EXPERIMENTAL DESIGNS

What is a SMART?

The Sequential, Multiple Assignment, Randomized Trial (SMART) is an experimental design used to construct an optimized adaptive intervention.

In the SMART experimental design, study participants progress through multiple stages. At each stage, a participant may be randomized to one of two or more intervention options. Each stage of randomization helps researchers compare the relative effectiveness of multiple intervention options.

Why use a SMART?

Researchers in behavioral science and other fields may need to answer a number of scientific questions before they recommend an adaptive intervention or evaluate its effectiveness. SMARTs are for researchers who want to answer multiple questions at multiple stages as a means of maximizing the potential impact of their adaptive intervention.

Why use a SMART?

Researchers in behavioral science and other fields may need to answer a number of scientific questions before they recommend an adaptive intervention or evaluate its effectiveness. SMARTs are for researchers who want to answer multiple questions at multiple stages as a means of maximizing the potential impact of their adaptive intervention.

What types of questions can a SMART answer?

What types of questions can a SMART answer?

Intervention sequencing questions.

What intervention option should we offer first?

Among individuals who do not respond to first stage treatment, what is the effect of augmenting treatment compared to the effect of intensifying treatment?

Among individuals who respond to first stage treatment, what is the best frequency for continuing treatment?

Temporal interaction effect questions.

Are there positive or negative interaction effects between the intervention options delivered sequentially?

Are there later-stage treatment options that compromise the benefits of earlier treatment options?

Which first-stage treatment yields insights that inform a more optimal second stage treatment decision?

Intervention tailoring questions.

Should the first-stage intervention differ based on comorbid health conditions, history of prior treatment, or other factors known prior to starting treatment?

How should changes in patients’ health metrics determine intervention options in stage 2 and beyond?

What should trigger the transition from stage one to stage two—adherence, therapeutic response, or some combination of the two?

Questions about defining response.

What is the best way to define response and non-response to first-stage treatment?

How stringent or lenient should we make the cutoff that defines response and non-response to first-stage treatment?

How often should individuals be monitored in an adaptive intervention?

An optimized adaptive intervention…

Takes advantage of positive synergies between sequential intervention options

Avoids negative interactions between sequential intervention options

Capitalizes on between-person heterogeneity to provide the best intervention option for each individual

Is feasible to deliver in real-world practice settings

Makes accommodations for a heterogenous target population

Is replicable by future interventionists and future behavioral scientists

Constructing an optimized adaptive intervention.

We think of the questions listed above as optimization questions because their answers can help researchers construct a high-quality adaptive intervention that has the potential to improve health outcomes in the long-term for a greater number of individuals.

These questions are fundamentally different from those addressed by confirmatory randomized trials, which focus on evaluating how well a treatment works.

CASE STUDY

A SMART for Constructing a Mobile-technology Assisted Adaptive Intervention for Weight Loss

This SMART is designed to construct an adaptive intervention that integrates mobile technology in the treatment of obese and overweight adults. Each of the optimization questions below corresponds to a component of the SMART design schematic.

Optimization Questions

GOAL
To determine the effects of first-stage intervention options.

QUESTION
Does offering an App alone initially lead to weight loss by month 6 that is noninferior to offering App + Coaching?

GOAL
To determine the effects of second-stage intervention options.

QUESTION
Is it more beneficial, in terms of weight loss at 6 months, to offer vigorous or modest augmentation to those who did not respond to the initial intervention?

GOAL
To identify moderators.

QUESTION
Does the effect of first stage intervention options vary by baseline information (e.g., gender, BMI); does the effect of second-stage intervention options vary by baseline and time varying moderators (socioeconomic status, self-efficacy, extent of self-monitoring)?

GOAL
To compare adaptive interventions.

QUESTION
Is it better, in terms of weight loss at 6 months, to (a) start with the App alone, and then augment modestly for non-responders and continue (stay the same) for responders, or (b) start with App+Coaching, and then augment vigorously for non-responders and continue for responders?

SMART Resources

Learning Modules

Software

Example SMARTs

Frequently Asked Questions: SMARTs

References

Ghosh, P., Nahum-Shani, I., Spring, B., & Chakraborty, B. (2020). Noninferiority and equivalence tests in sequential, multiple assignment, randomized trials (SMARTs). Psychological Methods, 25(2), 182.

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

Murphy, S. A. (2005). An experimental design for the development of adaptive treatment strategies. Statistics in Medicine, 24(10), 1455-1481.

Nahum‐Shani, I., Ertefaie, A., Lu, X., Lynch, K. G., McKay, J. R., Oslin, D. W., & Almirall, D. (2017). A SMART data analysis method for constructing adaptive treatment strategies for substance use disorders. Addiction, 112(5), 901-909.

Pfammatter, A. F., Nahum-Shani, I., DeZelar, M., Scanlan, L., McFadden, H. G., Siddique, J., … & Spring, B. (2019). SMART: study protocol for a sequential multiple assignment randomized controlled trial to optimize weight loss management. Contemporary Clinical Trials, 82, 36-45.

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