TEXAS MICROCHIP SENSOR POISED TO REDUCE HEALTH CARE COSTS
By Nicolaos Christodoulides, Pierre N. Floriano, John T. McDevitt & Michael Williams
Health insurance costs are a major fraction of the expense doing business, especially for small companies and start-up firms. With health care premiums soaring, many small business owners are asking their employees to cover more of the financial costs or cutting benefits entirely. Per capita health care costs in 1970 were on the order of $350. Today these costs are in excess of $8,000 per person, and rising.
A key factor for these health care expenditures is associated with the current focus of the medical community on reactive medicine. Reactive medicine means simply waiting for the disease to appear before initiating treatment or life behavioral adjustments. Instead of waiting for the physical symptoms of the disease to evolve, it is possible to get early warning signs from biomarkers. Biomarkers are molecular tags that serve as keys that provide insights into the wellness and illness status of patients. (Figure 1)
A lot of these biomarkers are now hidden behind closed doors and restrict timely access to information that is so critical to delivery of effective health care. Even for emergency health care circumstances like cardiac heart disease and stroke our society now lacks timely access to the diagnostic biomarkers that can help better manage the treatment of patients. This slow information flow serves to decrease the quality of care and leads to poor outcomes and high costs.
Similarly, the current lack of timely access to critical biomarker-based screening and diagnostic information forces health care providers into a mere reactive mode designed to deal with a health problem only at its later – and most often – more deadly and costly stages. Unfortunately, traditional health care has been relying on this least effective and most expensive approach.
Case in point is diabetes. The physical pain, suffering and health costs associated with this highly prevalent, high impact disease may significantly be reduced if the disease is altogether prevented through lifestyle changes or early detection. Unfortunately, the early stages of diabetes have very few symptoms, so the diabetic may not even know he or she has the disease. In fact, it is estimated that of the 20.8 millions of Americans who have diabetes, 6.2 million (or nearly 1 in 3) are not even aware they have the disease. For these people, diabetes will remain undetected years down the line, until sugar (glucose) levels sore uncontrollably and complications begin to emerge. Likewise, individuals with undiagnosed Diabetes Mellitus type 2 are also at a significantly higher risk for stroke, coronary heart disease, and peripheral vascular disease. They also have a greater likelihood of having dyslipidemia, hypertension, and obesity. Screening for early detection and prompt treatment are critical for the reduction of the burden of diabetes and its complications. In Texas, the total cost of diabetes is currently $12.5 billion a year, according to the American Diabetes Association, with $8.1 billion in direct medical expenses and $4.4 billion in indirect costs from absenteeism, unemployment and reduced productivity. According to a report released in November 2010 by an Austin health policy think tank, about 8 million adult Texans, or 24 percent of the population, will be diagnosed with diabetes by 2040, only adding to the dire economic and human costs.
Early detection is also critical for other high impact conditions, including cancer and cardiovascular disease (CVD), the top 2 disease killers today. Every 25 seconds, an American has a coronary event, and approximately every minute, someone dies of one.
The estimated direct and indirect costs of CVD for 2010 were a staggering $503.2 billion, making it a continuing major contributor to the escalating price tag of health care in the U.S. There are more than eight million visits to emergency departments annually for chest pain or other symptoms consistent with acute coronary syndrome. The challenge to clinicians has been rapid identification of those who require admission for urgent management and those with a benign cause who can be discharged directly from the emergency department. For about one in three patients with CVD the first symptom recognized that they have CVD is they die. Clearly this is not acceptable and more focus on preventive medicine with early disease detection is in order.
There is some hope – a new approach is emerging: proactive/preventative medicine. This approach promotes the general wellness of the subject to prevent diseases from happening in the first place, as well as providing a platform that maximizes prevention and aims to treat the root causes of the disease process. Even though primary prevention is the first line of defense that avoids the actual initiation and development of a disease, secondary prevention aimed at early detection of disease is equally critical, as it allows for increasing opportunities for interventions to prevent progression of the disease and emergence of clinical symptoms. Simply put, it is much better if we capture a disease before it gets out of hand.
Some new developments from the scientific community are also bringing significant hope that new medical microdevice tools will help to usher in a new era of affordable health care.
Society has witnessed similar game changing technologies in the software, electronics and internet industries. Computers get more powerful – and less expensive – every year. There’s no reason the same can’t be true for health care diagnostic tools. This is the basis for the Rice University-led Texas initiative now underway that will bring better and more cost-effective diagnostics to the U.S. and the world.
The rewards of years of research into biomarkers – the molecular tags in our bodies that serve as harbingers of both wellness and disease – are about to be realized.
Here’s where the Biomarker Highway enters. Until now, there has been no effective vehicle to drive these biomarkers to approval by the Food and Drug Administration. Consequently, thousands of biomarkers – many of them important clues to our most vexing medical problems – have been tracked down in the last decade and then abandoned, virtually stuck at dead ends. The three major phases of biomarker discovery, biomarker validation and clinical implementation are usually completed on distinct instruments and by different groups. This biomarker pipeline suffers from the lack of standard methods, protocols, reagents, and a streamlined multi-marker approval process. (Figure 2)
Also hindering the rate of translation of new biomarkers in clinical practice is the lack of an effective technology platform to validate biomarkers in large studies, bias inherent to quality issues with clinical trial design, and the empirical nature of biomarker research.
Despite tens of thousands of scientific articles describing advances in cancer and cardiac biomarkers, the rate of approval of new protein analytes over the past 15 years has remained steady, averaging a low 1.5 new proteins per year. Unless FDA approval is secured, biomarkers will remain academic curiosities and will not enter widespread clinical practice. These statistics are sobering, but they also point to tremendous opportunities for new technologies that will greatly enhance bench-to-bedside translation. While the biomarker derived information content is abundant, lacking now are the tools and the standards to retrieve this information in clinically relevant settings along with efficient multi-marker approval strategies.
Clearly, these trends cannot be sustained. Likewise, the traditional paradigm of expensive and complicated medical diagnostic devices needs to change. The next generation of medical devices needs to be created to deliver both high performance and exceptional value at reduced cost. Fortunately, the microelectronics and software industries reveal some clues to address these problems. For the past three decades the cost reductions for processor power is on the order of 48 percent per year.
The ability to process large amounts of information at the point-of-need is common in the field of electronics, yet a similar capacity to process complex molecular disease and wellness signatures at the point-of-care has not yet been fully demonstrated. Here, the electronics industry provides great inspiration for cost reductions, while at the same time producing ever-increasing performance. For the past four decades the number of transistors in the integrated circuit has doubled every 18 months in a fashion predicted by “Moore’s Law.” This rapid advancement in the electronics areas fueled by advanced microfabrication methods has enabled a continued rise in computing power spawning everything from the personal computer, to video-game consoles, portable music devices, digital watches, to smart-phones.
During the past few years we have witnessed tremendous progress in the area of smart phones. The smart phone does much more than make and take calls. It has become a portable computer, a source of music, a place to surf the internet, a GPS, a display, a digital camera and camcorder. It has also become a universal hub for hundreds of thousands of specialized applications. The smart phone has changed our lives.
To make transformative changes in health care we need new tools that can talk to the biomarkers.
The marriage of microelectronics with micro-fabrication methods fashioned and developed by bioengineers and steered by expert insight of clinicians, creates an ideal environment for the development of the next generation of affordable and accessible, portable point-of-care diagnostic devices. Indeed, this is where the ultimate bending of the health care costs is expected and projected.
To help move forward these areas, Rice University has pioneered the development of powerful, programmable sensors that can serve as universal clinical tools that can revolutionize the diagnostics industry and electronic medical record management. This new technology has recently been recognized as “Best of What’s New” by Popular Science magazine and “Best Advance of the Year” by the Science Coalition.
These modern diagnostic tools have the potential to replace hundreds of thousands of dollars’ worth of laboratory equipment while getting test results to patients in minutes instead of days. The Rice programmable bio-nano-chip (PBNC) system is unique today in its capacity to exceed the performance of modern macroscopic instruments using a chip-based approach. Further, the technology is embodied in a universal platform allowing for new test configurations to be quickly adapted to the modular platform.
These medical microdevice approaches are now moving through seven major clinical trials with the aid of clinical leaders in the areas of cardiac heart disease, oral cancer, ovarian cancer, prostate cancer, drugs of abuse and trauma diagnostics (Table 1).
These trials serve as training grounds to nucleate a new information rich diagnostic infrastructure.
To establish a more efficient pathway for biomarkers to move into practice will require new coordinated programs whereby these bio-signatures are smoothly inserted into the medical microdevices like the PBNC system for validation and clinical implementation.
For the seven Texas-based clinical trials, a common diagnostic core has been used in the discovery, validation and clinical implementation stages. This common structure has helped to move along the device development process and evoked the first evidence that Moore’s law (i.e. scalability with cost reductions) can be applied to medicine. This is a key step in bending down the health care cost curve.
While these developments are quite promising, the full potential of the medical microdevice revolution will require additional coordination to tap into the intrinsic information content in a way analogous to the establishment of the information highway. To empower the information highway our society has well-defined science and engineering bases alongside scalable electronics and software tools that help to usher in the next generation devices. Likewise, we have electronics hardware and software industry standards and goals that help the industry move forward in a predictable manner.
The analogous structure for the health care industry would involve the formation of the “biomarker highway” along with a new goal of increasing the rate of biomarker tests per unit time (i.e. Moore’s law applied to medicine). A key tool that can empower the biomarker highway is the universal data-gathering hub embodied in the PBNC. The PBNC has now hit the tipping point in terms of performance and cost. In the past, point-of-care testing (POCT) has been inferior to remote lab testing in two respects. This near-patient testing mode has been both more expensive and yielded inferior results to the remote lab. The new PBNC has started to outperform the remote lab and do so with reduced cost. This critical transition is expected to have transformative changes in the way diagnostic tests are used in clinical practice as well as for wellness testing. To take advantage of these new developments, it will be essential that new standards and common medical microdevice approval process are put into place in the next few years. Further acceleration of the new technologies will occur through cross agency programs that span the discovery, validation and regulatory approval steps.
The Internet brought the benefits of the information age to everyone. Bioinformatics, when combined with medical microdevices, new standards and new approval processes, can do the same for health care. Rich biomarker data combined with microfabrication techniques will provide the means to deploy quick, affordable point-of-care diagnostics for a wide variety of ailments. Early discovery of disease will save lives and dramatically cut costs.
Their collective success will be transformative in the truest sense of the word. This highway’s destination is a new age of individualized medicine.
John T. McDevitt, a pioneer in “programmable bio-nano-chip” technology, received his Ph.D. in Chemistry from Stanford. He serves as the Brown-Wiess Professor of Chemistry and Bioengineering at Rice, as the Principal Investigator for seven major clinical trials, including the “Texas Cancer Diagnostics Pipeline,” and as the Director for “Early Disease Detection Gulf Coast Consortium Cluster,” a network of over 100 clinical researchers devoted to next generation of affordable diagnostics. firstname.lastname@example.org
Nicolaos Christodoulides received his Ph.D. in Immunology from The University of Texas at Austin. As the Assay Director for the “programmable bio-nano-chip” technology at Rice University, he oversees the development of high performance, portable diagnostic tests currently validated in seven clinical trials for high impact clinical applications; including cardiac disease, cancer, trauma and drugs of abuse. email@example.com
Pierre N. Floriano holds a Ph.D. in Analytical/Physical Chemistry from Louisiana State University. He serves as the Director of Microfluidics, Image and Data Analysis for the “programmable bio-nano-chip” technologies at Rice University as applied to the lab’s seven clinical trials. firstname.lastname@example.org
Michael E. Williams is the Senior Media Relations Specialist at Rice University. He serves as the Science and Engineer feature writer for the Public Affairs Office of Rice University.
The authors wish to thank the sponsors of their research: Cancer Prevention Research Institute of Texas (CPRIT), the United Kingdom’s Home Office Centre for Applied Science and Technology (CAST), the University of Texas Health Science Center at Houston, the National Institutes of Health (NIH) through the National Institute of Dental and Craniofacial Research (Award Number 1U01DE017793 and 1RC2DE020785). The content of this article is solely the responsibility of the authors and does not necessarily represent or reflect the official views of the NIH or the government, and other sponsors.