Definition and application of minimal clinically important difference and minimal important change in functional constipation symptom scales_Chinese Journal of Evidence-Based Medicine

Authors：

XU Shaofen ¹ , KANG Yimin ¹ , TIAN Jing ¹ , PENG Qiaoyu ¹ , XU Qinyong ² , TANG Tingying ¹ , CHEN Xinlin ¹ , LIU Fengbin ³ , QIN Zongshi ⁴ ,  HOU Zhengkun ^1,3,5

1. Guangzhou University of Chinese Medicine, Guangzhou 510006, P. R. China;
2. Binhaiwan Central Hospital of Dongguan, Dongguan 523900, P. R. China;
3. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, P. R. China;
4. Peking University Clinical Research Institute, Beijing 100191, P. R. China;
5. Yuexi Branch, The First Affiliated Hospital of Guangzhou University of Chinese Medicine (Maoming Dianbai District Chinese Medicine Hospital), Maoming 525400, P. R. China;

Corresponding?author：

HOU Zhengkun, Email: fenghou5128@126.com

Keywords：

Minimal clinically important difference; Minimal important change; Clinical efficacy evaluation; Patient-reported outcomes

DOI：

10.7507/1672-2531.202506033

Video：

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Objective To systematically investigate the application status of the minimal clinically important difference (MCID) and minimal important change (MIC) in intragroup and intergroup analyses of functional constipation symptom scales from 2000 to 2025, and provide a reference for the standardized formulation of clinical efficacy evaluation criteria for functional constipation in China. Methods Randomized controlled trials (RCTs) and meta-analyses on functional constipation were retrieved from WangFang Data, CNKI, PubMed, Embase, and CENTRAL databases between January 1, 2000, and January 7, 2025. Three reviewers independently screened the literature, extracted information on the characteristics of MIC/MCID reported in the studies, and conducted descriptive quantitative analyses. Results A total of 337 studies were evaluated for readability, with 291 studies meeting the inclusion criteria. Among eligible studies, 6 used MIC/MCID thresholds, and 38 reported responder definitions, including 5 using MIC and 1 using MIC and MCID. Discrepancies were observed between the expected and actual values of MIC/MCID. Six included studies provided explicit citation support for their selected MIC/MCID thresholds. Conclusion The application and interpretation of MIC and MCID thresholds face fundamental challenges. Using functional constipation research as an example, researchers often derive MIC-like thresholds through intergroup comparisons of individual change proportions and mistakenly equate them with MCID. This conceptual confusion may lead to clinical interpretation bias due to neglecting the essential differences between the two thresholds. Additionally, issues include lack of methodological justification for responder analysis, broad threshold ranges, and near-absence of blinded evaluations. It is recommended that researchers clarify the definitions and analytical pathways of the two thresholds during RCT design, avoid misusing intergroup statistics as individual efficacy criteria, and strengthen the methodological rigor of blinded design and threshold validation.

1.	DA. D. 羅馬IV功能性胃腸病. 腸-腦互動異常. 第2卷: 中文翻譯版. 北京: 科學出版社, 2016.
2.	Chen Z, Peng Y, Shi Q, et al. Prevalence and risk factors of functional constipation according to the Rome criteria in China: a systematic review and meta-analysis. Front Med (Lausanne), 2022, 9: 815156.
3.	Koloski NA, Jones M, Wai R, et al. Impact of persistent constipation on health-related quality of life and mortality in older community-dwelling women. Am J Gastroenterol, 2013, 108(7): 1152-1158.
4.	Liang J, Zhao Y, Xi Y, et al. Association between depression, anxiety symptoms and gut microbiota in Chinese elderly with functional constipation. Nutrients, 2022, 14(23): 5013.
5.	Bharucha AE, Wald A. Chronic constipation. Mayo Clin Proc, 2019, 94(11): 2340-2357.
6.	Tack J, Carbone F, Chang L, et al. Patient-reported outcomes in disorders of gut-brain interaction. Gastroenterology, 2024, 166(4): 572-587.
7.	King MT. A point of minimal important difference (MID): a critique of terminology and methods. Expert Rev Pharmacoecon Outcomes Res, 2011, 11(2): 171-184.
8.	楊麗虹, 劉少南, 吳大嶸, 等. 最小臨床意義差值的概念及其估算方法. 中國循證醫學雜志, 2020, 20(11): 1345-1352.
9.	Qin Z, Zhu Y, Shi DD, et al. The gap between statistical and clinical significance: time to pay attention to clinical relevance in patient-reported outcome measures of insomnia. BMC Med Res Methodol, 2024, 24(1): 177.
10.	Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 2021, 372: n71.
11.	Sterne JAC, Savovi? J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019, 366: l4898.
12.	Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ, 2017, 358: j4008.
13.	Riezzo G, Orlando A, D'Attoma B, et al. Randomised clinical trial: efficacy of Lactobacillus paracasei-enriched artichokes in the treatment of patients with functional constipation--a double-blind, controlled, crossover study. Aliment Pharmacol Ther, 2012, 35(4): 441-450.
14.	Abbott R, Ayres I, Hui E, et al. Effect of perineal self-acupressure on constipation: a randomized controlled trial. J Gen Intern Med, 2015, 30(4): 434-439.
15.	Dimidi E, Zdanaviciene A, Christodoulides S, et al. Randomised clinical trial: bifidobacterium lactis NCC2818 probiotic vs placebo, and impact on gut transit time, symptoms, and gut microbiology in chronic constipation. Aliment Pharmacol Ther, 2019, 49(3): 251-264.
16.	Piche T, Dapoigny M. Comparative efficacy and safety of lactulose plus paraffin vs polyethylene glycol in functional constipation: a randomised clinical study. United European Gastroenterol J, 2020, 8(8): 923-932.
17.	Steels E, Erhardt R, Harnett J, et al. Efficacy of a prebiotic formulation for treatment of functional constipation and associated gastrointestinal symptoms in adults: a randomised controlled trial. Adv Integr Med, 2023, 10(2): 43-50.
18.	姜麗芳, 吳潔, 符強, 等. 針刺會陰治療嚴重慢性功能性便秘臨床療效觀察. 中國針灸, 2023, 43(2): 128-132.
19.	Yiannakou Y, Tack J, Piessevaux H, et al. The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference. Aliment Pharmacol Ther, 2017, 46(11-12): 1103-1111.
20.	Marquis P, De La Loge C, Dubois D, et al. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol, 2005, 40(5): 540-551.
21.	Dubois D, Gilet H, Viala-Danten M, et al. Psychometric performance and clinical meaningfulness of the patient assessment of constipation-quality of life questionnaire in prucalopride (RESOLOR) trials for chronic constipation. Neurogastroenterol Motil, 2010, 22(2): e54-63.
22.	Rentz AM, Yu R, Müller-Lissner S, et al. Validation of the bowel function index to detect clinically meaningful changes in opioid-induced constipation. J Med Econ, 2009, 12(4): 371-383.
23.	Frank L, Kleinman L, Farup C, et al. Psychometric validation of a constipation symptom assessment questionnaire. Scand J Gastroenterol, 1999, 34(9): 870-877.
24.	Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol, 1997, 32(9): 920-924.
25.	Cheng CW, Bian ZX, Zhu LX, et al. Efficacy of a Chinese herbal proprietary medicine (Hemp Seed Pill) for functional constipation. Am J Gastroenterol, 2011, 106(1): 120-129.
26.	Chang L, Chey WD, Imdad A, et al. American Gastroenterological Association-American College of Gastroenterology clinical practice guideline: pharmacological management of chronic idiopathic constipation. Gastroenterology, 2023, 164(7): 1086-1106.
27.	Alavi K, Thorsen AJ, Fang SH, et al. The American Society of Colon and Rectal Surgeons clinical practice guidelines for the evaluation and management of chronic constipation. Dis Colon Rectum, 2024, 67(10): 1244-1257.
28.	中國中西醫結合學會消化系統疾病專業委員會. 功能性便秘中西醫結合診療專家共識(2025年). 中國中西醫結合消化雜志, 2025, 33(3): 195-216.
29.	FDA. Patient-focused drug development: collecting comprehensive and representative input. 2018.
30.	Shaw PA, Johnson LL, Proschan MA. Intermediate topics in biostatistics//Gallin JI, Ognibene FP, Johnson LL. Principles and practice of clinical research. London: Academic Press, 2018, 384-409.
31.	de Vet HC, Foumani M, Scholten MA, et al. Minimally important change values of a measurement instrument depend more on baseline values than on the type of intervention. J Clin Epidemiol, 2015, 68(5): 518-524.
32.	Wang YC, Hart DL, Stratford PW, et al. Baseline dependency of minimal clinically important improvement. Phys Ther, 2011, 91(5): 675-688.
33.	Chiarotto A, Vanti C, Cedraschi C, et al. Responsiveness and minimal important change of the pain self-efficacy questionnaire and short forms in patients with chronic low back pain. J Pain, 2016, 17(6): 707-718.
34.	Schuller W, Ostelo RW, Janssen R, et al. The influence of study population and definition of improvement on the smallest detectable change and the minimal important change of the neck disability index. Health Qual Life Outcomes, 2014, 12: 53.
35.	Farrar JT, Young JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain, 2001, 94(2): 149-158.
36.	Terluin B, Roos EM, Terwee CB, et al. Assessing baseline dependency of anchor-based minimal important change (MIC): don't stratify on the baseline score! Qual Life Res, 2021, 30(10): 2773-2782.

1. DA. D. 羅馬IV功能性胃腸病. 腸-腦互動異常. 第2卷: 中文翻譯版. 北京: 科學出版社, 2016.
2. Chen Z, Peng Y, Shi Q, et al. Prevalence and risk factors of functional constipation according to the Rome criteria in China: a systematic review and meta-analysis. Front Med (Lausanne), 2022, 9: 815156.
3. Koloski NA, Jones M, Wai R, et al. Impact of persistent constipation on health-related quality of life and mortality in older community-dwelling women. Am J Gastroenterol, 2013, 108(7): 1152-1158.
4. Liang J, Zhao Y, Xi Y, et al. Association between depression, anxiety symptoms and gut microbiota in Chinese elderly with functional constipation. Nutrients, 2022, 14(23): 5013.
5. Bharucha AE, Wald A. Chronic constipation. Mayo Clin Proc, 2019, 94(11): 2340-2357.
6. Tack J, Carbone F, Chang L, et al. Patient-reported outcomes in disorders of gut-brain interaction. Gastroenterology, 2024, 166(4): 572-587.
7. King MT. A point of minimal important difference (MID): a critique of terminology and methods. Expert Rev Pharmacoecon Outcomes Res, 2011, 11(2): 171-184.
8. 楊麗虹, 劉少南, 吳大嶸, 等. 最小臨床意義差值的概念及其估算方法. 中國循證醫學雜志, 2020, 20(11): 1345-1352.
9. Qin Z, Zhu Y, Shi DD, et al. The gap between statistical and clinical significance: time to pay attention to clinical relevance in patient-reported outcome measures of insomnia. BMC Med Res Methodol, 2024, 24(1): 177.
10. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 2021, 372: n71.
11. Sterne JAC, Savovi? J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019, 366: l4898.
12. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ, 2017, 358: j4008.
13. Riezzo G, Orlando A, D'Attoma B, et al. Randomised clinical trial: efficacy of Lactobacillus paracasei-enriched artichokes in the treatment of patients with functional constipation--a double-blind, controlled, crossover study. Aliment Pharmacol Ther, 2012, 35(4): 441-450.
14. Abbott R, Ayres I, Hui E, et al. Effect of perineal self-acupressure on constipation: a randomized controlled trial. J Gen Intern Med, 2015, 30(4): 434-439.
15. Dimidi E, Zdanaviciene A, Christodoulides S, et al. Randomised clinical trial: bifidobacterium lactis NCC2818 probiotic vs placebo, and impact on gut transit time, symptoms, and gut microbiology in chronic constipation. Aliment Pharmacol Ther, 2019, 49(3): 251-264.
16. Piche T, Dapoigny M. Comparative efficacy and safety of lactulose plus paraffin vs polyethylene glycol in functional constipation: a randomised clinical study. United European Gastroenterol J, 2020, 8(8): 923-932.
17. Steels E, Erhardt R, Harnett J, et al. Efficacy of a prebiotic formulation for treatment of functional constipation and associated gastrointestinal symptoms in adults: a randomised controlled trial. Adv Integr Med, 2023, 10(2): 43-50.
18. 姜麗芳, 吳潔, 符強, 等. 針刺會陰治療嚴重慢性功能性便秘臨床療效觀察. 中國針灸, 2023, 43(2): 128-132.
19. Yiannakou Y, Tack J, Piessevaux H, et al. The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference. Aliment Pharmacol Ther, 2017, 46(11-12): 1103-1111.
20. Marquis P, De La Loge C, Dubois D, et al. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol, 2005, 40(5): 540-551.
21. Dubois D, Gilet H, Viala-Danten M, et al. Psychometric performance and clinical meaningfulness of the patient assessment of constipation-quality of life questionnaire in prucalopride (RESOLOR) trials for chronic constipation. Neurogastroenterol Motil, 2010, 22(2): e54-63.
22. Rentz AM, Yu R, Müller-Lissner S, et al. Validation of the bowel function index to detect clinically meaningful changes in opioid-induced constipation. J Med Econ, 2009, 12(4): 371-383.
23. Frank L, Kleinman L, Farup C, et al. Psychometric validation of a constipation symptom assessment questionnaire. Scand J Gastroenterol, 1999, 34(9): 870-877.
24. Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol, 1997, 32(9): 920-924.
25. Cheng CW, Bian ZX, Zhu LX, et al. Efficacy of a Chinese herbal proprietary medicine (Hemp Seed Pill) for functional constipation. Am J Gastroenterol, 2011, 106(1): 120-129.
26. Chang L, Chey WD, Imdad A, et al. American Gastroenterological Association-American College of Gastroenterology clinical practice guideline: pharmacological management of chronic idiopathic constipation. Gastroenterology, 2023, 164(7): 1086-1106.
27. Alavi K, Thorsen AJ, Fang SH, et al. The American Society of Colon and Rectal Surgeons clinical practice guidelines for the evaluation and management of chronic constipation. Dis Colon Rectum, 2024, 67(10): 1244-1257.
28. 中國中西醫結合學會消化系統疾病專業委員會. 功能性便秘中西醫結合診療專家共識(2025年). 中國中西醫結合消化雜志, 2025, 33(3): 195-216.
29. FDA. Patient-focused drug development: collecting comprehensive and representative input. 2018.
30. Shaw PA, Johnson LL, Proschan MA. Intermediate topics in biostatistics//Gallin JI, Ognibene FP, Johnson LL. Principles and practice of clinical research. London: Academic Press, 2018, 384-409.
31. de Vet HC, Foumani M, Scholten MA, et al. Minimally important change values of a measurement instrument depend more on baseline values than on the type of intervention. J Clin Epidemiol, 2015, 68(5): 518-524.
32. Wang YC, Hart DL, Stratford PW, et al. Baseline dependency of minimal clinically important improvement. Phys Ther, 2011, 91(5): 675-688.
33. Chiarotto A, Vanti C, Cedraschi C, et al. Responsiveness and minimal important change of the pain self-efficacy questionnaire and short forms in patients with chronic low back pain. J Pain, 2016, 17(6): 707-718.
34. Schuller W, Ostelo RW, Janssen R, et al. The influence of study population and definition of improvement on the smallest detectable change and the minimal important change of the neck disability index. Health Qual Life Outcomes, 2014, 12: 53.
35. Farrar JT, Young JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain, 2001, 94(2): 149-158.
36. Terluin B, Roos EM, Terwee CB, et al. Assessing baseline dependency of anchor-based minimal important change (MIC): don't stratify on the baseline score! Qual Life Res, 2021, 30(10): 2773-2782.

Chinese Journal of Evidence-Based Medicine

Latest ArticlesDefinition and application of minimal clinically important difference and minimal important change in functional constipation symptom scales

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