Recognition and Management of Primary Biliary Cholangitis ... · primary biliary cholangitis (PBC)....

Recognition and Management of Primary Biliary Cholangitis (PBC)A Chronic Inflammatory Liver Disease

Final Live Activities Outcomes Report

December 24, 2018

Presented to Intercept Pharmaceuticals • Grant ID Hep 628

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Impact

Pre to Post-Test Results By Learning Objectivev 112% Improvement: Review the epidemiology of primary biliary

cholangitis (PBC)

v 11% Improvement: Describe the pathophysiology of PBC

v 94% Improvement: Recognize how to evaluate a patient for PBC

v 40% Improvement: Discuss the treatment of PBC, including the treatment

of extrahepatic manifestations

v 1,574 attendees were reached via both online and live formats, with significant gains observed across cohorts and

modalities from Pre-Test to Post-Test.

v Despite their substantial improvements, learners remain challenged in their diagnosis of PBC and when further tests such

as a biopsy or fibroscan might be necessary to confirm a diagnosis. Additionally, learners failed to retain knowledge on PBC

pharmacotherapy.

v Learners demonstrated significant net increases in Competence, Confidence and practice strategy in the 4-week Post

Curriculum Assessment. The greatest net increase was in their reported intent to order an anti-mitochondrial test in patients

with cholestatic liver enzymes, from a very low Pre-Test rating to a moderately high rating in the Post Curriculum

Assessment.

Executive Summary1,574*Total Attendees

4 Cities

618*On Site

956*Simulcast / Virtual

Symposium

0%

20%

40%

60%

80%

100%

LO 1 LO 2 LO 3 LO 4

Pre-Test Post-Test

+10.77%*+112.17%* +93.86%*

(N = 508–592)

v This curriculum focused on the epidemiology,

pathophysiology, diagnosis, and treatment of

primary biliary cholangitis (PBC).

v Substantial improvements were measured in

learners’ knowledge of the epidemiology of PBC

and its recognition in patients presenting with liver

disease.

*These numbers represent the total number of attendees, irrespective of assessment participation

+40.36%*


Course Directors

Activity Planning Committee

Gregg Sherman, MD

Michelle Frisch, MPH, CCMEP

Stephen Webber

Sandy Bihlmeyer M.Ed

Alan Goodstat, LCSW

Sheila Lucas, CWEP

FacultyKalyan Ram Bhamidimarri, MD, MPHAssociate Professor/ Transplant HepatologyUniversity of Miami/ Miami Transplant Institute Miami, FL

Kalyan Ram Bhamidimarri, MD, MPHAssociate Professor/ Transplant HepatologyUniversity of Miami/ Miami Transplant Institute Miami, FL


Commercial SupportThe Emerging Challenges in Primary Care: 2018 series of CME activities were supported through educational grants or donations from the following companies:

vGrifols

vLilly USA, LLC

vIntercept Pharmaceuticals, Inc.

vNovo Nordisk, Inc.

vSanofi Genzyme and Regeneron

Pharmaceuticals

vSanofi US

vActelion Pharmaceuticals US, Inc.

vAmgen, Inc.

vAstraZeneca Pharmaceuticals LP

vBoehringer Ingelheim

Pharmaceuticals, Inc.

vER/LA Opioid Analgesic REMS

Program Companies


Overview


Curriculum Overview

Clinical Highlights eMonograph -

eMonograph containing key teaching points

from the CME Activity was distributed 1 week

after the meeting to all attendees.

5 Accredited Live Regional Symposia

September 22, 2018 – Oct 27, 2018

1 Accredited Live Virtual Symposium:

Sept 22, 2018

Online Enduring webcast CME Activity :

vLaunch Date: Oct. 8, 2018

vEnd Date: Oct. 7, 2019

vHosted at: http://naceonline.com/CME-

Courses/course_info.php?course_id=1044

http://naceonline.com/CME-Courses/course_info.php?course_id=1044


Learning Objectives

v Review the epidemiology of primary biliary cholangitis (PBC)

v Describe the pathophysiology of PBC

v Recognize how to evaluate a patient for PBC

v Discuss the treatment of PBC, including the treatment of extrahepatic manifestations


Learning outcomes were measured using matched Pre-Test and Post-Test scores for Knowledge, Competence, Confidence, and practice strategy and across all of the curriculum’s Learning Objectives.

Outcomes Metric Definition Application

Percentage change This is how the score changes resulting from the education are measured. The change is analyzed as a relative percentage difference by taking into account the magnitude of the Pre-Test average.

Differences between Pre-Test, Post-Test, and PCA score averages

P value (p) This is the measure of the statistical significance of a difference in scores. It is calculated using dependent or independent samples t-tests to assess the difference between scores, taking into account sample size and score dispersion. Differences are considered significant for when p ≤ .05.

Significance of differences between Pre-Test, Post-Test, and PCA scores and among cohorts

Effect size (d) This is a measure of the strength/magnitude of the change in scores (irrespective of sample size). It is calculated using Cohen's d formula, with the most common ranges of d from 0-1: d < .2 is a small effect, d=.2-.8 is a medium effect, and d > .8 is a large effect.

Differences between Pre-Test and Post-Test score averages

Power This is the probability (from 0 to 1) that the “null hypothesis” (no change) will be appropriately rejected. It is the probability of detecting a difference (not seeing a false negative) when there is an effect that is dependent on the significance (p), effect size (d), and sample size (N).


Percentage non-overlap This is the percentage of data points at the end of an intervention that surpass the highest scores prior to the intervention. In this report, it will reflect the percentage of learners at Post-Test who exceed the highest Pre-Test scores.


Outcomes Methodology


Participation

2018 Meeting/Simulcast Date Attendees

Virtual Symposium 9/22/18 601

Uniondale, NY 10/6/18 286

Uniondale, NY Simulcast 10/6/18 355

San Mateo, CA 10/13/18 94

Denver, CO 10/20/18 128

San Diego, CA 10/27/18 110

Total 1,574


Level 1 Participation

Demographics Patient Reach

1,574* Total Attendees

4 Cities

618* On Site

956*Simulcast / Virtual Symposium

Participation

*These numbers represent the total number of attendees, irrespective of assessment participation


57.89%

23.12%

11.09%3.01% 3.01% 1.88%

NP MD PA RN DO Other

Profession Years in Practice

Patient Care Focus: 91%

27.08%

16.49% 17.71%

38.72%

< 5 5–10 11–20 > 20

Level 1: Demographics and Patient Reach

75.78%

7.93% 4.59% 3.97% 3.97%

Primary Care-Family Practice,Internal Medicine

Other EmergencyMedicine/ Critical

Care

Hospitalist Cardiology

Specialties:Endocrinology 2.09%Gastroenterology 1.04%Psychiatry/Neurology 0.42%Rheumatology 0.21%

Patients seen each week, in any clinical setting:

0% 10% 20% 30% 40%

> 75

51–75

26–50

≤ 25

Specialty

Average number of patients seen each week: 45


Level 2-5:Outcomes Metrics


45.28%(49.78%)

80.85%(39.35%)

34.89%(46.78%)

66.55%(37.39%)

96.06%(19.45%) 89.56%

(30.58%)

67.64%(46.78%)

93.41%(20.32%)

Review the epidemiology of primarybiliary cholangitis (PBC)

Describe the pathophysiology of PBC Recognize how to evaluate a patient forPBC

Discuss the treatment of PBC, includingthe treatment of extrahepatic

manifestations

Learning Objectives Analysis

Learning Objective 1 Learning Objective 2 Learning Objective 3 Learning Objective 4

v Significant gains (ranging from 11% to 112%) were achieved on all Learning Objectives.

• The greatest gain (112%) was on the Learning Objective on the epidemiology of PBC, from a low Pre-Test score (45%) to the highest Post-Test score (96%).

v Post-Test averages were high (90% and higher) on three of the four Learning Objectives. The one Learning Objective with a low Post-Test score (68%) addressed the evaluation of a patient for PBC.

• The Learning Objective on the evaluation of patients for PBC also showed the lowest Pre-Test score (35%); despite its substantial 93% gain, the Post-Test score remained low.

(N = 508–592)

Pre-Test Post-Test

+112.17%* +10.77%* +93.86%* +40.36%*

*significant at the p ≤ 0.05 level


Learning Domain Analysis(N = 493–626)

Pre-Test Post-Test

v Significant and substantial gains (45%–94%) were achieved in all learning domains.

v The very high Post-Test score in Knowledge (93%) was driven by substantial score increases and high Post-Test scores across all Knowledge items in this activity.

v Although learners demonstrated a 94% increase in Competence score, the Post-Test average in this domain remained low (68%), due to difficulty on the recognition and diagnosis of PBC.

v Learners showed a substantial increase in their reported Confidence in recognizing features consistent with PBC, from a very low Pre-Test rating to a moderate Post-Test level.

v Learners also reported substantially increased intent to order anti-mitochondrial tests, from a very low Pre-Test rating to a moderately high Post-Test rating.

1.72(0.87)

3.14(0.94)

Confidence

64.24%(29.96%)

34.89%(47.66%)

92.91%(16.00%)

67.64%(46.78%)

Knowledge Competence

1.72 (1.08)

3.80 (1.12)

Practice

+82.21%* +63.02%*


+44.61%* +93.86%*


Curriculum/Activity Intervention Effect

Learning Domain Effect Size* % Non-OverlapKnowledge 1.192 68.90%

Competence 0.693 49.34%

Effect Size Definition: This is a standardized measure of the strength/magnitude of the change in scores, irrespective of sample size. This metric quantifies the association between outcome and exposure to education, in a way which makes meta-analysis possible. There exist many types of effect size measures, each appropriate in different situations. We select Cohen’s d for this analysis, which is a standardized difference in mean. Most commonly, d ranges from 0–1: d < 0.2 is a small effect, d = 0.2–0.8 is a medium effect, and d > 0.8 is a large effect.


Learning Domain by Professional Cohort

v Nurse practitioners (NPs) and physicians demonstrated statistically significant gains in all learning domains.

v In all learning domains, physicians demonstrated higher Post-Test scores compared to NPs.• NPs had substantially lower Post-Test scores in Competence, Confidence and practice

strategy; in Knowledge, the score difference was relatively modest (92% vs 97%).• NPs also had lower Pre-Test scores than physicians in all domains. Even with substantially,

greater gains in Knowledge and practice strategy, the Post-Test scores of NPs remained lower than those of physicians.


Learning DomainNurse Practitioner Physician

N Pre-Test Post-Test % Change N Pre-Test Post-Test % Change

Knowledge 197 56.77%(29.03%)

92.34%(15.28%) +62.67%* 100 75.75%

(24.58%)97.00%(9.32%) +28.05%*

Competence 167 34.13%(47.42%)

64.67%(47.80%) +89.47%* 84 38.10%

(48.56%)76.19%

(42.59%) +100.00%*

Confidence 156 1.46(0.69)

2.76(0.84) +89.04%* 80 1.96

(0.94)3.65

(0.90) +85.99%*

Practice 153 1.26(0.73)

3.52(1.17) +179.27%* 85 2.31

(1.05)4.26

(0.80) +84.69%*


*significant at the p ≤ 0.05 level; unmatched data

At follow-up:

v Statistically significant net gains were measured from Pre-Test to the Post Curriculum Assessment (PCA) in all areas except for Knowledge.

v In Knowledge, only a modest non-significant net increase was observed, due to a high level of score slippage that occurred from Post-Test to the PCA. Although a significant net gain of 29% was measured in Competence, the score slippage that was observed in both Competence and Knowledge resulted in low PCA scores, reinforcing the need for continued education on the management of PBC.

v The greatest net increases (73% and 112%) were observed in Confidence and practice strategy, in part due to minimal score decreases from Post-Test to the PCA.

4-Week Retention Analysis

64.24%(29.96%)

34.89%(47.66%)

92.91%(16.00%)

67.64%(46.78%)

64.68%(47.82%) 47.78%

(50.04%)

0%20%40%60%80%

100%

Knowledge CompetencePre-Test Post-Test PCA

+29.03%*

1.72(0.87)

1.72(1.08)

3.14(0.94)

3.80(1.12)

2.98(0.96)

3.64(1.12)

1.00

2.00

3.00

4.00

5.00

Confidence PracticePre-Test Post-Test PCA

+0.68% +73.26%* +111.63%*

(N = 311)


Disease state awareness Diagnostic evaluation Timely Referral

Screening protocols Pharmacotherapy

Please select the specific areas of skills, or practice behaviors, you have improved regarding the diagnosis and treatment of patients with PBC since this CME activity. (Select all that apply.)N=369

(4-week Post Assessment)

55% 48% 62%

48% 42%


Insurance/financial issues Lack of KnowledgeFormulary restrictions

Time constraints System Constraints

What specific barriers have you encountered that may have prevented you from successfully implementing strategies for patients with PBC since this CME activity? (Select all that apply) N=369

(4-week Post Assessment)

49%

51%37%

42%53%


Identified Learning Gap, 1 of 2: Diagnosis of PBC by serum AMA level

Despite an 88% improvement, learners remained challenged on a Competence question which provided a patient vignette and asked whether this patient could be diagnosed with or without the need for biopsy or fibroscan:

Competence:

A 54-year-old overweight woman presents with a 2-year history of signs and symptoms consistent with PBC, including fatigue, pruritus, and elevated LFTs (ALP ~3x ULN for last year). She does not use alcohol or drugs. Workup rules out viral hepatitis, biliary obstruction, and other common causes of liver disease. Blood test identifies serum AMA titer 1:168. Does this patient have PBC?

• At Post-Test, 65% of learners correctly answered: “yes.”

• On the Post-Curriculum Assessment, 48% of learners correctly answered: “yes.”


Identified Learning Gap, 2 of 2: Use of cholestyramine and UDCA pharmacotherapy in PBC treatment

Following strong improvements between Pre-Test and Post-Test, learners demonstrated substantial score slippage between the Post-Test and Post-Curriculum Assessment for two Knowledge questions. These questions both evaluated learner understanding of the role of drug therapy in the treatment of the PBC patient.

Knowledge:

Which of the following agents is considered first-line pharmacotherapy for pruritus associated with PBC?

• At Post-Test, 89% of learners correctly answered: “cholestyramine.”

• On the Post-Curriculum Assessment, 65% of learners correctly answered: “cholestyramine.”

Which of the following factors is associated with good prognosis among patients with PBC?

• At Post-Test, 95% of learners correctly answered: “response to UDCA.”

• On the Post-Curriculum Assessment, 55% of learners correctly answered: “response to UDCA.”


Overall Educational Impact

v Significant improvements (ranging from 45% – 94%) were seen across all learning domains.

• The cohort analysis of professions showed that physicians demonstrated higher Pre-Test and Post-Test scores than NPs in all learning domains, despite greater gains by NPs in Knowledge, Confidence and practice strategy.

• Live onsite learners demonstrated higher Pre-Test and Post-Test averages than online participants in all learning domains; onsite learners also achieved greater score increases in Competence, Confidence and practice strategy.

• Analysis of learning retention in the PCA showed that significant net gains (ranging from 29% – 112%) from Pre-Test were measured in Competence, Confidence and practice strategy. The exception was Knowledge, in which little net change (-2%) was measured. The greatest net increase was measured in learners’ reported intent to order an anti-mitochondrial test in patients with cholestatic liver enzymes (1.7 at Pre-Test, 3.6 at PCA).

v Significant improvements (ranging from 11% – 112%) were measured across all Learning Objectives. High Post-Test scores were measured on all Learning Objectives, with the exception of the Learning Objective on recognizing how to evaluate a patient for PBC.

• This Learning Objective had a Post-Test score of 68%, despite of a 94% increase from the Pre-Test.

v The analysis of the Knowledge and Competence domains identified persistent learning gaps related to the diagnosis of PBC by serum AMA levels, and to the role of pharmacotherapy in the treatment of PBC patients.

• Despite an 88% improvement on the Competence question, learners remained challenged on whether a biopsy or fibroscan is necessary to diagnose a patient with PBC.

• 65% of learners correctly diagnosed the patient with PBC at Post-Test. 24% of learners incorrectly selected “need liver biopsy for diagnosis” and 10% incorrectly selected “need fibroscan for diagnosis”.

• After substantial improvements in score between the Pre-Test and Post-Test, learners demonstrated strong score decreases between the Post-Test and PCA on Knowledge questions related to the use of cholestyramine and UDCA in PBC treatment.


Appendix


Learning Objectives Analysis – Live Onsite vs. Live Online Audience• “Live onsite learners” include only those attending in-person meetings.

• ”Live online learners” include those from both the Simulcast and Virtual Symposium.


v Onsite learners demonstrated higher Pre-Test and Post-Test averages on all Learning Objectives, compared to live online learners.

v Live online learners demonstrated greater score increases on three of the four Learning Objectives.

Learning ObjectiveLive Onsite Learners Live Online Learners


Review the epidemiology of primary biliary cholangitis (PBC) 342 48.54%

(49.98%)97.37%

(16.01%) +100.60%* 166 38.55%(48.67%)

93.37%(24.87%) +142.19%*

Describe the pathophysiology of PBC 355 82.82%(37.72%)

90.14%(29.81%) +8.84%* 162 76.54%

(42.37%)88.27%

(32.18%) +15.32%*

Recognize how to evaluate a patient for PBC 333 37.24%

(48.34%)73.57%

(44.09%) +97.58%* 180 30.56%(46.06%)

56.67%(49.55%) +85.45%*

Discuss the treatment of PBC, including the treatment of extrahepatic manifestations

381 71.92%(34.92%)

95.28%(16.32%) +32.48%* 211 56.87%

(39.70%)90.05%

(25.68%) +58.33%*



• “Live onsite learners” include only those attending in-person meetings.

• ”Live online learners” include those from both the Simulcast and Virtual Symposium.

Learning Domain Analysis – Live Onsite vs. Live Online Audience

v Both live onsite and live online learners demonstrated substantial and significant score increases across all learning domains.

v Live onsite learners demonstrated higher Pre- and Post-Test averages across all learning domains, and greater score increases in all domains except Knowledge.

Learning DomainLive Onsite Learners Live Online Learners


Knowledge 405 68.97%(28.00%)

94.32%(13.48%) +36.75%* 221 55.58%

(31.47%)90.31%

(19.53%) +62.48%*

Competence 333 37.24%(48.34%)

73.57%(44.09%) +97.58%* 180 30.56%

(46.06%)56.67%

(49.55%) +85.45%*

Confidence 343 1.73(0.90)

3.24(0.98) +86.72%* 150 1.69

(0.79)2.91

(0.79) +71.65%*

Practice 344 1.74(1.08)

3.86(1.14) +122.28%* 162 1.69

(1.08)3.68

(1.06) +117.52%*


67.92%

7.51%

12.29%

12.29%

92.28%

1.22%

1.76%

4.74%

44.33%

5.75%

21.83%

28.09%

4. Common in women over age 40 years

3. Mean age at presentation is < 20 years

2. Male preponderance

1. Prevalence is similar to hepatitis C

Which of the following is true regarding the epidemiology of PBC?

Which is the key pathophysiologic mechanism in PBC?

1.71%

16.72%

70.65%

5.80%

5.12%

0.43%

2.60%

90.01%

6.66%

0.29%

1.94%

10.84%

79.61%

0.81%

6.80%

5. Medications

4. Obesity

3. Immune mediated bile duct destruct ion

2. Environmental allergies

1. Excess alcohol

Knowledge Questions:

+108.15%

+13.07%

x

x

N = 591–738, main activity, 293, PCA

Pre-Test Post-TestNote: Data is unmatched

PCA


3.41%

2.73%

64.85%

29.01%

0.42%

0.14%

89.17%

10.28%

3.78%

1.89%

65.67%

28.66%

4. Probiotics

3. Diazepam

2. Cholestyramine

1. Diphenhydramine

Which of the following agents is considered first-line pharmacotherapy for pruritus associated with PBC?

Knowledge Questions, continued:

+35.78%x

N = (631–720), main activity, 293, PCA

Pre-Test Post-TestNote: Data is unmatched

4.10%

27.65%

12.97%

55.29%

0.14%

3.93%

1.40%

94.52%

1.90%

24.56%

6.81%

66.72%

4. Presence of varices

3. Younger age at diagnosis

2. Serum bilirubin level >4x ULN

1. Response to UDCA

Which of the following factors is associated with good prognosis among patients with PBC?

+41.67%x

PCA


12.63%

31.74%

7.85%

47.78%

9.96%

24.12%

1.40%

64.52%

24.50%

39.24%

1.99%

34.27%

4. Need fibroscan for diagnosis

3. Need liver biopsy for diagnosis

2. No

1. Yes

A 54-year-old overweight woman presents with a 2-year history of signs and symptoms consistent with PBC, including fatigue, pruritus, and elevated LFTs (ALP ~3x ULN for last year). She does not use alcohol or drugs. Workup rules out viral hepatitis,biliary obstruction, and other common causes of liver disease. Blood test identifies serum AMA titer 1:168. Does this patienthave PBC?

Competence Question

+88.25%

N = (604–713), main activity, 293, PCA

Note: Data is unmatchedPre-Test Post-Test

x

PCA


Confidence Question:How confident are you in your ability to recognize features consistent with PBC?

Confidence & Practice QuestionsN = (574–702)

Practice Question:How often do you order an anti-mitochondrial test in patients with cholestatic liver enzymes?

Pre-Test Post-Test Note: Data is unmatched

8.32%

22.53%

22.38%

2.73%

0.87%

2.96%

13.07%

33.97%

5. Very confident

4. Pretty much confident

3. Moderately confident

2. Slightly confident

1. Not at all confident

29.20%

35.90%

21.08%

8.55%

5.27%

3.31%

4.79%

11.74%

19.83%

5. Always

4. Frequently

3. Sometimes

2. Rarely

1. Never

Recognition and Management of Primary Biliary Cholangitis ... · primary biliary cholangitis (PBC)....

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