On 2017 May 05, Anil Makam, MD, MAS commented:

We thank Dr. Atkin and colleagues for publishing long-term outcomes after a one-time screening flexible sigmoidoscopy.(1) Although we agree that this strategy reduces the relative risk of colorectal cancer (CRC) diagnoses and death, we disagree with the methods the authors used to calculate the absolute magnitude of benefit, which is critical in determining whether screening is actually worth the burden, harms and cost.(2) By relying on per protocol analyses, the authors overestimate the absolute benefit of flexible sigmoidoscopy given healthy user and adherer biases inherent in preventive health interventions— i.e., those who adhere to CRC screening also have other behaviors that reduce their overall risk of cancer and death (e.g. diet, smoking habits, exercise, etc.) independent of the screening test itself.(3, 4) There is strong evidence for the presence of these biases in the UK Flexible Sigmoidoscopy Screening Trial given the marked differences in all-cause mortality within the invited group when stratified by those who were adherent versus those who were not adherent to flexible sigmoidoscopy (20.7% versus 29.5%), a screening test that does not reduce overall mortality. Assessing the absolute benefits for screening from the intention-to-treat analyses gives the most accurate estimates and avoids the pitfalls of these biases. This approach results in markedly attenuated estimates of the benefits (Table). Because screening does not save lives (number needed to screen of infinity for all-cause mortality), accurate estimates of the absolute benefit on reducing CRC diagnoses and CRC-related death are key to informing decision aid development and shared decision making.

See Table here: https://twitter.com/AnilMakam/status/860490959225847809

Anil N. Makam, MD, MAS; Oanh K. Nguyen, MD, MAS

Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA

We declare no competing interests.

REFERENCES (1) Atkin W, Wooldrage K, Parkin DM, Kralj-Hans I, MacRae E, Shah U, Duffy S, Cross AJ. Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial. Lancet. 2017. (2) Makam AN, Nguyen OK. An Evidence-Based Medicine Approach to Antihyperglycemic Therapy in Diabetes Mellitus to Overcome Overtreatment. Circulation. 2017;135(2):180-195. (3) Shrank WH, Patrick AR, Brookhart MA. Healthy user and related biases in observational studies of preventive interventions: a primer for physicians. J Gen Intern Med. 2011;26(5):546-550. (4) Imperiale TF, Monahan PO, Stump TE, Glowinski EA, Ransohoff DF. Derivation and Validation of a Scoring System to Stratify Risk for Advanced Colorectal Neoplasia in Asymptomatic Adults: A Cross-sectional Study. Ann Intern Med. 2015;163(5):339-346.

On 2017 May 05, Anil Makam, MD, MAS commented:

We thank Dr. Atkin and colleagues for publishing long-term outcomes after a one-time screening flexible sigmoidoscopy.(1) Although we agree that this strategy reduces the relative risk of colorectal cancer (CRC) diagnoses and death, we disagree with the methods the authors used to calculate the absolute magnitude of benefit, which is critical in determining whether screening is actually worth the burden, harms and cost.(2) By relying on per protocol analyses, the authors overestimate the absolute benefit of flexible sigmoidoscopy given healthy user and adherer biases inherent in preventive health interventions— i.e., those who adhere to CRC screening also have other behaviors that reduce their overall risk of cancer and death (e.g. diet, smoking habits, exercise, etc.) independent of the screening test itself.(3, 4) There is strong evidence for the presence of these biases in the UK Flexible Sigmoidoscopy Screening Trial given the marked differences in all-cause mortality within the invited group when stratified by those who were adherent versus those who were not adherent to flexible sigmoidoscopy (20.7% versus 29.5%), a screening test that does not reduce overall mortality. Assessing the absolute benefits for screening from the intention-to-treat analyses gives the most accurate estimates and avoids the pitfalls of these biases. This approach results in markedly attenuated estimates of the benefits (Table). Because screening does not save lives (number needed to screen of infinity for all-cause mortality), accurate estimates of the absolute benefit on reducing CRC diagnoses and CRC-related death are key to informing decision aid development and shared decision making.

See Table here: https://twitter.com/AnilMakam/status/860490959225847809

Anil N. Makam, MD, MAS; Oanh K. Nguyen, MD, MAS

Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA

We declare no competing interests.

REFERENCES (1) Atkin W, Wooldrage K, Parkin DM, Kralj-Hans I, MacRae E, Shah U, Duffy S, Cross AJ. Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial. Lancet. 2017. (2) Makam AN, Nguyen OK. An Evidence-Based Medicine Approach to Antihyperglycemic Therapy in Diabetes Mellitus to Overcome Overtreatment. Circulation. 2017;135(2):180-195. (3) Shrank WH, Patrick AR, Brookhart MA. Healthy user and related biases in observational studies of preventive interventions: a primer for physicians. J Gen Intern Med. 2011;26(5):546-550. (4) Imperiale TF, Monahan PO, Stump TE, Glowinski EA, Ransohoff DF. Derivation and Validation of a Scoring System to Stratify Risk for Advanced Colorectal Neoplasia in Asymptomatic Adults: A Cross-sectional Study. Ann Intern Med. 2015;163(5):339-346.