GI and Hepatology News

Introduction

Colorectal cancer (CRC) screening significantly reduces CRC incidence and mortality, but only 65% of eligible individuals report being up-to-date with screening.¹ Colonoscopy is the most widely used opportunistic screening method in the United States and is associated with many barriers to uptake. Providing patients a choice of colonoscopy and/or stool-based tests, improves screening adherence in randomized controlled trials.^2,3 Non-invasive screening options have expanded from stool occult blood and multi-target DNA tests, to multi-target stool RNA tests, and novel blood-based tests, the latter only U.S. Food and Drug Administration (FDA) approved for patients who refuse colonoscopy and stool-based tests. This review summarizes the test characteristics of stool and blood CRC screening options and provides guidance on clinical implications of their use.

Stool Occult Blood Tests

Guaiac-based fecal occult blood testing (gFOBT) significantly reduces CRC mortality by 33%-35% when implemented on an annual or biennial basis.^4,5 Fecal immunochemical testing (FIT) has supplanted gFOBT with advantages including independence from dietary restriction and medication-related interference, use of antibodies specific to human globin, and the need for only a single stool sample.

The most common threshold for a positive FIT in the U.S. is ≥ 20 micrograms (μg) of hemoglobin per gram (g) of stool. FIT is approved by the FDA as a qualitative positive or negative result based on a threshold value.⁶ A meta-analysis summarized test characteristics of commercially available FITs at various detection thresholds.⁷ The CRC sensitivity and specificity was 75% and 95% for ≥ 20 ug hemoglobin/g stool, and 91% and 90% for 10 ug hemoglobin/g stool, respectively. The sensitivity for advanced adenomas ranged from 25% at 20 μg/g to 40% at a 10 μg/g. Programmatic use of FIT in adults ages ≥ 50 years at 20 ug/g of stool, in cohort and case control studies, has been shown to significantly reduce CRC mortality by 33%-40% and advanced stage CRC by 34%.^8,9

Over 57,000 average-risk individuals ages 50–69 years were randomized to biennial FIT or one-time colonoscopy and followed for 10 years.¹⁰ CRC mortality and incidence was similar between the groups: 0.22% with FIT vs. 0.24% with colonoscopy and 1.13% with FIT vs. 1.22% with colonoscopy, respectively. Thus, confirming biennial FIT screening is non-inferior to one-time colonoscopy in important CRC-related outcomes.
 

Multi-Target Stool Tests

Two multitarget stool DNA tests (mt-sDNA) known as Cologuard™ and Cologuard Plus™ have been approved by the FDA. Both tests include a FIT (with a positivity threshold of 20 μg hemoglobin per gram of stool) combined with DNA methylation markers. The test result is qualitative, reported as a positive or negative. Cologuard™ markers include methylated BMP3, NDRG4, and mutant KRAS while Cologuard Plus™ assesses methylated LASS4, LRRC4, and PPP2R5C. The respective mt-sDNA tests were studied in 9989 of 12,776 and 20,176 of 26,758 average-risk individuals undergoing colonoscopy and the results were compared to a commercially available FIT (with a positivity threshold of 20 μg hemoglobin/gram of stool).^11,12 In both trials, the sensitivity for CRC and advanced precancerous lesions was higher with the mt-sDNA tests compared to FIT but had a significantly lower specificity for advanced precancerous lesions versus FIT (see Table 1). An age-related decline in specificity was noted in both trials with mt-sDNA, a trend not observed with FIT. This reduction may be attributed to age-related DNA methylation.

Multi-Target Stool RNA Test

A multi-target stool RNA test (mt-sRNA) commercially available as ColoSense™ is FDA-approved. It combines FIT (at a positivity threshold of 20 μg hemoglobin/gram of stool) with RNA-based stool markers. The combined results of the RNA markers, FIT, and smoking status provide a qualitative single test result. In the trial, 8,920 adults aged ≥45 underwent the mt-sRNA test and FIT followed by colonoscopy (13). The mt-sRNA showed higher sensitivity for CRC than FIT (94.4% versus 77.8%) and advanced adenomas (45.9% versus 28.9%) but lower CRC specificity (84.7% vs 94.7%) (Table 1). Unlike mt-sDNA-based tests, mt-sRNA showed consistent performance across age groups, addressing concerns about age-related declines in specificity attributed to DNA methylation. 
 

Blood-Based Tests

In 2014, the first blood-based (BBT) CRC screening test known as Epi proColon™ was FDA but not Centers for Medicare & Medicaid Services (CMS) approved for average-risk adults ≥50 years of age who are offered and refused other U.S Preventive Services Task Force (USPSTF) endorsed CRC screening tests. It is a qualitative test for detection of circulating methylated Septin 9 (mSeptin9). The accuracy of mSeptin9 to detect CRC was assessed in a subset of 7941 asymptomatic average risk adults undergoing screening colonoscopy.¹⁴ The sensitivity and specificity for CRC were 48% and 91.5%, respectively. The sensitivity for advanced adenomas was 11.2%. An increase in sensitivity to 63.9% and reduction in specificity to 88.4% for CRC was demonstrated in a sub-analysis of available samples where an additional (third) polymerase chain replicate was performed. Epi proColon™ is not currently reimbursed by Medicare and not endorsed in the latest USPSTF guidelines.

Technologic advancements have improved the detection of circulating tumor markers in the blood. The Shield™ BBT approved by the FDA in 2024 for average risk adults ≥ 45 years integrates three types of cfDNA data (epigenetic changes resulting in the aberrant methylation or fragmentation patterns, and genomic changes resulting in somatic mutations) into a positive or negative test result. In the trial, 22,877 average-risk, asymptomatic individuals ages 45–84 were enrolled and clinical validation was performed in 7,861 of the participants.¹⁵ The sensitivity for CRC was 83.1% which decreased to 55% for stage I tumors (see Table 1). CRC specificity was 89.6% and the sensitivity for advanced adenomas and large sessile serrated lesions was 13.2%.

Another BBT SimpleScreen™, which is not yet FDA-approved, analyzed circulating, cell-free DNA methylation patterns in 27,010 evaluable average-risk, asymptomatic adults ages 45–85 years undergoing screening colonoscopy.¹⁶ The sensitivity and specificity for CRC was 79.2% and 91.5%, respectively. Similar to Shield, the sensitivity for stage I CRC was low at 57.1%. The sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5% which did not meet the prespecified study criteria. 
 

Effectiveness and Cost Effectiveness

Modeling studies have evaluated novel noninvasive CRC screening tests compared to FIT and colonoscopy.^17-20 One compared a hypothetical BBT performed every 3 years that meets the minimum CMS threshold CRC sensitivity and specificity of 74% and 90%, respectively, to other established CRC screening tests beginning at age 45.¹⁷ Every 3-year BBT reduced CRC incidence and mortality by 40% and 52%, respectively compared to no screening. However, the reductions were much lower than yearly FIT (72% and 76%, respectively), every 10 year colonoscopy (79% and 81%, respectively), and triennial mt-sDNA (68% and 73%, respectively). The BBT resulted in fewer quality-adjusted life-years per person compared to the alternatives.

Additionally, FIT, colonoscopy, and mt-sDNA were less costly and more effective. Advanced precancerous lesion detection was a key measure for a test’s effectiveness. BBT characteristics would require a CRC sensitivity and specificity of >90% and 90%, respectively, and 80% sensitivity for advanced precancerous lesions at a cost of ≤$120–$140 to be cost-effective compared to FIT at comparable participation rates.

Another analysis simulated colorectal neoplasia progression and compared clinical effectiveness and cost between annual FIT, every 3 year stool mt-sRNA, every 3 year stool mt-sDNA tests, every 3 year stool Shield™; these outcomes were compared to colonoscopy every 10 years and no screening in adults ≥ age 45 over different adherence rates.¹⁹ At real-world adherence rates of 60%, colonoscopy prevented most CRC cases and associated deaths. FIT was the most cost-effective strategy at all adherence levels. Between the multi-target stool tests and Shield™, mt-sRNA was the most cost-effective. Compared to FIT, mt-sRNA reduced CRC cases and deaths by 1% and 14%.

The third study evaluated CRC incidence and mortality, quality-adjusted life-years and costs with annual FIT, colonoscopy every 10 years, mt- sDNA tests, mt-sRNA test, and BBTs.²⁰ The latest mt-sDNA (Colguard plus™) and mt-sRNA achieved benefits approaching FIT but the Shield™ test was substantially less effective. The authors hypothesized that if 15% of the population substituted Shield™ for current effective CRC screening strategies, an increase in CRC deaths would occur and require 9-10% of the unscreened population to uptake screening with Shield to avert the increases in CRC deaths due to the substitution effect.
 

Clinical Implications

The effectiveness of non-invasive screening strategies depends on their diagnostic performance, adherence, and ensuring a timely colonoscopy after a positive test. Two claims-based studies found 47.9% and 49% of patients underwent follow-up colonoscopy within 6 months of an abnormal stool or BBT CRC screening test, respectively.^21-22

Conclusions

Non-invasive stool mt-sDNA and mt-sRNA have higher effectiveness than the new BBTs. BBTs can lead to increased CRC mortality if substituted for the FDA and CMS-approved, USPSTF-endorsed, CRC screening modalities. If future BBTs increase their sensitivity for CRC (including early-stage CRC) and advanced precancerous lesions and decrease their cost, they may prove to have similar cost-effectiveness to stool-based tests. Currently, BBTs are not a substitute for colonoscopy or other stool tests and should be offered to patients who refuse other CRC screening modalities. A personalized, risk-adapted approach, paired with improved adherence and follow-up are essential to optimize the population-level impact of CRC screening and ensure equitable, effective cancer prevention.

Dr. Gupta is based at the Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore. Dr. Burke and Dr. Macaron are based at the Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio. Dr. Gupta and Dr. Macaron declared no conflicts of interest in regard to this article. Dr. Burke declared research support from Emtora Biosciences. She is a current consultant for Lumabridge, and has been a consultant for Sebela and Almirall. She also disclosed support from Myriad, Genzyme, Ferring, Merck, Sharp and Dohme, Abbvie, Salix, and Natera.

References

1. Benavidez GA, Sedani AE, Felder TM, Asare M, Rogers CR. Rural-urban disparities and trends in cancer screening: an analysis of Behavioral Risk Factor Surveillance System data (2018-2022). JNCI Cancer Spectr. 2024 Nov 1;8(6):pkae113

2. Galoosian A, Dai H, Croymans D, et al. Population Health Colorectal Cancer Screening Strategies in Adults Aged 45 to 49 Years: A Randomized Clinical Trial. JAMA. 2025 Aug 4:e2512049. doi: 10.1001/jama.2025.12049. Epub ahead of print. 

3. Pilonis ND, Bugajski M, Wieszczy P, et al. Participation in Competing Strategies for Colorectal Cancer Screening: A Randomized Health Services Study (PICCOLINO Study). Gastroenterology. 2021 Mar;160(4):1097-1105.

4. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106–1114.

5. Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet. 1996 Nov 30;348(9040):1467-71. doi: 10.1016/S0140-6736(96)03430-7. PMID: 8942774.

6. Burke CA, Lieberman D, Feuerstein JD. AGA Clinical Practice Update on Approach to the Use of Noninvasive Colorectal Cancer Screening Options: Commentary. Gastroenterology. 2022 Mar;162(3):952-956. doi: 10.1053/j.gastro.2021.09.075. Epub 2022 Jan 28. PMID: 35094786.

7. Imperiale TF, Gruber RN Stump TE, et al. Performance characteristics of fecal immunochemical tests for colorectal cancer and advanced adenomatous polyps: a systematic review and meta-analysis. Ann Intern Med 2019; 170(5):319-329

8. Doubeni CA, Corley DA, Jensen CD, et al. Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death. JAMA Netw Open. 2024 Jul 1;7(7):e2423671. doi: 10.1001/jamanetworkopen.2024.23671. 

9. Chiu HM, Jen GH, Wang YW, et al. Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers. Gut. 2021 Dec;70(12):2321-2329. doi: 10.1136/gutjnl-2020-322545. Epub 2021 Jan 25.

10. Castells A, Quintero E, Bujanda L, et al; COLONPREV study investigators. Effect of invitation to colonoscopy versus fecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial. Lancet. 2025;405(10486):1231–1239

11. 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

12. Imperiale TF, Porter K, Zella J, et al. Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):984-993

13. Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget Stool RNA Test for Colorectal Cancer Screening. JAMA. 2023 Nov 14;330(18):1760-1768. 

14. Church TR, Wandell M, Lofton-Day C, et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 2014; 63:317–325.

15. Chung DC, Gray DM 2nd, Singh H, et al. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):973-983.

16. Shaukat A, Burke CA, Chan AT, et al. Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer. JAMA. 2025 Jul 1;334(1):56-63.

17. Ladabaum U, Mannalithara A, Weng Y, et al. Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening with Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy. Gastroenterology. 2024 Jul;167(2):378-391.

18. van den Puttelaar R, Nascimento de Lima P, Knudsen AB, et al. Effectiveness and cost-effectiveness of colorectal cancer screening with a blood test that meets the Centers for Medicare & Medicaid Services coverage decision. Gastroenterology 2024;167:368–377.

19. Shaukat A, Levin TR, Liang PS. Cost-effectiveness of Novel Noninvasive Screening Tests for Colorectal Neoplasia. Clin Gastroenterol Hepatol. 2025 Jun 23:S1542-3565(25)00525-7. doi: 10.1016/j.cgh.2025.06.006. Epub ahead of print. PMID: 40562290.

20. Ladabaum U, Mannalithara A, Schoen RE, Dominitz JA, Lieberman D. Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer. Ann Intern Med. 2024 Dec;177(12):1610-1620.

20. Ciemins EL, Mohl JT, Moreno CA, Colangelo F, Smith RA, Barton M. Development of a Follow-Up Measure to Ensure Complete Screening for Colorectal Cancer. JAMA Netw Open. 2024 Mar 4;7(3):e242693. doi: 10.1001/jamanetworkopen.2024.2693. 

21. Zaki TA, Zhang NJ, Forbes SP, Raymond VM, Das AK, May FP. Colonoscopic Follow-up After Abnormal Blood-Based Colorectal Cancer Screening Results. Gastroenterology. 2025 Jul 21:S0016-5085(25)05775-0. doi: 10.1053/j.gastro.2025.07.019. Epub ahead of print. PMID: 40744392.

 

Introduction

Colorectal cancer (CRC) screening significantly reduces CRC incidence and mortality, but only 65% of eligible individuals report being up-to-date with screening.¹ Colonoscopy is the most widely used opportunistic screening method in the United States and is associated with many barriers to uptake. Providing patients a choice of colonoscopy and/or stool-based tests, improves screening adherence in randomized controlled trials.^2,3 Non-invasive screening options have expanded from stool occult blood and multi-target DNA tests, to multi-target stool RNA tests, and novel blood-based tests, the latter only U.S. Food and Drug Administration (FDA) approved for patients who refuse colonoscopy and stool-based tests. This review summarizes the test characteristics of stool and blood CRC screening options and provides guidance on clinical implications of their use.

Stool Occult Blood Tests

Guaiac-based fecal occult blood testing (gFOBT) significantly reduces CRC mortality by 33%-35% when implemented on an annual or biennial basis.^4,5 Fecal immunochemical testing (FIT) has supplanted gFOBT with advantages including independence from dietary restriction and medication-related interference, use of antibodies specific to human globin, and the need for only a single stool sample.

The most common threshold for a positive FIT in the U.S. is ≥ 20 micrograms (μg) of hemoglobin per gram (g) of stool. FIT is approved by the FDA as a qualitative positive or negative result based on a threshold value.⁶ A meta-analysis summarized test characteristics of commercially available FITs at various detection thresholds.⁷ The CRC sensitivity and specificity was 75% and 95% for ≥ 20 ug hemoglobin/g stool, and 91% and 90% for 10 ug hemoglobin/g stool, respectively. The sensitivity for advanced adenomas ranged from 25% at 20 μg/g to 40% at a 10 μg/g. Programmatic use of FIT in adults ages ≥ 50 years at 20 ug/g of stool, in cohort and case control studies, has been shown to significantly reduce CRC mortality by 33%-40% and advanced stage CRC by 34%.^8,9

Over 57,000 average-risk individuals ages 50–69 years were randomized to biennial FIT or one-time colonoscopy and followed for 10 years.¹⁰ CRC mortality and incidence was similar between the groups: 0.22% with FIT vs. 0.24% with colonoscopy and 1.13% with FIT vs. 1.22% with colonoscopy, respectively. Thus, confirming biennial FIT screening is non-inferior to one-time colonoscopy in important CRC-related outcomes.
 

Multi-Target Stool Tests

Two multitarget stool DNA tests (mt-sDNA) known as Cologuard™ and Cologuard Plus™ have been approved by the FDA. Both tests include a FIT (with a positivity threshold of 20 μg hemoglobin per gram of stool) combined with DNA methylation markers. The test result is qualitative, reported as a positive or negative. Cologuard™ markers include methylated BMP3, NDRG4, and mutant KRAS while Cologuard Plus™ assesses methylated LASS4, LRRC4, and PPP2R5C. The respective mt-sDNA tests were studied in 9989 of 12,776 and 20,176 of 26,758 average-risk individuals undergoing colonoscopy and the results were compared to a commercially available FIT (with a positivity threshold of 20 μg hemoglobin/gram of stool).^11,12 In both trials, the sensitivity for CRC and advanced precancerous lesions was higher with the mt-sDNA tests compared to FIT but had a significantly lower specificity for advanced precancerous lesions versus FIT (see Table 1). An age-related decline in specificity was noted in both trials with mt-sDNA, a trend not observed with FIT. This reduction may be attributed to age-related DNA methylation.

Multi-Target Stool RNA Test

A multi-target stool RNA test (mt-sRNA) commercially available as ColoSense™ is FDA-approved. It combines FIT (at a positivity threshold of 20 μg hemoglobin/gram of stool) with RNA-based stool markers. The combined results of the RNA markers, FIT, and smoking status provide a qualitative single test result. In the trial, 8,920 adults aged ≥45 underwent the mt-sRNA test and FIT followed by colonoscopy (13). The mt-sRNA showed higher sensitivity for CRC than FIT (94.4% versus 77.8%) and advanced adenomas (45.9% versus 28.9%) but lower CRC specificity (84.7% vs 94.7%) (Table 1). Unlike mt-sDNA-based tests, mt-sRNA showed consistent performance across age groups, addressing concerns about age-related declines in specificity attributed to DNA methylation. 
 

Blood-Based Tests

In 2014, the first blood-based (BBT) CRC screening test known as Epi proColon™ was FDA but not Centers for Medicare & Medicaid Services (CMS) approved for average-risk adults ≥50 years of age who are offered and refused other U.S Preventive Services Task Force (USPSTF) endorsed CRC screening tests. It is a qualitative test for detection of circulating methylated Septin 9 (mSeptin9). The accuracy of mSeptin9 to detect CRC was assessed in a subset of 7941 asymptomatic average risk adults undergoing screening colonoscopy.¹⁴ The sensitivity and specificity for CRC were 48% and 91.5%, respectively. The sensitivity for advanced adenomas was 11.2%. An increase in sensitivity to 63.9% and reduction in specificity to 88.4% for CRC was demonstrated in a sub-analysis of available samples where an additional (third) polymerase chain replicate was performed. Epi proColon™ is not currently reimbursed by Medicare and not endorsed in the latest USPSTF guidelines.

Technologic advancements have improved the detection of circulating tumor markers in the blood. The Shield™ BBT approved by the FDA in 2024 for average risk adults ≥ 45 years integrates three types of cfDNA data (epigenetic changes resulting in the aberrant methylation or fragmentation patterns, and genomic changes resulting in somatic mutations) into a positive or negative test result. In the trial, 22,877 average-risk, asymptomatic individuals ages 45–84 were enrolled and clinical validation was performed in 7,861 of the participants.¹⁵ The sensitivity for CRC was 83.1% which decreased to 55% for stage I tumors (see Table 1). CRC specificity was 89.6% and the sensitivity for advanced adenomas and large sessile serrated lesions was 13.2%.

Another BBT SimpleScreen™, which is not yet FDA-approved, analyzed circulating, cell-free DNA methylation patterns in 27,010 evaluable average-risk, asymptomatic adults ages 45–85 years undergoing screening colonoscopy.¹⁶ The sensitivity and specificity for CRC was 79.2% and 91.5%, respectively. Similar to Shield, the sensitivity for stage I CRC was low at 57.1%. The sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5% which did not meet the prespecified study criteria. 
 

Effectiveness and Cost Effectiveness

Modeling studies have evaluated novel noninvasive CRC screening tests compared to FIT and colonoscopy.^17-20 One compared a hypothetical BBT performed every 3 years that meets the minimum CMS threshold CRC sensitivity and specificity of 74% and 90%, respectively, to other established CRC screening tests beginning at age 45.¹⁷ Every 3-year BBT reduced CRC incidence and mortality by 40% and 52%, respectively compared to no screening. However, the reductions were much lower than yearly FIT (72% and 76%, respectively), every 10 year colonoscopy (79% and 81%, respectively), and triennial mt-sDNA (68% and 73%, respectively). The BBT resulted in fewer quality-adjusted life-years per person compared to the alternatives.

Additionally, FIT, colonoscopy, and mt-sDNA were less costly and more effective. Advanced precancerous lesion detection was a key measure for a test’s effectiveness. BBT characteristics would require a CRC sensitivity and specificity of >90% and 90%, respectively, and 80% sensitivity for advanced precancerous lesions at a cost of ≤$120–$140 to be cost-effective compared to FIT at comparable participation rates.

Another analysis simulated colorectal neoplasia progression and compared clinical effectiveness and cost between annual FIT, every 3 year stool mt-sRNA, every 3 year stool mt-sDNA tests, every 3 year stool Shield™; these outcomes were compared to colonoscopy every 10 years and no screening in adults ≥ age 45 over different adherence rates.¹⁹ At real-world adherence rates of 60%, colonoscopy prevented most CRC cases and associated deaths. FIT was the most cost-effective strategy at all adherence levels. Between the multi-target stool tests and Shield™, mt-sRNA was the most cost-effective. Compared to FIT, mt-sRNA reduced CRC cases and deaths by 1% and 14%.

The third study evaluated CRC incidence and mortality, quality-adjusted life-years and costs with annual FIT, colonoscopy every 10 years, mt- sDNA tests, mt-sRNA test, and BBTs.²⁰ The latest mt-sDNA (Colguard plus™) and mt-sRNA achieved benefits approaching FIT but the Shield™ test was substantially less effective. The authors hypothesized that if 15% of the population substituted Shield™ for current effective CRC screening strategies, an increase in CRC deaths would occur and require 9-10% of the unscreened population to uptake screening with Shield to avert the increases in CRC deaths due to the substitution effect.
 

Clinical Implications

The effectiveness of non-invasive screening strategies depends on their diagnostic performance, adherence, and ensuring a timely colonoscopy after a positive test. Two claims-based studies found 47.9% and 49% of patients underwent follow-up colonoscopy within 6 months of an abnormal stool or BBT CRC screening test, respectively.^21-22

Conclusions

Non-invasive stool mt-sDNA and mt-sRNA have higher effectiveness than the new BBTs. BBTs can lead to increased CRC mortality if substituted for the FDA and CMS-approved, USPSTF-endorsed, CRC screening modalities. If future BBTs increase their sensitivity for CRC (including early-stage CRC) and advanced precancerous lesions and decrease their cost, they may prove to have similar cost-effectiveness to stool-based tests. Currently, BBTs are not a substitute for colonoscopy or other stool tests and should be offered to patients who refuse other CRC screening modalities. A personalized, risk-adapted approach, paired with improved adherence and follow-up are essential to optimize the population-level impact of CRC screening and ensure equitable, effective cancer prevention.

Dr. Gupta is based at the Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore. Dr. Burke and Dr. Macaron are based at the Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio. Dr. Gupta and Dr. Macaron declared no conflicts of interest in regard to this article. Dr. Burke declared research support from Emtora Biosciences. She is a current consultant for Lumabridge, and has been a consultant for Sebela and Almirall. She also disclosed support from Myriad, Genzyme, Ferring, Merck, Sharp and Dohme, Abbvie, Salix, and Natera.

References

1. Benavidez GA, Sedani AE, Felder TM, Asare M, Rogers CR. Rural-urban disparities and trends in cancer screening: an analysis of Behavioral Risk Factor Surveillance System data (2018-2022). JNCI Cancer Spectr. 2024 Nov 1;8(6):pkae113

2. Galoosian A, Dai H, Croymans D, et al. Population Health Colorectal Cancer Screening Strategies in Adults Aged 45 to 49 Years: A Randomized Clinical Trial. JAMA. 2025 Aug 4:e2512049. doi: 10.1001/jama.2025.12049. Epub ahead of print. 

3. Pilonis ND, Bugajski M, Wieszczy P, et al. Participation in Competing Strategies for Colorectal Cancer Screening: A Randomized Health Services Study (PICCOLINO Study). Gastroenterology. 2021 Mar;160(4):1097-1105.

4. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106–1114.

5. Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet. 1996 Nov 30;348(9040):1467-71. doi: 10.1016/S0140-6736(96)03430-7. PMID: 8942774.

6. Burke CA, Lieberman D, Feuerstein JD. AGA Clinical Practice Update on Approach to the Use of Noninvasive Colorectal Cancer Screening Options: Commentary. Gastroenterology. 2022 Mar;162(3):952-956. doi: 10.1053/j.gastro.2021.09.075. Epub 2022 Jan 28. PMID: 35094786.

7. Imperiale TF, Gruber RN Stump TE, et al. Performance characteristics of fecal immunochemical tests for colorectal cancer and advanced adenomatous polyps: a systematic review and meta-analysis. Ann Intern Med 2019; 170(5):319-329

8. Doubeni CA, Corley DA, Jensen CD, et al. Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death. JAMA Netw Open. 2024 Jul 1;7(7):e2423671. doi: 10.1001/jamanetworkopen.2024.23671. 

9. Chiu HM, Jen GH, Wang YW, et al. Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers. Gut. 2021 Dec;70(12):2321-2329. doi: 10.1136/gutjnl-2020-322545. Epub 2021 Jan 25.

10. Castells A, Quintero E, Bujanda L, et al; COLONPREV study investigators. Effect of invitation to colonoscopy versus fecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial. Lancet. 2025;405(10486):1231–1239

11. 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

12. Imperiale TF, Porter K, Zella J, et al. Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):984-993

13. Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget Stool RNA Test for Colorectal Cancer Screening. JAMA. 2023 Nov 14;330(18):1760-1768. 

14. Church TR, Wandell M, Lofton-Day C, et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 2014; 63:317–325.

15. Chung DC, Gray DM 2nd, Singh H, et al. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):973-983.

16. Shaukat A, Burke CA, Chan AT, et al. Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer. JAMA. 2025 Jul 1;334(1):56-63.

17. Ladabaum U, Mannalithara A, Weng Y, et al. Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening with Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy. Gastroenterology. 2024 Jul;167(2):378-391.

18. van den Puttelaar R, Nascimento de Lima P, Knudsen AB, et al. Effectiveness and cost-effectiveness of colorectal cancer screening with a blood test that meets the Centers for Medicare & Medicaid Services coverage decision. Gastroenterology 2024;167:368–377.

19. Shaukat A, Levin TR, Liang PS. Cost-effectiveness of Novel Noninvasive Screening Tests for Colorectal Neoplasia. Clin Gastroenterol Hepatol. 2025 Jun 23:S1542-3565(25)00525-7. doi: 10.1016/j.cgh.2025.06.006. Epub ahead of print. PMID: 40562290.

20. Ladabaum U, Mannalithara A, Schoen RE, Dominitz JA, Lieberman D. Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer. Ann Intern Med. 2024 Dec;177(12):1610-1620.

20. Ciemins EL, Mohl JT, Moreno CA, Colangelo F, Smith RA, Barton M. Development of a Follow-Up Measure to Ensure Complete Screening for Colorectal Cancer. JAMA Netw Open. 2024 Mar 4;7(3):e242693. doi: 10.1001/jamanetworkopen.2024.2693. 

21. Zaki TA, Zhang NJ, Forbes SP, Raymond VM, Das AK, May FP. Colonoscopic Follow-up After Abnormal Blood-Based Colorectal Cancer Screening Results. Gastroenterology. 2025 Jul 21:S0016-5085(25)05775-0. doi: 10.1053/j.gastro.2025.07.019. Epub ahead of print. PMID: 40744392.

 

Introduction

Colorectal cancer (CRC) screening significantly reduces CRC incidence and mortality, but only 65% of eligible individuals report being up-to-date with screening.¹ Colonoscopy is the most widely used opportunistic screening method in the United States and is associated with many barriers to uptake. Providing patients a choice of colonoscopy and/or stool-based tests, improves screening adherence in randomized controlled trials.^2,3 Non-invasive screening options have expanded from stool occult blood and multi-target DNA tests, to multi-target stool RNA tests, and novel blood-based tests, the latter only U.S. Food and Drug Administration (FDA) approved for patients who refuse colonoscopy and stool-based tests. This review summarizes the test characteristics of stool and blood CRC screening options and provides guidance on clinical implications of their use.

Stool Occult Blood Tests

Guaiac-based fecal occult blood testing (gFOBT) significantly reduces CRC mortality by 33%-35% when implemented on an annual or biennial basis.^4,5 Fecal immunochemical testing (FIT) has supplanted gFOBT with advantages including independence from dietary restriction and medication-related interference, use of antibodies specific to human globin, and the need for only a single stool sample.

The most common threshold for a positive FIT in the U.S. is ≥ 20 micrograms (μg) of hemoglobin per gram (g) of stool. FIT is approved by the FDA as a qualitative positive or negative result based on a threshold value.⁶ A meta-analysis summarized test characteristics of commercially available FITs at various detection thresholds.⁷ The CRC sensitivity and specificity was 75% and 95% for ≥ 20 ug hemoglobin/g stool, and 91% and 90% for 10 ug hemoglobin/g stool, respectively. The sensitivity for advanced adenomas ranged from 25% at 20 μg/g to 40% at a 10 μg/g. Programmatic use of FIT in adults ages ≥ 50 years at 20 ug/g of stool, in cohort and case control studies, has been shown to significantly reduce CRC mortality by 33%-40% and advanced stage CRC by 34%.^8,9

Over 57,000 average-risk individuals ages 50–69 years were randomized to biennial FIT or one-time colonoscopy and followed for 10 years.¹⁰ CRC mortality and incidence was similar between the groups: 0.22% with FIT vs. 0.24% with colonoscopy and 1.13% with FIT vs. 1.22% with colonoscopy, respectively. Thus, confirming biennial FIT screening is non-inferior to one-time colonoscopy in important CRC-related outcomes.
 

Multi-Target Stool Tests

Two multitarget stool DNA tests (mt-sDNA) known as Cologuard™ and Cologuard Plus™ have been approved by the FDA. Both tests include a FIT (with a positivity threshold of 20 μg hemoglobin per gram of stool) combined with DNA methylation markers. The test result is qualitative, reported as a positive or negative. Cologuard™ markers include methylated BMP3, NDRG4, and mutant KRAS while Cologuard Plus™ assesses methylated LASS4, LRRC4, and PPP2R5C. The respective mt-sDNA tests were studied in 9989 of 12,776 and 20,176 of 26,758 average-risk individuals undergoing colonoscopy and the results were compared to a commercially available FIT (with a positivity threshold of 20 μg hemoglobin/gram of stool).^11,12 In both trials, the sensitivity for CRC and advanced precancerous lesions was higher with the mt-sDNA tests compared to FIT but had a significantly lower specificity for advanced precancerous lesions versus FIT (see Table 1). An age-related decline in specificity was noted in both trials with mt-sDNA, a trend not observed with FIT. This reduction may be attributed to age-related DNA methylation.

Multi-Target Stool RNA Test

A multi-target stool RNA test (mt-sRNA) commercially available as ColoSense™ is FDA-approved. It combines FIT (at a positivity threshold of 20 μg hemoglobin/gram of stool) with RNA-based stool markers. The combined results of the RNA markers, FIT, and smoking status provide a qualitative single test result. In the trial, 8,920 adults aged ≥45 underwent the mt-sRNA test and FIT followed by colonoscopy (13). The mt-sRNA showed higher sensitivity for CRC than FIT (94.4% versus 77.8%) and advanced adenomas (45.9% versus 28.9%) but lower CRC specificity (84.7% vs 94.7%) (Table 1). Unlike mt-sDNA-based tests, mt-sRNA showed consistent performance across age groups, addressing concerns about age-related declines in specificity attributed to DNA methylation. 
 

Blood-Based Tests

In 2014, the first blood-based (BBT) CRC screening test known as Epi proColon™ was FDA but not Centers for Medicare & Medicaid Services (CMS) approved for average-risk adults ≥50 years of age who are offered and refused other U.S Preventive Services Task Force (USPSTF) endorsed CRC screening tests. It is a qualitative test for detection of circulating methylated Septin 9 (mSeptin9). The accuracy of mSeptin9 to detect CRC was assessed in a subset of 7941 asymptomatic average risk adults undergoing screening colonoscopy.¹⁴ The sensitivity and specificity for CRC were 48% and 91.5%, respectively. The sensitivity for advanced adenomas was 11.2%. An increase in sensitivity to 63.9% and reduction in specificity to 88.4% for CRC was demonstrated in a sub-analysis of available samples where an additional (third) polymerase chain replicate was performed. Epi proColon™ is not currently reimbursed by Medicare and not endorsed in the latest USPSTF guidelines.

Technologic advancements have improved the detection of circulating tumor markers in the blood. The Shield™ BBT approved by the FDA in 2024 for average risk adults ≥ 45 years integrates three types of cfDNA data (epigenetic changes resulting in the aberrant methylation or fragmentation patterns, and genomic changes resulting in somatic mutations) into a positive or negative test result. In the trial, 22,877 average-risk, asymptomatic individuals ages 45–84 were enrolled and clinical validation was performed in 7,861 of the participants.¹⁵ The sensitivity for CRC was 83.1% which decreased to 55% for stage I tumors (see Table 1). CRC specificity was 89.6% and the sensitivity for advanced adenomas and large sessile serrated lesions was 13.2%.

Another BBT SimpleScreen™, which is not yet FDA-approved, analyzed circulating, cell-free DNA methylation patterns in 27,010 evaluable average-risk, asymptomatic adults ages 45–85 years undergoing screening colonoscopy.¹⁶ The sensitivity and specificity for CRC was 79.2% and 91.5%, respectively. Similar to Shield, the sensitivity for stage I CRC was low at 57.1%. The sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5% which did not meet the prespecified study criteria. 
 

Effectiveness and Cost Effectiveness

Modeling studies have evaluated novel noninvasive CRC screening tests compared to FIT and colonoscopy.^17-20 One compared a hypothetical BBT performed every 3 years that meets the minimum CMS threshold CRC sensitivity and specificity of 74% and 90%, respectively, to other established CRC screening tests beginning at age 45.¹⁷ Every 3-year BBT reduced CRC incidence and mortality by 40% and 52%, respectively compared to no screening. However, the reductions were much lower than yearly FIT (72% and 76%, respectively), every 10 year colonoscopy (79% and 81%, respectively), and triennial mt-sDNA (68% and 73%, respectively). The BBT resulted in fewer quality-adjusted life-years per person compared to the alternatives.

Additionally, FIT, colonoscopy, and mt-sDNA were less costly and more effective. Advanced precancerous lesion detection was a key measure for a test’s effectiveness. BBT characteristics would require a CRC sensitivity and specificity of >90% and 90%, respectively, and 80% sensitivity for advanced precancerous lesions at a cost of ≤$120–$140 to be cost-effective compared to FIT at comparable participation rates.

Another analysis simulated colorectal neoplasia progression and compared clinical effectiveness and cost between annual FIT, every 3 year stool mt-sRNA, every 3 year stool mt-sDNA tests, every 3 year stool Shield™; these outcomes were compared to colonoscopy every 10 years and no screening in adults ≥ age 45 over different adherence rates.¹⁹ At real-world adherence rates of 60%, colonoscopy prevented most CRC cases and associated deaths. FIT was the most cost-effective strategy at all adherence levels. Between the multi-target stool tests and Shield™, mt-sRNA was the most cost-effective. Compared to FIT, mt-sRNA reduced CRC cases and deaths by 1% and 14%.

The third study evaluated CRC incidence and mortality, quality-adjusted life-years and costs with annual FIT, colonoscopy every 10 years, mt- sDNA tests, mt-sRNA test, and BBTs.²⁰ The latest mt-sDNA (Colguard plus™) and mt-sRNA achieved benefits approaching FIT but the Shield™ test was substantially less effective. The authors hypothesized that if 15% of the population substituted Shield™ for current effective CRC screening strategies, an increase in CRC deaths would occur and require 9-10% of the unscreened population to uptake screening with Shield to avert the increases in CRC deaths due to the substitution effect.
 

Clinical Implications

The effectiveness of non-invasive screening strategies depends on their diagnostic performance, adherence, and ensuring a timely colonoscopy after a positive test. Two claims-based studies found 47.9% and 49% of patients underwent follow-up colonoscopy within 6 months of an abnormal stool or BBT CRC screening test, respectively.^21-22

Conclusions

Non-invasive stool mt-sDNA and mt-sRNA have higher effectiveness than the new BBTs. BBTs can lead to increased CRC mortality if substituted for the FDA and CMS-approved, USPSTF-endorsed, CRC screening modalities. If future BBTs increase their sensitivity for CRC (including early-stage CRC) and advanced precancerous lesions and decrease their cost, they may prove to have similar cost-effectiveness to stool-based tests. Currently, BBTs are not a substitute for colonoscopy or other stool tests and should be offered to patients who refuse other CRC screening modalities. A personalized, risk-adapted approach, paired with improved adherence and follow-up are essential to optimize the population-level impact of CRC screening and ensure equitable, effective cancer prevention.

Dr. Gupta is based at the Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore. Dr. Burke and Dr. Macaron are based at the Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio. Dr. Gupta and Dr. Macaron declared no conflicts of interest in regard to this article. Dr. Burke declared research support from Emtora Biosciences. She is a current consultant for Lumabridge, and has been a consultant for Sebela and Almirall. She also disclosed support from Myriad, Genzyme, Ferring, Merck, Sharp and Dohme, Abbvie, Salix, and Natera.

References

1. Benavidez GA, Sedani AE, Felder TM, Asare M, Rogers CR. Rural-urban disparities and trends in cancer screening: an analysis of Behavioral Risk Factor Surveillance System data (2018-2022). JNCI Cancer Spectr. 2024 Nov 1;8(6):pkae113

2. Galoosian A, Dai H, Croymans D, et al. Population Health Colorectal Cancer Screening Strategies in Adults Aged 45 to 49 Years: A Randomized Clinical Trial. JAMA. 2025 Aug 4:e2512049. doi: 10.1001/jama.2025.12049. Epub ahead of print. 

3. Pilonis ND, Bugajski M, Wieszczy P, et al. Participation in Competing Strategies for Colorectal Cancer Screening: A Randomized Health Services Study (PICCOLINO Study). Gastroenterology. 2021 Mar;160(4):1097-1105.

4. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106–1114.

5. Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet. 1996 Nov 30;348(9040):1467-71. doi: 10.1016/S0140-6736(96)03430-7. PMID: 8942774.

6. Burke CA, Lieberman D, Feuerstein JD. AGA Clinical Practice Update on Approach to the Use of Noninvasive Colorectal Cancer Screening Options: Commentary. Gastroenterology. 2022 Mar;162(3):952-956. doi: 10.1053/j.gastro.2021.09.075. Epub 2022 Jan 28. PMID: 35094786.

7. Imperiale TF, Gruber RN Stump TE, et al. Performance characteristics of fecal immunochemical tests for colorectal cancer and advanced adenomatous polyps: a systematic review and meta-analysis. Ann Intern Med 2019; 170(5):319-329

8. Doubeni CA, Corley DA, Jensen CD, et al. Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death. JAMA Netw Open. 2024 Jul 1;7(7):e2423671. doi: 10.1001/jamanetworkopen.2024.23671. 

9. Chiu HM, Jen GH, Wang YW, et al. Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers. Gut. 2021 Dec;70(12):2321-2329. doi: 10.1136/gutjnl-2020-322545. Epub 2021 Jan 25.

10. Castells A, Quintero E, Bujanda L, et al; COLONPREV study investigators. Effect of invitation to colonoscopy versus fecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial. Lancet. 2025;405(10486):1231–1239

11. 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

12. Imperiale TF, Porter K, Zella J, et al. Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):984-993

13. Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget Stool RNA Test for Colorectal Cancer Screening. JAMA. 2023 Nov 14;330(18):1760-1768. 

14. Church TR, Wandell M, Lofton-Day C, et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 2014; 63:317–325.

15. Chung DC, Gray DM 2nd, Singh H, et al. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):973-983.

16. Shaukat A, Burke CA, Chan AT, et al. Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer. JAMA. 2025 Jul 1;334(1):56-63.

17. Ladabaum U, Mannalithara A, Weng Y, et al. Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening with Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy. Gastroenterology. 2024 Jul;167(2):378-391.

18. van den Puttelaar R, Nascimento de Lima P, Knudsen AB, et al. Effectiveness and cost-effectiveness of colorectal cancer screening with a blood test that meets the Centers for Medicare & Medicaid Services coverage decision. Gastroenterology 2024;167:368–377.

19. Shaukat A, Levin TR, Liang PS. Cost-effectiveness of Novel Noninvasive Screening Tests for Colorectal Neoplasia. Clin Gastroenterol Hepatol. 2025 Jun 23:S1542-3565(25)00525-7. doi: 10.1016/j.cgh.2025.06.006. Epub ahead of print. PMID: 40562290.

20. Ladabaum U, Mannalithara A, Schoen RE, Dominitz JA, Lieberman D. Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer. Ann Intern Med. 2024 Dec;177(12):1610-1620.

20. Ciemins EL, Mohl JT, Moreno CA, Colangelo F, Smith RA, Barton M. Development of a Follow-Up Measure to Ensure Complete Screening for Colorectal Cancer. JAMA Netw Open. 2024 Mar 4;7(3):e242693. doi: 10.1001/jamanetworkopen.2024.2693. 

21. Zaki TA, Zhang NJ, Forbes SP, Raymond VM, Das AK, May FP. Colonoscopic Follow-up After Abnormal Blood-Based Colorectal Cancer Screening Results. Gastroenterology. 2025 Jul 21:S0016-5085(25)05775-0. doi: 10.1053/j.gastro.2025.07.019. Epub ahead of print. PMID: 40744392.

 

You are in the middle of a busy clinic day and think, “there has to be a better way to do this.” Suddenly, a better way to do something becomes obvious. Maybe it’s a tool that simplifies documentation, a device that improves patient comfort, or an app that bridges a clinical gap. Many physicians, especially early career gastroenterologists, have ideas like this, but few know what to do next.

This article is for the curious innovator at the beginning of their clinical career. It offers practical, real-world guidance on developing a clinical product: whether that be hardware, software, or a hybrid. It outlines what questions to ask, who to consult, and how to protect your work, using personal insights and business principles learned through lived experience.

1. Understand Intellectual Property (IP): Know Its Value and Ownership

What is IP?

Intellectual property refers to your original creations: inventions, designs, software, and more. This is what you want to protect legally through patents, trademarks, or copyrights.

Who owns your idea?

This is the first and most important question to ask. If you are employed (especially by a hospital or academic center), your contract may already give your employer rights to any inventions you create, even those developed in your personal time.

What to ask:

• Does my employment contract include an “assignment of inventions” clause?
• Does the institution claim rights to anything developed with institutional resources?
• Are there moonlighting or external activity policies that affect this?

If you are developing an idea on your personal time, with your own resources, and outside your scope of clinical duties, it might still be considered “theirs” under some contracts. Early legal consultation is critical. A specialized IP attorney can help you understand what you own and how to protect it. This should be done early, ideally before you start building anything. 
 

2. Lawyers Aren’t Optional: They’re Essential Early Partners

You do not need a full legal team, but you do need a lawyer early. An early consultation with an IP attorney can clarify your rights, guide your filing process (e.g. provisional patents), and help you avoid costly missteps.

Do this before sharing your idea publicly, including in academic presentations, pitch competitions, or even on social media. Public disclosure can start a clock ticking for application to protect your IP.
 

3. Build a Founding Team with Intent

Think of your startup team like a long-term relationship: you’re committing to build something together through uncertainty, tension, and change.

Strong early-stage teams often include:

• The Visionary – understands the clinical need and vision
• The Builder – engineer, developer, or designer
• The Doer – project manager or operations lead

Before forming a company, clearly define:

• Ownership (equity percentages)
• Roles and responsibilities
• Time commitments
• What happens if someone exits

Have these discussions early and document your agreements. Avoid informal “handshake” deals that can lead to serious disputes later.
 

4. You Don’t Need to Know Everything on Day One

You do not need to know how to write code, build a prototype, or get FDA clearance on day one. Successful innovators are humble learners. Use a Minimum Viable Product (MVP), a simple, functional version of your idea, to test assumptions and gather feedback. Iterate based on what you learn. Do not chase perfection; pursue progress. Consider using online accelerators like Y Combinator’s startup school or AGA’s Center for GI Innovation and Technology. 
 

5. Incubators: Use them Strategically

Incubators can offer mentorship, seed funding, legal support, and technical resources, but they vary widely in value (see Table 1). Many may want equity, and not all offer when you truly need. 


Ask Yourself:

• Do I need technical help, business mentorship, or just accountability?
• What does this incubator offer in terms of IP protection, exposure, and connections?
• Do I understand the equity trade-off?
• What services and funding do they provide?
• Do they take equity? How much and when?
• What’s their track record with similar ventures?
• Are their incentives aligned with your vision?

6. Academic Institutions: Partners or Pitfalls?

Universities can provide credibility, resources, and early funding through their tech transfer office (TTO).


Key Questions to Ask:

• Will my IP be managed by the TTO?
• How much say do I have in licensing decisions?
• Are there royalty-sharing agreements in place?
• Can I form a startup while employed here?

You may need to negotiate if you want to commercialize your idea independently. 
 

7. Do it for Purpose, Not Payday

Most founders end up owning only a small percentage of their company by the time a product reaches the market. Do not expect to get rich. Do it because it solves a problem you care about. If it happens to come with a nice paycheck, then that is an added bonus.

Your clinical training and insight give you a unique edge. You already know what’s broken. Use that as your compass. 
 

Conclusion

Innovation isn’t about brilliance, it’s about curiosity, structure, and tenacity (see Table 2). Start small. Protect your work. Choose the right partners. Most importantly, stay anchored in your mission to make GI care better.

Dr. Muratore is based at UNC Rex Digestive Health, Raleigh, North Carolina. She has no conflicts related to this article. Dr. Wechsler is based at the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. She holds a patent assigned to Trustees of Dartmouth College. Dr. Shah is based at the University of Michigan, Ann Arbor, Michigan. He consults for Ardelyx, Laborie, Neuraxis, Salix, Sanofi, and Takeda and holds a patent with the Regents of the University of Michigan.

You are in the middle of a busy clinic day and think, “there has to be a better way to do this.” Suddenly, a better way to do something becomes obvious. Maybe it’s a tool that simplifies documentation, a device that improves patient comfort, or an app that bridges a clinical gap. Many physicians, especially early career gastroenterologists, have ideas like this, but few know what to do next.

This article is for the curious innovator at the beginning of their clinical career. It offers practical, real-world guidance on developing a clinical product: whether that be hardware, software, or a hybrid. It outlines what questions to ask, who to consult, and how to protect your work, using personal insights and business principles learned through lived experience.

1. Understand Intellectual Property (IP): Know Its Value and Ownership

What is IP?

Intellectual property refers to your original creations: inventions, designs, software, and more. This is what you want to protect legally through patents, trademarks, or copyrights.

Who owns your idea?

This is the first and most important question to ask. If you are employed (especially by a hospital or academic center), your contract may already give your employer rights to any inventions you create, even those developed in your personal time.

What to ask:

• Does my employment contract include an “assignment of inventions” clause?
• Does the institution claim rights to anything developed with institutional resources?
• Are there moonlighting or external activity policies that affect this?

If you are developing an idea on your personal time, with your own resources, and outside your scope of clinical duties, it might still be considered “theirs” under some contracts. Early legal consultation is critical. A specialized IP attorney can help you understand what you own and how to protect it. This should be done early, ideally before you start building anything. 
 

2. Lawyers Aren’t Optional: They’re Essential Early Partners

You do not need a full legal team, but you do need a lawyer early. An early consultation with an IP attorney can clarify your rights, guide your filing process (e.g. provisional patents), and help you avoid costly missteps.

Do this before sharing your idea publicly, including in academic presentations, pitch competitions, or even on social media. Public disclosure can start a clock ticking for application to protect your IP.
 

3. Build a Founding Team with Intent

Think of your startup team like a long-term relationship: you’re committing to build something together through uncertainty, tension, and change.

Strong early-stage teams often include:

• The Visionary – understands the clinical need and vision
• The Builder – engineer, developer, or designer
• The Doer – project manager or operations lead

Before forming a company, clearly define:

• Ownership (equity percentages)
• Roles and responsibilities
• Time commitments
• What happens if someone exits

Have these discussions early and document your agreements. Avoid informal “handshake” deals that can lead to serious disputes later.
 

4. You Don’t Need to Know Everything on Day One

You do not need to know how to write code, build a prototype, or get FDA clearance on day one. Successful innovators are humble learners. Use a Minimum Viable Product (MVP), a simple, functional version of your idea, to test assumptions and gather feedback. Iterate based on what you learn. Do not chase perfection; pursue progress. Consider using online accelerators like Y Combinator’s startup school or AGA’s Center for GI Innovation and Technology. 
 

5. Incubators: Use them Strategically

Incubators can offer mentorship, seed funding, legal support, and technical resources, but they vary widely in value (see Table 1). Many may want equity, and not all offer when you truly need. 


Ask Yourself:

• Do I need technical help, business mentorship, or just accountability?
• What does this incubator offer in terms of IP protection, exposure, and connections?
• Do I understand the equity trade-off?
• What services and funding do they provide?
• Do they take equity? How much and when?
• What’s their track record with similar ventures?
• Are their incentives aligned with your vision?

6. Academic Institutions: Partners or Pitfalls?

Universities can provide credibility, resources, and early funding through their tech transfer office (TTO).


Key Questions to Ask:

• Will my IP be managed by the TTO?
• How much say do I have in licensing decisions?
• Are there royalty-sharing agreements in place?
• Can I form a startup while employed here?

You may need to negotiate if you want to commercialize your idea independently. 
 

7. Do it for Purpose, Not Payday

Most founders end up owning only a small percentage of their company by the time a product reaches the market. Do not expect to get rich. Do it because it solves a problem you care about. If it happens to come with a nice paycheck, then that is an added bonus.

Your clinical training and insight give you a unique edge. You already know what’s broken. Use that as your compass. 
 

Conclusion

Innovation isn’t about brilliance, it’s about curiosity, structure, and tenacity (see Table 2). Start small. Protect your work. Choose the right partners. Most importantly, stay anchored in your mission to make GI care better.

Dr. Muratore is based at UNC Rex Digestive Health, Raleigh, North Carolina. She has no conflicts related to this article. Dr. Wechsler is based at the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. She holds a patent assigned to Trustees of Dartmouth College. Dr. Shah is based at the University of Michigan, Ann Arbor, Michigan. He consults for Ardelyx, Laborie, Neuraxis, Salix, Sanofi, and Takeda and holds a patent with the Regents of the University of Michigan.

You are in the middle of a busy clinic day and think, “there has to be a better way to do this.” Suddenly, a better way to do something becomes obvious. Maybe it’s a tool that simplifies documentation, a device that improves patient comfort, or an app that bridges a clinical gap. Many physicians, especially early career gastroenterologists, have ideas like this, but few know what to do next.

This article is for the curious innovator at the beginning of their clinical career. It offers practical, real-world guidance on developing a clinical product: whether that be hardware, software, or a hybrid. It outlines what questions to ask, who to consult, and how to protect your work, using personal insights and business principles learned through lived experience.

1. Understand Intellectual Property (IP): Know Its Value and Ownership

What is IP?

Intellectual property refers to your original creations: inventions, designs, software, and more. This is what you want to protect legally through patents, trademarks, or copyrights.

Who owns your idea?

This is the first and most important question to ask. If you are employed (especially by a hospital or academic center), your contract may already give your employer rights to any inventions you create, even those developed in your personal time.

What to ask:

• Does my employment contract include an “assignment of inventions” clause?
• Does the institution claim rights to anything developed with institutional resources?
• Are there moonlighting or external activity policies that affect this?

If you are developing an idea on your personal time, with your own resources, and outside your scope of clinical duties, it might still be considered “theirs” under some contracts. Early legal consultation is critical. A specialized IP attorney can help you understand what you own and how to protect it. This should be done early, ideally before you start building anything. 
 

2. Lawyers Aren’t Optional: They’re Essential Early Partners

You do not need a full legal team, but you do need a lawyer early. An early consultation with an IP attorney can clarify your rights, guide your filing process (e.g. provisional patents), and help you avoid costly missteps.

Do this before sharing your idea publicly, including in academic presentations, pitch competitions, or even on social media. Public disclosure can start a clock ticking for application to protect your IP.
 

3. Build a Founding Team with Intent

Think of your startup team like a long-term relationship: you’re committing to build something together through uncertainty, tension, and change.

Strong early-stage teams often include:

• The Visionary – understands the clinical need and vision
• The Builder – engineer, developer, or designer
• The Doer – project manager or operations lead

Before forming a company, clearly define:

• Ownership (equity percentages)
• Roles and responsibilities
• Time commitments
• What happens if someone exits

Have these discussions early and document your agreements. Avoid informal “handshake” deals that can lead to serious disputes later.
 

4. You Don’t Need to Know Everything on Day One

You do not need to know how to write code, build a prototype, or get FDA clearance on day one. Successful innovators are humble learners. Use a Minimum Viable Product (MVP), a simple, functional version of your idea, to test assumptions and gather feedback. Iterate based on what you learn. Do not chase perfection; pursue progress. Consider using online accelerators like Y Combinator’s startup school or AGA’s Center for GI Innovation and Technology. 
 

5. Incubators: Use them Strategically

Incubators can offer mentorship, seed funding, legal support, and technical resources, but they vary widely in value (see Table 1). Many may want equity, and not all offer when you truly need. 


Ask Yourself:

• Do I need technical help, business mentorship, or just accountability?
• What does this incubator offer in terms of IP protection, exposure, and connections?
• Do I understand the equity trade-off?
• What services and funding do they provide?
• Do they take equity? How much and when?
• What’s their track record with similar ventures?
• Are their incentives aligned with your vision?

6. Academic Institutions: Partners or Pitfalls?

Universities can provide credibility, resources, and early funding through their tech transfer office (TTO).


Key Questions to Ask:

• Will my IP be managed by the TTO?
• How much say do I have in licensing decisions?
• Are there royalty-sharing agreements in place?
• Can I form a startup while employed here?

You may need to negotiate if you want to commercialize your idea independently. 
 

7. Do it for Purpose, Not Payday

Most founders end up owning only a small percentage of their company by the time a product reaches the market. Do not expect to get rich. Do it because it solves a problem you care about. If it happens to come with a nice paycheck, then that is an added bonus.

Your clinical training and insight give you a unique edge. You already know what’s broken. Use that as your compass. 
 

Conclusion

Innovation isn’t about brilliance, it’s about curiosity, structure, and tenacity (see Table 2). Start small. Protect your work. Choose the right partners. Most importantly, stay anchored in your mission to make GI care better.

Dr. Muratore is based at UNC Rex Digestive Health, Raleigh, North Carolina. She has no conflicts related to this article. Dr. Wechsler is based at the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. She holds a patent assigned to Trustees of Dartmouth College. Dr. Shah is based at the University of Michigan, Ann Arbor, Michigan. He consults for Ardelyx, Laborie, Neuraxis, Salix, Sanofi, and Takeda and holds a patent with the Regents of the University of Michigan.

Introduction

For many of us in gastroenterology, landing that first attending job feels like the ultimate victory lap — the reward for all those years of training. We sign the contract, relocate, and imagine this will be our “forever job.” Reality often plays out differently.

In fact, 43% of physicians change jobs within five years, while 83% changed employers at least once in their careers.¹ Even within our field — which is always in demand — turnover is high; 1 in 3 gastroenterologists are planning to leave their current role within two years.² Why does this happen? More importantly, how do we navigate this transition with clarity and confidence as an early-career GI?
 

My Story: When I Dared to Change My “Forever Job”

When I signed my first attending contract, I didn’t negotiate a single thing. My priorities were simple: family in Toronto and visa requirements. After a decade of medical school, residency, and fellowship, everything else felt secondary. I was happy to be back home.

The job itself was good — reasonable hours, flexible colleagues, and ample opportunity to enhance my procedural skills. As I started carving out my niche in endobariatrics, the support I needed to grow further was not there. I kept telling myself that this job fulfilled my values and I needed to be patient: “this is my forever job. I am close to my family and that’s what matters.”

Then, during a suturing course at the American Society of Gastrointestinal Endoscopy, I had a casual chat with the course director (now my boss). It took me by surprise, but as the conversation continued, he offered me a job. It was tempting: the chance to build my own endobariatrics program with real institutional backing. The catch? It was in a city I had never been to, with no family or friends around. I politely said “no, thank you, I can’t.” He smiled, gave me his number, and said, “think about it.”

For the first time, I allowed myself to ask, “could I really leave my forever job?”
 

The Power of a Circle and a Spreadsheet

I leaned on my circle — a close group of fellowship friends who each took a turn being someone’s lifeline. We have monthly Zoom calls to talk about jobs, family, and career aspirations. When I shared my dilemma, I realized I wasn’t alone; one friend was also unhappy with her first job. Suddenly, we were asking one another, “can we really leave?”

I hired a career consultant familiar with physician visa issues — hands down, the best money I ever invested. The job search felt like dating: each interview was a first date; some needed a second or third date before I knew if it could be a match.

After every interview, I’d jump on Zoom with my circle. We’d screen-share my giant Excel spreadsheet — our decision matrix — with columns for everything I cared about:

• Institute
• Administrative Time
• Endobariatric support
• Director Title
• Salary
• On-call
• Vacation
• Proximity to airport
• Cost of living
• RVU percentage
• Endoscopy center buy-in
• Contract duration
• Support staff
• CME

We scored each job, line by line, and not a single job checked all the boxes. As I sat there in a state of decision paralysis, it became clear that this was not a simple decision.
 

The GI Community: A Small, Supportive World

The GI community is incredibly close-knit and kind-hearted. At every conference, I made a point to chat with as many colleagues as I could, to hear their perspectives on jobs and how they made tough career moves. Those conversations were real — no Google search or Excel sheet could offer the perspective and insight I gained by simply asking and leaning on the GI community.

Meanwhile, the person who had first offered me that job kept checking in, catching up at conferences, and bonding over our love for food and baking. With him, I never felt like I was being ‘interviewed’ — I felt valued. It did not feel like he was trying to fill a position with just anyone to improve the call pool. He genuinely wanted to understand what my goals were and how I envisioned my future. Through those conversations, he reminded me of my original passions, which were sidelined when so immersed in the daily routine. 

I’ve learned that feeling valued doesn’t come from grand gestures in recruitment. It’s in the quiet signs of respect, trust, and being seen. He wasn’t looking for just anyone; he was looking for someone whose goals aligned with his group’s and someone in whom he wanted to invest. While others might chase the highest salary, the most flexible schedule, or the strongest ancillary support, I realized I valued something I did not realize that I was lacking until then: mentorship.
 

What I Learned: There is No Such Thing As “The Perfect Job”

After a full year of spreadsheets, Zoom calls, conference chats, and overthinking, I came to a big realization: there’s no perfect job — there’s no such thing as an ideal “forever job.” The only constant for humans is change. Our circumstances change, our priorities shift, our interests shuffle, and our finances evolve. The best job is simply the one that fits the stage of life you’re in at that given moment. For me, mentorship and growth became my top priorities, even if it meant moving away from family.

What Physicians Value Most in a Second Job

After their first job, early-career gastroenterologists often reevaluate what really matters. Recent surveys highlight four key priorities:

• Work-life balance:

In a 2022 CompHealth Group healthcare survey, 85% of physicians ranked work-life balance as their top job priority.³

• Mentorship and growth:

Nearly 1 in 3 physicians cited lack of mentorship or career advancement as their reason for leaving a first job, per the 2023 MGMA/Jackson Physician Search report.⁴

• Compensation:

While not always the main reason for leaving, 77% of physicians now list compensation as a top priority — a big jump from prior years.³

• Practice support:

Poor infrastructure, administrative overload, or understaffed teams are common dealbreakers. In the second job, physicians look for well-run practices with solid support staff and reduced burnout risk.⁵

Conclusion

Your first job doesn’t have to be your last. What matters is knowing when it’s time to evolve. Welcome the uncertainty, talk to your circle, lean on your community, and use a spreadsheet if you need to — but don’t forget to trust your gut. There’s no forever job or the perfect path, only the next move that feels most true to who you are in that moment.

Dr. Ismail (@mayyismail) is Assistant Professor of Clinical Medicine (Gastroenterology) at Temple University in Philadelphia, Pennsylvania. She declares no conflicts of interest.

References

1. CHG Healthcare. Survey: 62% of physicians made a career change in the last two years. CHG Healthcare blog. June 10, 2024. Accessed August 5, 2025.


2. Berg S. Physicians in these 10 specialties are less likely to quit. AMA News. Published June 24, 2025. Accessed July 2025. 


3. Saley C. Survey: Work/life balance is #1 priority in physicians’ job search. CHG Healthcare Insights. March 10, 2022. Accessed August 2025. 


4. Medical Group Management Association; Jackson Physician Search. Early‑Career Physician Recruiting & Retention Playbook. October 23, 2023. Accessed August 2025. 


5. Von Rosenvinge EC, et al. A crisis in scope: Recruitment and retention challenges reported by VA gastroenterology section chiefs. Fed Pract. 2024 Aug. doi:10.12788/fp.0504.

Introduction

For many of us in gastroenterology, landing that first attending job feels like the ultimate victory lap — the reward for all those years of training. We sign the contract, relocate, and imagine this will be our “forever job.” Reality often plays out differently.

In fact, 43% of physicians change jobs within five years, while 83% changed employers at least once in their careers.¹ Even within our field — which is always in demand — turnover is high; 1 in 3 gastroenterologists are planning to leave their current role within two years.² Why does this happen? More importantly, how do we navigate this transition with clarity and confidence as an early-career GI?
 

My Story: When I Dared to Change My “Forever Job”

When I signed my first attending contract, I didn’t negotiate a single thing. My priorities were simple: family in Toronto and visa requirements. After a decade of medical school, residency, and fellowship, everything else felt secondary. I was happy to be back home.

The job itself was good — reasonable hours, flexible colleagues, and ample opportunity to enhance my procedural skills. As I started carving out my niche in endobariatrics, the support I needed to grow further was not there. I kept telling myself that this job fulfilled my values and I needed to be patient: “this is my forever job. I am close to my family and that’s what matters.”

Then, during a suturing course at the American Society of Gastrointestinal Endoscopy, I had a casual chat with the course director (now my boss). It took me by surprise, but as the conversation continued, he offered me a job. It was tempting: the chance to build my own endobariatrics program with real institutional backing. The catch? It was in a city I had never been to, with no family or friends around. I politely said “no, thank you, I can’t.” He smiled, gave me his number, and said, “think about it.”

For the first time, I allowed myself to ask, “could I really leave my forever job?”
 

The Power of a Circle and a Spreadsheet

I leaned on my circle — a close group of fellowship friends who each took a turn being someone’s lifeline. We have monthly Zoom calls to talk about jobs, family, and career aspirations. When I shared my dilemma, I realized I wasn’t alone; one friend was also unhappy with her first job. Suddenly, we were asking one another, “can we really leave?”

I hired a career consultant familiar with physician visa issues — hands down, the best money I ever invested. The job search felt like dating: each interview was a first date; some needed a second or third date before I knew if it could be a match.

After every interview, I’d jump on Zoom with my circle. We’d screen-share my giant Excel spreadsheet — our decision matrix — with columns for everything I cared about:

• Institute
• Administrative Time
• Endobariatric support
• Director Title
• Salary
• On-call
• Vacation
• Proximity to airport
• Cost of living
• RVU percentage
• Endoscopy center buy-in
• Contract duration
• Support staff
• CME

We scored each job, line by line, and not a single job checked all the boxes. As I sat there in a state of decision paralysis, it became clear that this was not a simple decision.
 

The GI Community: A Small, Supportive World

The GI community is incredibly close-knit and kind-hearted. At every conference, I made a point to chat with as many colleagues as I could, to hear their perspectives on jobs and how they made tough career moves. Those conversations were real — no Google search or Excel sheet could offer the perspective and insight I gained by simply asking and leaning on the GI community.

Meanwhile, the person who had first offered me that job kept checking in, catching up at conferences, and bonding over our love for food and baking. With him, I never felt like I was being ‘interviewed’ — I felt valued. It did not feel like he was trying to fill a position with just anyone to improve the call pool. He genuinely wanted to understand what my goals were and how I envisioned my future. Through those conversations, he reminded me of my original passions, which were sidelined when so immersed in the daily routine. 

I’ve learned that feeling valued doesn’t come from grand gestures in recruitment. It’s in the quiet signs of respect, trust, and being seen. He wasn’t looking for just anyone; he was looking for someone whose goals aligned with his group’s and someone in whom he wanted to invest. While others might chase the highest salary, the most flexible schedule, or the strongest ancillary support, I realized I valued something I did not realize that I was lacking until then: mentorship.
 

What I Learned: There is No Such Thing As “The Perfect Job”

After a full year of spreadsheets, Zoom calls, conference chats, and overthinking, I came to a big realization: there’s no perfect job — there’s no such thing as an ideal “forever job.” The only constant for humans is change. Our circumstances change, our priorities shift, our interests shuffle, and our finances evolve. The best job is simply the one that fits the stage of life you’re in at that given moment. For me, mentorship and growth became my top priorities, even if it meant moving away from family.

What Physicians Value Most in a Second Job

After their first job, early-career gastroenterologists often reevaluate what really matters. Recent surveys highlight four key priorities:

• Work-life balance:

In a 2022 CompHealth Group healthcare survey, 85% of physicians ranked work-life balance as their top job priority.³

• Mentorship and growth:

Nearly 1 in 3 physicians cited lack of mentorship or career advancement as their reason for leaving a first job, per the 2023 MGMA/Jackson Physician Search report.⁴

• Compensation:

While not always the main reason for leaving, 77% of physicians now list compensation as a top priority — a big jump from prior years.³

• Practice support:

Poor infrastructure, administrative overload, or understaffed teams are common dealbreakers. In the second job, physicians look for well-run practices with solid support staff and reduced burnout risk.⁵

Conclusion

Your first job doesn’t have to be your last. What matters is knowing when it’s time to evolve. Welcome the uncertainty, talk to your circle, lean on your community, and use a spreadsheet if you need to — but don’t forget to trust your gut. There’s no forever job or the perfect path, only the next move that feels most true to who you are in that moment.

Dr. Ismail (@mayyismail) is Assistant Professor of Clinical Medicine (Gastroenterology) at Temple University in Philadelphia, Pennsylvania. She declares no conflicts of interest.

References

1. CHG Healthcare. Survey: 62% of physicians made a career change in the last two years. CHG Healthcare blog. June 10, 2024. Accessed August 5, 2025.


2. Berg S. Physicians in these 10 specialties are less likely to quit. AMA News. Published June 24, 2025. Accessed July 2025. 


3. Saley C. Survey: Work/life balance is #1 priority in physicians’ job search. CHG Healthcare Insights. March 10, 2022. Accessed August 2025. 


4. Medical Group Management Association; Jackson Physician Search. Early‑Career Physician Recruiting & Retention Playbook. October 23, 2023. Accessed August 2025. 


5. Von Rosenvinge EC, et al. A crisis in scope: Recruitment and retention challenges reported by VA gastroenterology section chiefs. Fed Pract. 2024 Aug. doi:10.12788/fp.0504.

Introduction

For many of us in gastroenterology, landing that first attending job feels like the ultimate victory lap — the reward for all those years of training. We sign the contract, relocate, and imagine this will be our “forever job.” Reality often plays out differently.

In fact, 43% of physicians change jobs within five years, while 83% changed employers at least once in their careers.¹ Even within our field — which is always in demand — turnover is high; 1 in 3 gastroenterologists are planning to leave their current role within two years.² Why does this happen? More importantly, how do we navigate this transition with clarity and confidence as an early-career GI?
 

My Story: When I Dared to Change My “Forever Job”

When I signed my first attending contract, I didn’t negotiate a single thing. My priorities were simple: family in Toronto and visa requirements. After a decade of medical school, residency, and fellowship, everything else felt secondary. I was happy to be back home.

The job itself was good — reasonable hours, flexible colleagues, and ample opportunity to enhance my procedural skills. As I started carving out my niche in endobariatrics, the support I needed to grow further was not there. I kept telling myself that this job fulfilled my values and I needed to be patient: “this is my forever job. I am close to my family and that’s what matters.”

Then, during a suturing course at the American Society of Gastrointestinal Endoscopy, I had a casual chat with the course director (now my boss). It took me by surprise, but as the conversation continued, he offered me a job. It was tempting: the chance to build my own endobariatrics program with real institutional backing. The catch? It was in a city I had never been to, with no family or friends around. I politely said “no, thank you, I can’t.” He smiled, gave me his number, and said, “think about it.”

For the first time, I allowed myself to ask, “could I really leave my forever job?”
 

The Power of a Circle and a Spreadsheet

I leaned on my circle — a close group of fellowship friends who each took a turn being someone’s lifeline. We have monthly Zoom calls to talk about jobs, family, and career aspirations. When I shared my dilemma, I realized I wasn’t alone; one friend was also unhappy with her first job. Suddenly, we were asking one another, “can we really leave?”

I hired a career consultant familiar with physician visa issues — hands down, the best money I ever invested. The job search felt like dating: each interview was a first date; some needed a second or third date before I knew if it could be a match.

After every interview, I’d jump on Zoom with my circle. We’d screen-share my giant Excel spreadsheet — our decision matrix — with columns for everything I cared about:

• Institute
• Administrative Time
• Endobariatric support
• Director Title
• Salary
• On-call
• Vacation
• Proximity to airport
• Cost of living
• RVU percentage
• Endoscopy center buy-in
• Contract duration
• Support staff
• CME

We scored each job, line by line, and not a single job checked all the boxes. As I sat there in a state of decision paralysis, it became clear that this was not a simple decision.
 

The GI Community: A Small, Supportive World

The GI community is incredibly close-knit and kind-hearted. At every conference, I made a point to chat with as many colleagues as I could, to hear their perspectives on jobs and how they made tough career moves. Those conversations were real — no Google search or Excel sheet could offer the perspective and insight I gained by simply asking and leaning on the GI community.

Meanwhile, the person who had first offered me that job kept checking in, catching up at conferences, and bonding over our love for food and baking. With him, I never felt like I was being ‘interviewed’ — I felt valued. It did not feel like he was trying to fill a position with just anyone to improve the call pool. He genuinely wanted to understand what my goals were and how I envisioned my future. Through those conversations, he reminded me of my original passions, which were sidelined when so immersed in the daily routine. 

I’ve learned that feeling valued doesn’t come from grand gestures in recruitment. It’s in the quiet signs of respect, trust, and being seen. He wasn’t looking for just anyone; he was looking for someone whose goals aligned with his group’s and someone in whom he wanted to invest. While others might chase the highest salary, the most flexible schedule, or the strongest ancillary support, I realized I valued something I did not realize that I was lacking until then: mentorship.
 

What I Learned: There is No Such Thing As “The Perfect Job”

After a full year of spreadsheets, Zoom calls, conference chats, and overthinking, I came to a big realization: there’s no perfect job — there’s no such thing as an ideal “forever job.” The only constant for humans is change. Our circumstances change, our priorities shift, our interests shuffle, and our finances evolve. The best job is simply the one that fits the stage of life you’re in at that given moment. For me, mentorship and growth became my top priorities, even if it meant moving away from family.

What Physicians Value Most in a Second Job

After their first job, early-career gastroenterologists often reevaluate what really matters. Recent surveys highlight four key priorities:

• Work-life balance:

In a 2022 CompHealth Group healthcare survey, 85% of physicians ranked work-life balance as their top job priority.³

• Mentorship and growth:

Nearly 1 in 3 physicians cited lack of mentorship or career advancement as their reason for leaving a first job, per the 2023 MGMA/Jackson Physician Search report.⁴

• Compensation:

While not always the main reason for leaving, 77% of physicians now list compensation as a top priority — a big jump from prior years.³

• Practice support:

Poor infrastructure, administrative overload, or understaffed teams are common dealbreakers. In the second job, physicians look for well-run practices with solid support staff and reduced burnout risk.⁵

Conclusion

Your first job doesn’t have to be your last. What matters is knowing when it’s time to evolve. Welcome the uncertainty, talk to your circle, lean on your community, and use a spreadsheet if you need to — but don’t forget to trust your gut. There’s no forever job or the perfect path, only the next move that feels most true to who you are in that moment.

Dr. Ismail (@mayyismail) is Assistant Professor of Clinical Medicine (Gastroenterology) at Temple University in Philadelphia, Pennsylvania. She declares no conflicts of interest.

References

1. CHG Healthcare. Survey: 62% of physicians made a career change in the last two years. CHG Healthcare blog. June 10, 2024. Accessed August 5, 2025.


2. Berg S. Physicians in these 10 specialties are less likely to quit. AMA News. Published June 24, 2025. Accessed July 2025. 


3. Saley C. Survey: Work/life balance is #1 priority in physicians’ job search. CHG Healthcare Insights. March 10, 2022. Accessed August 2025. 


4. Medical Group Management Association; Jackson Physician Search. Early‑Career Physician Recruiting & Retention Playbook. October 23, 2023. Accessed August 2025. 


5. Von Rosenvinge EC, et al. A crisis in scope: Recruitment and retention challenges reported by VA gastroenterology section chiefs. Fed Pract. 2024 Aug. doi:10.12788/fp.0504.

Fresenius Kabi USA has initiated a voluntary nationwide recall of three lots of famotidine injection, USP 20 mg/2 mL (10 mg/mL, 2 mL vial), according to a company announcement posted on the FDA website. 

The recall affects the following lot numbers 6133156 and 6133194, with expiration dates of August 2026, and lot number 6133388, with an expiration date of October 2026.

The recall stems from “out-of-specification endotoxin results in certain reserve samples of one lot,” the company said. The two additional lots are being recalled as a precaution. 

Elevated endotoxin levels may lead to severe systemic reactions, including sepsis, septic shock, inflammatory and life-threatening immune responses, and potentially death. 

Nonserious adverse events have been reported in association with lot 6133156, including chills, altered mental status, changes in respiratory status, fever/increased body temperature, shivering, and shaking. 

Famotidine injection is indicated in some hospitalized patients with pathological hypersecretory conditions or intractable ulcers or as an alternative to the oral dosage forms for short-term use in patients unable to take oral medication for certain conditions, including active duodenal ulcer, benign gastric ulcer or gastroesophageal reflux disease, or maintenance therapy for duodenal ulcer patients at reduced dosage after healing of an active ulcer.

Clinicians should be alert for symptoms potentially related to endotoxin exposure in patients who have received the affected product; document use of the product in affected lots (if already administered) and monitor patients carefully; and inform prescribing clinicians and nursing staff so they can monitor for signs of endotoxin-related reaction.

Patients should be advised to contact their physician or healthcare provider if they experienced any problems that may be related to receiving the affected drug. 

Clinicians should check their inventory for famotidine injection USP 20 mg/2 mL vials; discontinue use, dispensing, and distribution of affected lots; and segregate and quarantine any affected units to prevent inadvertent use. 

For questions or product return coordination, contact Fresenius Kabi USA Quality Assurance at 1-866-716-2459 or email at [email protected].

Adverse events or quality issues related to this recall should be reported to Fresenius Kabi (1-800-551-7176) and to the FDA MedWatch program. 
 

A version of this article appeared on Medscape.com.

Fresenius Kabi USA has initiated a voluntary nationwide recall of three lots of famotidine injection, USP 20 mg/2 mL (10 mg/mL, 2 mL vial), according to a company announcement posted on the FDA website. 

The recall affects the following lot numbers 6133156 and 6133194, with expiration dates of August 2026, and lot number 6133388, with an expiration date of October 2026.

The recall stems from “out-of-specification endotoxin results in certain reserve samples of one lot,” the company said. The two additional lots are being recalled as a precaution. 

Elevated endotoxin levels may lead to severe systemic reactions, including sepsis, septic shock, inflammatory and life-threatening immune responses, and potentially death. 

Nonserious adverse events have been reported in association with lot 6133156, including chills, altered mental status, changes in respiratory status, fever/increased body temperature, shivering, and shaking. 

Famotidine injection is indicated in some hospitalized patients with pathological hypersecretory conditions or intractable ulcers or as an alternative to the oral dosage forms for short-term use in patients unable to take oral medication for certain conditions, including active duodenal ulcer, benign gastric ulcer or gastroesophageal reflux disease, or maintenance therapy for duodenal ulcer patients at reduced dosage after healing of an active ulcer.

Clinicians should be alert for symptoms potentially related to endotoxin exposure in patients who have received the affected product; document use of the product in affected lots (if already administered) and monitor patients carefully; and inform prescribing clinicians and nursing staff so they can monitor for signs of endotoxin-related reaction.

Patients should be advised to contact their physician or healthcare provider if they experienced any problems that may be related to receiving the affected drug. 

Clinicians should check their inventory for famotidine injection USP 20 mg/2 mL vials; discontinue use, dispensing, and distribution of affected lots; and segregate and quarantine any affected units to prevent inadvertent use. 

For questions or product return coordination, contact Fresenius Kabi USA Quality Assurance at 1-866-716-2459 or email at [email protected].

Adverse events or quality issues related to this recall should be reported to Fresenius Kabi (1-800-551-7176) and to the FDA MedWatch program. 
 

A version of this article appeared on Medscape.com.

Fresenius Kabi USA has initiated a voluntary nationwide recall of three lots of famotidine injection, USP 20 mg/2 mL (10 mg/mL, 2 mL vial), according to a company announcement posted on the FDA website. 

The recall affects the following lot numbers 6133156 and 6133194, with expiration dates of August 2026, and lot number 6133388, with an expiration date of October 2026.

The recall stems from “out-of-specification endotoxin results in certain reserve samples of one lot,” the company said. The two additional lots are being recalled as a precaution. 

Elevated endotoxin levels may lead to severe systemic reactions, including sepsis, septic shock, inflammatory and life-threatening immune responses, and potentially death. 

Nonserious adverse events have been reported in association with lot 6133156, including chills, altered mental status, changes in respiratory status, fever/increased body temperature, shivering, and shaking. 

Famotidine injection is indicated in some hospitalized patients with pathological hypersecretory conditions or intractable ulcers or as an alternative to the oral dosage forms for short-term use in patients unable to take oral medication for certain conditions, including active duodenal ulcer, benign gastric ulcer or gastroesophageal reflux disease, or maintenance therapy for duodenal ulcer patients at reduced dosage after healing of an active ulcer.

Clinicians should be alert for symptoms potentially related to endotoxin exposure in patients who have received the affected product; document use of the product in affected lots (if already administered) and monitor patients carefully; and inform prescribing clinicians and nursing staff so they can monitor for signs of endotoxin-related reaction.

Patients should be advised to contact their physician or healthcare provider if they experienced any problems that may be related to receiving the affected drug. 

Clinicians should check their inventory for famotidine injection USP 20 mg/2 mL vials; discontinue use, dispensing, and distribution of affected lots; and segregate and quarantine any affected units to prevent inadvertent use. 

For questions or product return coordination, contact Fresenius Kabi USA Quality Assurance at 1-866-716-2459 or email at [email protected].

Adverse events or quality issues related to this recall should be reported to Fresenius Kabi (1-800-551-7176) and to the FDA MedWatch program. 
 

A version of this article appeared on Medscape.com.

Duodenal mucosal resurfacing (DMR) — an investigational endoscopic procedure — helped patients maintain weight loss, and in some cases, even lose additional weight, 3 months after discontinuing GLP-1 receptor agonist therapy, initial results of the open-label, multistage REMAIN-1 trial showed.

In addition, “the procedure was well tolerated, with only minor, transient TEAEs [treatment-emergent adverse events] consistent with routine upper endoscopy,” said Shailendra Singh, MD, of West Virginia University in Morgantown, West Virginia, who presented the findings at The Obesity Society’s Obesity Week 2025 meeting in Atlanta.

DMR uses hydrothermal ablation to treat the duodenal mucosa, which may be dysfunctional in both obesity and impaired glucose tolerance. A previous pooled clinical trial analysis of more than 100 patients with type 2 diabetes demonstrated that DMR helped patients maintain body weight loss up to 48 weeks post-procedure.

Metabolic therapeutics company Fractyl Health, Burlington, Massachusetts, developed the procedure, called Revita, and is sponsoring the current study. The trial’s aim is to determine the effect of DMR on weight-loss maintenance in patients with ≥ 15% total body weight loss using a GLP-1 RA in both an open-label arm and a prospective, randomized, double-blind, sham-controlled multicenter arm.
 

‘Encouraging Preliminary Findings’

The open-label arm included 15 DMR-treated participants (mean age, 49 years, 87% female ), all of whom had taken tirzepatide for a minimum of 5 months and a maximum of 3 years prior to DMR and had lost at least 15% of their total body weight.

Participants had a mean pre-GLP-1 RA weight of 104.8 kg and a mean weight prior to DMR of 79.4 kg, for a mean total body weight loss from the start of GLP-1 RA of 23.8%. Weight loss was heterogeneous and reflective of the real-world patient population taking GLP-1 medications, according to the poster presentation.

Participants discontinued their GLP-1 medication, underwent the DMR procedure, and were followed for 3 months. A total of 12 of 13 patients maintained or lost weight at that point, with 6 of 13 losing additional weight.

Specifically, participants experienced a median of 0.46% weight change (approximately 1 lb) compared with the 5%-6% weight regain (10-15 lb) observed after GLP-1 discontinuation in the literature.

The procedure was well tolerated, with most patients experiencing no TEAEs and none experiencing an event greater than grade 1. Grade 1 events occurred in three patients; 23% were transient in nature, lasting 2-5 days, and were similar to those typically seen with a routine upper endoscopy.

“These encouraging preliminary findings suggest that DMR may safely achieve durable weight maintenance for patients who wish to discontinue GLP-1 RA therapy,” the study authors stated.

Randomization is anticipated in early 2026, with 6-month topline data and a potential premarket approval filing expected in the second half of 2026.
 

A version of this article appeared on Medscape.com.

Duodenal mucosal resurfacing (DMR) — an investigational endoscopic procedure — helped patients maintain weight loss, and in some cases, even lose additional weight, 3 months after discontinuing GLP-1 receptor agonist therapy, initial results of the open-label, multistage REMAIN-1 trial showed.

In addition, “the procedure was well tolerated, with only minor, transient TEAEs [treatment-emergent adverse events] consistent with routine upper endoscopy,” said Shailendra Singh, MD, of West Virginia University in Morgantown, West Virginia, who presented the findings at The Obesity Society’s Obesity Week 2025 meeting in Atlanta.

DMR uses hydrothermal ablation to treat the duodenal mucosa, which may be dysfunctional in both obesity and impaired glucose tolerance. A previous pooled clinical trial analysis of more than 100 patients with type 2 diabetes demonstrated that DMR helped patients maintain body weight loss up to 48 weeks post-procedure.

Metabolic therapeutics company Fractyl Health, Burlington, Massachusetts, developed the procedure, called Revita, and is sponsoring the current study. The trial’s aim is to determine the effect of DMR on weight-loss maintenance in patients with ≥ 15% total body weight loss using a GLP-1 RA in both an open-label arm and a prospective, randomized, double-blind, sham-controlled multicenter arm.
 

‘Encouraging Preliminary Findings’

The open-label arm included 15 DMR-treated participants (mean age, 49 years, 87% female ), all of whom had taken tirzepatide for a minimum of 5 months and a maximum of 3 years prior to DMR and had lost at least 15% of their total body weight.

Participants had a mean pre-GLP-1 RA weight of 104.8 kg and a mean weight prior to DMR of 79.4 kg, for a mean total body weight loss from the start of GLP-1 RA of 23.8%. Weight loss was heterogeneous and reflective of the real-world patient population taking GLP-1 medications, according to the poster presentation.

Participants discontinued their GLP-1 medication, underwent the DMR procedure, and were followed for 3 months. A total of 12 of 13 patients maintained or lost weight at that point, with 6 of 13 losing additional weight.

Specifically, participants experienced a median of 0.46% weight change (approximately 1 lb) compared with the 5%-6% weight regain (10-15 lb) observed after GLP-1 discontinuation in the literature.

The procedure was well tolerated, with most patients experiencing no TEAEs and none experiencing an event greater than grade 1. Grade 1 events occurred in three patients; 23% were transient in nature, lasting 2-5 days, and were similar to those typically seen with a routine upper endoscopy.

“These encouraging preliminary findings suggest that DMR may safely achieve durable weight maintenance for patients who wish to discontinue GLP-1 RA therapy,” the study authors stated.

Randomization is anticipated in early 2026, with 6-month topline data and a potential premarket approval filing expected in the second half of 2026.
 

A version of this article appeared on Medscape.com.

Duodenal mucosal resurfacing (DMR) — an investigational endoscopic procedure — helped patients maintain weight loss, and in some cases, even lose additional weight, 3 months after discontinuing GLP-1 receptor agonist therapy, initial results of the open-label, multistage REMAIN-1 trial showed.

In addition, “the procedure was well tolerated, with only minor, transient TEAEs [treatment-emergent adverse events] consistent with routine upper endoscopy,” said Shailendra Singh, MD, of West Virginia University in Morgantown, West Virginia, who presented the findings at The Obesity Society’s Obesity Week 2025 meeting in Atlanta.

DMR uses hydrothermal ablation to treat the duodenal mucosa, which may be dysfunctional in both obesity and impaired glucose tolerance. A previous pooled clinical trial analysis of more than 100 patients with type 2 diabetes demonstrated that DMR helped patients maintain body weight loss up to 48 weeks post-procedure.

Metabolic therapeutics company Fractyl Health, Burlington, Massachusetts, developed the procedure, called Revita, and is sponsoring the current study. The trial’s aim is to determine the effect of DMR on weight-loss maintenance in patients with ≥ 15% total body weight loss using a GLP-1 RA in both an open-label arm and a prospective, randomized, double-blind, sham-controlled multicenter arm.
 

‘Encouraging Preliminary Findings’

The open-label arm included 15 DMR-treated participants (mean age, 49 years, 87% female ), all of whom had taken tirzepatide for a minimum of 5 months and a maximum of 3 years prior to DMR and had lost at least 15% of their total body weight.

Participants had a mean pre-GLP-1 RA weight of 104.8 kg and a mean weight prior to DMR of 79.4 kg, for a mean total body weight loss from the start of GLP-1 RA of 23.8%. Weight loss was heterogeneous and reflective of the real-world patient population taking GLP-1 medications, according to the poster presentation.

Participants discontinued their GLP-1 medication, underwent the DMR procedure, and were followed for 3 months. A total of 12 of 13 patients maintained or lost weight at that point, with 6 of 13 losing additional weight.

Specifically, participants experienced a median of 0.46% weight change (approximately 1 lb) compared with the 5%-6% weight regain (10-15 lb) observed after GLP-1 discontinuation in the literature.

The procedure was well tolerated, with most patients experiencing no TEAEs and none experiencing an event greater than grade 1. Grade 1 events occurred in three patients; 23% were transient in nature, lasting 2-5 days, and were similar to those typically seen with a routine upper endoscopy.

“These encouraging preliminary findings suggest that DMR may safely achieve durable weight maintenance for patients who wish to discontinue GLP-1 RA therapy,” the study authors stated.

Randomization is anticipated in early 2026, with 6-month topline data and a potential premarket approval filing expected in the second half of 2026.
 

A version of this article appeared on Medscape.com.

PHOENIX — Duvakitug, a novel anti-TL1a monoclonal antibody, demonstrated statistically significant differences in endoscopic response rates compared to placebo in adults with moderately to severely active Crohn’s disease, according to results from the phase 2b RELIEVE UCCD study.

“Additional clinical and endoscopic endpoints supported the primary endpoint of endoscopic response observed with duvakitug,” study author Vipul Jairath, MB ChB, DPhil, MRCP, professor of medicine at the Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada, reported.

These findings “support further development of duvakitug as a treatment option” for these patients, said Jairath, who presented the data at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

In the 14-week randomized controlled induction study, 138 adults aged 18-75 years with moderately to severely active Crohn’s disease were randomized to receive a 2250-mg loading dose of duvakitug or placebo subcutaneously, followed by either duvakitug 450 mg, 900 mg, or placebo every 2 weeks. Each arm of the study contained 46 patients, with a mean age of about 40 years, and a mean duration of disease of 9-11 years. The mean Simple Endoscopic Score for Crohn’s Disease (SES-CD) score at baseline was 12.

Half to two thirds of the patients had taken advanced therapies, either approved or investigational. The trial participants were allowed to take concomitant corticosteroids, 5-aminosalicylic acid drugs, and immunosuppressants (including 6-mercaptopurine, azathioprine, and methotrexate).

Notably, the primary endpoint of endoscopic response — defined as ≥ 50% reduction from baseline in SES-CD score — was achieved in almost half of the patients taking the 900-mg higher dose (22 of 46 patients). The endoscopic response was achieved in 13 of 27 patients who had previous experience with advanced therapies, including approved biologics (anti-TNF, anti-integrins, anti-interleukin [IL]-12/23, or anti-IL-23), and JAK inhibitors.

In the high-dose arm, 26% of participants achieved endoscopic remission, and 54% achieved clinical remission.

Just 13% of patients in the duvakitug arms had a treatment-related adverse event, with serious adverse events slightly higher in the 450 mg arm than in the 900 mg arm (13% vs 2%). The most common side effects were anemia, headache, and nasopharyngitis. One patient in the 900 mg group and four in the lower-dose group discontinued due to an adverse event.

When asked to comment by GI & Hepatology News, Jordan Axelrad, MD, MPH, co-director of the Inflammatory Bowel Disease Center at the NYU Langone Health, New York City, said the “results demonstrate that duvakitug is a promising therapy for patients with Crohn’s disease, with 14-week induction placebo-adjusted endoscopic response rates rivaling or exceeding our currently FDA-approved advanced, effective therapies.”

The efficacy in patients with prior exposure to advanced therapies is especially noteworthy, as it is “a population in which most existing and investigational agents show limited clinical benefit,” said Axelrad, who is also an associate professor of medicine at the NYU Grossman School of Medicine, New York City.

Axelrad said there were no concerning safety signals, “which strengthens its appeal for clinical use.”

He said he sees promise in the anti-TL1a inhibitor class, noting that TL1A “is a key cytokine that spans innate and adaptive mucosal inflammation and also directly influences fibroblast and epithelial biology, contributing to intestinal fibrosis and barrier dysfunction.”

Because therapies in the class simultaneously target inflammatory and fibrotic pathways, “TL1A inhibition offers the potential for more durable disease control than conventional cytokine-directed therapies,” he said.

But, noted Axelrad, it is early in duvakitug’s development. “We certainly need a larger cohort in a phase 3 study with maintenance data,” he said.

Jairath disclosed having financial relationships with AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris Pharmaceuticals, AstraZeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Endpoint Health, Enthera, Ferring Pharmaceuticals, Flagship Pioneering, Fresenius Kabi, Galapagos NV, Genentech, Gilde Healthcare, GlaxoSmithKline, Innomar, JAMP, Johnson & Johnson, Merck, Metacrine, Mylan, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Shire, Sorriso Pharmaceuticals, Syndegen, Takeda, TD Securities, Teva, Topivert, Ventyx Biosciences, and Vividion Therapeutics. Axelrad reported receiving research grants from BioFire Diagnostics, Genentech, Janssen, and Takeda; consultant, advisory board fees or honorarium from Abbvie, Abviax, Adiso, BioFire Diagnostics, Biomerieux, Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Pfizer, Sanofi, Takeda, and Vedanta.

A version of this article appeared on Medscape.com . 

PHOENIX — Duvakitug, a novel anti-TL1a monoclonal antibody, demonstrated statistically significant differences in endoscopic response rates compared to placebo in adults with moderately to severely active Crohn’s disease, according to results from the phase 2b RELIEVE UCCD study.

“Additional clinical and endoscopic endpoints supported the primary endpoint of endoscopic response observed with duvakitug,” study author Vipul Jairath, MB ChB, DPhil, MRCP, professor of medicine at the Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada, reported.

These findings “support further development of duvakitug as a treatment option” for these patients, said Jairath, who presented the data at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

In the 14-week randomized controlled induction study, 138 adults aged 18-75 years with moderately to severely active Crohn’s disease were randomized to receive a 2250-mg loading dose of duvakitug or placebo subcutaneously, followed by either duvakitug 450 mg, 900 mg, or placebo every 2 weeks. Each arm of the study contained 46 patients, with a mean age of about 40 years, and a mean duration of disease of 9-11 years. The mean Simple Endoscopic Score for Crohn’s Disease (SES-CD) score at baseline was 12.

Half to two thirds of the patients had taken advanced therapies, either approved or investigational. The trial participants were allowed to take concomitant corticosteroids, 5-aminosalicylic acid drugs, and immunosuppressants (including 6-mercaptopurine, azathioprine, and methotrexate).

Notably, the primary endpoint of endoscopic response — defined as ≥ 50% reduction from baseline in SES-CD score — was achieved in almost half of the patients taking the 900-mg higher dose (22 of 46 patients). The endoscopic response was achieved in 13 of 27 patients who had previous experience with advanced therapies, including approved biologics (anti-TNF, anti-integrins, anti-interleukin [IL]-12/23, or anti-IL-23), and JAK inhibitors.

In the high-dose arm, 26% of participants achieved endoscopic remission, and 54% achieved clinical remission.

Just 13% of patients in the duvakitug arms had a treatment-related adverse event, with serious adverse events slightly higher in the 450 mg arm than in the 900 mg arm (13% vs 2%). The most common side effects were anemia, headache, and nasopharyngitis. One patient in the 900 mg group and four in the lower-dose group discontinued due to an adverse event.

When asked to comment by GI & Hepatology News, Jordan Axelrad, MD, MPH, co-director of the Inflammatory Bowel Disease Center at the NYU Langone Health, New York City, said the “results demonstrate that duvakitug is a promising therapy for patients with Crohn’s disease, with 14-week induction placebo-adjusted endoscopic response rates rivaling or exceeding our currently FDA-approved advanced, effective therapies.”

The efficacy in patients with prior exposure to advanced therapies is especially noteworthy, as it is “a population in which most existing and investigational agents show limited clinical benefit,” said Axelrad, who is also an associate professor of medicine at the NYU Grossman School of Medicine, New York City.

Axelrad said there were no concerning safety signals, “which strengthens its appeal for clinical use.”

He said he sees promise in the anti-TL1a inhibitor class, noting that TL1A “is a key cytokine that spans innate and adaptive mucosal inflammation and also directly influences fibroblast and epithelial biology, contributing to intestinal fibrosis and barrier dysfunction.”

Because therapies in the class simultaneously target inflammatory and fibrotic pathways, “TL1A inhibition offers the potential for more durable disease control than conventional cytokine-directed therapies,” he said.

But, noted Axelrad, it is early in duvakitug’s development. “We certainly need a larger cohort in a phase 3 study with maintenance data,” he said.

Jairath disclosed having financial relationships with AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris Pharmaceuticals, AstraZeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Endpoint Health, Enthera, Ferring Pharmaceuticals, Flagship Pioneering, Fresenius Kabi, Galapagos NV, Genentech, Gilde Healthcare, GlaxoSmithKline, Innomar, JAMP, Johnson & Johnson, Merck, Metacrine, Mylan, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Shire, Sorriso Pharmaceuticals, Syndegen, Takeda, TD Securities, Teva, Topivert, Ventyx Biosciences, and Vividion Therapeutics. Axelrad reported receiving research grants from BioFire Diagnostics, Genentech, Janssen, and Takeda; consultant, advisory board fees or honorarium from Abbvie, Abviax, Adiso, BioFire Diagnostics, Biomerieux, Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Pfizer, Sanofi, Takeda, and Vedanta.

A version of this article appeared on Medscape.com . 

PHOENIX — Duvakitug, a novel anti-TL1a monoclonal antibody, demonstrated statistically significant differences in endoscopic response rates compared to placebo in adults with moderately to severely active Crohn’s disease, according to results from the phase 2b RELIEVE UCCD study.

“Additional clinical and endoscopic endpoints supported the primary endpoint of endoscopic response observed with duvakitug,” study author Vipul Jairath, MB ChB, DPhil, MRCP, professor of medicine at the Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada, reported.

These findings “support further development of duvakitug as a treatment option” for these patients, said Jairath, who presented the data at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

In the 14-week randomized controlled induction study, 138 adults aged 18-75 years with moderately to severely active Crohn’s disease were randomized to receive a 2250-mg loading dose of duvakitug or placebo subcutaneously, followed by either duvakitug 450 mg, 900 mg, or placebo every 2 weeks. Each arm of the study contained 46 patients, with a mean age of about 40 years, and a mean duration of disease of 9-11 years. The mean Simple Endoscopic Score for Crohn’s Disease (SES-CD) score at baseline was 12.

Half to two thirds of the patients had taken advanced therapies, either approved or investigational. The trial participants were allowed to take concomitant corticosteroids, 5-aminosalicylic acid drugs, and immunosuppressants (including 6-mercaptopurine, azathioprine, and methotrexate).

Notably, the primary endpoint of endoscopic response — defined as ≥ 50% reduction from baseline in SES-CD score — was achieved in almost half of the patients taking the 900-mg higher dose (22 of 46 patients). The endoscopic response was achieved in 13 of 27 patients who had previous experience with advanced therapies, including approved biologics (anti-TNF, anti-integrins, anti-interleukin [IL]-12/23, or anti-IL-23), and JAK inhibitors.

In the high-dose arm, 26% of participants achieved endoscopic remission, and 54% achieved clinical remission.

Just 13% of patients in the duvakitug arms had a treatment-related adverse event, with serious adverse events slightly higher in the 450 mg arm than in the 900 mg arm (13% vs 2%). The most common side effects were anemia, headache, and nasopharyngitis. One patient in the 900 mg group and four in the lower-dose group discontinued due to an adverse event.

When asked to comment by GI & Hepatology News, Jordan Axelrad, MD, MPH, co-director of the Inflammatory Bowel Disease Center at the NYU Langone Health, New York City, said the “results demonstrate that duvakitug is a promising therapy for patients with Crohn’s disease, with 14-week induction placebo-adjusted endoscopic response rates rivaling or exceeding our currently FDA-approved advanced, effective therapies.”

The efficacy in patients with prior exposure to advanced therapies is especially noteworthy, as it is “a population in which most existing and investigational agents show limited clinical benefit,” said Axelrad, who is also an associate professor of medicine at the NYU Grossman School of Medicine, New York City.

Axelrad said there were no concerning safety signals, “which strengthens its appeal for clinical use.”

He said he sees promise in the anti-TL1a inhibitor class, noting that TL1A “is a key cytokine that spans innate and adaptive mucosal inflammation and also directly influences fibroblast and epithelial biology, contributing to intestinal fibrosis and barrier dysfunction.”

Because therapies in the class simultaneously target inflammatory and fibrotic pathways, “TL1A inhibition offers the potential for more durable disease control than conventional cytokine-directed therapies,” he said.

But, noted Axelrad, it is early in duvakitug’s development. “We certainly need a larger cohort in a phase 3 study with maintenance data,” he said.

Jairath disclosed having financial relationships with AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris Pharmaceuticals, AstraZeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Endpoint Health, Enthera, Ferring Pharmaceuticals, Flagship Pioneering, Fresenius Kabi, Galapagos NV, Genentech, Gilde Healthcare, GlaxoSmithKline, Innomar, JAMP, Johnson & Johnson, Merck, Metacrine, Mylan, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Shire, Sorriso Pharmaceuticals, Syndegen, Takeda, TD Securities, Teva, Topivert, Ventyx Biosciences, and Vividion Therapeutics. Axelrad reported receiving research grants from BioFire Diagnostics, Genentech, Janssen, and Takeda; consultant, advisory board fees or honorarium from Abbvie, Abviax, Adiso, BioFire Diagnostics, Biomerieux, Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Pfizer, Sanofi, Takeda, and Vedanta.

A version of this article appeared on Medscape.com . 

PHOENIX — Gastroenterologists want more training in how to safely deliver moderate sedation during endoscopic procedures, and a majority would be interested in providing physician-directed propofol sedation, especially after in-person or online training, according to results from an ongoing survey presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The dwindling supply of anesthesiology professionals in the US puts pressure on endoscopists, Dayna S. Early, MD, professor of medicine in the Gastroenterology Division at the Washington University, director of endoscopy at Barnes-Jewish Hospital, both in St. Louis, and chair of an ACG task force on anesthesia issues, told meeting attendees. However, preliminary results from the survey found that only about 4% of respondents said they used solely endoscopist-directed moderate sedation.

This could be because — as the survey also showed — GI fellows are not receiving adequate training in moderate sedation, which requires no interventions to maintain a patient airway, she reported. About 80% of program directors and 75% of senior fellows responding to the survey said they received training in moderate/conscious sedation during their fellowship.

These numbers are not impressive, said Early.

The Accreditation Council for Graduate Medical Education (ACGME) requires gastroenterology fellows to demonstrate competence in conscious sedation, along with other core skills, she explained. “What if I substituted training in mucosal biopsy or training in colonoscopy with polypectomy, which are other core requirements? I think you’d be shocked.”

The survey was small, with only 92 of 250 program directors and 33 of 655 fellows responding, but Early said the task force continues to collect responses.

 

Is Existing Training Enough?

Ten percent of fellows who replied to the survey did not participate in any moderate sedation procedures during training. And about a third of program directors said fellows participated in less than 100 such procedures.

“We really don’t know if that’s enough, in this era of competency-based assessment, which really values competency measures over numbers,” said Early.

Of the fellows who did receive training, 37% received hands-on training, a quarter received didactic lecture training, 11% used online modules, and 17% received a combination of the above training methods.

Just two thirds of program directors said they or their fellows were competent in moderate sedation, while close to 70% of fellows judged themselves competent.

While the majority of program directors (80%) knew that training in conscious sedation was a core ACGME requirement, only around a quarter of fellows were aware of the requirement.

Most gastroenterologists rely on anesthesiologists or certified registered nurse anesthetists (CRNAs) to deliver moderate or deep sedation, said Early, citing results from a separate survey sent to practicing clinicians.

 

Ongoing Shortages of CRNAs and Anesthesiologists

Shortages of anesthesiologists and CRNAs will continue to limit endoscopy procedure volume, especially in rural areas of the US, said Early.

The nation is expected to be short by 450,000 CRNAs this year and by 6300 anesthesiologists within a decade, she reported. Anesthesia providers are burned out or nearing retirement age, and there are not enough residency programs to produce new anesthesiologists at the rate needed to meet the demand, she said.

Gastroenterologists have become reliant on anesthesia providers, but adding a clinician is more expensive and “doesn’t appear to resolve and improve safety as compared with endoscopist-directed sedation for routine procedures,” said Early.

When practicing clinicians were asked if they’d be interested in providing physician-directed propofol sedation, 20% said yes, while 35% said no. But 16% said they would want to provide moderate sedation after completing in-person training, and 19% said they would after completing online training.

It may take time for gastroenterologists to get appropriate training and reduce reliance on anesthesia providers, Early said. But she said it may be increasingly possible in states allowing endoscopist-directed, nurse-administered propofol, and with medications such as remimazolam, a rapid-acting benzodiazepine that has shown similar efficacy and lower adverse event rates than propofol.

There will have to be a really deliberate step in order to take back control of endoscopic sedation from anesthesia and start performing more modest sedation, she said.

Early reported having no conflicts.

A version of this article first appeared on Medscape.com.

PHOENIX — Gastroenterologists want more training in how to safely deliver moderate sedation during endoscopic procedures, and a majority would be interested in providing physician-directed propofol sedation, especially after in-person or online training, according to results from an ongoing survey presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The dwindling supply of anesthesiology professionals in the US puts pressure on endoscopists, Dayna S. Early, MD, professor of medicine in the Gastroenterology Division at the Washington University, director of endoscopy at Barnes-Jewish Hospital, both in St. Louis, and chair of an ACG task force on anesthesia issues, told meeting attendees. However, preliminary results from the survey found that only about 4% of respondents said they used solely endoscopist-directed moderate sedation.

This could be because — as the survey also showed — GI fellows are not receiving adequate training in moderate sedation, which requires no interventions to maintain a patient airway, she reported. About 80% of program directors and 75% of senior fellows responding to the survey said they received training in moderate/conscious sedation during their fellowship.

These numbers are not impressive, said Early.

The Accreditation Council for Graduate Medical Education (ACGME) requires gastroenterology fellows to demonstrate competence in conscious sedation, along with other core skills, she explained. “What if I substituted training in mucosal biopsy or training in colonoscopy with polypectomy, which are other core requirements? I think you’d be shocked.”

The survey was small, with only 92 of 250 program directors and 33 of 655 fellows responding, but Early said the task force continues to collect responses.

 

Is Existing Training Enough?

Ten percent of fellows who replied to the survey did not participate in any moderate sedation procedures during training. And about a third of program directors said fellows participated in less than 100 such procedures.

“We really don’t know if that’s enough, in this era of competency-based assessment, which really values competency measures over numbers,” said Early.

Of the fellows who did receive training, 37% received hands-on training, a quarter received didactic lecture training, 11% used online modules, and 17% received a combination of the above training methods.

Just two thirds of program directors said they or their fellows were competent in moderate sedation, while close to 70% of fellows judged themselves competent.

While the majority of program directors (80%) knew that training in conscious sedation was a core ACGME requirement, only around a quarter of fellows were aware of the requirement.

Most gastroenterologists rely on anesthesiologists or certified registered nurse anesthetists (CRNAs) to deliver moderate or deep sedation, said Early, citing results from a separate survey sent to practicing clinicians.

 

Ongoing Shortages of CRNAs and Anesthesiologists

Shortages of anesthesiologists and CRNAs will continue to limit endoscopy procedure volume, especially in rural areas of the US, said Early.

The nation is expected to be short by 450,000 CRNAs this year and by 6300 anesthesiologists within a decade, she reported. Anesthesia providers are burned out or nearing retirement age, and there are not enough residency programs to produce new anesthesiologists at the rate needed to meet the demand, she said.

Gastroenterologists have become reliant on anesthesia providers, but adding a clinician is more expensive and “doesn’t appear to resolve and improve safety as compared with endoscopist-directed sedation for routine procedures,” said Early.

When practicing clinicians were asked if they’d be interested in providing physician-directed propofol sedation, 20% said yes, while 35% said no. But 16% said they would want to provide moderate sedation after completing in-person training, and 19% said they would after completing online training.

It may take time for gastroenterologists to get appropriate training and reduce reliance on anesthesia providers, Early said. But she said it may be increasingly possible in states allowing endoscopist-directed, nurse-administered propofol, and with medications such as remimazolam, a rapid-acting benzodiazepine that has shown similar efficacy and lower adverse event rates than propofol.

There will have to be a really deliberate step in order to take back control of endoscopic sedation from anesthesia and start performing more modest sedation, she said.

Early reported having no conflicts.

A version of this article first appeared on Medscape.com.

PHOENIX — Gastroenterologists want more training in how to safely deliver moderate sedation during endoscopic procedures, and a majority would be interested in providing physician-directed propofol sedation, especially after in-person or online training, according to results from an ongoing survey presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The dwindling supply of anesthesiology professionals in the US puts pressure on endoscopists, Dayna S. Early, MD, professor of medicine in the Gastroenterology Division at the Washington University, director of endoscopy at Barnes-Jewish Hospital, both in St. Louis, and chair of an ACG task force on anesthesia issues, told meeting attendees. However, preliminary results from the survey found that only about 4% of respondents said they used solely endoscopist-directed moderate sedation.

This could be because — as the survey also showed — GI fellows are not receiving adequate training in moderate sedation, which requires no interventions to maintain a patient airway, she reported. About 80% of program directors and 75% of senior fellows responding to the survey said they received training in moderate/conscious sedation during their fellowship.

These numbers are not impressive, said Early.

The Accreditation Council for Graduate Medical Education (ACGME) requires gastroenterology fellows to demonstrate competence in conscious sedation, along with other core skills, she explained. “What if I substituted training in mucosal biopsy or training in colonoscopy with polypectomy, which are other core requirements? I think you’d be shocked.”

The survey was small, with only 92 of 250 program directors and 33 of 655 fellows responding, but Early said the task force continues to collect responses.

 

Is Existing Training Enough?

Ten percent of fellows who replied to the survey did not participate in any moderate sedation procedures during training. And about a third of program directors said fellows participated in less than 100 such procedures.

“We really don’t know if that’s enough, in this era of competency-based assessment, which really values competency measures over numbers,” said Early.

Of the fellows who did receive training, 37% received hands-on training, a quarter received didactic lecture training, 11% used online modules, and 17% received a combination of the above training methods.

Just two thirds of program directors said they or their fellows were competent in moderate sedation, while close to 70% of fellows judged themselves competent.

While the majority of program directors (80%) knew that training in conscious sedation was a core ACGME requirement, only around a quarter of fellows were aware of the requirement.

Most gastroenterologists rely on anesthesiologists or certified registered nurse anesthetists (CRNAs) to deliver moderate or deep sedation, said Early, citing results from a separate survey sent to practicing clinicians.

 

Ongoing Shortages of CRNAs and Anesthesiologists

Shortages of anesthesiologists and CRNAs will continue to limit endoscopy procedure volume, especially in rural areas of the US, said Early.

The nation is expected to be short by 450,000 CRNAs this year and by 6300 anesthesiologists within a decade, she reported. Anesthesia providers are burned out or nearing retirement age, and there are not enough residency programs to produce new anesthesiologists at the rate needed to meet the demand, she said.

Gastroenterologists have become reliant on anesthesia providers, but adding a clinician is more expensive and “doesn’t appear to resolve and improve safety as compared with endoscopist-directed sedation for routine procedures,” said Early.

When practicing clinicians were asked if they’d be interested in providing physician-directed propofol sedation, 20% said yes, while 35% said no. But 16% said they would want to provide moderate sedation after completing in-person training, and 19% said they would after completing online training.

It may take time for gastroenterologists to get appropriate training and reduce reliance on anesthesia providers, Early said. But she said it may be increasingly possible in states allowing endoscopist-directed, nurse-administered propofol, and with medications such as remimazolam, a rapid-acting benzodiazepine that has shown similar efficacy and lower adverse event rates than propofol.

There will have to be a really deliberate step in order to take back control of endoscopic sedation from anesthesia and start performing more modest sedation, she said.

Early reported having no conflicts.

A version of this article first appeared on Medscape.com.