Design Document for

A Medical Education Curriculum For VA Physicians: The Immune System As A Therapeutic

Target In Chronic Diseases
By Matthew Vincenti, Ph.D.
Purpose of the Course Dramatic advances in the field of immunology over that past decade have provided significant improvements in the treatment of
chronic diseases. For example, autoimmune diseases such as rheumatoid arthritis are now commonly treated with targeted
therapies that impede the ability of a patients immune system to attack the connective tissues of the joints. Similarly,
immunotherapy is now believed to be the most promising approach to treating deadly malignancies, such as melanoma and
lung cancers. Importantly, the broad application of immunotherapies in cancer is relatively new, with many therapies still in
clinical trials. These recent important theoretical and applied advances in the field of immunology have created an inherent
knowledge gap, where many practicing physicians are not aware of this latest medical information. This knowledge gap may be
most acute in older physicians who attended medical school many years ago, but may also exist for recent medical school
graduates (i.e. residents), who have not had the clinical context to apply this information. Moreover, as the clinical applications
of immune-based therapies expand, new concepts in immunology will develop, further extending the knowledge gap. These felt
and anticipated needs in graduate medical education (GME) and continuing medical education (CME) could have dramatic
effects on the quality of patient care at Veterans Affairs (VA) medical centers, which treat an aging Veteran population. This is
particularly true of VA facilities in rural areas, which are often geographically isolated from major medical centers and
universities. An inability to apply this latest medical information may result in Veterans not receiving the most effective
treatments for their chronic diseases. This situation fulfills the third opportunity for addressing a performance problem identified
by Rossett (1999): the need to develop personnel so that they can continue to contribute to the VA mission (employee growth).
Reference:
Rossett, A. (1999) Analysis of human performance technology. In H.D. Stolovitch & E.J. Keeps (Eds), Handbook of performance
technology: Improving individual and organizational performance worldwide. (pp. 139-162) San Francisco: Jossey-Bass/Pfeiffer.

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Audience Description

The target learners for this educational program include physicians practicing at VA Medical Centers in rural areas, including
Primary Care Physicians, Specialty Care Physicians and Medical Residents. This group of learners possesses the following
general characteristics:
1. The entire audience will consist of adult learners.
2. The primary audience will consist of learners that have completed medical school and have previously completed a
formal course in immunology.
3. Demographically, the learners will be a fairly even mix of men and women, with all racial and ethnic backgrounds
potentially represented.
4. Given that this particular training is not mandatory, learners who choose to participate are likely to be interested and
motivated.
5. Learners will have high expectations that the content will be provided clearly and have direct applicability to their patient
care mission.

Major Course
1. Apply the current concepts and principles of immune regulation toward effective diagnosis and treatment of their Veteran
Objectives (Terminal) patients.
2. Evaluate clinical trials using novel immune-based therapies with respect to their risks and benefits to VA patients.
3. Design research projects that investigate the immunological basis of chronic diseases in the Veteran population.
Course Enabling
Objectives

Towards Terminal Objective 1:

1. Recognize the cellular proteins known as immune checkpoint regulators along with their cellular and molecular functions.
2. Recognize the generic and commercial names of immune checkpoint inhibitor therapies along with their molecular targets.
3. Recognize the clinical applications of immune checkpoint inhibitor therapies along with their potential side effects.

RLO Enabling
Objective

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1. Recognize the cellular proteins known as immune checkpoint regulators along with their cellular and molecular functions.

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Learning Assessment
for Course

Learners will be assessed through multiple choice and true/false quizzes taken at the end of the live presentations and RLO. For
the RLO, learners may take the quiz up to ten times and must answer at least 80% of the questions correctly in order to receive
CME credit. In discussion groups, SME/facilitators will formatively assess learners based on active and thoughtful participation.
A summative assessment will be performed at the end of the course through a learner questionnaire. This questionnaire will
assess the learners perspectives on whether the terminal objectives were met and how the training impacted their clinical
practices.

Learning Assessment
for RLO

The learning assessment for the RLO will consist of a practice exercise followed by an assessment quiz.
1. The practice exercise will involve a clinical scenario in which learners apply the concepts of immune checkpoint
regulation to the treatment of lung cancer. This branching scenario will allow the learner to select an immune checkpoint
regulator to target and then provide outcomes for that selection. The learner will then be asked to choose from two
explanations for the clinical outcome. Correct responses will allow the learner to proceed on to the assessment quiz.
Incorrect responses will give the learner the option of reviewing the tutorial or proceeding to the assessment quiz.
2. The formal assessment will consist of two screens of questions that specifically address the enabling objective. The first
will ask the learner to select all the correct protein interactions between immune checkpoint regulators and their
receptors. The second screen will require the learner to match immune checkpoint regulators with descriptions of their
immune functions.

Instructional Delivery The course content will be delivered through synchronous and asynchronous formats. Synchronous delivery approaches will
method for Course
include face-to-face presentations and discussion groups, including remote learner participation through videoconferencing.
(overall)
Asynchronous delivery approaches will include online RLO and discussion groups, as well as learner-SME interactions through
email.
Instructional Strategy The RLO will begin with an Absorb Activity in the form of a tutorial on T cell activation and immune checkpoint regulation.
for RLO
Next, the learner will practice applying the content in a Do Activity consisting of a clinical scenario with branching that
provides direct feedback on the learners choices.
Media

The RLO will be a multimedia interactive module with the following characteristics:
1. Immune cell interactions will be depicted by animated graphics.
2. Graphics will be supported with audio narration.
3. Animated focusing techniques will be synchronized with narration.
4. An optional text version of the narration will be provided for learners with hearing disabilities or those who benefit from
text reinforcement. This text will also be downloadable.

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508 Accommodations

The design of the RLO and live Power Point presentations will follow the recommendations of the GSA Multimedia 508 checklist
http://www.gsa.gov/portal/mediaId/117666/fileName/Multimedia_508_Checklist_(1).action
Specifically:
1. Navigation will be possible using a keyboard-only interface.
2. Every graphic depiction (both content and navigation) will be supported by an alt text link, which will provide a clear
description of the graphic content presented.
3. A text script of the audio narration will be accessible to learners with appropriate proximity and synchronization with the
graphics. This text script will be downloadable for future reference.
4. Animations used to demonstrate concepts and provide learner focus will be accompanied by text captions.
5. Graphics and text will be created with sufficient contrast so that color is not required for comprehension or navigation.
6. Graphics and animations will be free of strobe, flickering or flashing effects.

Course Structure
Description

This course will consist of three modules, each supporting one of the three terminal objectives.
1. For terminal objective1, learners will participate in a live overview lecture of immunology to ensure that all are equipped
with the essential terminology (30-60 minutes). This content will also be available as an online video for future
reference. Following the overview lecture, three RLOs (15-20 minutes each) will be provided to support each of the
enabling objectives of terminal objective 1. Following the lecture and RLOs, learners will participate in a live case
presentation and discussion, in which they can apply the concepts of immune checkpoint regulation to the clinical setting
(60 minutes).
2. For terminal objective 2. Learners will participate in a group discussion of clinical trials using immune checkpoint
inhibitor therapies (60 minutes).
3. For terminal objective 3, learners will participate in an exercise where they design a research project that interrogates the
use of immune checkpoint inhibitors in a clinical setting (60 minutes).

Seat Time of Course

Approximately 5 hours.

Seat Time of RLO

Approximately 20 minutes

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RLO Outline

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I) Absorb Activity: Tutorial of T cell activation and immune checkpoint regulators.

A) T lymphocytes regulate immunity by recognizing foreign antigens.
1) T cell receptors (TCR/CD3) bind to antigen associated with major histocompatibility molecules (MHC) on antigen
presenting cells (APC).
(a) T cells recognize foreign antigens presented by myeloid cells and dendritic cells.
(b) T cells recognize tumor antigens on tumor cells.
2) T cell responses to antigen and MHC depend upon the balance between activating and repressing co-receptor signals.
(a) CD28 on T cells binds to CD80 or CD86 on APC to expand T helper subsets and activate the immune response.
(b) CTLA4 competes with CD28 for CD80 and CD86, leading to reduced T helper activation and expansion of
immunosuppressive T regulatory cells.
(c) PD1 is expressed on activated T cells and binds to PDL1 or PDL2 on APC to turn off the immune response.
B) CTAL4 and PD1 are immune checkpoints with clinical significance.
1) CTLA4 is a therapeutic target in autoimmunity and cancer.
(a) CTLA4-immunoglobulin fusion proteins (CTLA4-Ig) mimic CTLA4 function in the treatment of autoimmune
diseases such as rheumatoid arthritis.
(b) Anti-CTLA4 monoclonal antibodies can extend the lives of patients with melanoma.
2) Antibodies to PD1 or PDL1/2 enhance anti-tumor immunity.
(a) PDL1 and PDL2 are expressed at elevated levels in the tumor microenvironment, resulting in the repression of
tumor infiltrating T lymphocytes.
(b) Antibodies to PD1 and PDL1/2 have shown dramatic benefits for the treatment of non-small cell lung cancer
(NSCLC) and other cancers.
II) Do Activities: Practice and Assessment.
A) Scenario-based learning with branching: Treating patients diagnosed with stage IV NSCLC and considering immune
checkpoint inhibitor therapies.
1) Which immune cell surface proteins would you target?
(a) If CTLA4, go to II.2.
(b) If CD28, go to II.3.
(c) If PD1 or PDL1/L2, go to II.2.
(d) If TCR/CD3, go to II.3
2) Tumor growth is inhibited, but patient develops pneumonitis. Why?
(a) Therapy suppresses the immune system and causing infection. Incorrect. If chosen, give option of returning to
section I or on to assessment IIB.
(b) Therapy stimulates the immune system causing autoimmunity. Correct, if chosen, go on to assessment IIB.
3) Tumor grows at a faster rate and patient develops pneumonia. Why?
(a) Therapy suppresses the immune system causing infection. Correct, if chosen, go on to assessment IIB.
(b) Therapy stimulates the immune system causing autoimmunity. Incorrect. If chosen, give option of returning to
section I or on to assessment IIB.
B) Assessment: Demonstrate the ability to Recognize the cellular proteins known as immune checkpoint regulators along
with their cellular and molecular functions.
1) Drag and drop: Match CTLA4, PD1, PDL1/L2, CD28, TCR/CD3 to their immune functions.
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(a) Is expressed on all T cells, binds to CD80/86 and stimulates immunity.

(b) Is expressed on all T cells, binds to antigen in a complex with MHC and stimulates immunity.
(c) Is expressed on all T cells, binds to CD80/86 and dampens immunity.
(d) Is expressed on activated T cells, binds to receptors on APC and tumor cells to dampen immunity.
(e) Is expressed on tumor cells and APC, binds to receptors on T cells to dampen immunity.
2) Multiple correct answers: choose the correct interactions between immune checkpoint regulators and their ligands.
(a) CTLA4 & CD80/86
(b) TCR/CD3 & CD28
(c) PD1 & PDL1/L2
(d) CTLA4 & CD28
(e) CD28 & CD80/86

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RLO Flowchart

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Screens/Pages in RLO 16 screens.

Knowledge Checks or [Mod 4 estimated number of knowledge checks or other interactions]
Other Assessments or
____Dichotomous (T/F, Y/N, etc.)
Practices for RLO
____Multiple Choice
__1__Multiple Select
__1__Drag and Drop
__1__Clinical case scenario with branching. See flowchart above.
____Other describe
Rollovers/click events [Mod 4 estimated number of individual rollover or click event items/objects, outside of navigation elements]
__10__Rollovers
__15__Click Events
RLO Navigation

Radio buttons will be provided for learner-controlled forward and backward navigation of the RLO.
1. Learners will be able to control your progress by selecting the various radio buttons located on the bottom left portion of
the screen. All radio buttons will have rollover identification.
2. The progress bar located on the bottom center region indicates where you are in the playtime of the course.
3. Radio buttons located on the bottom right portion of the screen provide access to audio control, closed captioning, the
table of contents and exit from the course.
4. In addition to using the mouse, learners will be also able to toggle through and highlight tabs and buttons using the tab or
arrow keys. Once highlighted, tabs and buttons will be selectable with the return/enter key.

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Screen Layouts for

RLO

Naviga on Instruc ons

Title

LearningObjec ve

Content Slide

Quiz Ques on

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QuizFeedback

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Naviga on with Table of Contents

Prac ce Scenario

Creditsand Exit

Development Tools
for RLO

Storyboarding will be performed using Adobe Captivate and Microsoft Power Point. RLO authoring will be performed in Adobe
Captivate 9. All graphics will be created in Microsoft Power Point, Adobe Captivate 9, or imported from free assets available
online. Audio narration will be created in Captivate using the Speech Management audio option with text-to-speech created using
NeoSpeech computer-generated voices.

Ownership

Matthew Vincenti, Ph.D. will develop the initial course and will maintain the course. This course is being developed for the
Department of Veterans Affairs in support of its clinical workforce development and credentialing.

Development Time of
entire course and
RLO

The development time for this course is based on estimates provided by the Chapman Alliance
(http://www.chapmanalliance.com/howlong/). The three RLO are considered Level 1 eLearning, Complex Projects, with a
development time ratio of 125:1. Therefore, it is estimated that each 20 minute RLOs will require 42 hours to develop (125 hours
total). The Instructor lead trainings (ILT) involve Complex Subject Matter, with a development time ratio of 82:1. Therefore,
it is estimated that the four hours of ILT will require 328 hours to develop. In total, this course will require 435 hours or 56.6
business days to develop.

Support requirements
for RLO and course

1. Purchase of RLO production software is required, such as Adobe Captivate 9.

2. Purchase of a Learning Management System (LMS), such as Blackboard.
3. PhDs with expertise in immunology and MDs with expertise in Oncology, will be required to serve as SME an facilitate
the ILT sessions. These SME will provide support as part of their clinical and academic missions and therefore will not
be compensated.
4. Administrative support from the VA Office of Information Technology (OI&T) in order to procure the required software
and make it available on the VA network.

Project
Sign-off [optional]

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Please sign below indicating agreement with the proposed course plan and approving start-up of the storyboard and development
phases.

Instructional Designer

Date

Project Manager/Sponsor

Date

10

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