# Trial protocol and statistical analysis plan

Source: https://onco.cc/terms/trial-protocol/  
OnCo record `trial-protocol` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The protocol is the rulebook a trial is run by, written before it starts: who can join, what they get, what is measured and when, and how the answer will be calculated; the statistical analysis plan spells out the last part in detail so nobody can choose the analysis after seeing the data.

## Summary

A protocol is a long document, often more than a hundred pages, that states the rationale and objectives, the design, the eligibility criteria, the treatments and their dose modifications, the schedule of visits and assessments, the endpoints and how each is defined and measured, the sample size and its justification, the interim analyses and stopping rules, the safety reporting rules, and the governance (sponsor, steering committee, data monitoring committee, ethics oversight). The SPIRIT statement lists what a protocol should contain, and journals increasingly publish protocols so that the final report can be checked against them. The statistical analysis plan is a companion document finalised before the data are unblinded that fixes the analysis populations, the handling of missing data and intercurrent events, the order in which endpoints are tested and the alpha each receives, the pre-specified subgroups and the sensitivity analyses. Together they are what makes pre-specified mean something.

Protocols change. Amendments add sites, adjust eligibility when recruitment is slow, revise dose modifications in response to toxicity, or, more consequentially, change the primary endpoint or the sample size; each amendment goes back to the ethics committee and regulators and is dated in the registry record, so a reader can see what changed and when. Deviations are departures from the protocol for individual patients (a missed scan, a dose given outside its window) and are logged and classified by seriousness; a pattern of deviations at one site is a monitoring finding. The strict week-twelve event definition written into BELINDA's protocol, combined with a long manufacturing interval, is a documented example of protocol choices deciding a trial's verdict: the trial found no difference in event-free survival where two similar trials found a large one.

For readers, the protocol answers the questions a paper leaves out: exactly who was eligible, what counted as progression, how many analyses were planned, and whether the headline analysis was the one specified. Registries link to protocols for many trials, and supplementary appendices to trial papers usually contain them. A result that cannot be traced to a pre-specified analysis in a dated protocol is a hypothesis, however small its p-value.

## Fields

- Kind: Term
- Last checked: 2026-09-17
- Also known as: trial protocol; study protocol; the protocol; protocol; protocol amendment; protocol amendments; amended protocol; protocol deviation; protocol deviations; protocol violation; protocol synopsis; schedule of assessments; schedule of events; protocol-defined; protocol-specified; per the protocol; eligibility criteria; investigator's brochure; investigator brochure; case report form; CRF; eCRF; SPIRIT; SPIRIT statement; SAP; statistical analysis plan; statistical analysis plans; analysis plan; pre-specified analysis plan; hierarchy of endpoints; testing hierarchy; data cut-off date; database lock

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Clinical_trial_protocol
- Wikipedia: https://en.wikipedia.org/wiki/Clinical_trial_protocol
- SPIRIT statement: standard protocol items for clinical trials: https://www.spirit-statement.org/
- ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework: https://www.ich.org/page/efficacy-guidelines
- ICH E6 Good Clinical Practice: https://www.ich.org/page/efficacy-guidelines

## Connected records

- terms: [Accrual and enrolment](https://onco.cc/terms/accrual/), [Basket, umbrella, and platform trials](https://onco.cc/terms/basket-umbrella-platform/), [Data monitoring committee (DSMB, IDMC)](https://onco.cc/terms/data-monitoring-committee/), [Estimands and intercurrent events (ICH E9(R1))](https://onco.cc/terms/estimand/), [Ethics review (IRB, research ethics committee)](https://onco.cc/terms/ethics-review/), [Group sequential design, stopping rules and alpha spending](https://onco.cc/terms/group-sequential-design/), [Phase 1, 2 and 3 trials](https://onco.cc/terms/trial-phases/), [Pre-specified vs post-hoc analysis](https://onco.cc/terms/prespecified-vs-post-hoc/), [Primary, secondary and co-primary endpoints](https://onco.cc/terms/primary-endpoint/), [Trial lifecycle: from protocol to label](https://onco.cc/terms/trial-lifecycle/), [Trial registration and results reporting (ClinicalTrials.gov, EU CTR)](https://onco.cc/terms/trial-registration/), [Umbrella trial](https://onco.cc/terms/umbrella-trial/), [Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover](https://onco.cc/terms/trial-failure-modes/)
- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)
- trials: [Add-Aspirin](https://onco.cc/trials/add-aspirin/), [BELINDA](https://onco.cc/trials/belinda/), [KEYNOTE-522](https://onco.cc/trials/keynote-522/)

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