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Logo of jneuromotThis ArticleAims and ScopeInstructions to AuthorsE-SubmissionJournal of Neurogastroenterology and Motility
 
J Neurogastroenterol Motil. 2010 April; 16(2): 222–223.
Published online 2010 April 28. doi:  10.5056/jnm.2010.16.2.223
PMCID: PMC2879850

Reply

We appreciate the comments from Dr. Hye-Kyung Jung. There have been several issues in clinical trials on irritable bowel syndrome (IBS) such as duration of trial, study design, on demand or repeated cycles of treatment, and optimal efficacy endpoint.1,2 Among these, optimal endpoint issue is one of the most important factors to prove efficacy of therapeutic agent in a clinical trial,3 however, widely accepted and validated outcome measures is unavailable at present. Contrary to other gastrointestinal diseases such as gastroesophageal reflux disease or inflammatory bowel disease which are diagnosed and assessed by endoscopy, laboratory, and radiologic evaluation, successful treatment of IBS in outpatient office or assessment of effect in IBS clinical trial could be measured only by symptom improvement.4

Binary endpoints, such as adequate relief and satisfactory relief, have been used most commonly as primary endpoint in most IBS clinical trials. However there is a question whether it is enough as primary endpoint5,6 therefore it should be reinforced by secondary (supportive) efficacy endpoints in the clinical research. Although IBS symptom and quality of Life (QOL) score could be used as secondary endpoint, the utility of QOL score in IBS clinical trial has not been explored as satisfactory7 and some authors suggest that QOL score should be considered as a tertiary endpoint.4

One of the important purposes of our study was to validate the usefulness of QOL as an endpoint and we found that QOL score was comparable to symptom score in IBS clinical trial. QOL provides important information to clinicians about the aspects of health care that "actually get to the patient"8 and The European Agency for the Evaluation of Medicinal Product and Rome III committee emphasized QOL assessments as important secondary outcomes.2,9

The problem is that there has been no consensus about the definition of responder in the outcomes by symptoms or QOL scoring system. We were also troubled with the definition of "clinically meaningful change" in scoring system when we designed our study protocol. The magnitude of score changes which means clinically important improvement in individual symptom or QOL has not been defined in IBS trials.2 Some studies considered as little as 10% reduction in visual analog scale rating of symptom severity10 or 1 step on 7-step ordinal scale9 as clinically meaningful, whereas other studies used 50% reduction in an aggregate symptom severity index11 or questionnaire.5 A statistically significant p-value also does not imply whether a particular finding is "clinically meaningful change."

Therefore we recommend clinical researchers to use QOL as an endpoint in IBS clinical trials and hope that further studies will be carried out to figure out what is the magnitude of "clinically meaningful change" in symptoms and QOL scoring system.

Footnotes

Conflicts of interest: None.

References

1. Corazziari E, Bytzer P, Delvaux M, et al. Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2003;18:569–580. [PubMed]
2. Design of Treatment Trials Committee. Irvine EJ, Whitehead WE, et al. Design of treatment trials for functional gastrointestinal disorders. Gastroenterology. 2006;130:1538–1551. [PubMed]
3. Camilleri M, Mangel AW, Fehnel SE, Drossman DA, Mayer EA, Talley NJ. Primary endpoints for irritable bowel syndrome trials: a review of performance of endpoints. Clin Gastroenterol Hepatol. 2007;5:534–540. [PubMed]
4. Schoenfeld P, Talley NJ. Measuring successful treatment of irritable bowel syndrome: is "satisfactory relief" enough? Am J Gastroenterol. 2006;101:1066–1068. [PubMed]
5. Whitehead WE, Palsson OS, Levy RL, Feld AD, VonKorff M, Turner M. Reports of "satisfactory relief" by IBS patients receiving usual medical care are confounded by baseline symptom severity and do not accurately reflect symptom improvement. Am J Gastroenterol. 2006;101:1057–1065. [PubMed]
6. Passos MC, Lembo AJ, Conboy LA, et al. Adequate relief in a treatment trial with IBS patients: a prospective assessment. Am J Gastroenterol. 2009;104:912–919. [PMC free article] [PubMed]
7. Lembo A, Ameen VZ, Drossman DA. Irritable bowel syndrome: toward an understanding of severity. Clin Gastroenterol Hepatol. 2005;3:717–725. [PubMed]
8. Koller M, Neugebauer EA, Augustin M, et al. Assessment of quality of life in health services research - conceptual, methodological and structural prerequisites. Gesundheitswesen. 2009;71:864–872. [PubMed]
9. Committee for Proprietary Medicinal Products (CPMP) Committee for Propriety Medicinal Products (CPMP): points to consider on adjustment for baseline convariates. Stat Med. 2004;23:701–709. [PubMed]
10. Bardhan KD, Bodemar G, Geldof H, et al. A double-blind, randomized, placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2000;14:23–34. [PubMed]
11. Payne A, Blanchard EB. A controlled comparison of cognitive therapy and self-help support groups in the treatment of irritable bowel syndrome. J Consult Clin Psychol. 1995;63:779–786. [PubMed]

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