Randomize Everyone: Creating Valid Instrumental Variables for Learning Health Care Systems
Phase: NA
Conditions: Disk Herniated Lumbar
Sponsor: Dartmouth-Hitchcock Medical Center

 
 
Official Title: 
 
EHR Embedded Comparative Effectiveness Studies--CPS (EHR-
CPS) 
NCT number: 
NCT04520009 
Document Type:  
Study Protocol; Statistical Analysis Plan 
Date of the 
Document: 
08.05.21 
 
 

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D-HH IRB OVERSIGHT:
One of the following must be true in order to submit to the D-HH IRB. Please check all 
that apply:
☐ The Principal Investigator is employed by D-H
☐ The study will utilize any D-H data or specimens
☒ The study will enroll D-H patients or recruit from D-H sites
☒ The study will utilize any D-H resources, e.g. study procedures will occur 
at D-H locations and/or use of D-H equipment or shared resources
PROTOCOL TITLE:
EHR Embedded Comparative Effectiveness Studies
PRINCIPAL INVESTIGATOR:
Tor D. Tosteson, ScD
Professor of Biomedical Data Science
Director, Division of Biostatistics
603 653-3677
Tor.tosteson@dartmouth.edu
Clinical Co-Investigators:
John A. Batsis, MD, FACP, AGSF, FGSA, FTOS
Associate Professor of Medicine and The Dartmouth 
Institute for Health Policy & Clinical Practice
Section of General Internal Medicine
John.A.Batsis@hitchcock.org
Auden C. McClure, MD, MPH
Assistant Professor of Pediatrics & Medicine
Auden.C.McClure@hitchcock.org
Adam M. Pearson, MD, MS 
Assistant Professor of Orthopaedics
Adam.M.Pearson@hitchcock.org>
Dawne M. Mortenson, RN
Center for Pain and Spine
Dawne.M.Mortenson@hitchcock.org

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VERSION NUMBER/DATE:
Include the version number and date of this protocol.
REVISION HISTORY
Revision #
Version 
Date
Summary of Changes
Consent 
Change?
4
092320
Change language for WWC clinic changes 
due to COVID and process modification; 
change from single-site to multi-site trial; 
change to tear-off sheet to gather patient 
contact information for CPS (done via 
Redcap in WWC)
Yes

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Table of Contents
1.0
Study Summary..............................................................................................................................4
2.0
Objectives*.......................................................................................................................................5
3.0
Background* ...................................................................................................................................5
4.0
Study Endpoints* ..........................................................................................................................5
5.0
Study Intervention/Investigational Agent.........................................................................5
6.0
Procedures Involved*..................................................................................................................7
7.0
Data and Specimen Banking*...................................................................................................9
8.0
Sharing of Results with Subjects*..........................................................................................9
9.0
Study Timelines*...........................................................................................................................9
10.0
Inclusion and Exclusion Criteria* ..........................................................................................9
11.0
Vulnerable Populations*.........................................................................................................10
12.0
Local Number of Subjects.......................................................................................................10
13.0
Recruitment Methods...............................................................................................................10
14.0
Withdrawal of Subjects*..........................................................................................................11
15.0
Risks to Subjects*.......................................................................................................................11
16.0
Potential Benefits to Subjects* .............................................................................................12
17.0
Data Management* and Confidentiality ...........................................................................12
18.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*........................12
19.0
Provisions to Protect the Privacy Interests of Subjects.............................................14
20.0
Compensation for Research-Related Injury ...................................................................14
21.0
Economic Burden to Subjects ...............................................................................................14
22.0
Consent Process..........................................................................................................................14
23.0
Process to Document Consent in Writing........................................................................17
24.0
Setting .............................................................................................................................................18
25.0
Resources Available..................................................................................................................18
26.0
Multi-Site Research* .................................................................................................................19

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Study Summary
Study Title
EHR Embedded Comparative Effectiveness Study
Study Design
Survey and interview assessment of parallel group 
randomization embedded into clinical processes and EHR 
Systems
Primary Objective
Evaluation of the feasibility, quality, and acceptability of 
informatics systems and consent procedures for EHR 
embedded comparative effectiveness research.
Secondary 
Objective(s)
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
The demonstration interventions are: Initial visit with 
Dietitian (RD) then Health Coach (HC) or initial visit with 
Health Coach (HC) then Dietitian (RD) in Weight & 
Wellness Center (WWC); and activity restriction versus 
activity as tolerated post discectomy (see below for full 
descriptions)
IND/IDE # 
N/A
Study Population
1) Patients and providers in the D-H Weight & Wellness 
Center (WWC) of the Department of Medicine enrolling 
in obesity management programs; 2) patients 
undergoing spine surgery for disc herniation in the DH 
Center for Pain and Spine (CPS).
Sample Size
For the WWC: 30 for RD then HC initial visit, 30 for HC 
then RD initial visit; For the CPS: 30 for activity 
restriction/30 for activity as tolerated.
Study Duration for 
individual 
participants
6 months of follow-up for CPS patients; follow-up for 
WWC patients is dependent on when the intervention 
was completed which could range from 1-6 months.
Study Specific 
Abbreviations/ 
Definitions 
Health Coach (HC); Registered Dietitian (RD) Weight and 
Wellness Clinic (WWC); Dartmouth Hitchcock Medical 
Center (DHMC); Center for Pain and Spine (CPS)

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Objectives*
Evaluation of the feasibility, ease of use, quality, and acceptability of 
informatics systems and consent procedures for EHR embedded comparative 
effectiveness research.
Estimate survey-based patient-participation, approval of EHR processes, and 
assigned treatment completion rates for embedded randomization 
procedures in the Weight and Wellness Clinic comparing visit order for initial 
Health Coach (HC) and Registered Dietitian (RD) visits (part of initial WWC 
multidisciplinary evaluation at approximately 2 weeks). 
Hypothesis: Patients participation and approval rates of the process will be 
greater than 80%.
Estimate survey-based patient-participation, approval of EHR processes, and 
assigned treatment completion rates for embedded randomization 
procedures in the Center for Pain and Spine comparing activity restriction 
versus activity as tolerated following discectomy in the Center for Pain and 
Spine (CPS).
Hypothesis: Patients participation and approval rates of the process will be 
greater than 80%.
Following study completion, verify treatment status and determine EHR 
outcomes through chart review and records from the D-H data warehouse.
Background*
It is commonly acknowledged that patient-clinician decision making is inadequately 
supported by evidence on the comparative effectiveness of alternative therapies. In 
response to this need, efforts to reform health care delivery—such as the Affordable 
Care Act—have included large investments in improving electronic health record 
systems (EHR) as a potential source of evidence development. The expectation is 
that the large quantity of organized and accessible health care records will 
ultimately provide a resource for conducting comparative effectiveness research on 
an ongoing basis to guide “learning health care systems.”  [IOM (Institute of 
Medicine). Digital Data Improvement Priorities for Continuous Learning in Health 
and Health Care: Workshop summary. Washington, D.C.: The National Academies 
Press; 2013.]
 This protocol will evaluate the feasibility, quality, and acceptability of informatics 
systems and consent procedures for EHR embedded comparative effectiveness 
research based in eDH, our Dartmouth-Hitchcock EHR. 
Two initial demonstrations evaluating the new systems will be conducted targeting 
obesity interventions in the D-H Weight & Wellness Center (WWC): initial visits with 

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Dietitian (RD) then Health Coach (HC) or initial visits with Health Coach (HC) then 
Dietitian (RD); and in the CPS:  activity restriction versus activity as tolerated 
following discectomy.
In the WWC, the demonstration will focus on patients who are returning for their 
RD and HC visit. These visits are scheduled after the initial provider visit.  These 
visits are a part of normal clinical care and are scheduled interchangeably as part of 
the initial WWC multidisciplinary evaluation.  
In spine surgery, patients undergoing lumbar discectomy commonly have post-
operative restrictions related to bending, twisting, and lifting, as well as return to 
work. However, it is also common to have these activities allowed as tolerated 
[Carragee EJ, Helms E, O'Sullivan GS. Spine;1996;21(16):1893-1897], and both 
approaches are used in the DHMC Center for Pain and Spine. 
Study Endpoints*
WWC: System recorded activity and patient surveys/interviews for the quality, and 
acceptability of informatics systems and consent procedures. 
CPS: System recorded activity and patient surveys/interviews for the quality, and 
acceptability of informatics systems and consent procedures. Treatment status and 
patient reported outcomes as available retrospectively in the EHR.
Study Intervention/Investigational Agent
In the WWC obesity and related complications are managed by a WWC provider and 
obesity specific medications are prescribed as needed. Team care is provided by 
dietitians and health coaches. Progress is monitored at provider visits every 1-3 
months with an aim to provide skills and support for sustained lifestyle change with 
a goal of 5-10% weight loss. Due to the COVID19 pandemic visits are  now offered as 
a hybrid of in-person and telehealth visits. 
In the WWC, the demonstration will focus on patients eligible and willing to be 
randomized for the order of their initial RD and HC visits. Both visits  are offered as 
part of routine clinical care following the first provider visit and are consistent with 
current best practice medical guidelines for obesity. 
WWC Arm A: Scheduling the initial RD visit first and then the HC visit as part of 
standard care. 

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WWC Arm B: Scheduling the initial HC visit first and then RD visit as part of 
standard care. 
CPS Arm A: Standard post-operative activity instructions (i.e., no bending, 
twisting, or lifting more than 10 lbs for 4 weeks, no return to work until 
cleared to do so).
CPS Arm B: Instructions advising activity as tolerated and return to work 
based on patient discretion
Procedures Involved*
The software will identify patients for consent and randomized treatment 
assignments in obesity treatment and spine surgery.  Eligible patients will be 
identified and approached during patient visits to consent for participation.
Initial pilot testing will take place at each demonstration center. Clinicians and 
support staff will be trained in using the EPIC based systems and clinical workflows. 
This feedback will be used to make final revisions to the systems and procedures for 
the demonstrations as necessary.
All potentially eligible patients in demonstration protocols will be initially identified 
through EPIC system alerts. Alerts will be triggered by surgeon orders for 
discectomy in the CPS and by entering into the pathway order screen in the WWC. 
If the clinicians confirm that eligibility criteria are met, the patients will be asked if 
they would consider participation in a research project. If the patient is in person 
and agrees, the demonstration protocol will be explained and information sheet will 
be handed out. If the patient is not in person the information sheet will be mailed or 
emailed out to the participant via RedCap link. They will be asked to consent to be 
assigned randomly to one of the comparative effectiveness interventions and to 
participate in the follow-up survey and potentially a follow up semi-structured 
interview (see below). This follow up survey may be done in person via paper 
survey, sent via RedCap link, or participants can answer the survey questions 
verbally over the phone and a research assistant will enter responses directly into 
RedCap.   
The software will return a computer-generated treatment assignment, with random 
block sizes chosen to balance the number in each comparison group. A code will be 
stored in the patient record to indicate the assigned treatment. The provider will be 
notified of the assigned treatment and place the proper orders in EPIC. In the WWC, 
this will be done using the pre-defined pathway order screen in EPIC.

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We will use a brief post-visit survey (<5 min) with all patients who are approached 
about participating in the two studies. The survey will focus on the consent process, 
reasons for deciding to consent or to not consent, and a few demographics (e.g., 
gender, age, race, education level).  The survey will be anonymous and will be given 
to the patient at the end of their visit or after their consent phone call. This brief 
post-visit survey may be done in person via paper survey, sent via RedCap link, 
paper survey via mail, or participants can answer the survey questions verbally over 
the phone and a research assistant will enter responses directly into RedCap. 
Invitations to participate in the survey will be sent up to four times by mail or email,    
For patients in the CPS who have decided to enroll we will use the sheets to also 
gather their contact information for possible interviewing. To allow us to get 
feedback from unenrolled patients, the information sheet will have a tear off section 
with blanks for the patient’s contact information. That sheet will be torn off before 
being given to an unenrolled patient who will remain anonymous. 
All the demonstration interventions are considered standard of care at DHMC. Risks 
will be monitored according to clinical standards as currently employed in the 
participating clinics. 
A follow-up survey will be sent after 1 to 6 months  to ask whether they received the  
assigned treatment, their perceptions of the study processes, and some basic 
demographic information.  The survey and semi-structured interviews will be 
conducted by the Center for Program Design and Evaluation at Dartmouth (CPDE) 
and overseen by Dr. Schifferdecker, study Co-I. Identifying information (e.g., name, 
email, address, phone number) will only be used to contact the participant and send 
them a survey or administer it by phone, and to assess their interest in being 
interviewed. Invitations to participate in the survey will be sent up to four times by 
mail or email, and paper surveys will be mailed as a last resort to non-respondents 
with a paid return envelope. 
Participants who agree to be contacted for the semi-structured interview will be 
asked their preference for setting up an interview (e.g., by email or phone). CPDE 
staff will use the participant’s preference to contact them to set up an interview 
time. All interviews will be conducted by phone, audio-recorded, and transcribed for 
analysis. 
Following study completion treatment status and patient reported outcomes 
determined through retrospective chart review based on EHR data.
Data and Specimen Banking*

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Study data are derived from responses to the surveys. Patient level data files will be 
maintained until a final report is released. Full name, email and phone number will 
be entered into RedCap database and will only be stored with the study team. 
Sharing of Results with Subjects*
Summary results from the demonstrations will be available as a published final 
report from the funding agency (PCORI), and in scientific publications. Information 
on the location and timing of summary results will be communicated to 
participating patients during the consent process.
Study Timelines*
The anticipated start date for enrollment into the study is September 1, 2020. 
Approximately three months is expected for enrollment. Patients will be contacted 
1-6 months following enrollment for follow-up surveys. The estimated date for 
completion of the last enrollment is December 1, 2020, with the last follow-up 
survey completed by March 1, 2021. The primary data analyses will be executed on 
a blinded basis as survey data are accrued, and summarized by the end of March.

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Inclusion and Exclusion Criteria*
CPS
Inclusion Criteria: Adults (>18) able to consent, with sufficient fluency in English; 
indications for discectomy; able to restrict activities or to resume activities as 
tolerated.
Exclusion Criteria: Pregnant women; Prisoners; Children (<18).
WWC
Inclusion Criteria: Adults (>18) able to consent, with sufficient fluency in English; 
initial RD and HC visits are part of routine care as recommended by the provider; 
willing to be randomized. 
Exclusion Criteria: Pregnant women; Prisoners; Children (<18).
Vulnerable Populations*
N/A
Local Number of Subjects
WWC: 60 patients total, 30 in each treatment arm.
CPS: 60 patients total, 30 in each treatment arm.
Recruitment Methods
Patients will be identified during clinic visits using pre-defined events recorded in 
the EHR. For WWC, the identifying event will be entering into the program order 
entry program during the second clinic visit for patients enrolling in obesity 
pathways. For the CPS, the identifying event will be the surgeon ordering 
discectomy. Following confirmation of eligibility criteria, recruitment and consent 
process will be initiated. 
Risk descriptions will be provided for both the standard of care options in the WWC 
and CPS according to established clinical practice. 
Withdrawal of Subjects*
It is unlikely that patients will be withdrawn unless the study terminates 
prematurely. In this case, participating patients and providers will be notified. 
Partial withdrawal from procedures will not affect the continued data collection, 
unless the patient also withdraws permission to use their data. No plans are in place 
to collect survival data.
Risks to Subjects*

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No clinical risks beyond those of standard of care treatment are anticipated. Patients 
will be informed of these risks according to currently used procedures in the clinics 
and during the consent process. Patients will be contacted for follow-up 
questionnaires, and risks/protections regarding privacy will be discussed in the 
consent process.
Potential Benefits to Subjects*
There are no direct benefits.
Data Management and Confidentiality*
Data collected through the surveys and interviews will be subject to strict 
confidentiality safeguards. The brief post-visit survey  and follow up survey may be 
conducted using DH RedCap account, which is a standard and secure online survey 
platform. Interview audio recordings will be transcribed and analyzed; the audio 
will be destroyed at the completion of the full study (around March 2021). In 
addition, the following procedures will be used to minimize risk: 1) unique 
identifiers will be assigned to each participant, and any potential identifiers (e.g., 
name) in surveys or transcripts will be removed prior to entering data into software 
for analysis; and 2) only the members of the study team will have access to a list 
linking unique IDs to participants; this list will be stored on a password protected 
computer. Information will be kept on password-protected secure computers and 
electronic files. 
Access to retrospective EHR data is requested following study completion for all 
study participants to examine clinical and outcomes for assessing the quality and 
feasibility of the EHR process. The following data elements are requested: 
For  WWC:

Age

Sex

Race

Ethnicity

Date of enrollment/treatment group assignment

Date of initial Health Coach and Dietitian visits

Patient Weight and Height at initial and subsequent visits

Patient Reported Outcomes: PROMIS quality-of-life measure functional 
status questionnaire, and self-efficacy
For CPS:

Age

Sex

Race

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
Ethnicity

Date of enrollment/treatment group assignment

Date of surgery

Patient discharge instructions for chart review by resident to verify activity 
restrictions

Patient Reported Outcomes: PROMIS quality-of-life measure functional status 
questionnaire.

Oswestry Disability Index
The following table gives estimates of the accuracy of the estimates for the primary 
outcomes with the planned demonstration sample sizes, with a range of 
participation and adherence rates.
Parameters for 
Sample Size
90% CI half-width for 
participation and 
adherance rates in 
each arm 
N
30
Rate: 80%
13%
Rate: 70%
15%
Rate: 60%
16%
Provisions to Monitor the Data to Ensure the Safety of Subjects*
The interventions are all standard of care and considered to be minimal risk.  Safety 
concerns will be addressed as part of routine clinical practice. 
Provisions to Protect the Privacy Interests of Subjects
For the surveys and interviews, de-identified data are only linked through separate 
logs that are stored on password protected computers. 
Compensation for Research-Related Injury
The WWC and CPS assigned treatments are considered standard of care and 
minimal risk. There will be no compensation to participants for study-related 
injuries beyond those offered in routine clinical practice. 
Economic Burden to Subjects
No costs outside of usual care are anticipated.  Those patients being asked to 
participate in interviews at either the beginning or end of the study will be given/sent $30 
VISA gift cards, and those patients responding to surveys at the end of the study will be 
sent $20 VISA gift cards.
Consent Process

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The consent process may take place in person at the WWC, or over the phone, or via 
videoconference. The participant will be asked to provide their preferred email 
during this conversation or address if they do not have email or internet  Both 
phone and videoconference process will be standardized and involve using the 
script provided for the WWC for the initial RD and HC visit order. The information 
sheet will be emailed to the participant via a RedCap link or mailed if unable to be 
emailed.
In CPS for the post-discectomy Activity Restriction/Activity as Tolerated,  following 
the SOP: Informed Consent Process for Research (HRP-090). 
Process to Document Consent in Writing
Given the minimal risk, a waiver of documentation of written consent is requested 
for this protocol. Note that all data are collected via anonymous survey, and no 
HIPPA data are collected.
Note that both WWC and the CPS have reviewed and approved this protocol. 
Consent scripts are attached as well as a detailed information sheet for each 
comparison, covering all required consent elements.
A waiver of HIPPA authorization is requested for the retrospective use of EHR data 
and chart reviews for patients who are no longer participating in the study. The data 
are requested to assess the feasibility of our embedded systems and processes, and, 
as in other retrospective EHR chart reviews, it is not practicable to obtain consent. 
The privacy risks are mitigated by the use of deidentified analytic data sets, which 
are securely stored. The files linking the study IDs to patient records will be 
destroyed at the conclusion of the study. PHI will not be reused or disclosed 
following the conclusion of the study.
Setting
The study will be conducted in the Department of Medicine D-H Weight & Wellness 
Center Clinic and in the Department of Orthopedic Surgery Center for Pain and 
Spine. All interventions are standard of care and will be performed at these sites. 
The DH Research Ethics Committee serves as an advisory board and includes 
community representation. 
Resources Available
There are approximately 150 patients per year/75 per 6 months who undergo 
lumbar discectomy at DHMC, of whom we plan to enter 30 to each of the two arms 
for activity restriction following discectomy.
Current WWC volume is estimated at approximately 600 patients per year (300 
during the randomization period of 6 months, with capacity for up to 30. We plan to 
enroll 30 in the RD then HC initial visit, 30 for HC then RD initial visit;

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The participating clinic investigators are all part of the research team and have been 
meeting multiple times per month since the beginning of the study to plan the 
procedures and informatics. The first two weeks of the accrual period will be used 
to conduct the testing and provide final guidance for the clinical staff.
The facilities used for conducting the research include the clinic sites, the 
Department of Biomedical Data Science, Divisions of Biostatistics and Biomedical 
Data Sciences, The Dartmouth Institute, and the D-H Analytics Institute. The project 
supports approximately 40% FTE for the Investigators and Co-Investigators and 
120% FTE for staff in supporting roles as research assistants and programmers. 
Informed consent will be performed by clinic investigators and clinic assistants, 
most of whom are regular participants in team meetings. Scripts and training will be 
reviewed prior to initiation of the demonstration projects.
Multi-Site Research*
One of our Co-Investigators, Dr. John Batsis, has moved to the University of 
North Carolina (UNC).  To maintain his involvement in this and other of his 
studies at Geisel and at Dartmouth-Hitchcock, we have changed the 
designation of this trial to a multi-site trial, including UNC.  The appropriate  
materials for this change were uploaded in MOD00011236.