Advanced Epidemiology

PHE 515 – Homework 1: Intervention Studies
30 points

NAME:___________________________________

Objectives
• To understand the design and analysis of clinical trials
• To understand the importance of randomization in clinical trials
• To understand the principle of the intention-to-treat analysis
• To understand the concept of number needed to treat

Procedure
• Read:Diabetes Prevention Program (DPP) Research Group. (2002). Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine, 346(6), 393-403.
• Read pages 623-624 (Eligibility Criteria, Recruitment and Staged Screening Process) and page 628 (Biostatistical considerations, Sample size goal): Diabetes Prevention Program (DPP) Research Group. (1999). Design and methods for a clinical trial in the prevention of type 2 diabetes. Diabetes Care, 22, 623-634.

Questions

1. Related to the study design and type of trial conducted in the DPP study.
a. What were the aims of this study? What is the design?(3 points)

b. What were the randomization groups? (3 points)

c. What was the primary outcome of the trial? (1 point)

d. Were there any secondary outcomes? (2 points)

e. Explain the concept of blinding and if/how it was applied in the DPP study.(3 points)

2. Consider Table 1 in the NEJM(2002) paper. Discuss why you think that the randomization scheme was successful (or not) comparing the baseline characteristics of the two groups.(2 points)

3. Consider the presentation of the analysis and results of the effect of the randomization group on cumulative incidence of diabetes in Figure 2, Table 2, and on page 397 of the NEJM (2002) paper.
a. Describe the three curves shown in Figure 2. Which randomization group (intervention) seems to have the greatest impact on diabetes occurrence?(1 point)

b. What type of measure of incidence is shown in Figure 2?(1 point)

c. Compare the measures shown in Figure 2 and the incidence measures shown in Table 2. What is the key difference and which do you think is preferable and why?(2 points)

4. In the Diabetes Care (1999) paper, the DPP investigators describe their sample size goal and the assumptions they made in designing the study.
a. Compare the assumed diabetes incidence (termed “hazard rate”) in the placebo group with the actual diabetes incidence rate observed in the trial.(3 points)

b. Describe briefly the sample size the investigators aimed at and what considerations went into this process. Compare the target number to the actual number included in the trial. Judging from these numbers, do you think the trial was “over-” or “under-”powered to detect an effect of Intense Lifestyle/Metformin intervention on diabetes occurrence?(4 points)

5. The trial was stopped early – in fact by a full year (NEJM, 2002 paper, p. 394, right column). What do you think contributed to the early closure of the trial?(5 points)