Exporting Science

On a recent visit to the campus of my alma mater, I had a chance to visit some of the biomedical research laboratories. One of those is under the direction of a tenured professor who is making new biodegradable blood vessels the size of a coronary artery that will last long enough to allow for new fibrous tissue to form and replace the degrading substance. Even more exciting is the fact that the new vessel does not initiate an inflammatory reaction, since the vessel lumen will not be a site for platelet activation and in-situ thrombosis.

The professor was just as excited that a venture capitalist had just obtained the license to develop the technology and was about to begin human testing of the vessel in Asia.

Unfortunately, that is where a host of new devices and drugs are being tested.

Compared with the pharmaceutical industry trials, which have used a mixture of domestic and international sites for new drugs research, device trials have used international and particularly European sites for the development of new products. The development of new stents, for instance, was almost exclusive to Europe, and provided this therapy to Europeans far earlier than to Americans. This migration is a result of a more-receptive approval environment and the fact that human testing in Europe and Asia is recruitment for trials is faster and less expensive.

Since 1999, the number of new Premarket Approvals (PMAs) – the Food and Drug Administration’s regulatory process that is required before a novel device with significant patient health risks can get to market – has decrease significantly. In 2000, the FDA approved approximately 60 PMAs; by 2009, the number of approvals had decreased to 15. According to a device industry–supported survey of 176 of 750 potential medical technology companies (FDA Impact on U.S. Medical Technology Innovation, November 2010), the approval process for a PMA was 54 months in the United States and 11 months in Europe. The survey enumerates a number of process problems that confront the FDA, but the major issue noted by the companies surveyed was that the FDA has become much more risk averse and concerned about safety.

The rush to market, of course, is the driving force behind the increased concern of these delays. Venture capitalists that provide the resources for many small device companies see time as money. They are driven more by their desire to get their product to market quickly and they have a limited concern or appreciation for patient safety. Despite the spate of recent safety problems both in cardiology and orthopedics, they tend to minimize the importance of those problems. The safety aspects of many devices may not, of course, be knowable in the short term and not be measurable in the time frame of an 18- or 24-month clinical trial, but may lie in the distant future.

Much of this overseas migration of science is a result of the significantly lower infrastructure costs in Europe and – especially – in Asia. The per-patient costs in India, for instance, are a fraction of what they are in the United States, and the access to patients who can participate in trials is much more easily obtained. This is largely a result of closer physician involvement in the recruiting of patients, and the reluctance of both patients and doctors in the United States to participate in the clinical research trials. Patients hesitate because of a suspicious environment about clinical trials, and doctors are reluctant because they are too busy and are underpaid for their participation. The paradox of this process is that devices and drugs that are tested outside the United States may, because of their cost, be available only to U.S. patients. Whether clinical data obtained in foreign populations are applicable to the U.S. population is also uncertain.

A recent letter from 41 members of Congress, including 6 from Minnesota (which is the U.S. capital of new device companies), has placed increased pressure on the FDA to expedite the approval process and to bring the testing home to the United States ("Members of Minn. delegation urge FDA to speed medical device approvals," Minnesota Independent, Nov. 8, 2011). Of course the return of testing to our shores would be very advantageous to the approval process, but that same acceleration of the process could result in significant patient hazards. The balance between expeditious approval and safety has been an issue that has been going back and forth for the last 20 years, and will continue to be played out in the future.

On a recent visit to the campus of my alma mater, I had a chance to visit some of the biomedical research laboratories. One of those is under the direction of a tenured professor who is making new biodegradable blood vessels the size of a coronary artery that will last long enough to allow for new fibrous tissue to form and replace the degrading substance. Even more exciting is the fact that the new vessel does not initiate an inflammatory reaction, since the vessel lumen will not be a site for platelet activation and in-situ thrombosis.

The professor was just as excited that a venture capitalist had just obtained the license to develop the technology and was about to begin human testing of the vessel in Asia.

Unfortunately, that is where a host of new devices and drugs are being tested.

Compared with the pharmaceutical industry trials, which have used a mixture of domestic and international sites for new drugs research, device trials have used international and particularly European sites for the development of new products. The development of new stents, for instance, was almost exclusive to Europe, and provided this therapy to Europeans far earlier than to Americans. This migration is a result of a more-receptive approval environment and the fact that human testing in Europe and Asia is recruitment for trials is faster and less expensive.

Since 1999, the number of new Premarket Approvals (PMAs) – the Food and Drug Administration’s regulatory process that is required before a novel device with significant patient health risks can get to market – has decrease significantly. In 2000, the FDA approved approximately 60 PMAs; by 2009, the number of approvals had decreased to 15. According to a device industry–supported survey of 176 of 750 potential medical technology companies (FDA Impact on U.S. Medical Technology Innovation, November 2010), the approval process for a PMA was 54 months in the United States and 11 months in Europe. The survey enumerates a number of process problems that confront the FDA, but the major issue noted by the companies surveyed was that the FDA has become much more risk averse and concerned about safety.

The rush to market, of course, is the driving force behind the increased concern of these delays. Venture capitalists that provide the resources for many small device companies see time as money. They are driven more by their desire to get their product to market quickly and they have a limited concern or appreciation for patient safety. Despite the spate of recent safety problems both in cardiology and orthopedics, they tend to minimize the importance of those problems. The safety aspects of many devices may not, of course, be knowable in the short term and not be measurable in the time frame of an 18- or 24-month clinical trial, but may lie in the distant future.

Much of this overseas migration of science is a result of the significantly lower infrastructure costs in Europe and – especially – in Asia. The per-patient costs in India, for instance, are a fraction of what they are in the United States, and the access to patients who can participate in trials is much more easily obtained. This is largely a result of closer physician involvement in the recruiting of patients, and the reluctance of both patients and doctors in the United States to participate in the clinical research trials. Patients hesitate because of a suspicious environment about clinical trials, and doctors are reluctant because they are too busy and are underpaid for their participation. The paradox of this process is that devices and drugs that are tested outside the United States may, because of their cost, be available only to U.S. patients. Whether clinical data obtained in foreign populations are applicable to the U.S. population is also uncertain.

A recent letter from 41 members of Congress, including 6 from Minnesota (which is the U.S. capital of new device companies), has placed increased pressure on the FDA to expedite the approval process and to bring the testing home to the United States ("Members of Minn. delegation urge FDA to speed medical device approvals," Minnesota Independent, Nov. 8, 2011). Of course the return of testing to our shores would be very advantageous to the approval process, but that same acceleration of the process could result in significant patient hazards. The balance between expeditious approval and safety has been an issue that has been going back and forth for the last 20 years, and will continue to be played out in the future.

On a recent visit to the campus of my alma mater, I had a chance to visit some of the biomedical research laboratories. One of those is under the direction of a tenured professor who is making new biodegradable blood vessels the size of a coronary artery that will last long enough to allow for new fibrous tissue to form and replace the degrading substance. Even more exciting is the fact that the new vessel does not initiate an inflammatory reaction, since the vessel lumen will not be a site for platelet activation and in-situ thrombosis.

The professor was just as excited that a venture capitalist had just obtained the license to develop the technology and was about to begin human testing of the vessel in Asia.

Unfortunately, that is where a host of new devices and drugs are being tested.

Compared with the pharmaceutical industry trials, which have used a mixture of domestic and international sites for new drugs research, device trials have used international and particularly European sites for the development of new products. The development of new stents, for instance, was almost exclusive to Europe, and provided this therapy to Europeans far earlier than to Americans. This migration is a result of a more-receptive approval environment and the fact that human testing in Europe and Asia is recruitment for trials is faster and less expensive.

Since 1999, the number of new Premarket Approvals (PMAs) – the Food and Drug Administration’s regulatory process that is required before a novel device with significant patient health risks can get to market – has decrease significantly. In 2000, the FDA approved approximately 60 PMAs; by 2009, the number of approvals had decreased to 15. According to a device industry–supported survey of 176 of 750 potential medical technology companies (FDA Impact on U.S. Medical Technology Innovation, November 2010), the approval process for a PMA was 54 months in the United States and 11 months in Europe. The survey enumerates a number of process problems that confront the FDA, but the major issue noted by the companies surveyed was that the FDA has become much more risk averse and concerned about safety.

The rush to market, of course, is the driving force behind the increased concern of these delays. Venture capitalists that provide the resources for many small device companies see time as money. They are driven more by their desire to get their product to market quickly and they have a limited concern or appreciation for patient safety. Despite the spate of recent safety problems both in cardiology and orthopedics, they tend to minimize the importance of those problems. The safety aspects of many devices may not, of course, be knowable in the short term and not be measurable in the time frame of an 18- or 24-month clinical trial, but may lie in the distant future.

Much of this overseas migration of science is a result of the significantly lower infrastructure costs in Europe and – especially – in Asia. The per-patient costs in India, for instance, are a fraction of what they are in the United States, and the access to patients who can participate in trials is much more easily obtained. This is largely a result of closer physician involvement in the recruiting of patients, and the reluctance of both patients and doctors in the United States to participate in the clinical research trials. Patients hesitate because of a suspicious environment about clinical trials, and doctors are reluctant because they are too busy and are underpaid for their participation. The paradox of this process is that devices and drugs that are tested outside the United States may, because of their cost, be available only to U.S. patients. Whether clinical data obtained in foreign populations are applicable to the U.S. population is also uncertain.

A recent letter from 41 members of Congress, including 6 from Minnesota (which is the U.S. capital of new device companies), has placed increased pressure on the FDA to expedite the approval process and to bring the testing home to the United States ("Members of Minn. delegation urge FDA to speed medical device approvals," Minnesota Independent, Nov. 8, 2011). Of course the return of testing to our shores would be very advantageous to the approval process, but that same acceleration of the process could result in significant patient hazards. The balance between expeditious approval and safety has been an issue that has been going back and forth for the last 20 years, and will continue to be played out in the future.