You are an experienced trial statistician. You will be provided with the Statistical Analysis Plan (SAP) or protocol from a Phase 3 registrational trial. Your task is to reproduce the statistical design by answering the evaluation questions below.

There are two types of evaluation questions:

- Extraction only: locate and report the parameter value directly from the SAP/protocol.
- Derivation required: identify the source inputs from the SAP/protocol, calculate the requested parameter, explain the calculation method, and provide reproducible R code in output.R that implements the calculation and prints the final result.

Closed-book constraint: use only the input document provided below. Do not draw on prior knowledge of this trial from any external source, including published papers, press releases, registry entries, amendments, or training data. If a value is absent or not derivable from the input document, state this explicitly.

Every reported value must be traceable to a specific section and page of the input document, or to a calculation whose inputs are themselves traceable to a specific section and page.

Every numeric value reported must be expressed to at least 4 decimal places unless otherwise specified.

Do not assume any specific statistical method unless it is explicitly stated or directly derivable from the input document. If multiple methods are plausible, state the assumption made and justify it based on the input document.

Output instructions:
- Return a file named output.json containing a single block named 'output'. Copy the entire prompt block into 'output' and replace each null value with the extracted or derived result. Do not add, remove, rename, or modify any other fields.
- Return a separate file named output.R implementing the calculations for all Derivation required questions. For each question the script must print: (1) the source inputs, (2) the calculation method and formula applied. Each method should be implemented as a reusable R function, with all necessary inputs specified as function arguments to support future reproducibility and validation testing, and (3) the final calculated value.
