# Presentation: 311947

## National Drug Abuse TreatmentClinical Trials Network

- February 13, 2003
- Betty Tai, Ph.D.
- Director, Center for the Clinical Trials Network,
- NIDA/NIH

## Who could want a more lovely way

***Who could want a more lovely way***
***To spend Valentine’s Day***
***Than talking about how we may***
***Implement protocols the CTN way***

## CTN’s Mission

***CTN’s Mission***

***To Improve Drug Abuse Treatment***
***Throughout the Nation...***
***Using ******SCIENCE****** as the Vehicle***

## Uniqueness of CTN

**Blending Research and Practice**
**Bi-directional Collaboration**
**Multi-node, Multi-site RCTs**
**Rigorous Scientific Standards**
**Real World Approach**
**Dissemination End-products Targeted**

## CTN

***Where the Rubber Meets the Road***

***A Paradigm Shift: Transferability, Acceptability, Sustainability ***

## CTN Development Update

***CTN Development Update***

## National Drug Abuse Treatment Clinical Trials Network Node

***RRTC ******–****** Regional Research and Training Center***
***CTP ******–****** Community-Based Treatment Program***

## National Drug Abuse Treatment

*** ******Clinical Trials Network***

**17 Regional Research and Training Centers**** working in partnership with ****115 Community-Based Treatment Programs**** across ****27 States**

## Infrastructure

## CTN Administrative Overview

## Steering Committee

- Research Portfolio

- Operations

- External Affairs

- Executive Committee

## Review

**Review**

**Data**
**Informatics**

## CTN Rules

- CTN Bylaws
- CTN Node Performance Index
- CTN Operations Guidebook
- CTN Study Integrity Monitoring Standards
- Medication Trials
- Behavioral Trials
- CTN Study Safety Monitoring System

## Protocol

**Protocol**
**Development**

## CTN Protocol Portfolio – 2002

- <date/time>

***CTN Protocol Portfolio ******–****** 2002***

| Project # | Protocol Title | LI |
| --- | --- | --- |
| CTN 0001 | Bup/Nal vs Clonidine for Inpatient Opiate Detox | Ling |
| CTN 0002 | Bup/Nal vs Clonidine for Outpatient Opiate Detox | Ling |
| CTN 0003 | Bup/Nal: Comparison of Three Taper Schedules for Opiate Detox | Amass |
| CTN 0004 | MET (Motivational Enhancement Treatment) To Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse | Carroll |
| CTN 0005 | MI (Motivational Interviewing) To Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse | Carroll |
| CTN 0006 | Motivational Incentives for Enhanced Drug Abuse Recovery: Methadone Clinics | Stitzer |
| CTN 0007 | Motivational Incentives for Enhanced Drug Abuse Recovery: Drug Free Clinics | Stitzer |
| CTN 0008 | Baseline Survey | Greenlick |
| CTN 0009 | Smoking Cessation Treatment With Transdermal Nicotine Replacement Therapy in Substance Abuse Rehabilitation Program | Reid |
| CTN 0010 | Bup/Nal in the Treatment of Adolescent and Young Adult Heroin Addicts | Woody |
| CTN 0011 | Telephone Enhancement of Long-Term Engagement | Hubbard |
| CTN 0012 | Infections Screening in Substance Abuse Treatment Programs  | Brown |
| CTN 0013 | Motivational Interviewing for Pregnant Women Seeking Substance Abuse Treatment | Winhusen |
| CTN 0014 | Brief Strategic Family Therapy for Adolescent Drug Abusers | Szapocznik |
| CTN 0015 | Women’s Treatment for Substance Use Disorders and Trauma in Inpatient Rehabilitation and Intensive Outpatient Settings | Hien |
| CTN 0016 | Patient Feedback: A Performance Improvement Study | Forman |
| CTN 0017 | HIV/HCV Intervention in Drug Treatment Settings | Booth |
| CTN 0018 | HIV/STD Safer Sex Skills Groups for Men | Calsyn |
| CTN 0019 | HIV/STD Safer Sex Skills Groups for Women | Tross |
| CTN 0020 | Job Seekers Training for Clients with Drug Dependence | Svikis |
| CTN 0021 | MET or MI:  Spanish version | Carroll |

## Current CTN Portfolio (21 Protocols) By Intervention Type

## Current CTN Portfolio (21 Protocols)Total Projected Enrollment by Intervention Type

## Current CTN Portfolio (21 Protocols)Protocols Involving Special Populations

## Status of Current Trials:> 1,900 Patients Enrolled

| Protocol
NIDA-CTN- | Short Title | Number
Randomized | Enrollment Target |
| --- | --- | --- | --- |
| 0001 | Bup/Nx Inpatient | 113 | Closed |
| 0002 | Bup/Nx Outpatient | 233 | Closed |
| 0004 | MET | 349 | 600 |
| 0005 | MI | 400 | Closed |
| 0006 | Incentives Drug-Free | 410 | 400 |
| 0007 | Incentives Methadone | 391 | 400 |
| 0011 | TELE | 13 | 360 |

## CTN Special Interest Groups

- HIV/AIDS
- Adolescent
- Women and Gender
- Co-morbidity
- Court-involved Patients
- Ethnic Minority
- Behavioral Therapy
- Buprenorphine
- Treatment match
- Smoking
- Homelessness
- Spirituality

## Generate snapshots of current practice 
Identify empirically supported interventions
Develop high quality research concepts
4 AIDS concepts
3 Women concepts
2 Adolescent concepts
3 Co-morbidity concepts
Identify and develop special research tools
Develop long range research plan 
Serve as expert resources

- Identify empirically supported interventions
- Develop high quality research concepts
- 4 AIDS concepts
- 3 Women concepts
- 2 Adolescent concepts
- 3 Co-morbidity concepts
- Identify and develop special research tools
- Develop long range research plan
- Serve as expert resources

***CTN Special Interest Group***

## CTN as Research Platform

- Currently 4 RO1s from Services Research Branch
- Managed by CTN Research Liaison Sub-C
- A new PA released from SRB
- Bup/NX Post Marketing Survey from Pharmaceutical Co.
- Other collaborations welcome

## National CTN Symposia: 2003

- 4/03 – AATOD
- 5/03 – ASAM,  NCDEU
- 6/03 – NASADAD, CPDD, RSA
- 7/03 – SCT
- 8/03 – APsychologicalA
- 9/03 – ICTAB-10, Blending Meeting

## CTN By-Products

- Appreciation of Research/Science in the CTPs
- Change of Practice Attitudes
- Buprenorphine detox for patients in drug-free clinics
- TAU has been greatly modified
- Training
- GCP/CAB training on regular basis
- 80 therapists trained/certified for MI
- LIs training in leading complex clinical trials
- NIDA’s presence in Community Treatment Programs

## CTN Challenges

- Gaps Between Researchers
- 	and Practitioners
- Culture
- Interests
- Clinical Trials in Real-World Settings
- Protocol Design & Analysis
- Protocol Implementation

## Concept Selection CriteriaResearchers’ perspectives

- Need scientific evidence
- Need pilot data
- Need dose response
- Need sample size/power considerations
- Need adequate data analysis
- Need data to focus future studies
- Need assurance of data integrity

## Evidence Criteria

**Researchers**
- Published in JAMA
- Replicated
- Large sample with good power

**Practitioners**
- Everyone is doing it
- State mandated
- It worked for my patients

**How to address bi-directionality issues?**
**How to develop “science-based” practice?**** **

## Concept Selection CriteriaPractitioners’ perspectives

**Need relevance in real life settings**
- How much internal/external validity?
- How representative are the samples?
- How does this deviate from practice?
- How expensive? Who pays for this?
- Any impact on long-term outcome?
- Do my patients accept it?

## Challenges: Research Design and AnalysisDetermining Control Treatment

**Placebo control **
- Ethics
- Feasibility
**Bup/Nx vs. clonidine detox trial**
- Open trial for feasibility
- Patients’/clinicians’ bias uncontrolled

**Pharmacotherapies**

## Challenges: Research Design and AnalysisDetermining Control Treatment

**Standardized control**
- Relevance for individual sites
**Treatment-as-usual (TAU) control**
- Wide variability of TAU between and within sites and over time
- Difficulty of analyzing multi-site, multi-TAU data
**	****Many trials need to describe and monitor TAUs**

**Behavioral Therapies**

## Implementation Challenges:Accommodating the Real World 

- User friendly
- Transferable
*KISS *
- Protocol language
- Standardized procedures across sites
- Quality data output
- Quality Assurance

## Training
Research experience varies
Fidelity and monitoring
Staff turnover
Assessment batteries
Which instruments?  Validated? 
How much time?
Redundancy?
Open vs. blinded
Bleeding or contamination

- Research experience varies
- Fidelity and monitoring
- Staff turnover
**Assessment batteries**
- Which instruments?  Validated?
- How much time?
- Redundancy?
**Open vs. blinded**
- Bleeding or contamination

***Implementation Challenges:******Accommodating the Real World ***

## Opportunities

**A Frontier of Research**
**Researchers and Practitioners are**
- Fully aware of the challenges
- Determined to conquer them
- Willing to cooperate

## CTN trials completed in 2002:

**CTN trials completed in 2002:**

**Buprenorphine/Naloxone Detoxification**
**Change in programs’ attitudes **
**Change in medical management of opiate addiction**
**Adolescent, Dose Tapering trials**
**Motivational Enhancement Therapy/Motivational Interviewing (MET/MI)**
**80 therapists trained/certified **
**Complement to usual practice **
**Spanish MET trial**

## Completed and Ongoing Studies

**Medication Therapies**
- Buprenorphine/Naloxone Detoxification
- Inpatient/Outpatient
**Behavioral Therapies**
- Motivational Enhancement Therapy (MET)/Motivational Interviewing (MI)
- Motivational Incentives Therapy
- Drug-Free Clinics/Methadone Clinics
- TELE Engagement Procedure
**Surveys**
- Baseline Survey of CTPs

## Studies to Begin Enrollment in 2003

- Bup/Nx Tapering Schedules
- Smoking Cessation Treatment in Substance Rehabilitation Programs
- Bup/Nx for Adolescents
- Infections and Substance Abuse Survey
- MET for Pregnant Substance Users
- Brief Strategic Family Therapy
- Women’s Treatment for Trauma and Substance Use Disorders

## Studies Under Development

- Patient Feedback
- HIV/HCV Risk Reduction Intervention in Drug Treatment Settings
- HIV/STD Safer Sex Skills for Men/Women
- Job Seekers Training
- MET for Spanish Speaking Individuals
- HIV Risk Reduction Intervention for Adolescents
- Family Management Skills
- Community Reinforcement and Family Training
- SSRI Treatment of Comorbid Depression and Substance Dependence
- Individual 12-Step Facilitation