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Addressing the position of Edaravone within the management of Amyotrophic Lateral Sclerosis and Gaps in Care and access: expert Panel ideas

background

Amyotrophic lateral sclerosis (ALS) is a modern, disabling, and deadly neurodegenerative ailment that factors muscle weakness, incapacity, and at last death.1 it's most common in adults over the age of 60 years and affects 13,000 to 17,000 people within the u.s. with 5,000 new circumstances diagnosed each year.2

although the explanation for most ALS is unknown, genetic mutations are the underlying explanation for ALS in some patients. at present, more than forty genetic defects concerned in a variety of cellular pathways appear to trigger the disorder. This includes processing of ribonucleic acid molecules that can also cause ALS-linked motor neuron degeneration, whereas other genetic mutations can cause defects within the herbal procedure by which malfunctioning proteins are broken down and recycled to construct new ones.3

enlargement within the C9orf72 gene is essentially the most often universal reason for both ALS and frontotemporal dementia with motor neuron-like inclusions. clinical features of ALS and frontotemporal dementia can also take place in each familial and sporadic instances and characterize involvement of diverse mind regions from the equal neurodegenerative manner. The current hypothesis about gene and environmental interactions imply that environmental components can make contributions, however no such factors had been established3; although, certain environmental factors are suspected to be expertise risk components. These consist of exposure to smoking, different toxins, or infectious agents; real trauma; real endeavor; certain weight loss program and behavioral or occupational components; and publicity to certain toxins.three

diagnosis and ailment evaluation

ALS is essentially diagnosed based on symptom historical past, a real exam, and a sequence of exams to rule out illnesses with identical or overlapping symptoms.three ALS is defined via the presence of each higher and lower motor neuron signs. frequently, muscle and imaging exams akin to electromyography and nerve conduction reports are used to exclude other causes of indicators; these checks can reveal selected abnormalities that may additionally imply disorders similar to peripheral neuropathy or myopathy in place of ALS.three

ALS Functioning ranking Scale Revised

in the remaining few a long time, the ALS Functioning rating Scale Revised (ALSFRS-R) has become a greatly authorized measure of ALS progress, regardless of some limitations.4 This scale is a validated simple outcome measure used via medical trialists and regulatory our bodies to assess the cost of progression of disorder. point adjustments in ALSFRS-R can reflect clinically meaningful decline in functioning.4

The ALSFRS-R measures pastime degrees for 12 objects, together with speech, salivation, swallowing, handwriting, cutting meals and dealing with utensils, dressing and hygiene, delivering mattress, strolling, hiking stairs, dyspnea, orthopnea, and respiratory insufficiency. A patient is evaluated by way of 5 stages per item (0,1,2,3,4) with 4 indicating the optimum functionality and nil, the bottom functionality.

jap ALS Severity Classification Scale

besides the fact that children ALSFRS-R is the favourite scale for dimension of functioning in patients with ALS, the jap ALS severity classification scale additionally defines feature in patients with ALS and has been used as an inclusion criterion in clinical trials.5 This scale includes ratings from 1 via 5, that are described in desk 1.5

patient Burden

weakness is the defining symptom of ALS; it might probably have an effect on basically all volitionally managed muscular tissues. Early indicators of ALS encompass muscle twitching and muscle cramps, lack of muscle handle in arms and hands, impaired use of fingers or legs, weak spot and fatigue, tripping and falling, dropping gadgets, slurred or thick speech, and problem projecting the voice.2 because the ailment progresses, signs intensify and consist of shortness of breath, difficulty respiratory, problem swallowing, and paralysis.2 ALS is usually relentless in development, with an average survival of three to five years from symptom onset.6

financial Burden

The consequences of an evaluation confirmed that the estimated countrywide financial burden of ALS, including clinical, nonmedical, and indirect prices, ranged from $256 million to $1.02 billion in 2010 US bucks.7 With an estimated enhance of ALS instances, this burden is anticipated to enhance, proportionally, 34% by means of 2040.7

In 2010, annual charges for ALS were estimated at $31,121 per affected person. current facts from the Magellan Rx management database display annual costs for patients with ALS, except for those handled with edaravone, are equivalent, at $48,867 per affected person in scientific and pharmacy costs, excluding nonmedical and oblique fees associated with ALS. updated total medical, nonmedical, and oblique charges are vital with a view to precisely investigate the cost of novel cures.

present State of medication

No treatment has yet been discovered for ALS. currently, treatments goal to control signs, avoid complications, and Improve fine of lifestyles.three Care is superior supplied through a multidisciplinary crew regularly comprising physicians; pharmacists; actual, occupational, and speech therapists; nutritionists; social workers; respiratory therapists; scientific psychologists; and residential care and hospice nurses.3 a correct group can give sufferers with individualized remedy plans and acceptable device to Improve fine of life where viable.

medication plans for sufferers with ALS typically consist of a combination of drug therapy, real therapy, speech remedy, nutritional support, and breathing assist, counting on the affected person’s sickness progression and symptoms.3 at the time of this booklet, 2 drug healing procedures are authorised with the aid of the FDA for ALS: riluzole (Rilutek, Sanofi-Aventis) and edaravone (Radicava, Mitsubishi Tanabe Pharma the united states).

treatment guidelines

The American Academy of Neurology (AAN) launched updated guidelines in 2009 and reaffirmed these guidelines in January 2020.eight in keeping with the AAN, instructions are affirmed when the methodology continues to be sound and either there is not any new evidence or there's new facts that could now not change conclusions or options. The guidelines include a level A recommendation for riluzole, meaning it should be provided to gradual disease symptom progression in sufferers with ALS. When the instructions had been at first released, riluzole was the handiest FDA-authorized drug for ALS, explaining why there become no point out of edaravone (it turned into authorised in 2017); although, the guidelines had been reaffirmed devoid of modification after edaravone received FDA approval. The AAN does not at present have a booklet discussing the function of edaravone in the medicine of ALS; practice parameter and first-class size updates published on account that the most fresh guidelines have been launched protected no mention of edaravone.9,10 the lack of tips around edaravone and its location in ALS therapy may raise questions around the AAN’s intent in omitting edaravone for payers when constructing management techniques and outlining acceptable coverage standards. presently, there's an AAN ALS best Measures working neighborhood to revise a 2013 Neurology high-quality Measures paper, which might also address the position of edaravone within the medicine of ALS.eleven

The instructions additionally consist of recommendations for nutritional healing procedures (enteral foodstuff by way of percutaneous endoscopic gastrostomy may still be regarded to stabilize physique weight and extend survival) and respiratory cures (noninvasive ventilation may still be regarded to deal with respiratory insufficiency in ALS).8

the most recent guideline to handle the location in remedy for edaravone and riluzole in sufferers with ALS changed into posted in November 2020 in the Canadian clinical association Journal. This tenet suggested the use of edaravone in a selected neighborhood of sufferers with ALS: these with a disorder duration of under 2 years, with a compelled a must have ability (FVC) of 80%, a score of improved than 2 for all ALSFRS-R gadgets, and a confirmed constant decline within the ALSFRS-R over a three month interval.12

Overview of remedyRiluzole

Riluzole received FDA approval in 1995 for the remedy of ALS. The medication is an oral pill typically dosed at 50 mg twice each day. the first trial become a randomized, double-blind look at of one hundred fifty five patients with ALS; outcomes confirmed riluzole had a big impact on rate of survival and time to tracheostomy or loss of life, which turned into about 90 days longer in the riluzole-handled community than in the manage neighborhood.13

In a 2nd trial, 959 sufferers had been randomly assigned to 50 mg, a hundred mg, or 200 mg of riluzole or placebo day by day for three hundred and sixty five days in North the united states and for 18 months in Europe.13 The outcomes showed no change between the placebo group and the 50-mg community. although, more suitable early survival charges had been followed in sufferers that got either a hundred mg or 200 mg every day; the median survival time became 60 days longer in the riluzole community receiving one hundred mg or 200 mg than in the manage group.13 There turned into no change accompanied in survival between the 100-mg and 200-mg riluzole corporations; besides the fact that children, there turned into an increase in antagonistic events within the 200-mg community when compared with the one hundred-mg group. antagonistic activities associated with riluzole include asthenia, spasticity, nausea, and gentle elevations in aminotransferase ranges.13

Edaravone

The FDA approved edaravone in can also 2017 for the medicine of ALS.14 Edaravone is an intravenous infusion administered with the aid of a health practitioner or caregiver; the preliminary treatment cycle is 14 days of every day infusion, adopted with the aid of a 14-day drug-free period.14 Subsequent remedy cycles include dosing on 10 of 14 days, adopted by using 14-day drug-free durations. opposed routine associated with edaravone encompass bruising and gait disturbance, along with more severe dangers such as hives, swelling, shortness of breath, and allergy symptoms to sodium bisulfite.14

The preliminary section 3 study, MCI186-16, did not display efficacy of edaravone for ALS compared with placebo.15 A publish hoc subgroup analysis changed into performed and focused on 2 newly defined subgroups: efficacy-expected subpopulation (EESP; patients with compelled a must have means [FVC] ≥eighty% and as a minimum 2 points on all ALSFRS-R gadgets) and superior-efficacy-anticipated subpopulation inside EESP (dpEESP2y; onset of sickness within 2 years).15 The put up hoc evaluation had a chief conclusion point of alternate in ALSFRS-R rating throughout the 24-week remedy period. The evaluation showed efficacy in the dpEESP2y subgroup; trade in baseline of the least-squares suggest (± standard error values) in ALSFRS-R rating become 2.20(±1.03) for EESP and 3.01(±1.03) in dpEESP2y.15

in response to the findings within the put up hoc evaluation of MCI186-16, the section 3 MCI186-19 examine had inclusion standards of definite or likely ALS; normal respiratory characteristic (defined as FVC≥80%); ratings of at least 2 on all objects of the ALSFRS-R; length of ailment of 2 years or much less from symptom onset; aged 20 to 75 years; and deterioration of ALSFRS-R rating all through a 12-week pre-study remark period of 1 to 4 facets.sixteen These inclusion criteria resulted in a homogeneous community of patients with a quick expense of decline, the place the functional rating scale turned into not expected to promptly have a flooring effect. a total of 137 participants acquired both edaravone or placebo.

results confirmed 33% less functional loss within the edaravone-treated neighborhood than within the placebo community in a 24-week length.sixteen Edaravone confirmed a clinically tremendous impact, with change from baseline in ALSFRS-R of 5.01(± 0.64) and −7.50(± 0.sixty six) for edaravone and placebo, respectively.16 Over 6 cycles of treatment, 13% on edaravone vs 6% on placebo confirmed no decline in ALSFRS-R scores (0 features); 39% on edaravone vs 13% on placebo showed minimal feature decline (<3points); and 9% on edaravone vs 24% on placebo showed massive functional decline (>9points).sixteen

After the preliminary 24-week medication duration of MCI186-19, individuals were given the choice to enter an open-label extension of the study.16 a total of 123 patients opted to take part in the extension; 65 have been previously given edaravone and fifty eight had been in the past in the placebo neighborhood. In a submit hoc evaluation of the extension study results, an estimate of doubtless progression in members given the placebo vs edaravone within the preliminary remedy length become used to predict development inside every group with no trade in medicine over the subsequent 24 weeks.sixteen evaluation of the projected progress compared with the real rate of development amongst those given edaravone for the complete forty eight weeks and those that switched from placebo to edaravone

showed that the projected decline for the placebo community changed into better than the genuine decline within the sufferers who switched from placebo to edaravone (13.0 vs 10.9 elements, respectively).16 according to the FDA middle for Drug contrast and research clinical evaluate of edaravone, the results of the extension showed there turned into not a major difference in elevated disability the usage of either the jap scale or the ALSFRS-R between the placebo- edaravone and edaravone-simplest sufferers.17

Gaps in managementCurrent Payer guidelines for Edaravone

Edaravone is typically lined on the scientific benefit and, across most guidelines, strict standards have to be met earlier than insurance is provided, each initial and persevered. The standards commonly align with the inclusion standards for the phase three MCI186-19 analyze and encompass ailment duration of two years or much less, FVC of as a minimum 80%, and an ALSFRS-R score of at least 2 on all items. besides the fact that children, the use of those standards apart from a large choice of alternative standards varies greatly amongst payers. The criteria for endured coverage differ as smartly; some of those criteria include neurologist attestation of scientific benefit, slowing decline of ALSFRS-R rating (no longer described), cumulative ALSFRS-R rating of at least 3, and no requirement for invasive air flow, or any aggregate of these. the lack of consensus throughout payer policy standards for insurance and carrying on with coverage of edaravone can also create a barrier for sufferers who might advantage from remedy. desk 2 and desk 3 display the disparity between criteria required for initial and continued insurance over a sampling of 13 payer guidelines.

Panel Insights and suggestions coverage criteria

When discussing no matter if the coverage criteria warranted revisiting or enhancing, the payer panelists cited that administrative burden is a major consideration. it is fundamental to be sure that insurance standards have precise medical aim in defining a suitable patient for therapy as opposed to merely making a burden for all stakeholders—suppliers, payers, and patients. In assessing the 3 leading coverage standards, the dialogue weighed the price of criteria inclusion towards the executive burden. Payers expressed that in this house, streamlining authorization and insurance techniques and cutting back burden will probably not influence in further sufferers being handled however could get rid of a barrier for providers, payers, and sufferers. moreover, payers mentioned that in many circumstances these criteria are not absolute. If a person patient’s provider feels the treatment may be advisable, the case might be reviewed and the company’s enter should be considered.

normal, besides the fact that children some payers did not believe adjustments would necessarily outcomes in additional sufferers being accepted for medication with edaravone, others agreed there's opportunity to revisit certain policy criteria for edaravone coverage to give access for a broader patient inhabitants that might benefit from remedy.

sickness length

the vast majority of the panel agreed that the requirement of ailment length of two years or much less warranted revisiting. The KOLs expressed that limiting access to treatment in accordance with ailment duration didn't have clinical value. specifically, because of the model in

sickness progression, a patient diagnosed young with slow disorder progression might meet all insurance standards aside from disease period but may be prohibited from insurance. The KOLs also cited that ailment onset can not be precisely assessed in many patients with ALS.

in keeping with facts in the publish hoc evaluation of MCI186-19, a couple of payers were convinced that the population of patients who may also improvement from edaravone extends past those with a disorder period of two years or much less. information from the MCI186-19 trial means that the purposeful decline in sufferers who switched to edaravone after receiving the placebo become comparable to folks that had been initiated on edaravone previous in disorder progression.17 There become typical consensus that an opportunity exists to reassess this criterion and to determine when a affected person should birth therapy to benefit from it clinically. At this element, most payers agreed the existing ailment period criterion creates a niche for patients who could still benefit from medicine through flattening the scope of linear sickness development.

FVC of at the least eighty%

There was consensus among a majority of the panel that removing of the FVC criterion from coverage policies may still be considered. probably the most payer members noted that their respective fitness plan had already removed the criterion in line with obtainable literature. results from a submit hoc analysis of MCI186-19 validated that ALS sufferers with FVC of eighty% obtained giant improvement from medicine with edaravone, indicating that baseline FVC may additionally no longer be an appropriate criteria for deciding upon sufferers eligible for treatment.18 basic, the KOLs and most payers agreed that inclusion of this criterion didn't quite simply outline a patient inhabitants and might no longer be a fundamental threshold to check insurance.

Even the place a small minority did not agree that the FVC criterion should be removed from coverage policies, they did agree that an exception for patients with severe bulbar dysfunction could be appropriate. A bulbar dysfunction exception is at the moment existing in some policies having a requirement of FVC of as a minimum 80%. This exemption can observe to people with documentation of extreme bulbar dysfunction who're incapable of competently performing an FVC look at various.

ALSFRS-R score of as a minimum 2 on All gadgets

The KOLs expressed that requiring a selected score on each particular person merchandise of the ALSFRS-R is an influence measure–related subject and not applicable in medical care. The rationale this inclusion criterion turned into covered in clinical trials changed into to steer clear of complete lack of sufferers on ALSFRS-R objects (ie, floor impact); outcomes from a put up hoc analysis of MCI186-16 confirmed efficacy among early stage ALS sufferers, or those with scores of at least 2 points on ALSFRS-R gadgets.19 consequently, the inclusion standards for MCI186-19 became determined for that reason.19 evaluation of MCI186-19 effects imply that edaravone has a clinically significant effect in preserving feature for ALS patients.20 in particular, there become a first rate reduction in sufferers experiencing a decline in ALSFRS-R rating from three to 2 for gadgets together with swallowing, ingesting motion, going for walks, and hiking stairs.20 These findings suggest edaravone can play a job in maintaining feature in some patients with ALS, however this would be confined if access is limited to these with handiest selected ALSFRS-R ratings. making use of a rating across all items can create a challenge for sufferers with reasonable disease development who have a delayed diagnosis. KOLs explained that efficacy is accompanied in sufferers who obtain edaravone with progressed disease; sufferers who may also not meet the required ranking on all ALSFRS-R objects may nevertheless acquire a medical advantage from medication.

across the payer individuals, there was settlement that a measure has to be in vicinity to check the patients who would most benefit from remedy. currently, payers consider the ALSFRS-R is the most facts-based measure; despite the fact, a number of payers expressed activity in revisiting these standards to increase flexibility. One alternative discussed became weighting distinct items of the ALSFRS-R rating greater than others, most likely in response to which objects are extra carefully linked to clinical improvement with edaravone.

Payers additionally expressed that ALSFRS-R objects may point out the potential of sufferers to live independently; having this requirement in location would allow clinical advantage, or slowing decline, to be superior quantified. records suggests that early intervention with edaravone is associated with a reduction of occurrence of loss of life, tracheostomy, everlasting assisted air flow, and hospitalization in patients with ALS.21 although, KOLs mentioned that in terms of deciding on a patient’s capability to live independently, the japanese ALS severity classification generally is a more correct size. Requiring a patient to have a selected ranking on this very basic practical scale may better classify which sufferers are capable of are living independently.

continued coverage standards for Edaravone

As in the past referred to, continued insurance guidelines fluctuate more largely than preliminary coverage guidelines. In some situations, the KOLs noted there does not seem to be clinical evidence to justify one of the crucial criteria that definite policies consist of. definite payers were based on KOLs and viewed some persisted coverage standards as inappropriate. These payers felt that reauthorization guidelines could be streamlined to in the reduction of administrative burden. Some payers noted they would hold 2 standards: (1) invasive ventilation isn't required, and (2) the capacity to operate most each day activities. besides the fact that children, most payers mentioned that, apart from cases the place invasive air flow is required, their review method takes the particular person’s growth whereas being handled with edaravone under consideration to make an advised choice on coverage continuation.

There turned into consensus among the many neighborhood that essentially the most critical criterion for endured insurance is an attestation of clinical benefit from the treating neurologist. certain payers felt that, together with a neurologist attestation, some documentation of slowing decline should be protected to justify persevered remedy. This documentation and attestation may be regarded in making a coverage resolution and, in accordance with the individual patient needs, may lift greater weight toward approval than coverage renewal criteria on my own.

Payers did observe it might be advisable to have a clearer choice of which measures outline when a affected person will continue to advantage from medication with edaravone. KOLs stated that if there is still motor function to be preserved, most patients will advantage from continuation but in follow, they also consider the affected person’s burden of treatment with an infused treatment. evidence does suggest edaravone is associated with reduction in decline in ALSFRS-R ratings.20 Payers agreed they might search for an attestation from the neurologist when reviewing a patient’s request to proceed therapy.

instructions for treatment of sufferers With ALS

because the treatment panorama for ALS changes, the KOLs mentioned there's an ongoing effort through experts in the ALS space to replace instructions, and there's a existing need for a consensus guiding principle to be reviewed and counseled by the AAN and the American affiliation of Neuromuscular and Electrodiagnostic drugs (AANEM). An endorsement of consensus can be looked at in lieu of updates made all over a evaluate of the existing reaffirmed instructions from 2019.

Payers mentioned that while, in their experience, instructions aren't always referenced in policies, the guidelines are 1 resource used to assist verify applicable coverage criteria. Some payers noted that the guidelines are second to FDA approval criteria when it comes to evidence to aid constitution guidelines and, in the absence of comprehensive finished guidelines in a remedy house, designing an appropriate, evidence-primarily based policy is difficult. A consensus guiding principle would be positive in cutting back remedy version and boundaries to medicine and in increasing consistency in coverage and management.

although guidelines will also be designed and structured in keeping with purchasable literature, facts, and proof, a resource equivalent to a suggestion or an expert consensus observation can be beneficial and noticeable in choosing a evidently defined affected person inhabitants appropriate for therapy. Payers mentioned that instructions are not a necessity in setting up guidelines, however when purchasable, payers will refer to and count on them as a significant resource.

can charge Effectiveness in ALS medicine

overall, payers cited that charge-effectiveness measures and statistics would not weigh heavily in coverage selections for this therapy since the total budget influence is not significant. KOLs mentioned that many patients select no longer to beginning edaravone remedy or decide to discontinue therapy since the benefit of slowed ailment development does not outweigh the burden of medication administration by the use of infusion. because the population of patients with ALS is already a small fraction of the payers’ member populations, the finances affect of the small variety of sufferers receiving edaravone can be insignificant ample that charge and value-effectiveness evaluations would now not weigh within the resolution-making system in a meaningful method.

Future needs and issues

relocating ahead, the participants concluded there's a necessity to strategy the AAN and AANEM for a reassessment of the guidelines, ensuring that a transparent stance on all available cures is included. These guidelines will create a way of realizing and can allow for cohesiveness across guidelines, helping to in the reduction of obstacles to medication and needless burden on stakeholders.

at the time of the panel, payers mentioned that actual-world effect information would be foremost in helping to examine broader patient populations that might improvement from treatment, backyard of those that meet the coverage criteria. facts might assist a transparent definition of patients for initial medicine in addition to these for whom endured medication can be applicable and clinically effective. In may additionally 2021, precise-world proof introduced at the European network for the remedy of ALS established that persisted edaravone medication can also Improve common survival in sufferers with ALS when compared with ALS sufferers treated predominantly with riluzole.22 further, identical true-world outcomes may well be used to assist clear instructions and determinations on the role of edaravone in ALS remedy.

The panel concluded that the obtainable facts coupled with the different starting and continuation policy criteria warranted a reassessment of coverage standards with the probability of certain standards being eliminated, such because the ailment period and FVC standards, and other criteria being restructured, similar to ALSFRS-R scores, and that medication guidelines from groups like the AAN would be positive and effective in assisting to more suitable structure insurance guidelines to ensure entry for acceptable sufferers. typical, clear assistance and consensus on the role of edaravone in the medication of ALS should lead to extra consistent policy criteria for starting and continuation of remedy, resulting in appropriate access to look after patients with ALS.

Acknowledgements

The authors well known Haita Makanji, PharmD, and Stacy Inman, PharmD, for facilitating the panel discussion and proposing writing suggestions; and Carole Kallas for providing administrative aid.

writer affiliations: priority fitness, Grand Rapids, MI (CJB); unbiased fitness, Buffalo, big apple (MB); Magellan health, Scottsdale, AZ (CC); Georgetown university clinical, Washington, DC (JC); CenCal health, Santa Barbara, CA (JJ); BlueCross BlueShield of Western new york, Buffalo, the big apple (LL); Mayo medical institution, Jacksonville, FL (BO); Moda health, Portland, OR (CR); Magellan Rx management, Middletown, RI (LS); health New England, Springfield, MA (GT).

Funding source: financial aid for this work became offered via Mitsubishi Tanabe prescription drugs and facilitated with the aid of Magellan Rx administration.

creator disclosures: Dr Barrington, Burruano, Dr Choi, Dr Januska, Dr Lachuk, Dr Oskarsson, Dr Rodriguez, Speicher, and Dr Tereso have obtained honoraria from Magellan Rx management; Dr Choi has also bought gives you from Massachusetts accepted clinic, Washington tuition, and Biogen; Dr Oskarsson has held board membership at the ALS affiliation, Western ALS examine group, and ALS home health scientific requirements group; Dr Oskarsson has also acquired promises from Mitsubishi Tanabe Pharma, MediciNova, Inc, Biogen, Cytokinetics, AZ Therapeutics, Eisai, Roche, and GlaxoSmithKline; Dr Oskarsson has also bought honoraria from Mitsubishi Tanabe, MediciNova, Inc, Biogen, and Biohaven, Tsumura & Co.; Dr Carney and Speicher have been employed at Magellan Rx management.

Authorship tips: idea and design (CJB, MB, CC, JC, JJ, LL, CR, LS, GT); Acquisition of records (CC, JJ, LL, BO, LS); analysis and interpretation of information (CJB, MB, CC, JC, LL, BO, CR, LS, GT); Drafting of the manuscript (CJB, MB, JC, LL, BO, CR, LS, GT); vital revision of the manuscript for vital intellectual content (JJ, LS); Administrative, technical, or logistic assist (LS).

handle correspondence to: Lindsay Speicher, JD. email: lspeicher@ magellanhealth.com

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