TARGET-LD and CQC Registry Site Application
Overview Information
Call for Applications to Participate: TARGET-LD: An Observational Study with Chronic Liver Disease
Call for Applications Cycle: Cycle 1, 2025
Supporting Organizations: AASLD and Target RWE
Announcement Type: New
Purpose: The purpose of this application announcement is to solicit applications for clinical sites to participate in the observational TARGET-LD study to broadly study outcomes for patients with chronic liver disease (CLD) and cirrhosis. TARGET-LD was developed to bring together a consortium of investigators to build a large real-world database to evaluate the natural history, care, and health outcomes related to the management of chronic liver disease of diverse etiologies and cirrhosis. The study is also designed to expand the AASLD Cirrhosis Quality Collaborative (CQC) and will establish learning health networks focused on quality of care for patients with CLD/ cirrhosis.
Funding: Selected sites enter into contract with the study sponsor, Target RWE, which provides support for the technical work to develop and maintain the study of data transfers, PI and research staff, and patient enrollment into the Engaged Cohort for PROs and biospecimens. Participating sites receive curated individual site data and can access the study database to participate in the broader research aimsof the protocol for data analysis and publication.
Contracts are negotiated with each site.
A budget cap will be set with each funding cycle.
Anticipated Number of Awards: AASLD and Target RWE intend to select at least 2 meritorious sites annually
Key Dates
Application Open: March 17, 2025
Application Due Date: April 15, 2025 (5:00 pm local time)
Application Review Date: Review will be conducted immediately upon receipt of applications and run through May 16
Finalist Pre-Notifications with Tech Diligence/ Org Support Process: May 27-June 20, 2025
Final Decisions: Acceptance notifications will be sent by July 18, 2025.
Study start up activities initiated at site beginning late July 2025
Application Instructions
Application Content:
Applicants must complete the application questionnaire and agree to the start up timeline expectations. Only one applicant per organization may submit.
Eligibility Information
Eligible Applicants:
Investigators from organization, both academic (teaching organizations/facilities) and community (non-teaching organizations/facilities) practices, based in the U.S. and providing care to patients with chronic liver diseases.
Applicants are expected to complete study start up, including test data transfer within 6 months of receiving start-up package.
This requires a wholly engaged Pl to ensure:
- Research team is clear this is a priority and must happen- when a roadblock presents, the team immediately engages their PI
- The team propels IRB submissions, budget negotiations, and contracting- tracking and driving progress with necessary organizational cross functional groups.
- Tech teams are engaged very early on to meet and plan project with TRWE technical team.
- Tech budget is shared quickly to support negotiations.
- Data security, privacy reviews are undertaken in early phases.
- Organization must support study disease cohort which requires sharing de-identified structured and unstructured data (or identified data with BAA)
The above Start up work is done in parallel
ORG Support Letter (only required for finalists): If you are selected as a finalist, applicants have a 4-week period to arrange a meeting with organization decision makers (i.e. privacy office, data governance committee, other senior leadership) to review and preliminarily agree to study data extract technical requirements to proceed. If the Org tech requirements endorsement is not achieved in the 4wk time period or if Organization declines, this does not prevent applying in future cycle.
Applicant investigators must be active members of AASLD.
Selected investigators/site designee must commit to annual attendance at The Liver Meeting (TLM) and scheduled conference calls throughout participation in the study for study updates. TLM registration and travel is not provided as part of the study.
Secondary Technical Requirement Review Period for Organizations post applicant selection
- In parallel to contracting/IRB, organizations are provided data de-identication tech tools and support to beta test tools within organizational firewall for unstructured data for 12 weeks
- Must give second final commitment during this time to finalize otherwise end study start up process latest at 12 weeks
Preference is given to sites that can use the study central IRB.
Preference is given to applicants willing to actively lead the CQC initiative at organization and build a local improvement team
Foreign Institutions:
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Application Review
Objective Review Process:
Applications will be evaluated for merit, organizations support for the EHR data extract and ability to meet study start up timelines by a review group converted by AASLD and including members of Target RWE.
Reviewers will evaluate applications based on the following:
Technical Support/data extract feasibility at institution
Ability to meet study timelines (IRB, contracting, data extract)
Site Personnel/Resources for research
Organizational support for EHR data extracts
ORG Support Letter (only required for finalists): If you are selected as a finalist, applicants have a 4-week period to arrange a meeting with organization decision makers (i.e. privacy office, data governance committee, other senior leadership) to review and preliminarily agree to study data extract technical requirements to proceed. If the Org tech requirements endorsement is not achieved in the 4wk time period or if Organization declines, this does not prevent applying in future cycle.
Technical Requirement/Organization Support: A secondary review, including and commitment for study tech requirements will be granted and must be achieved within 12wk to continue study start up.
Successful applicants will need to complete a confidentiality agreement with Target RWE within 2 weeks of selection and will undergo a negotiation process for study budget determination.
Evaluation Process:
In addition to technical merit and start up timeline compliance, applications will be evaluated for AASLD membership and TLM attendance.
Questions Regarding this Call for Applications:
Questions may be submitted via email to Joy Peter at jpeter@targetrwe.com
Background and Study Overview
Care for individuals with chronic liver disease and cirrhosis aims to slow the progression of disease and to prevent or treat symptoms and complications using a variety of clinical and self-management support interventions. There have been great scientific breakthroughs over the past few years in the treatment paradigms for patients with chronic liver disease and cirrhosis. Yet, in spite of these important advances in technology and treatments, liver-related mortality has remained relatively unchanged over the last three decades. Between 4-12% of patients with cirrhosis have been found to develop at least one decompensating event annually, with the most common events consisting of ascites, hepatic encephalopathy or variceal hemorrhage with 40% of cirrhotic patients developing hepatic encephalopathy within 5 years. Although numerous studies have demonstrated deficiencies in the quality of healthcare delivery for these patients, there has been a paucity of studies evaluating how healthcare delivery can be improved.
There is an increasing need to develop multiple pathways that unlock the potential of real-world data (RWD) and real-world evidence (RWE) to improve patient outcomes and inform clinical trial design, especially in underserved patient populations. Our current approach to healthcare is informed mostly by clinical trials with sample sizes in the hundreds or few thousands which limits generalizability to broader patient populations and can be impractical due to costs and feasibility. The rapid integration of EHRs has made longitudinal clinical data available for research, making real-world data (RWD) and the real-world evidence (RWE) derived from them an increasingly important tool in modern healthcare systems. By aggregating real-world health and disease information from tens of thousands to hundreds of thousands or more diverse patients via EHR systems, the scale and scope of studies of a wide range of diseases, both common and rare, are improved by adding statistical power to detect associations between various complex factors and a wide variety of outcomes. The increasing utilization of RWD is further enhanced by the growing sophistication of epidemiologic and statistical methods that can facilitate principled learning. These include the development and refinement of causal inference methods, which permit the control of very large numbers of covariates, and extend naturally to complex, longitudinal data, which allow (under certain assumptions) for the estimation of the effects of different care pathways for chronic disease.
Given the gaps between best-practice and current practice and the potential for clinical data to be used for research, the American Association for the Study of Liver Diseases (AASLD) created the Cirrhosis Quality Collaborative (CQC) to establish quality measures and improve care for patients with cirrhosis. In 2023, AASLD partnered with Target RWE to expand the goals of CQC and to build on surging interest in real-world evidence for patients with a variety of liver diseases, creating the TARGET-LD Study. TARGET-LD aims to improve the understanding and management of patients with chronic liver disease and cirrhosis and brings together a consortium of investigators to build a large real-world database to evaluate the natural history, care, and health outcomes related to the management of chronic liver disease of diverse etiologies and cirrhosis. Additionally, through this collaboration, the study will purposefully integrate healthcare, support continuous improvement of healthcare, and enable technological innovation in a Learning Health Network (LHN) as part of the quality focused initiatives. Ultimately, the LHN aims to connect members to promote learning and improvements in the quality, safety, and value of care for patients living with chronic liver disease and cirrhosis.
The study protocol leverages EMR-based data sets with collection of large, de-identified EHR extracts (structured and unstructured data). The EHR data is collected under an IRB approved, waiver of informed consent and is set up as part of an automated data file transfer process (typically via SFTP) which greatly reduces the work of study teams (budget is provided to support study teams and the technical work to establish and maintain the extract). The study also enrolls a subset of patients from clinics who consent to complete PROs and have biospecimen collection. This study design allows data to be rapidly collected on very large sample sizes of all etiologies and complications of liver disease allowing each liver disease to be studied separately and enables quick use of the data for analyses and publication. Contributing sites/investigators are provided access to their curated datasets to support organizational initiatives and further research.
Under TARGET-LD, we will maintain disease-specific Steering Committees (MASH/MASLD, HBV, cirrhosis, PBC, MetALD, among others) to ensure the unique objectives of research across etiologies are met and to foster a collaborative environment for input on data analyses, findings and publication. Participating sites and investigators can propose and participate in authoring/coauthoring abstracts and manuscripts, data can be used for grant submissions and for performing PCORI-funded studies. Centers are encouraged to engage and support early-stage clinicians via this consortium.
Primary Objectives
- To characterize the natural history of disease in patients with CLD/Cirrhosis
- To assess safety and effectiveness of CLD/cirrhosis treatments and treatments for complications of either condition.
- To establish learning health networks focused on quality of care for patients (Cirrhosis Quality Collaborative- CQC).
- Identify deficiencies and best practices in care of patients with CLD/cirrhosis.
- Evaluate outcomes from targeted learning content in the management of patients with CLD/cirrhosis.
Study duration: 15 years
TARGET-LD includes two cohorts: Disease Cohort and Engaged Cohort.
Participants in the Disease Cohort are enrolled under a waiver of informed consent and included based on ICD-10 codes for select diagnosis of CLD/cirrhosis with data received from participating site electronic medical records (EMRs). The Disease Cohort patient data includes pseudonymized medical records (with electronic transmission of structured and unstructured data) from up to the prior 5 years retrospectively from the date of the respective site IRB approval as well as prospective records for up to 15 years, or until a study completion/exit criterion is met.
Entry Criteria for the Disease Cohort
Adult (18 years of age and older) patients at the time of enrollment with a diagnosis of CLD/cirrhosis by select ICD-10 codes in the EHR interface.
Participants in the Engaged Cohort consent to the completion of Patient Reported Outcomes (PRO) surveys and optional collection of blood samples or other biospecimens.
Entry Criteria for the Engaged Cohort
Adult (18 years of age and older) patients diagnosed and managed for these conditions and invited to participate and able to provide consent.
CQC IMPROVEMENT TEAM:
The CQC has proposed a learning health network (LHN)1 to support sites with an organized effort of shared learning and improvement for a network specialty care sites under the TARGET-LD protocol. The LHN infrastructure aims to support members to purposefully integrate healthcare, continuous improvement of healthcare, technological innovation, and research as they seek to close gaps in care and treatment outcomes for all patients with cirrhosis.
Key principles of the LHN include:
- Effective leadership to build shared responsibility for improving outcomes
- Transparent measurement and data sharing
- Collaboration patients/families, clinicians, and researchers
- Participation in continuous learning
- Effective resources and reduced transactional costs
CQC site PI or designated leader will participate in:
- Identification of quality care gaps and improvement opportunities
- Training in and use of structured QI methods
- Application of a improvement process at the organizational and network level
- Development of tools and methods to inform, empower, and activate patients to increase participation in care
- Utilization and ongoing expansion of the collaborative LHN
CQC sites will be able to view from their registry the following measures of quality care:
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1.This model is informed by the Institute of Medicine’s concept of a “learning health system” (LHS), in which learning occurs as a result of every clinical encounter and the resulting knowledge and innovation is applied at the point of care.