Value of Information for Clinical Trial Design: The Importance of Considering All Relevant Comparators

Abstract

Value of Information (VOI) analyses calculate the economic value that could be generated by obtaining further information to reduce uncertainty in a health economic decision model. VOI has been suggested as a tool for research prioritisation and trial design as it can highlight economically valuable avenues for future research. Recent methodological advances have made it increasingly feasible to use VOI in practice for research; however, there are critical differences between the VOI approach and the standard methods used to design research studies such as clinical trials. We aimed to highlight key differences between the research design approach based on VOI and standard clinical trial design methods, in particular the importance of considering the full decision context. We present two hypothetical examples to demonstrate that VOI methods are only accurate when (1) all feasible comparators are included in the decision model when designing research, and (2) all comparators are retained in the decision model once the data have been collected and a final treatment recommendation is made. Omitting comparators from either the design or analysis phase of research when using VOI methods can lead to incorrect trial designs and/or treatment recommendations. Overall, we conclude that incorrectly specifying the health economic model by ignoring potential comparators can lead to misleading VOI results and potentially waste scarce research resources.

Fig. 1

The incremental costs and effectiveness for a health economic model comparing the novel painkiller with the current SoC. Points in the shaded area indicate that the novel painkiller is cost effective and points elsewhere indicate that the SoC is cost effective. The x-axis shows the effectiveness differential in terms of QALYs, while the y-axis shows the difference in population costs. The ICER is shown as a red cross. SoC standard of care, ICER incremental cost-effectiveness ratio, QALYs quality-adjusted life-years

Fig. 2

The incremental costs and effectiveness measures for a full health economic model evaluating the novel painkiller (grey dots) and physiotherapy (black dots) for the treatment of chronic back pain. The black dots are almost all in the shaded area, indicating that physiotherapy is cost effective compared with the SoC. The black dots are lower and to the right of the grey dots, indicating the physiotherapy is cost effective compared with the novel painkiller. SoC standard of care

Fig. 3

Cost-effectiveness plane for the health economic analysis comparing a novel drug (black dots), exercise (blue triangles) and CBT (grey crosses) against the SoC for mild-to-moderate depression. This model is illustrative and does not evaluate treatments for depression. SoC standard of care, CBT cognitive behavioural therapy