Per-protocol vs. intention-to-treat analysis

Per-protocol analysis and intention-to-treat (ITT) analysis are two methods of analyzing data in clinical trials.

Per-protocol analysis refers to the analysis of data from only those participants in a clinical trial who followed the study protocol precisely. In per-protocol analysis, participants who deviate from the protocol are often excluded from the analysis.

Intention-to-treat analysis, on the other hand, is the analysis of all randomized participants according to their original assigned treatment group, regardless of whether they received or completed the assigned treatment. In ITT, all participants are included in the analysis, regardless of whether they followed the study protocol.

The primary advantage of per-protocol analysis is that it can provide more accurate estimates of treatment efficacy, as it only includes participants who received the full intended treatment. However, per-protocol can introduce selection bias, as participants who follow the protocol may differ systematically from those who do not.

ITT, on the other hand, is considered the gold standard method of analysis in clinical trials. The primary advantage of ITT is that it accounts for non-adherence, dropouts, and other protocol deviations, which are common in real-world settings. ITT provides unbiased estimates of treatment effects, as it includes all randomized participants, regardless of their adherence to the protocol.

Per-protocol analysis is superior to ITT analysis when you want to measure the effect of receiving a treatment under optimal conditions, such as in non-inferiority trials or when analyzing adverse effects of treatments. However, per protocol analysis can introduce bias if the groups being compared are no longer similar due to dropouts or deviations from the protocol. 

Both methods have their advantages and disadvantages and should be chosen based on the research question and the specific context of the trial.

References:

1. Signifience - Intention-to-Treat (ITT) vs. Per Protocol (PP) : How to choose the right clinical trial population 

2. Intention-to-treat and per-protocol analysis (researchgate.net) 

3. Intention-to-treat and per-protocol analysis | CMAJ 

4. Intention to treat and per protocol analysis in clinical trials - PubMed (nih.gov) 

5. Understanding the Intention-to-treat Principle in Randomized Controlled Trials - PubMed (nih.gov) 

6. Intent-to-Treat (ITT) vs Completer or Per-Protocol Analysis in Randomized Controlled Trials - Chittaranjan Andrade, 2022 (sagepub.com)