Clinical Study on Patients Receiving Opioid Therapy.
Hypothesis. Numerous studies have shown that patients receiving
opiate therapy for pain will use other drugs or not follow their
prescribed medication regimens. (Katz ,2003 )The reasons for
these deviations have not been identified in common medical
practice. Therefore this study is focused on identification of those
changes in clinical status that result in abnormal behavior.
Background: Several studies have shown that patients on chronic
opioid management for pain do not adhere to their medication
regimen (Katz, 2002, 2003) . These deviations include: not taking
the prescribed drug, taking other non-prescribed medications, and
using illicit drugs such as THC, methamphetamine, or
cocaine.(Pesce et al 2011) The recent introduction of LC-MS/MS
for the identification and quantification of drugs in urine has made
it possible to identify this aberrant behavior (Mickel et al 2009),
but the reasons for this non adherence and use of other drugs has
not been well established. The purpose of this long-term study is to
identify the possible causes of this behavior. The causes may
include lack of pain relief, depression, diversion, and bingeing to
get “high”. As these patients require pain medications, but are not
adhering to the medication regimen, determining possible causes is
important to maintain the patient’s well being, as well as protecting
the physician patient relationship.
For example at what point does failure in the treatment of pain
cause the patient to seek other drugs? Can this be approximated
from a correlation between behavior as determined from the LCMS/MS drug test results and the VAS scale? Is the patient so
depressed or lethargic that they need a stimulant and are using
cocaine or methamphetamine for that purpose?
Methods
Patient selection: Patients on chronic opioid therapy who are being
examined for compliance and possible aberrant behavior using
urine drug testing. These patients will have agreed to urine drug
testing as part of their medical therapy.
Physician assessment. The participating physician will maintain
records which include VAS score, depression score, and reason for
aberrant behavior as given by the patient.
The patient’s mental health status will be evaluated by the Anxiety
assessment tool GAD-2 and depression by the PHQ-2 tool.
Expected results: The first hypothesis to be tested is whether or not
there is a correlation between the VAS score and aberrant
behavior. A second hypothesis to be tested is whether or not the
patient shows marked depression as evidenced by physician history
and whether the patient is on antidepressant drugs. A third
hypothesis is that changes in the patient’s personal life may result
in stress causing the patient to turn to “recreational” drug for relief.
For evaluating the correlation between VAS score and aberrant
behavior, the type of drug use or misuse must be scored. For
evaluating antidepressant use of LC-MS/MS data is essential, as it
has been demonstrated that the patient’s physician may not know if
the patient is taking an antidepressant (Bordson 2013). Therefore
these drugs should be included in the test panel. The third
hypothesis can be tested by comparing the type of aberrant
behavior to changes in home life or social status.
Study design
The proposed clinical trial is an ongoing 1 to 3 year observational
study of 1500 to 2500 volunteers undergoing chronic opioid
therapy who have agreed to be monitored for adherence using
urine drug testing. In one analysis each patient will serve as their
own control and the failure rate calculated. In a second analysis the
data will be pooled to determine the aberrant behavior rate for the
total patient pool, and then for the proximate cause of the behavior.
All volunteers will have Birdrock urine drug testing performed.
Subjects
Patients who are on chronic opioid therapy
Number of volunteers
Approximately 1500 to 2500 volunteers.
Inclusion Criteria
The volunteers need to meet the following criteria
Prepare and sign the informed consent form.
Be at least 18 years of age
Currently on chronic opioid therapy
Be willing to fill out study question forms
Exclusion criteria
Diminished mental capacity with an inability to understand the
study protocol or the questionnaires, or the inability to read/write
English.
Anything that would make it not possible to be in compliance with
the study.
A participant is free to withdraw from the study at any time if they
so request.
Associate Investigator time commitment:
Orientation 1 hour
Study Schedule:
Visit
Visit 1
Informed
X
consent
Inclusion
X
criteria
met/not met
Evaluation
x
with GAD-2
and PHQ-2
tools.
Urine drug
x
screen
Urine drug
Y/N if no
screen
why?
consistent?
Visit 2
Visit 3
Visit 4
x
x
x
x
x
x
Y/N if no
why?
Y/N if no
why?
Y/N if no
why?
Estimate of physician time per patient:
Visit
Discussion
of study
with patient
Review of
patient
UDS
results and
patient drug
regimen
Visit 1
15 minutes
of time
Visit 2
Visit 3
Visit 4
15 minutes
of time
15 minutes
of time
15 minutes
of time
15 minutes
of time
Ethics and compliance.
The study will be in compliance with the Code of Federal
Regulations on the Protection of Human Subjects (45 CFR Part
46), the Declaration of Helsinki, the International Conference on
Harmonization Guidelines for Good Clinical Practice (ICH E6),
and the privacy and informed consent policies of Birdrock
Laboratories.
Fair Market Valuation of Physician Compensation.
This has been calculated from data provided by Huron Healthcare.
Visit 1 Screening Visit (Day 0)
The participating physician Investigator will select the study
volunteers based on a review of their medical record.
Under the supervision of the participating physician, trained
physician assistants, office staff, or other qualified individuals will:
Review the potential volunteer medical records for eligibility to
enter the study.
Explain the purpose of the study to the potential patient volunteers.
Obtain and document the volunteer’s consent form.
Document the volunteer’s medical history including pain history,
and medication history (including specific medications, doses,
when and for how long, known or serious adverse medication
events)
Collect the following physical and demographic data: age, gender,
height, weight, vital signs.
The as required by the patient’s medical condition and treatment
protocol for opioid therapy (medical necessity) , appropriate
laboratory tests will be ordered. As a condition for entrance into
the study a urine drug screen will be ordered from Birdrock
Laboratories.
At this visit the office staff will coordinate study visits of the
patient with their ongoing physician follow up visits.
Visit 2 (30 to 180 days after first visit) After review of the
volunteers UDT, the physician investigator will code the results as
aberrant or consistent with the medication history. Additional
documentation will also be collected and coded. This will include
pain history, and medication history (including specific
medications, doses, when and for how long, known or serious
adverse medication events) as well as depression history and vital
signs. After reviewing all the data, the investigator will decide at
which time a follow up UDT is necessary
Visit 3 TO 6 (30 to 180 days after previous visit) After review of
the volunteers UDT, the physician investigator will code the results
as aberrant or consistent with the medication history. The same
follow up medical history as described in visit 2 will be obtained.
After reviewing all the data, the investigator will decide at which
time a follow up UDT is necessary.
For the study volunteers, Birdrock will bill the patient’s insurance
carrier for the clinical reference laboratory services used clinically.
Each study site will bill any other medical necessary services in the
standard manner.
De-identification of patient protected health information.
A randomized alphanumeric code will be assigned to each patient.
This code identifier will be kept by each physician investigator for
their study volunteers. The summarized data for each patient will
be sent to the Principal Investigator using the patient’s assigned
code.
Data generation and record keeping
The request for UDT testing along with medication history and
medical necessity as well as the patient’s sample will be sent to
Birdrock Laboratories as part of the usual patient care. The patient
will be given an alphanumeric code. Only the patient’s test results,
medication list, depression score, pain score, will be returned to the
principal investigator.
Publication Policy
The Principal Investigator is free to publish, present or use any
information derived from this study for instructional, research or
publications.
Final Report
PI will provide quarterly summaries of the study to the Principal
and other Investigators.
Premature Termination or Suspension of the Study
This study may be suspended or terminated if there is reasonable
cause. Written notice will be sent to all participating parties and the
IRB.
References:
Katz, et al Behavioral Monitoring and Urine Toxicology Testing in
Patients Receiving Long-Term Opioid Therapy Anesthesia &
Analgesia: 2003; 97:
1097-1102
Katz, N, and Fanciullo, G Role of Urine Toxicology Testing in the
Management of Chronic Opioid Therapy Clinical Journal of Pain:
2002 18: S76-S82
Pesce et al, Illicit Drug Use in the Pain Patient Population
Decreases with Continued Drug Testing Pain Physician 2011;
14:189-193
West R. Observations of medication compliance by measurement
of urinary drug concentrations in a pain management population.
Journal of Opioid Management 2010, 6:253-257