HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Delos Cosgrove Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cosgrove, D. Search for Related Content PubMed PubMed Citation Articles by Cosgrove, D.

Eur J Cardiothorac Surg 2004;26:S27-S31
© 2004 Elsevier Science NL

Review

View from North America's cardiac surgeons

Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA

	Abstract

Top Abstract 1. Introduction 2. Trends in cardiac... 3. Factors influencing change 4. Options for progress Appendix References

 
Over the last 50 years, cardiac surgery has evolved into a dominant specialty for the treatment of heart disease, especially coronary heart disease which remains the world's leading cause of death. The advent of effective stenting for coronary heart disease has coincided with a plateau and then reduction in the volume of coronary surgery in most developed health care economies over the last few years. Similarly an ageing population coupled with changes in the epidemiology of valve disease from predominantly rheumatic to predominantly degenerative disease is reflected in an increasing demand for surgery for mitral regurgitation and aortic stenosis in the elderly frequently coupled with coronary surgery. Many surgical practices depend on high volume coronary surgery so this growth in valve surgery will have only limited impact on the threat from a reduction in coronary surgery. It is imperative that the specialty explores new innovations since the long-term future of the specialty is inextricably dependent on pioneering activities similar to those of the founding fathers of the specialty.

Key Words: Cardiac surgery • Future • Epidemiology • Age

	1. Introduction

Top Abstract 1. Introduction 2. Trends in cardiac... 3. Factors influencing change 4. Options for progress Appendix References

 
Since the end of World War II, cardiac surgery has experienced an explosive growth, both in the number and variety of procedures performed and the total volume of cardiac surgery performed both in the United States and Europe. During this time, there has been marked decrease in the surgical risk and a vast improvement in the outcomes for a wide variety of patients. For the first time in the late 1990s and early 2000, cardiac surgery's potential has been called into question by advances in other specialties and technologies. It is the norm for surgery to be the first treatment for a number of diseases and then be replaced by medical and preventative therapies. This has not previously happened in cardiac surgery. This has led to a general sense of despair amongst practitioners, concern for the future of the specialty, and personal security. I will attempt to analyze the trends in cardiac surgery, dissect out those factors which will influence a cardiac surgeon's future, and suggest opportunities for improvements in patient care and specialty growth.

	2. Trends in cardiac surgery

Top Abstract 1. Introduction 2. Trends in cardiac... 3. Factors influencing change 4. Options for progress Appendix References

 
The STS/AATS practice survey provides an accurate picture of what's happened to individual surgeon's volume between 1999 and 2003. In 1999, the mean number of cases performed was 284, and in 2003, the mean number was 244, a 14% reduction. The distribution curve of surgical volume shows a marked shift to the left over time with almost 10% of surgeons doing fewer than 100 cases, and only 4% of surgeons doing more than 400 cases in 2003.

Data from the Center for Disease Control and National Center for Health Statistics shows a progressive rise in heart operations which peaked in 1996, then plateaued, and began a decline in 1999. Almost exactly paralleling this curve, is the volume of coronary artery bypass grafting, which showed a similar peak, plateau, and decline starting in 1999 and 2000. This occurred at the same time as a rapid rise in PTCA, which exceeded the number of coronary bypass operations done, and a continuing rise in the number of cardiac catherizations, which exceeded 1.2 million. Closer analysis of this data suggests that the fall in coronary bypass grafting in the United States coincided with the introduction in 1996 of coronary artery stenting. The rise in stent insertions exceeded the number of coronary bypass grafts by 1998. Until 1996, the incidence of PTCA and coronary artery bypass grafting paralleled each other in growth, and there was not a decrease in coronary bypass grafting until the introduction of stents in that year. Data from a controlled population in The Northern New England Data Registry shows a progressive increase in coronary bypass grafting per 100,000 population from 1990 through 1996, a plateau from 1996 to 2000, and a sharp decrease in coronary bypass operations per 100,000 in 2001, 2002, and 2003.

Valve operations in the United States were approximately 40,000 per year until 1987, when growth began, and by 2000, 130,000 valve operations were performed annually. The growth is seen in both mitral valve surgery and aortic valve surgery. The largest growth in mitral valve surgery was in the area of mitral valve repair. Mitral valve surgery in the Northern New England Registry increased 2.4 times between 1990 and 1999. In the same registry, there was a large growth in aortic valve procedures, increasing from 20 per 100,000 population to 33 per 100,000. The incidence of coronary artery disease and the prevalence of coronary artery bypass surgery have dictated that most cardiac surgical practices are composed almost in toto of coronary artery bypass surgery and valves, with the former representing 80–85% in most practices. It is clear, that any diminution in application of this surgical therapy would have profound effects on surgical volume, in spite of the growing valve practice.

All of these factors have influenced the practice at The Cleveland Clinic, and a detailed analysis of distribution of cases may be instructive as to new opportunities to pursue. From 1993 to 2003, the total cardiac surgical volume at The Cleveland Clinic increased from 3200 to 4000 cases. This occurred inspite of a marked reduction in the number of isolated coronary revascularizations, including primary operations and reoperations. This decline started in 2000 and has continued unabated to the present. This decline would have been even more severe had the patient population not been expanded to include older patients. Currently, 67% of our patient population is greater than 65 years of age, and the fastest growing portion of the population, those greater than 75, which in 2003 reached 28%. This trend has been similar in affiliated community hospitals, and particularly noticeable in hospitals with extremely interventional cardiologists.

Over the last ten years the volume of valve surgery has increased from 1000 cases a year to 2400. This experience has been equally divided between aortic and mitral procedures, being stimulated in large part by our interest in mitral valve repair, which has now reached 80% of mitral valve operations.

Increasing volume of great vessel surgery has continued the surgical growth with a five-fold increase in the number of aortic operations. This is, in part, stimulated by improved diagnostic techniques and reticence to approach this disease in a community hospital setting.

Experience with surgical approaches to atrial fibrillation began in 1990 with the Maze procedure and has grown dramatically over the last four years to almost 500 ablations for atrial fibrillation. This growth was stimulated by the early adoption of the Atricure device which made the procedure rapid and effective, and the policy that all patients with atrial fibrillation were candidates for intervention. This change in technology resulted in the use of the new technology rather than expansion of the cut and sew Cox Maze III procedure.

Cardiac transplantation for heart failure has remained constant nationally, as it has at The Cleveland Clinic. However, surgery for heart failure has continued to increase as the number of transplants has leveled off, with the number of left ventricular resections or DOR procedures increasing. The use of left ventricular assists has not expanded as expected, principally because of the limitations of the devices.

Septal Myectomy for IHSS have increased five-fold, attributable largely to a specific interest in this disease process, and the increasing use of echocardiography for diagnosis.

An additional niche, which has contributed to the growth, is the large percentage of patients undergoing reoperations. We have seen a growth in the incidence of reoperations both for coronary revascularization and valve reoperations, and currently 25% of all surgical cases are reoperations.

	3. Factors influencing change

Top Abstract 1. Introduction 2. Trends in cardiac... 3. Factors influencing change 4. Options for progress Appendix References

 
There are multiple factors influencing surgical volume including demographics, epidemiology, technology, implementation of new diagnostic and therapeutic techniques, the economy, and finally innovation. It is impossible to ignore the huge influence of demographics on surgical volume. From 1998 to 2025, the world's population is expected to grow from 5.8 to 8 billion people. Growth in the United States is expected to go from its current 270 million people to between 400 and 550 million by 2050. At the same time, Western Europe's population, which is almost 400 million, is expected to remain flat and then begin to decline in 2030. This difference in growth rates in population is principally accounted for by two factors. The first is the lower number of children per woman, which is currently 1.3 in Europe, and 1.9 in the United States. In addition, there will be approximately three times the immigration into the United States as there is into Western Europe. The aging of the world's population will affect all continents. Most notably, the percentage of those patients in Europe greater than 60 years of age will increase from 20 to 30% in 2030, and in North America from 15 to 25%. In the United States the number of patients greater than 65 years has been increasing throughout the past century. There will be a huge jump in this population in 2020, when the so-called baby-boomers reach 65. There will, however, be a substantial difference between the United States and Europe in the mean age of its population. Currently, the mean age in both areas is 37. By 2050, the mean age will be the same in the United States, but will have grown alarmingly to 53 in Western Europe. This huge increase in the number of elderly patients should increase the number of patients at risk for cardiovascular disease and hence increase the potential for patients requiring surgical interventions. As medicine advances, so have the diagnostic procedures and number of physicians. Both of these factors should increase the incidence of diagnosed disease, further adding to the reservoir of potential surgical candidates.

With time, there will be changes in the epidemiology of diseases and the health of the populace. Worldwide, coronary artery disease will continue to be the 1 cause of death, as it is in the United States. Two disturbing trends in the population of the United States may well accelerate the incidence of coronary artery disease. The Center for Disease Control reports an alarming rise in the incidence of obesity, which has reached 30% of the adult population, with 65% of the US population being overweight. This is paralleled by an explosion in the incidence of diabetes, both factors increasing the potential for the incidence of coronary artery disease. A similar and perhaps associated epidemiologic trend has been the five times increase in the incidence of congestive heart failure over the last 30 years. This is an area which is currently without satisfactory therapy.

The epidemiology of valve disease has changed enormously. Rheumatic valve disease in the United States is increasingly rare, and has been replaced by degenerative disease. The most common cause of aortic insufficiency is aortic dilatation, and the most common cause of aortic stenosis is degenerative disease, both diseases of aging, which will probably be seen with more prevalence as the population continues to gray. Mitral insufficiency has replaced mitral stenosis and mixed lesions as rheumatic fever has disappeared. Currently, myxomatous disease is the most common cause of mitral insufficiency and the number of potential candidates increases as surgical indications therapy improves and as the number of elderly increases.

I will not address surgical techniques as they have been assigned individually to other presenters.

The adoption of new surgical techniques and indications for surgical procedures have a major influence on surgical volume. Cardiac surgeons have been notoriously slow to adopt new surgical techniques. In 1973, it was abundantly clear that internal mammary artery graft had superior patency compared to vein grafts. This technology, however, was not widely adopted nor considered the standard of care until 1986 when an article by Loop, et al in the New England Journal of Medicine, (NEJM 1986:314;1–6) brought the cardiology world's attention to the superiority of this graft in terms of long-term survival, patency and freedom from cardiac events. It was not that the surgeons adopted this, but rather that their cardiologic colleagues insisted that they adopt this technology. A similar approach can be seen in the adoption curve for mitral valve repair. Both the STS Data Bank and the Medicare Registry show that only 30% to 40% of all mitral valves are repaired. Many centers now have achieved 80% repair and it is incumbent upon surgeons to become more rapid adapters of this new technology. Changes in medical referral patterns can also vastly influence surgical practice. An article in the New England Journal of Medicine from the Mayo Clinic (NEJM 1996; 335:1421) showing the natural history of mitral valve prolapse and recommending earlier surgical interventions, made a whole new category of asymptomatic patients previously not considered candidates for surgical intervention, become surgical candidates. This has had a major impact in increasing mitral valve surgery throughout the United States.

It is well recognized that cardiac surgery is an expensive therapy. A look at the incidence of cardiac surgical procedures worldwide suggests that it is far more prevalent in wealthy countries than in less wealthy countries. It is also noteworthy that there has been a downturn in the incidence of aortic valve surgery in the last three years, paralleling the downturn in the economy.

	4. Options for progress

Top Abstract 1. Introduction 2. Trends in cardiac... 3. Factors influencing change 4. Options for progress Appendix References

 
Many of the factors which have been mentioned previously are not subject to alterations by the surgical community. The one which is perhaps the most open to influence is innovation. Michael Porter wrote in the Harvard Business Review that ‘innovation is the only true, long-term solution to high quality, affordable health care.’ Both factors will be necessary if we are to expand our influence through surgical therapy. There are a number of factors which tend to foster innovation. These include the explosion of knowledge which we are currently experiencing. Currently, 90% of all the world scientists who have ever lived are alive. More new knowledge has been created in the last 40 years than in the previous 5000, and the total amount of knowledge doubles every two and one-half years. This knowledge explosion is seen in the doubling in the number of pages in the Annals of Thoracic Surgery, and over the last 10 years the logarithmic increase in the number of patents granted, all of which makes most techniques obsolete within 7 years. The end of the cold war has brought about a shift in the emphasis in federally sponsored research. Physical sciences and engineering have remained flat while the spending for life science new capital markets has become available to foster innovation. Currently three-quarters of the R&D funding in the United States is sponsored by a business or a venture capitalist. They have become the diMedici's of the medical world. In 2000, at least $6 billion was invested in health care startups by venture capitalists. Nearly one-quarter of that went to medical devices, which would be directly applicable to our specialty. Finally, information technology and telecommunications are finally reaching the health care field. Information technology has previously been primarily the province of clinical research and health care administration, however, it is gradually making its presence felt in the practice of medicine. The 18th, 19th, and first 90 years of the 20th century mark the industrial age, where the principal science was chemistry. The last decade of the 20th century was known as the Information Age, where physics brought us computations and telecommunications. The first part of the 21st century is expected to be the post-Information Age, where biology will be the predominant science, and information technology and data storage will probe biotechnology. Telecommunication has made it possible to eradicate the barriers of time and distance. It is now possible to demonstrate surgical procedures and have real-time meetings simultaneously worldwide. This should bring more great minds to a problem, hastening solutions. There are a number of factors impeding medical innovation. These include complexity of devices and projects, increasing costs, expansion in the United States of the regulatory process, both in terms of PMA and 510K applications. The funding for new technology, once it is approved, is a laborious process and Medicare/Medicaid services currently have 130,000 pages of regulation, which is more than the Internal Revenue Service. With a long, expensive process, with little surety of either success or reimbursement for any new therapy, enthusiasm for investment is dampened.

Our future is inexplicably tied to pioneering activities similar to those of the founders of our specialty. The greatest risk to our specialty is not taking one. Which one of these chances which we take will be successful? Shakespeare wrote, ‘If you can look into the seeds of time and say, which grain will grow and which will not, speak then unto me.’ I cannot speak to you about this. Only time will tell.

	Appendix

Top Abstract 1. Introduction 2. Trends in cardiac... 3. Factors influencing change 4. Options for progress Appendix References

 
Conference discussion

Dr T. Gardner (Philadelphia, Pennsylvania): I would like to make an observation, that may represent a new direction in terms of investment in biomedical research in the United States.

All of you know that the National Institutes of Health is the principal government research engine in the United States and has been tremendously influential and enabling in so many ways in the advances in biomedicine and biomedical technology over the last 50 years.

The former director of the NIH several years ago was Bernadine Healy, who, as you know, is a cardiologist; the next director, Harold Varmus, is a microbiologist, basic scientist, and is very much gene and molecularly-oriented; and the current director of the NIH is Elias Zerhouni, an Algerian native who came to the United States about 25 years ago to train after medical school in Algeria. He is a radiologist and magnetic resonance imager. His appointment represents a very interesting evolution of people directing the NIH.

The first thing that Dr Zerhouni said after accepting his new position at NIH was that we need to break down the silos that exist among the diverse community of researchers at the NIH. As you may know, NIH is organized into many different Institutes, and he has called for a new road map for NIH functioning that is based on much more collaboration and teamwork.

But I want to emphasize that his appointment as Director of this vast research enterprise, while perhaps a chance thing, does represent an interesting change in the direction in research priorities in the US. I am sure that we can expect more emphasis on translational research and on research efforts that involve much greater collaboration among diverse groups of investigators. The opportunities for participation in cutting-edge research by cardiothoracic surgeons should be enhanced. Also, we can expect greater general interest in and support for biotechnical advances.

Dr Cosgrove : Tim (Tim Gardner), as a parallel to that I might say that in the United States, of all the R&D funding, three-quarters of that is non-federal, or three-quarters of that comes from corporations and venture capital-backed research.

Mr B. Keogh (Birmingham, UK): Toby (Delos Cosgrove), the Cleveland Clinic has led the way in many developments in cardiac surgery, which are no better illustrated than the 1986 publication on use of the internal mammary artery, and there are numerous other examples of that. May I ask you where you are putting your strategic money now?

Dr Cosgrove : I am not sure that it is strategic money, but we think that there is an enormous opportunity in atrial fibrillation. You can see the explosive growth we have had there. I made a very large investment in heart failure about 10 years ago, and frankly, it hasn't paid off, and I have been surprised at that, and I think it is principally because the devices have not progressed as fast as they should. I think that valve surgery will continue to grow.

My sense is that we are going to learn the same thing about aortic valve disease as we have learned in the past about mitral valve disease: you are better off to operate on it earlier. We looked at 12,000 aortic valve replacements, and from Gene Blackstone's amazing statistical capabilities, he has not been able to tell the advantage for life-prolonging for any prosthesis. So I doubt that by changing prostheses we are going to improve the long-term outcomes of valves, and I think we are going to need to operate on valves earlier before the ventricles become hypertrophied and fibrotic if we are going to get better results, and that is going to be a long education process.

Dr F. Mohr (Leipzig, Germany): You have been the Past President of the AATS and also chairing the largest department in the States. You have shown your data compared to United States data. For example, look at mitral valve repair, and I could ask about completeness of arterial revascularization or using IMA; it may be 70 or 80%, I don't know, in the United States. How would you address that members of our Society or the members of your team really fulfill the perfection we need?

If we listen to the cardiologists, they accept, let's say, ‘imperfect’ results, and the new generation really does it without any thought, if I may say so from my own experience. They just know there is a lesion, it is going to be dilated, quickly done, and they don't care what is happening in 5 years. The surgical training and the personality always was different, and we were aiming for perfect results, and you clearly showed in your data it is not the truth or if you look all over.

Do you have an answer for that?

Dr Cosgrove : Well, I think that anybody that starts into an operation needs to do as good an operation as possible to do, and I think arterial grafting is a good example of that. However, let me give you my perspective on coronary artery disease. I think our department, if we were as heavily reliant on coronary artery disease as we had been, would have seen a substantial diminution in cardiac surgical volume, and we specifically started out to try to develop other areas of cardiac surgery. I personally don't think that we are going to be able to recapture coronary artery surgery from the cardiologists.

This is an example of what has gone on with Bilroth, I think it is an example of what has gone on with polio. Orthopedic surgeons only operated on polio, and when polio went away, orthopedic surgery didn't go away. They found every other joint in the body and every other muscle that they could operate on, and there are more of them and busier now than they were before.

If we spend all of our time trying to resurrect or wrestle back from the cardiologists that disease process, I think we are doomed to failure. And frankly, I think what we are seeing is the natural evolution of going from surgery being the first into an area, to medicine, perhaps stenting and PTCA as halfway between surgery and medicine, eventually statins will get there, and eventually it will be a preventative disease. We cannot treat a worldwide epidemic with coronary bypass surgery; from an economic standpoint, it has to be something else. So if we as surgeons are going to continue to have work, we have to find other things to do, I think, over the long period of time.

Dr A. Haverich (Hannover, Germany): You made an enthusiastic plea towards innovation in cardiac surgery. My question is, where does that innovation come from and what is the contribution of the cardiac surgeon within that innovation? Does innovation mean that we hop on industrial developments early on? Does innovation mean that we switch from coronary surgery to maybe valve surgery and atrial fibrillation?

I read the presidential address of Ed Verrier, the President of the Western Thoracic Surgical Society. He complained that only I think 1.2% of the NIH grant money was going into cardiac surgery, whereas cardiology, for instance, was much more active there, and by the end of the day, here for the European scenery, we also have to find strategies on how to strengthen our research capabilities in terms of getting into innovative procedures.

The question to you is, what is the impetus also for lab work in terms of biological implants?

Dr Cosgrove : I don't think I can tell you going forward, but let me just give you an example that has come from a series of different things. I mean, I frankly came in 1979 to Alain Carpentier to learn mitral valve repair; and then I involved Edwards in helping me develop some things; I got 3M to help me develop an aortic cannula; multiple other companies I have dragged into my ‘web,’ if you will, to try and do things. I found out about the AtriCure device as one of my venture capital activities for the Cleveland Clinic, and I had been looking for something for atrial fibrillation for a long period of time and chanced upon this as I was sorting out all the other technologies. And certainly aortic surgery we have taken from the stents; the elephant trunks are now having their distal anastomoses done stented, and it is getting more and more.

So I think there has to be partnership between what we do as surgeons in the laboratory, what we do in the operating room recognizing a problem, what we learn from industry and how we can collaborate with industry. At the end of the day, if there is a product involved, we are not going to make it; industry is. So I have had happy correlations with both, and I think most industries will tell you that they don't have the laboratories to do these sorts of things.

Let me tell you one other thing that I think that is a big area for us, and Gerry (Gerald Buckberg) is going to talk a little bit about this, but I think atrial fibrillation in terms of people developing atrial fibrillation 5 years after valve surgery or 5 years after whatever is a big problem, and I will bet you if you look at a lot of the sudden deaths and a lot of the strokes that happened, it has happened because of atrial fibrillation, whether it is recognized or unrecognized in all of our registries. So if we are going to improve the results, I think we have to think about that. And candidly, I think the left atrial appendage ought to go in anybody that gets their chest cracked, because I don't want one, but I will bet you that over time that that's going to be something that is added to our armamentarium.

Dr D. Birnbaum (Regensburg, Germany): I dare to object a little bit for your investment in atrial fibrillation. As we know many people are going this way in a straightforward medical application at the moment. Despite the results are not so much convincing everybody would do it with the pretension of a settled standard. Couldn't it be that the ease how we can burn tissue around lines, which we think are the right ones, is the reason for such an attractive suggestion of a method en vogue? Do we really know what we are doing in treating atrial fibrillation? Did we investigate into understanding about the complexity of atrial fibrillation, reasons, incidence and then treat the reasons?

And this is a plea:

We heard that three-quarters of all research is given by industry. Why is this the situation? What is the background for this? Why don't we have research funds to understand first what we want to do and then develop a device? So our societies should vote to investigate basic research in the field of atrial fibrillation!

Dr Cosgrove : I agree with you. We don't understand what lesion set is, but without trying various lesion sets and then going back and analyzing them, we are not going to solve that problem. We are going to have to make some mistakes, and if we are unwilling to make the mistakes and try and analyze them and learn from them and publish them and share them, we are never going to get any better. So frankly, we are out there trying to make mistakes, and we have already learned a lot from the mistakes we have made with our atrial fibrillation surgery so far and I expect we are going to make more and probably also learn more in the process.

	Footnotes

 
Presented at the EACTS Symposium for the Future of Cardiac Surgery, Frankfurt, Germany, July 1–2, 2004.

	References

Top Abstract 1. Introduction 2. Trends in cardiac... 3. Factors influencing change 4. Options for progress Appendix References

 

1. Christensen CM, Raynor ME. The innovator's solution, creating and sustaining successful growth. Harvard Business School Press; 2003.
2. Christensen CM. The innovator's dilemma: when new technologies cause great firms to fail. Harvard Business School Press; 1997.
3. Cosgrove DM. The innovation imperative. J Thorac Cardiovasc Surg 2000:839-842.
4. Drucker PF. Innovation and entrepreneurship. Harper Business, Division of Harper Collins Publisher; 1985.
5. Foster RN. Innovation: the attacker's advantage. Summit Books, Division of Simon & Schuster, Inc; 1986.
6. Loop FD, Lytle BW, Cosgrove DM, Stewart RW, Goormastic M, Williams GW, Golding LAR, Gill CC, Taylor PC, Sheldon W, Proudfit WL. Influence of internal-mammary-artery graft. BEHN 1986;314:1-6.
7. Mathews R, Watts W. The deviant's advantage, how fringe ideas create mass markets. Crown Business, Crown Publishing Group, Division of Random House, Inc; 2002.
8. Teisberg EO, Porter ME, Brown GB. Innovation: medicine's best cost-cutter. New York Times February 27, 1994.
9. Teisberg EO, Porter ME, Brown GB. Making competition in health care work. Harvard Business Rev July–August 1994;72(4):131-141.
10. Teisberg EO, Porter ME, Brown GB. Finding a lasting cure for U.S. Health care. Harvard Business Rev September–October 1994;72(5):45-52.
11. Teisberg EO, Porter ME, Brown GB. The debate on health care reform continues. Harvard Business Rev November–December 1994;72(6).
12. U.S. Department of Health and Human Services, FDA; March, 2004. Innovation stagnation, challenge and opportunity on the critical path to new medical products..
13. White SP. New ideas about new ideas, insights on creativity from the world's leading innovators. Perseus Publishing; 2002.

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Delos Cosgrove Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cosgrove, D. Search for Related Content PubMed PubMed Citation Articles by Cosgrove, D.