Trial concepts, protocols development & review

• Concept and objectivesThe question the study answers, the decision it informs, and which outcome would change what you do next.
• Population and eligibilityCriteria tested against the patients who actually attend clinics: prior therapy, biomarker testing, organ function, brain metastases, performance status, and whether each criterion is needed or merely inherited from another protocol.
• Endpoints and assessmentsWhether the primary and key secondary endpoints fit the decision, how imaging, response criteria and any central review will work, and how interpretable the data will be if assessments are missed.
• Dose, safety management and treatment modificationThe escalation or optimization design, dose-modification rules, stopping criteria and monitoring.
• Data and medical-review readinessWhether the planned data collection will let a reviewer follow each patient’s chronology and answer the key clinical questions.
• Feasibility and burdenThe visit schedule and procedures as patients and sites will experience them, and the points most likely to generate deviations or amendments.

A protocol is the cheapest place to find a problem. Once sites are active, an ambiguous eligibility criterion or dose-modification rule is repeated across every site, and an endpoint that does not fit the decision cannot be repaired by analysis.

Early-phase designs are also expected to show that a dose was chosen on more than maximum tolerability, which makes the dose-selection logic worth testing before the first patient is treated.

• At concept stage,when the study question is still being shaped.
• On the final draft,before sites, budgets and data collection are committed.
• When deviations or amendments accumulateand the cause may sit in the design.
• Before a pivotal study,to confirm the design can carry a registrational decision.

1. Read for intent We establish what the study is meant to decide before reviewing how it is written.
2. Trace each key decision to its data From objective to endpoint, assessment, CRF field and analysis.
3. Walk the patient through it From screening to follow-up, and from the viewpoint of a site coordinator and a medical reviewer.
4. Rank by consequence Issues to resolve before finalization are separated from those that can be managed during conduct, each with a proposed resolution.

• A prioritized issue register with evidence, impact and proposed resolution
• Annotated comments on the protocol and schedule of assessments, within the agreed scope
• A clinical-to-data consistency checklist
• A review meeting with your team and agreed priorities

• StructureA defined document set and review cycle, with optional input from clinical operations and biostatistics. Turnaround is agreed after we see the complexity and the materials.
• What we need from youThe draft protocol, schedule of assessments, study objectives and the design assumptions. CRFs or an analysis plan help if available.
• Roles and limitsA review identifies risks and options. It does not guarantee that amendments will be avoided or that a regulator will accept the design. Formal sample-size work and site-level feasibility analysis are scoped separately with the relevant specialists.