National Drug Abuse Treatment Clinical Trials Network February 13, 2003 Betty Tai, Ph.D. Director, Center for the Clinical Trials Network, NIDA/NIH February.

National Drug Abuse TreatmentClinical Trials Network

National Drug Abuse TreatmentClinical Trials Network

February 13, 2003

Betty Tai, Ph.D.Director, Center for the Clinical Trials Network,

NIDA/NIH

February 13, 2003

Betty Tai, Ph.D.Director, Center for the Clinical Trials Network,

NIDA/NIH

Who could want a more lovely way

To spend Valentine’s Day

Than talking about how we may

Implement protocols the CTN 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 MissionCTN’s Mission

To Improve Drug Abuse TreatmentThroughout the Nation…

Using SCIENCE as the Vehicle

To Improve Drug Abuse TreatmentThroughout the Nation…

Using SCIENCE as the Vehicle

Uniqueness of CTNUniqueness of CTN

• Blending Research and Practice

• Bi-directional Collaboration

• Multi-node, Multi-site RCTs

• Rigorous Scientific Standards

• Real World Approach

• Dissemination End-products Targeted

• 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 RoadWhere the Rubber Meets the Road

A Paradigm Shift: Transferability, Acceptability, Sustainability

A Paradigm Shift: Transferability, Acceptability, Sustainability

CTN Development UpdateCTN Development Update

FY 2000FY 2000 FY 2001FY 2001 FY 2003FY 2003FY 2002FY 2002

7 Protocol Projects………12………21………26………7 Protocol Projects………12………21………26………

DisseminationDissemination

New Research Agenda (HIV, CJS, etc.)New Research Agenda (HIV, CJS, etc.)

New Concepts & Protocols (Ongoing)New Concepts & Protocols (Ongoing)

Build & Maintain Infrastructure……5…….11………14……….17Build & Maintain Infrastructure……5…….11………14……….17

Establish Policies and SOPsEstablish Policies and SOPs

National Drug Abuse Treatment Clinical Trials Network Node

National Drug Abuse Treatment Clinical Trials Network Node

RRTC – Regional Research and Training CenterCTP – Community-Based Treatment Program

RRTC – Regional Research and Training CenterCTP – Community-Based Treatment Program

CTPCTP

CTP

CTP

CTPCTP

CTP

CTP

CTP

CTP

RRTCRRTC

National Drug Abuse Treatment Clinical Trials Network

National Drug Abuse Treatment Clinical Trials Network

Oregon NodeOregon NodeOHSUOHSU

Washington NodeWashington NodeU. WashingtonU. Washington

Pacific NodePacific NodeUCLAUCLA

Rocky Mountain NodeRocky Mountain NodeU. ColoradoU. Colorado

Florida NodeFlorida NodeU. MiamiU. Miami

Great Lakes NodeGreat Lakes NodeWayne State U.Wayne State U.

Ohio Valley NodeOhio Valley NodeU. CincinnatiU. Cincinnati

South Carolina NodeSouth Carolina NodeMUSCMUSC

North Carolina NodeNorth Carolina NodeDukeDuke

California/Arizona NodeCalifornia/Arizona NodeUCSF/U. ArizonaUCSF/U. Arizona

Southwest NodeSouthwest NodeU. New MexicoU. New Mexico

Northern NE NodeNorthern NE NodeMcLean/HarvardMcLean/Harvard

New England NodeNew England NodeYaleYaleNew York NodeNew York Node

NYUNYULong Island NodeLong Island Node

NY State Psych. Inst.NY State Psych. Inst.

Delaware Valley NodeDelaware Valley NodeU. PennsylvaniaU. Pennsylvania

Mid-Atlantic NodeMid-Atlantic NodeJHU/MCVJHU/MCV

17 Regional Research and Training Centers17 Regional Research and Training Centers working in partnership with working in partnership with 115 Community-Based 115 Community-Based

Treatment ProgramsTreatment Programs across across 27 States27 States

17 Regional Research and Training Centers17 Regional Research and Training Centers working in partnership with working in partnership with 115 Community-Based 115 Community-Based

Treatment ProgramsTreatment Programs across across 27 States27 States

Infrastructure

CTN Administrative Overview

NIDA GrantsManagement

Branch

Ad HocOversight

PRB

DSMB

CCTN

ContractSupport

CTN Nodes

Repository

Steering Committee

NIDA Director New England New York

Delaware Valley

Mid-Atlantic

Oregon Pacific

South Carolina

Florida

Great Lakes Ohio Valley

RockyMountain

Long Island

WashingtonNorth

Carolina

California/Arizona

New Mexico

NorthernNew England

Steering Committee

Research Portfolio Operations External Affairs

Executive Committee

AdministrationOD

Science Operations Dissemination

Center for the Clinical Trials Network

Steering Committee

Research Portfolio Operations External Affairs

Executive Committee

ReviewData

Informatics

CTN RulesCTN Rules

• CTN Bylaws

• CTN Node Performance Index

• CTN Operations Guidebook

• CTN Study Integrity Monitoring Standards– Medication Trials– Behavioral Trials

• CTN Study Safety Monitoring System

• CTN Bylaws

• CTN Node Performance Index

• CTN Operations Guidebook

• CTN Study Integrity Monitoring Standards– Medication Trials– Behavioral Trials

• CTN Study Safety Monitoring System

Research Concept Generation

NIDA CTN

CTN Steering

Committee

Network Oversight Board

NIDA Director

Concepts

CTN Nodes

CTPs

ProtocolDevelopment

CTN Protocol Portfolio – 2002CTN Protocol Portfolio – 2002Project # 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 0004MET (Motivational Enhancement Treatment) To Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse

Carroll

CTN 0005MI (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 0009Smoking 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 0015Women’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) By Intervention Type

Medication (5)

Services/Non-treatment (5)

MET/MI (4)

HIV (3)

Incentives (2)

CBT (1)

Family (1)

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

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

Medication n=2400

HIV Behavioral n=1500

Non-HIV Behavioral

n=4900

Current CTN Portfolio (21 Protocols)Protocols Involving Special PopulationsCurrent CTN Portfolio (21 Protocols)

Protocols Involving Special Populations

No Special Population (15)

Women (3)

Adolescents (2)

Spanish Speakers (1)

Status of Current Trials:> 1,900 Patients Enrolled

Status of Current Trials:> 1,900 Patients Enrolled

ProtocolNIDA-CTN-

Short TitleNumber

RandomizedEnrollment

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 GroupsCTN Special Interest Groups1. HIV/AIDS2. Adolescent3. Women and Gender4. Co-morbidity5. Court-involved Patients6. Ethnic Minority7. Behavioral Therapy8. Buprenorphine 9. Treatment match 10. Smoking11. Homelessness12. Spirituality

1. HIV/AIDS2. Adolescent3. Women and Gender4. Co-morbidity5. Court-involved Patients6. Ethnic Minority7. Behavioral Therapy8. Buprenorphine 9. Treatment match 10. Smoking11. Homelessness12. Spirituality

1. Generate snapshots of current practice 2. Identify empirically supported interventions3. Develop high quality research concepts

4 AIDS concepts 3 Women concepts 2 Adolescent concepts 3 Co-morbidity concepts

4. Identify and develop special research tools5. Develop long range research plan 6. Serve as expert resources

1. Generate snapshots of current practice 2. Identify empirically supported interventions3. Develop high quality research concepts

4 AIDS concepts 3 Women concepts 2 Adolescent concepts 3 Co-morbidity concepts

4. Identify and develop special research tools5. Develop long range research plan 6. Serve as expert resources

CTN Special Interest GroupCTN Special Interest Group

CTN as Research PlatformCTN 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

• 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: 2003National 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

• 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-ProductsCTN 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

• 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 ChallengesCTN Challenges

• Gaps Between Researchers and Practitioners– Culture– Interests

• Clinical Trials in Real-World Settings– Protocol Design & Analysis– Protocol Implementation

• Gaps Between Researchers and Practitioners– Culture– Interests

• Clinical Trials in Real-World Settings– Protocol Design & Analysis– Protocol Implementation

Concept Selection CriteriaResearchers’ perspectives

Concept Selection CriteriaResearchers’ 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

• 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 CriteriaEvidence Criteria

• Researchers– Published in JAMA– Replicated– Large sample with

good power

• Researchers– Published in JAMA– Replicated– Large sample with

good power

• Practitioners– Everyone is doing it– State mandated– It worked for my

patients

• 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 CriteriaPractitioners’ perspectives

Concept Selection CriteriaPractitioners’ perspectives

Need relevance in real life settings

1. How much internal/external validity?

2. How representative are the samples?

3. How does this deviate from practice?

4. How expensive? Who pays for this?

5. Any impact on long-term outcome?

6. Do my patients accept it?

Need relevance in real life settings

1. How much internal/external validity?

2. How representative are the samples?

3. How does this deviate from practice?

4. How expensive? Who pays for this?

5. Any impact on long-term outcome?

6. Do my patients accept it?

Challenges: Research Design and AnalysisDetermining Control Treatment

Challenges: Research Design and AnalysisDetermining Control Treatment

Placebo control • Ethics • Feasibility

Bup/Nx vs. clonidine detox trial• Open trial for feasibility • Patients’/clinicians’ bias uncontrolled

Placebo control • Ethics • Feasibility

Bup/Nx vs. clonidine detox trial• Open trial for feasibility • Patients’/clinicians’ bias uncontrolled

PharmacotherapiesPharmacotherapies

Challenges: Research Design and AnalysisDetermining Control Treatment

Challenges: Research Design and AnalysisDetermining 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

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 TherapiesBehavioral Therapies

Implementation Challenges:Accommodating the Real World

Implementation Challenges:Accommodating the Real World

• User friendly

• Transferable

• KISS

• Protocol language

• Standardized procedures across sites

– Quality data output

– Quality Assurance

• 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

• Training– 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

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

• 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

Clinical Trials NetworkClinical Trials Network

Completed and Ongoing StudiesCompleted and Ongoing StudiesMedication 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

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

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

• 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 DevelopmentStudies 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

• 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