Assess whether to drop a secondary endpoint that will dominate the AdCom

SITUATION After a boxed-warning proposal from the review division, scientific-advice briefing book is what clinical-development physician can touch in a biologics company planning a biosimilar pathway. Pharma & Life Sciences will live with Proceed under protocol versus Pause the pathway on this Clinical and Evidence Strategy file.

DECISION Clinical-development physician in a biologics company planning a biosimilar pathway must choose Proceed under protocol / Pause the pathway / Escalate safety review / Hold using scientific-advice briefing book after a boxed-warning proposal from the review division.

HYPOTHESES TO TEST 1. Authorize Proceed under protocol now; scientific-advice briefing book already has the discriminator after a boxed-warning proposal from the review division. 2. Keep Pause the pathway in force until scientific-advice briefing book is completed after a boxed-warning proposal from the review division for clinical-development physician. 3. Treat scientific-advice briefing book as Escalate safety review because both readings appear after a boxed-warning proposal from the review division. 4. Refuse a Pharma & Life Sciences close: clinical-development physician does not have the decision to drop a secondary turns on in scientific-advice briefing book.

ANALYSIS REQUIRED 1. Separate an isolated adverse event from a systemic quality issue. 2. Test a protocol deviation versus a safety signal versus a filing gap on to drop a secondary. 3. Check whether scientific-advice briefing book supports the labeled claim clinical-development physician would keep. 4. For this Pharma & Life Sciences Clinical and Evidence Strategy file, read scientific-advice briefing book against a boxed-warning proposal from the review division and write the one fact that would move to drop a secondary for clinical-development physician.

RECOMMENDATION Choose Proceed under protocol / Pause the pathway / Escalate safety review / Hold on this Pharma & Life Sciences / Clinical and Evidence Strategy packet (scientific-advice briefing book after a boxed-warning proposal from the review division). If scientific-advice briefing book cannot force a Pharma & Life Sciences label under Clinical and Evidence Strategy, stop. If scientific-advice briefing book after a boxed-warning proposal from the review division cannot support Proceed under protocol versus Pause the pathway on this Pharma & Life Sciences Clinical and Evidence Strategy close, clinical-development physician must state the unresolved clinical or safety evidence requirement explicitly.

COMMAND RETURNS - Bottom-line Pharma & Life Sciences option on to drop a secondary, then the evidence in scientific-advice briefing book, then the action for clinical-development physician - Hypothesis scorecard against scientific-advice briefing book: supported / rejected / untestable - What changes to drop a secondary if a boxed-warning proposal from the review division is later withdrawn - Named option among Proceed under protocol, Pause the pathway, Escalate safety review and the fact that kills the others