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 outcomes, 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 drug’s mechanism of action and the type of endpoint being assessed 14 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