The detection rate was defined as the percentage of examinations that found at least one adenoma or adenocarcinoma. There were a total of 264,972 colonoscopies eligible for analysis of interval cancers (cancers diagnosed within 6 months of the index colonoscopy were excluded). They detected 712 interval cancers, 60% of which were proximal, and there was a median interval of 39 months from index colonoscopy to diagnosis of cancer. Adenoma detection rates varied widely among the 136 physicians, from 10% to 60% for male patients and 4% to 46% for female patients. The researchers defined quintiles of adenoma detection rates from 16.6% to 38.9%.They found that the risk of an interval CRC, an advanced stage CRC, and a fatal CRC all declined with increasing adenoma detection rates. For example, compared with the lowest quintile, patients of physicians in the highest quintile had hazard ratios of 0.52 for interval CRC (95% CI, 0.39-0.69) and 0.38 for fatal CRC (0.22 - 0.65).
Mark H. Ebell, MD, MS
University of Georgia
Another reason to use Cologuard - Lab analyzers are consistent and not in a hurry
High adenoma detection rate during colonoscopy associated with lower incidence of colorectal cancer
Does a gastroenterologist's adenoma detection rate make a difference in the subsequent incidence of colorectal cancer?
There is a consistent, linear, inverse relationship between higher adenoma detection rates and a lower rate of colorectal cancer (CRC) and CRC death. I'll be asking my gastroenterologist about his detection rate before my next colonoscopy! (LOE = 2b)
Corley DA, Jensen CD, Marks AR, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 2014;370(14):1298-1306.
The adenoma detection rate has been proposed as a quality measure, with professional societies recommending a rate of at least 15% for female patients and 25% for male patients. But is this a valid quality measure? These researchers at Kaiser Permanente identified all patients who received colonoscopy between 1998 and 2010 and who had at least 6 months of follow-up. Patients were followed up for 10 years, or until a diagnosis of CRC, or until they left the insurance plan. The population had a median age of 64 years, 52% were women, and 57.4% of the colonoscopies were diagnostic (ie, in a symptomatic patient). Gastroenterologists had to perform 300 or more total colonoscopies (75 or more screening colonoscopies) during the study period to be included, and colonoscopies included screening, surveillance, and diagnostic procedures. The detection rate was defined as the percentage of examinations that found at least one adenoma or adenocarcinoma. (cont)
Although t his looks like a clear advantage for fecal DNA (60 of 65 cancers detected, compared with 48 of 65 for FIT), it is important to look a bit further. The lower specificity for fecal DNA meant that there were nearly 3 times as many false positive results that would have required a follow-up colonoscopy if fecal DNA was the sole screening test (1231, vs 472 for FIT). Using fecal DNA, there would have been 22 colonoscopies per cancer detected, compared with 11 using FIT. Also, fecal DNA testing requires the entire stool specimen, collected using a small bucket that hangs in the toilet, and costs approximately $400 to $800 (FIT costs approximately $3 to $40). Remember, because CRC takes several years to progress from adenoma to cancer, a FIT test could be performed annually at a much lower cost and likely detect many of the initially missed cancers in subsequent years.
Mark H. Ebell, MD, MS
University of Georgia
The below is an evidence based service that goes out to thousands of docs. Came out today. They are usually spot on. I think they missed the boat on several areas such as cost, compliance with yearly FIT, ease of use of device etc.
Accuracy of fecal DNA and fecal immunochemical test for colorectal cancer detection
How accurate are the new fecal DNA and fecal immunochemical tests as screening tests for colorectal cancer?
Fecal DNA is more sensitive but less specific than fecal immunochemical testing (FIT), and as a result has a higher false positive rate. The fecal DNA test is also more expensive than other noninvasive alternatives such as FIT. We do not know which test will be better at reducing mortality. (LOE = 2b)
Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget Stool DNA Testing for Colorectal-Cancer Screening. N Engl J Med 2014;370(14):1287-1297.
Diagnostic test evaluation
Fecal DNA testing looks for abnormalities characteristic of the DNA in colorectal cancer (CRC), while fecal immunochemical testing (FIT) is an improved version of the older tests that detect fecal occult blood but only requires a single stool specimen. Adults aged 50 years to 85 years, at average risk for CRC, who were undergoing screening colonoscopy were invited to participate in the study. A total of 11,016 agreed, and underwent the required tests. Of that group, 689 were excluded because of an insufficient specimen for fecal DNA or a specimen that leaked in shipping (ick!), 304 others were excluded because of inadequate colonoscopy, and 34 had an insufficient sample for FIT. Of the final group of 9989 participants, 65 received a diagnosis of cancer. Fecal DNA testing was 92% sensitive and 87% specific, while FIT was 74% sensitive and 95% specific. (cont.)
Biotech - off the top of my head CMS will reimburse $500 for breast MRI screen in high risk women and $1000 for BRCA testing. Both screening tests.
Ranjo - You know I'm a big EXAS believer. But remember it is not a yearly test - so you have to divide the below revenues by 3 to get a yearly number over time.
Great pick up Sailing! I never saw that mentioned before. That doesn't mean they'll change it but the premise is very interesting. Since FOBT is rated an "A" recommendation it's hard to imagine Cologuard not being an "A".
The contexual questions are also very interesting:
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
What are the current rates of overall screening for colorectal cancer and screening with specific tests in the United States?
What is the adherence to testing for each of the currently available screening tests? What is the adherence to followup diagnostic colonoscopy for abnormal screening test results (i.e., fecal testing, flexible sigmoidoscopy, CT colonography)?
Do rates of screening or adherence to screening tests vary by important subpopulations (i.e., by age, sex, race/ethnicity)?
What is the likelihood of progression or regression of small adenomas (i.e., measuring 6 to 9 mm) to colorectal cancer?
Does the natural history (progression or regression) of adenomas vary by race/ethnicity?
What is the distribution of colorectal lesions (colorectal cancer, advanced adenomas, small adenomatous polyps) by location in the colon (e.g., proximal versus distal colon)?
Does the distribution of lesions in the colon vary by important subpopulations (i.e., by age, sex, race/ethnicity)?
Are there differences in adenoma (and advanced adenoma) prevalence or count by race/ethnicity?
I think these strongly favor Cologuard as ADHERENCE is in several criteria. Likelihood of progression of 6-9mm adenomas. These are very unlikely to progress and this is where cologuard doesn't perform as well - that's a good thing. They talk about distribution by location where Cologuard excels compared to Colonoscopy on the R side with sessile lesions
Cost isn't even mentioned - if folks want to hold that against us.
People are using about $22 per FIT test but that is not the only cost. My office has to first purchase the kits ($187 for 25). Patient are supposed to do 2 stool samples for FIT - so that's $15. I need to pay a lab tech to run the test. I need to have someone send out a letter to the patient about the test results. I need to pay postage. So, although the payment claim may be $22 a year, add another $20 or so in product and personnel cost and your at $40+ or so. Multiply that times 3 and your at $120+. All of a sudden $300-$400 doesn't look so bad for a superior test and someone else is doing all of the work and follow up.
Kleeno - "There would be no liability since FIT is an approved test. Only if ColoGuard is mandated to be used instead of FIT due to superiority, would it lead to liability."
I don't believe that is quite accurate. Physicians should disclose approved options to the patient. If they just give an FOBT/FIT without disclosing that more specific and sensitive tests are available they could open themselves up to liability. Just like if someone offered Cologuard without mentioning colonoscopy as an alternative they might set themselves up for liability if a cancer is missed. So, I think it's fine to order a FIT but I'd also document that alternatives were explained to keep myself safe.
Using - it takes all types. Congrats on your profits and good luck. I hope you visit and invest in Exact again (at much higher levels :))
CMS will cover once it's FDA approved - the question is at what price?
BCBS and all other insurers will cover for a number of reasons. One is that it is cost effective and papers will be coming out proving that. Second is something called HEDIS - look it up. Colorectal cancer screening is a HEDIS measure. Payors must pass HEDIS measures or they are punished and fined. So they want their members screened by any approved method. Getting 1 Colosure is much more likely than 3 yearly FIT's. Hospital systems and Docs are also graded on HEDIS scores and they need to meet their performance measures. For all those not getting colonoscopy ( about half of folks) getting a Cologuard every 3 years will assure compliance.
Their will be folks on every part of the healthcare delivery system eager and incentivized to use Cologuard.
Using - Very few of us expected EPI to pass with vastly inferior #'s to Exas. So the fact that they got a 5-4 vote suggests to me an overwhelming + vote for Exas.
I agree living - I think this vote assures a positive vote tomorrow yet leaves the competition question wide open. And even if it ends up passing I doubt it will get much traction- if any- in the medical guideline community
The number needed to screen to detect 1 advanced precancerous lesions was 31 with the multitarget stool DNA test vs. 55 with the fecal immunochemical test. The specificity for no colorectal cancer or advanced precancerous lesion was 86.6% with the multitarget stool DNA test vs. 94.9% with the fecal immunochemical test. For detection of either colorectal cancer or advanced precancerous lesions, the multitarget DNA test had a positive predictive value of 23.6% and negative predictive value of 94.7%, and the fecal immunochemical test had positive predictive value of 32.6% and negative predictive value of 93.6%.
These results show that stool DNA testing is associated with significantly higher sensitivity than fecal immunochemical testing for detection of colorectal cancer and advanced precancerous lesions, at the expense of lower specificity. For a screening test for cancer, the higher sensitivity is more important, as long as there are not too many false positives, which appears to be the case here. Although the DNA testing had a higher detection rate for identifying colorectal cancers compared to the immunochemical testing, the greater ability to detect precancerous lesions is at least as significant, since the optimal goal is to prevent cancer. Further studies are required to determine the optimal interval screening duration for stool DNA testing, and to address other practical aspects of testing, such as stool collection and ensuring samples have sufficient DNA. The cost of DNA testing must also be considered, particularly since many individuals who do not currently have routine screening may not have access to this technology. Moreover, randomized trials are needed to determine whether stool DNA testing improves clinical outcomes such as mortality when compared to other screening tests.
During colonoscopy, 65 persons (0.7%) were found to have colorectal cancer and 757 persons (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps ≥ 1 cm in greatest dimension). For detection of any colorectal cancer, the multitarget stool DNA test had a sensitivity of 92.3% vs. 73.8% with the fecal immunochemical test (p = 0.002). The corresponding number needed to screen to detect 1 case of colorectal cancer was 166 with the multitarget stool DNA test vs. 208 with the fecal immunochemical test. Similarly, for detection of advanced precancerous lesions, the multitarget stool DNA test had a sensitivity of 42.4% vs. 23.8% with the fecal immunochemical test (p
I know everyone is focused on FDA but this just came in my email:
In Colorectal Cancer Screening, Multitarget Stool DNA Test Appears to Have Higher Sensitivity Than Fecal Immunochemical Test
Reference: N Engl J Med 2014 Mar 19 early online (level 2 [mid-level] evidence)
Colorectal cancer is a major cause of morbidity and mortality in the United States (CA Cancer J Clin 2013 Jan;63(1):11). The American Cancer Society and American Gastroenterological Association recommend screening for colorectal cancer beginning at age 50 years, and list both stool DNA test and fecal immunochemical test as options for detecting cancer (CA Cancer J Clin 2008 May-Jun;58(3):130 full-text). The diagnostic performance of a new stool DNA test was compared to the fecal immunochemical test for detection of colorectal cancer in a recent cohort study of 11,016 asymptomatic persons aged 50-84 years with average risk for colorectal cancer.
All patients had the multitarget DNA test and fecal immunochemical test done from a single stool sample prior to planned routine screening colonoscopy (reference standard). The DNA test consisted of a hemoglobin immunoassay plus quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and beta-actin. Patients with a personal or family history of colorectal cancer or a personal history of colorectal neoplasia, digestive cancer, or inflammatory bowel disease were excluded. A total of 9,989 patients (91%) were analyzed after exclusion of 1,027 with uninterpretable or missing results for any screening test, including problems with collection of the stool sample for the DNA test and technical failure due to insufficient DNA. The cutoffs for a positive result were defined as ≥ 183 on the composite score from a logistic-regression algorithm for the DNA test, and 100 ng/mL hemoglobin for the fecal immunochemical test.
I think the shorts spread their bets around and figure most biotechs lose so they'll be ahead in the end. Also, I think they overestimate the negative number of only 42% precancerous lesions found failing to understand the power of repeated testing and high sensitivity in more advanced lesions
What keeps me feeling good about adcom is
1) Conroy is smart and he wouldn't have built a multi million dollar lab and be hiring staff for launch if he thought there was a chance of FDA failure.
2) FIt tests are already FDA approved and Cologuard is clearly superior, so why wouldn't Cologuard be approved
3) Deep-C protocol was reviewed by the FDA prior to it's beginning and all primary and secondary endpoints were met - so why would the goalposts be moved now. (Yes, I remember AMRN Ranjo!)
This isn't that complicated. FIT is FDA approved. Cologuard is much better test in cancer and precancer detection. It will be approved. The question is how fast will the uptake be.