The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Implications of Heterogeneity of Treatment Effect for Reporting and Analysis of Randomized Trials in Critical Care
Open accessAbstract
Randomized clinical trials (RCTs) are conducted to guide clinicians' selection of therapies for individual patients. Currently, RCTs in critical care often report an overall mean effect and selected individual subgroups. Yet work in other fields suggests that such reporting practices can be improved. Specifically, this Critical Care Perspective reviews recent work on so-called "heterogeneity of treatment effect" (HTE) by baseline risk and extends that work to examine its applicability to trials of acute respiratory failure and severe sepsis. Because patients in RCTs in critical care medicine-and patients in intensive care units-have wide variability in their risk of death, these patients will have wide variability in the absolute benefit that they can derive from a given therapy. If the side effects of the therapy are not perfectly collinear with the treatment benefits, this will result in HTE, where different patients experience quite different expected benefits of a therapy. We use simulations of RCTs to demonstrate that such HTE could result in apparent paradoxes, including: (1) positive trials of therapies that are beneficial overall but consistently harm or have little benefit to low-risk patients who met enrollment criteria, and (2) overall negative trials of therapies that still consistently benefit high-risk patients. We further show that these results persist even in the presence of causes of death unmodified by the treatment under study. These results have implications for reporting and analyzing RCT data, both to better understand how our therapies work and to improve the bedside applicability of RCTs. We suggest a plan for measurement in future RCTs in the critically ill.
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Cited by
Famous, K. R., Delucchi, K., Ware, L. B., Kangelaris, K. N., Liu, K. D., Thompson, B. T., & Calfee, C. S. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201603-0645oc · Cited by 820
Clinical trials in acute respiratory distress syndrome: challenges and opportunities
Matthay, M. A., McAuley, D. F., & Ware, L. B. (2017) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(17)30188-1 · Cited by 284
Moskowitz, A., Huang, D. T., Hou, P. C., Gong, J., Doshi, P. B., Grossestreuer, A. V., Andersen, L. W., Ngo, L., Sherwin, R. L., Berg, K. M., et al. (2020) · JAMA · doi:10.1001/jama.2020.11946 · Cited by 253
Balanced crystalloids versus saline in the intensive care unit. The SALT randomized trial.
Semler, M. W., Wanderer, J. P., Ehrenfeld, J. M., Stollings, J. L., Self, W. H., Siew, E. D., Wang, L., Byrne, D. W., Shaw, A. D., Bernard, G. R., et al. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201607-1345oc · Cited by 249
Wade, D. M., Mouncey, P. R., Richards-Belle, A., Wulff, J., Harrison, D. A., Sadique, M. Z., Grieve, R. D., Emerson, L. M., Mason, A. J., Aaronovitch, D., et al. (2019) · JAMA · doi:10.1001/jama.2019.0073 · Cited by 124
Metadata
- Authors
- Iwashyna, T. J., Burke, J. F., Sussman, J. B., Prescott, H. C., Hayward, R. A., & Angus, D. C.
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-11-01
- Volume
- 192
- Issue
- 9
- Pages
- 1045-1051
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W1924238075
- Cited by
- 276
- References
- 25
- FWCI
- 18.69
- Type
- journal article
- Language
- en
- Open access
- green
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- Iwashyna, T. J., Burke, J. F., Sussman, J. B., Prescott, H. C., Hayward, R. A., & Angus, D. C. (2015). Implications of Heterogeneity of Treatment Effect for Reporting and Analysis of Randomized Trials in Critical Care. American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.201411-2125cp
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