Master Protocol Screening

Unlike traditional trial matching which evaluates a patient against a single protocol, master protocol screening executes concurrent eligibility checks across all active sub-study arms in a single pass. The engine decomposes each arm's criteria into atomic predicates, evaluates shared inclusion factors once, and branches only on arm-specific biomarkers. This eliminates redundant data retrieval and reduces screening latency by 40-60% compared to sequential arm-by-arm evaluation.

Master protocols—particularly umbrella and basket trials—use molecular biomarkers as the primary routing logic. The screening system must:

• Parse genomic variant data (e.g., EGFR exon 19 deletion, BRAF V600E)
• Cross-reference against each arm's molecular eligibility criteria
• Handle complex Boolean logic (e.g., "EGFR+ AND ALK- OR ROS1+")
• Resolve conflicting matches when a patient qualifies for multiple arms using predefined prioritization rules based on arm capacity, randomization ratio, or sponsor preference

A defining feature of master protocols is the common control arm shared across multiple experimental arms. The screening engine must:

• Identify patients eligible for the control arm independently of experimental arm eligibility
• Apply randomization-aware filtering to ensure control-eligible patients are not excluded by experimental arm criteria
• Maintain proper stratification across arms to preserve statistical validity
• Track control arm enrollment caps separately from experimental arm accrual targets

Master protocols are living documents where sub-study arms frequently open, close, or suspend enrollment independently. The screening engine must maintain real-time awareness of:

• Arm accrual status: Closed to enrollment, temporarily suspended, or actively recruiting
• Slot availability: Remaining enrollment capacity per arm and per site
• Protocol amendments: Mid-study changes to eligibility criteria that must be immediately reflected in screening logic
• Adaptive randomization ratios: Shifting allocation probabilities based on interim efficacy analyses

Master protocol screening uses an object-oriented criteria model where:

• Master-level criteria (e.g., disease type, age range, ECOG status) are defined once and inherited by all sub-arms
• Arm-specific criteria (e.g., biomarker status, prior therapy lines) extend the base definition
• The engine evaluates master criteria first as a pre-filter gate, then branches to arm-specific logic only for patients who pass
• This architecture prevents criteria duplication, simplifies amendment management, and ensures consistency across the protocol

When a patient qualifies for multiple experimental arms simultaneously, the screening engine must execute a deterministic conflict resolution strategy. Common approaches include:

• Sponsor-defined priority: Pre-ranked arm preference based on portfolio strategy
• Biomarker specificity: Assign to the arm with the most restrictive molecular match
• Randomization-weighted: Allocate based on current randomization ratios to maintain balance
• Site-level capacity: Route to arms with available slots at the patient's preferred site
• Patient preference: Present all qualifying arms and allow informed choice where protocols permit

The process of breaking down a complex, multi-part clinical trial eligibility criterion into its atomic, independently evaluable logical components. For a master protocol, this involves parsing a criterion like 'EGFR-mutant NSCLC with progression on prior TKI therapy' into discrete facts: diagnosis, genomic variant, prior therapy, and progression event. This decomposition allows a single patient profile to be simultaneously validated against the unique logic trees of multiple sub-studies.

A clinical trial screening system design that combines deterministic rule-based filtering with probabilistic semantic matching to maximize both precision and recall. In a master protocol context, hard constraints like lab values are evaluated deterministically, while fuzzy concepts like 'measurable disease' are assessed using patient vector embeddings. This architecture ensures strict safety exclusions are never violated while still identifying patients for biomarker-agnostic arms.

The AI capability to interpret and validate time-dependent clinical constraints against a patient's longitudinal record. Master protocols often contain complex temporal logic, such as:

• Washout periods: 'At least 14 days since last chemotherapy'
• Disease progression timelines: 'Progression within 6 months of platinum-based therapy'
• Sequence validation: 'Surgery must have occurred before radiation' This requires clinical event sequencing and patient timeline reconstruction to resolve.

The assignment of relative importance scores to individual inclusion and exclusion criteria to prioritize patient matches based on the criticality of each requirement. In master protocol screening, weighting enables a ranked assignment of patients to the most appropriate sub-study arm. A patient may technically qualify for multiple arms, but criteria weighting combined with eligibility scoring generates a quantitative match score that guides the optimal allocation.

The automated process of detecting and integrating changes to a clinical trial's eligibility criteria from formal protocol amendments into the active screening logic. Master protocols are living documents that frequently add or close sub-study arms. This capability ensures that the eligibility rule engine is dynamically updated without manual code changes, maintaining screening accuracy as the protocol evolves across its lifecycle.

The process of mapping synonymous clinical terms and varying units of measure within trial criteria to a standard ontology for consistent automated interpretation. A master protocol may reference 'renal insufficiency' in one arm and 'CKD Stage 3' in another. Normalization using medical ontology alignment (SNOMED CT, LOINC) ensures that a patient's eGFR value is correctly evaluated against both semantically equivalent expressions.