CASE SNAPSHOT 02

Pivotal Design / Rare Disease & Complex CNS

Pivotal trials must do more than test a hypothesis. They must create evidence that can survive regulatory review, HTA scrutiny, payer assessment, and operational reality.

CONTEXT

The situation

A rare disease / complex CNS program required a pivotal architecture that could satisfy regulators while remaining credible for HTA, payer, investor, and launch-year decision-making.

DECISION CHALLENGE

What had to be resolved

Endpoint and estimand choices exposed the program to interpretability risk
HTA/HEOR evidence needs were not sufficiently reflected in early design choices
Operational noise risk from baseline instability, rater variability, and read strategy
Competitive positioning required a defensible value narrative beyond statistical significance

OUR INTERVENTION

What changed in the decision system

Aligned endpoint and estimand strategy with FDA/EMA expectations and HTA/HEOR logic
Built operational guardrails around baseline control, rater strategy, and reading approach
Developed decision gates linking clinical signal, regulatory feasibility, payer relevance, and launch differentiation
Strengthened the evidence narrative for internal governance, investors, and external stakeholders

OUTCOMES

What the programme gained

Submission-ready protocol package
Payer-credible evidence narrative
Clearer differentiation logic for launch and partnering discussions
Reduced risk of a statistically positive but commercially weak trial

STRATEGIC IMPLICATION

Pivotal design must integrate regulatory, payer, commercial, and operational logic before the protocol is locked.

RELATED CAPABILITY

Regulatory, HTA & Evidence Strategy

Align pivotal architecture with regulatory, payer and operational decision requirements before the design becomes difficult to change.

A SIMILAR DECISION?

Use the evidence before the next irreversible commitment.

Bring the live decision, the next hard milestone and the uncertainty that is currently exposed.