Optimizing delivery of a behavioral pain intervention in cancer patients using a sequential multiple assignment randomized trial SMART

Abstract

Background/aims Pain is common in cancer patients and results in lower quality of life, depression, poor physical functioning, financial difficulty, and decreased survival time. Behavioral pain interventions are effective and nonpharmacologic. Traditional randomized controlled trials (RCT) test interventions of fixed time and dose, which poorly represent successive treatment decisions in clinical practice. We utilize a novel approach to conduct a RCT, the sequential multiple assignment randomized trial (SMART) design, to provide comparative evidence of: 1) response to differing initial doses of a pain coping skills training (PCST) intervention and 2) intervention dose sequences adjusted based on patient response. We also examine: 3) participant characteristics moderating intervention responses and 4) cost-effectiveness and practicality. Methods/design Breast cancer patients (N=327) having pain (ratings ≥5) are recruited and randomly assigned to: 1) PCST-Full or 2) PCST-Brief. PCST-Full consists of 5 PCST sessions. PCST-Brief consists of one 60-minute PCST session. Five weeks post-randomization, participants re-rate their pain and are re-randomized, based on intervention response, to receive additional PCST sessions, maintenance calls, or no further intervention. Participants complete measures of pain intensity, interference and catastrophizing. Conclusions Novel RCT designs may provide information that can be used to optimize behavioral pain interventions to be adaptive, better meet patients’ needs, reduce barriers, and match with clinical practice. This is one of the first trials to use a novel design to evaluate symptom management in cancer patients and in chronic illness; if successful, it could serve as a model for future work with a wide range of chronic illnesses.

Precision Medicine

“…At the second stage, responders are randomized to a maintenance therapy or no further treatments whereas non-responders are randomly assigned to a maintenance therapy or more intensive treatment. See Kelleher et al (2017) for additional trial details.…”

“…In a SMART, a patient is randomized at each point in the treatment process where there is clinical equipoise and thus each patient may be randomized multiple times throughout the trial. Figure 2 shows a schematic for a two-stage SMART for evaluating behavioral interventions for cancer pain management (Kelleher et al 2017). In the first stage subjects were randomized with equal probability to one of two variants of Pain Coping Skills Training (PCST); in the second stage, responders were randomized to either a maintenance therapy or no further treatment whereas non-responders were randomized to either maintenance therapy or an intensified treatment.…”

Feasibility and Acceptability of a Remotely Delivered, Web-Based Behavioral Intervention for Men With Prostate Cancer: Four-Arm Randomized Controlled Pilot Trial

“…Overall, future studies are challenged to identify the minimum dose of health coaching needed for participant satisfaction and meaningful behavior change while maintaining scalability. These studies should consider innovative study designs that efficiently support testing multiple intervention components (eg, multiphase optimization strategy framework) [ 51 , 52 ].…”

Sequential, Multiple Assignment, Randomized Trial Designs in Immuno-oncology Research

“…The end goal of the trial is to provide definitive evidence for treatment pathways to be used in practice. The SMART design has been used in oncology (19,20), mental health (21), and other areas (22), but this is the first description of using a SMART in immuno-oncology to our knowledge.…”