Outcomes in SCS Trials Ali Rezai MD

Clinical Trial Outcomes What are outcomes? What are the different types of outcomes? How are they measured? What are some of the challenges? Outcomes in SCS trials

What are “Outcomes”? Outcomes are variables or data points measured in trials to determine the impact of an intervention on a certain measure Safety, feasibility, tolerability, efficacy Different audiences may be interested in different measures Patients / families, healthcare providers, regulators, payors

Different Types of Outcomes Patient centric (subjective and objective) Survival, subjective pain scores, quality of life, satisfaction Surrogate – includes biomarkers 6 minute walk distance – transplant or mortality Cholesterol – cardiovascular mortality Composite Major adverse cardiac events (MACE); pain score + opioid dose reduction

How are Outcomes Measured? Patient reported Pain NRS scores, subjective measures Family reported Pediatrics, Patients with cognitive deficits Provider reported Physical measures, objective measures

Challenges of Outcomes Different audiences disagree about the relevance / value of particular ones Questions about validity of selected measures Impact of placebo / sham on measuring outcomes Generalizability to non-study conditions or populations Variability and reliability of subjective measures (e.g. pain) Uni-dimensional measures used for multi-dimensional constructs

Efficacy Outcomes in Chronic Pain* 11-point (0-10) numerical rating scale of pain intensity Usage of rescue analgesics Categorical rating of pain intensity (none, mild, moderate, severe) when necessary Physical functioning (either one of two measures) – Multidimensional Pain Inventory Interference Scale or Brief Pain Inventory Interference Items Emotional functioning (at least one of two measures) – Beck Depression Inventory or Profile of Mood States Participant ratings of global improvement and satisfaction with treatment Patient Global Impression of Change Symptoms and adverse events – Passive capture of spontaneously reported adverse events and symptoms and use of open-ended prompts Participant disposition – Detailed information regarding participant recruitment and progress through the trial, including all information specified in the CONSORT guidelines *Dworkin, Pain 113 (2005) 9–19

Relevant Outcomes in SCS Trials

Safety Procedure Related Bleeding, infection, wound Neurologic injury Neurological Sensory and motor deficits Device Related Infection, erosion, failed hardware, disconnection Stimulation Related Other New pain syndromes Worsening of pain Poor hardware placement

Feasibility Impact considerations of treatment on patient and support system Technical / procedural

Efficacy – Pain Intensity VAS NRS Faces Dose of concomitant opioid or other analgesics Responder analysis

Efficacy – Pain Quality McGill Pain Questionnaire (Short Form) Pain Detect Questionnaire Brief Pain Inventory

Efficacy – Quality of Life / Functional Patient Reported Outcomes Measurement Information System (PROMIS-29) Oswestry disability index (ODI) SF-36 EQ5D QALY Days out of work

Efficacy – Satisfaction with Treatment Patient Satisfaction Provider Satisfaction

Topics for Discussion Validity / Reliability Placebo / sham effect Generalizability Duration of measurement: <3 months, 3, 6, 12, >12 months When to include a responder analysis Objective measurements for pain including surrogates Biomarkers, imaging, EEG, function, others… Composites for pain, multi-dimensional