§ I · Clinical Development

Don’t Just Design for Approval. Design for Access.

Bridge the gap between Regulatory success and HTA value. Optimize your protocol to satisfy Regulators and Payers simultaneously.

Minimize Risks Align Regulatory & Payer Increase Study ROI
§ II

The Strategic Questions We Answer

i.

Lead Indication Strategy

“Which indication offers the fastest route to high-value reimbursement?”

Success ProbabilityPredictive modeling of “Major Added Benefit” ratings across different indications.

Strategic SelectionPrioritize indications where HTA evidence requirements align naturally with regulatory endpoints.

ii.

Comparator Strategy

“How do we select a comparator that satisfies Regulators and Payers simultaneously?”

Acceptance ProbabilityPredict the likelihood of G-BA/HAS accepting your chosen ACT (Appropriate Comparator Therapy).

Superiority ModelingQuantify the risk of missing statistical significance against a stronger, payer-preferred comparator.

Pricing AnchorsBenchmark against the cost of accepted comparators to forecast your pricing ceiling.

0.00 0.25 0.50 0.75 1.00 ACT* 0.88 Fig. ii.
iii.

Endpoint Strategy

“Which clinical endpoints effectively bridge the gap between regulatory significance and reimbursable value?”

Payer HierarchyDistinguish between obligatory endpoints (Mortality/Morbidity) and “nice-to-haves” (QoL) that fail to drive price.

Objection MitigationHistorical analysis of endpoint-related “red flags” and model-derived recommendations on how to mitigate them.

Joint ProbabilityP(C ∩ H)Integrated modeling of Clinical Success (significance) vs. HTA Success (relevance).

iv.

Patient Subgroup Strategy

“How can we define patient subgroups to maximize the magnitude of the ‘Added Benefit’ rating?”

Benefit-Risk OptimizationIdentify subgroups with the highest effect size to safeguard your “Added Benefit” rating.

Fragmentation RiskPredict if HTA bodies will split your indication into sub-cohorts and align stratification to match.

Commercial AlignmentEnsure your clinical subgroups match the target commercial product profile (TPP).

v.

Future Readiness (SoC Evolution)

“Will this study design still be relevant in the 5–7 years it takes to finish?”

SoC ForecastingPredictive modeling of the Standard of Care landscape at the time of your submission, not just today.

Evidence BridgingIdentify necessary Indirect Cross-Trial Comparisons (ITC) early to prepare for a market where your comparator might become outdated.

§ III · A Lesson in Misalignment

The SGLT2 Inhibitor Withdrawal

The cost of misaligning clinical design with HTA requirements is measured in billions.

Real-World Failure
i.

The Strategy

AstraZeneca and Janssen designed Phase III programs testing against placebo or DPP-4 inhibitors. This satisfied regulatory agencies.

ii.

The HTA Reality

The German G-BA designated a cheaper generic (sulfonylurea) as the appropriate comparator.

iii.

The Result

Because trials did not compare against the G-BA’s choice, both drugs received “no added benefit” ratings.

iv.

The Impact

Price negotiations failed. Both companies were forced to withdraw these major assets from the German market entirely.

Lost Revenue Potential Billions of Dollars
§ IV

Don’t Let This Happen to Your Asset.

Identify comparator mismatches, endpoint gaps, and population issues before you enroll patient #1.

Stress-Test My Protocol