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Author(s): Rajesh Mangrulkar, MD, 2009
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Patients and PopulationsMedical Decision-Making: The Information
Cycle
Rajesh S. Mangrulkar, M.D.
Fall 2008
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…
• She decides not to get tested.50%
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?
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
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%
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
Basic Probabilistic RulesExamples 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.
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
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)?
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
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)?
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)
Applying Bayes Theorem
• P (BRCA | no breast ca) =
0.15
------------------- = 26%
0.15 + 0.4375
• 26% is significantly lower than 50% (our prior probability)
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
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.
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.
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
Riddle me this...
• How many questions do clinicians ask while they care for patients?
• How can knowledge of question structure improve the efficiency of the information retrieved?
4 per patient
(1) Targeting Information Resources(2) Generating Search Terms
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)
Research: Questions New Knowledge
R. Mangrulkar
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
• Step 1: Question Search for Answer• Step 2: Assess the strength of answer• Step 3: Weigh against:
– Patient Values– Physician Values– Society’s Values
Patient Care: Questions Decisions
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.
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...
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.
What makes a good question?
• #1: Could you suggest a place for my “friend” and I to eat close by?
• #2: Can you help us find a vegetarian Thai 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?
• Purposes– Target resources– Define search terms– Define what you and the patient care about
• Two Types– Background– Foreground
The Well-Structured Clinical Question
The Riddler
How much dirt is in a hole 3 acres square and 200 feet deep?
What has neither flesh, bone, nor nail yet has 4 fingers and a thumb?
When is the top of a mountain like a saving's account?
Why is a bear like a fallen tree?
Which president wears the largest hat?
54/67 (81%) of allquestions posedby the Riddler wereBackground-type
None, because it's a hole
A glove
When it peaks one's interest
A bear lumbers and a fallen tree becomes lumber
The one with the biggest head
Anatomy of a Background Question
• What• How• Where • When• Who• Why
• Disorder
• Syndrome
• Finding
• Health state
• Concern
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?
• Background: Designed to improve general knowledge about a subject
• Foreground: Patient-specific questions, strong implications for decisions, often with comparisons
Background vs. Foreground Questions
An Evolution in Question Type
0
10
20
30
4050
60
70
80
90
100
M1-M2 M3-M4 Residency Practice
Foreground
Background
R. Mangrulkar
• Background: Designed to improve general knowledge about a subject
• Foreground: Patient-specific questions, strong implications for decisions, often with comparisons
Background vs. Foreground Questions
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.
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?
Sources for Background Questions
• Course notes, lectures, syllabi
• Textbooks– MD Consult– Stat!Ref– Up-To-Date
• Review articles
• Practice Guidelines
• Background: Designed to improve general knowledge about a subject
• Foreground: Patient-specific questions, strong implications for decisions, often with comparisons
Background vs. Foreground Questions
Foreground Questions -- Examples
• 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?
• 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?
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?
PICO: A Tool to Structure the Foreground Question
TherapyTherapy DiagnosisDiagnosis
P Patient Pop Disease
I Intervention Test
C Comparison Gold Standard
O Outcome Accuracy
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
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?
Sources for Foreground Questions
• MEDLINE
• Practice Guidelines
• Evidence Based-Databases– Cochrane Library– ACP Journal Club