School of Social and Community Medicine, University of Bristol, Bristol, UK.
Value Health. 2013 Jan-Feb;16(1):185-94. doi: 10.1016/j.jval.2012.09.012.
The primary outcomes in trials are usually disease-specific measures (DSMs) designed to be responsive to changes in the condition caused by treatment. For purposes of cost-effectiveness analysis, treatment effects on the DSM are often "mapped" into treatment effects on a generic health-related quality-of-life (QOL) scale, such as EuroQol five-dimensional questionnaire. Trialists have the option of including generic QOL measures as trial outcomes. We consider the relative efficiency (estimate divided by its standard error) of treatment effects derived from the DSM, the generic QOL, the generic QOL indirectly estimated from the mapped DSM, and a pooled estimate combining the direct and indirect information on the generic QOL. By using a "common factor" theory of the relationship between the DSM and the generic QOL, we define the circumstances under which indirectly estimated generic QOL is more efficient than the direct one and when a pooled QOL estimate is more efficient than the DSM estimate. As long as the DSM is more responsive, there is always a threshold sample size above which the indirect estimate has better precision than the direct estimate. This threshold, however, increases as the (1) relative responsiveness ratio of the DSM to the generic QOL increases, (2) precision of the estimated mapping coefficient increases, and (3) true effect becomes smaller. The pooled estimate on the generic QOL may be more efficient than the DSM itself unless the reliability of the DSM is particularly high. Trials powered on DSMs are likely to have sufficient power to detect treatment effect on the generic QOL if a pooled estimate is used. We conclude that generic QOL instruments should be routinely included in randomized controlled trials. Information on mapping coefficients and on relative responsiveness should be collected more systematically to facilitate both evidence synthesis and trial design.
主要结局指标通常是为响应治疗引起的疾病变化而设计的特定疾病措施 (DSM)。出于成本效益分析的目的，治疗对 DSM 的影响通常会“映射”到通用健康相关生活质量 (QOL) 量表上的治疗效果，例如 EuroQol 五维问卷。试验者可以选择将通用 QOL 措施作为试验结果。我们考虑了从 DSM、通用 QOL、从映射 DSM 间接估计的通用 QOL 和结合通用 QOL 直接和间接信息的综合估计中得出的治疗效果的相对效率（估计值除以其标准误差）。通过使用 DSM 和通用 QOL 之间关系的“共同因素”理论，我们定义了间接估计的通用 QOL 比直接估计更有效的情况，以及组合直接和间接通用 QOL 信息的综合 QOL 估计更有效的情况。只要 DSM 更具响应性，就始终存在一个阈值样本量，超过该阈值，间接估计的精度就比直接估计的精度好。然而，这个阈值随着 (1)DSM 相对于通用 QOL 的相对响应比增加，(2)估计映射系数的精度增加，以及 (3)真实效果变小而增加。除非 DSM 的可靠性特别高，否则综合通用 QOL 估计可能比 DSM 本身更有效。如果使用综合估计，则在 DSM 上进行的试验很可能具有足够的效力来检测通用 QOL 上的治疗效果。我们得出的结论是，通用 QOL 工具应常规纳入随机对照试验。应更系统地收集有关映射系数和相对响应性的信息，以促进证据综合和试验设计。
