An open-label randomized trial is conducted to compare a new nonsteroidal anti-inflammatory agent (AG) and low-dose colchicine for the treatment of gout flares in primary care. A total of 400 adults with gout flares were randomized 1:1 to AG for 7 days or low-dose colchicine three times per day for 4 days. The primary outcome was change in pain intensity from baseline measured over the first 7 days. At Day 7 follow-up, about 25% of participants in the low-dose colchicine group had switched treatment to AG, and about 15% of participants in the low-dose colchicine group had stopped treatment altogether. The primary investigator decided to preserve the original randomization for the data analysis. Which of the following describes the data analysis approach adopted by the primary investigator?

Question

An open-label randomized trial is conducted to compare a new nonsteroidal anti-inflammatory agent (AG) and low-dose colchicine for the treatment of gout flares in primary care.  A total of 400 adults with gout flares were randomized 1:1 to AG for 7 days or low-dose colchicine three times per day for 4 days.  The primary outcome was change in pain intensity from baseline measured over the first 7 days.  At Day 7 follow-up, about 25% of participants in the low-dose colchicine group had switched treatment to AG, and about 15% of participants in the low-dose colchicine group had stopped treatment altogether.  The primary investigator decided to preserve the original randomization for the data analysis.  Which of the following describes the data analysis approach adopted by the primary investigator?

Quizplus · Accepted Answer

Explanation: 11ec2b69_bdfe_1b8b_8f63_45aed9928b8c_MD0005_00 An intention-to-treat (ITT) analysis compares treatment groups in a randomized trial by including all subjects as initially allocated after randomization regardless of what happens during the study period. The rationale is that if subjects have such a poor treatment response (or are so inconvenienced by treatment administration or adverse effects) as to not follow protocol specifications or drop out of the study, then their outcomes should be attributed to that intervention (ie, nonadherence is related to the practical benefits of treatment). ITT analysis also helps avoid the effects of attrition (eg, loss to follow-up, dropout) and crossover (eg, switching to another assigned intervention), which may disrupt the benefit of randomization and introduce bias in the estimation of the effect of the intervention. ITT analysis may lead to conservative estimates of the effect of interventions. If attrition or crossover is significant, ITT analysis may be less likely to identify a statistically significant difference between treatments (ie, shift toward the null hypothesis). However, results will reflect the expected effect of the intervention in a practical clinical setting. (Choices A, D, and E) Correlation, regression, and stratified analyses are statistical methods used to analyze data regardless of which data (ie, excluding or including data of drop-off and nonadherent participants) are included in the analysis. Therefore, these statistical methods may be used on an ITT or a per-protocol (PP) analysis. (Choice C) In a PP analysis, only those patients who strictly adhered to a research protocol (ie, excluding all nonadherent and drop-off patients) are included in the final data analysis; therefore, the benefit of randomization can be lost with significant subject attrition (eg, sicker subjects selectively dropping out, introducing bias). PP analysis can also overestimate the effect of the intervention in a practical clinical setting, particularly when the treatment is somehow aversive to patients. Educational objective: Intention-to-treat analysis includes each subject in their initial randomization group even if subjects stop the intervention or shift to a different intervention. This approach tends to provide a conservative but more valid estimate of the intervention effect in clinical settings (ie, real-world scenarios).

An Open-Label Randomized Trial Is Conducted to Compare a New