Introduction to RECIST 1.1 (2)

 

Best Overall Response (BOR)

The Best Overall Response is the best response recorded from the start of treatment until the end of treatment.

  • Categories: Each patient is assigned one of the following: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), or Inevaluable (NE).

  • Confirmation Requirement: In non-randomized trials where response is the primary endpoint, a BOR of PR or CR requires confirmation by a repeat assessment.

  • Stable Disease (SD): To be considered the BOR, SD must meet a protocol-specified minimum time interval from baseline (generally not less than 6–8 weeks).

Objective Response Rate (ORR)

The ORR is typically defined as the proportion of patients who achieve a confirmed PR or CR.

  • Denominator: All eligible patients (or all treated patients) should be included in the denominator for the calculation.

  • Reporting: It is preferred that 95% two-sided confidence limits are provided for the calculated response rate.

Progression-Free Survival (PFS): Censoring and Rules

PFS is the time from the start of treatment (or randomization) until the first date that progressive disease (PD) or death is objectively documented.

  • Frequency of Assessment: PFS is highly influenced by the frequency of follow-up; assessments should follow a strict calendar schedule to avoid bias.

  • Censoring for Missing Data: If no imaging or measurement is done at a specific time point, the patient is considered Inevaluable (NE) for that interval.

  • Clinical Deterioration: Patients who stop treatment due to a global deterioration of health without objective evidence of PD are reported as "symptomatic deterioration," which is a reason for stopping therapy rather than an objective descriptor of PD.

  • New Lesions: The appearance of any new malignant lesion is considered unequivocal progression and triggers the PD date.

Overall Survival (OS)

While the provided text focuses on anatomical measurement, it acknowledges that agents producing tumor shrinkage often have a reasonable chance of demonstrating improvement in overall survival in randomized phase III studies.

Duration of Response (DOR)

  • Overall Response (CR/PR): Measured from the time measurement criteria are first met for CR or PR (whichever is recorded first) until the first date that recurrent or progressive disease is objectively documented.

  • Reference Point: The smallest sum of diameters recorded on study is used as the reference for determining the subsequent date of progression.

  • Complete Response (CR): Measured from the time criteria are first met for CR until the first date that recurrent disease is documented.

Comments

Post a Comment

Popular posts from this blog

Understanding Binding vs. Non-Binding Futility Analysis in Clinical Trials

Image
  1.What is the difference between binding futility and non-binding futility analysis ? In clinical trials,   futility analysis   is a type of interim analysis used to determine whether it is unlikely that a study will achieve its objectives if it continues as planned. This helps avoid wasting resources and exposing participants to ineffective treatments. Futility analyses can be   binding   or   non-binding , and the distinction is important for trial design and interpretation. 🔹 Binding Futility Analysis Definition : If the futility boundary is crossed, the trial  must be stopped . Implication : It is part of the formal decision-making process and is enforced by the protocol or statistical analysis plan. Use Case : Often used when ethical or resource concerns demand early termination if the treatment is clearly not effective. 🔹 Non-Binding Futility Analysis Definition : If the futility boundary is crossed, the trial  may continue ...
Read more

Use FDA Suggestions on Missing Data and Sensitivity Analyses

  The U.S. FDA provides guidance and expectations on how to handle missing data in clinical trials, especially in the context of estimands and sensitivity analyses . Below is a detailed summary based on key regulatory documents and practices. 📘 1. Key FDA Guidance Documents A. FDA (2019): "Estimands and Sensitivity Analyses in Clinical Trials" Focus: Aligning analysis with the trial objective and handling intercurrent events , like treatment discontinuation or dropout. Introduces the estimand framework from ICH E9(R1). Emphasizes sensitivity analysis under plausible MNAR assumptions. 🔗 Link: FDA Estimand Guidance (PDF) 📌 2. FDA Expectations at a Glance Topic FDA View Primary analysis Can assume MAR (e.g., MMRM) if justified Sensitivity analysis Must explore MNAR scenarios (not just MAR) Multiple imputation Acceptable if properly implemented Pattern-mixture models Encouraged as part of sensitivity analyses Reference-based imputation (CIR, J2R) Inc...
Read more

Analysis of Repeated Measures Data using SAS (1)

Image
 1. Basic Concepts of Repeated Measures: In this basic setup of a completely randomized design with repeated measures, there are two factors, treatments and time. Treatment is called the between-subjects factor because levels of treatment can change only between subjects; all measurements on the same subject will represent the same treatment. Time is called a within-subjects factor because different measurements on the same subject are taken at different times.  In repeated measures experiments, interest centers on (1) how treatment means differ, (2) how treatment means change over time, and (3) how differences between treatment means change over time. 2. Four-step procedure for mixed model analysis: Step 1: Model the mean structure, usually by specification of the fixed effects. Step 2: Specify the covariance structure, between subjects as well as within subjects. Step 3: Fit the mean model accounting for the covariance structure. Step 4: Make statistical inference bas...
Read more