TY - JOUR
T1 - Beyond subgroup analysis
T2 - Improving the clinical interpretation of treatment effects in stroke research
AU - Lu, Mei
AU - Lyden, Patrick D.
AU - Brott, Thomas G.
AU - Hamilton, Scott
AU - Broderick, Joseph P.
AU - Grotta, James C.
N1 - Funding Information:
The authors thank Lula Adams for editing. This work was supported in part by NIH contracts # N01-NS-02382, N01-NS-02374, N01-NS-02377, N01-NS-02381, N0-NS-02379, N0-NS-02373, N0-NS-02376, N01-NS-02378 and N01-NS-02380, Grant P01-NS23393 from the National Institute of Neurological Disorders and Stroke, Bethesda, MD. Appendix A See . Tables A1 and A2
PY - 2005/4/30
Y1 - 2005/4/30
N2 - In large clinical trials designed to determine efficacy of an experimental treatment, patients are enrolled with presence or absence of various risk factors, such as diabetes or history of atrial fibrillation. A treatment-by-risk factor interaction indicates that the treatment effect may depend on the risk factor presence or absence. It is important to identify such interaction, since a treatment may fail or cause adverse events in the presence of the risk. Although statistical methods exist to identify such interaction, they are underutilized in clinical stroke research. This paper reviews the notion of treatment-by-risk factor interaction and identifies two types of interaction, quantitative and qualitative, using a graphical technique and statistical testing. We illustrate how to avoid drawing the erroneous conclusions regarding the treatment effect on subgroups when failing to detect an interaction, and provide rigorous tools to estimate the treatment effect on subgroups when an interaction is observed. Applications are presented using the data collected from the NINDS t-PA stroke studies. In stroke clinical trials, a treatment-by-risk factor interaction must be considered if the data permit. The graphical approach provides a heuristic illustration of interactions. Qualitative interactions are more important than quantitative interactions on therapeutic conclusion. Results of NINDS t-PA stroke studies confirmed our previous conclusions on the treatment t-PA benefit within 3-h therapeutic window. No subgroup of patients would lead a physician to withhold the t-PA treatment.
AB - In large clinical trials designed to determine efficacy of an experimental treatment, patients are enrolled with presence or absence of various risk factors, such as diabetes or history of atrial fibrillation. A treatment-by-risk factor interaction indicates that the treatment effect may depend on the risk factor presence or absence. It is important to identify such interaction, since a treatment may fail or cause adverse events in the presence of the risk. Although statistical methods exist to identify such interaction, they are underutilized in clinical stroke research. This paper reviews the notion of treatment-by-risk factor interaction and identifies two types of interaction, quantitative and qualitative, using a graphical technique and statistical testing. We illustrate how to avoid drawing the erroneous conclusions regarding the treatment effect on subgroups when failing to detect an interaction, and provide rigorous tools to estimate the treatment effect on subgroups when an interaction is observed. Applications are presented using the data collected from the NINDS t-PA stroke studies. In stroke clinical trials, a treatment-by-risk factor interaction must be considered if the data permit. The graphical approach provides a heuristic illustration of interactions. Qualitative interactions are more important than quantitative interactions on therapeutic conclusion. Results of NINDS t-PA stroke studies confirmed our previous conclusions on the treatment t-PA benefit within 3-h therapeutic window. No subgroup of patients would lead a physician to withhold the t-PA treatment.
KW - Cerebral ischemia
KW - Clinical trials
KW - Qualitative or quantitative interaction
KW - Subgroup analysis
KW - Treatment-by-risk factor interaction
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U2 - 10.1016/j.jneumeth.2004.10.002
DO - 10.1016/j.jneumeth.2004.10.002
M3 - Article
C2 - 15814153
AN - SCOPUS:16244373706
SN - 0165-0270
VL - 143
SP - 209
EP - 216
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
IS - 2
ER -