientists are able to view, identify, and reach out to patients proactively
-Pluri serves as data repository in which scientists can garner initial data of interest
-Pluri serves as a hypothesis generator, by providing big data for rare disease population which was previously limited to large universities with specific referral patterns. 

Pluri aims to remain free to individual users and patients. Pluri will generate revenue by seeking funding from institutional entities that utilize the following services:

-hypothesis generator using patient data obtained from Pluri
-clinical trial scientists' messages sent out to recruit patients
-clinical expert's messages sent out to referred patients
-recruitment correspondences sent to Pluri members
-patients are able to auction their personal medical data by providing access rights to parts of medical data to specific bidders (clinical trial scientists, pharmaceuticals or clinical experts), and Pluri will seek small commission from each transanctions.  

We have not raised any revenue as our prototype is not designed to capture revenue at this time. 

No investment funding opportunities have been sought after by Pluri so far. 

Pluri has previously applied to grant opportunities such as Chan Zuckerberg Initiative (Rare as one), LG NOVA Challenge, and Robert Wood Johnson Foundation Awards, but these did not result in an award. Our efforts to winning funding support continues.