Studying Neurosurgical Implants for Parkinson Disease: a Question of Design

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Studying Neurosurgical Implants for Parkinson Disease: A Question of Design

1MinnesotaCenter for Health Care Ethics, Minneapolis

2St. OlafCollege, Northfield, Minnesota

3University of South Florida, Tampa

Appendix E-1. Researchers’ Assessments of Surgical StudyDesigns for Deep Brain Stimulation (DBS) and Cellular Implants for Parkinson Disease (PD)

Feasible and Appropriate

A.Placebo-surgery–controlled trials of cellular implants

Feasible to blind to implantation

Scientifically appropriate, because responses to cellular implants are plausibly placebo responses

Ethically appropriate because study risks can be reasonable in light of benefits and subjects can be adequately respected and protected

B. Randomized, blinded trials of DBS in alternative targets in the brain

C. Randomized trials of DBS vs. best medical therapy with delayed surgery

D. Other controlled studies of DBS, with outcomes assessed by independent, blinded evaluators

Feasible, but Ethical Appropriateness Uncertain

A. Randomized trials of immediate vs. delayed stimulation after DBS implant

Ethical appropriateness of delayed stimulation disputed

B. Studies of DBS for early-stage PD

Ethical appropriateness of risks and benefits disputed, given variability of disease progression and availability of satisfactory treatments

C. Case series with randomization to DBS evaluation conditions (medication on/off and stimulation on/off)

Ethical appropriateness of subjects’ discomfort during the medication-off/simulation-off condition disputed

Appendix E-1, continued.

Infeasible and Inappropriate

A. Placebo-surgery–controlled trials of DBS

Infeasible to blind subjects to device implantation

Scientifically inappropriate, because magnitude and immediacy of responses to DBS are unlikely to be placebo responses

Ethically inappropriate because study risks are unreasonable in light of benefits and subjects cannot be adequately respected and protected

Placebo-surgery arm is unacceptably grueling as surgery is lengthy and subjects are awake
Placebo-surgery arm requires extensive active deception of subjects

B. Randomized blinded trials of DBS vs. best medical therapy

Infeasible to successfully recruit and retain subjects given magnitude and immediacy of responses to DBS

Infeasible to blind awake subjects to device implantation

Infeasible to blind subjects to stimulation because of transient sensory phenomena

C. Randomized, non-blinded trials of DBS vs. best medical therapy

Infeasible to successfully recruit and retain subjects given magnitude and immediacy of responses to DBS

D. Randomized, double-blind evaluations of DBS stimulation on/off

Infeasible (or at least difficult) to blind subjects and evaluators to stimulation changes because of transient sensory phenomena

Ethically inappropriate given subjects’ discomfort with medication-off, stimulation-off condition

Prehn Appendix (E) A-1 Researchers Assessments of Study Designs Supported by NINDS Grant #NS40883 1