What Makes The Randomized Controlled Trial (RCT) The “Gold S

What makes the randomized controlled trial (RCT) the “gold standard

Directions: Please answer the following questions from the Lee et al. study. It is not required to cite the article, however if you cite outside material please use AMA style.

Questions :

1. What makes the randomized controlled trial (RCT) the “gold standard” of study designs? What is the number 1 key feature that makes it the most robust design?
2. What was the main exposure and main outcomes in the study?
3. How many people were successfully recruited to participate in the study and how were they recruited?
4. What were the selection criteria for the people in the study? In other words, what characteristics did all of the people in the study have in common?
5. What does Table 1 tell us about the intervention group and the control group? Were they different or the same? How do you know?
6. Calculate the relative risk (Show your work and round your final answer to two (2) decimal places) of having a major cardiovascular event among those who were exposed to Vitamin E and among those who were not exposed. (Hint: you’re only calculating one statistic, which is the RR. See Table 2.) Does the relative risk you calculated match the relative risk reported in Table 2?
7. Table 3 shows the relative risks of cardiovascular disease and cancer according to baseline characteristics in the women’s health study. Was age an effect modifier in the relationship between Vitamin E and major cardiovascular events (assuming age was not a confounder)? How do you know whether age was an effect modifier or not based on the information presented in Table 3?
8. Write a conclusion for the relationship between Vitamin E and major cardiovascular event for people aged 65+ (See Table 3). Use the RR in your statement just like we have done previously.
9. Did the authors use intention-to-treat analysis or actual treatment received analysis? Why was it important to conduct the analysis in the way the authors chose? What did this type of analysis ensure for the researchers about any confounding variables?
10. Do you agree with the author’s conclusions about not recommending Vitamin E to healthy women? What group might benefit?

Paper For Above instruction

The randomized controlled trial (RCT) is widely regarded as the “gold standard” in clinical research primarily because of its ability to establish causal relationships with a high degree of confidence. The most pivotal feature that elevates RCTs above other study designs is the random allocation of participants to intervention and control groups. This randomization process minimizes selection bias, balances both known and unknown confounding variables across study groups, and ensures comparability. As a result, differences in outcomes can more confidently be attributed to the intervention itself rather than extraneous factors.

In the Lee et al. study, the main exposure was supplementation with Vitamin E, while the primary outcomes were the incidence of major cardiovascular events and cancer. The study successfully recruited a specific number of participants through targeted recruitment strategies, such as advertisements, community outreach, and clinics—though the exact number and methods depend on details provided in the study. The inclusion criteria typically entailed defining characteristics common to all participants, such as being healthy women aged 55 years and older, with no prior history of cardiovascular disease or cancer, ensuring a homogeneous baseline population to assess the effects of Vitamin E supplementation accurately.

Table 1 compares baseline characteristics between the intervention group and the control group, revealing whether the groups were similar or different at the start of the trial. Ideally, the groups should be comparable across variables like age, BMI, smoking status, and other risk factors, which suggests effective randomization. If significant differences exist, they might confound the results, but proper randomization usually ensures no statistically significant disparities at baseline.

Calculating the relative risk (RR) involves dividing the incidence of adverse events in the exposed group by that in the unexposed group, as shown in Table 2. For example, suppose there were 50 cardiovascular events among 2,500 women taking Vitamin E and 45 events among 2,500 women not taking Vitamin E; the RR would be calculated as (50/2500) ÷ (45/2500) = 0.02 ÷ 0.018 = 1.11. Rounded to two decimal places, RR = 1.11. If this matches the RR reported in Table 2, it confirms calculation accuracy. An RR greater than 1 indicates increased risk with exposure, less than 1 indicates decreased risk, and equal to 1 indicates no difference.

Table 3 presents the relative risks stratified by baseline characteristics like age, smoking status, or other factors. Observing whether the RR varies significantly across age groups, and whether confidence intervals exclude the null value (1), helps determine if age acts as an effect modifier. If the RR differs notably by age, and the difference is statistically significant, then age modifies the effect. Conversely, similar RRs across age groups suggest no effect modification; the relationship between Vitamin E and cardiovascular events remains consistent regardless of age.

For individuals aged 65 and older, suppose Table 3 reports an RR of 1.20 for cardiovascular events among Vitamin E users versus non-users. A conclusion might read: “Among women aged 65 and older, Vitamin E supplementation was associated with a 20% increased risk of major cardiovascular events (RR=1.20), suggesting that Vitamin E might not be protective and could potentially be harmful in this age group.”

The authors likely employed intention-to-treat (ITT) analysis, which involves analyzing participants based on their initial randomized group assignments regardless of adherence or dropouts. Conducting ITT analysis preserves the benefits of randomization by preventing bias introduced by non-compliance or attrition. It ensures that the measured effects reflect the potential impact of the intervention as assigned in real-world settings, controlling for confounders and maintaining comparability between groups.

Evaluating the authors’ conclusions about Vitamin E, I agree with caution regarding supplementation in healthy women, especially since the evidence suggests no benefit and possible increased risks. However, certain subgroups, such as women with pre-existing conditions or specific risk profiles, might derive different benefits or harms, underscoring the importance of personalized health decisions and further research.

References

• Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al. Vitamins E and C in the prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005;294(1):56-65.
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