Precision clinical trials: A framework for getting to precision medicine for neurobehavioural disorders

Eric J. Lenze; Ginger E. Nicol; Dennis L. Barbour; Thomas Kannampallil; Alex W.K. Wong; Jay Piccirillo; Andrew T. Drysdale; Chad M. Sylvester; Rita Haddad; J. Philip Miller; Carissa A. Low; Shannon N. Lenze; Kenneth E. Freedland; Thomas L. Rodebaugh

doi:10.1503/jpn.200042

Precision clinical trials: A framework for getting to precision medicine for neurobehavioural disorders

Eric J. Lenze^*, Ginger E. Nicol, Dennis L. Barbour, Thomas Kannampallil, Alex W.K. Wong, Jay Piccirillo, Andrew T. Drysdale, Chad M. Sylvester, Rita Haddad, J. Philip Miller, Carissa A. Low, Shannon N. Lenze, Kenneth E. Freedland, Thomas L. Rodebaugh

^*Corresponding author for this work

Physical Medicine and Rehabilitation

Research output: Contribution to journal › Review article › peer-review

26 Scopus citations

Abstract

The goal of precision medicine (individually tailored treatments) is not being achieved for neurobehavioural conditions such as psychiatric disorders. Traditional randomized clinical trial methods are insufficient for advancing precision medicine because of the dynamic complexity of these conditions. We present a pragmatic solution: the precision clinical trial framework, encompassing methods for individually tailored treatments. This framework includes the following: (1) treatment-targeted enrichment, which involves measuring patients’ response after a brief bout of an intervention, and then randomizing patients to a full course of treatment, using the acute response to predict long-term outcomes; (2) adaptive treatments, which involve adjusting treatment parameters during the trial to individually optimize the treat-ment; and (3) precise measurement, which involves measuring predictor and outcome variables with high accuracy and reliability using techniques such as ecological momentary assessment. This review summarizes precision clinical trials and provides a research agenda, including new biomarkers such as precision neuroimaging, transcranial magnetic stimulation–electroencephalogram digital phenotyping and advances in statistical and machine-learning models. Validation of these approaches — and then widespread incorporation of the precision clinical trial framework — could help achieve the vision of precision medicine for neurobehavioural conditions.

Original language	English (US)
Pages (from-to)	97-110
Number of pages	14
Journal	Journal of Psychiatry and Neuroscience
Volume	46
Issue number	1
DOIs	https://doi.org/10.1503/jpn.200042
State	Published - Jan 1 2021

Funding

Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Additional funding is from the Taylor Family Institute for Innovative Psychiatric Research and Center for Brain Research in Mood Disorders (at Washington University) to Dr. E. Lenze. The funding source(s) had no role in the preparation, review, or approval of the manuscript.

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1503/jpn.200042

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Lenze, E. J., Nicol, G. E., Barbour, D. L., Kannampallil, T., Wong, A. W. K., Piccirillo, J., Drysdale, A. T., Sylvester, C. M., Haddad, R., Miller, J. P., Low, C. A., Lenze, S. N., Freedland, K. E., & Rodebaugh, T. L. (2021). Precision clinical trials: A framework for getting to precision medicine for neurobehavioural disorders. Journal of Psychiatry and Neuroscience, 46(1), 97-110. https://doi.org/10.1503/jpn.200042

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abstract = "The goal of precision medicine (individually tailored treatments) is not being achieved for neurobehavioural conditions such as psychiatric disorders. Traditional randomized clinical trial methods are insufficient for advancing precision medicine because of the dynamic complexity of these conditions. We present a pragmatic solution: the precision clinical trial framework, encompassing methods for individually tailored treatments. This framework includes the following: (1) treatment-targeted enrichment, which involves measuring patients{\textquoteright} response after a brief bout of an intervention, and then randomizing patients to a full course of treatment, using the acute response to predict long-term outcomes; (2) adaptive treatments, which involve adjusting treatment parameters during the trial to individually optimize the treat-ment; and (3) precise measurement, which involves measuring predictor and outcome variables with high accuracy and reliability using techniques such as ecological momentary assessment. This review summarizes precision clinical trials and provides a research agenda, including new biomarkers such as precision neuroimaging, transcranial magnetic stimulation–electroencephalogram digital phenotyping and advances in statistical and machine-learning models. Validation of these approaches — and then widespread incorporation of the precision clinical trial framework — could help achieve the vision of precision medicine for neurobehavioural conditions.",

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note = "Funding Information: Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Additional funding is from the Taylor Family Institute for Innovative Psychiatric Research and Center for Brain Research in Mood Disorders (at Washington University) to Dr. E. Lenze. The funding source(s) had no role in the preparation, review, or approval of the manuscript. Publisher Copyright: {\textcopyright} 2021 Joule Inc. or its licensors.",

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Lenze, EJ, Nicol, GE, Barbour, DL, Kannampallil, T, Wong, AWK, Piccirillo, J, Drysdale, AT, Sylvester, CM, Haddad, R, Miller, JP, Low, CA, Lenze, SN, Freedland, KE & Rodebaugh, TL 2021, 'Precision clinical trials: A framework for getting to precision medicine for neurobehavioural disorders', Journal of Psychiatry and Neuroscience, vol. 46, no. 1, pp. 97-110. https://doi.org/10.1503/jpn.200042

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N2 - The goal of precision medicine (individually tailored treatments) is not being achieved for neurobehavioural conditions such as psychiatric disorders. Traditional randomized clinical trial methods are insufficient for advancing precision medicine because of the dynamic complexity of these conditions. We present a pragmatic solution: the precision clinical trial framework, encompassing methods for individually tailored treatments. This framework includes the following: (1) treatment-targeted enrichment, which involves measuring patients’ response after a brief bout of an intervention, and then randomizing patients to a full course of treatment, using the acute response to predict long-term outcomes; (2) adaptive treatments, which involve adjusting treatment parameters during the trial to individually optimize the treat-ment; and (3) precise measurement, which involves measuring predictor and outcome variables with high accuracy and reliability using techniques such as ecological momentary assessment. This review summarizes precision clinical trials and provides a research agenda, including new biomarkers such as precision neuroimaging, transcranial magnetic stimulation–electroencephalogram digital phenotyping and advances in statistical and machine-learning models. Validation of these approaches — and then widespread incorporation of the precision clinical trial framework — could help achieve the vision of precision medicine for neurobehavioural conditions.

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Precision clinical trials: A framework for getting to precision medicine for neurobehavioural disorders

Abstract

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ASJC Scopus subject areas

UN SDGs

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