A randomized, double-blinded clinical trial was conducted to assess the role of a multidrug chemotherapy regimen for the treatment of newly diagnosed stage III and IV stomach cancer. In the study, 150 patients were enrolled in the treatment group and received the new multidrug treatment, and 100 patients were enrolled in the control group and were treated with standard first-line therapy. All patients were followed for 24 months. A total of 120 patients in the treatment group (80%) and 80 patients in the control group (80%) died during this follow-up period. Despite these calculations, the investigators concluded that the new multidrug regimen was more effective than standard therapy. Which of the following most likely accounts for the conclusion reached by the study investigators?
A)2-year mortality risk was calculated
B)Observer bias may be present
C)Selective survival bias may be an issue
D)The results were confounded
E)Time-to-event data was analyzed

Question

A randomized, double-blinded clinical trial was conducted to assess the role of a multidrug chemotherapy regimen for the treatment of newly diagnosed stage III and IV stomach cancer.  In the study, 150 patients were enrolled in the treatment group and received the new multidrug treatment, and 100 patients were enrolled in the control group and were treated with standard first-line therapy.  All patients were followed for 24 months.  A total of 120 patients in the treatment group (80%) and 80 patients in the control group (80%) died during this follow-up period.  Despite these calculations, the investigators concluded that the new multidrug regimen was more effective than standard therapy.  Which of the following most likely accounts for the conclusion reached by the study investigators?
A)2-year mortality risk was calculated
B)Observer bias may be present
C)Selective survival bias may be an issue
D)The results were confounded
E)Time-to-event data was analyzed

Quizplus · Accepted Answer

Explanation: 11ec2b69_c0ef_957a_8f63_f19737a833b8_MD0005_00 Time-to-event data is collected when the elapsed time before an event occurs is of significant interest. It accounts not only for the total number of events in both groups, but also for the timing of the events, which can be important when assessing treatment benefit. It is commonly used in survival analysis where the event of interest is death. In this example, patients in the treatment group may, on average, have a longer survival time than the patients in the control group despite an equivalent 2-year mortality risk (Choice A). For instance, the median survival time could be ~7 months in the control group and ~19 months in the treatment group (as seen in the above graph). Therefore, a time-to-event analysis would explain the conclusion that the treatment group did better than the control group. (Choice B) Observer bias can occur when observers misclassify data due to preconceived expectations regarding the investigational treatment. It can be prevented by performing a double-blind study in which neither participants nor investigators are aware of individual treatment assignments. (Choice C) Selective survival bias occurs when patients are selected from the entire disease population (prevalent cases) instead of just those that are newly diagnosed (incident cases). As patients with more aggressive disease die sooner and are less likely to be enrolled, this can result in a study population with a higher proportion of more benign cases. However, this study was limited to only newly diagnosed patients. (Choice D) Randomization is an effective tool to control for confounding, as the association between a potential confounder and the choice of treatment group will most likely be broken by random assignment. Educational objective: Survival analysis is commonly used to assess mortality benefit in prospective studies and clinical trials. It accounts not only for the number of events in both groups, but also for the timing of the events throughout the follow-up period.

A Randomized, Double-Blinded Clinical Trial Was Conducted to Assess the Role