Comments to the Anesthesiology and Respiratory Therapy Devices Panel at the Food and Drug Administration Regarding the Sedasys® Computer-Assisted Personalized Sedation System
Submitted by Carlea Bauman, President
C3: Colorectal Cancer Coalition
May 28, 2009
These comments are submitted on behalf of C3: Colorectal Cancer Coalition (C3), a non-profit, nonpartisan advocacy organization that is committed to the fight against colon and rectal cancer.
We appreciate the opportunity to comment on the Food and Drug Administration’s (FDA) Anesthesiology and Respiratory Therapy Devices Panel’s (ARTDP) consideration of the Sedasys® Computer-Assisted Personalized Sedation system.
C3 pushes for research to improve screening, diagnosis, and treatment of colorectal cancer; for policy decisions that make the most effective colorectal cancer prevention and treatment available to all; and for increased awareness that colorectal cancer is preventable, treatable, and beatable. C3 believes in fully disclosing sources of financial support, per our disclosure policy, which can be viewed at www.FightColorectalCancer.org/funding.htm. C3 has received no funding from Ethicon Endo-Surgery, Inc. or Johnson & Johnson (J&J). We were briefed on the Sedasys system by company representatives, and have prepared these comments prior to reviewing the FDA briefing information.
Neither these companies nor any of our other corporate supporters have influenced our comments on this issue.
Approximately 1.6 million Americans are screened for colorectal cancer with colonoscopy each yeari. These people balance the risk of a colonoscopy with the significant benefit of preventing colorectal cancer or finding early-stage, curable disease. As patient advocates, our first concern is that colonoscopy is as safe as possible. One risk that colonoscopy patients face comes from sedation. Our second concern is that people are comfortable during the procedure and are satisfied with their care.
We have reviewed data presented to us by Ethicon Endo-Surgery and J&J, but have not reviewed the briefing documents for this meeting. We see potential benefits and risks to patients, but at this time, we cannot make a recommendation regarding approval. Instead, we will share our perspective with you, and ask that you address our questions and comments during your discussion.
Some of the potential benefits to patients that we see with the Sedasys system are:
- For patients undergoing colonoscopy without an anesthetist in the room, the system helps monitor patients in ways that may not be routine now, with the capnometry and an automated response monitor.
- We believe that the continuous infusion of propofol as opposed to a bolus may allow more precise dosing for patients.
- In addition, the safeguards described are reassuring. We think that requiring that propofol be administered with concurrent oxygen and restricting the size of the loading dose will be beneficial to the patient.
At the same time, we have questions about potential risks, which we hope will be discussed by the panel.
In the 1000 person trial, Sedasys was compared to standard colonoscopy sedation. The primary endpoint was an Area Under the Curve calculation of oxygen de-saturation. The trial was randomized, but not blinded. The patient population was carefully selected to reduce risk to patients.
- Control Arm: We are somewhat concerned about the choice of control arm. Rather than compare propofol delivered via the Sedasys computer assisted personalized sedation automated system to standard sedation with midazolam and an opiate should not the CAPS system have been compared to administration of the same medication (propofol) by an anesthesiologist? We understand that due to the nature of the trial design, it would have been impossible to conduct as a blinded trial. At the same time, the results of non-blinded trials are more likely to be biased than results from blinded trials. We would like to understand how FDA and this committee will take this potential bias into account.
- Valid Endpoint: The primary endpoint, area under the curve of oxygen desaturation, seems to make sense intuitively. We would like to know if this endpoint has been validated to the FDA’s and this committee’s satisfaction.
- Exclusion Criteria: The trial excluded patients at higher risk for problems during sedation. We would like to understand whether the FDA and this committee believe that these exclusion criteria are sufficient for the product label, or whether additional exclusion criteria should be included. We are especially concerned that only 50 individuals over 70 were included in the trial, and, if approval is recommended, urge you to consider an upper age limit on the use of the device.
- Real-life, high volume use: The trial tested a complex automated system that made sure the patient was breathing adequately while minimally to moderately sedated and that deep sedation requiring respiratory assistance was avoided. Sedasys was tested at eight sites, in approximately 500 people, with no serious adverse events. While the trial was large for a device trial, if Sedasys is used more widely in many different community endoscopy settings with many more patients, there is a greater risk of serious adverse events related to deep sedation or the need for respiratory assistance, as well as quality control issues with the machine itself. If this committee votes for approval, we would like to understand what steps will be taken by the FDA and the manufacturers of Sedasys to minimize patient risk during launch and early use of the system.
People undergoing screening colonoscopy are trying to prevent disease; therefore, we must minimize the risk of colonoscopy. Our overriding concern is that people undergoing screening colonoscopy are safe and comfortable.
We greatly appreciate the opportunity to comment on the critical issues in front of you today, and look forward to listening to your discussion. Thank you very much for your consideration of our comments.