Navigating Regulatory Biostatistical Requirements | Page 3

The typical clinical trial lifecycle can be broken into several parts, each with unique aspects regarding the biostatistical requirements TRIAL PLANNING TRIAL CONDUCT Strategic planning: implications of desired label on endpoints and trial design Blind data review for accuracy and completeness Protocol development and review: e.g. sample size calculation, randomization, endpoints and objectives Ongoing data review to verify protocol adherence Development of statistical analysis plan (SAP) and tables, figures and listings (TFLs) Regulatory review of the study protocol before study start is conducted for study approval to ensure that: • It is designed to meet study objectives while ensuring that patient safety is protected. • The endpoints are appropriate for the study. • The sample size is appropriate for the study objectives. • The planned statistical analyses are appropriate for the study objectives. Similarly, all of these aspects are reviewed again once the sponsor has conducted the trial, both to ensure that the protocol and associated documents were followed as well as to examine any additional unplanned issues. Sufficient thought in the trial-planning stage reduces the time required in developing later submissions and responding to inquiries from regulatory authorities at the trial submission stage. During the trial, constant monitoring and addressing protocol issues as they occur also reduces time and issues at study completion. TRIAL CLOSEOUT/ ANALYSIS TRIAL SUBMISSION Interactions with regulatory agency Final analysis/TFLs Composing a clinical study report (CSR)/ integrated summary of safety (ISS) and integrated summary of effectiveness (ISE) Addressing regulatory questions about the trial As a result, the risk of a clinical trial failing to meet study objectives is reduced. Many venture-backed small- to mid-sized companies might not have had experience running a clinical trial or interacting with regulatory authorities, so they hire a contract research organization (CRO) to assist them. It is critical that the selected CRO has experience with all stages of the trial lifecycle. ‘‘ Sufficient thought in the trial-planning stage reduces the time required in developing later submissions and responding to inquiries from regulatory authorities at the trial submission stage. 3