Interoperability Review: Standards and the Patient: Alzheimer's Disease as an Example

Vol. 1
No. 2
Contributed by R. D. Kush, President and CEO, CDISC

Most Alzheimer's patients and their families would never consider putting the word 'standards' in the same sentence as this dreaded disease (unless perhaps they were talking about standards of care—a legitimate concern). For readers of the AMIA Standard's Standard, however, I thought this might be an appropriate topic to cover since standards have actually been integral to an initiative that holds much promise for spawning a breakthrough in the development of new therapies for Alzheimer's Disease.

In The New York Times, on October 27, 2010, an article by Sandra Day O'Connor, Stanley Prusiner, and Ken Dychtwald appeared, entitled, “The Age of Alzheimer's". Beginning in 2011, more than 10,000 individuals daily (over 4 million per year) will be facing higher risk of Alzheimer's for the next 19 years. Current spending in the U.S. is ~ $172 billion per year to care for Alzheimer's patients, not to mention the emotional and financial impact on family members. [Currently, there are ~ 30 million individuals with dementia.] The authors write: “So far, only a handful of medications have been approved by the Food and Drug Administration (FDA) to treat Alzheimer's, and these can only slightly and temporarily modify symptoms like forgetfulness, disorientation, and confusion. None actually slows the underlying neurodegeneration."
With this in mind, the Coalition Against Major Diseases (CAMD) was formed. This is an unprecedented collaboration led by the Critical Path Institute (C-Path). The Coalition was formed by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging (NIA), and a number of biopharmaceutical companies and research foundations/patient advocacy associations.
The biopharmaceutical companies agreed not only to share data from 11 industry-sponsored clinical research studies, but also to provide the data in a standard format, specifically the Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM). Providing data in this standard format enabled the creation of a database of information on more than 4,000 Alzheimer's Disease patients; this database is now posted openly for scientists to use in modeling the disease and assessimg new options for therapies.
Previously, the studies could not be appropriately compared against one another due to the fact that the data were not in a common format. Mapping to a common standard allowed the data to be aggregated into a single database. The substantial size of the resulting database studies is important in that it will enhance the statistical power of analyses. Placebo data can be compared vs. various treatments—even failed treatments. Additional data can also be added. In fact, during the course of creating the database, data fields specific to Alzheimer's efficacy assessments were used to augment the CDISC SDTM and to provide a new data acquisition standard, specifically a CDISC CDASH domain for Alzheimer's evaluation. (CDASH refers to Clinical Data Acquisition Standards Harmonization). There are now standard case report forms that can be used for future Alzheimer's studies. According to a Gartner Business Case analysis on CDISC standards, using CDISC standards 'up front' in the process (for data collection) can decrease the start-up time for a clinical trial by 70-90%. This eliminates the costly mapping to the standard at the 'back end'.
It was not a simple task to make this all happen. One challenge, according to Dr. Woosley, CEO of C-Path, included legal agreements required for companies to release the data (which are in a de-identified form per clinical research processes). Once data were released, however, the scientists had a 'feeding frenzy' looking at all of it. Another challenge was that, although there is a 'standard' evaluation form for Alzheimer's Disease, it was being used in at least 10 different ways by various clinical trial sponsors. Once these variations on the theme were identified, however, a true standard could be developed and is now openly available for future studies.
The Alzheimer's Disease standards package is posted openly on the CDISC website, as are all of the CDISC standards that support clinical research from protocol through analysis and reporting. Now, it is on to other diseases! Parkinson's Disease, Polycystic Kidney Disease, Oncology, Cardiovascular Diseases are some of the others in progress in terms of developing standards. Comments are being requested through the CDISC consensus-based standards development process, so please get involved and provide your comments . . . especially in your areas of expertise.
The Critical Path Initiative was launched during the tenure of Dr. Mark McClellan as FDA Commissioner and Dr. Janet Woodcock as Deputy Commissioner. The Critical Path Institute is an independent, non-profit organization with a mission to serve as the impartial facilitator of scientific efforts from government, academia, patient advocacy organizations, and the private sector to support the FDA's regulatory science initiatives. CDISC is partnering with C-Path, FDA, and others to develop and apply standards for additional disease areas.