Validating endpoints for therapeutic trials in fecal incontinence

Abstract

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 FI 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.

Relationship between symptoms and quality of life in fecal incontinence

“…Perhaps this explains the limited correlation between FI symptom severity and FIQOL in some studies 16 and underscores the importance of considering somatization when interpreting FIQOL.…”

Initial assessment of device mechanism of action and patient acceptance of a novel medical device: feasibility study of vaginal bowel control therapy for the treatment of faecal incontinence

“…In many therapeutic areas, this reduction in symptoms would not be sufficient for patient adoption, but the correlation of this endpoint with quality-of-life improvements has been demonstrated 29. Patient reports in this study that they would continue to use the VBC system for long-term usage if it provided this improvement provided substantiation of this endpoint as a valid one.…”

Surgical Interventions and the Use of Device-Aided Therapy for the Treatment of Fecal Incontinence and Defecatory Disorders

“…In clinical trials, severity is primarily evaluated by the frequency of FI using daily diaries; a 50% reduction in the number of episodes or days with FI is considered to be clinically significant improvement 7, 8 . Alternatively, the severity can be evaluated with questionnaire-based instruments such as the Wexner and Modified Manchester Health Questionnaires, the Fecal Incontinence Severity Score, previously known as the Fecal Incontinence Constipation Assessment (FICA) FI symptom severity instrument and the Fecal Incontinence Severity Index (FISI) to name a few 9, 8 .…”

“…Alternatively, the severity can be evaluated with questionnaire-based instruments such as the Wexner and Modified Manchester Health Questionnaires, the Fecal Incontinence Severity Score, previously known as the Fecal Incontinence Constipation Assessment (FICA) FI symptom severity instrument and the Fecal Incontinence Severity Index (FISI) to name a few 9, 8 . All of the available instruments incorporate the frequency and type of leakage.…”