Workshop on adaptive treatment strategies
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Workshop on Adaptive Treatment Strategies. Janet Levy, Ph.D. Jim McKay, Ph.D. Carl Pieper, Dr.Ph. Madhukar Trivedi, M.D. Purpose. EDUCATIONAL: What are “adaptive treatment strategies” (“dynamic treatment regimes”)?

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Workshop on Adaptive Treatment Strategies

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Workshop on Adaptive Treatment Strategies

Janet Levy, Ph.D.

Jim McKay, Ph.D.

Carl Pieper, Dr.Ph.

Madhukar Trivedi, M.D.


EDUCATIONAL: What are “adaptive treatment strategies” (“dynamic treatment regimes”)?

THOUGHT PROVOKING: How might they be applied within the community of treatment providers within our network?


Introductions: Janet Levy

Experimental Designs: Carl Pieper

Adaptive Treatment Strategies in:

The Addictions: Jim McKay

Mental Health: Madhukar Trivedi

The CTN: Janet Levy

Closing: Janet Levy


Innovations in the design of clinical trials have been in the service of pharmaceutical companies to facilitate drug development.

The results OFTEN do NOT inform clinical practice,

especially in mental health.

“A less considered aspect of the usual placebo-controlled

non-equivalence design is the disparity between the

decisions that it supports and those that pervade clinical

practice” p. 3250, Dawson and Lavori(2004).


Development of CTN0030, a trial for the treatment of prescription opioid dependence began in 2004.

Team wanted to design a study which would be “practical” (i.e. inform clinical practice).

Idea of re-randomizing those who relapse during “detoxification” surfaced quickly (to support inferences about which treatment is best following relapse).

How to frame the primary hypothesis? Is it about the first phase (detoxification?) OR is it about what to do for those who relapse early?

We struggled, the DSMB struggled!!


Work illustrating how one might design trials to support the development of clinical strategies in addiction and mental health was just beginning to be published in 2004!!

Dawson, R. and Lavori, P.W. (2004) Discuss the need for innovations in trial design to inform clinical practice.

Murphy, S.A. (2005). Presents preliminary sample size formulae to test hypotheses about strategies in a trial using multiple randomizations. Presents actual simple trial designs.

Murphy, S.A. et al, (with McKay, J.R.), (2006 and 2007). Provides further thinking around how to construct adaptive treatment strategies and how to design trials specifically for the development of long terms strategies.

The Promise of Adaptive Treatment Strategies

  • Help with adherence/drop out in out trials!!!

    • Treat adherence/drop out as another :

      • Intermediate outcome

      • Indication for a different “treatment”

      • Opens up the potential for including MANY more patients in our trials

  • Vehicle for “Integrated Care”

    • Use psychosocial treatments to facilitate Meds ?

    • Use meds to facilitate psychological effects?

  • Vehicle for “Stepped Care”

Carl Pieper, Dr. Ph.

Principal Investigator,

Clinical Trials Network,

National Institute on Drug Abuse

Assistant Research Professor,Dept. of Biometry & Bioinformatics,Duke University Medical Center.

Director and Chief, Computer and Statistics Laboratory, Center for Aging & Human Development, Duke University Medical Center

Senior Fellow, Center for Aging & Human Development,

Duke University

Jim McKay, Ph.D.

Professor of Psychology in Psychiatry at the University of Pennsylvania. 

Director of the joint Penn--TRI Center on the Continuum of Care in the Addictions. 

Co-director of the Center of Excellence in Substance Abuse Treatment and Education (CESATE) at the Philadelphia Veterans Affairs Medical Center."

Madhukar Trivedi, M.D.

Professor and director of the Mood Disorders Research Program and Clinic at the University of Texas Southwestern Medical Center in Dallas where he holds the Lydia Bryant Test Professorship in Psychiatric Research.

Director for the depression algorithm for the Texas Medication Algorithm Project (TMAP).

Co-director of the Dallas Coordinating Center of the NIMH funded project “Sequences Treatment and Alternatives to Relieve Depression (Star*D), of which he is co-principal investigator.


Questions about Clinical Decisioning in the CTN

1a. In your clinical practice, what clinical signs indicate that

A client is not responding well to treatment?

Questions about Clinical Decisioning in the CTN

1b. In your program, what treatment options are available when

the client is not responding to standard care, or the first

treatment he/she is provided?

Questions about Clinical Decisioning in the CTN

1c. In your clinical practice, what clinical signs indicate that a

client is responding well to treatment?

Questions about Clinical Decisioning in the CTN

1d. In your program, when the patient is doing well, what

treatment options are available besides more of the same

or discharge?

Questions about Clinical Decisioning in the CTN

2. Based on your own experience as a clinician, which clinical

decisions about patient care are the most challenging

(for any reason)?

Questions about Clinical Decisioning in the CTN

3. Based on your own experience as a clinician, which clinical

decisions are in most need of empirical research

(for any reason)?

Questions about Clinical Decisioning in the CTN

4. What do you do when a patient returns to treatment several

times without a prolonged period of success between


Questions about Clinical Decisioning in the CTN

5. How long would you continue to apply a particular treatment

to a client before determining whether or not the treatment

is successful?


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  • Dawson, R., Lavori, P.W. Placebo-free designs for evaluating new mental health treatments: the use of adaptive treatment strategies. Statistics in Medicine. 2004, 23: 3249-3262.

  • Dawson R., Lavori, P.W. Comparison of designs for adaptive treatment strategies: baseline vs. adaptive randomization. Journal of Statistical Planning and Inference. (2003),117 : 365 – 385.

  • Lavori, P.W., Dawson, R. A design for testing clinical strategies: Biased – coin adaptive within – subject randomization. Journal of the Royal Statistical Association. 2000. 163: 29-38.

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  • Lavori, PW, Dawson, R.(2004) Dynamic treatment regimes: practical design considerations.Clinical Trials. (2004), 1: 9-20.

  • McKay, J.R., Lynch, K.G., Shepard, D.S., et al. The effectiveness of telephone – based continuing care in the clinical management of alcohol and cocaine use disorders: 12 month outcomes. Journal of Consulting and Clinical Psychology, (2004), 72: 967-979.

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  • Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wisldon K, Niederehe G, Fava M, STAR*D Study team. Bupropion-SR, Sertaline, or Venlafaxine-XR after failure of SSRIs for Depression. The New England Journal of Medicine.(2006),354:12: 1231-1242.

  • Thall, P.F., Wathen, J.K. Practical Bayesian adaptive randomization in clinical trials. European Journal of Cancer. (2007), 43: 859-866.

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