1. A SMART Design to Optimize a Palliative Care Intervention for Patient and Family Caregiver Outcomes Mi-Kyung Song, PhD, RN, FAAN University of North Carolina at Chapel Hill CANS 2015 SPECIAL TOPICS CONFERENCE

2. Disclosure statements (or confession) This presentation is rather about a tale of failure. It is about a grant application of a SMART trial submitted to NIH multiple times since 2009 with no success. My knowledge of SMART designs comes from those endeavors. 2

3. A story about how I got to think of a SMART design for my research

4. Why a new randomized design? A traditional RCT design won’t do? Individualization itself is almost always invisible in interventions and intervention studies.

5. Palliative care we know… A coordinated care of multiple components or services by (ideally) a multidisciplinary team – Effective symptom management – Clear communication among care team, patient and family – Psychosocial and spiritual support – Family caregiver support and post-bereavement support Well recognized as a means to improve patient and family caregiver outcomes 5 NCPQPC, 2013

6. Palliative care we know… (cont’d) Current evidence of palliative care – Types of palliative care interventions across studies vary. – Components and dosage received by individuals within and across studies are, if known, largely heterogeneous. 6 Chai & Meier, 2011; Aimmermann et al., 2008; Abernethy et al., 2010

7. Palliative care we do not know yet… Which components of palliative care or combinations of components are most responsible for improving patient and/or family caregiver outcomes How to adapt a palliative care intervention to an individual’s changing course over time Clinical decisions underlying palliative care practice have not been tested 7 Chai & Meier, 2011; Aimmermann et al., 2008; Abernethy et al., 2010

8. Unit of palliative care targeted Both the patient and family caregiver as the unit of palliative care, but Most non-ICU palliative care interventions have been patient-targeted – Caregiver outcomes are expected to improve with improvements in patients’ conditions 8 Hanks et al., 2002;Rummans et al., 2006; Lorenz et al., 2008; Candy et al., 2011

9. Traditional RCTs: ‘all-or-none’ Participants randomized to an intervention arm receive fixed treatments/components throughout the trial (whether they need them or not) Varying needs of individuals may not be met May not be practical and too costly May lead to non-adherence, jeopardizing ITT comparisons 9

10. Traditional RCTs (cont’d) Yield limited information for developing intervention strategies wherein type and dose/intensity change in response to an individual’s treatment response. 10 Unutzer et al., 2001; Brooner & Kidorf, 2002; Lavori et al, 2000; Connell et al, 2007; Almirall, et al., 2012

11. Adaptive intervention framework An adaptive intervention strategy that allows more flexible management – A decision point midway, for example, into the trial address the critical question faced by clinicians: What should I do when a patient is not responsive to the initial treatment? (how to adapt?) 11 Lavori & Dawson, 2000; Dawson & Lavori, 2015

12. An adaptive intervention strategy: Is to optimize an intervention in order to maximize the targeted outcome Includes a sequence of decision rules to apply over time that specify – Whether, how and/or when to alter the previous treatment In type, dosage/intensity, or mode of delivery 12

13. Sequential multiple assignment randomization trials (SMARTs) When a decision point occurs, it prompts the introduction of a second (or more) randomization to evaluate alternatives (e.g., changing the treatment, augmenting, maintaining,…etc.) Designs to develop an adaptive intervention 13 Murphy, 2005

14. Components of a SMART What make up an adaptive intervention: – A set of treatment options – Tailoring variables for deciding changes in intervention – Decision rules on sequencing alternatives based on the tailoring variables Outcome(s) 14 -Example-

15. A SMART: To develop a palliative symptom management intervention for lung transplant recipients and their family caregivers

16. The purpose To develop an adaptive intervention strategy (a sequence of two interventions for symptoms: patient-targeted and dyad targeted) that produces the greatest improvements in patient and caregiver outcomes – Patients’ overall symptom distress and quality of life – Caregivers’ burden and quality of life 16

17. Study design 17

18. Pitfalls Unfamiliarity in the audience – e.g., when qualitative research proposals submitted to NIH for the first time Lack of specificity in tailoring variables – e.g., symptom distress vs a specific symptom – More suitable: weight loss, depression, anxiety, blood glucose level, alcohol dependence 18

19. Distinction: An adaptive trial design What is adaptive is the study design, not the intervention. – Based on interim analyses 19

20. Conclusions: SMART designs… Are suitable for a certain type of research questions – Hold utility in developing an adaptive intervention or a sequence of interventions Need to be kept as simple as possible Are better with simple, specific tailoring variables Require very thoughtful planning 20

21. Acknowledgement A team of investigators who were part of the tale – Annette DeVito Dabbs, PhD, RN, FAAN, University of Pittsburgh – Sandra Ward, PhD, RN, FAAN, University of Wisconsin- Madison – Michael Kosorok, PhD, University of North Carolina at Chapel Hill 21