The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference

Y Yiannakou, J Tack, H Piessevaux, D Dubois, E M M Quigley, M Y Ke, S Da Silva, A Joseph, R Kerstens, Y Yiannakou, J Tack, H Piessevaux, D Dubois, E M M Quigley, M Y Ke, S Da Silva, A Joseph, R Kerstens

Abstract

Background: The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined.

Aim: To determine the minimal important difference in PAC-SYM score, and the optimum cut-off value for defining responders.

Methods: The minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor.

Results: Data from 2884 patients were included. Minimal important difference estimates ranged from -0.52 to -0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution-based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates.

Conclusions: Anchor-based methods gave consistent results for the minimal important difference, at approximately -0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg -0.75) could be used in clinical trials to reduce the placebo response rate.

© 2017 Shire International GMBH. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Estimates of the minimal important difference in the PAC‐SYM score (A) overall and (B) for each of the six clinical trials, using five anchors defined by expert consensus. Error bars show 95% confidence intervals. PAC‐SYM, Patient Assessment of Constipation‐Symptoms; SCBM, spontaneous complete bowel movement
Figure 2
Figure 2
Estimates of the minimal important difference for each of the individual subscales of the PAC‐SYM questionnaire, using five anchors defined by expert consensus. Error bars show 95% confidence intervals. PAC‐SYM, Patient Assessment of Constipation‐Symptoms; SCBM, spontaneous complete bowel movement

References

    1. Belsey J, Greenfield S, Candy D, Geraint M. Systematic review: impact of constipation on quality of life in adults and children. Aliment Pharmacol Ther. 2010;31:938‐949.
    1. Frank L, Kleinman L, Farup C, Taylor L, Miner P Jr. Psychometric validation of a constipation symptom assessment questionnaire. Scand J Gastroenterol. 1999;34:870‐877.
    1. Johanson JF, Wald A, Tougas G, et al. Effect of tegaserod in chronic constipation: a randomized, double‐blind, controlled trial. Clin Gastroenterol Hepatol. 2004;2:796‐805.
    1. Lin SR, Ke MY, Luo JY, et al. A randomized, double‐blind, placebo‐controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation. World J Gastroenterol. 2007;13:732‐739.
    1. Mihaylov S, Stark C, McColl E, et al. Stepped treatment of older adults on laxatives. The STOOL trial. Health Technol Assess. 2008; 12: iii‐iv, ix‐139.
    1. Barish CF, Drossman D, Johanson JF, Ueno R. Efficacy and safety of lubiprostone in patients with chronic constipation. Dig Dis Sci. 2010;55:1090‐1097.
    1. Ahmedzai SH, Leppert W, Janecki M, et al. Long‐term safety and efficacy of oxycodone/naloxone prolonged‐release tablets in patients with moderate‐to‐severe chronic cancer pain. Support Care Cancer. 2015;23:823‐830.
    1. Sakai T, Kubota H, Gawad A, et al. Effect of fermented milk containing Lactobacillus casei strain Shirota on constipation‐related symptoms and haemorrhoids in women during puerperium. Benef Microbes. 2015;6:253‐262.
    1. Marciniak CM, Toledo S, Lee J, et al. Lubiprostone vs Senna in postoperative orthopedic surgery patients with opioid‐induced constipation: a double‐blind, active‐comparator trial. World J Gastroenterol. 2014;20:16323‐16333.
    1. Huang TT, Yang SD, Tsai YH, et al. Effectiveness of individualised intervention on older residents with constipation in nursing home: a randomised controlled trial. J Clin Nurs. 2015;24:3449‐3458.
    1. Yiannakou Y, Piessevaux H, Bouchoucha M, et al. A randomized, double‐blind, placebo‐controlled, phase 3 trial to evaluate the efficacy, safety, and tolerability of prucalopride in men with chronic constipation. Am J Gastroenterol. 2015;110:741‐748.
    1. Thomas GP, Duelund‐Jakobsen J, Dudding TC, et al. A double‐blinded randomized multicentre study to investigate the effect of changes in stimulation parameters on sacral nerve stimulation for constipation. Colorectal Dis. 2015;17:990‐995.
    1. Sloots CE, Rykx A, Cools M, Kerstens R, De Pauw M. Efficacy and safety of prucalopride in patients with chronic noncancer pain suffering from opioid‐induced constipation. Dig Dis Sci. 2010;55:2912‐2921.
    1. Slappendel R, Simpson K, Dubois D, Keininger DL. Validation of the PAC‐SYM questionnaire for opioid‐induced constipation in patients with chronic low back pain. Eur J Pain. 2006;10:209‐217.
    1. O'Brien CE, Anderson PJ, Stowe CD. Lubiprostone for constipation in adults with cystic fibrosis: a pilot study. Ann Pharmacother. 2011;45:1061‐1066.
    1. Muller‐Lissner S, Rykx A, Kerstens R, Vandeplassche L. A double‐blind, placebo‐controlled study of prucalopride in elderly patients with chronic constipation. Neurogastroenterol Motil. 2010;22:991‐998.
    1. Iyer SS, Randazzo BP, Tzanis EL, et al. Effect of subcutaneous methylnaltrexone on patient‐reported constipation symptoms. Value Health. 2011;14:177‐183.
    1. Iqbal F, Collins B, Thomas GP, et al. Bilateral transcutaneous tibial nerve stimulation for chronic constipation. Colorectal Dis. 2016;18:173‐178.
    1. Speed C, Heaven B, Adamson A, et al. LIFELAX ‐ diet and LIFEstyle versus LAXatives in the management of chronic constipation in older people: randomised controlled trial. Health Technol Assess. 2010;14:1‐251.
    1. Khan U, Mason JM, Mecci M, Yiannakou Y. A prospective trial of temporary sacral nerve stimulation for constipation associated with neurological disease. Colorectal Dis. 2014;16:1001‐1009.
    1. Camilleri M, Piessevaux H, Yiannakou Y, et al. Efficacy and safety of prucalopride in chronic constipation: an integrated analysis of six randomized, controlled clinical trials. Dig Dis Sci. 2016;61:2357‐2372.
    1. Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials. 1989;10:407‐415.
    1. Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo‐controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008;358:2344‐2354.
    1. Tack J, van Outryve M, Beyens G, Kerstens R, Vandeplassche L. Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut. 2009;58:357‐365.
    1. Quigley EM, Vandeplassche L, Kerstens R, Ausma J. Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation ‐ a 12‐week, randomized, double‐blind, placebo‐controlled study. Aliment Pharmacol Ther. 2009;29:315‐328.
    1. Ke M, Zou D, Yuan Y, et al. Prucalopride in the treatment of chronic constipation in patients from the Asia‐Pacific region: a randomized, double‐blind, placebo‐controlled study. Neurogastroenterol Motil. 2012;24:999‐e541.
    1. Piessevaux H, Corazziari E, Rey E, et al. A randomized, double‐blind, placebo‐controlled trial to evaluate the efficacy, safety, and tolerability of long‐term treatment with prucalopride. Neurogastroenterol Motil. 2015;27:805‐815.
    1. Revicki D, Hays RD, Cella D, Sloan J. Recommended methods for determining responsiveness and minimally important differences for patient‐reported outcomes. J Clin Epidemiol. 2008;61:102‐109.
    1. Beaton DE, Boers M, Wells GA. Many faces of the minimal clinically important difference (MCID): a literature review and directions for future research. Curr Opin Rheumatol. 2002;14:109‐114.
    1. Guyatt GH, Osoba D, Wu AW, et al. Methods to explain the clinical significance of health status measures. Mayo Clin Proc. 2002;77:371‐383.
    1. Zweig MH, Campbell G. Receiver‐operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993;39:561‐577.
    1. Hays RD, Revicki DA. Reliability and validity (including responsiveness) In: Fayers P, Hays R, eds. Assessing quality of life in clinical trials. 2nd ed New York: Oxford University Press; 2005:25‐39.
    1. Wells G, Beaton D, Shea B, et al. Minimal clinically important differences: review of methods. J Rheumatol. 2001;28:406‐412.
    1. Copay AG, Subach BR, Glassman SD, Polly DW Jr, Schuler TC. Understanding the minimum clinically important difference: a review of concepts and methods. Spine J. 2007;7:541‐546.
    1. Kaptchuk TJ, Friedlander E, Kelley JM, et al. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS ONE. 2010;5:e15591.
    1. Neri L, Conway PM, Basilisco G. Confirmatory factor analysis of the patient assessment of constipation‐symptoms (PAC‐SYM) among patients with chronic constipation. Qual Life Res. 2015;24:1597‐1605.

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