The second session on Thursday 4 November of the CDISC Interchange was comprised of four speakers who brought a true patient perspective and patient-oriented value to the picture of developing standards. This session was chaired by David Handelsman of SAS, CDISC Advisory Board Representative to the Board Strategy Committee.
The session opened by Dana Pinchotti of the American College of Cardiology with a presentation entitled “Data Standards and the National Cardiovascular Research Infrastructure”. The NCRI is a partnership with the American College of Cardiology Foundation (ACCF) and Duke Clinical Research Institute (DCRI) with a mission to integrate existing resources to efficiently execute large simple clinical research projects (including site recruitment and education; randomization and research data collection (DCRI); quality improvement registry data collection; data standards (CDISC, HL7); guideline development (ACCF). In other words, the NCRI and its operations requirements go far beyond standards development and database programming. The vision is to have fully integrated platforms between the National Cardiovascular Data Registry (NCDR), clinical research and electronic health records and to relate the pre-marketing clinical data with post-marketing clinical data. [The NCDR receives data from over 2,300 hospitals.] With respect to standards, the NCRI: a) utilizes Clinical Data Acquisition & Standards Harmonization (CDASH) in the development of a set of consensus data standards; b) represents the data using SDTM and HL7 RIM Mappings; and c) uses NCRI infrastructure to conduct a randomized clinical trial as a demonstration of interoperability between healthcare and research.
The work has been ongoing since 2006 when Duke worked with CDISC and HL7 to develop standards for Cardiology and also Tuberculosis. These efforts resulted in 21 standard data elements in the cardiovascular disease area. Newer initiatives have included the “Top 100” data elements from the ACC Informatics Committee and a draft set of FDA Cardiovascular endpoints, the latter of which, through the leadership of Dr. Karen Hicks, is now at the point of being open for public review on the CDISC website.
Ms. Pinchotti pointed out that, for the patient community, this work means:
- Efficiency of and Capacity for Evidence Synthesis
- Efficiency for Hypothesis Generation
- Efficient Development and Conduct of Clinical Research Initiatives
- Findings Dissemination
- Care Delivery Guideline Development
- Quality Monitoring
The resulting impact includes the potential for economic efficiencies and reduced health care cost and the potential for quality improvement in patient care. CDISC continues to collaborate with FDA, ACC, Duke and many others to continue the development of standards to support research and patient care in the cardiovascular disease area.
Dr. Ronald Perrone, Professor of Medicine, Tufts University School of Medicine, gave the second presentation in this session: “Polycystic Kidney Disease and Data Standards: the PKD Outcomes Consortium.” Dr. Perrone showed the audience graphic photos of diseased kidneys and the impact of PKD on patients. He stated that the ideal therapeutic agent would block formation and/or growth of cysts at an early stage of life, thereby preventing the inexorable expansion, irreversible scarring, and structural distortion of kidneys, which are associated with all of the kidney complications of Autosomal Dominant Polycystic Kidney Disease (ADPKD). In this regard, adoption of total kidney volume as a target endpoint for regulatory approval will greatly accelerate the pace of clinical research and introduction of new therapies, thereby benefiting all PKD patients. Several meetings with FDA resulted in a recommendation from FDA to construct a disease model so as to ascertain the linkage between total kidney volume (TKV) and rate of size increase and the secondary features of ADPKD most commonly encountered: hypertension, hematuria, pain, abdominal fullness, renal stone, renal infection, creatinine clearance and QOL. However, the data residing in existing registries and being collected in ongoing clinical trials is not in a standardized format. Hence, Dr. Perrone collaborated with CDISC and the Critical Path Institute to standardize these data.
Specific aims of this collaboration are the following:
- Develop standard clinical data elements and definitions that are specific to ADPKD to enable the remapping of retrospective data and collecting prospective data in a standards format
- Develop the ADPKD standard with clinical (and standards) experts and obtain broad consensus through CDISC public comment; ensure input from both FDA and EMA
- Create a new database of aggregated data from existing multiple, longitudinal, and well-characterized research registries maintained over decades by the leading institutions in ADPKD clinical investigation
- Develop a quantitative disease progression model to examine the linkage between TKV and disease outcomes, such as hypertension, gross hematuria, kidney stones, urinary tract infections, ruptured intracranial aneurysms, development of end stage renal disease, and mortality
- These disease progression models will be utilized to generate scientific consensus on the utility and reliability of TKV as a biomarker and clinical endpoint for the progression of ADPKD
- The disease models will be used as evidence in a formal application to the FDA and the EMA for qualification of TKV as a biomarker ”fit for use” in evaluating the efficacy of new therapies and treatments for ADPKD
Data sources were Tufts University, Mayo Clinic, Emory University and University of Colorado. CDISC Operations Staff, Bron Kisler and Christine Tolk, have been leading the development of a set of CDISC standards for PKD and working with representatives of the Critical Path Institute along with Dr. Perrone and his staff. This process has provided input into ‘best practices’ for the development of disease area standards and has also pointed to the challenges of using clinical care data vs. clinical trials data for this purpose.
Dr. Perrone closed with the benefits to patients of this work. Specifically, these include the following:
- Our goal is to gain scientific consensus that TKV is the most sensitive and specific measure to predict progression of ADPKD including progressive loss of GFR, clinical outcomes, and the development of ESRD.
- Successful completion of this project will allow formal application to the FDA and the EMA for qualification of TKV as a biomarker ”fit for use” in evaluating the efficacy of new therapies and treatments for ADPKD.
- Adoption of such a biomarker will speed the development of clinical therapies to slow or stop the progression of ADPKD.
Dr. Jeff Allen, Executive Director of the Friends of Cancer Research spoke on the topic of “The Patient Protection and Affordable Care Act: Opportunity for a Linked Data Network.” He began with the definition of Comparative Effectiveness Research (CER): “Comparative Effectiveness Research (CER): “Conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat, and monitor health conditions in ‘real world’ settings.” He stated that additional CER for existing medical options may alleviate gaps in evidence and aid decision making. Unfortunately, at this point in time not even half of medical care is supported by adequate evidence about its effectiveness (IOM 2007). However, CER is key to reform efforts for the U.S. Healthcare System.
Dr. Allen introduced to the Interchange attendees the: Patient-Centered Outcomes Research Institute” (PCORI), which is a GAO standing appointed Committee with up to 15 members, including the directors of NIH and AHRQ and a stated goal “…to develop and improve the science and methods of comparative clinical effectiveness”. This committee will begin with tasks such as the following:
- Identify the values and limitations of existing study methods (RCT, Observational Studies, systematic literature reviews)
- Begin to examine new methods for generating the desired comparative evidence
- Help to determine the best approach and what the initial scope of work will be, taking into account resources and feasibility
- Examine what can be achieved through secondary analysis of existing data sets
Dr. Allen contends that the PCORI would be an ideal entity to oversee the establishment of a large-scale multi-source data network and in his presentation he elaborated upon what this would entail as well as the potential benefits and opportunities. He stated that a linked network capable of compounding data would help ensure that usable data is generated as a routine byproduct of care and that success will require data standards.
Dr. Adam Clark, Director of Scientific and Federal Affairs, FasterCures (formerly with Lance Armstrong Foundation and NCI) gave the final presentation of the session “EHRs and the Learning Healthcare System”. Dr. Clark opened his session with the statement: “Be it lack of medical breakthroughs, limited resources, or restrictive policies that are stalling progress, patients pay the price of delays in life or death consequences.”
Dr. Clark stated that key issues affecting Research Progress are as follows:
- Lack of communication, a common language, and standard data exchange between basic scientists, clinical researchers, and regulatory bodies
- Resistance to data transparency and dissemination
- Inadequate adoption of advanced technologies, expertise, and infrastructures to accelerate regulatory review and approval
He provided numerous examples of the slow research process, the fact that it takes too long and costs too much and the impact of fewer new treatments make it to patients. While our understanding of human biology has expanded greatly along with our ability to capture and exchange information, our research and care infrastructure has not kept pace. The solution, he stated, revolves around information exchange among all stakeholders:
In line with Dr. Fridsma’s opening presentation, Dr. Clark mentioned the three stages of “Meaningful Use” and the Learning Healthcare System “…to drive the process of discovery as a natural outgrowth of patient care; and to ensure innovation, quality, safety, and value in health care”
- Health Services Research
- Comparative Effectiveness Research
- Clinical Research and Regulatory Sciences
- Clinical Decision-Making and Reimburse
Also important is what Dr. Clark termed Consumerist Healthcare: Connecting Data and Research Through Individuals. This leverages patient portals and brings the patient into a focal point within the picture. He closed with a slide indicating the importance of linking Bench to Bedside and also the Boardroom.
Faster Cures is a nonprofit center and catalyst for action that works across sectors and diseases to transform the medical research enterprise to become more effective and efficient. Their mission is to accelerate the process of discovery and development of new medical solutions for deadly and debilitating diseases; Health Information Technology is both a foundation for and an enabler of 21st century biomedical research and care.
Dr. Rebecca Kush
CEO & President
Barracuda HydroBat