TY - JOUR

T1 - Statistical consideration when adding new arms to ongoing clinical trials

T2 - the potentials and the caveats

AU - Lee, K.M.

AU - Brown, L.C.

AU - Jaki, T.

AU - Stallard, N.

AU - Wason, J.

PY - 2021/3/10

Y1 - 2021/3/10

N2 - Background: Platform trials improve the efficiency of the drug development process through flexible features such as adding and dropping arms as evidence emerges. The benefits and practical challenges of implementing novel trial designs have been discussed widely in the literature, yet less consideration has been given to the statistical implications of adding arms. Main: We explain different statistical considerations that arise from allowing new research interventions to be added in for ongoing studies. We present recent methodology development on addressing these issues and illustrate design and analysis approaches that might be enhanced to provide robust inference from platform trials. We also discuss the implication of changing the control arm, how patient eligibility for different arms may complicate the trial design and analysis, and how operational bias may arise when revealing some results of the trials. Lastly, we comment on the appropriateness and the application of platform trials in phase II and phase III settings, as well as publicly versus industry-funded trials. Conclusion: Platform trials provide great opportunities for improving the efficiency of evaluating interventions. Although several statistical issues are present, there are a range of methods available that allow robust and efficient design and analysis of these trials.

AB - Background: Platform trials improve the efficiency of the drug development process through flexible features such as adding and dropping arms as evidence emerges. The benefits and practical challenges of implementing novel trial designs have been discussed widely in the literature, yet less consideration has been given to the statistical implications of adding arms. Main: We explain different statistical considerations that arise from allowing new research interventions to be added in for ongoing studies. We present recent methodology development on addressing these issues and illustrate design and analysis approaches that might be enhanced to provide robust inference from platform trials. We also discuss the implication of changing the control arm, how patient eligibility for different arms may complicate the trial design and analysis, and how operational bias may arise when revealing some results of the trials. Lastly, we comment on the appropriateness and the application of platform trials in phase II and phase III settings, as well as publicly versus industry-funded trials. Conclusion: Platform trials provide great opportunities for improving the efficiency of evaluating interventions. Although several statistical issues are present, there are a range of methods available that allow robust and efficient design and analysis of these trials.

KW - Adding arms

KW - Bias

KW - Error rates

KW - Multiplicity

KW - Platform trials

U2 - 10.1186/s13063-021-05150-7

DO - 10.1186/s13063-021-05150-7

M3 - Journal article

VL - 22

JO - Trials

JF - Trials

SN - 1745-6215

IS - 1

M1 - 203

ER -