Feasibility of Conducting Genetics Research at Community Treatment Programs

1
Feasibility of Conducting Genetics Research at
Community Treatment Programs
Sonne SC1, Gentilin, SM1, Sampson R1, DeVane,
CL1, Thomas, C2,, Berrettini, W3
1Medical University of South Carolina,
2University of California, Los Angeles,
3University of Pennsylvania School of Medicine
ABSTRACT The addition of genetics research to
pharmacotherapy trials is becoming more and more
common. However, there has been some concern
among community treatment providers that genetics
research would be unacceptable to their clients.
The National Institute on Drug Abuse Clinical
Trials Network (NIDA CTN) is currently conducting
an add-on genetics substudy to a pharmacotherapy
trial comparing the effects of long-term
methadone and buprenorphine on liver function
(Starting Treatment with Agonist Replacement
Therapies, or START). The genetics substudy is
exploratory in nature, with three main goals 1)
To better understand the potential genetic
influence on opioid addiction (wk 2 sample) 2)
To better understand how opioid dependent
individuals metabolize buprenorphine and
methadone (wk 12 sample) and 3) To evaluate
feasibility of conducting a genetics sub-study
within the CTN. Although data are still being
collected to accomplish the first two goals,
there is good evidence to support the feasibility
of collecting genetic samples for analysis
through the CTN. To date, all 8 of the START
research sites have submitted samples for this
substudy. Of the START participants eligible to
enroll in the genetics substudy to date, 892 have
been approached to participate and 846 consented.
There have been 815 blood samples obtained for
the week 2 sample, which goes to the NIDA
repository, and 644 samples obtained and sent (at
week 12) to MUSC for pharmacogenetic analysis.
The genetics substudy has 4 different levels of
consent so that participants can choose how their
samples may be used in the future. Most
participants (79) have agreed to the most
liberal use of their samples. Taken together,
these data suggest that individuals in community
treatment settings are willing to participate in
genetic studies on addiction.
INTRODUCTION
RESULTS
RESULTS (Continued)
Table 1. Genetics Recruitment by Site
Although the study of genetics can be
successfully carried out within academic centers,
the feasibility of implementing such a study
within community treatment settings was unclear.
The Clinical Trials Network (CTN) has implemented
an ancillary study of genetics in conjunction
with another ongoing CTN trial, Starting
Treatment with Agonist Replacement Therapies, or
START. Areas of interest were the ability to
acquire necessary regulatory approvals across
participating sites, the additional burden to
research staff to execute the substudy, and the
receptiveness of potential study participants to
donate their genetic material for research
purposes.
Figure 1. Participant Level of Consent Across
Sites
Site Invited Refused Consented Week 2 Samples Collected Week 12 Samples Collected
Site A Site B Site C Site D Site E Site F Site G Site H All Sites 105 148 139 77 48 155 130 90 892 12 9 0 7 0 12 2 4 46 (5) 89 94 100 91 100 92 98 96 95 92 135 136 67 47 135 123 80 815 71 108 122 48 35 106 99 55 644
METHODS
In addition to determining the feasibility of
conducting a genetics substudy within the CTN,
other aims of this project were to 1) obtain
genetic samples to better understand the
potential genetic influence on opioid addiction
(wk 2 sample) and 2) to better understand how
opioid dependent individuals metabolize
buprenorphine and methadone (wk 12 sample).
These samples were obtained during regularly
scheduled START blood draws START study week 2
Participants provided three 7 ml tubes of blood
that are sent to the Rutgers University Cell and
DNA Repository for later analysis of the genetic
influence on opioid addiction. START study week
12 Participants provided one 7ml tube of blood
and a urine sample to the Medical University of
South Carolinas Drug Disposition Laboratory to
evaluate the pharmacogenetics of buprenorphine
and methadone in opioid dependent individuals.
Participants
As can be seen in Table 1, the majority of START
participants invited to be in the genetics
substudy agreed and signed informed consent. The
decrease in the number of samples collected
between Week 2 and Week 12 was largely due to
attrition of participants from the START study.
Study participants who drop out of START are no
longer eligible to continue in the genetics study.

• Subjects
• All participants currently enrolled in the START
  study are eligible to participate in the genetics
  sub-study.
• Regulatory
• All 8 of the sites participating in the START
  study obtained IRB approval of the genetic
  substudy from their respective IRBs.
• Informed consent forms were separate documents
  from the START study.
• Participants received on average 25 compensation
  for each of the two visits when genetics samples
  were collected. Amount of remuneration varied
  slightly by site.
• Support
• A 42 page Operations Manual was developed in
  addition to the protocol to provide specific
  detail to the sites regarding study procedures.
• Web based group trainings were initially held
  prior to study initiation and individual training
  was conducted via conference call for new staff
  as needed
• A member of the genetics team attends regularly
  scheduled START conference calls with the sites
  to discuss issues related to the genetics study
  and provide ongoing support.

Table 2. Levels of Consent
As can bee seen in Figure 1, the majority of
participants consented to the most liberal use of
their genetic material.
Consent Levels Participants ()
Level 1 START genetics study only 71 (8.8)
Level 2 START genetics study genetics studies for opioid dependence 36 (4.5)
Level 3 Level 2 substance abuse and/or related medical problems 205 (25.5)
Level 4 START genetics study all other genetics research 492 (61.2)
CONCLUSIONS / DISCUSSION

• These data suggest that individuals seeking
  treatment for substance abuse in community
  treatment settings are willing to participate in
  a genetics study.
• Most participants willingly consent to the most
  liberal use of their genetic material including
  storage of samples indefinitely for future use.
• Although this study is ongoing, progress to date
  suggests it is feasible to conduct a genetics
  study through the NIDA Clinical Trials Network.
• Site staff received significant training and
  support from the START lead team in conjunction
  with the genetics researchers, which has aided in
  the successful conduct of this trial.
• Acceptability of genetic testing by community
  treatment program staff as well as research staff
  may play an important role in the level of
  consent given by research participants.
• The burden to participants was minimized by
  having genetics samples obtained at the same time
  as regularly scheduled START blood draws

Table 2 describes the level of consent chosen by
the 804 participants who supplied at least a
valid week 2 sample. Of note, level 3 was the
highest level of consent approved by the IRB for
2 sites. These 2 sites represented 142 (69.2) of
the 205 who consented at this level.
Sponsored by the National Drug Abuse Treatment
Clinical Trials Network