CURE Drug Repurposing Collaboratory

Overview

The Problem

There are approximately 10,000 known diseases, but only 2,500 of them are addressed by FDA-approved drugs. That leaves around 7,500 diseases without FDA approved treatment, many of which are rare diseases, diseases in pregnant women, children and neonates, as well as neglected tropical diseases and emerging/reemerging infectious diseases. Many existing drugs might work to treat these diseases, but often there are no commercial or regulatory incentives – or there are actual disincentives — to do the extensive clinical testing required to show they are effective.

The Solution

In response to these challenges, the CURE Drug Repurposing Collaboratory (CDRC) was founded to explore whether already marketed drugs can be repurposed for diseases that are not commercially attractive. CDRC is strongly interested in capturing data from diverse populations, including pediatric patients and pregnant women, as well as under-served populations.

As part of this process, a roadmap will be developed for the efficient generation of evidence, in order for FDA to update labeling. This includes creating a path of potential scenarios, depending upon the context of the specific indication, unmet patient needs, the engagement of the drug sponsor or the first NDA holder and the status of current legislation. The data gathered through the CURE ID app can be used to inform the design of clinical trials, to evaluate the effectiveness and safety of a marketed therapy intended for repurposing, or to support treatment guideline development.

The path chosen will depend on the drug(s) in question (patented vs generic), the disease epidemiology and natural history (availability and procurement of sufficient data), and the existing legislative mechanisms (sponsor, payer, and/or patient support). Although many of the challenges of drug repurposing are global, regulators need to address these locally and within the existing regulatory systems. As regulators globally pilot programs, an ability to provide lessons learned and potentially share information to harmonize processes will enable pharma and manufacturers to better align by reducing complexity, lowering costs, and ensuring safe and effective treatments for all patients.

The Impact

The Collaboratory, led by Critical Path Institute (C-Path), works in a transparent, open forum, with a diverse set of global stakeholders including, but not limited to, clinicians, scientists, U.S. Health and Human Services (HHS) agencies, non-government organizations, foundations and societies in order to:

  • Evaluate drug leads through advanced analytics to identify candidates for repurposing as new treatments.
  • Inform the design of clinical trials of existing marketed drugs for new indications.
  • Generate real-world evidence for expanding drug labels.
  • Provide a regulatory roadmap to advance drug repurposing and expedite the availability of safe and efficacious treatments for diseases with limited or no treatment options.
  • Promote the CURE ID platform to enable the global health community to openly share patient treatment outcomes.

CDRC Annual Meeting Resources

2021 FAQ Icon

Day 1 Panel Discussions: Session 1: Rare Diseases
Moderators: Matt Might (UAB) and Shira Strongin (FDA)
Panelists: Andy Crouse (UAB), Ethan Perlstein (Perlara), Eva Morava-Kozicz (Mayo), Lisa Schill (RASopathies Network), Omid Karkouti (Rarebase), Clare Thibodeaux (Cures Within Reach), Sandra Sermone (ADNP Kids Research Foundation)

Session 2: Rare Oncology
Moderators: Leslie Doros (FDA) and Sonia Singh (FDA)
Panelists: Bill Tap (MSKCC), Denise Reinke (U Michigan), Kris Ann Schultz (Children’s MN), Pan Pantziarka (Anticancer Fund), Breelyn Wilky (U Colorado)

Day 2 Panel Discussions: Session 3: Special Populations
Moderators: Matt Laughon (UNC) and Kate Borkowski (FDA)
Panelists: Anup Challa (Vanderbilt), Rachel Greenberg (Duke), Mili Duggal (FDA), Matt Robinson (Hopkins), Khyzer Aziz (Hopkins), Perdita Taylor-Zapata (NICHD), Kanwaljit Singh (INC), Prabha Viswanathan (FDA), Genny Taylor (UNC), David Kimberlin (UAB), Jason Lang (Duke), Barbara Goodman (Cures Within Reach)

Session 4: Regulatory
Moderators: David Simon (Harvard) and Marco Schito (C-Path)
Panelists: Jonathan Darrow (Harvard), John Liddicoat (Cambridge), Sundeep Agrawal (FDA), Daniel O’Connor (MHRA), Lydie Meheus (Anticancer Fund), Heather Stone (FDA), Perdita Taylor-Zapata (NICHD), Nitin Bagul (TGA), César Hernandez Garcia (AEMPS Spain), Momir Radulović (Slovenian Medicines Agency), Agnes Klein (Health Canada)

Day 3 Panel Discussions: Session 5: Electronic Health Records

Panel 1 Moderators: Smith Heavner (C-Path) and Aysun Tekin (Mayo Clinic)
Panelists: Rahul Kashyap (VIRUS Registry), Matt Robinson (JHU), Paul Nagy (JHU), Matt Roe (Verana Health), Laura Merson (Oxford)

Panel 2 Moderator: Laura Merson (Oxford) and Smith Heavner (C-Path)
Panelists: Will Stevens (RECOVERY Trial, University of Oxford), Ann-Marie Mallon (NHS Digital), Kalynn Kennon (IDDO), Miguel Pedrera Jimenez (Hospital 12 de Octubre, Madrid, Spain)

CDRC 2021 Annual Meeting: The Collaboratory

 

Session 1 

  1. Shira Strongin’s Story
  2. Congenital disorders of glycosylation
  3. Individualized drug repurposing for the long tail of genetic diseases
  4. Repurposing Ketamine from Club to Clinic
  5. Repurposing- Case Study

Session 2

  1. The Use of Repurposed Drugs in Sarcoma
  2. Rare Oncology Session Sarcoma Drug Repurposing
  3. Engaging Sarcoma Patient Advocates
  4. Propanolol in Angiosarcoma- the story so far
  5. From Bedside to Registry… and Back Again

Session 3

  1. Ranking Diseases in Pregnancy for Drug Repurposing
  2. Neonatal Global Rank Score Development
  3. Congenital CMV Treatment Options
  4. The Pediatric Trials Networks experience
  5. Need to Develop Survey Tools
  6. Repurposing of montelukast for infants with bronchopulmonary dysplasia

Session 4

  1. Introduction & Work Group Goals
  2. Role of non-profit organizations in non-commercial repurposing
  3. Oncology Center of Excellence Project Renewal
  4. Regulatory Views- ILAP Initiative
  5. Closing the gap in generic drug repurposing
  6. Policy Issues in Drug Repurposing

Session 5

  1. Use of SDTM and ADaM with electronic healthcare data
  2. The ISARIC COVID-19 Data Platform
  3. Mapping EHR data to inform clinical characterization
  4. SCCM Discovery VIRUS COVID-19 Registry
  5. Virus Registry with OHDSI: Automating ETL from EMRs

 

C-Path’s Cure Drug Repurposing Collaboratory will host a three-day annual meeting in a virtual format, November 16-18, 2021.

Together, with key stakeholder groups including clinicians, researchers, foundations, nonprofits, patient advocates and regulators, CDRC will host a public webinar this November to discuss how the Collaboratory can capture real-world data that generate hypothesis regarding treatment efficacy using repurposed drugs to address diseases of high unmet clinical need. The meeting will include key opinion leaders from numerous disease communities as well as experts on automated EHR data extraction and ways in which these resources can be leveraged to develop partnerships to inform large adaptive platform trials.

What to expect:
Day One will be hosted by the Rare Diseases and Rare Oncology Coordinating Committees.

Topics will include:

  • Repurposing case study
  • AI tool predicted ketamine may help ADNP-driven autism
  • The use of repurposed drugs in rare sarcoma subtypes and current examples
  • Patient perspective on drug repurposing for sarcoma
  • Registries for rare tumors and case report form

Day Two will be hosted by the Regulatory, Legislative and Policy working group and the Special Populations Coordinating Committee. Topics will include:

  • Regulatory challenges in drug repurposing
  • U.S. FDA Project Renewal to update drug labels
  • MHRA ILAR Initiative to support alternative regulatory pathways
  • Congenital CMV treatment options and existing guidelines
  • Generating RWD to inform clinical trials
  • Survey tools

Day Three will include sessions dedicated to electronic health record data extraction for COVID-19. Topics will include:

  • Developing registries to leverage RWD from EHRs
  • Data harmonization and common data models
  • International collaboration and data sharing
  • Automating extraction of EHR data

Agenda 

Speaker Bios

Additional Resources

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Download the CURE ID app at (https://cure.ncats.io/) and begin submitting cases today. It takes a couple of minutes and every case report counts.

For questions or additional information about participating in CURE ID and the CDRC, please email cdrc@c-path.org.

Accomplishments

A significant number of accomplishments were completed in Year 9 across several diseases (infectious, non-communicable), clinical trials (decentralized outpatient, inpatient embedded in clinical practice), and the development of tools to automate the extraction of quality key data variables from electronic health records. Specifically, this includes:

Drug Repurposing FAQ Icon
  • Stood up the Medicines Repurposing International Network (MERIT) in collaboration with NHS. The network consists of fourteen organizations spanning eight countries plus the European Union and the World Health Organization. The network supports collaboration and communication between publicly funded drug repurposing initiatives.
  • Assisted in the development, consensus, finalization, and deployment of a sarcoma clinical case report form for CURE ID with input from multiple stakeholders.
  • Initiated contract with xCures to extract data from sarcoma patient EHRs for PEComa cases.
    Students from Clemson University School of Medicine and Interns from CDRC extracted PEComa cases from the literature to CURE ID.
  • Established and led monthly sarcoma workgroup calls for patients, clinicians and FDA OCE (Oncology Centers of Excellence) to develop a sarcoma pilot within CURE ID.
  • Engaged with stakeholders to determine potential to share data with CURE ID (Broad Institute, National Cancer Institute (NIH), EHE Foundation, and the Insituto Nationale dei Tumori in Milan).
  • Aligned with community of international sarcoma clinicians on development of a global master protocol for ultra rare sarcomas and the launch of such a trial (PUSH).
  • Partnered with Sarcoma Foundation of America who agreed to host a patient centered webinar (Jan 18, 2024) that introduces the initiative with CDRC, clinician and xCures perspectives followed by questions from patients.
  • Engaged Aadi Bio Science to promote CURE ID to their prescriber network to recruit physicians and patients to participate in the sarcoma pilot.\
  • Engage with NCI regarding data sharing for rare sarcomas.
Infectious Diseases FAQ Icon
  • Partnered with HeHealth to review and edit the Mpox CRF on CURE ID and to promote outreach to patients.
  • Created an international STI surveillance group under the auspices of WHO with existing surveillance efforts in the US, Canada, and the UK to partner on a project to identify repurposed drugs for Neisseria gonorrhea with additional countries as observers. This group helped create the CRF for Neisseria gonorrhea.
  • Organized a monthly Long COVID Clinical Think Tank call series consisting of 27 clinical trialists regulators, academicians and foundations across the US, Canada, and Europe to review and discuss challenges in setting up and designing clinical trials for this disease.
  • Created an international implantation mycosis workgroup under the auspices of WHO to partner with treatment clinics in Brazil, Mexico and Madagascar on a project to identify repurposed drugs for four distinct fungal infections with additional countries as observers.
  • Developed and finalized a case report form for Implantation Mycosis, sent to NCATS and is now available on CURE ID.
Rare Diseases FAQ Icon
  • Finalized clinician and patient case report forms for RASopathies and submitted to NCATS for inclusion in CURE ID.
  • Established a patient group to provide stakeholder input.
  • Engage NCI regarding RASopathies and their registry.
Clinical Trials FAQ Icon
  • Long COVID Outpatient Decentralized Pilot Trial
    • Worked with Berry Consultants and clinical trial collaborators to develop and optimize decentralized trial design for the treatment of patients with Long COVID in the outpatient setting.
    • Identified Principal Investigator and co-Investigator to develop and finalized pilot protocol to assess the feasibility of methods and procedures for later use in a larger scale decentralized platform adaptive randomization clinical trial.
    • Obtained Emory IRB approval for randomized pilot trial treating Long COVID. Submitted IND amendment to FDA for pilot protocol.
    • Posted trial on ClinicalTrials.gov: NCT05946551.
    • Developed Part 11 compliant REDCap database for electronic data capture of trial data.
    • Trial enrollment anticipated to start mid-January, 2024.
  • Inpatient Trial
    • Worked with Berry Consultants and clinical trial collaborators to develop and optimize trial design for the treatment of patients with sepsis in the inpatient setting.
    • Identified Principal Investigator and co-Investigators.
    • Identified all necessary variables required to be extracted from EHRs for the trial.
    • Developed a modified Delphi process to generate consensus amongst partners regarding treatment options that should be evaluated first.
    • Working with Every Cure advanced AI engine to identify and rank repurposed drugs of interest to take to the clinic.
EHRs Data Extraction FAQ Icon
  • Data transfers received from 7 institutions (>75,000 COVID patients). Projected to exceed 10 institutions and 100K patients for the project.
  • Invited to lead RWD and data standards committee at SCCM. Specifically asked to bring regulatory perspective and build strategic partnership to elevate standard of evidence generated across critical care research. C-Path to co-facilitate stakeholder listening session at SCCM annual meeting in January 2024 to explore unmet needs and interest in drug repurposing and regulatory grade research in critical care.
  • Invited to serve on common data elements steering committee for National Trauma Research Registry. This project is backed by the DoD and specifically interested in receiving regulatory guidance from CDRC to enhance trauma research on repurposed drugs.
  • CDC Grant Sub-award: Pregnant People-Infant Linked Longitudinal Surveillance to sustain, improve, and expand surveillance efforts from entities that have data systems to identify pregnant people-infant linked longitudinal data. The goal is to ensure timely reporting of key exposures and outcomes that impact pregnant people and infants, to improve data quality and share evolving outcome data, to innovate clinical strategies, and to build a strong collaborative network.
Peer-Reviewed Publications FAQ Icon
Non Peer-Reviewed Publications FAQ Icon
Posters FAQ Icon
  • Making OMOP Happen: An Implementation Science Approach” Authors: Maya Younoszai, Pam Dasher, Danielle Boyce, and Smith Heavner accepted for the October 20th, 2023, OHDSI Symposium in New Jersey.
  • Repurposing in RASopathies”. Authors: Shira Strongin, and Heather Stone. Presented at the CDRC Annual Meeting in Washington, D.C.
  • Deploying the Edge Tool Suite to Extract Real-World Data: an Implementation Science Approach”. Authors: Maya Younoszai, Danielle Boyce, and Smith Heavner. Presented at the CDRC Annual Meeting in Washington, D.C.\
  • CURE Pregnancy Treatment Repository: Prioritizing Systematic Collection of Real-World Data to Identify Effective Treatments in a Special Population”. Authors: Mili Duggal, Reema Charles, Nalini Oliver, and Heather Stone. Presented at the CDRC Annual Meeting in Washington, D.C.
  • “Lowering the OMOP ETL Barrier for Clinical Registries”. Authors: Smith Heavner, Trayson Llano, Zachary Wang, Marco Schito, Heather Stone, Pam Dasher, Tresha Russel, Vishakha Kumar, Ben Saeks, Michael Cooke, Rahul Kashyap, Matt Robinson, and Paul Nagy. Presented at the CDRC Annual Meeting in Washington, D.C. and at 2023 OHDSI Symposium in New Jersey.
  • Landscape Analysis of Drug Treatments for PEComa” Authors: Jamila Johnson, Dakota Makulec, Reema Charles, Marco Schito, and Smith Heavner presented at the CDRC Annual Meeting in Washington, D.C.
  • Leveraging the EPIS Framework to Extract Real-World Data from the Electronic Health Record” Authors: Dasher P., Younoszai M., Boyce D., and Heavner S. Abstract accepted for 16th Annual Conference on the Science of Dissemination and Implementation Science. December 10- 13th, 2023 in Arlington, VA.
  • The Landscape of Infections Caused by Rare Bacterial Pathogens” Authors: Reema Charles, MBBS, MS, Barbara Milani, Daniel Argaw Dagne, Bisma Ali, Heather Stone, MPH, Marco Schito, Raghavendra Tirupathi, MBBS, MD, and Nalini Oliver at IDWeek 2023 in Boston.
  • Landscape Analysis to Identify Effective Drug Repurposing Candidates for the Treatment of Implantation Mycoses: Comparison of World Health Organization Survey Treatment Data” Authors: Reema Charles, MBBS, MS, Barbara Milani, Daniel Argaw Dagne, Bisma Ali, Heather Stone, MPH, Marco Schito, Raghavendra Tirupathi, MBBS, MD, and Nalini Oliver at IDWeek 2023 in Boston
  • Case Reports on CURE ID, and The Lesser Known Treponemal Infections: A Review of Non-Syphilitic Cases”Authors: Ashima Gupta, MBBS, Saarthak Malhotra, MBBS, Aasa Deepika Kuditipudi, MBBS, Reema Charles, MBBS, MS, Tahsin Farid, MD MPH, Raghavendra Tirupathi, MBBS, MD, and Barath Prashanth Sivasubramanian, M.B.B.S at IDWeek 2023 in Boston.
  • From OMOP to CDISC SDTM: Successes, Challenges, and Future Opportunities of Using EHR Data for Drug Repurposing in COVID-19” Authors: Wesley Anderson, Ruth Kurtycz, Tahsin Farid, Shermarke Hassan, Kalynn Kennon, Pam Dasher, Danielle Boyce, Will Roddy, Smith F. Heavner at OHDSI Global Symposium, 2023 New Jersey.
  • Developing an End-to-End Data and Analytics Pipeline Using AWS Resources and Natural Language Processing to Support the Analysis of Repurposed Drugs” Authors: Wesley Anderson, Roopal Bhatnagar, Smith Heavner, Marco Schito, Shu Chin Ma, Klaus Romero, Jagdeep Podichetty at ACoP 14 in Maryland.
Communications FAQ Icon
  • Rare Disease Day Impact Story: “Drug Repurposing Provides Big Impact for Patients and social media posts on publications https://c-path.org/impact_story/drug-repurposing-provides-big-impact-for-patients/
  • The CDRC co-Chair, Dr. David Fajgenbaum, Keynote address is on C-Path’s YouTube channel and can be accessed here.
  • The CDRC Annual Meeting Q&A interviews are officially posted on C-path’s YouTube channel and can be accessed from the CDRC website.
  • Smith Heavner, PhD, RN’s podcast episode on AACN’s leadership podcast. Leading Research and Impacting Patient Outcomes (blubrry.com).
  • SCCM’s Critical Connections Newsmagazine features Smith Heavner on page 18, “REDISCOVER-ICU”. The article talks about utilizing data to study drug repurposing beyond Covid-19 Critical Connections Summer 2023 by SCCM – Flipsnack.
  • In Honor of #JulySarcomaAwarenessMonth, CDRC wrote an Impact Story titled “By Bringing Patients’ Voices to the Forefront, Sarcoma Advocates Illustrate Community’s Innovative Impact” surrounding two dedicated partners, Denise Reinke and Lisa De Young. By Bringing Patients’ Voices to the Forefront, Sarcoma Advocates Illustrate Community’s Innovative Impact | Critical Path Institute (c-path.org).
  • In this podcast episode, listen to Ms. Heather Stone, FDA’s health science policy analyst in the FDA’s Office of Medical Policy, and Dr. Marco Schito, Executive Director of the Critical Path Institute’s CURE Drug Repurposing Collaboratory (CDRC) discuss CURE ID and the exciting plans to expand the tool beyond infectious diseases. CURE ID can be found online at https://cure.ncats.io or it can be downloaded from the App or Play store as “CURE ID”. Listen to the podcast here: https://lnkd.in/gFrA2VFT
  • Completed a Clinical Scholars Program with 8 CURE ID Clinical Scholars, second round of Clinical Scholars will begin in January 2024.
  • Developed outreach materials, partnerships, and tools to engage patients for sarcoma projects that were IRB approved posted on the Patient Center.
Presentations Delivered at Conferences FAQ Icon
  • Smith Heavner attended and presented “Leveraging the SCCM Discovery VIRUS COVID-19 Registry to Evaluate Drug Repurposing Research Dataset” at SCCM Annual meeting in San Francisco, CA January 20-24, 2023. Also successfully identified 16 additional sites to implement the Edge Tool in EHRs for the project.
  • CDRC Annual Meeting. April 18th – 20th, 2023 in Washington, D.C. Presentations from the Annual Meeting can be found on the CDRC Website along with speaker bios, and a detailed agenda. CDRC |
  • Marco Schito presented “US and UK government responses to the challenges” at the CeBIL symposium Sustainable health innovation, grand challenges & the law June 14th- 15th, COPENHAGEN
  • Heather Stone spoke on “CURE ID: The Potential to Identify Treatments for Rare Disease Through Drug Repurposing” at the Rare & Orphan Disease Conference. September 11, 2023 Washington, D.C.
  • Marco Schito presented virtually on “Repurposing and better use of clinical data”. Organized by the Spanish regulatory agency AEMPS on the 27th of September in Madrid, Spain regarding the funding challenges in drug repurposing as part of the MERIT regulatory working group.
  • Heather Stone participated as a panelist in panel “The Potential Impact on Drug Repurposing” at the NORD Rare Disease & Orphan Products Breakthrough Summit, Washington, DC. October 15-17, 2023.
  • Smith Heavner, presented on “Collecting and Leveraging Real- World Data” at the. The Health Research Alliance (HRA) Members Meeting, in Chicago, IL. October 16-17, 2023..
  • Keyla Tumas presented “Real-world data for repurposed drugs to treat implantation mycoses” at the Symposium: Neglected Implantation Mycoses: getting out from under the skin. 21st INFOCUS annual meeting for The Latin American Forum of Fungal Infections in Clinical Practice. Nov 16, Iguazu Falls, Brazil.
Conferences Attended FAQ Icon
  • RASNet (RASopathies Network) conference July 21-23, 2023, Denver, CO. Aligned with patient advocates, met rare disease clinicians, researchers, patients, and industry members.
  • Sarcoma Alliance for Research through Collaboration (SARC) Semi-annual meeting. June 2nd, 2023, Chicago, IL Leading into the annual meeting of the American Society of Clinical Oncology (ASCO).
  • ASCO June 2- 6, 2023, Chicago, IL- a unique and unparalleled opportunity to connect with one of the largest, most diverse audiences in global cancer care.
  • Drug Information Association (DIA) 2023 Global Annual Meeting June 25-29, 2023, Boston, MA. The DIA 2023 Global Annual Meeting invited industry, regulatory government, academics, and patients to network, problem-solve, and discuss global and local challenges facing the life sciences community.
  • Critical Care Datathon August 5th and 6th, New York. The Society of Critical Care Medicine’s (SCCM) Datathon is a collaborative event connecting clinicians with data scientists to develop pragmatic data-driven models applicable to the care of critically ill patients using de-identified critical care electronic health record datasets.
  • Dysautonomia International (DI) Conference July 14th and 15th in Washington, D.C. Connect with clinicians, patients, and care partners in the Long COVID community about CDRC and CURE ID work aimed at collecting data on use of drug repurposing in managing symptoms.
  • Data-Driven Drug Repurposing Workshop: Unlocking disease biology and advancing systematic approaches, October 2-4, Redwood City, CA. Hosted by the Chan Zuckerberg Initiative, this workshop brought key actors who are advancing data-driven approaches for drug repurposing.\
  • IDWeek October 11 -15, 2023 in Boston, MA. ID Week is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP).
  • ASTMH on October 18 – 22, 2023. American Society of Tropical Medicine and Hygiene (ASTMH) Annual Meeting was attended in Chicago, IL.
  • CTOS, The Connective Tissue Oncology Society Annual Meeting, from November 1st – 4th in Dublin, Ireland. Met with patient advocates, met oncology clinicians, researchers, patients, and industry members.
  • the BIONJ Patient Advocacy Summit on November 16th in Lawrenceville, NJ. This one-day summit was to educate, engage, and empower the patient advocacy community.

Roadmap

* The CURE ID mobile app is an FDA-NCATS collaboration to build an internet-based repository that allows the global clinical community to report novel uses of existing drugs to treat diseases through a website, a smartphone, or other mobile device. The repository captures the clinical outcomes when drugs are used for new indications, in new populations, in new doses, or in new combinations.

Stage 0 – Prioritize diseases FAQ Icon

The CURE Coordinating Committees will begin by initiating a comprehensive landscape analysis for diseases where drug repurposing is being utilized for patient treatment of diseases with high unmet medical need. The Collaboratory will finalize a list to identify disease and treatment combinations where FDA approved treatments do not exist or are inadequate. This may include categories encompassing additional infectious diseases (e.g., emerging diseases, drug resistant infections and neglected diseases), rare diseases (e.g., non-infectious, oncology) and diseases in special populations (pregnant women, neonates, pediatrics). Once completed, a set of pre-defined criteria will be finalized that will allow the list to be prioritized. Examples of criteria may be the availability of drug treatment data or the identification of an active and collaborative disease research and advocacy community. In addition, the group will be charged with defining the key questions that the analytics team will be requested to address, including any thresholds identified based on quantitative analysis of values captured. This will allow the application of predefined criteria to identify analysis output that could be flagged for the CURE Drug Repurposing Collaboratory to review. Finally, the CURE Drug Repurposing Collaboratory stakeholders will draft standard operating procedures to define parameters necessary to select a drug to go through a defined repurposing effort based on existing data, level of evidence (e.g., existing guidelines), as well as the legislative and regulatory climate.

Stage 1 – Hypothesis generation using real-world data FAQ Icon

There are many diseases and conditions where regulatory approved therapies are either absent or unsatisfactory and prescribers are forced to repurpose existing drugs for patients with difficult-to-treat diseases. This produces two significant challenges facing all communities relying on re-purposed drugs:

  • Many approved drugs have therapeutic uses that are never fully identified, investigated, or developed.
  • Many off-label drugs lack clinical data to support safe and effective for the alternative indication.

 

Initially, the failure by the pharmaceutical industry to invest in and pursue potential new uses is an innovation problem: there may be perceived barriers and firms may lack the necessary incentives to research and develop new uses of existing drugs approved for other indications, especially after they become generic. In addition, efforts have been initiated to capture a small number of deidentified data elements from data that is currently being captured (see data tools below) to ultimately populate the publicly accessible CURE ID data platform to generate hypothesis regarding the efficacy of repurposed drugs.

The problem of off-label use is one of both safety and efficacy: off-label uses are not supported by the same level of evidence as approved uses and are used at greater risk, both physically and monetarily, to the patient. Under these circumstances, physicians work with limited information to treat patients to the best of their abilities. However, as they do, the systematic collection of this anecdotal information could be utilized to inform others in similar situations.

Data capture tools:

  • Capturing treatment experiences from providers
    • CURE ID is an FDA/NCATS developed website and mobile app designed to capture case reports directly from healthcare providers worldwide. In these reports, the healthcare providers (clinicians, nurses, nurse practitioners, pharmacists…) describe how they are using existing drugs in new ways (i.e., drug repurposing) to treat diseases lacking adequate approved therapies. Reports can be generated directly in the app either as a quick submit feature with a minimum of answering 8 questions or by a full case report containing up to 40 data variables. Once submitted, the case report is added to the CURE ID data platform and reviewed by a CURE ID data curator who can engage with the submitter to address any quality concerns.

 

  • Capturing treatment experiences from the published literature
    • In addition to the provider submitted case reports, CURE ID and CDRC perform periodic literature reviews to identify published case reports that are transcribed into the app and referenced. We encourage authors to submit these cases to CURE ID directly. Alternatively, authors can contact us (email) directly when they publish a disease case report so that it can be included in the platform.

 

  • Capturing real-world data from electronic health records and disease registries
    • In addition, CURE ID is interested to enable automated and manual data collection from electronic health records (EHRs) and registries into the CURE ID case report form (CRF). The pilot for use of this technology will be for COVID-19. While COVID-19 now has an antiviral (Remdesivir) and the immune modulator Olumiant (baricitinib) as approved treatment options and good clinical trial data to support the use of dexamethasone, these therapies benefit subsets of patients infected with SARS-CoV-2, but there remains a need to identify additional safe and effective treatments. As of December 2021, Ritonavir-boosted nirmatrelvir (Paxlovid) and molnupiravir have received Emergency Use Authorizations from the FDA for the treatment of COVID-19.

 

CURE ID has secured a $8.2 million grant through the HHS Assistant Secretary for Planning and Evaluation (ASPE) Patient-Centered Outcomes Research Trust Fund (PCORTF) to automate the extraction of a limited subset of deidentified data from sites around the world for the purpose of the following:

  1. Expansion of the open-access CURE ID platform (https://cure.ncats.io or “CURE ID” app) to include EHR/registry data.
  2. Development and provision of a tool that will automate the extraction of data elements from EHRs and registries into CURE ID, leveraging consensus-based data standards and terminologies, where appropriate.
  3. Procurement and synthesis of data for all COVID-19 positive patients (with future expansion capabilities to other diseases) from at least 300 sites in the U.S. and around the world.

This infrastructure will be built for COVID-19 but will be designed in a sustainable manner so that it can be promptly deployed for future outbreaks of existing and emerging infectious diseases as well as leverage the infrastructure for diseases in the interpandemic period. This will provide real-time access to the global clinical experience of repurposing drugs when there is an immediate need to identify potential existing treatments in the absence of novel drug development.

The expanded CURE ID platform will include hundreds of thousands of cases, making it substantially larger than at present, given that cases are entered manually. This large collection of cases will enable the clinical, research and regulatory communities to identify signals of potentially safe and effective COVID-19 treatments from amongst the armamentarium of existing FDA approved therapeutics. These signals will enable the generation of robust clinical hypotheses and by doing so, may accelerate the identification and development of effective treatments.

 

Stage 2 – Confirming hypothesis in clinical trials FAQ Icon

While it has been clear for decades that the systems for clinical research in the US are broken, the COVID-19 pandemic has laid bare the limitations of these systems for answering the most important research questions to guide clinical practice in a timely, coordinated and efficient manner. A different approach is needed that seeks to integrate clinical research into clinical practice and make it easy to prioritize and rapidly answer the most pressing clinical questions.

CDRC’s vision for such an approach includes the development of a standing infrastructure for conducting research embedded within clinical practice in three different care settings. It proposes to take advantage of the scientific rigor afforded by randomization of trial participants to different treatment arms, while making the conduct of the trial so much less burdensome to healthcare providers, that it is possible for them to participate with little added effort.

The goal would be to conduct a series of trials under a common randomized clinical trial platform structure using repurposed and novel medications to treat COVID-19 and other serious illnesses.

The initiative will encompass a series of three separate but linked platform trial infrastructures:

  1. An acute outpatient trial infrastructure, based on a combination of telemedicine/virtual and site-based interventions

 

2. An acute inpatient trial infrastructure, based on embedding the trial within clinical practice through use of electronic health record (EHR) systems

3. A chronic outpatient trial infrastructure for long-term follow-up of chronic conditions (e.g., post-acute sequelae of COVID-19, post-ICU syndrome, etc.), leveraging telemedicine, drugs delivered by mail and an emphasis on electronic patient-reported outcomes

The goal is to design these trial platforms to be flexible and adaptable enough to be used both in the context of future outbreaks, as well as for study of diseases and health conditions in non-emergency settings.

The trials would all use master protocols with adaptive designs to enable the efficient and sustainable, but scientifically rigorous, evaluation of treatments, with particular emphasis on diseases with high unmet medical needs (that are not well-served by commercial interests) and the use of drugs that are already approved by the FDA or another stringent regulatory authority. They would utilize adaptive randomization so that treatments could be stopped due to futility and other drugs could be added to enable study of additional treatment options.

Stages 3 & 4 – Informing clinical practice and regulatory goals FAQ Icon

With nearly a third of all known diseases having approved drugs, a significant proportion of diseases have limited or no approved treatment options. One reason for the lack of treatment is that many of these diseases are not determined to be financially feasible for for-profit pharmaceutical companies to pursue. Diseases which still lack a medical treatment to slow, stop, or reverse their course result in mortality, but also result in distress, morbidity and reduced quality of life. As a result, doctors often prescribe drugs to patients off-label using their professional judgment or follow treatment guidelines which may lack sufficient safety or efficacy data. The current regulatory relabeling system works well for drugs on patent but the number of drugs that companies pursue supplements to existing labels sharply declines several years before losing patent exclusivity. Once a drug has become a generic, there are no incentives for manufacturers to pursue label supplements and the current system prevents others to pursue label updates even if they have relevant clinical data. In addition to financial incentives there are a host of other challenges that must be debated and discussed including reimbursement, patent law, existing legislative tools and new regulatory pathways.

To address these issues, a stakeholder group has been convened under the auspices of CDRC to gather stakeholder input to describe and identify the barriers to supplemental drug labels in the case of repurposed drugs. The real-world data gathered through the CURE ID app can be used to inform the design of clinical trials, evaluate the effectiveness and safety of a marketed therapy intended for repurposing, or support treatment guideline development. In partnership with regulators and in collaboration with other stakeholders, a strategy will be defined to promote a regulatory pathway for repurposed drugs through supplemental drug labeling that benefits patients and public health needs.

For questions or additional information about participating in CURE ID and the CDRC, please email CDRC@c-path.org.

Patient Center

CURE ID is expanding! We’re making it possible for patients and their care partners to share their thoughts on treatments. Right now, doctors share information, but we want to hear from you too. Your stories can help us understand how well medicines work, even the things we can’t see in tests or pictures.

Mpox FAQ Icon

Obtaining and Using TPOXX Tecovirimat for Treatment of Monkeypox

An overview of how to obtain and use Tecovirimat (TPOXX) during the 2022 monkeypox public health emergency under Expanded Access Investigation New Drug (EA-IND). Dr. Raghav Tirupathi, an infectious diseases expert and Clinical Director for Infectious Diseases at CDRC, shares his experience and insight.

 

Collaborators

Sarcoma FAQ Icon


Videos


Sarcoma Collaborators

 

Download the CURE ID app at (https://cure.ncats.io/) and begin submitting cases today. It takes a couple of minutes and every case report counts.

For questions or additional information about participating in CURE ID and the CDRC, please email cdrc@c-path.org.

FAQs

CDRC and CURE ID FAQs

What is CDRC? FAQ Icon

The Cure Drug Repurposing Collaboratory (CDRC) will provide a forum for the exchange of clinical practice data to inform potential new uses of existing drugs for areas of high unmet medical need, advancing research in these areas. The Collaboratory will also create a network connecting major treatment centers, academic institutions and researchers, private practitioners, government facilities and health care professionals around the world.

Who is involved in CDRC? FAQ Icon

CDRC is a public-private partnership initiated in June 2020 by C-Path and the U.S. Food and Drug Administration (FDA) in partnership with the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH). The collaboration CDRC is connected and working with, the FDA-NCATS CURE ID* platform.

What disease data does or will CDRC include? FAQ Icon

The initiative includes emerging/reemerging diseases, including COVID-19, anti-microbial drug resistant infections, neglected infectious diseases as well as rare oncology diseases where there are limited treatment options. The Collaboratory is strongly interested in capturing data from diverse populations including pediatric and pregnant women.

What is CURE ID? FAQ Icon

CURE ID is an internet-based repository that lets the clinical community report novel uses of existing drugs for difficult-to-treat infectious diseases through a website, a smartphone or other mobile device. The platform enables the crowdsourcing of medical information from health care providers to facilitate the development of new treatments for neglected diseases.

Who is involved in CURE ID? FAQ Icon

CURE ID is a collaboration between the FDA and the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH). FDA and NIH are also collaborating with the World Health Organization and the Infectious Disease Society of America to assess the global utility of the CURE ID.

Is CDRC and CURE ID part of a clinical study? FAQ Icon

No, this is data collected as part of the treatment that is done at the physician’s discretion during routine clinical care. The data based on this clinical care is simply captured after the fact and shared in a completely de-identified case report form.

How does the CDRC/CURE ID effort compare to the large efforts already underway (and launched) by NCATS, i.e., the N3C? FAQ Icon

The methods are meant to be seen as complimentary and part of the broader real-world evidence (RWE) initiatives at FDA and NIH. Some of the key differences that set this apart from N3C, the Evidence Accelerator, and others is that: 1) the CURE ID platform is global and would seek data from outside the US, in addition to national data sources; 2) data will be combined from several different types of sources – EHRs, but also registries, clinician-submitted cases, and cases extracted from the published literature; 3) the data would be completely accessible at the de-identified patient level to any health care professional or researcher, without a data use agreement, making it much more accessible; and 4) the information collected is quite high-level and uncomplicated in the form of a completely de-identified case report form. Similarities and differences between N3C and CURE ID:

Issue N3C CURE ID
Access by non-institutional members Restricted access: only allows access to synthetic data for non-institutionally affiliated users Open access: allows access to complete (real) de-identified data set for all users
Data use agreements Required to access data Not required to access data
Purpose of data collection COVID-specific to answer a wide range of potential research questions requiring complex and detailed information with which to conduct analyses Not disease specific to answer limited range of high level and priority treatment questions; limited detail required; purpose is for “rough cut” hypothesis generation
Scope of content EHRs only Combine data from EHRs, smaller registries, clinician-submitted case reports, and data extracted from the published literature
Geography of data collection US (domestic) only Global
Training  Requires 60-90 minutes of training Does not require any training
Data exchange Shares actual EHR data using one of several common data models Data is translated from the EHRs to the de-identified CURE ID case report form at the institutional site, facilitating ease of information sharing
Data location All access and analysis takes place within the N3C Data Enclave Data access is available on the CURE ID website/app, but the entire dataset can also be downloaded to facilitate research
Why should healthcare providers use the CURE ID app? What’s in it for them? FAQ Icon

By entering case studies into the app, health care providers have the opportunity to help uncover new uses for approved drugs and help people in need get life-saving treatments. Situations with disappointing results are equally important to enter, so that others can learn from those experiences and not replicate that treatment protocol. Health care providers may have data already. They are invited to join the CDRC disease working groups to help identify specific questions that they would like answered. Collected data metrics can be made available to this community and updated over time. People who contribute to the CURE ID app may also get recognition in the form of a certificate from FDA and NIH.

Can health care providers access the data through the app? FAQ Icon

Even if health care providers don’t have an experience to share, they can also use the app to search for novel uses of drugs and gain valuable insight, which can inform their future practice and clinical endeavors. People can also use the Discussion Forum to connect with others and share similar experiences and questions.

What does the timing look like for all these activities?  FAQ Icon

This is an ongoing effort initiated in June 2020 and will be a multi-year effort. Please contact CDRC, CDRC@c-path.org, for further information.

What are the next steps for CURE ID and CDRC? FAQ Icon

CURE ID continues to expand the number of clinicians involved, specific diseases it focuses on and methods of data capture (such as automating collection from EHRs and registries). The long-term goal is for the public-private partnership (CDRC) to oversee and coordinate collaboration between stakeholders.The mission of the group is to generate real-world evidence regarding the safety and effectiveness of the use of off-label drugs with high public health impact and low commercial viability/interest for drug repurposing.

How can I learn more? FAQ Icon

Visit the CURE ID website here. You can download the App from the App or Play Store by searching for “CURE ID.” A videocast of the Repurposing Generics workshop at which CURE ID was launched is available here. More information on the CURE ID platform is available on the FDA website here. To join the CURE Drug Repurposing Collaboratory, please send inquiries to CDRC@c-path.org.

View a demonstration and walk-through of the app and the entry of a case report here — Data extraction example.

What are the functionalities of the CURE ID app? FAQ Icon

To enter a case the user must a minimum of seven required questions. Once they do so they have the option to either “Quick Submit” or they can continue and answer any of the remaining 20 optional questions in the complete submission. They also have the option to save their case without submitting and return to it at a later date, or to submit it and update it later by going in and editing the case. If they wish, they are provided an option to anonymize a particular submission so that their name will not be visibly associated with the case or discussion.To enter a discussion the user can either specify a particular disease or choose “disease not specified.” They will then enter a free text title and body of the discussion post, which has a limit of 4,096 characters.
In addition, users can comment on case reports or discussion posts submitted by other users.

Case reports and discussions are uploaded in real-time and reviewed for quality and appropriateness within 12-24 hours by CURE ID moderators. Moderators may make small adjustments (i.e., remove personally identifiable information (hat is accidentally included) or seek additional information or clarifications from the report’s author. They will comment on the post with any changes that are made. If a report is deemed to be inappropriate or otherwise requiring deletion, it will be reviewed by a second moderator. If the second moderator concurs, the post may be removed, and the report’s author will be emailed with an explanation of the decision.

What kind of data is collected? FAQ Icon

If a user enters a case report the data is all entered in a completely de-identified fashion so as not to trigger any patient privacy concerns. Users should be certain that they don’t include any public health information (PHI) in the free-text entry fields. Because the data was collected for the purpose of clinical care and is shared in a deidentified manner, it is not considered research and thus, patient consent is not required.

Who has access to the data on CURE ID? FAQ Icon

Interested users who are licensed health care providers complete a very brief registration where they set up an email and password and state their medical qualifications. Once they have registered, a user can now explore the case reports, discussion posts, and clinical trials in the platform; they can submit their own case report or discussion post; or they can view the Newsfeed.Those who can currently enter data are clinicians, physicians, nurses, nurse practitioners, etc.
If you are not a health professional but can contribute to discussions (i.e., as a veterinarian, epidemiologist, infectious disease researcher, etc.) please contact CURE ID or CDRC to find out how you can download and use the app.

The platform is only open to licensed health care professionals so that clinicians will feel comfortable sharing their treatment experiences – both positive and negative – in a safe, clinical community. Registered users have access to all of the data and can contact the help desk for a download of all of the data in the database if they wish to conduct their own research with it.

The data in CURE ID will be digested by CDRC through a dedicated bioinformatic pipeline and the insights generated will be broadly shared with the public via CURE ID once the results have been reviewed and vetted within the Collaboratory.

What does “shared publicly” actually mean? FAQ Icon

Shared publicly means that once your data is transformed into the CURE ID format (and it is certain that any PII has been removed), the case report with patient-level data is openly displayed to users who have signed up to use the platform. The information is in addition to the other sources of case reports (electronic health records, registries, literature, etc.).

Would the deidentified data itself be shared? FAQ Icon

Yes, the deidentified data as translated into the case report form would be displayed in CURE ID and thus shared with other app users. One can also request to download the data. The intent here is to share what may be working but also what may not be working with other physicians who are desperately looking for ways in which to treat patients in the absence of data.

Are you also collecting adverse event data? FAQ Icon

Yes, we are collecting AEs and have set up a system to automatically share and upload any case reports that contain AEs with the FDA Medwatch AE reporting platform.

What do you mean by ‘combining the data,’ wouldn’t this make it easier to reidentify the individuals? FAQ Icon

No, not at all. The data won’t be combined with data on the same patients or link them, the data will be combined with other sources of case reports, such as registries and clinician-submitted cases to calculate an aggregate of patients treated with the same drug or drug regimens.

What kind of vetting or data use agreement would users need to agree to when using CURE ID? What type of enforcement would there be? FAQ Icon

Users do not have to sign a data use agreement of any kind. (see case report form for the snapshot of data elements being collected) during the course of routine clinical care (and therefore not human subjects research), ensuring that the data transferred is HIPAA compliant and completely de-identified per Safe Harbor requirements, the data can be transferred without a data use agreement. Typically, the individual or institution would translate the patient’s record or EHR/registry data into the CURE ID case report form at their site, before sending the de-identified case report form to the CURE ID platform. The data is then made openly accessible to all qualified clinicians and researchers who register on the site.

Is there a data use agreement associated with CDRC? FAQ Icon

At the present time, we are asking contributors to share data broadly which negates the rationale to implement a data use agreement since their data would be shared publicly through the CURE ID platform without restrictions.

Are we talking about clinical data here? What format: OMOP? FAQ Icon

Yes, it’s clinical data, but high level – for example: was the patient diagnosed with COVID-19 by PCR? After said diagnosis, what drugs were given to the patient? What was the outcome of treatment (did the patient die, admitted to ICU, discharged from ICU to floor, discharged from hospital, etc. – translated to the options of “patient improved,” “patient deteriorated,” etc.). The CDRC and CURE ID team can assist in creating a translation infrastructure which would then automate the transfer of information from your records to the CURE ID Case Report Form, and then we would upload the case reports and they would be reviewed by clinicians on our staff for quality and accuracy.

It would appear that CURE ID would be collecting care report forms, correct? Not collecting raw medical record data? FAQ Icon

Historically, yes, we have collected standardized CURE ID case report forms directly from clinicians and other health care providers using the electronic platform we developed. We have also used this same case report form as an extraction tool to review and enter published case reports into the database. View this as a transformation of your data to populate the simplified CURE ID case report form at your site. An automated system could be used to transform the EHR data at your institutional site into the CURE ID case report form, which would then be sent to NCATS for inclusion on the server.

Who should best fill out the report form? Is the idea to have clinical research coordinators at each of the hospitals or academic medical centers to participate? FAQ Icon

The ideal scenario would be to use automation to extract the information from the EHRs into the CURE ID template, using a series of rules and translations. However, we realize that that may not be possible. If that is the case, we would be happy to explore using data entry specialists, hired by your . It is also possible, that CURE ID could use a combination of the two – where some data is able to be automatically extracted from the EHRs into CURE ID, and other information requires a human.The development of AI tools will help to translate the data into the case report form, but have human curators review a prespecified portion to ensure that reports are being transformed correctly and that it is of high quality. Some tools have already been developed but will need to be refined to address this specific issue. Collaborators from USG resources and the informatics research community can be accessed to help address the challenges.

Should health care providers only enter experiences with off-(generic) drugs when used in a new way in the CURE ID app? FAQ Icon

No, health care providers are able to enter cases that utilize generic and/or branded drug products. It should be noted, however, that submitting a case report to CURE ID is not a substitute for reporting required under public health or legal requirements. There has been an emphasis on off-patent drugs because they are cheaper to purchase and, in theory, could be easier to access. If a drug, disease, or organism you are interested in reporting a case on is not in the drop-down menu of the app, it can be added by typing the text and then hitting enter.

What is an off-patent drug and what’s FDA’s role in this space? What are some inherent challenges with repurposing off-patent drugs? FAQ Icon

Off-patent drugs are regulatory-approved medical products that no longer have patent protection. Repurposing approved drugs for new clinical indications can potentially offer an efficient drug-development pathway for treatments of diseases and conditions that have few or no therapeutic options. Advantages of using off-patent drugs in this manner includes cost savings, in that such drugs are often available from a variety of manufacturers. In this same context, however, smaller profit margins may exist for companies that repurpose drugs in the same dosage and formulation for new indications, providing less incentive for repurposing.

Will you be looking at the treatment of the patient as a whole? FAQ Icon

No, the focus is on the treatment of this particular infection.

Data/Data Agreement FAQs

What are the functionalities of the CURE ID app? FAQ Icon

To enter a case the user must a minimum of seven required questions. Once they do so they have the option to either “Quick Submit” or they can continue and answer any of the remaining 20 optional questions in the complete submission. They also have the option to save their case without submitting and return to it at a later date, or to submit it and update it later by going in and editing the case. If they wish, they are provided an option to anonymize a particular submission so that their name will not be visibly associated with the case or discussion. To enter a discussion the user can either specify a particular disease or choose “disease not specified.” They will then enter a free text title and body of the discussion post, which has a limit of 4,096 characters.

In addition, users can comment on case reports or discussion posts submitted by other users.

Case reports and discussions are uploaded in real-time and reviewed for quality and appropriateness within 12-24 hours by CURE ID moderators. Moderators may make small adjustments (i.e., remove personally identifiable information that is accidentally included) or seek additional information or clarifications from the report’s author. They will comment on the post with any changes that are made. If a report is deemed to be inappropriate or otherwise requiring deletion, it will be reviewed by a second moderator. If the second moderator concurs, the post may be removed, and the report’s author will be emailed with an explanation of the decision.

What kind of data is collected? FAQ Icon

If a user enters a case report the data is all entered in a completely de-identified fashion so as not to trigger any patient privacy concerns. Users should be certain that they don’t include any public health information (PHI) in the free-text entry fields. Because the data was collected for the purpose of clinical care and is shared in a deidentified manner, it is not considered research and thus, patient consent is not required.

Who has access to the data on CURE ID? FAQ Icon

Interested users who are licensed health care providers complete a very brief registration where they set up an email and password and state their medical qualifications. Once they have registered, a user can now explore the case reports, discussion posts, and clinical trials in the platform; they can submit their own case report or discussion post; or they can view the Newsfeed. Those who can currently enter data are clinicians, physicians, nurses, nurse practitioners, etc.

If you are not a health professional but can contribute to discussions (i.e., as a veterinarian, epidemiologist, infectious disease researcher, etc.) please contact CURE ID or CDRC to find out how you can download and use the app.

The platform is only open to licensed health care professionals so that clinicians will feel comfortable sharing their treatment experiences – both positive and negative – in a safe, clinical community. Registered users have access to all of the data and can contact the help desk for a download of all of the data in the database if they wish to conduct their own research with it.

The data in CURE ID will be digested by CDRC through a dedicated bioinformatic pipeline and the insights generated will be broadly shared with the public via CURE ID once the results have been reviewed and vetted within the Collaboratory.

What does “shared publicly” actually mean? FAQ Icon

Shared publicly means that once your data is transformed into the CURE ID format (and it is certain that any PII has been removed), the case report with patient-level data is openly displayed to users who have signed up to use the platform. The information is in addition to the other sources of case reports (electronic health records, registries, literature, etc.).

Would the deidentified data itself be shared? FAQ Icon

Yes, the deidentified data as translated into the case report form would be displayed in CURE ID and thus shared with other app users. One can also request to download the data. The intent here is to share what may be working but also what may not be working with other physicians who are desperately looking for ways in which to treat patients in the absence of data.

Are you also collecting adverse event data? FAQ Icon

Yes, we are collecting AEs and have set up a system to automatically share and upload any case reports that contain AEs with the FDA Medwatch AE reporting platform.

What do you mean by ‘combining the data,’ wouldn’t this make it easier to reidentify the individuals? FAQ Icon

No, not at all. The data won’t be combined with data on the same patients or link them, the data will be combined with other sources of case reports, such as registries and clinician-submitted cases to calculate an aggregate of patients treated with the same drug or drug regimens.

What kind of vetting or data use agreement would users need to agree to when using CURE ID? What type of enforcement would there be? FAQ Icon

Users do not have to sign a data use agreement of any kind (see: case report form for the snapshot of data elements being collected) during the course of routine clinical care and therefore not human subjects research), ensuring that the data transferred is HIPAA compliant and completely de-identified per Safe Harbor requirements, the data can be transferred without a data use agreement. Typically, the individual or institution would translate the patient’s record or EHR/registry data into the CURE ID case report form at their site, before sending the de-identified case report form to the CURE ID platform. The data is then made openly accessible to all qualified clinicians and researchers who register on the site.

Is there a data use agreement associated with CDRC? FAQ Icon

At the present time, we are asking contributors to share data broadly which negates the rationale to implement a data use agreement since their data would be shared publicly through the CURE ID platform without restrictions.

Are we talking about clinical data here? What format: OMOP? FAQ Icon

Yes, it’s clinical data, but high level – for example: was the patient diagnosed with COVID-19 by PCR? After said diagnosis, what drugs were given to the patient? What was the outcome of treatment (did the patient die, admitted to ICU, discharged from ICU to floor, discharged from hospital, etc. – translated to the options of “patient improved,” “patient deteriorated,” etc.). The CDRC and CURE ID team can assist in creating a translation infrastructure which would then automate the transfer of information from your records to the CURE ID Case Report Form, and then we would upload the case reports and they would be reviewed by clinicians on our staff for quality and accuracy.

It would appear that CURE ID would be collecting care report forms, correct? Not collecting raw medical record data? FAQ Icon

Historically, yes, we have collected standardized CURE ID case report forms directly from clinicians and other health care providers using the electronic platform we developed. We have also used this same case report form as an extraction tool to review and enter published case reports into the database. View this as a transformation of your data to populate the simplified CURE ID case report form at your site. An automated system could be used to transform the EHR data at your institutional site into the CURE ID case report form, which would then be sent to NCATS for inclusion on the server.

Who should best fill out the report form? Is the idea to have clinical research coordinators at each of the hospitals or academic medical centers to participate? FAQ Icon

The ideal scenario would be to use automation to extract the information from the EHRs into the CURE ID template, using a series of rules and translations. However, we realize that that may not be possible. If that is the case, we would be happy to explore using data entry specialists, hired by your . It is also possible, that CURE ID could use a combination of the two – where some data is able to be automatically extracted from the EHRs into CURE ID, and other information requires a human.The development of AI tools will help to translate the data into the case report form, but have human curators review a prespecified portion to ensure that reports are being transformed correctly and that it is of high quality. Some tools have already been developed but will need to be refined to address this specific issue. Collaborators from USG resources and the informatics research community can be accessed to help address the challenges.

Should health care providers only enter experiences with off-(generic) drugs when used in a new way in the CURE ID app? FAQ Icon

No, health care providers are able to enter cases that utilize generic and/or branded drug products. It should be noted, however, that submitting a case report to CURE ID is not a substitute for reporting required under public health or legal requirements. There has been an emphasis on off-patent drugs because they are cheaper to purchase and, in theory, could be easier to access. If a drug, disease, or organism you are interested in reporting a case on is not in the drop-down menu of the app, it can be added by typing the text and then hitting enter.

What is an off-patent drug and what’s FDA’s role in this space? What are some inherent challenges with repurposing off-patent drugs? FAQ Icon

Off-patent drugs are regulatory-approved medical products that no longer have patent protection. Repurposing approved drugs for new clinical indications can potentially offer an efficient drug-development pathway for treatments of diseases and conditions that have few or no therapeutic options. Advantages of using off-patent drugs in this manner includes cost savings, in that such drugs are often available from a variety of manufacturers. In this same context, however, smaller profit margins may exist for companies that repurpose drugs in the same dosage and formulation for new indications, providing less incentive for repurposing.

Will you be looking at the treatment of the patient as a whole? FAQ Icon

No, the focus is on the treatment of this particular infection.

EHR/Forms FAQs

It would appear that CURE ID would be collecting care report forms, correct? Not collecting raw medical record data? FAQ Icon

Historically, yes, we have collected standardized CURE ID case report forms directly from clinicians and other health care providers using the electronic platform we developed. We have also used this same case report form as an extraction tool to review and enter published case reports into the database. View this as a transformation of your data to populate the simplified CURE ID case report form at your site. An automated system could be used to transform the EHR data at your institutional site into the CURE ID case report form, which would then be sent to NCATS for inclusion on the server.

Who should best fill out the report form? Is the idea to have clinical research coordinators at each of the hospitals or academic medical centers to participate? FAQ Icon

The ideal scenario would be to use automation to extract the information from the EHRs into the CURE ID template, using a series of rules and translations. However, we realize that that may not be possible. If that is the case, we would be happy to explore using data entry specialists. It is also possible, that CURE ID could use a combination of the two – where some data is able to be automatically extracted from the EHRs into CURE ID, and other information requires a human. The development of AI tools will help to translate the data into the case report form, but have human curators review a prespecified portion to ensure that reports are being transformed correctly and that it is of high quality. Some tools have already been developed but will need to be refined to address this specific issue. Collaborators from USG resources and the informatics research community can be accessed to help address the challenges.

Should health care providers only enter experiences with off-(generic) drugs when used in a new way in the CURE ID app? FAQ Icon

No, health care providers are able to enter cases that utilize generic and/or branded drug products. It should be noted, however, that submitting a case report to CURE ID is not a substitute for reporting required under public health or legal requirements. There has been an emphasis on off-patent drugs because they are cheaper to purchase and, in theory, could be easier to access. If a drug, disease, or organism you are interested in reporting a case on is not in the drop-down menu of the app, it can be added by typing the text and then hitting enter.

What is an off-patent drug and what’s FDA’s role in this space? What are some inherent challenges with repurposing off-patent drugs? FAQ Icon

Off-patent drugs are regulatory-approved medical products that no longer have patent protection. Repurposing approved drugs for new clinical indications can potentially offer an efficient drug-development pathway for treatments of diseases and conditions that have few or no therapeutic options. Advantages of using off-patent drugs in this manner includes cost savings, in that such drugs are often available from a variety of manufacturers. In this same context, however, smaller profit margins may exist for companies that repurpose drugs in the same dosage and formulation for new indications, providing less incentive for repurposing.

Will you be looking at the treatment of the patient as a whole? FAQ Icon

No, the focus is on the treatment of this particular infection.

For additional questions, please contact, CDRC@c-path.org.

Team

CDRC 2023

Marco Schito, PhD,
Executive Director, CDRC

Smith (Smitty) Heavner, PhD,
Senior Scientific Director, CDRC

Jagdeep (JD) Podichetty, PhD,
Director, Predictive Analytics

Keith Scollick,
Cloud Platform Engineer

Chandler Birch, MS,
Senior Project Manager, CDRC

Kitty Bogy,
Senior Project Coordinator, CDRC

Pamela Dasher,
Senior Project Manager, CDRC

Stacey Coe, MS, CCRP
Senior Clinical Research Coordinator, CDRC

Claire Bassetti, MPH,
Communications and Patient Engagement Manager, CDRC

Wes Anderson, PhD
Quantitative Medicine Scientist

Interns

Juliette Cnockaert

Dr. Ashima Gupta

For more information on the CURE Drug Repurposing Collaboratory, please email us at cdrc@c-path.org.

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