Clinical trial NCT03102918
Conditions: Cannabis Use Disorder
Keywords: Cannabidiol
Sponsor: Mclean Hospital
Start date: 2016-02-20; Completion date: 2017-08-30
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Investigators aim to determine Epidiolex's promise as a pharmacotherapy for cannabis use disorder. Investigators hypothesize that Epidiolex, when added to medical management, will result in greater reductions in marijuana use compared to placebo as measured by the 2 primary outcome measures: 1) quantitative THC levels and 2) self-report by Timeline Follow Back. Secondary outcome measures will include treatment retention, patient satisfaction, cannabis withdrawal, cannabis craving, depressive symptoms, anxiety symptoms, , compliance, and cigarette use.

Detailed description:
Investigators will conduct a Stage 1 pilot feasibility study at McLean Hospital to begin to evaluate Epidiolex as a pharmacotherapy for adults with cannabis use disorder. In this randomized, double-blind, placebo-controlled trial, cannabis-dependent subjects ages 18-65 will receive medical management over a 6-week period, with half receiving Epidiolex treatment and half receiving placebo. Participants will receive either up to 800 mg Epidiolex or placebo over a 6-week treatment period. Following treatment completion, participants will have a follow-up visits at 10 and 14 weeks. Primary outcomes will include self-report of cannabis smoking and results of quantitative urine drug screens for cannabis. Secondary outcome measures will include treatment retention, patient satisfaction, cannabis withdrawal, cannabis craving, depressive symptoms, anxiety symptoms, compliance, and cigarette use.

Arms: arm 1: Epidiolex arm 2: Placebo
Interventions: intervention 1: Cannabidiol intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive either up to 800 mg Epidiolex over a 6-week treatment period. intervention 2: Participants will receive placebo over a 6-week treatment period.

Protocol documents:
Prot_SAP_000.pdf: 
PARTNERS HUMAN RESEARCH COMMITTEE 
PROTOCOL SUMMARY 
Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
1 
 
Answer all questions accurately and completely in order to provide the PHRC with the relevant 
information to assess the risk-benefit ratio for the study.  Do not leave sections blank. 
 
PRINCIPAL/OVERALL INVESTIGATOR 
Kevin P. Hill, M.D., M.H.S.
 
PROTOCOL TITLE 
Cannabidiol Pharmacotherapy for Adults with Cannabis Use Disorder 
 
 
FUNDING 
Partial funding from Dr. Hill’s Sundry Account, medication and placebo provided by GW 
Pharmaceuticals.  
 
 
VERSION DATE 
3/1/17 
 
 
SPECIFIC AIMS 
Concisely state the objectives of the study and the hypothesis being tested. 
Aim 1: Assess the relationship of treatment with either cannabidiol or placebo, when 
added to medical management, on cannabis use patterns. 
 
 
.  
Aim 2: Assess the relationship of treatment with either cannabidiol or placebo, when 
added to medical management, on cannabis withdrawal and cannabis craving. 
 
 
  
Aim 3: Assess the relationship of treatment with either cannabidiol or placebo, when 
added to medical management, on other factors that may affect treatment outcome, 
such as depressive symptoms, anxiety symptoms, memory, and cigarette use. 
 
 
BACKGROUND AND SIGNIFICANCE 
Provide a brief paragraph summarizing prior experience important for understanding the 
proposed study and procedures. 
In the era of decriminalization of marijuana, medical marijuana, and legalization of 
marijuana, marijuana use has become a global concern.  More people in the world 
abuse cannabis than any other illicit drug. (WHO 2014)  There are over 18 million 
people in the United States that have used cannabis in the past month. (SAMSHA 
2013)  While only a fraction of those users develop problems with addiction, a small 
fraction of a large number can be a very large number—in this case there are millions of 
people in the United States and around the world that are addicted to cannabis and 
therefore require treatment. (Bobb and Hill 2014)   In addition, the Monitoring the Future 
study conducted annually in the United States has shown that marijuana use among 
adolescents has continued to rise while, chillingly, their perception of marijuana’s risk 
has declined. (Johnston et al. 2014)  In the face of these concerning statistics and 


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trends, there are no FDA-approved pharmacotherapies for cannabis use disorder 
despite a critical need. 
 
 
Epidiolex® is a promising cannabinoid that modulates multiple signaling systems, 
making it an intriguing possible pharmacotherapy for a wide range of medical problems, 
including addiction. (Russo 2011; Thomas et al. 2007)  In this Stage 1 feasibility study, 
treatment-seeking individuals ages 18-45 with cannabis use disorder will receive either 
Epidiolex up to 800 mg daily or matching placebo in addition to medical management 
over a 6-week treatment period.  This pilot study, if successful, would provide the 
impetus for a National Institutes of Health R01 grant proposal to conduct a larger clinical 
trial for this treatment.  Dr. Hill has conducted several clinical trials of treatments for 
cannabis use disorder and he currently is funded by a NIDA K99/R00 Pathway to 
Independence Award during which he has completed a pilot study of nabilone as a 
pharmacotherapy for cannabis use disorder and he is conducting a second larger 
clinical trial of nabilone pharmacotherapy as a part of this grant.  Two ongoing trials of 
cannabinoids for cannabis use disorder and another previously completed trial for 
participants with cannabis use disorder show that Dr. Hill can obtain investigational new 
drug (IND) approvals from the FDA, recruit, and carry out these trials at McLean.     
 
 
We aim to determine Epidiolex’s promise as a pharmacotherapy for cannabis use 
disorder.  We hypothesize that Epidiolex, when added to medical management, will 
result in greater reductions in marijuana use compared to placebo as measured by our 
2 primary outcome measures: 1) quantitative THC levels and 2) self-report by Timeline 
Follow Back.  Secondary outcome measures will include treatment retention, patient 
satisfaction, cannabis withdrawal, cannabis craving, depressive symptoms, anxiety 
symptoms, compliance, and cigarette use. 
 
 
Dr. Hill applied for and was granted IND 127385 by the FDA to study cannabidiol as 
a pharmacotherapy for cannabis use disorder. 
 
  
 
RESEARCH DESIGN AND METHODS 
Briefly describe study design and anticipated enrollment, i.e., number of subjects to be enrolled 
by researchers study-wide and by Partners researchers.  Provide a brief summary of the 
eligibility criteria (for example, age range, gender, medical condition).  Include any local site 
restrictions, for example, “Enrollment at Partners will be limited to adults although the sponsor’s 
protocol is open to both children and adults.”
8.1. 
Overview 
 
We will conduct a Stage 1 pilot feasibility study at McLean Hospital to begin to 
evaluate Epidiolex as a pharmacotherapy for adults with cannabis use disorder. In a 
randomized, double-blind, placebo-controlled trial, cannabis-dependent subjects ages 
18-65 will receive medical management over a 6-week period, with half receiving 
Epidiolex treatment and half receiving placebo.  Participants will receive either up to 800 
mg Epidiolex or placebo over a 6-week treatment period.  Following treatment 
completion, participants will have a follow-up visit at 10 and 14 weeks.    Primary 
outcomes will include self-report of cannabis smoking and results of quantitative urine 
drug screens for cannabis.  Secondary outcome measures will include treatment 
retention, patient satisfaction, cannabis withdrawal, cannabis craving, depressive 


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symptoms, anxiety symptoms, compliance, and cigarette use. Mixed models ANOVA 
will be used to analyze the data. 
 
8.2. 
Participants 
   A total of 60 cannabis-dependent volunteers (30 men, 30 women) will serve as 
subjects.  In order to meet the target sample of 30 completers (15 subjects per group), 
we expect to screen about 60 subjects and have about 60 sign the informed consent 
form.  Of those who sign the informed consent form, 24-30 will probably end up being 
randomized.      
All subjects must use a medically approved method of contraception to participate in 
the study (e.g. birth control pills, IUD, condoms).  Both men and women must agree to 
use reliable contraceptive precautions for the duration of the study and 3 months 
following discontinuation.  This includes condoms or other forms of birth control that are 
recommended and/or prescribed by the participant’s physician, such as oral 
contraceptive pills, diaphragm, or implantable medication.  During the physical, the 
physician will ensure that the potential volunteer is using adequate methods to prevent 
pregnancy. 
 
 
Briefly describe study procedures.  Include any local site restrictions, for example, “Subjects enrolled at McLean 
will not participate in the pharmacokinetic portion of the study.”  Describe study endpoints.
8. STUDY PROCEDURE 
8.2.1.a. Recruitment and Intake. 
Interested individuals will respond to advertisements by leaving a message (first 
name and call back number only) in the BPRL recruiting voice mailbox.  Research 
assistants will call them back with 24 to 48 hours and conduct an initial phone screen 
that takes about 15 minutes.  It will cover basic inclusion and exclusion criteria, as well 
as a brief description of the study to determine if the person is interested in participating. 
If the volunteer is appropriate and agrees to participate, they will be invited to come to 
the BPRL for a physical and psychiatric evaluation (SCID).  Treatment alternatives will 
also be offered to the prospective participant if they decide not to participate or are not 
eligible for participation.  
The initial assessment interview will be done by a research assistant and the study 
physician and take about 3 hours.  Volunteers will first be asked to sign the informed 
consent (see 8.2.1.b). Once they have agreed to participate, they will undergo a 
comprehensive evaluation that will include medical, psychiatric, and drug use histories 
as well as physical, psychiatric, and laboratory examinations. The study will be 
explained and an intake package, including all Drug and Alcohol and Mood and 
Impulsivity Assessments (see Table 8.1), will be administered.  More specifically, the 
participants will undergo the following screening procedures:a) Detailed history of 
cannabis use; b) Review of DSM-IV criteria for cannabis dependence; c) Medical history 
and concomitant medication record; d) Physical examination; e) Laboratory screen that 
includes CBC, electrolytes, and BUN/creatinine; f) Urine measurement of THC; g) 
Urinalysis and urine pregnancy test for women; h) 12-lead electrocardiograph (EKG) i) 
urine toxicology screen; j) blood alcohol testing; k) Columbia Suicide Severity Rating 
Scale (C-SSRS). Suicide risk will be assessed by the physician at each medical 
management visit. 


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8.2.1.b.Informed consent. 
 
Eligible participants will complete standard consent documentation.  Prior to the 
volunteer being asked any question about his/her health, the volunteer will be given a 
consent form to read.  The research assistant will go over it in detail with the volunteer.  
After a physician investigator answers any questions the volunteer may have 
concerning the study, he/she will be asked to provide their informed consent to the 
licensed physician investigator. If enrolled in the study, consent to communicate with 
their other clinicians will be obtained.  Clinicians will be notified of their patients’ 
enrollment in the study, thus allowing them to carefully monitor for changes in mood 
while they are undergoing treatment to stop use of cannabis. 
 
8.2.1.c.Randomization.   
 
Participants will be stratified according to their self-reported frequency of cannabis 
use in the past 30 days:  1) daily use; and 2) non-daily use.  The stratification procedure 
will guard against the possibility that one of the experimental conditions (i.e., CBD or 
placebo) will be overrepresented by daily users, while non-daily users will predominantly 
be randomized into the other condition. 
 
8.2.1.d.Availability and Flow of Subjects into Treatment.   
 
We plan to screen 100 participants in the course of 8 months to achieve our desired 
sample size.   
 
8.2.1.e.Study Visits.   
 
Participants will come to the clinic twice a week.  One visit will include a medical 
visit (dispensing of medication and medical management; see Sections 8.3.1.b, 8.3.2) 
and research assessments, including a urine screen (see Section 8.5.2.a and Table 
8.2).  The other visit will consist only of a urine screen (see Section 8.5.2.a).  After the 
6-week treatment period, participants will have follow-up assessments visit at 10 and 14 
weeks. During weeks 7-14, participants will have 1 weekly Diary/Actiwatch visit to hand 
in their daily diaries, have their Actiwatch data downloaded, and provide a urine sample.  
 
8.2.1.f.Clinical Emergencies.   
 
If a participant is intoxicated, the participant will be evaluated medically, sent home 
in a taxi when safe, and the appointment re-scheduled.  If a participant experiences a 
problem that requires clinical intervention during the course of the study (e.g., mania, 
suicidal ideation, or dangerous intoxication), we will evaluate the situation medically, 
make an appropriate recommendation, and help the participant to implement this plan.  
This could involve hospitalization at McLean, referral to the hospital's outpatient 
program, or other medical or psychiatric treatment, as clinically appropriate. 
 
8.2.1.g.Participant Payments.   
Volunteers will receive a $50 honorarium for attending the initial assessment 
interview as well as $50 for the baseline visit.  They may earn $20 for each urine 
sample given on a non-medical management day and $20 for attending each medical 
management visit.  For each of the weekly 10-15 minute follow-up visits, subjects will 
receive $25.  They may earn up to a total of $80 as a bonus for completing all of the 


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daily diaries.  Subjects will receive up to $620 for their participation in the study.  
Medication will be free. 
 
 
 
 FIGURE 1. Study Schema 
 
 
 
 
 
Volunteer Response to Announcement 
 
 
 
Phone Screen 
 
 
 
 
 
 
 
 
 
Inclusion, exclusion criteria 
 
Eligible and agrees to attend  
Initial assessment 
 
 
 
 
Ineligible 
 
 
 
 
 
 
 
 
 
 
 
Assessment Interview 
 
 
 
Baseline  
 
 
 
Informed Consent 
 
 
 
 
 
 
 
 
 
 
Diagnosis of Cannabis Use Disorder (DSM-IV) 
 
 
 
 
 
Clinical Laboratory Testing  
 
 
 
 
 
Urine THC measurement 
 
 
 
 
 
 
  
Randomization 
 
 
 
 
 
Ineligible 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BIS-11, PANAS, ASI 
 
 
 
 
 
MJ Goals, MJ Craving, MPRE 
 
 
 
 
 
QIDS, BAI, CSSRS, MJ Withdrawal, 
 
 
 
 
 
Weekly Drug Use 
 
 
 
 
 
Daily diaries, ActiWatch distributed 
 
6-week  
 
1) MM + CBD 
 
 
 
 
2) MM + PLA 
 
 MM begins* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 weeks ( MM ends) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10 weeks 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
14 weeks 
 
 
 
 
 
 
 
 
 
 
 
 
MJ Withdrawal, Weekly Drug  
and Alcohol Use Q’aire,  
MJ Craving, CSSRS 
BIS-11, PANAS, ASI, Weekly Drug and Alcohol 
Use Q’aire, MJ Withdrawal,  
, MJ Craving, MPRE, QIDS, BAI, CSSRS 
BIS-11, PANAS, ASI, Weekly Drug and Alcohol 
Use Q’aire, MJ Withdrawal,  
MJ Craving, MPRE, QIDS, BAI, CSSRS 


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End of Study, Data Analysis 
 
 
8.3. Treatment. 
8.3.1Cannabidiol. 
8.3.1.a.Rationale for Dose. 
 
Cannabidiol (Epidiolex®, GW Pharmaceutical, UK), a cannabinoid that modulates 
multiple signaling systems, has yet to be approved in the United States.  Both preclinical 
studies and clinical reports suggest that Epidiolex has promise as an addiction 
treatment (Russo 2011) perhaps in part due to its anti-anxiety effects or ability to 
produce extinction of conditioned place preference in animals. Epidiolex will be titrated 
to 800 mg daily in the Epidiolex group (although adjustments may be made to this 
maximum dose based upon participant’s response – this pilot study will determine the 
optimum dose to be used in a larger clinical trial to follow this pilot).  Although Epidiolex 
has not been studied as a pharmacotherapy for substance dependence, up to 1000 mg 
of Epidiolex has been well-tolerated in studies of its effectiveness as a treatment for 
treatment-refractory epilepsy.  
 
 
8.3.1.b.Procedures for Dispensing Medication.   
Participants will be randomized to receive either Epidiolex or placebo.  Dr. Hill or the 
research assistants will present 7 day prescriptions to the McLean pharmacy and the 
participant will receive a container containing 1 week of medication liquid or placebo 
liquid.  Participants will be asked to return unused medication at each weekly medical 
visit; study staff will then record the leftover amount for the study record.  The Epidiolex 
titration dose in the first week by day will be 100 mg, 100 mg, 200 mg, 200 mg, 400 mg, 
400 mg, 800 mg.  Epidiolex is 100 mg per 1 ml of liquid, so participants will take 1 ml 
once daily for 100 mg (between 7PM-9PM), 1 ml twice daily for 200 mg (7AM-9AM, 
7PM-9PM), 2 ml twice daily for 400 mg (7AM-9AM, 7PM-9PM), and 4 ml twice daily for 
800 mg (7AM-9AM, 7PM-9PM).  Participants will take 800 mg daily during weeks 2 
through 5 and then reverse the titration in week 6.  Participants will be assessed for side 
effects prior to each dosing increase and the study physician will decide if increasing the 
dose as scheduled is appropriate.  
 
 
8.3.1.c.Dose Adjustment.    
Subjects who experience uncomfortable side effects (e.g., drowsiness or vertigo) 
may have their dose lowered by 200 mg; a subject receiving active cannabidiol, for 
example, could then have a dose reduction from 8 ml of cannabidiol daily to 6 ml daily.  
If this leads to fewer side effects, the study physician will ask if the subject is willing to 
try the full dose again.  If not, or if the subject tries the full dose again and is unable to 
tolerate it, the subject will be maintained on the lower dose.  If a subject cannot tolerate 
the reduced daily dose, the medication will be discontinued, but the subject will continue 
to be followed for research visits. 
 
 
8.3.2. Medical Management Visits  
 
8.3.2.a. Weekly Visits with the Study Physician  


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Participants will be seen weekly during treatment by the study physician for medical 
visits.  In addition to dispensing the study medication, the physician will utilize Medical 
Management (MM) (Pettinati et al 2004), a manualized treatment that was used in the 
NIAAA COMBINE Study.  MM was derived from empirically-tested manualized 
therapies (Carroll and O'Malley 1996, Mason and Goodman 1997) that were originally 
designed to approximate a primary care approach to the treatment of alcohol 
dependence.  The treatment is delivered by a medical professional who monitors 
medication side effects, provides strategies to increase medication adherence (Volpicelli 
et al. 1997), and supports abstinence.  The initial 40-60 minute session includes 
reviewing the cannabis dependence diagnosis and negative consequences from 
smoking marijuana, recommending abstinence, providing medication information, and 
offering strategies to enhance medication adherence. In subsequent 15-25 minute 
visits, recent substance use, overall functioning, medication adherence, and side effects 
are discussed.  Session structure varies according to drug use status and medication 
adherence.  If a participant is not adherent to the medication regimen, the clinician 
evaluates the reasons and helps the subject devise plans to enhance medication 
adherence.  Participants who use cannabis are given common-sense behavioral 
recommendations, such as avoiding parties where marijuana will be present. Medication 
adherence will be assessed in several ways, as outlined below in Section 8.6.These 
sessions will be audiotaped and a sample will be rated by a senior clinician in order to 
ensure fidelity to the MM process. 
 
8.3. Safety Monitoring. 
 
Cannabidiol has been shown to have a favorable safety profile; it has been well-
tolerated in several clinical trials and no adverse events have been reported.  
Nonetheless, we will monitor safety through the standardized methods described above 
in the medical management visits.  We will have a low threshold for obtaining additional 
medical workup during the study if the subject reports medical symptoms.  If a 
participant has a clinically significant laboratory or other medical abnormality that cannot 
be attributed to another cause, the participant’s medication will be discontinued and the 
participant will be followed for research visits.  
 
 
The subjects will undergo the following screening procedures: a) Detailed history of 
cannabis use; b) Review of DSM-IV criteria for cannabis dependence; c) Medical history 
and concomitant medication record; d) Physical examination; e) Laboratory screen that 
includes CBC, electrolytes, and BUN/creatinine; f) Urine measurement of THC; g) 
Urinalysis and urine pregnancy test for women; h) 12-lead electrocardiograph (ECG); i) 
urine toxicology screen; j) blood alcohol testing; k) Columbia Suicide Severity Rating 
Scale (C-SSRS).The study physician will perform a physical examination and obtain an 
ECG at baseline and at 14 weeks.  Laboratory data (urinalysis, blood chemistries, 
complete blood count, electrolytes, and liver function tests) will be done at baseline, 
week 4 and at 14 weeks as well.  Any subject found to have abnormal liver function 
tests during the screening visit will be excluded from the study (Note: Abnormal is 
defined as values outside the normal ranges for ALT, 7 to 55 units per liter, AST, 8 to 48 
units per liter, and albumin, 3.5 to 5 grams per deciliter). If the patient’s clinical 
presentation during the course of the study raises concerns of their liver function, an 
additional set of laboratory test will be obtained.   If a subject’s liver functions tests 
become elevated to great than or equal to five times the upper limit of normal during the 


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course of the study they will be withdrawn from the study drug. Women of childbearing 
potential will have urine pregnancy tests at the screening visit and monthly during 
treatment; women who become pregnant will have their medication discontinued and 
will be referred to an obstetrician; like all subjects, they will still be followed for research 
visits.  Suicide risk will be assessed by the physician at each medical management visit. 
If a subject expresses active suicidal ideation or other severe psychiatric symptoms, we 
will evaluate the situation medically, make an appropriate recommendation, and help 
the participant to implement this plan.  They will be referred to an emergency room as 
deemed appropriate.  If they require a structured treatment program in order to treat 
their suicidal ideation or psychiatric symptoms, they will be withdrawn from the study. 
 
8.5. Research Measures. 
See Table 8.2 for the schedule of assessments.   
 
8.5.1. Diagnostic Assessment.   
 
To make the diagnoses of cannabis dependence, the Structured Clinical Interview 
for DSM-IV (SCID) (First 1996) will be used.   
 
8.5.2. Drug and Alcohol Use Assessment. 
 
8.5.2.a.Urine Screens.   
 
The primary outcome measure will be cannabis use, as measured by twice-weekly 
quantitative urine screens during treatment.  Cannabis is a particularly challenging drug 
of abuse for measuring outcome because of the false-positive urine screens that can 
occur as the result of long-term accumulation of cannabis metabolites. In an attempt to 
avoid false-positive results, we will obtain 2 supervised urine samples weekly:  1 at the  
medical management visit and 1 on another day, ordinarily with 3-4 days separation 
from the clinical visits (e.g., Monday-Thursday, Tuesday-Friday, or Monday-Friday); this 
should maximize the time frame covered by our urine screens.  We will send the urine 
samples to Quest Diagnostics Laboratory (Cambridge, MA, a NIDA-certified laboratory), 
where the urines will be screened by immunoassay for the THC metabolite 11-nor-
carboxy-∆ 9-tetrahydrocannabinol (THC-COOH) as well as other drugs of abuse.  Urine 
creatinine concentrations will also be measured to assess urine concentration.  The 
threshold for detection of THC-COOH will be 20 ng/ml. Samples positive for this 
metabolite will undergo further analysis by gas chromatography-mass spectroscopy to 
obtain quantitative THC-COOH concentration; we will then calculate the ratio of this 
metabolite to urine creatinine concentration.  We will adopt the method of Heustis and 
Cone (1998) to differentiate new marijuana use from residual drug excretion as a result 
of previous use; these recommendations are based on their controlled clinical studies of 
urinary excretion profiles of creatinine and marijuana metabolites following marijuana 
administration in humans.  We will label a urine negative (i.e., abstinent from cannabis) 
if 1) the ratio of THC-COOH to creatinine in the urine does not increase by >50% from 
the ratio obtained in the previous urine screen, and 2) the participant also reports using 
no cannabis since the previous urine test.    
 
8.5.2.b.Self-Report.   
 
We will use 3 methods of self-report in an effort to determine the most appropriate 
and effective method for use in this population.  An ActiWatch Score will be determined 
via compact, wrist-worn, battery-operated activity monitors that are excellent devices for 
monitoring multiple drug use, drug craving, and sleep/wake activity (Licata et al., under 


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review).  We will provide participants with a packet of 1 Daily Diary pages which 
participants will be asked to fill out between 7:00 and 9:00 a.m. each day and hand 
them in during their weekly visits to the lab.  The diary consists of a series of questions 
about cannabis and other drug use as well as eating and sleeping habits.  During the 
weekly visits, we plan to collect cannabis use data using the Timeline Followback(TLFB) 
(Sobel and Sobel 1992) protocol that was developed for alcohol.   
 
8.5.2.c.Other Drug and Alcohol Use Assessment. 
 
Severity of cannabis and other substance use and its associated problems will be 
assessed at baseline and weeks 6, 10, and 14 with the Addiction Severity Index (ASI, 
5th edition) (McLellan et al. 1992), a widely-used and independently-validated interview 
that measures the severity of problems in 7 areas of functioning that are frequently 
affected in patients with SUDs:  drug use, alcohol use, employment, legal status, 
medical condition, social functioning, and psychological status.  In addition to our 
primary focus on cannabis use (urine screens plus days of use), we will examine other 
substance use (using urine screens plus days of other substance use).  We will use this 
method to determine the number of days of cannabis use and of any substance use 
(and conversely, days of abstinence).  We will examine ASI composite scores as 
secondary measures of substance use outcome.  We will also use the self-administered 
Drug and Alcohol Use Questionnaire.  This measure, administered at baseline, 
addresses the context of lifetime and recent drug and alcohol use, as well as 
sociodemographic data.  At each treatment visit, patients will complete a brief Weekly 
Drug and Alcohol Use Inventory, indicating their number of days using marijuana, other 
drugs, and alcohol during the previous week.  The Marijuana Goals Questionnaire 
(Griffin et al. 1989) is a brief questionnaire administered at baseline to assess treatment 
goals, specifically, whether a participant is seeking abstinence or reduction in cannabis 
use.  A 12-item self-administered questionnaire, the Marijuana Craving Questionnaire 
(MCQ), will be used to assess craving at baseline and weekly during treatment and at 
the 14-week follow-up visit (Heishman et al. 2009).  A short form of the Marijuana 
Withdrawal Checklist (MWC) will be used to assess withdrawal symptoms at baseline 
and weekly during treatment and at the 10- and 14-week follow-up visits (Budney et al. 
1999). If there is a discrepancy among results obtained by these methods of substance 
use assessment, we will meet with the participant and have a conversation about their 
substance use.  After the conversation, we will use our clinical judgment to determine 
the level of use that we believe is most accurate for that participant.  A new 6-page 
questionnaire that we created, the Marijuana Perceptions of Risk and Experiences 
Questionnaire (MPRE), will be distributed at baseline, and once during weeks 6, 10 and 
14 to assess each participant’s perceptions of cannabis risk/harm and his or her 
motivations to quit/continue using cannabis throughout the course of treatment. 
 
8.5.3.Mood and Impulsivity Assessments.   
 
We will monitor participants’ mood throughout the study using 3 assessments. The 
Beck Anxiety Inventory (BAI) is a 21-item self-report measure that can be used to 
assess the severity of anxiety. The Quick Inventory of Depressive Symptomatology 
(QIDS-SR) is a short self-report questionnaire for depressive symptoms used 
successfully in the STAR*D project.  The Positive and Negative Affect Scale(PANAS) is 
a 20-item self-report scale in which mood variables are rated by participants on a 1-5 
scale.  The Barratt Impulsiveness Scale (BIS-11) is a commonly used tool to measure 
impulsivity in various neuropsychological disorders as well as in substance abuse.  


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Three dimensions can be assessed using this scale, which include Cognitive 
Impulsivity, Motor Impulsivity, and Non-planning Impulsivity. 
 
 
Table 8.1  Schedule of Measures 
Measure  
 
 
     
 
     Baseline    Weekly   Weeks 10 &14   
Diagnostic Assessment 
1. 
Structured Clinical Interview for DSM-IVa  
X 
 
 
 
 
 
 
 
Drug and Alcohol Assessment 
2.    Quantitative Urine Toxicological Analysisb 
X 
Xb 
X 
 
 
 
 
3.    Addiction Severity Index 
X 
 
X 
 
 
4. 
Drug and Alcohol Use Questionnaire 
X 
5. 
Weekly Drug and Alcohol Use Inventory 
X 
X  
X 
 
 
6. 
Marijuana Goals Questionnaire 
X 
 
 
 
 
7. 
Marijuana Craving Questionnaire 
X 
X 
X 
 
 
8. 
Marijuana Withdrawal Checklist 
X 
X 
X 
 
 
9.  
Marijuana Perceptions of Risk and  
 
Experiences  
X                   
X                         
 
Mood and Impulsivity Assessment 
10.    Quick Inventory of 
 
Depressive Symptomatology 
X 
 
X  
 
 
11.    Beck Anxiety Inventory 
X 
 
X 
 
 
12. 
Positive and Negative Affect Scale 
X 
 
X 
 
 
13.  Barratt Impulsiveness Scale 
X 
 
X  
 
 
 
 
Medical & Safety Assessment (medical visits) 
14. 
Physical examination 
X 
 
Xf 
 
 
15. 
ECG 
X 
 
Xf 
 
 
16. 
Urine pregnancy testd 
X 
 
Xf 
 
 
17. 
Laboratory testse 
X 
Xe 
Xf 
 
 
18.  Client Satisfaction Questionnaire 
 
 
Xf 
19. 
Adverse Events & Side Effects 
X 
X 
X 
 
 
20. 
Columbia Suicide Severity Rating Scale 
X 
X 
X 
 
 
 
aFull SCID at baseline 
bTwice a week during treatment;  
cWeeks 3 and 6 only 
dMonthly after screening 
eTests include urinalysis, liver function tests, electrolytes, complete blood count, & blood chemistries (also 
tested during week 4) 
f Week 14 only 
 
 
8.6.Medication Adherence Assessment.  The proposed studies involve chronic 
administration of medication given under double-blind conditions. Two methods of 
medication adherence will be used as multiple methods are preferred (Weiss 2004): 1) 
measurement of residual volume will be made; 2) participants will record when they take 
their doses on the ActiWatch-Score device; If there is a discrepancy among results 
obtained by these methods, we will meet with the participant and have a conversation 
about their medication adherence.  After the conversation, we will use our clinical 
judgment to determine the level of adherence that we believe is most accurate for that 
participant. 
 
8.7. 
Data Management 


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All data collected will be de-identified with participant ID numbers and used for 
research purposes only.  Written records will be kept in a locked file cabinet in a locked 
office.  They will be destroyed after 7 years.  Computerized data files will also be de-
identified with participant ID numbers and kept in a password protected file on a 
password protected computer. 
 
8.8.  Statistical Analysis 
 
The primary data analysis will be an intent-to-treat analysis, which includes all 
randomized participants.  Of note, every attempt will be made to continue assessing 
participants even if they drop out of treatment. In addition, we will replicate all analyses 
with the completers only.  The primary and secondary outcome variables are intended 
to explore various aspects of response to therapy and to help define a clinically 
meaningful response. The primary outcome measures, Actiwatch-scores, daily diaries, 
TLFB self-report data, in addition to quantitative urinary THC metabolites, have been 
chosen for their ability to indicate daily use of cannabis by relying on self-report of use.  
 Specifically, for assessing the effect of CBD on cannabis use patterns, we propose 
to use the generalized estimating equations (GEE) approach to longitudinal analysis, 
appropriately accounting for the positive correlation among repeated urine screen 
assessments within the same individual.   
Analyses of secondary substance use outcomes will focus on the number of days of 
cannabis use and of any substance use (and conversely, days of abstinence) during 
treatment and post-treatment follow-up.  In addition, we will also examine the ASI Drug 
and Alcohol composite scores.  Frequency of days of cannabis use (and any substance 
use and days of abstinence) will be analyzed via a log-linear (or Poisson) regression 
model, controlling for pre-treatment frequency of days of cannabis use.  Although log-
linear regression methods are considered appropriate for the analysis of count or 
frequency data, in many biomedical applications, count data have variability that far 
exceeds that predicted by the Poisson distribution; we expect that days of cannabis use 
(and any substance use and days of abstinence) will not be an exception.  Linear mixed 
effects models will be used to examine the effect of treatment group on changes in the 
ASI Drug and Alcohol composite scores during treatment and post-treatment follow-up 
assessments (as determined by the group-by-time interaction in the linear mixed effects 
regression models).  The linear mixed effects model will include random intercepts and 
slopes to appropriately account for correlation among repeated measures and 
heterogeneity of variance over time; the model will be fit using PROC MIXED in SAS.  
In secondary analyses of mood outcomes, mood episodes will be assessed during 
treatment and post-treatment follow-up, using the QIDS, BAI, and PANAS; changes in 
risk of mood episodes during treatment and post-treatment follow-up assessments will 
be analyzed via a logistic regression model (similar to the logistic model above) that will 
be fit using the GEE approach (as implemented in PROC GENMOD in SAS) to account 
for correlation among repeated binary outcomes on the same individual.  To examine 
the effect of CBD on changes in risk for mood episodes during treatment and post-
treatment follow-up, the logistic regression model will include the effects of treatment 
condition and the baseline measure of the outcome.   
 
 
 
 


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Briefly describe study procedures.  Include any local site restrictions, for example, “Subjects 
enrolled at Partners will not participate in the pharmacokinetic portion of the study.”  Describe 
study endpoints.
 
Study procedures are described above. 
 
 
The primary outcome measures will be quantitative urinary THC metabolites, 
Actiwatch-scores, daily diaries, and TLFB self-report data.  In secondary analyses of 
mood outcomes, mood episodes will be assessed during treatment and post-treatment 
follow-up, using the QIDS, BAI, and PANAS.   
 
 
For studies involving treatment or diagnosis, provide information about standard of care at 
Partners (e.g., BWH, MGH) and indicate how the study procedures differ from standard care.  
Provide information on available alternative treatments, procedures, or methods of diagnosis.
The standard of care for cannabis dependence is psychotherapy; our treatment 
centers upon a medication. 
 
 
Describe how risks to subjects are minimized, for example, by using procedures which are 
consistent with sound research design and which do not unnecessarily expose subjects to risk or 
by using procedures already being performed on the subject for diagnostic or treatment purposes.
Care will be taken to minimize risk.  In addition to carefully screening prior to 
enrollment, we have scheduled regular laboratory visits during which we will carefully 
monitor response to medication or placebo with respect to side effects and changes in 
mood. 
 
 
Describe explicitly the methods for ensuring the safety of subjects.  Provide objective criteria for 
removing a subject from the study, for example, objective criteria for worsening disease/lack of 
improvement and/or unacceptable adverse events.  The inclusion of objective drop criteria is 
especially important in studies designed with placebo control groups.
Safety Monitoring. 
 
Cannabidiol has been shown to have a favorable safety profile; it has been well-
tolerated in several clinical trials and no adverse events have been reported.  
Nonetheless, we will monitor safety through the standardized methods described above 
in the CBT visits.  We will have a low threshold for obtaining additional medical workup 
during the study if the subject reports medical symptoms.  If a participant has a clinically 
significant laboratory or other medical abnormality that cannot be attributed to another 
cause, the participant’s medication will be discontinued and the participant will be 
followed for research visits. 
 
 
 
FORESEEABLE RISKS AND DISCOMFORTS 
Provide a brief description of any foreseeable risks and discomforts to subjects.  Include those 
related to drugs/devices/procedures being studied and/or administered/performed solely for 


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research purposes.  In addition, include psychosocial risks, and risks related to privacy and 
confidentiality.  When applicable, describe risks to a developing fetus or nursing infant.
The screening process and questions related to a subject’s psychiatric history 
may cause discomfort.  Subjects may experience side effects when taking Epidiolex, 
including fatigue, drowsiness, and dizziness.   
 
 
 
EXPECTED BENEFITS 
Describe both the expected benefits to individual subjects participating in the research and the 
importance of the knowledge that may reasonably be expected to result from the study.  Provide 
a brief, realistic summary of potential benefits to subjects, for example, “It is hoped that the 
treatment will result in a partial reduction in tumor size in at least 25% of the enrolled subjects.”  
Indicate how the results of the study will benefit future patients with the disease/condition being 
studied and/or society, e.g., through increased knowledge of human physiology or behavior, 
improved safety, or technological advances. 
At the completion of this study, we hope to have improved our understanding of 
the relationship of CBD on cannabis use.    
 
 
 
EQUITABLE SELECTION OF SUBJECTS 
The risks and benefits of the research must be fairly distributed among the populations that stand 
to benefit from it.  No group of persons, for example, men, women, pregnant women, children, 
and minorities, should be categorically excluded from the research without a good scientific or 
ethical reason to do so.  Please provide the basis for concluding that the study population is 
representative of the population that stands to potentially benefit from this research.
Men, women, and minorities will all be recruited.  Pregnant women and children 
will be excluded in part due to the lack of data on the safety of Epidiolex in these 
groups. 
 
 
 
When people who do not speak English are excluded from participation in the research, provide 
the scientific rationale for doing so.  Individuals who do not speak English should not be denied 
participation in research simply because it is inconvenient to translate the consent form in 
different languages and to have an interpreter present.
 
Proficiency in English is necessary for a long-term treatment study that includes 
4 medical management sessions and ensures that the participants can properly convey 
any subtle side effects that relate to their safe participation in this study. 
 
 
 
For guidance, refer to the following Partners policy: 
          Obtaining and Documenting Informed Consent of Subjects who do not Speak English


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          https://partnershealthcare-public.sharepoint.com/ClinicalResearch/Non-
English_Speaking_Subjects.1.10.pdf
 
 
 
RECRUITMENT PROCEDURES 
Explain in detail the specific methodology that will be used to recruit subjects.  Specifically 
address how, when, where and by whom subjects will be identified and approached about 
participation.  Include any specific recruitment methods used to enhance recruitment of women 
and minorities.
9. Human Subjects and Recruitment Strategies: 
 
9.1. 
Sample Size: 
 
In order to meet the target sample of 30 completers, we expect to recruit 60 
participants, ages 18-65 45, and have approximately 60 of them sign the informed 
consent form. 
9.2. 
Advertising: 
 
Participants will be recruited via websites, newspaper advertisements, flyers on 
campus, and word-of-mouth.  We will not specifically recruit participants from particular 
patient units at McLean.  Participants may not be inpatients at McLean at the time of 
their participation in the study.  
9.3. 
Inclusion criteria 
 
1) Age range 18-65 45 years; 2) DSM-IV diagnosis of cannabis dependence, based 
on the Structured Clinical Interview for DSM-IV (SCID); 3) express a desire to quit 
cannabis use within the next 30 days; 4) have used cannabis on 4 days within the past 
30 days (i.e., an average of 1 day per week); 5) for women of childbearing age, a 
negative pregnancy test at screening with agreement to use adequate contraception to 
prevent pregnancy and monthly pregnancy tests; for men, contraception will be 
discussed at the beginning of the study with the study physician; 6) consent for us to 
communicate with their prescribing clinician; 7) furnish the names of 2 locators, who 
would assist study staff in locating them during the study period; 8) live close enough to 
McLean Hospital to attend study visits; 9) plan to stay in the Boston area for the next 3 
months; and 10) are willing and able to sign informed consent. 
9.4. 
Exclusion criteria 
 
1) Current diagnosis of other drug or alcohol dependence (excluding nicotine); 2) 
recent (within 3 months) significant cardiac disease; 3) current serious psychiatric 
illness or history of psychosis, schizophrenia, bipolar type I disorder; 4) current medical 
condition (including significant laboratory abnormalities, such as abnormal liver function 
tests) that could prevent regular study attendance; 5) mental retardation or organic 
mental disorder; 6) acutely dangerous or suicidal behavior; 7) currently in a residential 
treatment setting in which substance use is monitored and restricted, since the 
restricted access to drugs could represent an important confounding variable; 8) 
pregnant, nursing, or, if a woman of childbearing potential, not using a form of birth 
control judged by the investigator to be effective; 9) concomitant daily treatment with 
opioid analgesics, sedative hypnotics, or other known CNS depressants; 10) known 


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hypersensitivity to cannabinoids or sesame oil ; 11) disease of the gastrointestinal 
system, liver, or kidneys that may impede metabolism or excretion of CBD; 12) inability 
to read or write in English; 13) a history of seizures, head trauma or other history of 
CNS insult that could predispose the subject to seizures; 14) currently taking valproic 
acid, lamotrigine, or proparanolol, medications metabolized by UGT1A9 or UGT2B7 
enzymes (CBD may affect these UGT levels). 
 
 
Provide details of remuneration, when applicable.  Even when subjects may derive medical 
benefit from participation, it is often the case that extra hospital visits, meals at the hospital, 
parking fees or other inconveniences will result in additional out-of-pocket expenses related to 
study participation.  Investigators may wish to consider providing reimbursement for such 
expenses when funding is available
Participant Payments.   
 
Volunteers will receive a $50 honorarium for attending the initial assessment 
interview as well as $50 for the baseline visit.  They may earn $20 for each urine 
sample given on a non-medical management day and $20 for attending each medical 
management visit.  For each of the weekly 10-15 minute follow-up visits, subjects will 
receive $25.  They may earn up to a total of $80 as a bonus for completing all of the 
daily diaries.  Subjects will receive up to $620 for their participation in the study.  
Medication will be free. 
 
 
For guidance, refer to the following Partners policies: 
          Recruitment of Research Subjects 
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Recruitment_Of_Research_Subjects.pdf
 
          Guidelines for Advertisements for Recruiting Subjects
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Guidelines_For_Advertisements.1.11.pdf
 
          Remuneration for Research Subjects
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Remuneration_for_Research_Subjects.pdf
 
 
CONSENT PROCEDURES 
Explain in detail how, when, where, and by whom consent is obtained, and the timing of consent 
(i.e., how long subjects will be given to consider participation).  For most studies involving more 
than minimal risk and all studies involving investigational drugs/devices, a licensed physician 
investigator must obtain informed consent.  When subjects are to be enrolled from among the 
investigators’ own patients, describe how the potential for coercion will be avoided.
Informed consent. Eligible subjects will complete standard consent 
documentation.  Prior to the volunteer being asked any question about his/her health, 
the volunteer will be given a consent form to read.  The research assistant will go over it 
in detail with the volunteer.  After a physician answers any questions the volunteer may 


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have concerning the study, he/she will be asked to provide their informed consent.  If 
enrolled in the study, consent to communicate with their other clinicians will be obtained.  
Clinicians will be notified of their patients’ enrollment in the study, thus allowing them to 
carefully monitor for changes in mood while they are undergoing treatment to stop use 
of cannabis. 
 
 
 
NOTE: When subjects are unable to give consent due to age (minors) or impaired decision-
making capacity, complete the forms for Research Involving Children as Subjects of Research 
and/or Research Involving Individuals with Impaired Decision-making Capacity, available on 
the New Submissions page on the PHRC website: 
      https://partnershealthcare.sharepoint.com/sites/phrmApply/aieipa/irb 
 
For guidance, refer to the following Partners policy: 
     Informed Consent of Research Subjects:
     https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Informed_Consent_of_Research_Subjects.pdf
 
 
 
DATA AND SAFETY MONITORING 
Describe the plan for monitoring the data to ensure the safety of subjects.  The plan should 
include a brief description of (1) the safety and/or efficacy data that will be reviewed; (2) the 
planned frequency of review; and (3) who will be responsible for this review and for determining 
whether the research should be altered or stopped.  Include a brief description of any stopping 
rules for the study, when appropriate.  Depending upon the risk, size and complexity of the 
study, the investigator, an expert group, an independent Data and Safety Monitoring Board 
(DSMB) or others might be assigned primary responsibility for this monitoring activity.        
 
NOTE: Regardless of data and safety monitoring plans by the sponsor or others, the principal 
investigator is ultimately responsible for protecting the rights, safety, and welfare of subjects 
under his/her care. 
Safety Monitoring.Cannabidiol has been shown to have a favorable safety profile; it has 
been well-tolerated in several clinical trials and no adverse events have been reported.  
Nonetheless, we will monitor safety through the standardized methods described above 
in the medical management visits.  We will have a low threshold for obtaining additional 
medical workup during the study if the subject reports medical symptoms.  If a 
participant has a clinically significant laboratory or other medical abnormality that cannot 
be attributed to another cause, the participant’s medication will be discontinued and the 
participant will be followed for research visits.  
 
 
As discussed above in Section 8.2.i.a, the study physician will perform a physical 
examination and obtain an ECG at baseline and at 14 weeks.  Laboratory data 
(urinalysis, blood chemistries, complete blood count, electrolytes, and liver function 
tests) will be done at baseline, 4 weeks, and 14 weeks as well.  CBD should not be 
taken with alcohol, sedatives, hypnotics, or other psychoactive substances because 
they could potentiate the central nervous system effects of Epidiolex.  Thus, urine 


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toxicology and blood alcohol testing will be done weekly along with the twice weekly 
quantitative THC urine screens during treatment.  Women of childbearing potential will 
have urine pregnancy tests weekly each time a urine sample is given in addition to 
pregnancy tests at the screening visit and monthly during treatment; women who 
become pregnant will have their medication discontinued and will be referred to an 
obstetrician; like all participants, they will still be followed for research visits. 
 
 
Unanticipated problems involving risks to subjects or others, including adverse 
events, will be reported to the PHRC in accordance with PHRC unanticipated problems 
reporting guidelines. 
 
 
 
 
Describe the plan to be followed by the Principal Investigator/study staff for review of adverse 
events experienced by subjects under his/her care, and when applicable, for review of sponsor 
safety reports and DSMB reports.  Describe the plan for reporting adverse events to the sponsor 
and the Partners’ IRB and, when applicable, for submitting sponsor safety reports and DSMB 
reports to the Partners’ IRBs.  When the investigator is also the sponsor of the IND/IDE, include 
the plan for reporting of adverse events to the FDA and, when applicable, to investigators at 
other sites.   
 
NOTE: In addition to the adverse event reporting requirements of the sponsor, the principal 
investigator must follow the Partners Human Research Committee guidelines for Adverse Event 
Reporting
The Principal Investigator assumes responsibility for ensuring informed consent, 
data management, and the detection and reporting of adverse events.  In general, the 
data to be reviewed will include screening data, baseline data, efficacy data, safety 
data, quality assurance data, accrual status including projections, and any other data 
that will help in the assessment of the effectiveness of the clinical trial.   
The risk associated with participating in this study is moderate. Epidiolex, while 
not yet FDA-approved has been well-tolerated in other clinical trials with few side 
effects.  Consequently, serious side effects associated with this treatment are not 
expected. There will be on-call medical coverage to respond to any adverse events 
throughout the clinical trial. 
The Principal Investigator will conduct a review of all adverse events and 
determine the attribution and grade of severity of the adverse event by using the 
following scales: 
 
Attribution of Risk Categories: 
Definite:  Adverse event(s) will clearly be related to investigational agent(s) or 
other intervention 
Probable: Adverse event(s) will likely be related to investigational agent(s) 
Possible:   
Adverse event(s) may be related to investigational agent(s) 
Unlikely:  Adverse event(s) will doubtfully be related to investigational agent(s) 
Unrelated: 
Adverse event(s) will clearly not be related to the investigational 
agents(s) 
Grades of Risk: 


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0: No adverse event or within normal limits 
1:  Mild adverse event 
2:  Moderate adverse event 
3:  Severe adverse event resulting in hospitalization or prolongation of existing 
hospitalization, a persistent or significant disability/incapacity, or a congenital 
anomaly/birth defect 
4:  Life-threatening or disabling adverse event 
5:  Fatal adverse event 
 
Serious adverse events (SAEs) include any untoward medical occurrence that at 
any dose results in death or the immediate risk of death, hospitalization or the 
prolonging of an existing hospitalization, persistent or significant disability/incapacity or 
a congenital anomaly/birth defect. Subjects will be terminated from participation if the 
investigator feels that subjects' health or well-being may be threatened by continuation 
in the study. Serious unanticipated adverse events will be reported within 48 hours to 
the Partners IRB and NIDA. We will directly report to the FDA whenever their magnitude 
or frequency exceeds expectations. The principal investigator will evaluate the adverse 
event and determine whether the adverse event affects the Risk/Benefit ratio of the 
study and whether modifications to the protocol are required. In addition, he will conduct 
a review of all adverse events at least semi-annually, and he will evaluate the frequency 
and severity of the adverse events and determine if modifications to the protocol or 
consent form are required. 
 
 
 
MONITORING AND QUALITY ASSURANCE 
Describe the plan to be followed by the principal investigator/study staff to monitor and assure 
the validity and integrity of the data and adherence to the IRB-approved protocol.  Specify who 
will be responsible for monitoring, and the planned frequency of monitoring.  For example, 
specify who will review the accuracy and completeness of case report form entries, source 
documents, and informed consent.   
 
NOTE: Regardless of monitoring plans by the sponsor or others, the principal investigator is 
ultimately responsible for ensuring that the study is conducted at his/her investigative site in 
accordance with the IRB-approved protocol, and applicable regulations and requirements of the 
IRB.
 
The research assistants will be responsible for day-to-day monitoring of the 
validity and integrity of the data.  Dr. Hill will meet with the research assistants to 
discuss data monitoring on a monthly basis and will sample subject data folders monthly 
as well. 
 
 
 
For guidance, refer to the following Partners policies: 
          Data and Safety Monitoring Plans and Quality Assurance
            https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/DSMP_in_Human_Subjects_Research.pdf  
          


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          Reporting Unanticipated Problems (including Adverse Events)
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Reporting_Unanticipated_Problems_including_Adverse_Events.pdf
 
 
 
PRIVACY AND CONFIDENTIALITY 
Describe methods used to protect the privacy of subjects and maintain confidentiality of data 
collected.  This typically includes such practices as substituting codes for names and/or medical 
record numbers; removing face sheets or other identifiers from completed 
surveys/questionnaires; proper disposal of printed computer data; limited access to study data; 
use of password-protected computer databases; training for research staff on the importance of 
confidentiality of data, and storing research records in a secure location.   
 
NOTE: Additional measures, such as obtaining a Certificate of Confidentiality, should be 
considered and are strongly encouraged when the research involves the collection of sensitive 
data, such as sexual, criminal or illegal behaviors.
Data Management 
All data collected will be de-identified with subject ID numbers and used for 
research purposes only.  Written records will be kept in a locked file cabinet in a locked 
office.  They will be destroyed after 7 years.  Computerized data files will also be de-
identified with subject ID numbers and kept in a password protected file on a password 
protected computer. 
 
 
 
SENDING SPECIMENS/DATA TO RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
Specimens or data collected by Partners investigators will be sent to research collaborators 
outside Partners, indicate to whom specimens/data will be sent, what information will be sent, 
and whether the specimens/data will contain identifiers that could be used by the outside 
collaborators to link the specimens/data to individual subjects.
Not applicable 
 
 
Specifically address whether specimens/data will be stored at collaborating sites outside 
Partners for future use not described in the protocol.  Include whether subjects can withdraw 
their specimens/data, and how they would do so.  When appropriate, submit documentation of 
IRB approval from the recipient institution.
 
 
 


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RECEIVING SPECIMENS/DATA FROM RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
When specimens or data collected by research collaborators outside Partners will be sent to 
Partners investigators, indicate from where the specimens/data will be obtained and whether the 
specimens/data will contain identifiers that could be used by Partners investigators to link the 
specimens/data to individual subjects.  When appropriate, submit documentation of IRB 
approval and a copy of the IRB-approved consent form from the institution where the 
specimens/data were collected.