BCM Patient Registry

BCM Families Foundation

Blue Cone Monochromacy (BCM) is a rare retinal disease that affects 1 in 100,000 individuals worldwide. People are sparse everywhere and doctors usually see only some few patients with BCM in their entire carrier. This precludes the possibility of knowing the characteristics of the disease well, but also leaves a large fraction of people without a diagnosis, because local practioners don't know the disease. Today, after more than 14 years of work, we are in contact with only 20% of the affected people and we believe it is necessary to develop more effective diagnostic tools. The Patient Registry is fighting this disease by grouping all data and features of rare patients affected by BCM in a database and allowing our patient community to use their own data. More generally, we could leverage a connection with hundreds of patients affected by our rare disease, BCM, whose genetic diagnosis has been validated by expert clinicians, and obtain results of knowledge and prediction that would otherwise be unattainable. In the future, the data collected could be used to train a supervised learning algorithm and increase the chances of diagnosing the disease. Patient Reported Outcome measures could also be created and the knowledge of symptoms will be improved.

The BCM Patient Registry is an international registry collecting  data about individuals with Blue Cone Monochromacy (BCM), who provide information about themselves to the registry on a voluntary basis. The registry is an online webapp and allow people from 30 countries to enroll themself easily. The registry has been planned and developped to be compliant with privacy regulations of EEA, UK, Canada and the USA.

Accessibility of the WebApp has been studied for individuals affected by BCM and the WebApp allows people with low vision, poor color discrimination and photophobia to access it.

BCM is an X-linked disease that affects mainly males, with an average of 5 people affected per family. The BCM Registry is for individuals with a clinical and genetic diagnosis of Blue Cone Monochromacy. The patient can autonomously enrool in the Registry or parents of an affected child can enroll him.  Then an expert clinician who has visited the patient previously review his clinical and genetic reports and validate his diagnosis and his clinical and genetic data.

Today we have 14 clinicians listed in the Registry. If a patient don't find his own clinician, he can invite his clinican to join the Registry or the Registry Manager can assign him to a clinician in the list who can review patient data and contact his own clinician in order to validate his diagnosis. The aim is to collect data with high quality and to certify all diagnosis and causative mutations.

Finally, we build a family pedigree for each affected family, joining together members of the same family and capturing data about all affected members of each family.

The important point is that this is a patient registry dedicated to only 1 disease and owned and governed by a patient community.  This gives to patients the power to use their own data with the goal to improve the diagnosis and to find a cure.

The final target population are all the individuals in the world affected by BCM. Today we collect data in USA, Canada, the EAA and the UK, from people living with Blue Cone Monochromacy (BCM). In these countries there are thousands of individuals living with Blue Cone Monochromacy. Nowadays reaching a diagnosis and collecting information about this rare retinal disease is very difficult, with more than 80% of individuals who remain undiagnosed.

People who remain undiagnosed don't know the name of their disease and remain isolated and without the possibility of working toward a cure, for example by participating in clinical trial. Their data remain unknown and the lack of knowledge of their causative mutations does not allow others with the same causative mutation to reach the diagnosis. Their isolation does not allow them to be part of communities of people who try to improve the living conditions of all members of the community and to arrive at a cure.

The Patient Registry is collecting data and knowledge on BCM, and data on gene mutations and symptoms could be used to improve diagnoses, but also to learn more about the characteristics of the disease and prepare clinical trials for gene therapies. In the future, the data can be used to train supervised learning algorithms to improve diagnosis and predict prognosis.

The Patient Registry is collecting data of patients affected by a rare disease, Blue Cone Monochrmacy (BCM). In each country there are only few people affected and we would like to include as many data as possibile. Today patients in the US, Canada, the UK, and all EEA countries are allowed to participate. We would be glad to enlarge the number of countries, but there are legal barriers related with privacy regulations that are different country by country and state by state.

The BCM Patient Registry is innovative for 2 main reasons:

1)The BCM Patient Registry is a WebApp available online, and the interface is easily accessible by patients with low vision and symptoms of BCM. These features enable patients sparse everywhere to easily store their data in a single database, and increase the number of data about the disease.

2)The organizational model is innovative, because the registry is owned and governed by patients. This feature enable the patient organization to store and use data for any future application, for example AI supervised learning algorithms. The use of these data can change the life of undiagnosed patients and can enable scientists to perform clinical trials.

There are 3 possibile developments of our Registry that The amgen Prize can help us to develop.

1)
The first is the most important for diagnosis. We would like to include some few tests, mainly color vision tests, reading performance tests, and performance and orientation tests in a virtual context. Output of these tests could be used, together with all other clinical and genetic data, to train a supervised machine learning algorithm and create a WebApp for the diagnosis of BCM.

2)
We face with several legal barriers related with privacy regulations that are different country by country and state by state. Legal and operational cost to include more countries are high. Several countries for example require us to pay a Data Protection Officer to supervise only some few patients entries. We can consider including new countries for example in Central and South America, Turkey, Switzerland, Israel, and other North Africa and East countries. This is important to enlarge the database and enrich diversity.

3)
We can use data inside the registry and survey on the enrolled patients and their affected relatives to develop Patient Reported Outcomes, that could be very important for clinical trials.

I'm the President and founder of the BCM Families Foundation. In my family there are 4 people living with the Blue Cone Monochromacy, among them my children.

I'm in contact with almost all members of our community that collects today more than 1,000 affected individuals and hundreds of families.

I started working toward the cure in 2009 when my sons have been diagnosed by BCM. At that time I have started a forum and then a Facebook group building contacts with hundreds of people worldwide.

The Registry has been created to store in a database all these connections and to certify quality of collected data.

I think that, together with a staff of experts clinicians, privacy lawyers and AI consultants, I can be the right person to continue governing the Patient Registry and to create applications and outcomes from collected data.

Here you have the impact goals for the next year:

Reaching more than 300 connected patients from 30+ countries, storing their data and features, we can give life to the registry making its data feeding AI tools and starting planning Patient Reported Outcomes.

Here you have the impact goals for the next  five years:

Reaching more than 600 connected patients with a certified genetic diagnosis, and including tests and surveys we can feed AI algorithms and created Patient Reported Outcomes and aggredate data about Blue Cone Monochromacy. This will improve diagnosis, increasing diversity and equity in diagnosis. This will support the path toward the cure.

Blue Cone Monochromacy (BCM)  is a rare disease and knowledge on it is limited. We have created a database that contains the biggest number of data about patient with BCM in the world. The database can be increased by increasing the number of patients and the data stored for each patient.

Our expectation is that data and connections inside the registry can create new knowledge and make possible both to develop new diagnostic tools and to better prepare clinical trials.

Consultant part time:

1) 1 Registry Manager - total 1

Volunteers part time

1) 1 Registry manager + 3 volunteers - total 4

Contractors

1)Digital Video for the software maintenance

2) WIRB for the ethical committee

3) CMS for Data Protection Officer in EEA

4) Baker Hostetler for legal consultancy in the US and Canada

5) Aruba for domain registration

6) AWS for hosting

7) A graph designer

Total 7 service and consultant companies

The BCM Families Foundation started this project in 2018 and the Patient Registry WebApp went online on June 2019. The design of the project has been done by myself during 2018 and 2019 with some members of the Scietific Advisory Board (SAB), Dr. Samuel G. Jacobson for the clinical interface and Dr. Bernd Wissinger for the molecular genetics interface and with the software house, Digital Video.

The BCMFF has the governance of the registry since June 2019 - 5 years - and  I'm working on the project governance since it starts in 2018.

The BCM Patient Registry Project is governed and supervised by female staff.In particular, both registry managers are women and have a STEM education.
In addition to gender equity, which has often led BCMFF to fund projects involving young female scientists, our foundation is based on inclusivity. Individuals affected by BCM are often stigmatized and excluded and the network of families created by BCMFF is supportive in these situations.

We recognize that diversity for rare disease communities is a consequence of diversity in access to diagnosis. Patient communities are made up of individuals who have reached a certain diagnosis, which is often a complex and expensive path. Over the last 15 years, I personally and then BCMFF have activated a no-cost genetic diagnosis program, which can allow access to genetic diagnosis to everyone, in a simple and cost-free way. We believe this can allow us to achieve true diversity in the community and therefore also in the teams of volunteers who work.

Also for the diagnosis, we believe that the data stored in the patient registry can be used to build a simple and low-cost diagnostic tool based on a supervised machine learning algorithm – AI – that could lead to the diagnosis even in socio-economically disadvantaged or marginalized populations.

Another aspect of the rare disease is that people are scattered everywhere. We therefore activate online participation programs to allow everyone to connect. In-person participation in BCMFF events is always accompanied by travel expense reimbursement programs for disadvantaged families because we believe that overall, the comparison between heterogeneous people allows us to identify innovative, better tools and methods with results that cannot be obtained otherwise.

The business model of the BCM Patient Registry is

1) collect information from patients sparse everywhere

2) involve scientists in reviewing clinical and genetic data and validating data

3) involve volunteers in working to promote the registry

4) using data to create more knowledge about the disease

5) share and distribute statistical data and results

6) use data to improve diagnosis of undiagnosed individuals

7) use data to prepare clinical trials

The patients community will have back more efficient and accurate diagnosis and expedited and better prepared clinical trials.

The BCM Families Foundation lives of donations received from donors who are interested in our mission, to find a cure for Blue Cone Monochromacy. The BCM Registry is financial sustainable since 2019 because we decided to limit its features and activities about data, reducing expenses.

We selected to limited the number of data we store, the number of countries that we include. Moreover, we advertise the registry only through volunteers who are acting as testimonial and ambassadors. We limited the use of data because we haven't funds to make more than statistical aggregated analisys.

In the past 4 years, saving money considering only vital consultants for the registry, as the IRB annual review, the Data Protection officer, privacy lawyers, software maintenance and hosting companies, we see that we can cover expenses with donations that our foundation receives yearly.