Recent Scientific and Process Publications from the Clinical Trials Network

1. Recent Scientific and Process Publications from the Clinical Trials Network Betty Tai, Ph.D. Harold Perl, Ph.D. (CTN-0004) Carmen Rosa, M.S. (Valid Subgroup Analyses) Carol Cushing, B.B.A., R.N. (CTN-0030) Petra Jacobs, M.D. (CTN-0010)

2. Measuring Therapist Skills in Delivering Evidence Based Treatment CTN-0004

3. Treatment Fidelity is Critical Issuein Adopting EBTs • MET increases treatment engagement and reduces later substance use • MET is manual-based adaptation of MI • Little research on whether community therapists can implement MET with skill • Few practical tools to evaluate fidelity of real-world treatment • New rating scale measures therapist adherence and competence in MET CTN-0004 Drug and Alcohol Dependence 96 (1-2) July 2008, 37- 48

4. Independent Tape Rater Scale • Audiotapes of CTN-0004 sessions • 15 raters; 35 therapists; 5 outpatient programs • Psychometrically sound • Assesses practices that are consistent or inconsistent with model • Measures frequency and appropriateness of therapist practices • 2-factor scale reliably distinguished MET and TAU therapists • Fundamental MI skills • Advanced MI skills CTN-0004 Drug and Alcohol Dependence 96 (1-2) July 2008, 37- 48

5. Better MET Skills Lead to Better Clinical Outcomes • When therapists use MI skills more often and more competently • Clients express increased motivation to reduce or stop substance use (competent use of fundamental skills: r = .22, p < .001) • Clients present more negative drug screens during 4-week treatment phase (frequent use of advanced skills: r = .21, p < .001) • Expert training and in-clinic supervision & coaching increases therapist skill CTN-0004 Drug and Alcohol Dependence 96 (1-2) July 2008, 37- 48

6. Findings Utilized as Core of NIDA Blending Product • Many State AOD Directors now funding clinical supervision • Research instrument now being used as clinical tool

7. Valid Analysis to Address Health Disparities in Substance Abuse

8. Policies mandate inclusion and analyses of these data Researchers usually include participants, but don’t perform valid analyses Measures and analytic strategies may not apply equally for all groups This article addresses ways to improve these analyses Measurement Data analysis Improving Valid Analyses in Ethnic/Race Minorities Burlew et al JSAT 36 (2009) 25-43

9. Overall Norms Not Appropriate for All Ethnic Subgroups • MMPI-2 standardization sample • 993 Non-Hispanic Caucasians (NHCs) • 6 Asian Americans (AAs) • Overall mean = 11.06 (psychasthenia scale) • for NHCs on pt scale = 11.04 • for AAs on pt scale = 14.33 • Raw score of 21 for an AA is considered clinically significant for internal distress • Hypothetical example: 993 AAs and 6 NHCs • Overall mean in this population is 14.30 • Raw score of 21 now would be in normal range Burlew et al JSAT 36 (2009) 25-43

10. Recommendations: Measures Determine appropriateness for a specific group Evaluate characteristics of the standardization sample Examine effects of interviewer/rater race/ethnicity Burlew et al JSAT 36 (2009) 25-43

11. Example: Combining Ethnic Minorities Some analyses could be misleading Burlew et al JSAT 36 (2009) 25-43

12. Recommendations: Data Analysis • Sample size is challenging: • Target specific groups • Evaluate effect sizes • Apply statistical techniques for small samples • Race-comparison designs may not be optimal • Conduct within-group or between-groups analyses • Look at engagement or retention instead Burlew et al JSAT 36 (2009) 25-43

13. Conclusions • Need to increase valid analyses • Need to consider limitations and resources during study design • Education: CTN Workshop “Practical Approaches for Valid Subgroup Analysis in the CTN” March 24, 2009 – 1:00-3:30 pm @ North Bethesda Marriott Burlew et al JSAT 36 (2009) 25-43

14. Process Improvement: CTN-0030 CTN-0030

15. The Importance of Process Anyone responsible for organizing and conducting a multi-site study should have a full understanding of the complexity of the undertaking… — Lawrence Friedman Organizational design of a multi-site trial is as important to its success as is the experimental design. —Curtis Meinert

16. SPs: Simulated Patients Actors trained to portray a set of symptoms Widely used US medical schools for training/evaluation Other healthcare training-RNs PharmDs, MSWs Canada National Medical Licensing Exams US Medical Licensing Exam Growing trend to help Substance Use clinicians Clear advantage of using SPs instead of real Pts Limitations: study specific, subjective bias, cost CTN-0030

17. POATS Trial – SPs in Screening/Intake • SP trained to emulate patient • Construction worker • Back Pain • Out of Work • Prescription Opioid Dependence • Screening Visit 1 (research staff) • Consent • Inclusion/exclusion • Locater info • Baseline assessments Both Visits: Admin Research Team Observes & Takes notes SP Debrief • Screening Visit 2 • (medical staff) • Clinical assessment • Lab procedures SP Debrief CTN-0030

18. Process Change – POATS Trial Debriefing Topics Scheduling/Organizing Consent Medical/Counselor Interviews Case Report Forms Protocol Flow Participant Comfort Process Changes Ambiance Environment Checklists Summaries Training Time Allotment Extended Hours Calendars CTN-0030

19. Significance: Innovation in Improving Clinical Trials Process Uses study participant perspective Effective in training research staff Research process Clinical skills Embraced by the CTN Steering Committee Used in four CTN protocols Implications for improving recruitment CTN-0030

20. CTN-0010 CTN-0010

21. Context • Increased concerns about prescription opioid use • Usual Tx for opioid addicted youth: Detox and counseling • First RCT of continued agonist Tx in this young population CTN-0010

22. Study Design Screening Assent/Consent Randomization 15-21 y/o Opioid addicts (N=152) BUP/NX DETOX over 2 wks Dose Up to 14 mg BUP/NXTreatment and Taper for 12 wks Dose up to 24 mg Both arms received counseling for 12 wks Primary outcome measure (Opioid Positive Urine) @ week 4, 8, and 12 CTN-0010 Woody, G. E. et al. JAMA 2008;300:2003-2011.

23. Participant Characteristics • Participant Characteristics: • Mean age: 19 • Race/ethnicity: • –White: 73% • –Hispanic: 25% • Main problem • –Heroin: 55% • –Opioid analgesics: 34% • Median opioid use: 1 year • Injecting: 48% • Positive for hepatitis C: 18% CTN-0010 Woody, G. E. et al. JAMA 2008;300:2003-2011.

24. Primary Outcome: Opioid Positive Urines 12-Week BUP/NX DETOX CTN-0010 Woody, G. E. et al. JAMA 2008;300:2003-2011.

25. Secondary Outcomes • During weeks 1-12, pts on 12 wks BUP/NX vs. 2 wks had: • better retention (p<.001): 70% vs. 21% • less injecting (p=.01) • less reported use of cocaine (p<.001), • marijuana (p<.001) • no SAE resulting from BUP/NX CTN-0010 Woody, G. E. et al. JAMA 2008;300:2003-2011.

26. Conclusions • BUP/NX for 12 weeks is safe in this young population • Continuing BUP/NX for 12 weeks vs. 2 weeks improved outcome • Research on long term treatment and follow-up in this population might be a good next study CTN-0010 Woody, G. E. et al. JAMA 2008;300:2003-2011.