IS3. Dynamic Treatment Regimes in Clinical Trials and Observational Studies
Originally:
9:00 – 9:30 An Introduction to Dynamic Treatment Regimes - Marie Davidian
9:30 – 10:00 Estimating Mean Response of Treatment Duration Regimes in an Observational Study - Butch Tsiatis
10:00 – 10:30 SMART Designs for Developing Dynamic Treatment Regimes - Susan Murphy IS3. Dynamic Treatment Regimes in Clinical Trials and Observational Studies
Revised:
9:00 – 9:45ish An Introduction to Dynamic Treatment Regimes - Marie Davidian
9:45ish – 10:30 Estimating Mean Response of Treatment Duration Regimes in an Observational Study - Butch Tsiatis
Susan is the victim of Sunday’s bad weather in New York. . . An Introduction to Dynamic Treatment Regimes
Marie Davidian Department of Statistics North Carolina State University
http://www.stat.ncsu.edu/ davidian
Introduction to Dynamic Treatment Regimes 1 Outline
1. What is a dynamic treatment regime? 2. How can we make inferences on dynamic treatment regimes? 3. Dynamic treatment regimes in oncology 4. Constructing dynamic treatment regimes 5. Concluding remarks
Introduction to Dynamic Treatment Regimes 2 1. What is a dynamic treatment regime?
Clinical practice: Treatment of ongoing illness is itself ongoing Providers do not make a once-and-for-all decision, e.g., “take drug A no matter what happens to you, just keep taking it” Rather, providers manage a patient’s illness Among - and within - patient heterogeneity Providers routinely adjust, change , add , or discontinue treatment based on progress , side e ects , patient burden , compliance , etc. Providers think of this as “individualizing ” treatment to the patient
That is: Treatment in practice involves decisions made sequentially over time based on accruing observations on the patient Suggests thinking about and studying treatment this way . . .
Introduction to Dynamic Treatment Regimes 3 1. What is a dynamic treatment regime?
How are these decisions made? Clinical judgment based on experience Patient preference Practice guidelines based on pieced-together clinical evidence and expert opinion, e.g., NIH guidelines for treatment of HIV-infection at http://www.aidsinfo.nih.gov/
Dynamic treatment regime: Aka adaptive treatment strategy A set of sequential decision rules, each of which dictates how to make the decision on what to do next for a patient based on observation of the patient up to that point Allows treatment to be “individualized ” to the patient through a systematic set of rules that operationalize clinical practice
Introduction to Dynamic Treatment Regimes 4 1. What is a dynamic treatment regime?
Dynamic treatment regime: More precisely A sequence of decision points at which decisions on treatment are made At each point, the next step of treatment is determined according to information up to that point on the patient . . . . . . based on a decision rule that takes these variables as input and outputs the next treatment step for the patient May be thought of as an algorithm that dictates how treatment of a patient should proceed over time
A concrete example . . .
Introduction to Dynamic Treatment Regimes 5 1. What is a dynamic treatment regime?
Goals of cancer therapy: Induce remission of disease, usually using powerful chemo- therapeutic agents If remission, then maintain remission as long as possible before relapse/recurrence, e.g., by administering additional agents that intensify or maintain the e ects of the initial induction therapy If no remission, then maybe try something else to induce remission
Primary outcome of interest: A time-to-event, e.g., disease-free survival time
Note: We are currently discussing dynamic treatment regimes in the context of a single patient (we will talk about studies involving many subjects shortly. . . )
Introduction to Dynamic Treatment Regimes 6 1. What is a dynamic treatment regime?
A particular dynamic treatment regime: For a given patient Step 1 : Treat with one or more courses of rst-line induction chemotherapy A Intermediate outcome: Observe whether “response ” occurs “Response ” may be de ned as complete or partial remission, degree of tumor shrinkage, etc. Step 2 : If “response ” occurs, give maintenance therapy B . . . . . . else, if “response ” does not occur (so A did not induce a response), try second-line therapy B0
Decision rule: The decision rule to determine the step 2 treatment takes the variable “response or not ?” as input
Introduction to Dynamic Treatment Regimes 7 1. Dynamic treatment regimes for cancer
Schematically: The speci c regime “Give rst-line induction therapy A followed by maintenance B if response else if no response give second-line therapy B0 ”
Step 1 Step 2
(Induction Trt) (Intermediate (Maintenance or Outcome) Second-line Trt)
Introduction to Dynamic Treatment Regimes 8 1. What is a dynamic treatment regime?
Important: Individuals following the same regime can have di erent realized treatment experiences