Wearable Seizure Monitor (Embrace; Empatica, Boston, MA)

Cleared: January 8, 2019

Indication: Seizure detection in children at least age 6 years

Available as: a wearable device

This smartband device (Embrace; Empatica, Boston, MA) detects motion patterns and physiologic signals that may be associated with generalized tonic-clonic seizures and immediately alerts caregivers. The approval is for an expanded indication in children age 6 years or more. The device is the first nonEEG-based physiology signal seizure monitoring system cleared for use in children. Clinical testing in an epilepsy monitoring unit (EMU) (80 children age 6-21 years and 61 adults showed that 53 of 54 seizures identified were detected by the device (98% accuracy) with a false alarm rate in children of approximately 8%. The device was approved for use in adults in 2018.

Midazolam Nasal Spray (Nayzilam; UCB, Smyrna, GA)

Approved May 20, 2019

Indication: acute treatment of acute repetitive seizures (cluster seizures) in people age 12 years or more with epilepsy

Available as: single-dose 5 mg/0.1 mL nasal spray unit

Midazolam nasal spray (Nayzilam; UCB, Smyrna, GA) is more effective than placebo at stopping seizures within 10 minutes with no seizure recurrence within 6 hours (53.7% vs 34.3%; P=.011). Of note, median return to baseline function was within 90 minutes of treatment, similar to that seen with placebo. For participants who stopped a seizure cluster with nasal midazolam, there was a 20% likelihood of no seizure recurrence within 24 hours.

The initial dose is 1 spray (5-mg dose) into 1 nostril that may be repeated after 10 minutes in the opposite nostril if the treated individual has not responded to the initial dose. It is recommended that individuals not use nasal midazolam more than once every 3 days and no more than 5 times per month. Doses can be self-administered or adminstered by a caregiver, who is not required to be a health care professional.

Cenobamate (Xcopri; SK Life Sciences, Paramus, NJ)

Approved: November 21, 2019

Indication: partial-onset seizures in adults

Available as: tablets (12.5 mg, 25 mg, 50 mg, 100 mg, and 200 mg

Cenobamate (Xcopri; SK Life Sciences, Paramus, NJ) at doses of 100 mg, 200 mg, and 400 mg reduced median seizure frequency by 36%, 55%, and 55%, respectively vs 24% with placebo. At those doses, a 50% or more reduction in focal seizures compared with baseline occurred during the maintenance phase (40%, 56%, and 64%) vs placebo (25%). Treatment with cenobamate (200 mg) vs placebo resulted in 11% vs 1% of participants having no focal seizures. The recommended maintenance dose of cenobamate, following a titration, is 200 mg daily. Some may need additional titration to 400 mg daily, the maximum recommended dose.

Drug reaction with eosinophilia and systemic symptoms (DRESS), including a death, was reported during trials when cenobamate was titrated weekly or faster. However, there were no cases of DRESS in an open-label safety study of 1,339 people with epilepsy when cenobamate was started at 12.5 mg/day and adjusted every 2 weeks. A higher percentage of people taking cenobamate vs placebo had a shortening of the QT interval more than 20 msec. Cenobamate should not be used in those with hypersensitivity to cenobamate or with familial short QT syndrome.

Nasal Sumatriptan (Tosymra; Promius, Princeton, NJ)

Cleared: January 27, 2019

Indications: acute treatment of migraine with or without aura in adults

Available as: nasal spray delivery 10 mg/spray

A new formulation of sumatriptan (Tosymra; Promius, Princeton, NJ) delivers 10 mg intranasally to achieve median peak plasma concentration 5 minutes faster than injectable sumatriptan, 4 mg and 6 mg. In clinical trials, this formulation had significantly higher rates and extents of absorption compared with previously available sumatriptan nasal spray (Imitrex; GSK, Triangle Research Park, NC), which was given as a 20 mg dose. The recommended dose is 1 spray (10 mg); if pain control is not achieved at 1 hour, up to 2 additional doses, taken at least 1 hour apart, may be used up to a maximum of 3 doses every 24 hours.

Remote Neurostimulator (Nerivio; Theranica, Netanya, Israel)

Approved: May 29, 2019

Indication: acute treatment of migraine with or without aura in adults without chronic migraine

Available as: a handheld device controlled with an application on a smartphone (iOS or Android) for self-administration

This handheld neurostimulator (Nerivio; Theranica, Netanya, Israel) uses remote electrical neuromodulation applied to the arm or trunk for acute treatment of migraine. The device uses electronic pulses to create a conditioned pain modulation (CPM) response to treat migraine with or without aura in adults with episodic migraine.

Clinical data showed 66.7% of participants had pain relief within 2 hours. The de novo approval process is risk-based, classifying novel medical devices for which there is a reasonable assurance of safety and effectiveness for the intended use.

Galcanezumab-glnm (Emgality; Eli Lilly, Indianapolis, IN)

Expanded Indication Approved: June 4, 2019

Indication: expanded indication for prevention of episodic cluster headache

Available as: autoinjector of 100 mg/injection

Galcanezumab (Emgality; Eli Lilly, Indianapolis, IN) is the only agent in the new class of calcitonin gene-related peptide (CGRP) inhibitors approved for cluster headache. Individuals with cluster headache can administer a 300-mg dose at home through 3 consecutive subcutaneous injections at cluster headache period onset, followed by monthly doses until the period ends. Individuals with episodic cluster headache who were treated with galcanezumab vs placebo had significantly more reduction in headache frequency (−8.7 attacks/week vs −5.2 attacks/week; P=.036). Those treated with galcanezumab vs placebo were more likely to have a 50% reduction in headache attacks (71.4% vs 52.6%; P=.046).

Lasmitidan (Reyvow; Eli Lilly, Indianapolis, IN)

Approved: October 11, 2019

Indication: acute treatment of migraine with or without aura in adults

Available as: tablets (50 mg or 100 mg)

Lasmiditan (Reyvow; Eli Lilly, Indianapolis, IN) is a first-in-class novel serotonin 5-HT1F receptor agonist. In clinical trials, dizziness, fatigue, paresthesia, and sedation occurred. In human abuse potential studies, therapeutic doses were associated with less drug liking compared to the positive control alprazolam, but more than the negative placebo control. A recommended controlled substance classification is underway at the Drug Enforcement Administration (DEA)and is expected in early 2020.

Treatment with lasmiditan vs placebo resulted in significantly higher numbers of participants had freedom from pain and most bothersome symptoms as early as 60 minutes after treatment (P<.01). The proportion of participants reporting no disability from migraine was also significantly greater for those who took a 200-mg dose of lasmiditan vs placebo (P=.001).

No significant differences in response among articipants who rated themselves as nonresponders, poor responders, or good responder to triptans was seen. Participants who took 100 mg of lasmiditan vs placebo had statistically significant differences in freedom from pain at 2 hours (odds ratio [OR] 4.5 vs 1.8, P=.056) and MBS freedom (OR 3.2 vs 1.5, P=.042).

Ubrogepant (Ubrelvy; Allergan, Madison, NJ)

Approved: December 23, 2019

Indication: acute treatment of migraine with or without aura in adults

Available as: tablets (50 mg or 100 mg)

Ubrogepant (Ubrelvy; Allergan, Madison, NJ) is the first small molecule orally available calcitonin gene-related peptide (CGRP) antagonist approved for any indication. Ubrogepant is approved for acute treatment of migraine once an attack begins, not for prevention of migraine. Across all clinical trials, over 1,439 adults with a history of migraine were treated with ubrogepant or placebo. In all trials, treatment with ubrogepant provided freedom from pain and relief from most bothersome symptom for a higher proportion of people treated with ubrogepant vs placebo. Participants were allowed to take their usual acute treatment of migraine at least two hours after taking ubrogepant, and 23% of participants were taking a preventive medication for migraine.

The most common side effects participants in clinical trials reported were nausea, tiredness, and dry mouth. Ubrogepant is contraindicated with strong CYP3A4 inhibitors.

Inhalable Levodopa (Imbrija; Acorda Therapeutics, Ardsley, NY)

Approved: December 21, 2018

Indication: intermittent treatment of OFF episodes in patients with Parkinson disease treated with carbidopa/levodopa

Available as: capsules of 42 mg for use with specific inhalation device twice consecutively for full dose of 84 mg not to be taken more than once per off period or more than 5 times daily

Treatment with inhalable levodopa (Imbrija; Acorda Therapeutics, Ardsley, NY) improved motor function on the Unifed Parkinson’s Disease Rating Scale (UPDRS) compared with placebo within 30 minutes (-9.83 points and -5.91 points respectively; P=0.009). Onset of action occurred as early as 10 minutes. The most common adverse reactions were cough (15% vs. 2%), upper respiratory tract infection (6% vs. 3%), nausea (5% vs. 3%) and sputum discolored (5% vs. 0%).

Capsules are for use with the inhaler only and should not be swallowed or broken open. Inhalable levodopa should not be used with nonselective monoamine oxidase inhibitors (MAOIs) or within 2 weeks of MAOI discontinuation.

MRI-Safe Deep Brain Stimulation (Vercise Gevia; Boston Scientific, Marlborough, MA)

Approved: August 19, 2109

Indication: bilateral subthalamic nucleus (STN) stimulation as adjunctive therapy to reduce motor symptoms of moderate to advanced levodopa-responsive Parkinson disease not adequately controlled with medication

Available as: an implantable device

This deep brain stimulation (DBS) system (Vercise Gevia; Boston Scientific, Marlborough, MA) is a second-generation system that allows people with the device implanted to have MRI in the full-body 1.5 T environment, if needed. The first-generation device, approved in 2017, showed a 48% improvement in motor function vs sham implant as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) III scores.

Istradefylline (Nourianz; Kyowa Kirin, Tokyo, Japan)

Approved: August 27, 2019

Indication: adjunctive therapy to levodopa/carbidopa for symptoms of off periods of Parkinson disease

Available as: tablets (20 mg or 40 mg).

Istradefylline (Nourianz; Kyowa Kirin, Tokyo, Japan) is an adenosine A2A-receptor inhibitor that significantly decreased the percentage of daily awake “off” time, from baseline (~30-60 min on average across multiple studies) vs placebo and also increased on time without troublesome dyskinesia by a similar amount.

Side effects included dyskinesia or worsening of dyskinesia in 1% of participants. People with hallucinations, impulse control problems, or compulsive behaviors should use a lower dose or discontinue istradefylline.

Siponimod (Mayzent; Novartis, East Hanover, NJ)

Approved: March 27, 2019

Indication: relapsing forms of multiple sclerosis (MS) in adults

Available as: tablets (0.25 mg or 2 mg)

Siponimod (Mayzent; Novartis, East Hanover, NH) significantly reduced the risk of 3-month confirmed disability progression (CDP) by 21% vs placebo (P=.013) in participants with all stages of MS. Those with active relapses in the 2 years before starting treatment had a 33% reduction in CDP compared with those treated with placebo (P=.01). Siponimod also reduced annualized relapse rate (ARR) by 55%. Although there was no significant difference in the timed 25-foot walk test (T25FW), T2 lesion volume and gadolinium-enhancing lesions were reduced by 79% and 89%, respectively, with siponimod.

Before starting siponimod, liver enzyme (CYP) genotype, ECG, and cardiovascular risk profile are needed. Siponimod is contraindicated for patients with CYP2C9*3/*3 genotype and cardiovascular risk factors. Vaccination status should be assessed because infection risk increases with treatment. Titration is recommended. The most common side effects are headache, hypertension, and transaminase elevation; macular edema is a rare but serious side effect.

Cladribine (Mavenclad; EMD Serono, Rockland, MA)

Approved: March 29, 2019

Indication: relapsing forms of multiple sclerosis (MS) in adults

Available as: tablets (10 mg)

Cladribine (Mavenclad; EMD Serono, Rockland, MA) treatment resulted in a 58% relative reduction in annualized relapse rate (ARR) (.14 vs .33, P<.001), increased freedom from relapse over 2 years (81% vs 63%, P<.05), and reduced 3-month confirmed disability progression on Expanded Disability State Scale (EDSS)(P<.05). Median number of gadolinium-enhancing brain lesions and new or enlarging T2 lesions were also reduced.

Cladribine is recommended for people who have had inadequate response to, or cannot tolerate other drugs for MS. Cladribine is not recommended for use in clinically isolated syndrome (CIS). The most common side effects include respiratory tract infection, headache, and lymphopenia. Serious adverse reactions included malignancies, herpes zoster infections, and oral herpes. Safety and efficacy of more than 2 years of cladribine has not been studied.

Eculizumab (Soliris; Alexion, Boston, MA)

Approved: June 27, 2019

Indication: neuromyelitis optica spectrum disorder (NMOSD) in adults with antiaquaporin-4 (antiAQP4+) antibodies

Available as: Injection of 300 mg/30 mL (10 mg/mL) as a clear, colorless solution in a single-dose vial

Eculizumab (Soliris; Alexion, Boston, MA) provided sustained freedom from relapse of NMOSD for 96% of people with antiAQP4+ NMOSD for 144 weeks vs 45% of those treated with placebo as monotherapy or adjunctive therapy. Of those whose only immunosuppressive treatment was eculizumab, no relapse occurred over the 144 weeks, whereas 80% of those treated with placebo and no other immunosuppressive treatment did experience relapse.

The most common adverse events were upper respiratory tract infection (29% with eculizumab vs 13% with placebo), nasopharyngitis (21% vs 19%), diarrhea (16% vs 15%), back pain (15% vs 13%) and dizziness (15% vs 13%). Serious adverse events included pneumonia (3 people treated with eculizumab and 1 treated with placebo) and cellulitis, sepsis, and urinary tract infection (2 people treated with eculizumab for each event). A person with a history of comorbid pulmonary disease and active smoking who received both eculizumab and supportive immunosuppressant therapy died from infectious pleural effusion. No cases of meningococcal infection, which has been seen in other studies of eculizumab were observed in the studies for NMOSD. Eculizumab has a boxed alert for meningococcal infections which occurred with some fatalities.

Diroximel Fumarate (Vumerity; Biogen, Cambridge, MA and Alkermes, Dublin, Ireland)

Approved: October 29, 2019

Indication: relapsing forms of multiple sclerosis (MS) in adults

Available as: delayed-release capsule (231 mg)

Diroximel fumarate (Vumerity; Biogen, Cambridge, MA and Alkermes, Dublin, Ireland) is a novel second-generation oral fumarate with low rates of gastrointestinal side effects in clinical trials. In an ongoing safety study of diroximel fumarate there has been a low overall rate of discontinuation due to adverse events (6.3%). Less than 1% of participants discontinued diroximel fumarate because of gastrointestinal adverse events.Approval was based on pharmacokinetic bridging studies comparing diroximel fumarate to dimethyl fumarate (Tecfidera; Biogen, Cambridge, MA) to establish bioequivalence. This application relied, in part, on safety and efficacy findings previously filed for dimethyl fumarate with the FDA.

Amifampridine (Ruzurgi; Jacobus Pharmaceuticals, Princeton, NJ)

Approved: May 6, 2019

Indication: Lambert-Eaton syndrome in children

Available as: functionally scored tablets (10 mg)

Amifampridine (Ruzurgi; Jacobus Pharmaceuticals, Princeton, NJ) was approved for children with Lambert-Eaton syndrome based on clinical trials in adults, pharmacokinetic data, and safety studies in children age 6 to 17 years. In clinicial trials, no adults treated with amifampridine had declines in the timed up-and-go test (TUG) whereas 72% of adults treated with placebo had 30% or more decline (P<.0001). Dosing in children is weight-based with those weighing 45 kg or more having treatment initiated at 15 mg to 30 mg daily, in divided doses that is increased daily by 5 mg to 10 mg in up to 5 doses/day to a maximum daily dose of 100 mg. For those weighing less than 45 kg, initiation should be with 7.5 mg to 15 mg daily, in divided doses that is increased by 2.5 mg to 5 mg up to 5 doses/day and a maximum dose of 50 mg. For those who need doses in smaller increments or have trouble swallowing, a 1mg/mL suspension can be prepared.

Onasemnogene abeparvovec (Zolgensma; AveXis, Bannockbur, IL)

Approved: May 24, 2019

Indication: treatment of infants less than age 2 years with spinal muscular atrophy (SMA) with biallelic mutations in the survival motor neuron 1 (SMN1) gene

Available as: a 1-time intravenous infusion

Gene replacement with onasemnogene (Zolgensma; AveXis, Bannockbur, IL) resulted in survival without need of ventilatory story for 34 of 36 babies treated. Of the 34 children still in the trial, all are achieving motor milestones not usually seen in children with SMA, including sitting, talking, and, walking. Rapid motor function improvements were seen as early as 1 month after treatment, and no waning of effect has been seen over 4 years of treatment.

Adverse effects included elevated liver transaminases, making liver function monitoring mandatory. Untreated SMA causes progressive motor degeneration, loss of motor function, need for continuous ventilation, and death in early childhood.

Onasemnogene is priced at $2.125 million, approximately half of the cost of 10 years of the only other available treatment for SMA and the ultrarare disease cost-effectiveness threshold of $250,000 per quality-adjusted life-year (QALY).

Riluzole Administration via Percutaneous Gastrostomy (Rilutek; ITF Pharma, Berwyn, PA)

Approved: November 22, 2019

Indication: treatment of amyotrophic lateral sclerosis (ALS)

Available as: liquid suspension 5 mg/mL administered twice daily through percutaneous gastrostomy tube.

Riluzole oral suspension (Tiglutek; ITF Pharma, Berwyn, PA) has been approved for administration via percutaneous endoscopic gastronomy (PEG) tube based on a study showing bioequivalence with oral administration.

Golodirsen (Vyondys 53; Sarepta Therapeutics, Cambridge, MA)

Approved: December 12, 2019

Indication: Duchenne muscular dystrophy (DMD) with confirmed dystrophin mutation amenable to exon 53 skipping

Available as: intravenous infusion

Golodirsen (Vyondys 53; Sarepta Therapeutics, Cambridge, MA) is an antisense oligonucleotide treatment for a subset of DMD with a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. Approval was based on the surrogate endpoint of increased skeletal muscle dystrophin (from a baseline of 0.1% of normal levels to 1.02% of normal levels) after 48 or more weeks of treatment. Clinical benefit has not been established.

Hypersensitivity reactions have occurred with golodirsen. Renal toxicity was observed in animal studies and has been seen with other ASOs, including potentially fatal glomerulonephritis. The most common adverse reactions in at least 20% of participants treated with golodirsen and more frequently than with placebo were headache (41%), pyrexia (41%), fall (29%), abdominal pain (27%), nasopharyngitis (27%), cough (27%), vomiting (27%), and nausea (20%).

Solriamfetol (Sunosi; Jazz Pharmaceuticals, Philadelphia, PA)

Approved: March 22, 2019

Indication: excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA) that is also being treated for the underlying cause

Available as: functionally scored tablets (75 mg or 150 mg)

People with OSA treated with solriamfetol (Sunosi; Jazz Pharmaceuticals, Philadelphia, PA) had improved Maintenance of Wakefulness sleep latency test (MWT) and Epworth Sleepiness scale (ESS) scores compared with placebo (P<.005). Improvements were dose dependent and occurred after the first week of treatment. For thosewith narcolepsy, treatment with solriamfetol vs placebo improved the MWT and ESS (P<.0001). Improved wakefulness lasted approximately 9 hours. Solriamfetol remained effective after 6 months of treatment.

The Drug Enforcement Agency (DEA) has designated solriamfetol a schedule IV agent, meaning it has low potential for abuse or dependence. The most common treatment-emergent adverse reactions (incidence 5% and higher than placebo) were headache, nausea, decreased appetite, and anxiety.

Pitolisant (Wakix; Harmony Biosciences, Plymouth Meeting, PA)

Approved: August 14, 2019

Indication: excessive daytime sleepiness (EDS) in adults with narcolepsy

Available as: tablets (4.45 mg or 17.8 mg)

Pitolisant (Wakix; Harmony Bioscience, Plymouth Meeting, PA) is the first and only nonstimulant treatment for EDS in adults with narcolepsy and is not a controlled substance regulated by the Drug Enforcement Administration (DEA). In clinical trials, pitolisant treatment improved mean Epsworth Sleepiness Scale (ESS) scores by 1 to 1.2 points compared with treatment with placebo. In the participants with narcolepsy treated with pitolisant, the most common adverse events (occurring in 5% of participants and at twice the rate of placebo) were insomnia (6%), nausea (6%), and anxiety (5%). Pitolisant was effective as monotherapy and in combination with stimulant and anticataplexy treatments in people with residual EDS. No significant pharmacokinetic interactions were observed when pitolisant was coadministered with modafinil or sodium oxybate. The recommended dose is 17.8 mg to 35.6 mg daily after titration and should be adjusted in people with hepatic or renal impairments and those who are poor metabolizers of CYP2D6.

Lemborexant (Dayvigo; Eisai, Woodcliff Lake, NJ)

Approved: December 23, 2019

Indication: insomnia in adults characterized by difficulties with sleep onset and/or sleep maintenance

Available as: tablets (5 mg or 10 mg)

Participants treated with lemborexant (Dayvigo; Eisai, Woodcliff Lake, NJ) vs placebo had statistically significant improvements in latency to persistent sleep (LPS) from baseline to end of treatment and more improvement in sleep efficiency (SEF) and wake after sleep onset (WASO), as measured by polysomnography. No effects on ability to waken in response to sound were seen.

The most common side effects are somnolence (10%) and nightmares (1%). Lemborexant may have effects on nighttime postural stability and worsen measures of attention and memory. At the 10-mg dose, lemborexant may affect next-day driving. Lemborexant was not associated with rebound insomnia or withdrawal effects after discontinuation. The FDA has recommended to the Drug Enforcement Administration (DEA) that lemborexant be classified as a controlled substance.

Intrasaccular Flow Disrupter (Web Aneurysm Embolization System; Microvention, Aliso Viejo, CA)

Approved: December 31, 2018

Indication: use at the middle cerebral artery (MCA) bifurcation, internal carotid artery (ICA) terminus, anterior communicating artery (AComm) complex, or basilar artery apex in adults for endovascular treatment of saccular, wide neck, bifurcation intracranial aneurysms with dome diameter from 3 mm to 10 mm and either neck size at least 4 mm or dome-to-neck ratio between 1 and 2

Available as: a system consisting of a permanent nitinol (nickel titanium) self-expanding mesh ball implant with a delivery wire and controller used to detach the device from the delivery wire

In 150 participants in clinical trials treated with the intrasaccular flow disruptor (Web aneurysm embolization system; Microvention, Aliso Viego, CA), 54.77% achieved complete occlusion of an intracranial aneurysm within 1 year of the procedure without retreatment, recurrent subarachnoid hemorrhage, or clinically significant parent artery stenosis.

Intracranial Coil-Assist Stent (Neuroform Atlas Stent System; Stryker Neurovascular, Fremont, CA)

Approved: May 16, 2019

Indication: to hold in place coil devices used to plug brain aneurysms with a neck size of at least 4 mm or a dome-to-neck ratio less than 2 (wide-necked brain aneurysms)

Available as: a self-expandable metal (nitinol) tube-shape device (stent) and a guidance wire

Of 182 people treated with the intracranial coil-assist stent (Neuroform atlas stent system; Stryker Neurovascular, Fremont, CA), 85% had their aneurysm completely sealed off 1 year after placement without the need for retreatment or parent artery stenosis.

Careful patient selection is recommended based on clinical practice guidelines or tools to assess the lifetime risk of brain aneurysm rupture, including age, comorbidities, history of smoking, brain aneurysm features, history of asymptomatic subarachnoid hemorrhage or family history.

Other contraindications include absence of antiplatelet treatment before implantation, active bacterial infection, and previously implanted stent in same location.

Interpretive Oculomotor Assessment Aid (Eyebox; Oculogica, New York, NY)

Approved: December, 28, 2018

Indication: measurement and analysis of eye movements to aid concussion diagnosis within 1 week of head injury in people age 5 to 67 years in conjunction with a standard neurologic concussion assessment

Available as: stand with eye-tracking camera, video stimulus display, and computer programmed to analyze eye movements

When results of the interpretive assessment (Eyebox; Oculogica, New York, NY) were compared to a trial-specific clinical reference standard for concussion, defining concussion as a) alteration of consciousness (AOC) or mental status (AMS), score less than 23 on the SCAT 3 Standardized Assessment of Concussion (SAC) and more than 25 on the SCAT3 Symptom Severity Score (SSS) or b) no AOC/AMS but an SAC score less than 15 and SSS score more than 32 on the SCAT 3. Of 46 concussions identified with those criteria, the interpretive oculomotor assessment aid identified 37 as positive resulting in a measured sensitivity of 80.4% (66.1%, 91.9%). This corresponds to a false negative rate (FNR) of 19.6% (9/46). Of the 236 individuals who did not meet the clinical reference standard definition for concussion, the aid identified 156 as negative for concussion for specificity of 66.1% (59.7%, 72.1%)