Medical Device & Diagnostic Industry
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An MD&DI June 1999 Column
Devices Past and Future: Gauging the Pace of Change
Kshitij Mohan
When the arrival of a new millennium is almost coincident with the twentieth anniversary of a successful trade magazine, it is tempting and perhaps expected that editorials mark the occasion by expounding on the past and speculating on what is to come. So, whither medical devices?
The medical device industry, as we know it, is largely a spin-off from the post–World War II renaissance in Western, particularly American, science and technology. The technology came from the development of the means to kill our enemies, or race them to the moon, or elevate the living standards of a citizenry that recognized itself as the most powerful nation on this planet.
When the faint beeps from a Soviet Sputnik were heard on American radios, challenging our technology ego, we responded by putting the highest priority on our academic and governmental science and technology infrastructure. Funding for science education and research grew, creating surpluses of individuals trained in such exotic areas as advanced mathematics, theoretical physics, aeronautics, and astronautics. Many of these individuals, unable to fully utilize their talents in the fields in which they were trained, ended up devoting their energies to interdisciplinary fields such as medical physics, computer sciences, and bioengineering.
Meanwhile, the discovery of antibiotics and better infection control had created new opportunities for the application of surgery to address a wider variety of conditions. Advances in diagnostic imaging, implants, and new surgical tools such as lasers drove and were driven by the growing needs of the surgeons. Other than the in vitro diagnostics area, most of the innovation in medical devices was based on a synthesis of concepts from a variety of the physical sciences. The IVD industry, originally reliant on classical chemistry, was one of the earliest adopters of such emerging paradigms in biology as monoclonal antibodies, DNA probes, and the whole area of immunodiagnostics.
The field of medical devices achieved a clearer identity when there was a growing realization that their safety and effectiveness could not be shown using the same scientific and regulatory tools as for drugs. The realization that devices are not drugs, and, therefore, that the Federal Food, Drug, and Cosmetic Act was no longer adequate to regulate them, was an important one. It has been disheartening over the years to see that some FDA administrations did not realize this important fact, and were tempted to believe that many of the tools, including clinical trials, had the same role in the validation of devices as they did in the case of drugs. Recent regulators have been more enlightened. One hopes that, for medical device validation, the concept of "appropriate science"—rather than just the most resource-intensive or time-consuming science—will gain further strength.
The paradigm change in medical device regulation came in the early 1970s when Ted Cooper, then an assistant secretary of health in the Department of Health, Education, and Welfare, headed up a small group to produce the Cooper Report. This report laid out the conceptual framework for the scientific validation of the safety and effectiveness of medical devices. The framework was radically different from the model for drugs.
In May 1976, under the visionary leadership of Congressman Paul Rogers, then the chairman of one of the key congressional committees, the Medical Device Amendments to the FD&C Act became law. These amendments included some major departures from the model used for regulating the safety and effectiveness of drugs: the classification system for devices; the transitioning from preamendment devices to the postamendment products through the 510(k) notification scheme; a new definition of valid scientific evidence for medical devices that was much broader than that for drugs, going beyond "well-controlled clinical trials" to partially controlled clinical trials and even case studies; and the concept of "reasonable assurance of safety and effectiveness" based on risk/benefit considerations. Congress also realized that the economic constraints of small companies required that there be cash flow even in the investigational stage of device development. The law, therefore, included an investigational device exemption (IDE) process in which companies were allowed to charge for, but not make a profit from, devices being tested under an IDE.
The Medical Device Amendments were designed as a vehicle for encouraging growth in a young and exciting industry, and had the desired results. The device industry delivered. Physicians, engineers, materials scientists, and a variety of other professionals collaborated to create elegant new devices. Patients had access to reliable heart valves and to exquisite anatomical imaging through CAT scanners, magnetic resonance imaging, ultrasound imaging, and better image resolution in x-rays and fluoroscopy with less exposure to harmful ionizing radiation. A plethora of safe and effective implants were developed, along with in vitro diagnostics, drug delivery devices, and conventional as well as unique new surgical tools using lasers. The device industry flourished, maintaining a favorable international trade balance and enhancing clinical outcomes at a pace that led the rest of the world by a large margin. Most of these innovations were still within the broad scientific and medical paradigms of the previous few decades. But even the pattern of synthesis and incremental improvements brought remarkable changes.
Miniature cameras and fluoroscopy provided real-time imaging to the surgeon without requiring a direct line of sight, and clever mechanical contraptions allowed access and manipulation within the body. The age of keyhole surgery brought remarkable and early payoffs in such procedures as gall bladder removals, cardiac angioplasty, and other balloon catheter procedures. Lithotripsy went beyond keyhole surgery to incision-free surgery for crushing and flushing kidney stones. Remarkable refinements occurred in other areas such as electrophysiology, as better electrophysiological mapping, a broad range of cardiac pacemakers, and implantable defibrillators showed clinical success, creating enough confidence in these technologies to initiate developments to apply them in neurology.
THE CHALLENGES AHEAD
As we look at the portfolio of technologies and approaches based on the basic science paradigms of the past, there are growing indications that these technologies will not be adequate to address the challenges that remain. For example, developing minimally invasive techniques for cardiac bypass or valve replacement will be more difficult than it was to establish laparoscopic cholecystectomy. The range of available devices for what is needed in the neurology area is still limited. Definitive device-based treatments for congestive heart failure, synthetic vascular grafts for coronary use, and true biosensors (as distinct from colorimetry and spectrophotometry-based dipsticks) for glucose or other analytes that could be implanted to allow closed-loop drug delivery have yet to be developed, despite long and expensive attempts. The question then becomes—are there other scientific disciplines and paradigms emerging that may enable researchers to find answers to these unmet clinical needs and bring about the next major paradigm shift in medical device technology? If so, what are the barriers to deploying them?
In his Structure of Scientific Revolutions, Thomas Kuhn, who crossed over the fine line between physics and philosophy, postulated a classical model for scientific revolutions that could be extrapolated to technology development. In simple terms, this model implies that when the available scientific and technological paradigms are unable to meet the needs and demands put upon them to explain phenomena or provide solutions, new paradigms are created. These new paradigms are then harvested by a process of "normal science" till they no longer meet the demands placed upon them. The process then starts all over again.
Since the 1960s, enough advances have occurred in scientific disciplines other than the ones customarily exploited for applications in medical devices—as well as in those traditional ones—that the best of the medical device industry may be yet to come. Some of these advances, such as the wildfire progress of information technology and the further maturing of biological sciences, could well lead to a paradigm shift in our industry.
The use of information technology hardware and software tools will result in more artificial intelligence embedded in hardware products as well as in stand-alone software. The digitizing of images would make obsolete many film-based technologies and allow much greater use of artificial intelligence in diagnostics. Massive computing power applied to technologies such as MRI could produce real-time images that might further reduce the need for interventional diagnostics. Nuclear magnetic spectroscopy could eliminate some traditional chemistry-based diagnostics; wet chemistry–based diagnostics could be incorporated on microchips; and, using microfluidics, entire batteries of diagnostic tests could be fabricated as inexpensive, disposable labs-on-a-chip. The ability to mine useful information from incredibly large amounts of data, to move data around the globe instantaneously, and to remotely operate hardware through robotics all point to time and space becoming a much smaller barrier to the delivery of high-quality healthcare.
Similarly, the advances in cellular and molecular biology have great potential for creating devices that are combinations of synthetic materials, inert materials of biological origin, and live biological cells and tissues. The biocompatibility of synthetic materials could be greatly enhanced with appropriate cell growth on their surfaces. Small-diameter vascular grafts lined with endothelial cells could well demonstrate the patencies required of coronary grafts. Tissue engineering could allow the creation of specific organs or their components. Artificial skin is already available. The combination of growth factors or genes with appropriate delivery technologies could facilitate angiogenesis and arteriogenesis, and these blood vessels might be grown in a manner designed to sufficiently perfuse the heart or other organs without requiring bypass operations.
CONCLUSION
There are many companies—large and small—already working in the early stages of these developments. Some will succeed and many will fail, but new applications will be postulated and attempted. In a free and fertile environment, such developments will happen, but there are scenarios under which many of these changes could well be thwarted. Regulatory bodies, both in the United States and abroad, will need to learn how to deal with products that do not neatly fall into one of the three categories of drugs, devices, or biologics, but which may combine all three.
Reimbursement schemes for products will need to mature. The only conceptual framework for reimbursement for medical products is based on pharmacoeconomics—and even that is not used widely or appropriately. In the drug arena, the cost of the drug as a portion of the overall therapy does not vary as much as in the case of a device. The contribution of a drug to a favorable clinical outcome is also easier to evaluate than in the case of a device, which may or may not directly affect a clinical outcome. Given these wide variances—both on the cost side and on the benefit side—there is already a need for a "device economics" model. Absent a favorable payment environment, even the best technologies are likely to wither before blooming.
Other barriers to progress include the issue of perceived risk versus real risk. Recent attempts to bring about the elimination of PVC in medical products is one example of misplaced fears that ignore hard scientific evidence of the safe and effective use of a highly versatile material. As biological tissues, cellular therapies, xenotransplantation, and organogenesis play greater roles in device-biologics combination products, it will be a challenge to accurately calibrate the consumers' perception of risk.
Currently, most academic research organizations and industrial technology development groups are organized around different science and technology disciplines. The growing interdisciplinary nature of our industry will require greater use of matrixed organizational models in which experts from different disciplines can live in each others' worlds without forsaking their own.
If the past is prologue, at least in this country, we will eventually overcome these barriers. If we are proactive, we can speed up the changes—if not, we could end up delaying the advances we need to provide better healthcare.
Kshitij Mohan, PhD, is corporate vice president, research and technical services, at Baxter International Inc. (Deerfield, IL), where he serves on the company's operating management team. Prior to joining Baxter, he held several senior-level positions at FDA, including director of the Office of Device Evaluation and acting deputy director of CDRH. When MD&DI's first issue was published in 1979, he was a staff member in the White House Office of Management and Budget. A frequent contributor to MD&DI over the years, he sits on the magazine's current editorial advisory board.
