XVI. Non-Responder Protocol
XVI. 1 Step 1: Defining Non-Response – When and How
Non-response can only be judged at the right time and against the benchmark set for each indication; calling it too early is as serious an error as missing it.
Non-response must be defined against the correct benchmark for each indication. Premature declaration of non-response is a clinical error as consequential as failure to detect true non-response. The following definitions apply:
| Indication | Non-response definition and timing |
|---|---|
| rCDI | Persistent diarrhea (Bristol 6–7, ≥3 episodes/day) beyond day 7 post-induction. Evaluate same day. Repeat FMT standard practice. |
| Ulcerative Colitis | No clinically meaningful symptom reduction at week 8. No endoscopic improvement at week 12. Partial response at week 8 is NOT non-response – continue consolidation. |
| Crohn's Disease | No symptomatic improvement at week 12. Significant biomarker worsening (CRP, fecal calprotectin) after initial stabilization. |
| IBS | No global symptom improvement at week 12 on validated scale (IBS-SSS or equivalent). Note: symptom fluctuation is expected – single-timepoint worsening ≠ non-response. |
| Metabolic Syndrome | No improvement in primary metabolic marker (HbA1c, fasting glucose, or insulin sensitivity index) at week 24. |
Table 21 – Non-response definitions and response timelines by indication # Diagnostic thresholds, minimum treatment durations, and assessment windows for each clinical indication.