A large-scale clinical trial was conducted to assess the effect of a multivitamin supplement on the risk of future cardiovascular events. Study outcomes included cardiovascular mortality, nonfatal myocardial infarction, and coronary revascularization procedures. According to the study results, the overall relative risk of a cardiovascular event occurring in the placebo group compared to the treatment group was 1.5 (p = .30). However, when data accrued only during the fifth year of follow-up were examined, the relative risk of a cardiovascular event occurring in the placebo group compared to the treatment group was 2.05 (p = .01). Survival curves for the 2 groups are shown below:
Which of the following best explains the study results?

Question

A large-scale clinical trial was conducted to assess the effect of a multivitamin supplement on the risk of future cardiovascular events.  Study outcomes included cardiovascular mortality, nonfatal myocardial infarction, and coronary revascularization procedures.  According to the study results, the overall relative risk of a cardiovascular event occurring in the placebo group compared to the treatment group was 1.5 (p = .30).  However, when data accrued only during the fifth year of follow-up were examined, the relative risk of a cardiovascular event occurring in the placebo group compared to the treatment group was 2.05 (p = .01).  Survival curves for the 2 groups are shown below:
 Which of the following best explains the study results?

Quizplus · Accepted Answer

Explanation: Latencyis an important natural phenomenon of disease epidemiology. Most infectious diseases have relatively short latency periods (ie, time elapsed from initial exposure to clinically apparent disease). In contrast, chronic disease processes (eg, cancer, heart disease) have a long latency period between the inciting pathophysiologic events and the development of clinical signs and symptoms. The concept of a latency period can also be extended to risk factors and risk reducers. Sometimes, a significant amount of time must pass before exposure to a risk modifier has a clinically evident effect on the disease process. In addition, exposure to a risk modifier may need to continue for a prolonged time period before the disease outcome is significantly affected. In this study, multivitamin use did not appear to have a statistically significant effect on cardiovascular event overall (as p = .30 >.05 and therefore not statistically significant). However, when results from the fifth year only were examined, a statistically significant benefit to multivitamin use was found, as patients in the placebo group had an increased risk of cardiovascular events (relative risk = 2.05) that was statistically significant (p <.05). The difference is likely due to the fact that at least 3 years of continuous multivitamin use were required to reveal the protective effect of the exposure on cardiovascular outcomes. This is visualized on the survival plot; the survival curves run parallel to each other during the first 3 years (latent period) and then begin to separate during the third year of follow-up. (Choice B) The overall relative risk is not statistically significant as it is "diluted" by the earlier years of latency. However, the relative risk for only the fifth year of follow-up clearly demonstrates the beneficial effect of prolonged multivitamin therapy. (Choice C) The vignette gives no information regarding selection of study participants or their subsequent randomization into treatment groups. Therefore, the presence of selection bias cannot be ascertained. (Choice D) In this study, an extended period of continuous exposure was necessary for multivitamin use to affect cardiovascular outcomes. A shorter follow-up period would have missed this effect. (Choice E) The sample size is large enough to demonstrate the efficacy of multivitamin therapy as the p-value for the fifth year follow-up data was statistically significant (p = .01). Educational objective: The concept of a latent period can be applied to both disease pathogenesis and exposure to risk modifiers. Inciting pathologic events (or exposure to risk modifiers) sometimes occur years before clinical manifestations become evident. In addition, exposure to risk modifiers may need to continue over a long time period before disease outcome is affected.

A Large-Scale Clinical Trial Was Conducted to Assess the Effect