1. Outcomes in SCS Trials
Ali Rezai MD

2. 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

3. 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

4. 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

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

6. 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

7. 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

8. Relevant Outcomes in SCS Trials

9. 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

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

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

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

13. 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

14. Efficacy – Satisfaction with Treatment
Patient Satisfaction
Provider Satisfaction

15. 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