Research Strategies to Test Behavioral/Psychotherapy Treatments for Substance Use Disorders: Several Examples

Richard A. Rawson, Ph.DUCLA 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

45

55

0

10

20

30

40

50

60

female male

Gender

Per

cen

t

Ethnic Identification of Participants

60

2 3

17 18

0

10

20

30

40

50

60

Ethnic Identification

Per

cent

caucasian

african amer

native amer

asian/pac isl

hispanic

Marital Status of Participants

16

33

50

0

10

20

30

40

50

Marital Status

Per

cent

married/remar.

separated/div.

single/widowed

Employment Status of Participants

69

2

23

6

0

10

20

30

40

50

60

70

80

Employment Status

Pe

rce

nt

FT/PT

Retired/Disable

Unemployed

Student/Control Env.

Route of Methamphetamine Administration

24

11

64

0

10

20

30

40

50

60

70

Route of Administration

Per

cen

t U

sin

g b

y R

ou

te

nasal

smoke

iv

Changes from Baseline to Treatment-end

Days Paid for Work in Past 30

10.4

8.2

0

2

4

6

8

10

12

BL Tx end

Mea

n D

ays

Pai

d

Possible is 0-30; tpaired=6.01; p-value<0.000 (highly sig.)

Total Income (Past 30 days)of Participants

1211

1096

1000

1200

1400

BL Tx end

Mea

n To

tal I

ncom

e ($

)

tpaired=2.34; p-value=0.02 (sig.)

0.53

0.230.260.24

0.21

0.11

0.21 0.220.19

0.10

0.15

0.08

0.49

0.21

0.0

0.1

0.2

0.3

0.4

0.5

0.6

Me

an

Co

mp

os

ite

Sc

ore

BL

Tx end

ASI Composite Scores

Possible is 0-1;

Higher : worse problemtpaired: *p-value<0.03 (sig.),

**p-value<0.000 (highly sig.)

Days of Methamphetamine Use in Past 30 (ASI)

4.4

11.5

0

2

4

6

8

10

12

BL Tx end

Mea

n D

ays

Use

Possible is 0-30; tpaired=20.90; p-value<0.000 (highly sig.)

Days of Marijuana Use in Past 30 (ASI)

2.4

4.5

0

2

4

6

8

10

12

BL Tx end

Mea

n D

ays

Use

Possible is 0-30; tpaired=8.02; p-value<0.000 (highly sig.)

Days of Alcohol Use in Past 30 (ASI)

3.3

4.8

0

2

4

6

8

10

12

BL Tx end

Mea

n D

ays

Use

Possible is 0-30; tpaired=6.47; p-value<0.000 (highly sig.)

Beck Depression Inventory (BDI) Total Scores

9.9

15.4

0

5

10

15

20

BL Tx end

Mea

n To

tal S

core

Possible is 0-63; tpaired=16.87; p-value<0.000 (highly sig.)

BSI Scores (mean)BL1 Tx-end

Paired t *

Somatization 0.7 0.5 7.67

Obsessive-Compulsive 1.2 0.9 11.40

Interpersonal Sensitivity

1.0 0.7 11.40

Depression 1.2 0.8 11.98

Anxiety 0.9 0.6 11.24

Hostility 0.8 0.6 9.39

Phobic Anxiety 0.6 0.4 8.47

Paranoid Ideation 1.1 0.7 11.49

Psychoticism 0.9 0.6 10.701Possible, all scores, is 0-4; *all p-values<0.000 (highly sig.)

Positive Symptom Total (PST) from Brief Symptom Inventory (BSI)

18

26

0

10

20

30

BL Tx end

Mea

n #

sym

ptom

s

Possible is 0-53; tpaired=14.33; p-value<0.000 (highly sig.)

 Site (TAU length,

wks.)

TAUMean SD

Matrix 16-weekMean SD

 Site 1 (8) 17.2 25.2

Site 2 (12)

21.7 26.1

Site 3 (12)

6.3 28.4

Site 4 (16)

22.8 31.5

Site 5 (12)

15.4 25.7

Site 6 (12)

2.1 25.2

Site 7 (16)

13.8 35.4

Site 8 (12)

3.9 22.2

Overall summary 12.7 26.8

 

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 1

 8

 -20.07

 33.17

 <0.0001

Site 2 12 -9.49 4.98 0.026

Site 3 12 -8.39 3.68 0.055

Site 4 16 1.64 0.26 0.610

Site 5 12 -22.30 28.74 <0.0001

Site 6 12 -17.46 17.87 <0.0001

Site 7 16 -5.01 3.34 0.067

Site 8 12 -10.59 7.99 0.005

Table 7. Comparison of retention between groups within sites, with Matrix truncated to the length of TAU at each site

65.8459.15Not Completer

34.1640.85Completer

TAUMatrix 16

x2=4.68, p=0.031

Figure 4. Percent completing treatment, by group

3.75 4.29

8.04

3.38 3.29

7.28

0

2

4

6

8

10

8-wk 12-wk 16-wk

Tx-Length Group

mea

n nu

mbe

r of M

A-fre

e ur

ines

Matrix16

TAU

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 Data Truncated Data

Matrix16 TAU Matrix16 TAU

t pmean SD mean SD mean SD mean SD

Site 1 (8)

6.23 3.383.75 3.38

-0.76 0.45

Site 2 (12)

6.25 4.194.86 4.19

-0.94 0.35

Site 3 (12)

5.75 3.624.61 3.62

-1.52 0.13

Site 4 (16)

8.44 8.68.44 8.6

0.13 0.89

Site 5 (12)

5.19 1.724.30 1.72

-3.70 0.0003

Site 6 (12)

4.24 3.273.3 3.27

-0.04 0.97

Site 7 (16)

7.0 4.547.0 4.54

-1.50 0.14

Site 8 (12)

5.39 3.304.28 3.30

-1.23 0.22

Table 8. Summary of the number of MA-free urine samples provided by participants, by treatment group and site

Site (TAU length, wks.)

Raw Data Truncated Data

Matrix16 TAU Matrix16 TAU

t pmean SD mean SD mean SD mean SD

Site 1 (8)3.575 2.754 2.877 2.754

-0.982 0.328

Site 2 (12)3.753 2.474 3.377 2.474 -1.47 0.144

Site 3 (12)3.197 1.805 3.013 1.805 -2.16 0.033

Site 4 (16)6.140 5.560 6.140 5.560

-0.546 0.586

Site 5 (12)3.889 1.279 3.429 1.279

-3.393 0.001

Site 6 (12)2.429 2.342 2.314 2.342 0.2 0.841

Site 7 (16) 4.682 2.542 4.682 2.542

-1.586 0.121

Site 8 (12) 2.833 2.130 2.519 2.130

-0.551 0.583

Table 9. Longest MA abstinent period by treatment group and site

5.116.41

10.62

4.045.15

9.7

0

2

4

6

8

10

12

8-wk 12-wk 16-wk

Tx-Length Group

mea

n nu

mbe

r of v

isits

Matrix16

TAU

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 Resultby Attendance During Treatmentand Group

0%

20%

40%

60%

80%

100%

Percent of Data Visits Attended During Treatment

0%

20%

40%

60%

80%

100%

Percent of Data Visits Attended During Treatment

Matrix 16 TAU

clean missing dirty

4 9 2 4 8 6

4 0 1 3 9 74 2 1 4 2 0

M a tr ix 1 6 -w k . T A U

nu

mb

er

of

pa

rtic

ipa

nts

B a s e l in eD is c h a rg e6 -m o n th F U

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

6-mos. F.U. UA Resultby Attendance During Treatment and Group

0%

20%

40%

60%

80%

100%

Percent of Data Visits Attended During Treatment

0%

20%

40%

60%

80%

100%

Percent of Data Visits Attended During Treatment

Matrix 16 TAU

MA- missing MA+

68%66%6 Month Follow-up

66%69%Discharge

TAUMatrix 16

x2=4.68, p=0.031

Figure 5. Urinalysis Results: %Meth Negative

11.3 11.8

4 .3 4 .44 .4 4 .0

0

2

4

6

8

10

12

M atrix 16-w k. TAUmea

n n

um

ber

of

day

s o

f M

A u

se

Baseline

Discharge

6-m onth FU

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 Sessions12-Step Program

Involvement  

Site 1  

8 wks 1x/wk x 4-8 wks, 30-50 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

none recommended

  

Site 4  

16 wks 1x/wk x 16 wks, 10-15 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, 30-60 min each

3x/wk x 12 wks, 90 min each and

2x/wk x 12 wks, 60-90 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 1

 69

 73

 142

Site 2 78 77 155

Site 3 77 76 153

Site 4 50 57 107

Site 5 61 63 124

Site 6 73 70 143

Site 7 24 22 46

Site 8 54 54 108

Overall TOTAL

486 492 978

Table 3. Enrollment in the MTP by Site and Treatment Condition

Characteristic Summary

% Male 45

Age (Yrs.), mean (sd) 32.8 (8.0)

Ethnicity (%)  

Caucasian 60

African-American 2

American Indian 3

Asian/Pacific Islander 17

Hispanic 18

Educational Attainment Level (yrs.), mean (sd) 12.2 (1.7)

% Employed 69

% Married (and not separated) 16

Overall Substance Use Patterns-Lifetime (yrs.), mean (sd)  

Methamphetamine 7.54 (6)

Alcohol 7.6 (8.5)

Cocaine 1.75 (3.5)

Cannabis 7.15 (8)

Overall Substance Use Patterns—Days in Past 30, mean (sd)  

Methamphetamine 11.53 (9.6)

Alcohol 4.72 (7.3)

Cocaine 0.21 (1)

Cannabis 4.38 (8.3)

Preferred Route of Administration of MA (%)  

Oral 0

Nasal 11

Smoked 65

IV- injection 24

Table 4. MTP Participant Characteristics (taken from baseline ASI)

 Site (TAU length,

wks.)

TAUMean SD

Matrix 16-weekMean SD

 Site 1 (8) 17.2 14.0 25.2 17.9

Site 2 (12) 21.7 15.7 26.1 17.3

Site 3 (12) 6.3 3.6 28.4 18.2

Site 4 (16) 22.8 15.4 31.5 20.0

Site 5 (12) 15.4 19.8 25.7 20.0

Site 6 (12) 2.1 3.1 25.2 24.7

Site 7 (16) 13.8 14.5 35.4 19.1

Site 8 (12) 3.9 5.0 22.2 18.6

Overall summary 12.7 14.7 26.8 19.7

 

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 1

 8

 -20.07

 33.17

 <0.0001

Site 2 12 -9.49 4.98 0.026

Site 3 12 -8.39 3.68 0.055

Site 4 16 1.64 0.26 0.610

Site 5 12 -22.30 28.74 <0.0001

Site 6 12 -17.46 17.87 <0.0001

Site 7 16 -5.01 3.34 0.067

Site 8 12 -10.59 7.99 0.005

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 Data Truncated Data

Matrix16 TAU Matrix16 TAU

t pmean SD mean SD mean SD mean SD

Site 1 (8)6.23 5.41 3.38 2.95

3.75 2.91 3.38 2.95 -0.76 0.45

Site 2 (12)6.25 5.94 4.19 4.24

4.86 4.59 4.19 4.24 -0.94 0.35

Site 3 (12)5.75 5.51 3.62 3.67

4.61 4.28 3.62 3.67 -1.52 0.13

Site 4 (16)8.44 6.28 8.6 6.18

8.44 6.28 8.6 6.18 0.13 0.89

Site 5 (12)5.19 5.90 1.72 2.88

4.30 4.65 1.72 2.88 -3.70 0.0003

Site 6 (12)4.24 5.36 3.27 4.12

3.3 4.19 3.27 4.12 -0.04 0.97

Site 7 (16) 7.0 5.93 4.54 5.22

7.0 5.93 4.54 5.22 -1.50 0.14

Site 8 (12) 5.39 5.65 3.30 4.05

4.28 4.23 3.30 4.05 -1.23 0.22

Table 8. Summary of the number of MA-free urine samples provided by participants, by treatment group and site

Site (TAU length, wks.)

Raw Data Truncated Data

Matrix16 TAU Matrix16 TAU

t pmean SD mean SD mean SD mean SD

Site 1 (8)3.575 4.600 2.754 3.183 2.877 3.109 2.754 3.183

-0.982 0.328

Site 2 (12)3.753 5.105 2.474 3.306 3.377 4.271 2.474 3.306 -1.47 0.144

Site 3 (12)3.197 4.484 1.805 2.763 3.013 4.028 1.805 2.763 -2.16 0.033

Site 4 (16)6.140 5.771 5.560 5.218 6.140 5.771 5.560 5.218

-0.546 0.586

Site 5 (12)3.889 5.439 1.279 2.274 3.429 4.467 1.279 2.274

-3.393 0.001

Site 6 (12)2.429 3.843 2.342 3.671 2.314 3.491 2.342 3.671 0.2 0.841

Site 7 (16) 4.682 5.056 2.542 3.978 4.682 5.056 2.542 3.978

-1.586 0.121

Site 8 (12) 2.833 4.705 2.130 3.448 2.519 3.879 2.130 3.448

-0.551 0.583

Table 9. Longest MA abstinent period by treatment group and site

4 9 2 4 8 6

4 0 1 3 9 74 2 1 4 2 0

M a tr ix 1 6 -w k . T A U

nu

mb

er

of

pa

rtic

ipa

nts

B a s e l in eD is c h a rg e6 -m o n th F U

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

5.116.41

10.62

4.045.15

9.7

0

2

4

6

8

10

12

8-wk 12-wk 16-wk

Tx-Length Group

mea

n nu

mbe

r of v

isits

Matrix16

TAU

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

65.8459.15Not Completer

34.1640.85Completer

TAUMatrix 16

x2=4.68, p=0.031

Figure 4. Percent completing treatment, by group

3.75 4.29

8.04

3.38 3.29

7.28

0

2

4

6

8

10

8-wk 12-wk 16-wk

Tx-Length Group

mea

n nu

mbe

r of M

A-fre

e ur

ines

Matrix16

TAU

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

11.3 11.8

4 .3 4 .44 .4 4 .0

0

2

4

6

8

10

12

M atrix 16-w k. TAUmea

n n

um

ber

of

day

s o

f M

A u

se

Baseline

Discharge

6-m onth FU

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