- Email: [email protected]
Deep brain stimulation in early stage Parkinson's disease may reduce the relative risk of symptom worsening
Parkinsonism and Related Disorders 22 (2016) 112e113
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Correspondence
Deep brain stimulation in early stage Parkinson's disease may reduce the relative risk of symptom worsening
Keywords: Parkinson's disease Deep brain stimulation Subthalamic nucleus
To the editor, We thank the authors of this letter for their interest in the new findings from our study of deep brain stimulation (DBS) in early stage Parkinson's disease (PD). We agree that there is increasing off-label use of DBS in early stage PD, with anecdotes of success being recorded. It is important to note, however, that the Vanderbilt pilot trial does not establish the safety of DBS therapy in early stage Parkinson's disease. The U.S. Food and Drug Administration (FDA) limited the pilot study to 30 subjects (with 15 randomized to receive DBS). The safety of DBS in early stage PD can only be established in a phase III trial with a much larger cohort of participants. While the authors are correct that this manuscript does not discuss the surgical risks of DBS in early stage PD, our team has previously reported in detail the adverse events from the pilot trial, including perioperative adverse events [1,2]. There were four out of fifteen subjects in the DBS group who experienced clinically important worsening (27%), including the two subjects who experienced surgical or device-related adverse events. Therefore, the rates of clinically important worsening we report for the full cohort of the Vanderbilt pilot trial did include these two subjects. Comparatively, 54% of the optimal drug therapy group experienced clinically important worsening (7 out of 13). Overall, our results show that DBS in early stage Parkinson's disease imparts a 50% reduction in the relative risk of worsening when compared to medical therapy. This line of research has received some harsh criticism in the past centered on the ethics of offering a surgical intervention (and its associated risk) to research participants with early stage Parkinson's disease. Physicians and scientists expert in the field of Parkinson's disease can respectfully disagree on this issue. We are quite sensitive to the ethical issues raised, and it is for this reason that from the earliest stages of our pilot study we have striven to address such concerns. Most significantly, biomedical ethicists were actively engaged in the http://dx.doi.org/10.1016/j.parkreldis.2015.11.023 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
design and implementation of an expanded informed consent process for the pilot trial. It emphasized both the importance of patient self-determination in making sensitive choices of this type and also allowed us to learn from potential participants how they understood the risks facing them should they enroll in the pilot [3,4]. It is important to note, moreover, that the pilot trial had a 97% retention rate over five years of clinical investigation, which we believe is in large part due to the expanded informed consent process [5]. We are strongly committed to having biomedical ethicists engaged throughout the informed consent process of our future clinical trial testing DBS in early stage Parkinson's disease. The FDA places the safety of clinical trial participants as paramount and has approved the conduct of a prospective phase III, pivotal, double-blind, placebo-controlled clinical trial testing deep brain stimulation in participants with early stage Parkinson's disease. This trial has the possibility to demonstrate that DBS in early stage Parkinson's disease may offer better management of PD motor features, reduce the development of medicationassociated complications, and provide a better quality of life. The following sites have completed all of the necessary materials to join an application to form a consortium of centers committed to carrying out this trial: Beth Israel Deaconess Medical Center, Case Western Reserve University, Duke University, Emory University, Mayo Clinic Rochester, Michigan State University, Northwestern University, Stanford University, The Ohio State University, University of California, Los Angeles, University of California, San Francisco, University of Cincinnati, University of Colorado Denver, University of Florida, University of Michigan, University of Minnesota, University of Utah, and Vanderbilt University.
References [1] D. Charles, P.E. Konrad, J.S. Neimat, A.L. Molinari, M.G. Tramontana, S.G. Finder, et al., Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease, Park. Relat. Disord. 20 (7) (2014) 731. [2] E. Kahn, P.F. D'Haese, B. Dawant, L. Allen, C. Kao, P.D. Charles, et al., Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial, J. Neurol. Neurosurg. Psychiatry 83 (2) (2011) 164. [3] S.G. Finder, M.J. Bliton, C.E. Gill, T.L. Davis, P.E. Konrad, P.D. Charles, Potential subjects' responses to an ethics questionnaire in a phase 1 study of deepbrain stimulation in early Parkinson's disease, J. Clin. Ethics 23 (3) (2012) 193e202. [4] S.G. Finder, M.J. Bliton, Fortitude and Community: Response to Yee and Ford, 2012, 1pp. [5] P.D. Charles, R.M. Dolhun, C.E. Gill, T.L. Davis, M.J. Bliton, M.G. Tramontana, et al., Deep brain stimulation in early Parkinson's disease: enrollment experience from a pilot trial, Park. Relat. Disord. 18 (3) (2012) 268.
Correspondence / Parkinsonism and Related Disorders 22 (2016) 112e113
Mallory Hacker*, David Charles Department of Neurology, Vanderbilt University, Nashville, TN 37212, United States Stuart Finder Center for Healthcare Ethics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
113
* Corresponding author. E-mail address: [email protected] (M. Hacker).
13 November 2015
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Correspondence
Deep brain stimulation in early stage Parkinson's disease may reduce the relative risk of symptom worsening
Keywords: Parkinson's disease Deep brain stimulation Subthalamic nucleus
To the editor, We thank the authors of this letter for their interest in the new findings from our study of deep brain stimulation (DBS) in early stage Parkinson's disease (PD). We agree that there is increasing off-label use of DBS in early stage PD, with anecdotes of success being recorded. It is important to note, however, that the Vanderbilt pilot trial does not establish the safety of DBS therapy in early stage Parkinson's disease. The U.S. Food and Drug Administration (FDA) limited the pilot study to 30 subjects (with 15 randomized to receive DBS). The safety of DBS in early stage PD can only be established in a phase III trial with a much larger cohort of participants. While the authors are correct that this manuscript does not discuss the surgical risks of DBS in early stage PD, our team has previously reported in detail the adverse events from the pilot trial, including perioperative adverse events [1,2]. There were four out of fifteen subjects in the DBS group who experienced clinically important worsening (27%), including the two subjects who experienced surgical or device-related adverse events. Therefore, the rates of clinically important worsening we report for the full cohort of the Vanderbilt pilot trial did include these two subjects. Comparatively, 54% of the optimal drug therapy group experienced clinically important worsening (7 out of 13). Overall, our results show that DBS in early stage Parkinson's disease imparts a 50% reduction in the relative risk of worsening when compared to medical therapy. This line of research has received some harsh criticism in the past centered on the ethics of offering a surgical intervention (and its associated risk) to research participants with early stage Parkinson's disease. Physicians and scientists expert in the field of Parkinson's disease can respectfully disagree on this issue. We are quite sensitive to the ethical issues raised, and it is for this reason that from the earliest stages of our pilot study we have striven to address such concerns. Most significantly, biomedical ethicists were actively engaged in the http://dx.doi.org/10.1016/j.parkreldis.2015.11.023 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
design and implementation of an expanded informed consent process for the pilot trial. It emphasized both the importance of patient self-determination in making sensitive choices of this type and also allowed us to learn from potential participants how they understood the risks facing them should they enroll in the pilot [3,4]. It is important to note, moreover, that the pilot trial had a 97% retention rate over five years of clinical investigation, which we believe is in large part due to the expanded informed consent process [5]. We are strongly committed to having biomedical ethicists engaged throughout the informed consent process of our future clinical trial testing DBS in early stage Parkinson's disease. The FDA places the safety of clinical trial participants as paramount and has approved the conduct of a prospective phase III, pivotal, double-blind, placebo-controlled clinical trial testing deep brain stimulation in participants with early stage Parkinson's disease. This trial has the possibility to demonstrate that DBS in early stage Parkinson's disease may offer better management of PD motor features, reduce the development of medicationassociated complications, and provide a better quality of life. The following sites have completed all of the necessary materials to join an application to form a consortium of centers committed to carrying out this trial: Beth Israel Deaconess Medical Center, Case Western Reserve University, Duke University, Emory University, Mayo Clinic Rochester, Michigan State University, Northwestern University, Stanford University, The Ohio State University, University of California, Los Angeles, University of California, San Francisco, University of Cincinnati, University of Colorado Denver, University of Florida, University of Michigan, University of Minnesota, University of Utah, and Vanderbilt University.
References [1] D. Charles, P.E. Konrad, J.S. Neimat, A.L. Molinari, M.G. Tramontana, S.G. Finder, et al., Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease, Park. Relat. Disord. 20 (7) (2014) 731. [2] E. Kahn, P.F. D'Haese, B. Dawant, L. Allen, C. Kao, P.D. Charles, et al., Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial, J. Neurol. Neurosurg. Psychiatry 83 (2) (2011) 164. [3] S.G. Finder, M.J. Bliton, C.E. Gill, T.L. Davis, P.E. Konrad, P.D. Charles, Potential subjects' responses to an ethics questionnaire in a phase 1 study of deepbrain stimulation in early Parkinson's disease, J. Clin. Ethics 23 (3) (2012) 193e202. [4] S.G. Finder, M.J. Bliton, Fortitude and Community: Response to Yee and Ford, 2012, 1pp. [5] P.D. Charles, R.M. Dolhun, C.E. Gill, T.L. Davis, M.J. Bliton, M.G. Tramontana, et al., Deep brain stimulation in early Parkinson's disease: enrollment experience from a pilot trial, Park. Relat. Disord. 18 (3) (2012) 268.
Correspondence / Parkinsonism and Related Disorders 22 (2016) 112e113
Mallory Hacker*, David Charles Department of Neurology, Vanderbilt University, Nashville, TN 37212, United States Stuart Finder Center for Healthcare Ethics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
113
* Corresponding author. E-mail address: [email protected] (M. Hacker).
13 November 2015