Net clinical benefit
Clinical benefit is a favorable effect on a meaningful aspect of how a patient feels (e.g., symptom relief), functions (e.g., improved mobility) or survives as a result of treatment.
- Clinical benefit may be measured as an improvement or delay in the progression of a disease or condition (as manifested by how a patient feels/functions).
- Can be measured directly or indirectly.
- Indirect assessment needs justification for its value as a replacement for how patients survive, feel or function.
- Observed clinical benefit is described in labeling as a claim using words that represent the concept measured (should be meaningful and understandable to prescribers and patients).

# Considerations when defining clinical benefit in celiac disease drug development
1. Clarify the goal of the study drug
 Understand the mechanism of action of the drug
 Adjunct therapy to a gluten-free diet vs. sole therapy?
 Prevention of a flare vs. symptom treatment
2. Identify the target population (e.g., new diagnosis, nonresponsive
CeD, refractory CeD)
 Should provide adequate assurance that enrolled patients
have documented celiac disease and that their signs and
symptoms are due to celiac disease
 Should rule out other causes that mimic CeD
3. Identify signs/symptoms that would constitute a
clinically meaningful benefit in the target
population, if improved (e.g., abdominal pain or
diarrhea; histological improvement)
 What are key signs and symptoms experienced by celiac
disease patients whom you intend to treat with the drug?
 In other words, improvement in what signs and symptoms will
convince you that celiac patients have benefitted clinically
after treatment?
 Encourage patient involvement in the process
Considerations when defining clinical benefit
in celiac disease drug development 
Considerations when defining clinical benefit
in celiac disease drug development 
4. Select or develop clinical outcome assessment(s)
(COAs) to assess clinical benefit (e.g., patientreported
-utcomes, histologic assessment)
 How would you measure the key signs/symptoms
experienced by celiac patients to demonstrate clinical
benefit?
 How would you ensure that the drug targeted
signs/symptoms due to celiac disease and that underlying
disease has not worsened despite symptom improvement?
Considerations when defining clinical benefit in celiac disease drug development 
5. Establish a responder definition using selected
COA(s)
 What magnitude of change in score in the COA is considered
clinically meaningful and will provide convincing evidence that
the drug has shown clear benefit?
6. Determine appropriate timing of efficacy
assessment(s)
 Should be guided by the drugs mechanism of action and the
type of endpoint being assessed
Conclusions
- Best access for patients to an effective therapy is an approved drug.
- To support marketing approval, treatments must demonstrate
substantial evidence of effectiveness through adequate and wellcontrolled
investigations.
- To design an adequate and well-controlled clinical trial requires welldescribed
disease, acceptable endpoints, and tools/instruments to
adequately assess the intervention.
- Clinical benefit is a favorable effect on a meaningful aspect of how a
patient feels, functions, or survives as a result of treatment;
described in labeling as a claim.
- Early planning in the drug development process is critical to meet
challenges associated with defining appropriate efficacy endpoints
and outcome measurement