Where the Endpoint Is What the Camera Sees.
Regulatory strategy across gastroenterology — where approval turns on centrally read mucosal healing and symptoms only a patient can report.
GI Programs Must Prove What the Scope Sees and What the Patient Feels.
Inflammatory bowel disease set the template: co-primary endpoints pairing clinical remission — built from patient-reported stool frequency and rectal bleeding — with endoscopic improvement scored by a blinded central reader. Neither half is sufficient alone, and each brings its own methodological burden.
That pairing is why GI trials are unforgiving. A PRO instrument the agency has not accepted, or a central-reading charter that lets drift in, can invalidate an otherwise successful study. We build GI evidence packages where both endpoints are agreed before enrollment, not defended afterwards.
Symptoms come from the patient; healing comes from the central reader. The division wants both, aligned.
Clinical Remission Plus Endoscopic Improvement — Both, or Neither.
Modern IBD registrations are built on co-primary or hierarchical endpoints that pair how a patient feels with what the endoscopy shows. How you construct each half decides the trial's size, its read, and its label.
Remission
A patient-reported symptom score and a centrally read endoscopic score, both pre-specified and both required.
Patient-Reported Symptoms
Stool frequency and rectal bleeding subscores, collected on a qualified instrument the division has accepted for the claim you want.
Endoscopic Score
Mucosal healing scored by a blinded central reader against a defined index — the objective half the agency trusts most.
Histology
Increasingly requested as a supportive or exploratory measure — and increasingly the endpoint the next generation of trials will be judged on.
Gastroenterology Is Several Regulatory Fields Wearing One Name.
From biologics in IBD to endoscopes with a reprocessing problem, GI programs answer to different centers, different endpoints, and different failure modes.
Inflammatory Bowel Disease
The biologics and small molecules where co-primary symptom and endoscopic endpoints, central reading, and a crowded comparator field define the bar.
Hepatology
Where a liver biopsy was the endpoint, non-invasive markers are contested, and accelerated approval on histology is finally being tested at scale.
Functional GI Disorders
Symptom-defined diseases where the PRO instrument is the endpoint — and qualifying it is the whole regulatory program.
Endoscopy Devices
510(k) territory with a distinctive hazard: duodenoscope reprocessing, which turned cleaning validation into a public-health question.
Live Biotherapeutics
Fecal-derived and defined-consortia products regulated as biologics by CBER, with donor screening and potency problems no small molecule has.
GI-Targeted Delivery
Enteric coatings and colonic release where dissolution methods, food effect, and bioequivalence carry the CMC argument.
A modified questionnaire is a new questionnaire. Change two items and the qualification you inherited is gone.
If the Endpoint Is a Symptom, the Questionnaire Is the Trial.
Much of gastroenterology is defined by what patients report — abdominal pain, urgency, stool frequency, bloating. The FDA's patient-focused drug development guidances set a high bar for the instruments that measure those things: content validity established in the target population, psychometric performance demonstrated, and a scoring rule fixed in advance.
Sponsors routinely inherit a legacy instrument, modify two items for convenience, and destroy its qualification. We treat the PRO strategy as a regulatory workstream in its own right — qualified early, agreed with the division, and locked before the first patient reports anything.
GI Trials Fail on Method More Often Than on Molecule.
The therapeutics work more often than the trials do — because the endpoints are constructed, and construction errors are unrecoverable.
Symptom and endoscopic endpoints must both succeed. Two chances to fail, one chance to win — which is what the powering has to assume.
Blinded central readers, a written charter, and drift monitoring are expected. Local reads invite a question the sponsor cannot answer later.
PRO instruments need demonstrated content validity in the population you are studying. Borrowing and editing one forfeits that.
Six Failure Modes We Are Brought In to Prevent.
Every one of these is decided before enrollment and discovered after database lock.
An unqualified PRO
Using a modified or unvalidated symptom instrument for a primary endpoint, and losing the claim the whole trial was built to earn.
Central reading drift
A reader charter without adjudication or drift monitoring, producing an endoscopic score the division will not accept as reliable.
Placebo response underestimated
Powering a GI trial on optimistic assumptions in a field where placebo remission rates are high and variable by region.
Histology as an afterthought
Collecting biopsies without a pre-specified scoring index or reader plan, then finding the supportive evidence is unusable.
Reprocessing validation gaps
Bringing a reusable endoscope to market with cleaning validation that will not survive the scrutiny the duodenoscope outbreaks created.
MASH endpoint drift
Building a liver program on a non-invasive marker the division has not accepted in place of histology for the claim being sought.
Gastroenterology Regulatory Leadership on Both Halves of the Endpoint.
Our GI leads have qualified PRO instruments, written central-reading charters, and negotiated co-primary endpoints with the division that reviews them.
"In gastroenterology, the molecule is rarely the reason a program fails. The endpoint construction is. Fix that at End-of-Phase-2 and the rest is execution."
The discipline we bring across IBD, hepatology, functional GI, endoscopy, and live biotherapeutics.
Designing a GI Program? Settle the Endpoint Before You Enroll.
Bring senior gastroenterology regulatory leadership in while the PRO, the endoscopic score, and the reading plan are still open questions.
Senior-led. Embedded in your team. No junior hand-offs.