Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial: a randomised controlled trial

Melissa Pyle; John Norrie; Matthias Schwannauer; David Kingdon; Andrew Gumley; Douglas Turkington; Rory Byrne; Suzy Syrett; Graeme MacLennan; Robert Dudley; Hamish J. McLeod; Helen Griffiths; Samantha Bowe; Thomas R. E. Barnes; Paul French; Paul Hutton; Linda Davies; Anthony P. Morrison

doi:10.1186/s12888-016-0983-6

Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial: a randomised controlled trial

Melissa Pyle, John Norrie, Matthias Schwannauer, David Kingdon, Andrew Gumley, Douglas Turkington, Rory Byrne, Suzy Syrett, Graeme MacLennan, Robert Dudley, Hamish J. McLeod, Helen Griffiths, Samantha Bowe, Thomas R. E. Barnes, Paul French, Paul Hutton, Linda Davies, Anthony P. Morrison

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Abstract

BackgroundFor around a third of people with a diagnosis of schizophrenia, the condition proves to respond poorly to treatment with many typical and atypical antipsychotics. This is commonly referred to as treatment-resistant schizophrenia. Clozapine is the only antipsychotic with convincing efficacy for people whose symptoms are considered treatment-resistant to antipsychotic medication. However, 30–40 % of such conditions will have an insufficient response to the drug. Cognitive behavioural therapy has been shown to be an effective treatment for schizophrenia when delivered in combination with antipsychotic medication, with several meta-analyses showing robust support for this approach. However, the evidence for the effectiveness of cognitive behavioural therapy for people with a schizophrenia diagnosis whose symptoms are treatment-resistant to antipsychotic medication is limited. There is a clinical and economic need to evaluate treatments to improve outcomes for people with such conditions.
Methods/designA parallel group, prospective randomised, open, blinded evaluation of outcomes design will be used to compare a standardised cognitive behavioural therapy intervention added to treatment as usual versus treatment as usual alone (the comparator group) for individuals with a diagnosis of schizophrenia for whom an adequate trial of clozapine has either not been possible due to tolerability problems or was not associated with a sufficient therapeutic response. The trial will be conducted across five sites in the United Kingdom.
DiscussionThe recruitment target of 485 was achieved, with a final recruitment total of 487. This trial is the largest definitive, pragmatic clinical and cost-effectiveness trial of cognitive behavioural therapy for people with schizophrenia whose symptoms have failed to show an adequate response to clozapine treatment. Using a prognostic risk model, baseline information will be used to explore whether there are identifiable subgroups for which the treatment effect is greatest.
Trial registrationCurrent Controlled Trials ISRCTN99672552. Registered 29th November 2012.

Original language	English
Article number	280
Pages (from-to)	1-12
Number of pages	12
Journal	BMC Psychiatry
Volume	16
DOIs	https://doi.org/10.1186/s12888-016-0983-6
Publication status	Published - 5 Aug 2016

Bibliographical note

Acknowledgements
Thank you to all the participants who agreed to take part in the trial. This study was supported NHS Research Scotland (NRS), through Chief Scientist Office (CSO) and the Scottish Mental Health Research Network, and the Clinical Research Network-Mental Health. We are grateful to the Psychosis Research Unit (PRU) Service User Reference Group (SURG) for their consultation regarding the design of the study and contribution to the developments of study related materials. We are grateful to our Independent Trial Steering Committee and Independent Data Monitoring Committee for provided oversight of the trial.

Funding
This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme (project number10/101/02) and will be published in full in Health Technology Assessment. Visit the HTA programme website for further project information.
The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.

Keywords

Schizophrenia
Psychosis
Clozapine-resistant
Cognitive behavioural therapy
Randomised controlled trial

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Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial: a randomised controlled trial
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Cite this

Pyle, M., Norrie, J., Schwannauer, M., Kingdon, D., Gumley, A., Turkington, D., Byrne, R., Syrett, S., MacLennan, G., Dudley, R., McLeod, H. J., Griffiths, H., Bowe, S., Barnes, T. R. E., French, P., Hutton, P., Davies, L., & Morrison, A. P. (2016). Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial: a randomised controlled trial. BMC Psychiatry, 16, 1-12. [280]. https://doi.org/10.1186/s12888-016-0983-6

Pyle, M, Norrie, J, Schwannauer, M, Kingdon, D, Gumley, A, Turkington, D, Byrne, R, Syrett, S, MacLennan, G, Dudley, R, McLeod, HJ, Griffiths, H, Bowe, S, Barnes, TRE, French, P, Hutton, P, Davies, L & Morrison, AP 2016, 'Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial: a randomised controlled trial', BMC Psychiatry, vol. 16, 280, pp. 1-12. https://doi.org/10.1186/s12888-016-0983-6

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abstract = "BackgroundFor around a third of people with a diagnosis of schizophrenia, the condition proves to respond poorly to treatment with many typical and atypical antipsychotics. This is commonly referred to as treatment-resistant schizophrenia. Clozapine is the only antipsychotic with convincing efficacy for people whose symptoms are considered treatment-resistant to antipsychotic medication. However, 30–40 % of such conditions will have an insufficient response to the drug. Cognitive behavioural therapy has been shown to be an effective treatment for schizophrenia when delivered in combination with antipsychotic medication, with several meta-analyses showing robust support for this approach. However, the evidence for the effectiveness of cognitive behavioural therapy for people with a schizophrenia diagnosis whose symptoms are treatment-resistant to antipsychotic medication is limited. There is a clinical and economic need to evaluate treatments to improve outcomes for people with such conditions.Methods/designA parallel group, prospective randomised, open, blinded evaluation of outcomes design will be used to compare a standardised cognitive behavioural therapy intervention added to treatment as usual versus treatment as usual alone (the comparator group) for individuals with a diagnosis of schizophrenia for whom an adequate trial of clozapine has either not been possible due to tolerability problems or was not associated with a sufficient therapeutic response. The trial will be conducted across five sites in the United Kingdom.DiscussionThe recruitment target of 485 was achieved, with a final recruitment total of 487. This trial is the largest definitive, pragmatic clinical and cost-effectiveness trial of cognitive behavioural therapy for people with schizophrenia whose symptoms have failed to show an adequate response to clozapine treatment. Using a prognostic risk model, baseline information will be used to explore whether there are identifiable subgroups for which the treatment effect is greatest.Trial registrationCurrent Controlled Trials ISRCTN99672552. Registered 29th November 2012.",

keywords = "Schizophrenia, Psychosis, Clozapine-resistant, Cognitive behavioural therapy, Randomised controlled trial",

author = "Melissa Pyle and John Norrie and Matthias Schwannauer and David Kingdon and Andrew Gumley and Douglas Turkington and Rory Byrne and Suzy Syrett and Graeme MacLennan and Robert Dudley and McLeod, {Hamish J.} and Helen Griffiths and Samantha Bowe and Barnes, {Thomas R. E.} and Paul French and Paul Hutton and Linda Davies and Morrison, {Anthony P.}",

note = "Acknowledgements Thank you to all the participants who agreed to take part in the trial. This study was supported NHS Research Scotland (NRS), through Chief Scientist Office (CSO) and the Scottish Mental Health Research Network, and the Clinical Research Network-Mental Health. We are grateful to the Psychosis Research Unit (PRU) Service User Reference Group (SURG) for their consultation regarding the design of the study and contribution to the developments of study related materials. We are grateful to our Independent Trial Steering Committee and Independent Data Monitoring Committee for provided oversight of the trial. Funding This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme (project number10/101/02) and will be published in full in Health Technology Assessment. Visit the HTA programme website for further project information. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.",

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T1 - Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial

T2 - a randomised controlled trial

AU - Pyle, Melissa

AU - Norrie, John

AU - Schwannauer, Matthias

AU - Kingdon, David

AU - Gumley, Andrew

AU - Turkington, Douglas

AU - Byrne, Rory

AU - Syrett, Suzy

AU - MacLennan, Graeme

AU - Dudley, Robert

AU - McLeod, Hamish J.

AU - Griffiths, Helen

AU - Bowe, Samantha

AU - Barnes, Thomas R. E.

AU - French, Paul

AU - Hutton, Paul

AU - Davies, Linda

AU - Morrison, Anthony P.

N1 - Acknowledgements Thank you to all the participants who agreed to take part in the trial. This study was supported NHS Research Scotland (NRS), through Chief Scientist Office (CSO) and the Scottish Mental Health Research Network, and the Clinical Research Network-Mental Health. We are grateful to the Psychosis Research Unit (PRU) Service User Reference Group (SURG) for their consultation regarding the design of the study and contribution to the developments of study related materials. We are grateful to our Independent Trial Steering Committee and Independent Data Monitoring Committee for provided oversight of the trial. Funding This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme (project number10/101/02) and will be published in full in Health Technology Assessment. Visit the HTA programme website for further project information. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.

PY - 2016/8/5

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N2 - BackgroundFor around a third of people with a diagnosis of schizophrenia, the condition proves to respond poorly to treatment with many typical and atypical antipsychotics. This is commonly referred to as treatment-resistant schizophrenia. Clozapine is the only antipsychotic with convincing efficacy for people whose symptoms are considered treatment-resistant to antipsychotic medication. However, 30–40 % of such conditions will have an insufficient response to the drug. Cognitive behavioural therapy has been shown to be an effective treatment for schizophrenia when delivered in combination with antipsychotic medication, with several meta-analyses showing robust support for this approach. However, the evidence for the effectiveness of cognitive behavioural therapy for people with a schizophrenia diagnosis whose symptoms are treatment-resistant to antipsychotic medication is limited. There is a clinical and economic need to evaluate treatments to improve outcomes for people with such conditions.Methods/designA parallel group, prospective randomised, open, blinded evaluation of outcomes design will be used to compare a standardised cognitive behavioural therapy intervention added to treatment as usual versus treatment as usual alone (the comparator group) for individuals with a diagnosis of schizophrenia for whom an adequate trial of clozapine has either not been possible due to tolerability problems or was not associated with a sufficient therapeutic response. The trial will be conducted across five sites in the United Kingdom.DiscussionThe recruitment target of 485 was achieved, with a final recruitment total of 487. This trial is the largest definitive, pragmatic clinical and cost-effectiveness trial of cognitive behavioural therapy for people with schizophrenia whose symptoms have failed to show an adequate response to clozapine treatment. Using a prognostic risk model, baseline information will be used to explore whether there are identifiable subgroups for which the treatment effect is greatest.Trial registrationCurrent Controlled Trials ISRCTN99672552. Registered 29th November 2012.

AB - BackgroundFor around a third of people with a diagnosis of schizophrenia, the condition proves to respond poorly to treatment with many typical and atypical antipsychotics. This is commonly referred to as treatment-resistant schizophrenia. Clozapine is the only antipsychotic with convincing efficacy for people whose symptoms are considered treatment-resistant to antipsychotic medication. However, 30–40 % of such conditions will have an insufficient response to the drug. Cognitive behavioural therapy has been shown to be an effective treatment for schizophrenia when delivered in combination with antipsychotic medication, with several meta-analyses showing robust support for this approach. However, the evidence for the effectiveness of cognitive behavioural therapy for people with a schizophrenia diagnosis whose symptoms are treatment-resistant to antipsychotic medication is limited. There is a clinical and economic need to evaluate treatments to improve outcomes for people with such conditions.Methods/designA parallel group, prospective randomised, open, blinded evaluation of outcomes design will be used to compare a standardised cognitive behavioural therapy intervention added to treatment as usual versus treatment as usual alone (the comparator group) for individuals with a diagnosis of schizophrenia for whom an adequate trial of clozapine has either not been possible due to tolerability problems or was not associated with a sufficient therapeutic response. The trial will be conducted across five sites in the United Kingdom.DiscussionThe recruitment target of 485 was achieved, with a final recruitment total of 487. This trial is the largest definitive, pragmatic clinical and cost-effectiveness trial of cognitive behavioural therapy for people with schizophrenia whose symptoms have failed to show an adequate response to clozapine treatment. Using a prognostic risk model, baseline information will be used to explore whether there are identifiable subgroups for which the treatment effect is greatest.Trial registrationCurrent Controlled Trials ISRCTN99672552. Registered 29th November 2012.

KW - Schizophrenia

KW - Psychosis

KW - Clozapine-resistant

KW - Cognitive behavioural therapy

KW - Randomised controlled trial

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JO - BMC Psychiatry

JF - BMC Psychiatry

M1 - 280

ER -

Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial: a randomised controlled trial

Abstract

Bibliographical note

Keywords

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