Related Experiment Video
Updated: Jun 1, 2026

Strategies for Assessing Autistic-Like Behaviors in Mice
Published on: September 20, 2024
Assessing causal relationships between treatments and clinical outcomes: always read the fine print
1Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 6130 Executive Plaza, Bethesda, MD 20892, USA. freidlinb@ctep.nci.nih.gov
Abstract:
Changes in clinical practice should be driven by relevant and reliable evidence. Hence, adoption of a new therapy requires demonstrating that it provides (causes) benefit. Such evidence is generally obtained from intent-to-treat analyses of randomized clinical trials (RCTs). In this paper, we review other approaches to assessing the causal relationship between treatments and outcomes: (1) inference from non-randomized (observational) studies, (2) analysis of randomized studies where patients received treatments other than those to which they were randomized and (3) analysis of studies where the outcome of interest is sometimes unobservable because of a competing event (competing risks). We conclude that for the practice-changing demonstration of a favorable benefit-to-risk ratio, the gold standard is the intent-to-treat analysis of RCTs. At the same time, we illustrate how careful application of special statistical methods for assessment of treatment-outcome causation can be instrumental in complementing existing randomized evidence and guiding design of future research.
Related Concept Videos
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
Clinical Trials
There are four phases in a clinical trial. A phase one...
Blind Procedures
Blinding
Strategies for Assessing and Addressing Confounding
Confounding can be addressed at both the design phase of a study and through analytical methods after data...
Clinical Trials: Overview