Here are some examples of foreground clinical questions generated from the diabetes case: P - 42 year old woman with type 2 diabetes currently on glyburide I - Adding metformin to her regimen C - Continuing glyburide monotherapy O - Change in morning and evening blood sugar levels P - 42 year old woman with type 2 diabetes I - Adding metformin vs sulfonylurea as second agent C - Continuing glyburide monotherapy O - Glycemic control, side effect profile, cardiovascular/renal outcomes P - 42 year old woman with type 2 diabetes and elevated blood sugars I - Increasing glyburide dose vs adding metformin C - Continuing current gly

1. Author(s): Rajesh Mangrulkar, MD, 2009
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3. Patients and Populations
Medical Decision-Making: The Information
Cycle
Rajesh S. Mangrulkar, M.D.
Fall 2008

4. A Clinical Tale
• 20 year-old woman presents for genetic
testing
• Mother had breast and ovarian cancer,
likely has the BRCA gene (autosomal
dominant)
• With this assumption, the patient s
likelihood of having the gene is… 50%
• She decides not to get tested.

5. The Tale Continues…FFwd
• At age 75 she has not been diagnosed
with breast or ovarian cancer.
• Is her probability of having the BRCA
gene different at age 75 than it was at
age 20?
– Yes: it is lower
– How much lower?

6. Diagnostic Reasoning: Probabilistic
Reasoning
Probability: The likelihood of the
occurrence of an event.
• P (X) = the probability of event X
• P(BRCA) = the probability that a patient
carries the BRCA gene

7. Prior Probabilities
• Based on many factors:
– Clinician experience
– Patient demographics
– Characteristics of the patient presentations
(history and physical exam)
– Previous testing
– Genetic knowledge (in this case)
• P(BRCA) = 50%

8. Conditional Probabilities
• What is the probability of event B, given
an event A? Written as P(B | A).
– Example: P (BRCA | no breast cancer)
• Key concept:
– Conditional probabilities can be combined
with prior probabilities to create joint
probabilities

9. Basic Probabilistic Rules
Examples of types of Events
• Dependent events: occurrence of 1 depends
to some extent on the other
– Example: The same person passing step 1 of the
boards and then passing step 2 of the boards 2
years later.
• Independent events: both can occur
– Example: 2 different people passing step 1 of the
boards
• Mutually exclusive events: cannot both occur
– Example: A person getting >250 on step 1 of the
boards, or the same person getting 220-250 on
step 1.

10. Combining Probabilities of Events
• Pr (A B) = Pr (A) + Pr (B)
– If A and B are mutually exclusive events
• Pr (A B) = Pr (A) * Pr (B)
– If A and B are independent events
• Pr (A B) = Pr (A) * Pr (B|A)
– If A and B are dependent events (Joint
probability)
= OR = AND

11. Back to our story
75 yo woman whose mother very likely
had the BRCA gene, but who has not
herself been diagnosed with breast
cancer.
• Our patient wants to know:
– What is P (BRCA | no breast ca)?

12. Considering both sides…
• Step 1:
P (BRCA and no breast cancer)
= P(BRCA) * P(no breast ca | BRCA)
= 0.5 * 0.3 (from studies)
= 0.15
• Step 2:
P (NO BRCA and no breast ca)
= P(NO BRCA)*P(no breast ca|NO BRCA)
= 0.5 * 0.875(from studies)
= 0.4375

13. But that doesn t tell the full story…
• Joint probabilities
– P (BRCA and no breast ca) = 0.15
– P (NO BRCA and no breast ca) = 0.4375
• The assumption is that these are NOT
independent events.
• Again, our patient wants to know:
– What is P (BRCA | no breast ca)?

14. WARNING
CONFUSING
MATH
AHEAD

15. Step 3: Bayes Theorem
• Conditional probability is the relative proportion of the
relevant joint probability to the sum of all the joint
probabilities.
• P(BRCA | no breast ca) =
P(BRCA) * P (no breast ca | BRCA)
P (no breast ca)
• P (no breast ca) = sum of all the joint probabilities
• P (no breast ca & BRCA)
• P (no breast ca & NOT BRCA)

16. Applying Bayes Theorem
• P (BRCA | no breast ca) =
0.15
------------------- = 26%
0.15 + 0.4375
• 26% is significantly lower than 50% (our
prior probability)

17. Why is this important?
• Illustration of changing probabilities,
and shifting uncertainty…
…because of test results
…because of events
…because of time
• Fundamentally, clinicians deal with
probabilities and uncertainty with each
patient they encounter

18. Final tale: Diagnostic Reasoning
• The case: A 56 year old man without heart
disease presents with sudden onset of
shortness of breath.
• Description of the problem: Yesterday, after
flying in from California the day before, the
patient awoke at 3AM with sudden
shortness of breath. His breathing is not
worsened while lying down.

19. Diagnostic Reasoning: Your Intake
• Q: What other symptoms were you
feeling at the time?
• A: He has had no chest pain, no leg
pain, no swelling. He just returned
yesterday from a long plane ride. He
has no history of this problem before.
He takes an aspirin every day. He
smokes a pack of cigarettes a day.

20. Diagnostic Reasoning: Baby Steps
Prior to Lectures on 8/18…
• What are you thinking may be going on
at this time? In other words, generate a
differential diagnosis of possibilities…
• Assign likelihoods to each possibility
• Place the possibilities in descending
order of likelihood

21. Thread 1: Information Retrieval
Ask
Acquire Apply
Appraise
R. Mangrulkar

22. Riddle me this...
• How many questions do clinicians ask
while they care for patients? 4 per patient
• How can knowledge of question
structure improve the efficiency of the
information retrieved?
(1) Targeting Information Resources
(2) Generating Search Terms

23. Research: Questions New Knowledge
Early Hypothesis
(Basic Science theory, case reports, cross-sectional studies)
Mature Hypothesis
(Consistent support from observational studies)
Confirm Causal Link
(Large prospective randomized trials)
Optimal Decision Making
(Use information on treatment benefit, risks and costs from trials and
observational studies, simulation models)
R. Mangrulkar

24. Objectives of today s session
• By the end of this lecture, you should be
able to…
– demonstrate an understanding of the difference
between background and foreground clinical
questions
– appreciate how individual targeted searches for
the answers to clinical questions drive self-
directed learning that is crucial for all practitioners
– be able to craft foreground questions for both
diagnosis and treatment, using the PICO format

25. Patient Care: Questions Decisions
• Step 1: Question Search for Answer
• Step 2: Assess the strength of answer
• Step 3: Weigh against:
– Patient Values
– Physician Values
– Society s Values

26. A Tale: The Concierge
• The case: You and your friend are
at the Drake Hotel in Chicago,
and need to find a place to eat for
dinner.
• Description: You both are
vegetarian. You are both in the
mood for Asian cuisine. You only
have 2 hours to eat, so you don t
want to take a cab, car or train.
You both are on a tight budget so
entrees should not be expensive.

27. The Concierge: Scenario #1
• Q: Could you suggest a place for
my friend and I to eat close by?
• A: What kind of restaurant?
• Q: Well, it should be around here.
• A: We have dozens of excellent
restaurants close to the Drake.
• Q: Yeah, one of those…
• A: Can you be more specific?
• Q: Well, we re kind of in a hurry so
it should be close by...

28. The Concierge: Scenario #2
• Q: Can you help us find a restaurant?
• A: Sure. What are you looking for?
• Q: Well, we re in the mood for Thai
cuisine with an excellent vegetarian
selection. It should be walking
distance from here, with a nice view
of the city. Not too pricey, say $15 per
entrée.
• A: Ah! I have the perfect place…Thai
Peppers. Let me call ahead and let
them know you ll be coming.

29. What makes a good question?
• #1: Could you suggest a • #2: Can you help us find
place for my friend a vegetarian Thai
and I to eat close by? restaurant, walking
distance from here,
about $15 per entrée?
What aspects of the second question predicted
its success at retrieving a place that the
customers were satisfied with?

30. The Well-Structured Clinical Question
• Purposes
– Target resources
– Define search terms
– Define what you and the patient care about
• Two Types
– Background
– Foreground

31. Anatomy of a Background Question
• What
• How
• Where
• When
• Who
• Why

32. 54/67 (81%) of all
questions posed
by the Riddler were
The Riddler
Background-type
How much dirt is in a hole 3 acres square and 200 None, because it's a hole
feet deep?
What has neither flesh, bone, nor nail yet has 4 A glove
fingers and a thumb?
When is the top of a mountain like a saving's When it peaks one's interest
account?
A bear lumbers and a fallen tree
Why is a bear like a fallen tree? becomes lumber
Which president wears the largest hat? The one with the biggest head

33. Anatomy of a Background Question
• What • Disorder
• How • Syndrome
• Where • Finding
• When • Health state
• Who • Concern
• Why

34. Background Questions -- Examples
• Who should get influenza vaccine and when?
• Which drugs to treat HIV can cause
pancreatitis?
• What is the metabolic pathway for cholesterol
synthesis?
• Why do patients with sleep apnea have high
blood pressure?

35. Background vs. Foreground
Questions
• Background: Designed to improve
general knowledge about a subject
• Foreground: Patient-specific
questions, strong implications for
decisions, often with comparisons

36. An Evolution in Question Type
100
90
80
70
60
Foreground
50
Background
40
30
20
10
0
M1-M2 M3-M4 Residency Practice
R. Mangrulkar

37. Background vs. Foreground
Questions
• Background: Designed to improve
general knowledge about a subject
• Foreground: Patient-specific
questions, strong implications for
decisions, often with comparisons

38. Background Questions: A Case
Using the following case, jot down 3 questions with
your partner that may help you care for this patient:
A 42 year old woman comes to her primary care
practitioner s office for follow up of her diabetes. She
is currently on glyburide 10 mg twice daily. However,
her morning and evening blood sugars still stay
elevated. You are the medical student who sees
this patient with your attending. Afterwards, your
attending asks whether you think she should add
metformin to her regimen. You say that you don t
know because your knowledge of diabetes
medications are sketchy.

39. Background Questions
• What kind of medication is glyburide?
• In what classes of medication do metformin
and glyburide fall?
• What is the initial dosage of metformin?
• What are the adverse effects of metformin
that I must be cautious about?
• Is it safe to be on glyburide and metformin at
the same time?

40. Sources for Background Questions
• Course notes, lectures, syllabi
• Textbooks
– MD Consult
– Stat!Ref
– Up-To-Date
• Review articles
• Practice Guidelines

41. Background vs. Foreground
Questions
• Background: Designed to improve
general knowledge about a subject
• Foreground: Patient-specific
questions, strong implications for
decisions, often with comparisons

42. Foreground Questions -- Examples
• In patients with chronic • In patients with acute
atrial fibrillation over the chest pain of less than 6
age of 70, does warfarin hours duration, what is
anticoagulation reduce the diagnostic accuracy
the rate of stroke and of a single troponin level
death when compared when compared with
with aspirin? serial EKG s and
enzymes?
Therapy Diagnosis

43. Foreground Questions -- Examples
Therapy
• In patients with chronic atrial fibrillation over
the age of 70, does warfarin anticoagulation
reduce the rate of stroke and death when
compared with aspirin?
Diagnosis
• In patients with acute chest pain of less than
6 hours duration, what is the diagnostic
accuracy of a single troponin level when
compared with serial EKG s and enzymes?

44. PICO: A Tool to Structure the
Foreground Question
Therapy Diagnosis
P Patient Pop Disease
I Intervention Test
C Comparison Gold Standard
O Outcome Accuracy

45. Foreground Questions - Case
Using the PICO model, jot down 1 foreground
question with your partner that will help you care for
this patient:
A 42 year old woman comes to her primary care
practitioner s office for follow up of her diabetes. She
is currently on glyburide 10 mg twice daily. However,
her blood sugars still stay elevated. After you see
this patient, your attending asks whether you think
she should add metformin to her regimen.
Patient - Intervention - Comparison - Outcome

46. Foreground Questions - Therapy
• In type II diabetics, is metformin and glyburide
better than glyburide alone at lowering blood
sugar?
• Among women with type II diabetes, are there
more instances of low blood sugar events in
patients on both metformin and glyburide,
compared to glyburide alone?

47. Sources for Foreground Questions
• MEDLINE
• Practice Guidelines
• Evidence Based-Databases
– Cochrane Library
– ACP Journal Club

48. Additional Source Information
for more information see: http://open.umich.edu/wiki/CitationPolicy
Slide 21: Rajesh Mangrulkar
Slide 23: Rajesh Mangrulkar
Slide 36: Rajesh Mangrulkar