统计问题第133问：风险比

Question

Researchers investigated whether BCG revaccination at 19 months of age reduced child mortality. A randomised controlled trial was performed in Guinea-Bissau, west Africa. In total 1437 children were randomised to BCG revaccination and 1434 to no revaccination (controls). All trial participants had been vaccinated at birth and on the day of enrolment had low or no reactivity to tuberculin and were not severely sick.

Children were followed from 19 months until 5 years of age. During follow-up 77 children died. The hazard ratio of death for the revaccinated children, compared with controls, was 1.2 (95% confidence interval 0.77 to 1.89).

Which of the following statements, if any, are true?

·a) Revaccinated children had a 20% increased risk of death, compared with controls, at any time during follow-up.

·b) The hazard rate for the revaccination group was assumed to be constant during follow-up.

·c) Length of life of children in the control group was increased by 20%, compared with revaccinated children

·d) It can be inferred that the hazard ratio of death for revaccinated children, compared with controls, will be 1.2 until the age of 10 years.

提示：正确答案只有一个。

Answer

Answer a is true, while b, c, and d are false.

The trial investigated whether revaccination at 19 months of age influenced mortality. Children were followed until age 5. The length of survival after randomisation to treatment group was recorded. These times are referred to as time to event or survival data, described in a previous question. If death occurred during follow-up then the survival time is termed exact, otherwise it is termed censored (if a child was still alive at age 5 years).

The hazard ratio, also known as a relative hazard, compares the rate of death in the revaccinated group with that in the control group across the entire follow-up period. At any time during follow-up children in the revaccinated group were 1.2 times as likely—that is, 20% more likely—to die, compared with controls (a is true). This result was unexpected, and the authors reported that the trial was stopped early because of the unnecessary raised risk of mortality after revaccination.

The hazard ratio was calculated as the hazard rate of death for the revaccinated group divided by the hazard rate for control treatment. A hazard rate is derived as the probability of death in a time interval divided by the length of the interval and therefore represents the rate of death. The study period was divided into very short time intervals, and therefore the hazard rate for each represents the instantaneous rate of death. A hazard ratio above 1 indicates a raised hazard for the revaccinated group and below 1 a decreased hazard, while a value equal to 1 would indicate that the hazard of death for the revaccinated group was equal to that for the control group. The hazard rate for either treatment group may not be constant during the study period (b is false). It is assumed, however, that the ratio of the hazard rates between treatment groups is constant—that is, that they are proportional.

The 95% confidence interval for the population hazard ratio, 0.77 to 1.89, includes unity—the state of equipoise between the revaccinated and control groups in mortality at any time across the study period. Therefore, no statistically significant difference existed between treatment groups in their hazard rates at the 5% level of significance.

The hazard ratio does not estimate the extent to which revaccination shortened length of life compared with controls (c is false), only that revaccination increased the risk of death at any time during follow-up.

The hazard ratio was derived from the follow-up of children from 19 months of age until 5 years. It is not possible to infer that the hazard ratio of death for revaccinated children compared with controls will be 1.2 until the age of 10 years (d is false). Caution must be applied before extrapolating trial results beyond the period in which participants were studied—a longer study period until the age of 10 years would be needed to establish whether the observed increase in mortality in the revaccination group was maintained.

所以答案是选择 a 

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