A large-scale clinical trial is being planned to evaluate the effect of a nonselective beta blocker, propranolol, on the clinical course of portal hypertension. The comparison is with placebo. The primary outcomes of the study are all-cause mortality and major gastrointestinal hemorrhage. Secondary outcomes are minor gastrointestinal hemorrhage and the number of hospitalizations. Classification of the episodes of gastrointestinal hemorrhage into "major" and "minor" is based on clinical assessment as well as laboratory data such as change in hemoglobin level. The investigators are concerned about the possibility that major gastrointestinal hemorrhage events could be over-reported in the placebo group. Which of the following is the most useful technique to reduce this possibility?
A)Blinding
B)Matching
C)Randomization
D)Restriction
E)Stratified analysis

Question

A large-scale clinical trial is being planned to evaluate the effect of a nonselective beta blocker, propranolol, on the clinical course of portal hypertension.  The comparison is with placebo.  The primary outcomes of the study are all-cause mortality and major gastrointestinal hemorrhage.  Secondary outcomes are minor gastrointestinal hemorrhage and the number of hospitalizations.  Classification of the episodes of gastrointestinal hemorrhage into "major" and "minor" is based on clinical assessment as well as laboratory data such as change in hemoglobin level.  The investigators are concerned about the possibility that major gastrointestinal hemorrhage events could be over-reported in the placebo group.  Which of the following is the most useful technique to reduce this possibility?
A)Blinding
B)Matching
C)Randomization
D)Restriction
E)Stratified analysis

Quizplus · Accepted Answer

Explanation: Observer bias is defined as a misclassification of events that can result from knowing the exposure status of a patient. In this clinical scenario, physicians who are aware of participant allocation (ie, whether the participant was allocated to receive propranolol or placebo) may tend to classify hemorrhagic episodes as "major" if a patient belongs to placebo group and "minor" if a patient belongs to the treatment group. Blindingthe physicians to the treatment status of a patient can balance this effect. The other techniques listed are used to control confounding variables: (Choices B and D) Matching and restriction are typically employed in other study designs (eg, case control studies, cohort studies). The initial step in matching involves selecting variables that could be confounders (eg, age, race); cases and controls are then selected based on the matching variables so that both groups have a similar distribution in accordance with the variables. Restriction involves limiting study participation to individuals with specific characteristics. (Choice C) Randomization helps to balance numerous known and unknown extraneous factors (confounders) evenly between the treatment and placebo groups. It is commonly used in clinical trials. However, randomization would not prevent over-reporting if the physicians are not blinded. (Choice E) Stratified analysis is a statistical tool used to control confounding at the analysis stage of a study. Educational objective: Observer bias can be effectively reduced by using the blinding technique.

A Large-Scale Clinical Trial Is Being Planned to Evaluate the Effect