1. AAPM&R Annual Assembly October 3 rd, 2015 Matthew Smuck, MD Chief, Physical Medicine & Rehabilitation Associate Professor, Department of Orthopaedics Director, Wearable Health Lab Stanford University The Utility of Epidural Steroid Injections: Point - Counterpoint

2. DISCLOSURES Cytonics - Research support ($ - paid to institution) Lumo BodyTech - Advisor (stock options) BlueJay Mobile Health - Advisor (stock options) Vivametrica - Founder (20% owner) State Farm Auto Insurance - Expert Witness ($ - hourly) SIS - Board of Directors ($ - travel/honoraria) The Spine Journal - Executive Editorial Board ($ - travel)

3.  April 23, 2014 - the FDA released a Drug Safety Communication warning on risks of ESI, stating safety and effectiveness have not been established E PIDURAL S TEROID I NJECTIONS AND THE FDA

4.  April 23, 2014 - the FDA released a Drug Safety Communication warning on risks of ESI, stating safety and effectiveness have not been established › At this same time a multiple pain society workgroup (MPW) was working with another branch of the FDA on an “FDA Safe Use Initiative” regarding safe injection practices E PIDURAL S TEROID I NJECTIONS AND THE FDA

5.  The MPW includes the following 13 societies: › American Association of Neurological Surgeons › American Academy of Pain Medicine › American Academy of Physical Medicine and Rehabilitation › American Association of Neurological Surgeons › American College of Radiology › American Pain Society › American Society of Anesthesiologists › American Society of Regional Anesthesia and Pain Medicine › Congress of Neurological Surgeons › North American Neuromodulation Society › North American Spine Society › Spine Intervention Society › Society of Interventional Radiology E PIDURAL S TEROID I NJECTIONS AND THE FDA

6.  April 23, 2014 - the FDA released a Drug Safety Communication warning on risks of ESI, stating safety and effectiveness have not been established › At this same time a multiple pain society workgroup (MPW) was working with another branch of the FDA on an “FDA Safe Use Initiative” regarding safe injection practices  November 7, 2014 - the MPW mailed a response to the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee to explain the following: E PIDURAL S TEROID I NJECTIONS AND THE FDA

7.  A summary of MPW response to the FDA: › Safety is well established including studies of >16,000 consecutive ESIs E PIDURAL S TEROID I NJECTIONS AND THE FDA

8.  A summary of MPW response to the FDA: › Safety is well established including studies of >16,000 consecutive ESIs › Serious complications are reported, related to use of particulate steroids in TFESIs E PIDURAL S TEROID I NJECTIONS AND THE FDA

9.  A summary of MPW response to the FDA: › Safety is well established including studies of >16,000 consecutive ESIs › Serious complications are reported, related to use of particulate steroids in TFESIs › Risks of alternative medications are also well known (Opioids, NSAIDS) E PIDURAL S TEROID I NJECTIONS AND THE FDA

10.  A summary of MPW response to the FDA: › Safety is well established including studies of >16,000 consecutive ESIs › Serious complications are reported, related to use of particulate steroids in TFESIs › Risks of alternative medications are also well known (Opioids, NSAIDS) › There is ample evidence on the effectiveness of ESIs to: Improve pain and disability Reduce rates of surgery E PIDURAL S TEROID I NJECTIONS AND THE FDA

11.  A summary of MPW response to the FDA: › Safety is well established including studies of >16,000 consecutive ESIs › Serious complications are reported, related to use of particulate steroids in TFESIs › Risks of alternative medications are also well known (Opioids, NSAIDS) › There is ample evidence on the effectiveness of ESIs to: Improve pain and disability Reduce rates of surgery › Evidence best for disc herniation & radicular pain, may be less for other pathology E PIDURAL S TEROID I NJECTIONS AND THE FDA

12.  A summary of MPW response to the FDA: › Safety is well established including studies of >16,000 consecutive ESIs › Serious complications are reported, related to use of particulate steroids in TFESIs › Risks of alternative medications are also well known (Opioids, NSAIDS) › There is ample evidence on the effectiveness of ESIs to: Improve pain and disability Reduce rates of surgery › Evidence best for disc herniation & radicular pain, may be less for other pathology › Evidence is not reliable from studies involving heterogeneous populations (ie. back pain) and using inappropriate statistical analysis (group means instead of categorical data) E PIDURAL S TEROID I NJECTIONS AND THE FDA

13.  A summary of MPW response to the FDA: › Safety is well established including studies of >16,000 consecutive ESIs › Serious complications are reported, related to use of particulate steroids in TFESIs › Risks of alternative medications are also well known (Opioids, NSAIDS) › There is ample evidence on the effectiveness of ESIs to: Improve pain and disability Reduce rates of surgery › Evidence best for disc herniation & radicular pain, may be less for other pathology › Evidence is not reliable from studies involving heterogeneous populations (ie. back pain) and using inappropriate statistical analysis (group means instead of categorical data) › RCTs showing equivalence between epidural injection of anesthetic vs steroid should be interpreted to show that neither option works E PIDURAL S TEROID I NJECTIONS AND THE FDA

14.  Meanwhile, the MPW publishes the results of the Safe Use Initiative with unanimous agreement of the boards of each of the involved societies. Anesthesiology, 2015, V 122 No 5 E PIDURAL S TEROID I NJECTIONS AND THE FDA

15.  Highlights of the Safe Use Initiative recommendations: UNANIMOUS SUPPORT › Use only non-particulate steroids for Cervical TF ESIs Recommended for lumbar TF ESIs (circumstances may call for alternatives) › Image guidance with appropriate views › Review prior imaging before injection › Use facemask and sterile gloves › Avoid heavy sedation NEAR UNANIMOUS SUPPORT › Injection of contrast under real-time fluoroscopy (1 against) › Use extension tube (1 against) E PIDURAL S TEROID I NJECTIONS AND THE FDA

16.  Drs. Manchikanti and Falco published a rebuttal to the Safe Use Initiative. E PIDURAL S TEROID I NJECTIONS AND THE FDA

17.  Drs. Manchikanti and Falco published a rebuttal to the Safe Use Initiative. › Describes withdrawal of ASIPP from the MPW E PIDURAL S TEROID I NJECTIONS AND THE FDA

18.  Drs. Manchikanti and Falco published a rebuttal to the Safe Use Initiative. › Describes withdrawal of ASIPP from the MPW › Claims a lack of consensus among the remaining MPW societies E PIDURAL S TEROID I NJECTIONS AND THE FDA

19.  Drs. Manchikanti and Falco published a rebuttal to the Safe Use Initiative. › Describes withdrawal of ASIPP from the MPW › Claims a lack of consensus among the remaining MPW societies › Suggests a role for blunt needles and alternate needle placement E PIDURAL S TEROID I NJECTIONS AND THE FDA

20.  Drs. Manchikanti and Falco published a rebuttal to the Safe Use Initiative. › Describes withdrawal of ASIPP from the MPW › Claims a lack of consensus among the remaining MPW societies › Suggests a role for blunt needles and alternate needle placement › Argues against the mandated use of dexamethasone E PIDURAL S TEROID I NJECTIONS AND THE FDA

21.  Drs. Manchikanti and Falco published a rebuttal to the Safe Use Initiative. › Describes withdrawal of ASIPP from the MPW › Claims a lack of consensus among the remaining MPW societies › Suggests a role for blunt needles and alternate needle placement › Argues against the mandated use of dexamethasone › Suggests that anesthetics may be as good as steroids E PIDURAL S TEROID I NJECTIONS AND THE FDA

22.  Drs. Manchikanti and Falco published a rebuttal to the Safe Use Initiative. › Describes withdrawal of ASIPP from the MPW › Claims a lack of consensus among the remaining MPW societies › Suggests a role for blunt needles and alternate needle placement › Argues against the mandated use of dexamethasone › Suggests that anesthetics may be as good as steroids › Argues against use of lateral and oblique views in IL ESIs for reasons including that: “many physicians have not been trained in these techniques and are unaware of them.” E PIDURAL S TEROID I NJECTIONS AND THE FDA

23. A question for Dr. Manchikanti ? E PIDURAL S TEROID I NJECTIONS AND THE FDA

24.  Publications and guidelines often recommend “conservative” treatments before considering invasive treatments such as ESIs  While this initially appears rational, there are 3 problems that authors of these publications and guidelines rarely address A LTERNATIVES TO E PIDURAL S TEROID I NJECTIONS

25.  Problem #1 – How well do these alternatives work? › Randomized trials and systematic reviews of conservative treatments (physical therapy, mobilization, oral medications, etc.) often describe statistically significant differences between treatments groups, however the effect sizes are universally small › Not only are effect sizes small, most are below thresholds of clinical relevance, so more correctly interpreted to have no clinical benefit A LTERNATIVES TO E PIDURAL S TEROID I NJECTIONS

26.  Problem #2 – Are these alternatives safer? › Rates of serious complications from therapeutic ESI are very low less than the 1/100,000 for hematoma from epidural anesthesia › Serious risks of alternative medications are well known as documented in the following US annual rates: >15,000 opioid related deaths >16,000 NSAID-related deaths >100,000 hospitalized for serious GI complications from NSAIDS A LTERNATIVES TO E PIDURAL S TEROID I NJECTIONS

27.  Problem #3 – What alternatives? › Due to current dogma, most practitioners only consider ESIs after the “more conservative” alternatives have already failed. › For many, the alternatives have already been exhausted A LTERNATIVES TO E PIDURAL S TEROID I NJECTIONS

28. A question for Dr. Friedly ? A LTERNATIVES TO E PIDURAL S TEROID I NJECTIONS