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.

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Purpose

• 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?

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Agenda

• 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

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History
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).
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History
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!!
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History
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.
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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

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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
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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."

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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 (StarD), of
  which he is co-principal investigator.
• .

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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?
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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?
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Questions about Clinical Decisioning in the CTN
1c. In your clinical practice, what clinical
signs indicate that a client is responding well
to treatment?
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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?
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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)?
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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)?
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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 treatments?
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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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References
Brooner, R. K. Behavioral contingencies improve
counseling attendance in an adaptive treatment
model. Journal of Substance Abuse Treatment.
(2004), 27 223-232. Dawson, R. Lavori, P.W.,
Coryell, W.H., Endicott, J. Keller, M.B. Course
of treatment received by depressed patients.
Journal of Psychiatric Research. (1999), 33
233-242. 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. Lavori, P.W., Dawson, R. Rush, A.J.
Flexible treatment strategies in chronic
disease clinical and research implications.
Biological Psychiatry. (2000), 48
605-614. Lavori PW, Rush JA, Wisniewski
SR,Alpert J, Fava M, Kupfer DJ, Nierenberg A,
Quitkin FM, Sackeim HA, Thase ME, Trivedi
M.(2001). Strengthening clinical effectiveness
trials equipoise-stratified randomization.
Biological Psychiatry, 50 792-801.
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References
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. McKay, J.R. Is there a case for
extended interventions for alcohol and drug use
disorders? (2005), 100 1594-1610. McKay, JR.
Lynch, K.G., Shepard, D.S., Pettinati, H.M. The
effectiveness of telephone-based continuing care
for alcohol and cocaine dependence 24 month
outcomes. Archives of General Psychiatry. (2005),
62199-207. McKay, J.R. Continuing care in the
treatment of addictive disorders. Current
Psychiatry Reports. (2006), 8 355-362. McLellan,
A.T. Have we evaluated addiction treatment
correctly? Implications from a chronic care
perspective. Addiction, (2002), 97, 249-252.
McLellan, A.T., Lewis, D.C., OBrien, C.P.,
Kleber, H.D. Drug dependence, a chronic medical
illness. Implications for treatment, insurance,
and outcomes evaluation. Journal of the American
Medical Association. (2000), 284, No.13, 1689
1695.
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References
Murphy, SA, Van Der Laan, MJ, Robins, JM and
Conduct Problems Prevention Group. Marginal mean
models for dynamic regimes. Journal of the
American Statistical Association. (2001), 96, No.
456 1410 1423. Murphy, SA. Optimal dynamic
treatment regimes. Journal of the Royal
Statistical Society. 2003, 65 331-366. Murphy,
SA. (2005). An experimental design for the
development of adaptive treatment strategies.
Statistics in Medicine.241455-1481. Murphy,
SA., Lynch, K.G., Oslin, D.A., McKay, J.R.,
Tenhave, T. Developing adaptive treatment
strategies in substance abuse research. Drug and
Alcohol Dependence. (2006). Murphy, SA., Oslin,
D.W., Rush, A.J., Zhu, J. Methodological
challenges in constructing effective treatment
sequences for chronic psychiatric disorders.
Neuropsychopharmacology. (2007) 32
257-262. OMalley S.S., Rounsaville, B.J.,
Farren, C. Namkoong, K. Wu, R., Robinson, J.
OConnor, P.G.. Initial and maintenance
naltrexone treatment for alcohol dependence using
primary care vs specialty care. A nested sequence
of 3 randomized trials. Archives of Internal
Medicine.(2003), 163, 1695-1704.
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References
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, STARD Study team. Bupropion-SR, Sertaline, or
Venlafaxine-XR after failure of SSRIs for
Depression. The New England Journal of
Medicine.(2006), 35412 1231-1242. Thall, P.F.,
Wathen, J.K. Practical Bayesian adaptive
randomization in clinical trials. European
Journal of Cancer. (2007), 43 859-866. Trivedi,
M.H. et al, Medication augmentation after failure
of SSRIs for Depression. The New England Journal
of Medicine. (2006), 35412 1243-1252. Trivedi,
M. H. Fava, M. Marangell, L.B. Osser, D.N.,
Shelton, R.C. Use of treatment algorithms for
depression. Primary Care Companion to the Journal
of Clinical Psychiatry. 2006 8(5).