Clinical Models in Venous Thromboembolism: How to make the most of your history and physical exam...

Clinical Models in Venous Thromboembolism:

How to make the most of your history and physical exam

Eddy Lang CCFP(EM) CSPQMcGill Emergency RoundsOctober 2001

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Clinical Scenario #1: Mr. Tremblay

• 63 year old male with severe cough x 1 day

• No significant PMHx, non smoker

• Tachypnic able to speak complete sentences:

• VS: HR 105 BP 140/90 T 38.1C - rectal O2 Sat 93% RA

• No preceding URI Sx

• Central chest discomfort initially -now resolved

• Some decreased A/E left base

• CXR: small left-sided pleural effusion, minimal airspace disease

Clinical Scenario #2: Ms. Jones• 22 year old female

• 2 hour history of chest pressure and SOB

• Appears apprehensive, wearing oxygen starting to feel better

• VS: 120/90 RR 22/min Sat 100% HR 90 T = 36.9

• Smoker, OCPs

• Remote history of panic attacks; similar but not as severe

• No associated symptoms

• Unremarkable physical

Test and Treatment Thresholds in the Diagnostic Process

No further testing necessary

Treatment commences

Survey1. Would you order a ventilation/perfusion scan or helical CT in this patient (I don't need to know which)?

2. Would you order a D-Dimer test on this patient (assume non-elisa)?

3. Would you use the D-Dimer result to determine whether you would order any imaging i.e. helical CT or V/Q?

Survey Results

staff staff res res res staff resy y y n y n yn n n y n y nn n n y n y yy n n n n y nn y y n y y yn y y n y n y

Survey Results• Mr. Tremblay

•5/7 get V/Q•2/7 get D-dimer• 3/7 incorporate D-dimer in decision to image

•Ms Jones•2/7 get V/Q•5/7 get D-dimer•4/7 incorporate D-dimer in decision to image

Clinical Question

In patients who present with symptoms and signs suggestive of PE, can elements of the clinical examination in combination with simple tests allow me to determine which patients can be safely discharged without imaging procedures?

Clinical Question

In patients who present with a syndrome suggestive of PE, can a clinical prediction rule allow me to determine which patients need further work-up?

Educational Objectives

• Review the rationale for the development of clinical prediction rules in venous thromboembolism (VTE)

• Conduct structured critical appraisal of the best prediction rule / clinical model research in VTE

• Explore issues related to test selection in patients suspected of VTE

Top Ten Reasons to Dislike Clinical Prediction Rules

6. I don’t practice cookbook medicine

7. I refuse to do any math during my shift especially if I need a calculator

8. I’m way too busy to use these things

9. My “gestalt” clinical judgement is better than any prediction rule could be

10. They are just too damned complicated to use

Top Ten Reasons to Dislike Clinical Prediction Rules

1. Everyone knows the H and P stinks, let’s just get an MRI

2. Developed by nerdy academics who haven’t examined a patient in 30 years

3. I don’t believe in fortune telling

4. Except for Christian, everything from Ottawa annoys me!

5. They are a government plot designed to make us cut costs

Finding the evidence

Use of a Clinical Model for Safe Management of Patients with Suspected Pulmonary Embolism

Wells, Ginsberg, Anderson et al.

Annals of Internal Medicine - 1998

• Inclusion Criteria:• Consecutive inpatients and outpatients with suspected pulmonary

embolism whose symptoms had lasted less than 30 days were potentially eligible

• 5 centers, 16 physicians

• Exclusion Criteria:• Duration of Sx > 3 days• Anticoag > 72hrs.• Survival < 3 months• Suspected upper extremity DVT

Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

= 0.86 Wells, Ginsberg, Anderson et al.

Annals of Internal Medicine - 1998

Probability Model

Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

1885 eligible patients

Study Flow

484 ineligible

1401 eligiblepatients

150 lost

1239 evaluable patients

•147 declined to consent•13 lost to follow-up

734 low PTP3.4% PE

403 mod. PTP28% PE

102 high PTP78% PE

•Prolonged anticoagulation•expected survival< 3 mos.

Rates of Pulmonary Embolism According to Pretest Probability of Pulmonary Embolism and Results of Ventilation-Perfusion Lung Scanning

Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

Rates of venous thromboembolic events during the 3-month follow-up

• normal perfusion scans and normal initial ultrasonograms: – 2 of 332 [0.6%; 95% CI, 0.3% to 3.0%]

• non-high-probability ventilation-perfusion scans, low or moderate pretest probability, and normal serial ultrasonograms – 3 of 665 [0.5%; 95% CI, 0.1% to 1.3%]

Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

Cause of Death According to Whether Pulmonary Embolism Was Initially Diagnosed

Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer.

Wells, Anderson, Rodger, Stiell et al.

Annals of Int. Med. 2001

• Inclusion Criteria:• Consecutive emergency department patients (adults) with suspected pulmonary

embolism whose symptoms had lasted less than 30 days were potentially eligible

• 4 centers, 43 physicians

• Exclusion Criteria:• Suspected upper extremity DVT

• No Sx within 72 hrs

• Anticoag > 24 hrs.

• Expected survival < 3 mos.

• Contraindication to contrast

• Pregnancy

• Geographic inaccessibility

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

• Interventions:• Application of a clinical model• SimpliRED whole-blood agglutination D-dimer

• Primary Outcome:• Proportion of patients with VTE during 3-month follow-up

• Methodology• Intention to treat analysis• Upper range 95% CI = 1% VTE rate• Sample size 930

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Clinical Model• Hemoptysis - 1.0 pt.

• Malignancy 1.0 pt.

• HR > 100 - 1.5 pts.

• Immobilization ( 3 consec. Days) or surgery within 4 weeks - 1.5 pts.

• Previous DVT/PE - 1.5 pts.

• Clinical signs and Sx of DVT - 3.0 pts.

• PE as likely or more likely than alternate Dx - 3.0 pts.

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Clinical Model:Scoring

• Low PTP< 2.0 points

• Moderate PTP 2.0 but < 6.0

• High PTP 6.0

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Clinical Model:Performance

• Low PTP527 pts. (57%); 7 VTE events (1.3%)

• Moderate PTP339 pts. (36%); 55 VTE events (16.2%)

• High PTP64 pts. (7%); 24 VTE events (40.6%)

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Follow-up Data on 849 patients with VTE ruled out

• 17 suspected events; 6 low PTP, 9 mod PTP, 2 high PTP• VTE confirmed in 5 (0.6% 95% CI 0.2 to 1.4%)• Low PTP

– 4 suspected PE, 2 DVT; 1 PE confirmed (day 16) • Mod PTP

– 4 suspected PE, 5 DVT; 3 DVT confirmed• High PTP

– 2 suspected PE; 1 PE confirmed

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Compliance with Algorithm

• 92 patients had fewer tests than called for• 4/5 confirmed events occurred in this group• Among 81 patients initially diagnosed with PE: 7 patients labeled as a result of extra testing• 2/7 from low PTP group

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Do we believe this?

• Is there a need for the decision rule?• Was the rule derived according to methodologic standards?• Has the rule been prospectively validated and refined?• Has the rule been successfully implemented into clinical practice?• Would use of the rule be cost effective?• How would the rule be disseminated and implemented?

Methodologic Standards for Development of a Clinical Prediction Rule: The Researcher’s

Perspective

Stiell IG and Wells GA APRIL 1999 33:4 ANNALS OF EMERGENCY MEDICINE

• Were the patients chosen in an unbiased fashion and do they represent a wide spectrum of the severity of the disease?

• Was there a blinded assessment of the criterion standard for all patients?

• Was there an explicit and accurate interpretation of the predictor variables and the actual rule without

knowledge of the outcome? • Was there 100% follow-up of the patients enrolled?

Methodologic Standards for Validation of a Clinical Prediction Rule: The Clinician’s

perspective

Users Guide 2000AMA press

Were the patients chosen in an unbiased fashion and do they represent a wide

spectrum of the severity of the disease?

• “consecutive symptomatic patients”• 86 ultimately diagnosed with PE (9.5%)• Rule in rate of 17% in patients

undergoing imaging

Was there a blinded assessment of the criterion standard for all patients?

• “V/Q scans were interpreted by Nuclear Medicine physicians who had no knowledge of the clinical model or D-dimer ”•“Pulmonary angiography and venography were evaluated by the same criteria”• “A committee blinded to all patient outcomes adjudicated suspected outcome events”

Was there an explicit and accurate interpretation of the predictor variables

and the actual rule without knowledge of the outcome?

• Model and d-Dimer interpreted prior to imaging or F/U• No specific reporting of Kappa in this study

Was there 100% follow-up of the patients enrolled?

• Sixteen patients lost to follow-up because of relocation• No sensitivity analysis performed

Algorithm Performance

• 47% of patients did not require imaging

• 7% serial ultrasonography

• 1.1% pulmonary angiography

• Overall sensitivity 99.4% (95% CI 98.6 - 99.8%)

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Applicability

• Will the reproducibility of the test result and the interpretation be satisfactory in my clinical setting?

• Are the results applicable to the patients in my practice?

• Will the results change my management strategy?

• Will patients be better off as a result of this rule?

Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

Levels of Efficacy in Diagnostic Test Evaluation

How many different possible elements might be incorporated into the decision to select a given diagnostic test?

Levels of Efficacy in Diagnostic Test Evaluation

• Technical Efficacy• Diagnostic Accuracy Efficacy• Diagnostic Thinking Efficacy• Therapeutic Efficacy• Patient Outcome Efficacy• Societal Efficacy

Technical Efficacy

•Feasibility and acceptability•Operator dependence/training•Analytic sensitivity•Interferences and cross-reactivity of biochemical tests•Measurement inaccuracy (systematic measurement error)•Measurement imprecision (random measurement error)

Diagnostic Accuracy Efficacy

•Sensitivity and specificity•Predictive value•Likelihood ratios•Measures of area under the ROC curve

Diagnostic Thinking Efficacy

•Percentage of cases in which the final diagnosis changed after testing•Difference in clinicians’ subjectively estimated diagnostic probabilities before and after receipt of test info•Certainty or confidence in a diagnosis•Percentage of cases in a series in which the test was judged helpful to making the diagnosis•Cost/change in clinical diagnosis

Therapeutic Efficacy

•Percentage of times that management changed based on test information•Percentage of times that another test was avoided because of information from the test under investigation•Total cost of diagnostic strategies, cost/patient tested, or cost/change in management decision

Patient Outcome Efficacy

•Symptom severity•Functional outcome•Patient utility assessment•Expected value of test information in QUALYs•Morbidity avoided by testing or not testing•Mortality rate or life expectancy•Cost-effectiveness as cost/unit change in outcome variable

Societal Efficacy

•Benefit-cost analysis from societal viewpoint•Cost-effectiveness analysis from societal viewpoint

The PEDS Study

Pulmonary Embolism Diagnosis Study Investigators: Dr. S. Kahn, Dr. A. Hirsch, Dr. E. Lang, Dr.A. Guttman, Dr. M. Afilalo

Funded by CIHR Clinical Trials ProgramObjectives: To determine whether spiral CT can be relied on as a safe alternative to V/Q lung scanning as the initial diagnostic imaging procedure for the evaluation of patients with suspected PE.Inclusion Criteria: Patients with symptoms or signs suspected to be caused by acute pulmonary embolism (acute onset of new or worsening shortness of breath, chest pain, hemoptysis, presyncope or syncope).

Note: If you have potential study patients, BEFORE ORDERING A DIAGNOSTIC TEST FOR P.E. please contact:

For ED patients only: Chris Tselios pager# 440-4143For all in-patients: Carla Strulovitch pager # 981-7932

Start date:September 20th

Educational Objectives

• Review the rationale for the development of clinical prediction rules in venous thromboembolism (VTE)

• Conduct structured critical appraisal of the best prediction rule / clinical model research in VTE

• Explore issues related to test selection in patients suspected of VTE