Implementing novel trial methods to evaluate surgery for essential tremor

Jonathan A. Hyam, Erlick A C Pereira, Peter McCulloch, Shazia Javed, Puneet Plaha, Lucy Mooney, Beth A. Forrow, Carole Joint, Alan Whone, Steven Gill, Paul Glasziou, Tipu Z. Aziz, Alexander L. Green

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Abstract

Introduction. Deep brain stimulation (DBS) can provide dramatic essential tremor (ET) relief, however no Class I evidence exists. Materials and methods. Analysis methods: I) traditional cohort analysis; II) N-of-1 single patient randomised control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET patients were switched on and off for 3-min periods. Six pairs of on and off periods in each case, with the pair order determined randomly. Tremor severity was quantified with tremor evaluator and patient was blinded to stimulation. Patients also stated whether they perceived the stimulation to be on after each trial. Results. I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off, t = - 13.218, p < 0·0005. II) N-of-1: 60% of cases had 12 correct perceptions (p = 0·001), 20% had 11 correct perceptions (p = 0·013). III) S/N: > 80% tremor reduction occurred in 99/114 'On' trials (87%), and 3/114 'Off' trials (3%). S/N ratio for 80% improvement with DBS versus spontaneous improvement was 487,757-to-1. Conclusions. DBS treatment effect on ET is too large for bias to be a plausible explanation. Formal N-of-1 trial design, and S/N ratio method for presenting results, allows this to be demonstrated convincingly where conventional randomised controlled trials are not possible. Classification of evidence. This study is the first to provide Class I evidence for the efficacy of DBS for ET.

Original languageEnglish
Pages (from-to)334-339
Number of pages6
JournalBritish Journal of Neurosurgery
Volume29
Issue number3
DOIs
Publication statusPublished - 1 Jun 2015
Externally publishedYes

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Essential Tremor
Deep Brain Stimulation
Tremor
Signal-To-Noise Ratio
Noise
Electrodes
Cohort Studies
Randomized Controlled Trials

Cite this

Hyam, J. A., Pereira, E. A. C., McCulloch, P., Javed, S., Plaha, P., Mooney, L., ... Green, A. L. (2015). Implementing novel trial methods to evaluate surgery for essential tremor. British Journal of Neurosurgery, 29(3), 334-339. https://doi.org/10.3109/02688697.2014.997670
Hyam, Jonathan A. ; Pereira, Erlick A C ; McCulloch, Peter ; Javed, Shazia ; Plaha, Puneet ; Mooney, Lucy ; Forrow, Beth A. ; Joint, Carole ; Whone, Alan ; Gill, Steven ; Glasziou, Paul ; Aziz, Tipu Z. ; Green, Alexander L. / Implementing novel trial methods to evaluate surgery for essential tremor. In: British Journal of Neurosurgery. 2015 ; Vol. 29, No. 3. pp. 334-339.
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abstract = "Introduction. Deep brain stimulation (DBS) can provide dramatic essential tremor (ET) relief, however no Class I evidence exists. Materials and methods. Analysis methods: I) traditional cohort analysis; II) N-of-1 single patient randomised control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET patients were switched on and off for 3-min periods. Six pairs of on and off periods in each case, with the pair order determined randomly. Tremor severity was quantified with tremor evaluator and patient was blinded to stimulation. Patients also stated whether they perceived the stimulation to be on after each trial. Results. I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off, t = - 13.218, p < 0·0005. II) N-of-1: 60{\%} of cases had 12 correct perceptions (p = 0·001), 20{\%} had 11 correct perceptions (p = 0·013). III) S/N: > 80{\%} tremor reduction occurred in 99/114 'On' trials (87{\%}), and 3/114 'Off' trials (3{\%}). S/N ratio for 80{\%} improvement with DBS versus spontaneous improvement was 487,757-to-1. Conclusions. DBS treatment effect on ET is too large for bias to be a plausible explanation. Formal N-of-1 trial design, and S/N ratio method for presenting results, allows this to be demonstrated convincingly where conventional randomised controlled trials are not possible. Classification of evidence. This study is the first to provide Class I evidence for the efficacy of DBS for ET.",
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Hyam, JA, Pereira, EAC, McCulloch, P, Javed, S, Plaha, P, Mooney, L, Forrow, BA, Joint, C, Whone, A, Gill, S, Glasziou, P, Aziz, TZ & Green, AL 2015, 'Implementing novel trial methods to evaluate surgery for essential tremor' British Journal of Neurosurgery, vol. 29, no. 3, pp. 334-339. https://doi.org/10.3109/02688697.2014.997670

Implementing novel trial methods to evaluate surgery for essential tremor. / Hyam, Jonathan A.; Pereira, Erlick A C; McCulloch, Peter; Javed, Shazia; Plaha, Puneet; Mooney, Lucy; Forrow, Beth A.; Joint, Carole; Whone, Alan; Gill, Steven; Glasziou, Paul; Aziz, Tipu Z.; Green, Alexander L.

In: British Journal of Neurosurgery, Vol. 29, No. 3, 01.06.2015, p. 334-339.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Implementing novel trial methods to evaluate surgery for essential tremor

AU - Hyam, Jonathan A.

AU - Pereira, Erlick A C

AU - McCulloch, Peter

AU - Javed, Shazia

AU - Plaha, Puneet

AU - Mooney, Lucy

AU - Forrow, Beth A.

AU - Joint, Carole

AU - Whone, Alan

AU - Gill, Steven

AU - Glasziou, Paul

AU - Aziz, Tipu Z.

AU - Green, Alexander L.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Introduction. Deep brain stimulation (DBS) can provide dramatic essential tremor (ET) relief, however no Class I evidence exists. Materials and methods. Analysis methods: I) traditional cohort analysis; II) N-of-1 single patient randomised control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET patients were switched on and off for 3-min periods. Six pairs of on and off periods in each case, with the pair order determined randomly. Tremor severity was quantified with tremor evaluator and patient was blinded to stimulation. Patients also stated whether they perceived the stimulation to be on after each trial. Results. I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off, t = - 13.218, p < 0·0005. II) N-of-1: 60% of cases had 12 correct perceptions (p = 0·001), 20% had 11 correct perceptions (p = 0·013). III) S/N: > 80% tremor reduction occurred in 99/114 'On' trials (87%), and 3/114 'Off' trials (3%). S/N ratio for 80% improvement with DBS versus spontaneous improvement was 487,757-to-1. Conclusions. DBS treatment effect on ET is too large for bias to be a plausible explanation. Formal N-of-1 trial design, and S/N ratio method for presenting results, allows this to be demonstrated convincingly where conventional randomised controlled trials are not possible. Classification of evidence. This study is the first to provide Class I evidence for the efficacy of DBS for ET.

AB - Introduction. Deep brain stimulation (DBS) can provide dramatic essential tremor (ET) relief, however no Class I evidence exists. Materials and methods. Analysis methods: I) traditional cohort analysis; II) N-of-1 single patient randomised control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET patients were switched on and off for 3-min periods. Six pairs of on and off periods in each case, with the pair order determined randomly. Tremor severity was quantified with tremor evaluator and patient was blinded to stimulation. Patients also stated whether they perceived the stimulation to be on after each trial. Results. I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off, t = - 13.218, p < 0·0005. II) N-of-1: 60% of cases had 12 correct perceptions (p = 0·001), 20% had 11 correct perceptions (p = 0·013). III) S/N: > 80% tremor reduction occurred in 99/114 'On' trials (87%), and 3/114 'Off' trials (3%). S/N ratio for 80% improvement with DBS versus spontaneous improvement was 487,757-to-1. Conclusions. DBS treatment effect on ET is too large for bias to be a plausible explanation. Formal N-of-1 trial design, and S/N ratio method for presenting results, allows this to be demonstrated convincingly where conventional randomised controlled trials are not possible. Classification of evidence. This study is the first to provide Class I evidence for the efficacy of DBS for ET.

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Hyam JA, Pereira EAC, McCulloch P, Javed S, Plaha P, Mooney L et al. Implementing novel trial methods to evaluate surgery for essential tremor. British Journal of Neurosurgery. 2015 Jun 1;29(3):334-339. https://doi.org/10.3109/02688697.2014.997670