Microelectrodes in Epilepsy
Phase: NA
Conditions: Epilepsy
Sponsor: Dartmouth-Hitchcock Medical Center

Official Title: 
Microelectrodes in Epilepsy 
NCT number: 
Document Type: 
Study Plan (including statistical analysis plan)
Date of the 
Document: 
03/20/2020 Version Date 
06/22/2020 IRB updates finalized 
NCT05200455

CPHS Template v. 5.13.2009 
Study Plan v30Mar2020; D-HH#21933 
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Instructions: 
The following information in the format provided below is an application for Dartmouth-Hitchcock Health review. Read 
through each section and respond to each item (even if to indicate NA - not applicable). Please also review the 
CHECKLIST for Full Committee Submission. We have provided some guidance information under each question. 
 
Please define all acronyms at first use and attach a glossary if more than 3 acronyms are used in this application. 
 
When revising a D-HH reviewed Study Plan for further review, please track the changes. To turn on tracking in this 
document in Microsoft Word: 
1) Display the forms and reviewing toolbars. 
2) Unlock the form by clicking on the lock icon on the forms toolbar. 
3) Turn on change tracking by clicking the icon on the reviewing toolbar. 
4) Lock the form by clicking again on the lock icon on the forms toolbar. 
 
Attachments: 
Complete and submit Attachment(s) if applicable to the research study. 
Attachments may be downloaded from this webpage: http://www.dartmouth.edu/~cphs/tosubmit/forms/StudyPlanAttach 
Attachment A: Nonsignificant Risk Devices 
Attachment B: Placebo 
Attachment C: Genetic Research 
Attachment D: Employees and Students 
Attachment E: Illiterate Participants 
Attachment F: Research Involving Children 
Attachment G: Research Involving Individuals With Impaired Decision-Making Capacity 
(formerly referred to as incompetent) 
Attachment H: Request for Waiver of Participant Consent 
Attachment I: Request for Waiver of Participant Signed Consent Form 
Attachment J: Drugs or Biologics 
Attachment L: International Research 
Attachment M: Pregnant Women, Fetuses and Neonates 
================================================================== 
 
Local Principal Investigator: 
Department:   Neurology 
 
Study Title: Microelectrodes in Epilepsy 
Funding Source (Sponsor):   Department of Neurology Funds 
 
D-HH Study Plan Version Date: 
 
 
1.Abstract. 
Provide an abstract of the proposed research in language that can be understood by a non-scientist. 
The abstract should summarize the objectives of this project and the procedures to be used, with an 
emphasis on what will happen to the subjects. (Maximum 250 words) 
Dartmouth College and Dartmouth-Hitchcock Medical Center 
Committee for the Protection of Human Subjects 
CPHS Study Plan for Full Committee Review 
Template v. 5.13.2009 
Barbara Jobst, MD 
30Mar2020 

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2.Objectives & Hypotheses: 
List your research objectives and hypotheses. 
 
 
 
 
 
3.Introduction: 
a) Explain the background of this project so that we will understand why it is important to perform this 
research project. b) Summarize previously published data and pilot studies. Be sure to include a 
discussion of any data that do not support the study hypothesis. If a study similar to the one being 
proposed has already been completed, explain why the proposed study is necessary. c) For studies 
designed to compare or evaluate therapies, there should be a statement of the relative advantages or 
disadvantages of alternative modes of therapy. d) If not obvious, explain why human subjects are 
necessary. Include references for all published data cited. If a formal protocol for the study exists, page 
references to the protocol are acceptable. 
 
 
The standard-of-care for medically refractory epilepsy is resective brain surgery. In certain patients, 
precise localization of the epileptic focus is done using intracranial EEG (iEEG) recording. In this type 
of EEG recording, electrodes are placed on the brain surface or inserted into the brain through an 
opening in the skull.  In addition to standard electrode recording, several epilepsy centers have 
independently developed ultra thin microelectrode technology. Microelectrodes are only several 
micrometers thick and are uniquely useful because they are able to record the activity of single neurons 
in isolation. Such recording has tremendous clinical potential in epilepsy surgery and tremendous 
research potential in cognitive neuroscience. This IRB study plan outlines our clinical and research 
interests in the use of FDA approved, commercially available, dual macro-micro electrode system in 
patients who require intracranial EEG recording prior to epilepsy surgery. 
We have two fundamental objectives and hypotheses. Our first objective is to investigate the usefulness 
of microelectrode technology in epilepsy surgery. We hypothesize that microelectrode recording will 
provide unique and novel information on the specific epileptic potential of the implanted brain tissue. 
Our long-term aim is to improve our paradigms for epilepsy surgery.  Our second objective is to 
investigate the activity of single neurons during specific cognitive tasks. We hypothesize that such 
analysis will help to predict possible cognitive deficits of epilepsy surgery and provide unique insight 
into the fundamental mechanisms of cognition and behavior. 
Patients who have recurrent unprovoked seizures despite adequate treatment with antiepileptic
medications have medically refractory epilepsy (1). This condition affects approximately 30% of all
patients diagnosed with focal epilepsy in the United States. The standard of care for this group of 
patients is referral for epilepsy surgery. Epilepsy surgery has been well demonstrated to be an effective
treatment option for these patients with high seizure freedom rates and low morbidity in properly 
selected patients (2). Each patient referred for epilepsy surgery undergoes a pre-surgical evaluation with 
a goal of precise localization of the epileptogenic region and determining the probable cognitive and 
functional morbidity for the surgery. The pre-surgical evaluation frequently requires the recording of 
seizures using intracranial EEG (iEEG). In this technique, specially designed electrodes are surgically 
implanted into target regions of the patient's brain by a trained neurosurgeon and epileptiform activity is 
recorded. IEEG recording has a long track record of being an effective method of seizure localization 
(3) with a complication rate of 2-4% (4,5). This method has been used successfully at the DHMC 

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Epilepsy Center on hundreds of patients since 1992. The recording of iEEG for conventional clinical 
applications is done using a standard macroelectrode system. A macroelectrode is either a soft plastic 
strip with multiple 5 mm disc electrodes or a rigid 10 cm needle electrode with multiple contacts along 
its length. Macroelectrodes are designed to record the summated activity of relatively large groups of 
neurons located in the vicinity of the electrode contact. Although macroelectrode iEEG recording is the 
mainstay of surgical epilepsy with established clinical indications, significant limitations are known. 
 
Currently, several well-established epilepsy centers in the United States (for instance, UCLA and Mayo 
Clinic) are investigating the use of microelectrode systems in epilepsy surgery to supplement the  
standard macroelectrode recording.  Microelectrodes are ultra thin filament electrodes with tip diameters 
of 3 to 10 micrometers which are able to record the activity of small groups or even single neurons, i.e. 
single unit potential recording. Supplementary microelectrode recordings are obtained using 
commercially available, FDA-approved, dual macro-micro electrode systems. These dual systems do   
not require the insertion of separate and additional microelectrode catheters but use the standard iEEG 
electrode to deliver the microelectrodes to the target brain regions. The major benefit of this novel design 
is that the rate of complications from such dual electrode systems is the same and for the standard     
iEEG electrodes. 
 
The primary aim of supplementing standard iEEG recording with single unit recording is to obtain 
additional information about the epileptogenic potential of the brain region that is implanted. Initial 
research in this area was done in the 1980’s at UCLA Medical Center where microelectrode recordings of 
epileptogenic brain tissue showed anomalous bursting patterns, coupled neuronal firing, and increased 
local inhibition (6, 7). At the same center in the 1990’s high frequency oscillations called fast ripples 
were recorded in patients undergoing pre-surgical evaluation (8, 9) and Braquin et al Annals of 
Neurology 2002). Fast ripples are ultra-fast neuronal oscillations in the 80 to 1000 Hz range which have 
been proposed to be the exclusive signatures of epileptogenic cortex (10). Most recently, dual macro- 
micro system to record fast ripples and determined that they frequently appeared in the microelectrode 
recording and were not apparent in the standard macroelectrode recording (11). These findings suggest 
that fast ripples are generated by microscopic neuronal structures which are frequently too small to be 
recorded using the standard macroelectrode system. Therefore, single unit recording may offer clinically 
relevant information for epilepsy surgery. 
 
A second yet no less important aim of recording single unit potentials is to gain better understanding of 
the role of the epileptogenic cortex in cognitive function. Once localization of epileptogenic cortex is 
established, the functional role of this cortex and possible cognitive deficits following resection must be 
established.  Present paradigms require assessment of cognitive function during the electrical 
stimulation of macroelectrode contacts which can establish the eloquence of the underlying cortex. 
Recording of single unit potentials with microelectrodes during specifically designed neuropsychological 
tasks may offer unique insight into the function of epileptogenic cortex. For example, studies done at 
UCLA Medical Center have shown that the recording of single unit potentials during specific memory 
tasks has provided relevant information regarding the functional state of the hippocampus (12). 
Therefore, recording of single unit potential during specific cognitive tasks may provide important 
information on the functional integrity of the region of the brain where resection is planned. 
 
A third aim of recording single unit potentials is to investigate the activity of single neurons during 
specific cognitive tasks. For instance, single unit recording from the hippocampus using the dual macro- 
micro electrode system during specific cognitive tasks has generated a novel insight into the organization 
of the human semantic memory system (13). Currently, patients at DHMC undergoing iEEG recording 

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may have depth electrodes in the orbitofrontal region, the insula, the amygdala, and the hippocampus. 
Investigation of single unit activity in these patients during performance of specific tasks may generate 
unique and novel insight into the function of these brain regions in behavior. For instance, investigation 
of the role of mirror neurons in social behavior may be done by recording the activity of insular neurons 
during observation of facial expression. Furthermore, single unit activity in the orbitofrontal region 
during Go-No Go tasks may offer novel insight into the role of this brain region in impulse control. 
 
In summary, we have two concurrent goals for the use of microelectrode recording in patients 
undergoing iEEG for surgical treatment of medically refractory epilepsy. Our most salient goal is to 
augment the standard iEEG recording with additional microelectrode recording which may help to 
identify regions of epileptogenic cortex. Our second goal is to augment our ability to predict the 
cognitive risk of epilepsy surgery and investigate the role of the specific brain region in cognition and 
behavior. For these goals, we will utilize a safe, commercially available, FDA approved dual micro- 
macro electrode system. Our hypothesis is that such recording will elucidate specific characteristics of 
brain regions with epileptogenic potential, will offer novel insights into cognitive neuroscience, and help 
to predict neuropsychological outcomes of surgery. 
 
References: 
1. Kwan P, Brodie MJ. Early Identification of Refractory Epilepsy, NEJM 342 314-319, Feb 3 2000 
2. Wiebe S, Blume WT, Girvin JP, Eliasziw M. A Randomized, Controlled Trial of Surgery for 
Temporal-Lobe Epilepsy. NEJM 345:311-318, August 2, 2001 
3. Steven P, Ebersole J. Intracranial EEG in Temporal Lobe Epilepsy. Journal of Clinical 
Neurophysiology, September 1999 - Volume 16 - Issue 5 - p 399 
4. Hamer HM, Morris HH, Wyllie E, Lüders HO. Complications of invasive video-EEG monitoring 
with subdural grid electrodes. Neurology 2002;58:97-103 
5. Van Gompel JJ, Worrell G. Phase I trial: safety and feasibility of intracranial 
electroencephalography using hybrid subdural electrodes containing macro-and microelectrode arrays. 
Neurosurg Focus 25 (3):E23, 2008. 
6. Babb TL, Brown WJ. Neuronal, dendritic, and vascular profiles of human temporal lobe epilepsy 
correlated with cellular physiology in vivo. Adv Neurol. 1986;44:949-66. 
7. Colder BW, Wilson CL, Frysinger RC, Chao LC, Harper RM, Engel J Jr. Neuronal synchrony in 
relation to burst discharge in epileptic human temporal lobes. J Neurophysiol. 1996 Jun;75(6):2496-508. 
8. Bragin A, Engel J Jr, Wilson CL, Fried I, Buzsáki G. High-frequency oscillations in human brain. 
Hippocampus. 1999;9(2):137-42 
9. Bragin A, Wilson CL, Staba RJ, Reddick M, Fried I, Engel J Jr. Interictal high-frequency oscillations 
(80-500 Hz) in the human epileptic brain: entorhinal cortex. Ann Neurol. 2002 Oct;52(4):407-15. 
10. Staba RJ, Frighetto L, Behnke EJ, Mathern GW, Fields T, Bragin A, Ogren J, Fried I, Wilson CL, 
Engel J Jr. Increased fast ripple to ripple ratios correlate with reduced hippocampal volumes and neuron 
loss in temporal lobe epilepsy patients. Epilepsia. 2007 Nov;48(11):2130-8. Epub 2007 Jul 28. 
11. Greg A.Worrell,1 Andrew B.Gardner,3 S. Matt Stead,1,2 Sanqing Hu,1 Steve Goerss,4 Gregory J. 
Cascino,1 Fredric B. Meyer,4 Richard Marsh4 and Brian Litt3High-frequency oscillations in human 
temporal lobe: simultaneous microwire and clinical macroelectrode recordings. Brain February 7, 2008 
12. Cameron KA, Yashar S, Wilson CL, Fried I.. Human hippocampal neurons predict how well word 
pairs will be remembered. Neuron. 2001 Apr;30(1):289-98 
13. Gelbard-Sagiv H, Mukamel R, Harel M, Malach R, Fried I. Internally generated reactivation of 
single neurons in human hippocampus during free recall. Science. 2008 Oct 3;322(5898):96-101. Epub 
2008 Sep 4. 

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4.Design, procedures, materials and methods: 
Use a level of detail similar to what would be used when submitting an article for publication in a peer 
reviewed journal. Explain the study procedures, data collection, and analysis process. Please define 
terms and explain concepts which might be confusing to reviewers who are not expert in the area of the 
study. If a formal protocol for the study exists, page references to the protocol are acceptable. 
 
 
Patient selection. Patients with medically refractory epilepsy are referred to DHMC for surgical 
evaluation. The first stage of the evaluation includes inpatient video EEG monitoring, epilepsy protocol 
MRI, and a neuropsychological evaluation. Following the initial evaluation, each patient’s case is 
discussed in the epilepsy surgery conference. The conference is attended by all Dartmouth epilepsy 
neurologists and neurosurgeons. A consensus among all physicians is reached regarding further 
evaluation. Approximately 50% of patients require intracranial EEG (iEEG) recording prior to epilepsy 
surgery. If a patient requires iEEG, the strategy for the exact type of electrode implantation is  
determined at the same surgical conference. Subsequently, the need for iEEG monitoring is discussed 
with the patient in the outpatient clinic. Patients who meet clinical indication for iEEG recording will be 
asked to participate in the research study. If the patient agrees, certain standard electrodes will be 
substituted with the dual micro-macro electrodes during the iEEG recording. 
 
Electrodes.  Ad-tech is the largest manufacturer and supplier of intracranial electrodes for use in 
epilepsy surgery. Ad-tech standard macroelectrodes have been used at Dartmouth-Hitchcock Medical 
Center since 1992 in hundreds of iEEG cases. In addition to macroelectrodes, Ad-tech currently 
manufactures two types of dual macro-micro electrode systems that will be used in the study. The 
appropriate type of electrode system will be determined by the study team. 
 
One system is designed to mimic the original macroelectrode design with the addition of ultra-thin 
microelectrodes. The original macroelectrode dimensions and properties are retained and additional 
microelectrodes are positioned at the tip. Leads for the macro and micro electrode recording are separate 
and are connected to two distinct recording systems. Safety information for the use of the dual  
electrodes is provided from a single retrospective study of 24 patients who underwent the dual electrode 
implantation at Mayo Clinic. The complication rate for microelectrodes was 4% compared to 6% for 
standard electrode systems. Attachment #1 and Attachment #2 address the safety of the electrodes. 
 
The second system (Behnke Fried/Micro Inner Wire Bundle) consists of an outer macro contact depth 
electrode that accepts delivery of an inner micro wire bundle. The micro contacts extend past the tip of 
the macro depth electrode. 
 
Data Recording. Recording of iEEG using macroelectrodes has been routinely performed at Dartmouth 
using the Natus system. Recording of microelectrode potentials will be done using a separate Digital 
Lynx system or the clinical Natus system. The two systems are distinct and will not share information. 
The Digital Lynx system is a state-of-the-art microelectrode recording system manufactured by 
Neuralynx. Neuralynx provides the highest quality microelectrode recording equipment. The Digital 
Lynx system is not FDA approved for clinical use. However, it has been fully tested and meets the 
60601 medical safety standards, has the 60601-1 safety certification for medical devices, and has meets 
the 60601-2-26 safety standards for EEG equipment. This system is available for clinical use through 
the lab of Barbara Jobst. Attachment #3 addresses the safety of the Digital Lynx System. 

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5.Inclusion/Exclusion Criteria: 
Please provide detailed description of inclusion and exclusion criteria. If a formal protocol for the study 
exists, page references to the protocol are acceptable. 
 
 
 
 
 
6.Financial Considerations: 
Disclosure of financial impact on the participant is critical to informed consent. Insurance cannot be 
billed for research-related services outside the standard of care or paid for by the funding agency for the 
study. The department, the study or the participant may be responsible for payment for research-related 
services. Participants should know which tests, visits, or procedures will be billed to them or their 
insurance and which ones will be paid by the funding agency for the study or the department. 
 
a) List tests, visits, and procedures performed for only research purposes. These services are outside the 
standard of care. They would not be performed if the individual were not a research participant, and may 
not be billed to a health insurance plan. 
Note: 6a information must also be in "How is this different . . ." section of the consent form. 
Cognitive Tasks. Patients who agree to participate in microelectrode studies may be asked to participate
in a study which involves a cognitive task. Each task will be specifically designed to elicit a specific
cognitive function important to testing of the regions where electrodes are implanted. The task could be
a memory task, such as remembering of word pairs if electrodes reside in the hippocampus. The task 
may involve perception of facial emotion, mimicry of facial movements, mimicry of planned 
movements, smell appreciation, taste appreciation, appreciation of disgust, or visual spatial analysis. 
The type of task that a patient gets will depend on the region of the brain that is implanted by the
microelectrode. 
Data Analysis.  Data on neuronal discharge characteristics will be recorded using the 64 Chanel Digital
Lynx system running Cheetah software. The characteristics of fast ripples, and the data on neuronal
firing characteristics during specific cognitive tasks will by exported to Matlab software for statistical
analysis. Data analysis will be done by either the study team at DHMC/Dartmouth College, or by 
collaborators at Columbia University. 
Inclusion criteria: 
1. 18-65 year old 
2. male or female 
3. right or left handed 
4. IQ>70 
5. medically refractory focal epilepsy requiring intracranial EEG for pre-surgical evaluation deemed 
medically necessary 
6. no contraindications to intracranial electrode study 
7. able and willing to participate in research 
Exclusion criteria: 
1. does not meet the inclusion criteria 

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b) List the tests, visits, and procedures that may be standard care, but for which the funding agency for 
the study is paying. 
 
 
 
 
 
c) Will the funding agency for the study be responsible for the above costs? 
Yes 
No 
If No, describe who will be responsible (i.e., department or participant). 
The Department of Neurology will be responsible for all research costs outside of standard of care. 
 
 
 
 
 
 
 
7.Statistical Methods and Review Statement: 
a) Specify the primary endpoint, as well as other endpoint(s). 
 
 
 
b) State the statistical analysis plan, including all hypothesis tests (e.g., t-test, chi-square), and estimation 
methods related to the primary endpoint. If a formal protocol for the study exists, page references to the 
protocol are acceptable. 
 
 
 
 
c) Justify the sample size, using the concepts of power, type I error, and effect size if applicable. If a 
formal protocol for the study exists, page references to the protocol are acceptable. 
There is no predicted extra cost to the patient if they choose to participate in the study. We will purchase 
the research portion of the dual micro-macro electrode system using research funds. Use of Digital Lynx 
system, collection of data, data analysis, creating and administration of neurocogntive tasks will be done 
during research time of individuals in the study. Nothing that is done outside the standard of care will be 
billed to the patients. 
None 
PLEASE ENCLOSE THE DHMC BILLING GRID/PLAN. Also enclose the schedule of events or 
table listing all procedures from the sponsor protocol. A Billing Grid will not be applicable to this 
study as there is not a sponsor and all procedures are standard of care. There are only 2 points of 
contact with the patient regarding the study: 1. Consenting the patient after a routine office visit 
and 2. Standard of care surgical evaluation. 
The primary hypothesis is that high oscillations (fast ripples) occur in epileptogenic cortex and are 
absent in non-epileptogenic cortex. Our secondary hypothesis is that single unit activity recorded from 
various electrode positions in the brain will correlate with specific cognitive tasks. 
The recording of high frequency oscillations will require only basic statistical analysis using chi-square 
testing. The analysis of neuronal discharge characteristics and temporal association with specific 
cognitive tasks will be done using Matlab. 

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8.Data and Safety Monitoring: 
Describe plans for data and safety monitoring to ensure the safety of subjects and the quality of the data. 
As described in federal guidance “… a variety of types of monitoring may be anticipated depending on 
the nature, size, and complexity of the trial. In many cases, the principal investigator would be expected 
to perform the monitoring function.” This plan should include monitoring to determine: 
 
The progress of the trial, including periodic assessments of data quality and timeliness, participant 
recruitment, accrual and retention, participant risk versus benefit, and other factors that can affect study 
outcome. Monitoring should also consider factors external to the study when interpreting the data, such 
as scientific or therapeutic developments that may have an impact on the safety of the participants or the 
ethics of the study. 
 
Note: This section does not request information related to sponsor study monitor visits. This section 
requires a description of an adequate data and safety monitoring plan. 
 
 
 
 
9.Genetics: 
Does any part of the study involve genetic analysis of biological specimens? 
Yes 
No 
If yes, respond to Genetics Attachment C 
 
 
10.Instruments: 
Describe each instrument, if any, used to collect data in this study. 
 
Attach copies of any questionnaires, surveys, or interview questions. If the research involves interviews 
that could evolve as the research progresses, include a list of discussion topics and any “starter” 
questions for each topic that can reasonably be expected to be covered. If a draft of a written 
questionnaire or survey is attached, it should be clearly labeled as such and a final version should be sent 
to Dartmouth-Hitchcock Health (D-HH) IRB for review before data collection begins. 
 
 
 
11.Deception. 
Will deception of participants, including withheld information, be used in this research? 
Yes 
No 
If yes, complete a-d. 
 
a) Describe the deception being used in this study: 
We are planning to enroll up to 50 patients over an extended period of time. The power calculations and 
effect size, will depend on the cognitive task applied in the individual patient for the specific electrode 
array. 
The safety of dual macro-micro electrodes will be assessed with every patient. Complete data analysis 
will be done with every patient. 

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b) Explain why deception is necessary in this research: 
 
 
 
c) Describe the information provided to subjects when they decide to participate: 
 
 
 
d) Describe how the subjects will be provided with additional pertinent information after 
participation (debriefing): 
 
 
 
 
 
12.Timetables: 
a) Indicate length of participant involvement in the study: 
 
 
b) Estimate how long it will take to enroll enough participants to complete this study: 
 
 
13.Risks: 
The purpose of this section is to determine if subjects will be placed "at risk," which in general means 
exposed to the possibility of physical, psychological, social, economic, legal, dignitary or other harm as a 
consequence of any activity proposed in the research project. 
 
a) What is the overall risk classification of the research? 
 
Minimal 
Greater than minimal 
Significant  
Unknown 
 
Note: In the federal regulations on human subjects protection minimal risk means "The probability and magnitude of harm or 
discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or 
during the performance of routine physical or psychological examinations or tests." 
 
b) Describe any potential risks (physical, psychological, social, legal, economic, or other) and assess 
their likelihood and seriousness. Describe the procedures for protecting against or minimizing these 
risks, including risks to confidentiality, and assess their likely effectiveness. Please list risks from most 
severe/likely to least severe/unlikely. 
ongoing study. We think we can enroll 2-3 patients per year. 
This will be an 
Each participant will be enrolled into the 
study for the duration of their iEEG monitoring, this is an inpatient admission of less than two 
weeks. 

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The risk of participation in the study overall is only minimally greater that standard iEEG recording, 
although conclusive risk assessment is not available. The safety of dual micro-macro electrode systems 
has been annalyzed in a retrospective study done at the Mayo Clinic by Van Gompell et al. In this study, 
24 consecutive patients underwent long-term iEEG monitoring with implanted dual depth and subdural 
grid and strip electrodes; both clinical macroelectrodes and research microelectrodes were used. The 
patients included 18 women and 6 men with an average age of 35 (range 21–65). The mean hospital stay 
was 11 days (range 5–20), with mean duration of implantation 7.0 days (range 3–15). Data from the 198 
consecutive craniotomies for standard clinical subdural grid insertion (prior to surgery in the 24 patients 
described here) were used for comparison to investigate the relative risk of complications. The overall 
complication rate was 4.2% (only 1 patient had a complication), which did not significantly differ from 
the complication rate previously reported by the authors of 6.6% when standard subdural and depth 
intracranial electrodes were used. There were no deaths or permanent neurological deficits related to 
electrode implantation. In conclusion, he authors demonstrated the use of hybrid subdural strip and grid 
electrodes containing and standard clinical macroelectrodes. In this initial study in 24 patients, the 
complication rate is acceptable, and there does not appear to be increased risk associated with the use of 
hybrid electrodes compared with standard subdural and depth iEEG electrodes. Please refet to 
Attachments #1 and #2 for further details. 
 
Digital Lynx system is not FDA approved. However, it has been certified to be UL/EN 60601-1 and 
60601-22 compliant. Details are enclosed in attachment #3. 
 
A theoretical risk of potential physical neuronal injury by direct contact of a microelectrode with a 
neuron exists. This type of injury has not been reported in humans with use of microelectrodes. 
Potential injury by direct microelectrode contact would most likely be limited to single neurons or very 
small populations of neurons. No neurocognitive effect would be expected by injury to such small 
populations of neurons. 
 
 
14.Risk/Benefit analysis: 
Describe why the risks to subjects are reasonable in relation to the anticipated benefits to participants 
and in relation to the importance of the knowledge that may reasonably be expected to result from the 
study. 
 
 
 
 
15. Research Setting 
a) Is this a multi-center study? 
Yes 
No 
If yes: Are you the lead investigator? 
Yes 
No 
If you are NOT the lead investigator: 
Name of lead investigator: 
Institution where the lead investigator is located: 
The potential risk of this study is reasonable give the wealth of potential information which may be 
gained from this study. Potential benefits include improvement in prediction of neuropsychological 
outcomes, improvement in detection of epileptogenic brain regions, and novel understanding of 
neurocognitive mechanisms. 

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b) List all sites where research will take place and D-HH is the reviewing IRB (e.g. DHMC Alliance 
Hospitals, DHMC Clinics, WRJ VAMC): 
 
 
 
 
c) If you are the lead investigator of a multi-center study, list all sites where research will take place 
and D-HH is NOT the reviewing IRB: 
or check 
N/A 
 
Note: Each site taking part in the research should have appropriate institutional or IRB oversight. A 
Site Agreement or Federalwide Assurance may be required. The D-HH office can assist you with these 
arrangements. 
 
 
 
d) Does the study involve sites outside of the United States and Canada? 
Yes 
No 
If yes, are arrangements for the international site(s) being made by a multinational pharmaceutical or 
device sponsor or a cooperative oncology working group? 
Yes 
No 
If no, please complete Attachment L. 
 
 
 
 
16.Adequacy of Resources to Protect Subjects: 
a) Investigator (including co-investigators) has sufficient time to conduct and complete the research. 
Yes 
No 
 
b) Adequately qualified (including experience, training, supervision, and familiarity with the protocol) 
staff are available for this research. 
Yes 
No. 
 
c) Describe availability of psychological, social, or medical services, which include counseling or social 
support services, that may be required as a consequence of research participation. 
 
 
 
d) Describe psychological, social, or medical monitoring, ancillary care, equipment needed to protect 
participants (e.g. close proximity to resuscitation equipment or a plan for monitoring of emotional state 
during study procedures). 
 
 
DHMC - Lebanon 
Patients are routinely evaluated by neuropsychologists as part of routine work-up. As subjects will be 
inpatients during their participation in the study, epilepsy , neuropsychiatry, and psychology services 
will be available. 
The study will be conducted inside the Epilepsy Monitoring Unit (EMU) at DHMC. This unit is 
specifically equipped to deal with complications of epilepsy and epilepsy surgery. The unit has 
continuous video EEG monitoring, meets safety standards for operating an EMU, has specially trained 
and qualified nurses who are able to treat seizures. 

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e) Describe other resources needed for the protection of subjects in the conduct of this research (e.g. 
language translation services). 
 
 
 
f) Explain how the investigator has access to a population that would allow recruitment of the required 
number of subjects. 
 
 
 
 
17.Participant Population: 
Certain populations are considered vulnerable to coercion and undue influence. These populations are 
provided with additional protections when participating in a research study. The populations include: 
 prisoners 
 human embryos 
 fetuses 
 elderly people 
 people with an cognitive disability (also see #23 below) 
 people with a disabling psychiatric illness 
 people who are economically disadvantaged persons 
 people who are illiterate 
 
Refer to: 
Students, Employees Attachment D 
Illiterate Subjects 
Attachment E 
 
a) List vulnerable groups: 
or check 
None 
 
 
 
b) Describe additional protections: 
or check 
N/A 
 
 
 
 
18.Gender and Racial/Ethnic distribution: 
NIH guidelines state that research involving human participation should include minorities and both 
genders. 
Note: If one gender or minorities are excluded or are inadequately represented in this research, particularly in proposed 
population-based studies, a clear and compelling rationale for exclusion or inadequate representation should be provided. 
None 
Patients who have medically refractory epilepsy are referred to the DHMC Epilepsy Center for surgical 
evalaution. Each year, between 10-15 intracranial EEG studies are performed. Patients will be recruited 
from among all patient who meet the inclusion criteria. We anticipate that 5-8 patients per year will be 
recruited to participate in the study. 
People with a cognitive disability who meet the inclusion criteria, and are capable of performing the 
cognitive tasks, but are not capable of giving informed consent. 
The informed consent process for potential participants with a cognitive disability who have a legal 
guardian will include the participant and their legal guardian. As the risks associated with this study are 
minimal, no other additional protections would be needed. 

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Will eligibility for the study be based on gender, race, or ethnicity? 
Yes 
No 
If yes, explain: 
 
 
 
 
19.Pregnant Women: 
Are pregnant women eligible for enrollment into this study? 
Yes 
No 
If yes, respond to Research Involving Pregnant Women, Fetuses and Neonates: Attachment M 
If no, explain and include a process to determine pregnancy status. If a pregnancy test is required, note 
who will pay: 
 
 
 
 
20.Fetuses and Neonates: 
Are fetuses and neonates participants in the research? 
Yes 
No 
If yes, respond to Research Involving Pregnant Women, Fetuses and Neonates: Attachment M 
 
 
21.Children: 
Are children eligible for enrollment into this study? Under state law, a child is a person less than 18 
years old. 
Yes 
No 
If yes, respond to Children: Attachment F 
If no, present an acceptable justification for the exclusion: 
 
Note: NIH guidelines state that research involving human participation should include children unless there is appropriate 
justification for their exclusion. The investigator should address the rationale for selecting or excluding a specific age range 
of children, or an explanation of the reasons for excluding children as participants in the research. When children are 
included, the plan should also include a description of the expertise of the investigative team for dealing with children at the 
ages included, of the available facilities to accommodate the children, and a sufficient number of children to contribute 
meaningfully to the study analysis. 
 
 
 
 
22.Women of Child-Bearing Capability 
Are women of child-bearing capability eligible for enrollment into this study? 
Yes 
No 
If yes, describe potential harm to an unborn fetus from study activities and the process for determining 
pregnancy status if necessary. If a pregnancy test is required, note who will pay. If there is potential 
harm to an unborn fetus, the investigator should review with each individual a plan to avoid pregnancy. 
If the investigator regards these contraceptive plans as inadequate, the individual should be advised on 
how to achieve adequate contraception or should be excluded from the study. 

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If no, explain why this population is not eligible and how you will determine eligibility for each woman. 
 
 
 
 
23.Individuals With Impaired Decision-Making Capacity: 
Will participants potentially lacking capacity to provide informed consent be eligible to enroll in this 
study? 
Yes 
No 
If yes, respond to Research Involving Individuals With Impaired Decision-Making Capacity: 
Attachment G 
 
 
24.Recruitment: 
Describe how subjects will be recruited for participation in this study: 
Eligible participants may be identified from medical record information as a “preparatory to research” 
activity under the HIPAA Privacy Rule. Protected health information obtained as a preparatory to 
research activity may not be removed by a researcher from DHMC, including on mobile electronic 
storage devices. Contact with the identified participants, however, may not occur without prior D-HH 
approval of the recruitment plan for the study. This plan should describe how initial contact with 
participants will be made and by whom. Please note in general, individuals should not be contacted for 
recruitment into a research study by someone unknown to the individual. 
 
a) Will subjects be recruited by searching records (e.g., school records, medical records)? 
Yes 
No 
If yes, will this search include paper files? 
Yes 
No 
If yes, where will these paper files be located? 
 
If yes, will this search include electronic files? 
Yes 
No 
If yes, who maintains these electronic files? 
 
b) Will databases be utilized? 
Yes 
No 
If yes, please specify types and locations of databases: 
 
 
 
c) Will fliers or brochures be posted, mailed or otherwise distributed? 
Yes 
No 
 
d) Will letters be sent to potential participants? 
Yes 
No 
If yes, please provide the letter(s) for D-HH review. 
All patients undergoing surgical work up for epilspsy have a pregnancy test done. Patients who are 
pregnant are excluded from epilepsy surgery and will not be included in this study. 
Patients will be recruited from the clinical 
patient pool of patients of the Dartmouth Epilepsy Program. No specific or pre-exisisting database 
will be searched. 

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e) Will referral be utilized for recruitment? 
Yes 
No 
If yes, please be aware patients should first be informed about the study and agree to the contact before 
any referral. 
f) Will any other method be employed? 
Yes 
No 
If yes, please specify, in detail, what those methods will be: 
 
 
 
g) Does the research plan include “finder fees” or incentives (bonus payment, gift certificates) offered to 
study personnel for enrollment of participants? 
Yes 
No 
Note: As a rule, finder fees or incentives are not acceptable. Please justify any offered incentives. If incentives become 
available during the course of the study, please notify D-HH. 
 
 
 
Attach copies of any proposed flyers, posters, pamphlets, print advertisements, and scripts for on-air 
advertisements or telephone calls. All recruitment materials should be approved by D-HH prior to use. 
 
Note: Advertising should not use terms such as “new treatment,” “new medication,” or “new drug” without explaining that  
the test article is investigational. A phrase such as “receive new treatments” implies that research participants will be  
receiving newly marketed products of proven worth. Advertisements should not promise “free medical treatment,” when the 
intent is only to say participants will not be charged for taking part in the investigation. D-HH will determine if the promise   
of treatment without charge is an inappropriate inducement for study participation. Advertisements may state that participants 
will be paid, but should not emphasize the payment or the amount to be paid. The advertisement should include: the name and 
address of clinical investigator and research facility; the condition under study or the purpose of the research; in         
summary form, the criteria that will be used to determine eligibility for the study; a brief list of participation benefits, if any 
(e.g., a no-cost health examination); the time or other commitment required of the participants; and the location of the   
research activities; and the person or office from whom to obtain further information. 
 
25.Consent Process: 
The Principal Investigator (PI) is responsible for ensuring all participants have provided informed 
consent to participate in this study unless the consent process is waived or altered by D-HH. The PI may 
authorize other appropriately trained individuals to obtain consent from participants. 
 
Please file the consent form in the medical record of each research participant if study participation may 
affect other medical treatment. 
 
Explain how informed consent to research participation will be obtained. Please describe the consent 
process, including information about: 
 Who has been authorized by the PI to obtain consent 
 The time interval between providing information potential participants about a study and having 
the consent form signed 
 Any precautions taken to minimize the possibility of coercion or undue influence 
Patients who are candidates for intracranial EEG monitoring for presurgical evaluaion of medically 
refractory epilepsy will be asked in the outpatient clinic or over the telephone by their clinician if they 
would like to participate in a clinical study. If they do, they (and their legal guardian, if applicable) will 
be provided with all pertinent study information. 

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 Plans for responding to a potential participant or a legally authorized representative who does not 
speak English, such as the use of a translator or a translated consent form 
 Any aids used to simplify scientific or technical information, like a diagram 
 Plans to accommodate the probable literacy level of potential participants 
Dr. Barbara Jobst or a qualified, appropriately trained person designated by Dr. Jobst will be responsible 
for the consent process. All persons designated by Dr. Jobst to obtain consent will have completed the 
Protection of Human Subjects training, or the equivalent accepted by D-HH.  The patients will be seen  
in the outpatient epilepsy clinic to discuss intracranial EEG monitoring prior to epilepsy surgery. The 
consent will take place at the same clinic visit. Patients who do not have a clinic visit scheduled prior to 
admission (usually due to travel distance) will be contacted by their clinicial via telephone. If they are 
interested, a consent form will be sent to them for review, and their signature obtained on the day of their 
admission. Undue coersion will be minimized by the team approach to determining who is a candidate 
for intracranial EEG study. That is, the decision for iEEG and implant plan is made during epilepsy 
surgery conference and requires the unanimous approval of all involved physicians. Only patients who 
require iEEG will be approach to participate in the study. We will not obtain research testing on patient 
who cannot understand or speak English. We may show patients actual examples of the electrodes used 
for routine clinical care and the dual electrodes to help them make the decision. 
 
Patients who are not able to provide informed consent will be considered for participation in the study if: 
1) they meet the inclusion criteria; 2) they are interested in participating in the study and; 3) in the 
judgement of the research team they are capable of performing the cognitive tasks. In those instances the 
patient and their legal guardian will both participate in the informed consent process, with the legal 
guardian signing the consent form. 
 
I intend to obtain consent for research participation but I am requesting a waiver for the use of a 
signed and dated consent form. Please respond to the criteria listed in Attachment I and include an 
information sheet based on the D-HH template. 
 
I am requesting an alteration of the consent process to exclude certain information that is ordinarily 
required. A list of the essential elements of consent to research participation is available on the CPHS 
website:      http://www.dartmouth.edu/~cphs/tosubmit/ConsentElements.html. 
Please respond to Attachment H. 
 
I am requesting a waiver of the entire consent process and use of a consent form. Please respond to 
Attachment H. 
 
Explain why any alteration or waiver to the consent process or form is necessary. 
 
 
 
b) Authorization: Explain how an authorization for research use of protected health information (PHI) 
will be obtained. PHI is individually identifiable health information obtained from a health care  
provider or insurance plan. In general, the HIPAA Privacy Rule permits the use or disclosure of PHI for 
research purposes only with an authorization from each participant whose PHI will be involved. Only 
when certain criteria are satisfied can D-HH grant a waiver of authorization or of the use of a signed and 
dated authorization form. A waiver of authorization is necessary for recruitment procedures when 
patient information is used to identify and contact potentially eligible research participants. A single 

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form may combine the essential information for both consent and an authorization. The D-HH consent 
template contains this combination and is available on the D-HH website. 
 
Check all that apply: 
This study does not involve PHI. 
A single form combining an authorization with the consent form and based on the CPHS template is 
included with this application. 
A separate authorization form is included with this application. 
I am requesting a waiver of authorization for only the recruitment procedure. Please respond to 
Attachment H. 
I am requesting a waiver of signed and dated authorization. Please respond to Attachment I. 
I am requesting a waiver of authorization for the use or disclosure of PHI in this entire study. Please 
respond to Attachment H. 
 
In your explanation of the consent process above, please include information about obtaining 
authorization for the research use of PHI. 
 
 
26.Privacy and Confidentiality: 
Describe the plans to protect the privacy of subjects and maintain the confidentiality of the data. 
 
Note: Under certain circumstances, an invasion of privacy or breach of confidentiality may present a risk of serious harm to 
subjects (e.g., as when the research obtains information about subjects that would, if disclosed by the researcher, jeopardize 
jobs or lead to prosecution for criminal behavior). Under other circumstances, an invasion of privacy or breach of 
confidentiality can be a moral wrong 
 
a) Will any study activities involve an interaction or reveal information for which protection of 
participant privacy is necessary? 
Yes 
No 
If yes, please identify the activities and describe the plan to protect the privacy of participants. For 
example, a plan for protection of privacy might consist of conducting the assent process for an 
adolescent minor in a private setting, rather than in the presence of the minor’s parent. 
 
 
 
 
b) Will the data collected in the course of the study be considered sensitive, e.g., include information 
about a mental health disorder, HIV status, or SS#? 
Yes 
No 
If yes, provide the rationale for why these data are needed: 
 
 
Data recorded during the study will include the names of patients, their dates of birth, medical record 
numbers, and results of testing. This information will be kept on DHMC servers. Data sent from DHMC 
to collaborators at Columbia University will be de-identified. Access to the data will only be available 
for investigators involved in the study. 
De-identified EEG data collected for this study will be shared with other academic institutions, and 
added to public databases of EEG data. Data shared in this way will not include any identifying 
information. 

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If yes, could any of these data, if disclosed, damage financial standing, employability, insurability, or 
reputation? 
Yes 
No 
If yes, will a Certificate of Confidentiality be obtained? 
Yes 
No 
Any person engaged in research collecting information about illegal conduct from human research subjects may apply for a 
Certificate of Confidentiality. NIH provides detailed instructions for investigators wishing to make an application at 
http://grants.nih.gov/grants/policy/coc/index.htm. 
 
c) Describe specific physical, administrative, and technical safeguards employed to protect 
confidentiality of data, e.g., coding with the removal of identifiers, limitation of access to data, use of 
locked file cabinets, protection of computer-based data systems. 
 
 
 
 
d) Will data that identify individual subjects be published or in any way be disclosed to third parties 
other than project personnel? 
Yes 
No 
If yes, please explain here and incorporate the information in consent form: 
 
 
 
 
27.Responsibility for costs of injury or illness related to research: 
Will the sponsor or other funding agency be responsible for costs of injury or illness related to the 
research? 
Yes 
No 
 
If applicable, describe whether or not the sponsor will be responsible for investigational device removal 
if required: 
 
 
 
 
If the sponsor or other funding agency will not be responsible for costs of injury or illness related 
to research, please complete: 
a) The reasons why the sponsor or funding agency is not accepting responsibility for research-related 
injury. 
Sensitive patient information will be stored on DHMC servers. 
Use of microelectrodes is generally considered safe. A single retrospective annalysis of the use of the 
dual macro-micro electrode system has shown no significant complications above that for the use of 
macroelectrodes. Specific macroelectrode complications do occur. If any complications such as 
infection or hemorrhage occur, they will be attributable to the macroelectrode part, and not the 
microelectrode. Therefore, the cost of complications should be covered by the health insurance plan as 
these would be expected to occur in standard electrode patients. 

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b) Summary of risks as related to potential costs that could be incurred as a result of research-related 
injury or illness. 
 
 
 
c) Describe reasons for requesting that DHMC or Dartmouth College provide coverage for research- 
related injury or illness, which is not standard policy. 
 
 
 
 
28.Participant Remuneration: 
Will participants be paid for their time, reimbursed for travel or meal expenses, or receive any sort of 
"gift" for participating in this study? 
Yes 
No 
If yes, please describe in detail: 
 
Note: Participant remuneration is not considered a benefit of being in a research study. D-HH will consider the amount of 
payment in relation to the time needed and any inconvenience to participants. Payment, reimbursement, or gifts should not be 
in an amount that would be coercive to the participant population. 
 
If study is to be done at the VA, specific questions need to be answered if a participant is being paid "in excess of 
reimbursement for travel." Please contact the D-HH office if you need more information. 
 
 
 
 
 
29.Investigational Drug or Biological Agent: 
Respond to items below or check 
No investigational drug or biological agent involved. 
 
Are all agents approved by the FDA for the specific indication for which they are used in this study? 
Yes 
No 
If no, respond to a and b: 
 
a) Briefly discuss the plan for the storage, dispensing, handling, and disposal of investigational and 
FDA-approved drugs, devices, and biologics. When these activities are being done by the investigator, 
include a description of the procedures for inventory control and documentation. 
 
DHMC Investigational Pharmacy is managing all study drugs. 
Yes 
No 
If No please describe management plan below. 
 
 
We anticipate that any complications will be related to the implant or admission generally, and not 
specific to the research portion of the electrodes or the study tasks. 
All patients involved in the research study will be inpatients undergoing intracranial EEG monitoring. 
Participants will not be paid for participation in the study. There will be no additional travel expenses. 

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b) Check and respond to one of the following statements: 
If this study is being done under an Investigational New Drug (IND) application to the FDA please 
provide: IND # (Investigational New Drug): # 
and specify who holds the IND#: 
 
OR 
 
If the drug or biologic agent used in this study is not FDA approved for the indication in this study, 
but an IND # has not been obtained, please complete Attachment J. 
 
 
30.Placebo vs. Standard Care: 
Does any part of the study involve use of a placebo or procedures that are inconsistent with the standard 
of care at DHMC? 
Yes 
No 
If yes, respond to Placebo: Attachment B 
 
 
31.Medical Device: 
Respond to items below or check 
No devices involved. 
 
Is this device approved by the FDA for this indication? 
Yes 
No 
 
If no or if FDA approval is pending, respond to a, b, and c 
 
a) Is the device provided free of charge by the sponsor? 
Yes 
No 
 
b) Where are the devices used in the study stored? Who controls their use? 
 
 
c) Respond to (1), (2), (3), or (4) 
(1) If this study is being done under an Investigational Device Exemption (IDE) from the FDA 
please provide: IDE#: # 
or check here if the IDE is pending: 
Also check the FDA Device HCFA Reimbursement Category: 
A 
B2 
B3 
Please note: D-HH will not approve a study before an IDE # has been received. 
OR 
(2) If 510(k) notification for the device has been sent to FDA check here and either: 
provide a copy of the documentation verifying 510(k) clearance, or check here if 510(k) 
clearance is pending     . 
 
OR 

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(3) If the device is exempt from IDE requirements, check here 
and provide a copy of a letter 
from the FDA or sponsor stating that the device is exempt from IDE requirements under 
812.2(c). 
 
OR 
 
(4) If you are requesting a nonsignificant risk determination for the device from D-HH, please 
check here 
and complete Attachment A. 
 
Please note: D-HH may approve, disapprove, or require modifications in a protocol that has been 
approved or cleared by the FDA. 
 
 
32.Conflict of Interest Review: 
Dartmouth College, Dartmouth-Hitchcock Clinic, and Mary Hitchcock Memorial Hospital have adopted 
a policy on Conflict of Interest in Human Subject Research. Copies of the policy are available on the 
Dartmouth College, Office of Sponsored Projects web site at 
http://www.dartmouth.edu/~osp/policies.html. 
Definitions: 
“Conflict of interest” occurs when an independent observer may reasonably question whether an 
individual's professional actions or decisions are influenced by considerations of the individual’s private 
interests, financial or otherwise. 
Conflicting financial interests do not include: 
 salary and benefits from Dartmouth College, Dartmouth-Hitchcock Clinic, and Mary 
Hitchcock Memorial Hospital; 
 income from seminars, lectures, teaching engagements, or publishing sponsored by federal, 
state, or local entities, or from non-profit academic institutions, when the funds do not 
originate from corporate sources; 
 income from service on advisory committees or review panels for governmental or non- 
profit entities; 
 investments in publicly-traded mutual funds; 
 gifts and promotional items of nominal value; and 
 meals and lodging for participation in professional meetings. 
 
“Principal investigator or other key personnel” means the principal investigator and any other person, 
including students, who is responsible for the design, conduct, analysis, or reporting of research 
involving human subjects. 
Instructions: 
To assist institutional review of the proposed research for conflicts of interest, please respond to the 
question below. 
With regard to this proposed research study, does the principal investigator or other key 
personnel, or any of their spouses, domestic partners, or dependent children, hold a financial 
interest that would reasonably appear to affect or be affected by the proposed study, including but 
not limited to the following interests? 

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a. compensation for services (e.g., consulting fees or honoraria), or in-kind payments, other than 
from the researcher's primary employer, in the prior calendar year or projected over the next 
twelve months; 
b. royalty income or the right to receive future royalties under a patent license or copyright, when 
the proposed research is directly related to the licensed technology or work; 
c. equity interests (e.g., stocks, stock options or other ownership interests), including equity 
holdings where the value cannot readily be determined by reference to public prices; 
d. intellectual property rights (e.g., patents and copyrights), and royalties from such rights; 
e. gifts or funds available to the researcher from the sponsor of this study beyond the current 
project; 
f. funding expected to significantly exceed the projected costs of conducting this study; or 
g. another financial or private interest that may present a conflict of interest. 
 
 
No: The Principal Investigator or other key personnel do not have any financial interests listed in a. 
- g. above. 
Yes: The Principal Investigator or other key personnel do have financial interests listed in items a. - 
g. above. 
Only if you have answered yes to the question above about study-specific financial interests for a 
member of the research team, please provide the following additional information. 
Name of each individual with a listed financial interest: 
 
 
 
 
Attachment G 
Research Involving Individuals With Impaired Decision-Making Capacity 
 
Introductory Information: 
When a subject lacks capacity to give informed consent, the investigator should obtain written 
permission from a legally authorized representative prior to enrolling the subject in a research study. 
Federal Regulations define legally authorized representative as an "individual or judicial or other body 
Each individual on the above list should complete a Conflict of Interest Disclosure Form for Human 
Subject Research. The disclosure should include only those financial interests that are specifically 
relevant to this research study. 
The Conflict of Interest Disclosure Form for Human Subject Research is available on the CPHS website 
at the following url: 
http://www.dartmouth.edu/~cphs/tosubmit/forms/ 
Please complete and sign the Conflict of Interest Disclosure Form for Human Subject Research form. In 
an envelope marked "Confidential", send the form to the Director of the Office of Sponsored Projects, 
using the following address: 
CPHS/COI-HS, Hinman Box 6254. 

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authorized under applicable law to consent on behalf of a prospective subject to the subject's 
participation in the procedure(s) involved in the research" (45CFR46.102(c)). Neither Federal 
Regulations nor New Hampshire State Law provide specific information about who may or may not 
qualify as a legally authorized representative in a research setting. For the purposes of this policy 
statement, the options of defining a legally authorized representative include: 
 
a) Durable power of attorney for health care (DPAHC), 
b) Court appointed legal guardian 
c) Next-of-kin. 
 
A strict interpretation of NH state law does not provide for the use of next-of-kin as a surrogate decision 
maker for investigational activity. The argument for allowing next-of-kin to consent to participation in 
research activity for an individual who lacks capacity to consent is that, without such an option, it is 
often impractical or impossible to conduct important medical research on conditions where results with 
the best current therapy are suboptimal. When investigational therapy represents the best treatment 
option or when risks to the subject are small in relation to the potential benefit of research to society, a 
policy which creates a major obstacle to the conduct of important research activity is ethically unsound. 
 
With the above issues in mind, the Dartmouth CPHS has established the following policy for research 
studies that may involve adult subjects who lack capacity to give informed consent to participation in a 
research study. Please carefully review all items. 
 
Submission requirements: 
When initially submitting a protocol for review by the CPHS, the investigator will inform the CPHS in 
the appropriate section of the CPHS Study Plan (item #18) if the study may involve subjects who lack 
capacity to give informed consent to participate in the study being proposed. 
 
In addition, when a study may involve subjects who lack capacity to give informed consent, the 
investigator will use the form provided below to inform the CPHS of the requested options to provide 
permission for an individual who lacks capacity to participate in the research study and respond to 
specific CPHS questions. 
 
For all requests: 
Even with the permission of a DPAHC, or court appointed legal guardian, the D-HH will not permit a 
subject who lacks capacity to give informed consent to participate in a research study that offers little 
chance of DIRECT BENEFIT to the research subject over what they could receive outside the research 
setting and involves a meaningful increase in the risk of harm or discomfort, regardless of the potential 
gain to future subjects or society in general. 
Please complete a) and b): 
a) Does participating in this study offer the subject a chance of direct benefit over what they could 
receive outside the research setting? 
 
 
There is little chance that data gathered using the microelectrodes will inform decisions 
being made about epilepsy surgery for the participant or otherwise directly benefit the 
patient. 
 
 

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b) Is there an increase in the risk of harm or discomfort for the subject over what they would 
experience outside the research setting? 
 
 
To the best of our knowledge, the risk associated with implanting electrodes that include 
microelectrode contacts is no greater than that associated with implanting standard 
electrodes. 
 
The risk associated with the memory, speech and thinking tasks that participants will 
perform is very minimal. Participants can decline to continue the tasks at any time. 
 
 
 
When there is a meaningful chance of DIRECT BENEFIT to the research subject over what they could 
receive outside the research setting, D-HH will make a judgment decision about who may consent to 
participation in the study. The options include: DPAHC, court appointed legal guardian, and a 
properly motivated next-of-kin. 
 
Please indicate the option(s) requested to allow for consent if a subject is incompetent to provide 
consent: 
 
Durable power of attorney for health care (DPAHC) 
YES 
NO 
Court appointed legal guardian 
Next-of-kin. 
YES 
YES 
NO 
NO 
 
If a study requests the use of Next-of-Kin as the legally authorized representative, Please complete a)  
through e) below: 
 
a) Could the subject receive the same management that they will receive in the research study outside 
the setting of a research protocol? 
 
 
 
 
 
 
b) Will participation in the study increase the risk of harm or discomfort compared to what is expected 
with the management that the subject will receive if they do not participate in the research study? 
 
 
 
 
 
 
c) Will participating in the study increase the chance that the subject will experience a favorable 
outcome compared to what is expected with the management that the subject will receive if they do not 
participate in the research study? 
 
 
 
 
 
 
d) What is the magnitude of the benefit that future patients, or society in general, may experience as a 
result of the subject participating in this study? 
 
 
 
 
 

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e) The process of appointing a legal guardian may take several months. Would this type of delay 
compromise patient care? 
 
 
 
 
 
 
The CPHS will use the responses to the items a) – e) when discussing the option of allowing Next-of-Kin 
to enroll subjects into a research study. 
 
Signature section of the consent form: 
Below is the signature line to use when individuals lacking decision-making capacity may be enrolled 
into a research study. As described above, use of the next-of-kin option requires special CPHS 
approval: 
 
 
 
Participant Signature and Date 
Printed Name 
If participant lacks capacity to provide informed consent, sign below as appropriate: 
 
Power of Attorney for Health Care and Date 
Printed Name 
or 
Durable 
 
Court Appointed Legal Guardian and Date 
Printed Name 
or 
 
Next-of-kin and Date 
Printed Name 
 
 
Decision by the CPHS: 
 
The CPHS decision will be relayed to the investigator via the CPHS approval letter.