Lacy, B ELembo, A JMacDougall, J EShiff, S JKurtz, C BCurrie, M GJohnston, J M2015-02-022014Lacy, B E, A J Lembo, J E MacDougall, S J Shiff, C B Kurtz, M G Currie, and J M Johnston. 2014. “Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.” Neurogastroenterology and Motility 26 (3): 326-333. doi:10.1111/nmo.12264. http://dx.doi.org/10.1111/nmo.12264.1350-1925http://nrs.harvard.edu/urn-3:HUL.InstRepos:13890807Background: US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. Methods: Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. Key Results 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. Conclusions & Inferences Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies.en-USJournal Article2015-02-0210.1111/nmo.12264