Research Strategies to Test Behavioral/Psychotherapy Treatments for Substance Use Disorders: Several Examples Richard A. Rawson, Ph.D UCLA ISAP Cairo, Egypt Sept 27, 2004

Research on Behavioral/Psychotherapy Treatments: Considerations Many of the research design principles described for medication research apply We want to compare our experimental treatment with a standardized comparison condition. The comparison condition has to be minimal, but defensible from an ethical point of view.

Research on Behavioral/Psychotherapy Treatments: Considerations Except, with behavioral/psychotherapy: “Double-blind, placebo controlled trials not possible. “No treatment control groups” not ethical Major strategy is to compare different active treatments, or different “doses” of a therapy.

Research on Behavioral/Psychotherapy Treatments: Considerations Possible comparison groups Waiting list control Smaller (minimal) dose “Treatment as usual” Adding experimental treatment as an added piece of treatment on top of a standard treatment received by everyone in both groups Some control activity requiring the same amount of time, which is defensible as a clinical intervention (eg. bibliotherapy, viewing educational videotapes.

Research on Behavioral/Psychotherapy Treatments: Considerations Fidelity measures are critical (are they getting the therapy we want to test) Specific therapist effects How much of the “dose” do they actually receive? (as opposed to what they receive ideally)

Elements in a successful behavioral/psychotherapy treatment outcome study report Describe intervention(s) clearly Describe study population Describe fidelity and dose delivered information Describe analysis of major outcome during the treatment period Describe analysis of intervention effect post- treatment Describe relationship of subject characteristics and outcomes Describe relationship of treatment “dose” and outcomes Others

A Multi-Site Comparison of Psychosocial Approaches for the Treatment of Methamphetamine Dependence Richard A. Rawson, Ph.D. and The Methamphetamine Treatment Project Corporate Authors* Addiction (2004, June)

Project Goals: To study the clinical effectiveness of the Matrix Model To compare the effectiveness of the Matrix model to other locally available outpatient treatments To establish the cost and cost effectiveness of the Matrix model compared to other outpatient treatments To explore the replicability of the Matrix model and challenges involved in technology transfer

CSAT MTP Study Treatment as Usual Varied length Varied frequency Varied type Variable training No fidelity measures Matrix Model 3 visits per week 16 weeks long Content Standardized Training Standardized Fidelity to protocol insured

Sample Description

Baseline Demographics Participants Served (n)1016 Age (mean)32.8 years Education (mean)12.2 years Methamphetamine Use (mean)7.5 years Marijuana Use (mean)7.2 years Alcohol Use (mean)7.6 years

Gender Distribution of Participants

Ethnic Identification of Participants

Marital Status of Participants

Employment Status of Participants

Route of Methamphetamine Administration

Changes from Baseline to Treatment-end

Days Paid for Work in Past 30 Possible is 0-30; t paired =6.01; p-value<0.000 (highly sig.)

Total Income (Past 30 days) of Participants t paired =2.34; p-value=0.02 (sig.)

ASI Composite Scores Possible is 0-1; Higher : worse problem t paired : *p-value<0.03 (sig.), **p-value<0.000 (highly sig.)

Days of Methamphetamine Use in Past 30 (ASI) Possible is 0-30; t paired =20.90; p-value<0.000 (highly sig.)

Days of Marijuana Use in Past 30 (ASI) Possible is 0-30; t paired =8.02; p-value<0.000 (highly sig.)

Days of Alcohol Use in Past 30 (ASI) Possible is 0-30; t paired =6.47; p-value<0.000 (highly sig.)

Beck Depression Inventory (BDI) Total Scores Possible is 0-63; t paired =16.87; p-value<0.000 (highly sig.)

BSI Scores (mean) BL 1 Tx-end Paired t * Somatization Obsessive-Compulsive Interpersonal Sensitivity Depression Anxiety Hostility Phobic Anxiety Paranoid Ideation Psychoticism Possible, all scores, is 0-4; * all p-values<0.000 (highly sig.)

Positive Symptom Total (PST) from Brief Symptom Inventory (BSI) Possible is 0-53; t paired =14.33; p-value<0.000 (highly sig.)

Site (TAU length, wks.) TAU Mean SD Matrix 16-week Mean SD Site 1 (8) Site 2 (12) Site 3 (12) Site 4 (16) Site 5 (12) Site 6 (12) Site 7 (16) Site 8 (12) Overall summary Table 5. Summary of the number of clinical contacts made by participants, by treatment group and site

Figure 3. Participant retention throughout treatment, by site and treatment group

Site TAU length (wks.) Log-rank Chi-square p Site < Site Site Site Site < Site < Site Site Table 7. Comparison of retention between groups within sites, with Matrix truncated to the length of TAU at each site

Figure 4. Percent completing treatment, by group

Figure 5. Mean number of MA-free urine samples, by treatment length and treatment group (Matrix group data truncated to the length of TAU)

Site (TAU length, wks.) Raw DataTruncated Data Matrix16TAUMatrix16TAU tp meanSDmeanSDmeanSDmeanSD Site 1 (8) Site 2 (12) Site 3 (12) Site 4 (16) Site 5 (12) Site 6 (12) Site 7 (16) Site 8 (12) Table 8. Summary of the number of MA-free urine samples provided by participants, by treatment group and site

Site (TAU length, wks.) Raw DataTruncated Data Matrix16TAUMatrix16TAU tp meanSDmeanSDmeanSDmeanSD Site 1 (8) Site 2 (12) Site 3 (12) Site 4 (16) Site 5 (12) Site 6 (12) Site 7 (16) Site 8 (12) Table 9. Longest MA abstinent period by treatment group and site

Figure 2. Mean number of weekly data visits attended, by treatment length and treatment group (Matrix group data truncated to the length of TAU)

Discharge UA Result by Attendance During Treatment and Group Matrix 16TAU cleanmissingdirty

Figure 1. Overall participant follow-up by treatment condition and time point

6-mos. F.U. UA Result by Attendance During Treatment and Group Matrix 16 TAU MA-missingMA+

Figure 5. Urinalysis Results: %Meth Negative

Figure 6. Participant self-report of MA use (number of days during the past 30) at enrollment, discharge, and 6-month follow-up, by treatment condition

MTP Study Conclusions A multisite evaluation of a research-based intervention can be conducted in community sites during a 3 year period. Six research-naïve sites and 2 experienced sites successfully were trained and conducted all necessary research activities for a complex clinical trial. A complex psychosocial treatment protocol was successfully replicated at 8 sites over a 3 year period. Over 1000 MA-Users received free treatment.

MTP Study Conclusions Treatment for MA dependence associated with improvements in many domains including drug use, mj use, mood, Income Matrix treatment results in longer retention, more sessions attended, more treatment completers, more MA-negative Uas, longer periods of MA abstinence * Except for drug court site

MTP Study Conclusions Outcomes at discharge and follow-up demonstrated comparable results between Matrix and TAU Program compliance associated with superior urinalysis results at discharge and follow-up

MTP Study Conclusions The design of multi-site studies has to carefully consider priorities among the following issues: Priority of testing the null hypothesis of the primary study outcomes Flexibility to accommodate all investigators individual site priorities and site program variability

Site Duration of Treatment Intensive Phase Individual Sessions Group Sessions 12-Step Program Involvement Site 1 8 wks 1x/wk x 4-8 wks, min each 4x/wk x 4-8 wks, 3hr each, families attend 1x/wk required; 1x/wk x 4-8 wks Site 2 12 wks 1x/wk x 12 wks, 1 hr each 5x/wk x 2wk, 3x/wk x 2wks, 2x/wk x 8 wks recommended Site 3 12 wks 1x/wk x 12 wks, 1 hr each nonerecommended Site 4 16 wks 1x/wk x 16 wks, min each 3x/wk x 16 wks, 1 hr each required; 3x/wk x 16 wks Site 5 12 wks 1x/wk x 12 wks, min each 3x/wk x 12 wks, 90 min each and 2x/wk x 12 wks, min each required; 1x/wk x 12 wks Site 6 12 wks 1x/wk – 2x/mo x 12 wks, 1 hr each 2x/wk x 12 wks, 90 min each, families attend 1x/2 wks recommended Site 7 16 wks 1x/wk x 16 wks, 1 hr each 2x/wk x 16 wks, 2 hrs each recommended Site 8 12 wks 2x/wk x 12 wks, 1 hr each 1x/wk x 12 wks, 2 hrs each required; 6 meetings Table 2. Treatment-As-Usual: Elements of Treatment

Site TAU (n) Matrix 16-week (n) Total Site Site Site Site Site Site Site Site Overall TOTAL Table 3. Enrollment in the MTP by Site and Treatment Condition

CharacteristicSummary % Male45 Age (Yrs.), mean (sd)32.8 (8.0) Ethnicity (%) Caucasian60 African-American2 American Indian3 Asian/Pacific Islander17 Hispanic18 Educational Attainment Level (yrs.), mean (sd)12.2 (1.7) % Employed69 % Married (and not separated)16 Overall Substance Use Patterns-Lifetime (yrs.), mean (sd) Methamphetamine7.54 (6) Alcohol7.6 (8.5) Cocaine1.75 (3.5) Cannabis7.15 (8) Overall Substance Use Patterns—Days in Past 30, mean (sd) Methamphetamine11.53 (9.6) Alcohol4.72 (7.3) Cocaine0.21 (1) Cannabis4.38 (8.3) Preferred Route of Administration of MA (%) Oral0 Nasal11 Smoked65 IV- injection24 Table 4. MTP Participant Characteristics (taken from baseline ASI)

Site (TAU length, wks.) TAU Mean SD Matrix 16-week Mean SD Site 1 (8) Site 2 (12) Site 3 (12) Site 4 (16) Site 5 (12) Site 6 (12) Site 7 (16) Site 8 (12) Overall summary Table 5. Summary of the number of clinical contacts made by participants, by treatment group and site

Site TAU length (wks.) Log-rank Chi-square p Site < Site Site Site Site < Site < Site Site Table 7. Comparison of retention between groups within sites, with Matrix truncated to the length of TAU at each site

Site (TAU length, wks.) Raw DataTruncated Data Matrix16TAUMatrix16TAU tp meanSDmeanSDmeanSDmeanSD Site 1 (8) Site 2 (12) Site 3 (12) Site 4 (16) Site 5 (12) Site 6 (12) Site 7 (16) Site 8 (12) Table 8. Summary of the number of MA-free urine samples provided by participants, by treatment group and site

Site (TAU length, wks.) Raw DataTruncated Data Matrix16TAUMatrix16TAU tp meanSDmeanSDmeanSDmeanSD Site 1 (8) Site 2 (12) Site 3 (12) Site 4 (16) Site 5 (12) Site 6 (12) Site 7 (16) Site 8 (12) Table 9. Longest MA abstinent period by treatment group and site

Figure 1. Overall participant follow-up by treatment condition and time point

Figure 2. Mean number of weekly data visits attended, by treatment length and treatment group (Matrix group data truncated to the length of TAU)

Figure 3. Participant retention throughout treatment, by site and treatment group

Figure 4. Percent completing treatment, by group

Figure 5. Mean number of MA-free urine samples, by treatment length and treatment group (Matrix group data truncated to the length of TAU)

Figure 6. Participant self-report of MA use (number of days during the past 30) at enrollment, discharge, and 6-month follow-up, by treatment condition