Validating endpoints for therapeutic trials in fecal incontinence

Background A 50% or greater reduction in the frequency of fecal incontinence ( FI ) recorded with daily bowel diaries is the primary endpoint in clinical trials of FI . Whether this difference is clinically important is unknown. The relationship between FI symptoms recorded with daily and weekly instruments is unknown. The contribution of psychological factors to quality of life ( QOL ) in FI is unclear. Methods Fecal incontinence severity was assessed with daily bowel diaries and periodic questionnaires (fecal incontinence severity score [ FISS ], FIQOL , 36‐Item Short Form Health Survey [ SF ‐36], and hospital anxiety and depression scales) for 4 weeks before and during double‐blind randomization to placebo or clonidine in 44 women with FI . The reduction in FI frequency was compared to the minimal clinically important difference ( MCID ) computed from the FISS . Endpoints of FI were compared between daily and weekly diaries. Key Results The FISS exceeded the MCID in 75% and 83% of patients in whom the FI frequency declined by 50–74% and ≥75% respectively. Parameters of FI measured with daily and weekly instruments were significantly correlated. The daily parameters explained 71% of the inter‐patient variation in the FISS . The SF ‐36 health scores, rather than the FISS rating, explained a majority of the inter‐subject variation in FIQOL . Conclusions & Inferences Most patients who report a ≥50% reduction in FI frequency experience a clinically important improvement. Weekly questionnaires accurately assess the severity of FI . Self‐reported physical and mental health explained a greater proportion of the variance in FIQOL than FI symptom severity.