An orthotics and prosthetics company conducts a single-blind, randomized, parallel group trial to investigate the effects of custom foot orthoses with motion control shoes versus the effects of motion control shoes alone in individuals with patellofemoral joint osteoarthritis. Eligible subjects are randomized to receive either custom foot orthoses with motion control shoes or motion control shoes alone, to be worn for 4 months. A significant number of patients are lost to follow-up or are noncompliant to the assigned intervention during the study. However, results for the patients who completed the protocol are encouraging. Which of the following techniques is most appropriate to estimate the real effect of custom foot orthoses in the population?
A)As-treated analysis
B)Intention-to-treat analysis
C)Noninferiority analysis
D)Per-protocol analysis
E)Stratified analysis

Question

An orthotics and prosthetics company conducts a single-blind, randomized, parallel group trial to investigate the effects of custom foot orthoses with motion control shoes versus the effects of motion control shoes alone in individuals with patellofemoral joint osteoarthritis.  Eligible subjects are randomized to receive either custom foot orthoses with motion control shoes or motion control shoes alone, to be worn for 4 months.  A significant number of patients are lost to follow-up or are noncompliant to the assigned intervention during the study.  However, results for the patients who completed the protocol are encouraging.  Which of the following techniques is most appropriate to estimate the real effect of custom foot orthoses in the population?
A)As-treated analysis
B)Intention-to-treat analysis
C)Noninferiority analysis
D)Per-protocol analysis
E)Stratified analysis

Quizplus · Accepted Answer

Explanation: Intention-to-treat (ITT) analysis compares intervention 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 are doing so poorly as to switch interventions or to drop out of the study, then their outcome should be attributed to that intervention. Therefore, ITT analysis is usually conducted to avoid the effects of crossover (eg, noncompliance to assigned intervention) and attrition (eg, loss to follow-up, drop-out), which may disrupt the benefit of randomization and introduce bias in the estimation of the effect of the intervention. ITT analysis may lead to a more conservative estimate of the effect of the intervention. If attrition or crossover is significant, ITT analysis may be less likely to identify a statistically significant difference between interventions (shift toward the null hypothesis and reduced chances of false-positive conclusions). However, results will reflect the real effect of the intervention as intended in the population. In this example, if subjects with more severe osteoarthritis drop out or cross over at a higher rate, even an ineffective intervention may appear beneficial if the analysis is conducted only on those who finished the protocol. Therefore, excluding subjects who were lost to follow-up or noncompliant to the assigned intervention introduces bias and may result in a statistically significant effect applicable only to subjects who completed the protocol. ITT analysis reduces bias by producing a more conservative but more valid estimate of the effect of using foot orthoses and motion control shoes as compared to motion control shoes alone. (Choices A and D) In a per-protocol analysis, only data from subjects who completed the intervention originally allocated at randomization are analyzed. With as-treated analysis (a subtype of per-protocol analysis), subjects are evaluated based on the intervention they received rather than the intervention to which they were randomized. Therefore, the benefit of the randomization is lost. Usually, per-protocol analysis will overestimate the real effect of the intervention on the outcome. (Choice C) In noninferiority trials, the goal is to prove that a new drug or intervention is not unacceptably worse than an alternate drug or intervention. This study attempts to estimate the real effect of custom foot orthoses as compared to motion control shoes alone. (Choice E) Stratified analysis is used to evaluate the presence of potential confounding and effect modification at the analysis stage of a study. Educational objective: Intention-to-treat analysis (ITT) analyzes each subject based on randomization group (even if subjects stop the intervention or shift to a different intervention). This tends to provide a conservative but more valid estimate of the intervention effect. ITT is used to help preserve the benefits of randomization in superiority trials.

An Orthotics and Prosthetics Company Conducts a Single-Blind, Randomized, Parallel