2020 Symposia Series 1 Embracing New Treatment Options in the - - PowerPoint PPT Presentation

2020 Symposia Series 1

Embracing New Treatment Options in the Management of Migraine Headache

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• Apply current diagnostic criteria for differential diagnosis of migraine to

increase early recognition and treatment

• Employ current migraine guideline recommendations and management

strategies to establish improved patient treatment plans

• Identify the appropriate use of established and emerging treatment options

for migraine and related monitoring and safety options

Learning Objectives

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Migraine Is Common

Lipton RB, et al. Headache. 2001;41:646-657; Lipton RB, et al. Neurology. 2007;68:343-349. 20 30 40 50 60 70 80 100 5 10 15 20 25 30

Age (years) Migraine Prevalence (%)

Female Male

US Prevalence (%) Female Male Sex 17 6 Race White Black 17 14 6 4 Highest prevalence Age 30 to 39 years 24 7

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20 40 60 80

Migraine Is Debilitating

Feigin VL et al. Lancet Neurol. 2019, 18:459-480; Institute for Health Metrics and Evaluation (IHME). Findings from the Global Burden of Disease Study 2017. Seattle, WA: IHME, 2018; Linde M, et al. Cephalalgia. 2004;24:455-465.

Percentage of Migraineurs (N = 423) Very negative influence Quite negative influence Some negative influence 7 Sexual life 8 28 3 Love 6 22 2 Finding friends 8 3 Social position 10 24 8 Leisure time 14 37 4 6 Finances 20 4 Family situation 23 38 8 Pursuing studies 12 27 3 Pursuing career 8 16 Attendance at work 8 18 47

• 2nd most disabling episodic

condition after lower back pain

• Migraine is a chronic disease

with episodic manifestations

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Throbbing pain Release of CGRP

• Multiple potential sources or sites of action
• Headache and other symptoms
• Target for small-molecule antagonists and antibodies

Thalamus

• Sensitization of alteration of thalamocortical circuits
• Sensory sensitivity and allodynia
• Target for neuromodulation

Hypothalamus

• Activation in premonitory phase
• Premonitory symptoms
• Target for hypothalamic

peptides and modulators Cortex

• Cortical spreading depolarization, altered connectivity
• Migraine aura and cognitive symptoms
• Target for neuromodulation

Trigeminocervical Complex

• Pain transmission or sensitization
• Headache and neck pain
• Target for medications and neuromodulation

Pathophysiology of Migraine—Implications for Management

Charles A. Lancet Neurol. 2018;17:174-182.

Pain perception

Upper Cervical Nerves

• Pain transmission or

sensitization

• Neck and head pain
• Target for local injections and

neuromodulation

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Prodrome

• Fatigue
• Food craving
• Muscle pain
• Cognitive change
• Mood change
• Sensory disruption

Aura (if present)

• Visual

– Scintillating scotoma

• Sensory
• Motor

Headache

• Localization
• Throbbing
• Nausea
• Vomiting
• Photophobia
• Phonophobia

Postdrome

• Fatigue
• GI upset
• Cognitive

change

• Muscle pain
• Mood change

What Happens During a Migraine Attack?

Adapted from: American Migraine Foundation. americanmigrainefoundation.org/understanding-migraine/timeline-migraine-attack/. Accessed Apr 13, 2020.

≤1 hour ~4 to 72 hours

Clinical Phases of Migraine

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Case Study: Colleen, a 42-Year-Old Call Center Operator

Presenting Complaint

• “Tension headaches” that have become

more frequent and debilitating in the past 10 years

• Current headaches not relieved by

nonprescription NSAIDs

• Recurrent insomnia, occasional

constipation

NSAID = nonsteroidal anti-inflammatory drug.

History

• Minor headaches since she was in her teens
• No history of trauma or unusual stresses
• Bilateral tubal ligation
• Works from home most days

Physical Exam and Medications

• Height: 5 ft 6 in; weight: 186 lb; BMI: 30.0 kg/m2
• Hypertension controlled with amlodipine 5 mg/d

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• Frequency and patterns

‒ Any significant changes

• Location
• Duration
• Quality and intensity
• Time to peak intensity
• Preceding symptoms (eg, how the headache begins; triggers)
• Warning symptoms and aura
• Associated symptoms and level of disability
• Aggravating or relieving factors

What to Ask About When Taking a Thorough Headache History

Weatherall MW. Ther Adv Chronic Dis. 2015;6:115-123.

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Case Study (cont’d): Colleen’s History

• Unilateral pattern of pain, sometimes behind browbone
• Headaches often worse around menses
• Headaches 4 to 6 times a month for the last 2 years, lasting from a few

hours to up to a day

• Severity varies but is usually moderate or severe
• Interfere with work and household needs about 1 or 2 days a week
• Loud noises and bright lights make headaches worse; sometimes her

neck becomes sore

• Sometimes feels congested and has a runny nose
• Headaches often accompanied by nausea
• Neurologic exam within normal limits

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Typical Presentations of Common Forms of Headache

TENSION TYPE

• Pain “like a band”

squeezing the head

• Primary headache

per ICHD-3

MIGRAINE

• Unilateral pain
• Often with nausea and

visual changes

• Primary headache

per ICHD-3

CLUSTER

• Pain in and around one

eye

• Primary headache

per ICHD-3

“SINUS”

• Pain behind browbone

and/or cheekbones

• Secondary headache per

ICHD-3

• Unless clear signs of active

infection, often is a migraine headache

ICHD-3 = International Classification of Headache Disorders, 3rd edition. Cady RK, Schreiber CP. Otolaryngol Clin North Am. 2004;37:267-288; Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2018;38:1-211; brgeneral.org www.brgeneral.org/healthy-lifestyle-blog/2018/november/4-major-types-of-headaches-and-where- they-hurt/. Accessed Apr 22, 2020.

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Typical Presentations of Common Forms of Headache

ICHD-3 = International Classification of Headache Disorders, 3rd edition. Cady RK, Schreiber CP. Otolaryngol Clin North Am. 2004;37:267-288; Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2018;38:1-211; brgeneral.org www.brgeneral.org/healthy-lifestyle-blog/2018/november/4-major-types-of-headaches-and-where- they-hurt/. Accessed Apr 22, 2020.

TENSION TYPE

• Pain “like a band”

squeezing the head

• Primary headache

per ICHD-3

MIGRAINE

• Unilateral pain
• Often with nausea and

visual changes

• Primary headache

per ICHD-3

CLUSTER

• Pain in and around one

eye

• Primary headache

per ICHD-3

“SINUS”

• Pain behind browbone

and/or cheekbones

• Secondary headache per

ICHD-3

• Unless clear signs of active

infection, often is a migraine headache

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Migraine Tension-type ≥2 of the following

• Unilateral (59% of migraines)
• Pulsating (85% of migraines)
• Moderate to severe intensity lasting between 4 and

72 hours

• Aggravation by routine physical activity

≥2 of the following

• Bilateral
• Not pulsating
• Mild to moderate intensity
• Not aggravated by routine physical activity

≥1 of the following

• Nausea/vomiting (73% of migraines)
• Photophobia/phonophobia (~80% of migraines)
• No nausea/vomiting
• One or neither: photophobia/phonophobia

Not attributable to another disorder Not attributable to another disorder

Migraine vs Tension-type Headache: A Common Misdiagnosis

Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2018;38:1-211; Lipton RB, et al. Headache. 2001;41:646-657.

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Landmark Study: How Likely Is it That an Episodic Headache Is Migraine?

• Prospective, open-label study of patients with

episodic headache (N = 1203)

• >90% seen in primary care
• Self-report or physician diagnosis of migraine

almost always correct

• Self-report or physician diagnosis of

nonmigraine almost always later found

• ut to be migraine

Tepper SJ, et al. Headache. 2004;44:856-864.

Migraine

(n = 288) 76%

Unclassifiable

(n = 11) 3%

Episodic tension-type

(n = 11) 3%

Probable migraine

(n = 67) 18%

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Symptoms in the last 3 months:

❑

Light sensitivity with headache

❑

Nausea with headache

❑

Decreased ability to function with headache

ID Migraine™: Simplified Diagnostic Criteria for Migraine

Lipton RB, et al. Neurology. 2003;12:375-382.

Any 2 of the 3 above symptoms = migraine

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S

Systemic involvement (fever, myalgias, weight loss) Systemic disease (cancer, AIDS)

N

Neurologic symptoms or signs

O

Onset sudden (thunderclap headache)

O

Onset after age 50 years

P

Pattern of change: progressive headache/fewer headache-free periods; change in type of headache; headache associated with pregnancy; headache related to body position

Red Flags: SNOOP

Dodick DW. Adv Stud Med. 2003;3:87-92; Dodick DW. N Engl J Med. 2006;354:158-165.

Be alert to signs/symptoms of secondary headache.

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HIT-6

• Measures the impact headaches have
• n job, school, home and social

situations

• Total score ≥50 suggests significant

impact MIDAS

• Measures how migraines affect everyday

functioning

Headache Impact Test (HIT)-6 and Migraine Disability Assessment (MIDAS) Test

Kosinski M, et al. Qual Life Res. 2003;12:963-974.

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Case Study (cont’d)

• Clinical findings are consistent with migraine without aura
• Colleen is surprised because she thought migraines were always

associated with an aura

• Says that she is “just happy to know what is going on”
• Headaches have a significant impact on her daily activity

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Importance of a Headache Diary

• Helps identify

– Triggers – Location – Warning signals – Length – Stress, exercise, other related events

Date Time (start/finish) Intensity (rate 1-10: most severe being 10) Preceding Symptoms Triggers Medication (and dosage) Relief (complete/ moderate/none)

‒ Records intensity of pain ‒ Monitors treatment progress ‒ Sometimes required for prior authorization for certain medication coverage by insurers

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• Irregular meals, dehydration
• Irregular caffeine
• Chocolate, nuts, bananas, etc
• Irregular sleep (particularly

excessive sleep)

• Weather, changes in weather

Common Migraine Triggers

Hoffmann J, et al. Curr Pain Headache Rep. 2013;17:370.

• Light, sunlight exposure
• Sensitivity to odors (osmophobia)
• Stress or “let-down” from stress
• Air travel, change in barometric

pressure

• Menstrual period

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Six 8-oz glasses

• f water per day

Lifestyle Modification: Consistency Is Key

Robbins L. www.practicalpainmanagement.com/patient/conditions/headache/7-lifestyle-tips-help-prevent-migraines-headaches. Accessed Apr 13, 2020.

Don’t skip meals Caffeine <200 mg/d Sleep Exercise

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• Oral contraceptives
• Hormone replacement
• SSRIs
• Steroids (tapering)
• Decongestants
• Short-acting sedatives

Medications That May Exacerbate Migraines

SSRI = selective serotonin reuptake inhibitor. Allais G, et al. Neurol Sci. 2009;30(suppl 1):S15-S17; MacGregor EA. Curr Pain Headache Rep. 2009;13:399-403; Nierenburg Hdel C, et al.

• Headache. 2015;55:1052-1071.

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Acute Treatment Principles

• Establish what the patient’s goals are
• Treat at least two attacks with the same medication
• If medication is ineffective:

⎻ Ensure that no other medications are interfering with response ⎻ Ensure patient is taking the drug at the correct time ⎻ Maximize dose ⎻ Change formulation/route of administration ⎻ Change drug ⎻ Add drug ⎻ Try combination therapy (eg, sumatriptan + naproxen)

Goal: quickly restore patient to normal function in a safe and effective manner that minimizes additional medication exposure and resource use

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Case Study (cont’d): Colleen’s Regimen for Acute Attacks

• Colleen begins lifestyle modifications of drinking more water, reducing

caffeine to <200 mg/day, and getting more sleep and exercise

• You counsel her on keeping a headache diary
• You prescribe sumatriptan, 100 mg as needed, with instructions to take at
• nset of headache and repeat once in 24 hours if needed

‒ After 6 weeks on sumatriptan, Colleen’s headaches have not improved

• You discontinue sumatriptan, and prescribe rizatriptan oral disintegrating

tablet, 10 mg as needed, with instructions to take at onset of headache and repeat once in 24 hours as needed ‒ After 6 weeks on rizatriptan, Colleen’s headaches have not improved

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Triptans Ergots Nonspecific treatments Gepants Serotonin 5-HT1F Receptor Agonist Almotriptan Eletriptan Frovatriptan Naratriptan Rizatriptan Sumatriptan Sumatriptan + naproxen Zolmitriptan Dihydroergotamine Ergotamine + caffeine Antiemetics Aspirin +/‒ acetaminophen +/‒ caffeine Diclofenac, ketorolac, other NSAIDs Corticosteroids (IV; rescue therapy) Rimegepant Ubrogepant Lasmiditan

Treatment of Acute Migraine: Medications

Med Lett Drugs Ther. 2017;59:27-32.

• A variety of routes of administration (oral, nasal spray, suppository, etc) and combinations are available
• Products containing butalbital are sometimes used despite evidence that butalbital is not effective for

migraine pain and can cause rebound headache

• Reserve opiates only for limited use in very severe migraine

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Lasmiditan Rimegepant Ubrogepant Mechanism

• f Action

Serotonin 5-HT1F receptor agonist CGRP receptor antagonist CGRP receptor antagonist Indication Acute treatment of migraine with or without aura in adults Dosing 50 mg, 100 mg, or 200 mg orally, as needed (not to exceed 1 dose in 24 hrs) 75 mg orally or sublingual, as needed (not to exceed 1 dose in 24 hrs) 50 mg or 100 mg orally, as needed; may take 2nd dose ≥2 hours later; not to exceed 200 mg in 24 hrs Adverse Events Dizziness, fatigue, paresthesia, sedation, driving or machinery impairment for 8 hrs after taking Nausea Nausea and somnolence

Lasmiditan, Rimegepant, and Ubrogepant: New Options for Acute Migraine Treatment

Lasmiditan [prescribing information]. Eli Lilly and Company; 2019; Rimegepant [prescribing information]. Biohaven Pharmaceuticals, Inc; 2020; Ubrogepant [prescribing information]. Allergan; 2019..

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Case Study (cont’d)

• Colleen appears to be following lifestyle modifications
• You prescribe lasmiditan, 100 mg as needed
• Colleen reports success “sometimes,” but headaches worsening and still

missing work

• Review of headache diary:

‒ Headaches are more frequent than Colleen initially described, occurring at least twice a week ‒ Headaches still cause impairment and often require bedrest

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When Should Preventive Treatment for Episodic Migraine Be Considered/Offered?

Lipton RB, et al. Headache. 2015;55(suppl 2):103-122; Lipton RB, et al. Neurology. 2007;68:343-349; Silberstein SD, et al. Neurology. 2012;78:1337-1345.

• When patients have severe or frequent migraines: 3 or more days per month
• After failure or overuse of acute therapies
• When patients want to pursue another option
• Epidemiologic studies suggest that:

‒ ~38% of migraineurs would benefit from preventive therapy, but… ‒ Only 11% currently receive them

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Episodic vs Chronic Migraine: Definitions

Lipton RB, et al. Headache. 2015;55(suppl 2):103-122.

Episodic migraine:

• Headache <15 days/month

Chronic migraine:

• Headache ≥15 days/month

for >3 months

• Features of migraine headache

present for ≥8 days/month

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Principles of Preventive Pharmacotherapy

• Establish what the patient’s goals are
• Give each treatment an adequate trial
• Continue for at least several months
• Avoid interfering, overused, and contraindicated drugs
• Re-evaluate therapy
• Women of childbearing potential should understand risks
• Involve patients in their care to maximize adherence
• Consider comorbidities and choose medications to treat coexisting disorders when

possible

• Choose drugs based on efficacy, patient preferences, headache profile, adverse effects

D’Amico D, et al. Neuropsychiatr Dis Treat. 2008;4:1155-1167.

Goal: reduce frequency, duration, and severity of individual events and possibly reduce disease progression

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Considerations

• Check for teratogenicity
• Topiramate for patients

with obesity?

• β-blocker for hypertensive

nonsmokers ≤60 years of age?

• Triptan for MRM?
• Amitriptyline for patients

with insomnia, mood disorder, or depression?

• Anti-CGRP monoclonal

antibodies now also an

• ption

AAN/AHS Classification of Preventive Therapies for Episodic Migraine

Yellow = FDA approved for migraine prophylaxis. *For short-term prophylaxis of MRM. AAN/AHS = American Academy of Neurology/American Headache Society; ACE = angiotensin-converting enzyme; MRM = menstrual-related migraine; SSNRI = selective serotonin norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant. Silberstein SD, et al. Neurology. 2012;78:1337-1345.

Level A: Medications With Established Efficacy (≥2 class I studies) Level B: Medications That Are Probably Effective (1 class I or 2 class II studies) Level C: Medications That Are Possibly Effective (1 class II study)

Antiepileptic drugs Divalproex sodium Valproate sodium Topiramate Antidepressants/SSRI/SSNRI/TCA Amitriptyline Venlafaxine ACE inhibitors Lisinopril Angiotensin receptor blockers Candesartan -Blockers Atenolol Nadolol -Agonists Clonidine Guanfacine -Blockers Metoprololl Propranolol Timolol Triptans (MRM) Naratriptan* Zolmitriptan* Antiepileptic drugs Carbamazepine Triptans (MRM) Frovatriptan* -Blockers Nebivolol, pindolol Antihistamines Cyproheptadine

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• Anti-CGRP monoclonal antibodies*

‒ Eptinezumab ‒ Erenumab ‒ Fremanezumab ‒ Galcanezumab

• OnabotulinumtoxinA

FDA-Approved Preventive Therapies for Chronic Migraine

*Also FDA approved for prevention of episodic migraine. Med Lett Drugs Ther. 2017;59:27-32.

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Behavioral Interventions

• Relaxation training
• Biofeedback combined with

relaxation training

• Electromyography

biofeedback

• Cognitive behavioral therapy
• Combination treatment

Other Interventions for Prevention

Silberstein SD et al. Neurology Sep 2000, 55 (6) 754-762; American Migraine Foundation. americanmigrainefoundation.org/understanding- migraine/spotlight-neuromodulation-devices-headache/. Accessed Apr 13, 2020; Gaul et al. J Headache Pain. 2015;16:516.

Neuromodulation

• Single pulse transcranial

magnetic stimulation (sTMS)

• Noninvasive vagal nerve

stimulation (nVNS)

• External trigeminal nerve

stimulation (eTNS) Other

• Acupuncture
• Physical therapy with

massage and exercise

• Nutritional supplements

– Magnesium, riboflavin, CoQ10

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Collaborative Care of Migraine

• Migraine is a chronic disease and requires patients and clinicians to work

together toward common therapeutic goals

• Help patients understand and address all migraine-related health issues

and comorbidities

• Integrate assessment tools and relevant patient education into

management

• Recognize “stages” in the evolution of migraine so as to personalize care
• n the basis of disease progression

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Case Study (cont’d)

• Colleen is prescribed topiramate 25 mg once a day, then over

1 month gradually increased to 50 mg twice a day

• She continues to follow lifestyle modifications
• Review of headache diary after 1 month:

‒ Headaches continue to occur at least twice a week ‒ Headaches still cause impairment and often require bedrest

• Switched from amlodipine to propranolol 40 mg twice a day, gradually

increased to 60 mg twice a day

• Cognitive behavioral therapy prescribed

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• Landmark 1990 study showed that

CGRP—a potent vasoactive peptide—is released during migraine headache

• In 1993-1994, sumatriptan was

shown to inhibit CGRP release at the same time that it aborts a headache attack

• Led to development of drugs

specifically designed to block the actions of CGRP

CGRP-Targeted Therapies Were Specifically Designed for the Trigeminal Pain System and Headache

Control refers to headache-free period, while attack refers to headache period. Edvinsson L, et al. Nat Rev Neurol. 2018;14:338-350; Goadsby PJ, et al. Ann Neurol. 1990;28:183-187; Goadsby PJ, et al. Ann Neurol. 1993;33:48-56. 20 40 60 80 100 With Aura Without Aura With Sumatriptan

CGRP Release During Migraine Inhibited by Sumatriptan

Control Attack

Concentration of CGRP (pmol/L)

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Newer Therapies for Headache Disorders: Different Targets of Action

Onabot-A = onabotulinumtoxinA. Edvinsson L, et al. Nat Rev Neurol. 2018;14:338-350.

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Drug Indication(s) Dosing Examples of Common Adverse Events Eptinezumab EM, CM IV, quarterly URI, nasopharyngitis, fatigue, diarrhea,

• ropharyngeal pain

Erenumab EM, CM SC, monthly Injection site reactions, constipation Fremanezumab* EM, CM SC, monthly

• r quarterly

Injection site reactions Galcanezumab* EM, CM SC, monthly Injection site reactions

Newer FDA-Approved Therapies for Headache Disorders: Monoclonal Antibodies

*Has also been studied for cluster headache. CM = chronic migraine; EM = episodic migraine; SC = subcutaneous; URI = upper respiratory infection; UTI = urinary tract infection. ClinicalTrials.gov. clinicaltrials.gov/ct2/show/NCT03855137. Accessed Apr 13, 2020; ClinicalTrials.gov. clinicaltrials.gov/ct2/show/NCT02605174. Accessed Apr 13, 2020; ClinicalTrials.gov. clinicaltrials.gov/ct2/show/NCT03732638. Accessed Apr 13, 2020; Edvinsson L, et al. Nat Rev Neurol. 2018;14:338-350.

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Drug Indication(s) Dosing Examples of Common Adverse Events Status Serotonin 5-HT1F Receptor Agonist Lasmiditan Migraine relief Oral, PRN Dizziness, paresthesia, somnolence FDA approved CGRP Receptor Antagonists Atogepant EM, CM Oral, once or twice daily Nausea, fatigue, constipation, nasopharyngitis, UTI Phase 3 Rimegepant Migraine relief, EM, CM Oral, PRN Nausea, dizziness, UTI FDA approved for relief Phase 3 EM, CM Ubrogepant Migraine relief Oral, PRN Nausea, dizziness FDA approved

Newer Therapies for Headache Disorders: Other Agents Approved and in Development

ClinicalTrials.gov. clinicaltrials.gov/ct2/show/NCT03855137. Accessed Apr 13, 2020; ClinicalTrials.gov. clinicaltrials.gov/ct2/show/NCT02605174. Accessed Apr 13, 2020; ClinicalTrials.gov. clinicaltrials.gov/ct2/show/NCT03732638. Accessed Apr 13, 2020; Edvinsson L, et al. Nat Rev Neurol. 2018;14:338-350.

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CGRP/CGRP-R mAbs: Phase 3 Trials

• 4.3
• 8.2
• 3.7
• 6.6
• 3.7
• 4.6
• 4.7
• 4.8
• 3.2
• 5.6
• 1.8
• 4.2
• 2.2
• 2.5
• 2.8
• 2.7
• 9
• 8
• 7
• 6
• 5
• 4
• 3
• 2
• 1

Eptinezumab: EM Eptinezumab: CM Erenumab: EM Erenumab: CM Fremanezumab: EM Fremanezumab: CM Galcanezumab: EM Galcanezumab: CM

Most effective dose Placebo

Holland C et al, Neurology. 2018;91:e2211-e2221; Stauffer VL. JAMA Neurol. 2018;75:1080-1088; Dodick DW et al, JAMA 2018;319:5-14; VanderPluym J et al. Neurology. 2018;91:e1152-e1165; Goadsby PJ et al, N Engl J Med. 2017;377:2123-2132; Lipton et al. Neurology. 2019;92: e2250-e2260; Ashina M et al. Cephalalgia. 2020;40: 241-254; Silberstein SD, et al. N Engl J Med. 2017;377:2113-2122; Stauffer VL et al, JAMA

• Neurol. 2018;75:1080-1088; Sklijarveski V et al, Cephalagia 2018;38:1442-1454.

Reduction in Monthly Migraine Headache Days All statistically significant

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Case Conclusion

• Colleen is prescribed fremanezumab, a CGRP-targeted monoclonal

antibody for prevention of her episodic migraine because she prefers quarterly SC injection regimen

• At 6 months, she reports that her headaches occur no more than once or

twice a month; when they do occur, she uses lasmiditan

• She hasn’t missed a day of work in several months
• You recommend that she continue keeping her headache diary and taking

preventive therapy

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PCE Action Plan

✓ Consider migraine as the default diagnosis for recurring and disruptive headache ✓ Emphasize the importance of keeping a headache diary to identify triggers and the nature of headache and to assess treatment progress ✓ Provide patient education and encourage use of nonpharmacologic interventions for treatment/prevention ✓ Treat at least 2 acute migraines with same medication; consider alternatives if medication remains ineffective ✓ When starting preventive pharmacotherapy, consider comorbidities and respect patient preferences ✓ Participate in a collaborative care model of migraine treatment to improve communication and involve patients in decision-making

PCE Promotes Practice Change

2020 Symposia Series 1