SMART designs in cancer research: Past, present, and future

Abstract

Background Cancer affects millions of people worldwide each year. Patients require sequences of treatment based on their response to previous treatments to combat cancer and fight metastases. Physicians provide treatment based on clinical characteristics, changing over time. Guidelines for these individualized sequences of treatments are known as dynamic treatment regimens (DTRs) where the initial treatment and subsequent modifications depend on the response to previous treatments, disease progression and other patient characteristics or behaviors. To provide evidence-based DTRs, the Sequential Multiple Assignment Randomized Trial (SMART) has emerged over the past few decades. Purpose To examine and learn from past SMARTs investigating cancer treatment options, to discuss potential limitations preventing the widespread use of SMARTs in cancer research, and to describe courses of action to increase the implementation of SMARTs and collaboration between statisticians and clinicians. Conclusions There have been SMARTs investigating treatment questions in areas of cancer, but the novelty and perceived complexity has limited its use. By building bridges between statisticians and clinicians, clarifying research objectives, and furthering methods work, there should be in an increase in SMARTs addressing relevant cancer treatment questions. Within any area of cancer, SMARTs develop DTRs that can guide treatment decisions over the disease history and improve patient outcomes.

The use of PROMs and shared decision‐making in medical encounters with patients: An opportunity to deliver value‐based health care to patients

“…This seems to be largely due to a perceived lack of time, a lack of decision aids, or insufficient awareness of those tools that could help in risk communication. Alternatively, it may be that clinicians do know about available decision aids, but think they are not suitable for informing their individual patients, due to a lack of personalized estimates . In this respect, aggregated PROMs information on the level of treatment options is not routinely available and/or used in the three projects.…”

“…Alternatively, it may be that clinicians do know about available decision aids, but think they are not suitable for informing their individual patients, due to a lack of personalized estimates. 5,87,88 In this respect, aggregated PROMs information on the level of treatment options is not routinely available and/or used in the three projects. Facilitators for option talk are training in SDM, training in team collaboration (contributing to better knowledge/overview of options), and availability of clinical guidelines or quality standards describing all treatment options and the importance of SDM.…”

Adaptive Interventions in Child and Adolescent Mental Health

“…SMARTs have been used to develop adaptive interventions across a wide range of disciplines (see Kidwell (2014) for a review of the past, present and future of SMARTs in oncology). In oncology research, SMART designs have been used to develop adaptive interventions for prostate cancer (Thall, Wooten, Logothetis, Millikan, & Tannir, 2007; Wang et al, 2012).…”

DTR: AnRPackage for Estimation and Comparison of Survival Outcomes of Dynamic Treatment Regimes

“…In the high risk neuroblastoma study described above, four DTRs can be constructed: (i) treat with ABMT followed by cis-RA if no disease progression; (ii) treat with ABMT followed by no further therapy if no disease progression; (iii) treat with chemotherapy followed by cis-RA if no disease progression; and (iv) treat with chemotherapy followed by no further therapy if no disease progression. Evaluating the effect of a sequence of therapies is more efficient and more clinically meaningful than looking at the first-and second-stage therapies separately (Chakraborty and Murphy 2013;Kidwell 2014). Lunceford et al (2002) introduced the survival and mean restricted survival estimators for treatment regimes in a two-stage randomization design using two forms of inverse-probability weighting for second-stage randomization and censoring respectively.…”

“…Sequentially randomized designs, more recently known as sequential multiple assignment randomized trial (SMART) designs, are widely used in biomedical research, particularly in clinical trials, to assess and compare the effects of various treatment sequences (Robins 1986(Robins , 1987Lavori and Dawson 2000;Murphy 2005;Bembom and van der Laan 2007;Chakraborty and Murphy 2013;Kidwell 2014). In such designs, patients are initially randomized to one of the first-stage therapies.…”