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

SITUATION A pediatric ethicist objecting to the proposed design put RWE protocol that may not meet regulator expectations in front of 505(b)(2) development lead in a safety team sitting on a new disproportionate signal. This Pharma & Life Sciences / Pharmacovigilance close is to drop a secondary from RWE protocol that may not meet regulator expectations, and the live options are Proceed under protocol, Pause the pathway, Escalate safety review.

DECISION 505(b)(2) development lead in a safety team sitting on a new disproportionate signal must choose Proceed under protocol / Pause the pathway / Escalate safety review / Hold using RWE protocol that may not meet regulator expectations after a pediatric ethicist objecting to the proposed design.

HYPOTHESES TO TEST 1. 505(b)(2) development lead can defend Proceed under protocol from RWE protocol that may not meet regulator expectations after a pediatric ethicist objecting to the proposed design in a Pharma & Life Sciences challenge. 2. 505(b)(2) development lead cannot defend Proceed under protocol from RWE protocol that may not meet regulator expectations; Pause the pathway is what the extract actually supports after a pediatric ethicist objecting to the proposed design. 3. A pediatric ethicist objecting to the proposed design never reached the population in RWE protocol that may not meet regulator expectations — reopen intake, do not close to drop a secondary. 4. Two facts in RWE protocol that may not meet regulator expectations after a pediatric ethicist objecting to the proposed design conflict for 505(b)(2) development lead; hold this Pharmacovigilance file.

ANALYSIS REQUIRED 1. Trace CMC, labeling, or pharmacovigilance facts in RWE protocol that may not meet regulator expectations after a pediatric ethicist objecting to the proposed design. 2. Separate an isolated adverse event from a systemic quality issue. 3. Test a protocol deviation versus a safety signal versus a filing gap on to drop a secondary. 4. For this Pharma & Life Sciences Pharmacovigilance file, read RWE protocol that may not meet regulator expectations against a pediatric ethicist objecting to the proposed design and write the one fact that would move to drop a secondary for 505(b)(2) development lead.

RECOMMENDATION Choose Proceed under protocol / Pause the pathway / Escalate safety review / Hold on this Pharma & Life Sciences / Pharmacovigilance packet (RWE protocol that may not meet regulator expectations after a pediatric ethicist objecting to the proposed design). Lead with the Pharma & Life Sciences option RWE protocol that may not meet regulator expectations can support after a pediatric ethicist objecting to the proposed design, then the two facts that force it, then the Monday action for 505(b)(2) development lead in a safety team sitting on a new disproportionate signal.