National Coalition for Quality Colorectal Screening and Care

1. National Coalition for Quality Colorectal Screening and Care Stanford Plavin MD Vice Chairperson Board Certified Anesthesiologist and Patient Safety Advocate

2. The Coalition was formed by gastroenterologists, surgeons, primary care physicians, oncologists, anesthesiologists, patient advocacy groups, and concerned individuals to promote quality colorectal cancer screening and care, and to make a positive impact on the number of people who are not taking advantage of the life saving opportunities for colorectal cancer screening. • We are deeply concerned that the improper labeling of fospropofol will not promote safe and effective colorectal cancer screening.

3. NDA- 22-244Fospropofol • FDA stated mission is to protect the consumer and advance technology; “protect first” • Fospropofol is a prodrug form of propofol • Pro drug: Administered in active or less active form and then metabolized to in vivo form as an active metabolite: in this case Propofol • It should be treated as such and shown the respect of its parent drug

4. DRUGS OF THE FUTURE • Fospropofol disodium • Water-soluble prodrug of propofol designed to overcome some of the disadvantages of lipid based form: pain on injection and hyperlipidemia with long term use • Upon fospropofol injection, propofol is released from the prodrug and “equilibrates rapidly” into brain tissue to exert a dose-dependent “anesthetic” effect. Phase I studies showed that the released propofol induces anesthesia with even GREATER POTENCY than the lipid based propofol. • It was effective at maintaining sedation for colonoscopy. • Itself has significant shortcomings: kinetics, parasthesias

5. Gastroenterology and Fospropofol • Fospropofol inevitably will find widespread use among gastroenterologists if approved without the appropriate warning and labeling… leading to? • The AGA Institute stated: "In many instances, sedation related education is underrepresented in US gastroenterology professional training. Moreover, sedation related continuing education is not commonly available to mid-career endoscopists." (AGA Institute Review of Endosocopic Sedation. Cohen et al. Gastroenterology 2007;133:675-701)

6. Gastroenterology and Fospropofol • This will potentially expose millions of patients to a drug that gastroenterologists, even by the assessment of their own AGA Institute, are not trained to employ and administer safely.

7. Our Role: National Coalition for Quality Colorectal Screening and Care • Advocate for better sedation options, but with the safety and quality necessary • Sedation success: those percentages in the 90 plus range with fospropofol also had more than 25% who were considered in “deep sedation or greater”! • Improve patient access to screening; this drug may do just that but it needs to be studied further and properly labeled so as to protect the patients it is designed to serve. • Propofol is the active drug… That’s the bottom line and the FDA has already correctly ruled on that • Sedation is a continuum; all Medical societies agree, patient safety is first; label fospropofol accordingly and let time and evidenced based medicine sort out the details.

8. Observations • The onset of all narcotics and anxiolytics are different yet the labeling is these controlled substances are essentially the same. • Therefore the use of fospropofol which has different pharmacodynamics and kinetics but ultimately is PROPOFOL in the body; should be labeled the same and given the same RESPECT. • Let time and appropriate future studies dictate further modifications to drug labeling and not this process alone. • This is an ANESTHETIC drug; let the professionals such as anesthesiologists and anesthetists and those properly trained in general anesthesia and airway management handle these drugs.

9. Fospropofol Studies • The design of these studies seems to be skewed towards a bias of finding away around the labeling of its real active drug propofol • Accidents waiting to happen • Start slowly; expand its use slowly; less mishaps, less deaths, proper and appropriate growth and utilization of the drug if it is meant to be • Phase III studies are supposed to be done head to head with the competition of which is the best current treatment. • Everyone knows that the use of propofol for anesthesia for colonoscopy, endoscopy, and other procedures is the best current treatment; yet head to head studies were ignored. • Why, because it is the same drug with different onset and dynamics. It should be labeled the same. It’s not better

10. Institute for Safe Medical Practices:Propofol sedation: who should administer?(Institute for safe medical practices) • ONLY difference is “FOS” • Should have STRICT PRODUCT LABELING • Can have unpredictable and profound effects • No reversal agent • Legal barriers • Safe Practice recommendations CONCLUSION: SHOULD BE ADMINISTERED ONLY BY PERSONS WHO ARE (1) TRAINED IN THE ADMINISTRATION OF DRUGS THAT CAUSE DEEP SEDATION AND ANESTHESIA,( 2) ABLE TO INTUBATE THE PATIENT IF NECESSARY, AND (3) NOT INVOLVED SIMULTANEOUSLY IN THE PROCEDURE ITSELF THE GROWTH AND USE OF PROPOFOL FOR PROCEDURES SUCH AS COLONOSCOPY AND ENDOSCOPY HAS INCREASED DRAMATICALLY AND HAS DONE SO WITH PROPER CHECKS AND BALANCES. NO SENSE IS NOT DOING WHAT IS RIGHT!

11. Thank you on behalf of those thousands of physicians and patients who are not here to have their voice heard and their interests and safety protected and represented. • Stanford Plavin MD, Vice-Chairperson • www.preventingcolorectalcancer.org