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)?

WARNING

CONFUSINGMATHAHEAD

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

Ask

Acquire

Appraise

Apply

Ask

Acquire

Thread 1: Information Retrieval

R. Mangrulkar

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

Anatomy of a Background Question

• What• How• Where • When• Who• Why

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

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