Giải quyết các vấn đề lâm sàng: Cơ sở từ y học chứng cứ GiẢNG VIÊN : GS TS BS LÊ HOÀNG NINH

Giải quyết các vấn đề lâm sàng: Cơ sở từ y học chứng cứ

GiẢNG VIÊN : GS TS BS LÊ HOÀNG NINH

Nội dung bài học

• Mục tiêu • Các kỹ năng cần của y học chứng cứ

trong thực hành chăm sóc bệnh nhân:– Kỹ năng đặt câu hỏi đúng về tình huống lâm sàng

của bệnh nhân

– Kỹ năng tìm kiếm các chứng cứ hiện có trên y văn

– Kỹ năng đánh giá các chứng cứ trên y văn

– Kỹ năng ứng dụng chứng cứ trên bệnh nhân của thầy thuốc

Mục Tiêu

• Định nghĩa y học chứng cứ (EBM) • Tại sao thầy thuốc phải dùng y học chứng cứ

– Compare with expert-based medicine – How are we misled by:

• Surrogate outcomes • Personal observation • Pathophysiologic reasoning

• Mô tả các công cụ y học chứng cứ• Xây dựng câu hỏi lâm sàng tốt

Y học chứng cứ là gì?

“ sử dụng chứng cứ tốt nhất hiện có vào thực hành chăm sóc bệnh nhân”

Cái gì là quan trọng khi đọc y vănCái cần có ở y văn là

1. Các kết quả có liên quan tới bệnh nhân của bạn 2. Trả lời được câu hỏi về chăm sóc bệnh nhân mà bạn đang gặp

khó khăn3. Có thể làm bạn thay đổi thực hành chăm sóc bệnh nhân của

bạn4. Là chủ đề mà bạn đang quan tâm theo dõi5. Là cái mà bạn cần biết rõ hơn, chi tiết hơn, cụ thể hơn6. Bạn cần về POEM or DOE

• Patient-oriented evidence ( POEM: bằng chứng hướng tới bệnh nhân) that matters vs disease-oriented evidence ( DOE : bằng chứng hướng tới bệnh )

Y học chứng cứ“Evidence-based medicine (EBM) requires the

integration of the best research evidence with our clinical expertise and our patient’s unique values and circumstances”

EBM, 2006, Straus et al

Y học chứng cứ đòi hỏi lồng ghép bằng chứng tốt nhất với kinh nghiệm lâm sàng và tình

trạng , hoàn cảnh, điều kiện thực của bệnh nhân

Giá trị của việc học EBM:

( một thử nghiệm ngắn hạn) • Một thử nghiệm có nhóm chứng về giảng dạy đánh giá y

văn được thực hiện trên sinh viên y khoa• Nhóm thử nghiệm được học với thầy hướng dẫn đã qua

khóa huấn luyện lâm sàng về:– Đánh giá các thử nghiệm lâm sàng– Đánh giá các bài báo về test chẩn đoán và điều trị

• Nhóm chứng được học với các thầy bình thường không qua các khóa huấn luyện kể trên

Bennett et al. JAMA. 1987;257:2451-2454.

Giá trị việc học EBM: ( một thử nghiệm ngắn hạn tt)

• Sinh viên nhóm thử nghiệm có quyết định chẩn đoán và điều trị đúng tốt hơn và họ có thể lập luận, bình luận trước khi ra các quyết định của họ

• Những sinh viên trong nhóm chứng thường ra các quyết định không đúng trong chẩn đoán và điều trị.

• Sinh viên trong nhóm chứng thường dễ chấp nhận những đề nghị từ những nhân vật có thẩm quyền.Bennett et al. JAMA. 1987;257:2451-2454.

The Patient

• Patient is a 27-year-old woman with severe right lower quadrant pain. – initial peri-umbilical pain x 2 days migrating yesterday to

current site.

• Loss of appetite. No vomiting, diarrhea; no bowel movement

• no known infectious exposure/

suspicious ingestions, or recent travel

Hướng dẫn truyền thống trong thực hành y khoa

• Pathophysiology and pharmacology– Foundation of medical practice– Do what “makes sense”

• Expert opinion– In training: learning at the bedside from the master clinician– In practice: lectures and seminars with thought leaders

• Clinical experience– Successes, outcomes, and adverse events

in our own practice

Lồng ghép chứng cứ

• Kinh nghiệm lâm sàng:– Trải nghiệm – Cân nhắc, xem xét

• Bối cảnh bệnh nhân– Chất lượng cuộc sống – Chi phí – Những yếu tố khác…

Chứng cứ hiện có tốt nhất

Kinh nghiệm

lâm sàng

Hiện trạng và Bối cảnh bệnh nhân

Chất lượng cuộc sống

Chi phí

ĐiỀU TRỊ VÀ CHẨN ĐOÁN

Vấn đề của bệnh nhân

• Bệnh nhân nử 27 tuổi đau bụng dữ dội vùng bụng ¼ phải , dưới.

– initial peri-umbilical pain x 2 days migrating yesterday to current site.

• Biếng ăn

• Không nôn mửa, tiêu chảy, không có nhu động ruột

• Không rõ tiếp xúc với nguồn nhiễm trùng, suspicious ingestions, or recent travel

Xét Nghiệm

VS BP 120/78 P 16 T 39

Chest CTA. CV RRR s M/R/G

ABD: NML exam x decreased bowel tones and definite right lower quadrant pain, specifically at McBurney’s point.

no heptomegaly nor splenomegaly (enlarged liver or spleen). She has no rebound pain or involuntary

chuẩn 5 “A”

1. Ask the right question

2. Acquire the evidence

3. Appraise the evidence

4. Apply the evidence

5. Assess its impact

Concern:

• Case discussion: 27 year old woman with right lower quadrant (RLQ) abdominal pain

• Background information available from textbooks-– What typically presents as RLQ pain

– What is the clinical course of the different diagnoses

– Specifically, what is typical presentation of appendicitis

• Foreground information– How good is a CT scan for appendicitis?

Đặt Câu Hỏi Lâm Sàng

Câu Hỏi Lâm Sàng• Câu hỏi lý tưởng:

– Focused enough to be answerable

– Pertinent to clinical scenario

– Framed as Population receiving an Intervention (test or treatment) [as Compared to other test/treatment or placebo] associated with Outcome (disease or improvement)

PICOS

P roblem/population

I ntervention

C omparison

O utcome

S tudy design

Examples of tough questions

• Should I screen men for prostate cancer?

• Who is a good candidate for hormone replacement therapy?

• Are angiotensin receptor blockers now first-line for hypertension?

Examples of better questions• Would a PSA test reduce mortality in a 65 year-old

asymptomatic man? • What is the reduction in fracture risk associated

with hormone replacement therapy? • Is losartan more effective than atenolol at

preventing cardiovascular events in middle-aged hypertensive diabetic women?

PICOS

PICOS for confirmatory diagnosis of appendicitis

P: 27 year old woman with symptoms suggestive of appendicitis

I: CT Scan

C: Ultrasound

O: Accurate diagnosis without undue delay

S: ??

Hệ quả quan trọng• Hệ quả hướng tới bệnh nhân:

outcomes patients actually care about – Death (overall or disease-specific)– Heart attacks, strokes, amputations, bed sores, broken hips, renal

failure, etc.– Ability to perform activities of daily living

Versus• Hệ quả hướng tới bệnh:

– Biochemical, physiologic, pharmacologic, or laboratory measures

Comparing DOE and POE

Shaughnessy AF, Slawson DC. Getting the Most from Review Articles: A Guide for Readers and Writers. American Family Physician 1997 (May 1);55:2155-60.

ExampleDisease-Oriented

Evidence

Patient-Oriented Evidence that

Matters CommentAntiarrhythmic Therapy

Drug X PVCs on ECG

Drug X increases mortality

POE contradicts DOE

Type 2 Diabetes Aggressive Tx with insulin or oral agentscan keep BS low

Aggressive Tx does not reduce mortality or prevent most complications

POE contradicts standard teaching

ProstateScreening

PSA screening detects prostate cancer early

Does PSA screening mortality?

DOE exists, but POE is unknown

Background versus foreground information

• Case discussion: 27 year old woman with right lower quadrant (RLQ) abdominal pain

• Background information available from textbooks-– What typically presents as RLQ pain

– What is the clinical course of the different diagnoses

– Specifically, what is typical presentation of appendicitis

• Foreground information– How good is a CT scan for appendicitis?

Steps of EBM-5 A’s

• Ask• Acquire• Appraise• Apply• Assess

“Finding Evidence”: Sources (I)

• Primary research database (articles)– PubMed (aka MEDLINE), Pyschlit, CCTR

• Secondary research databases (synthesis)– Cochrane Library, Clinical Evidence, InfoPOEMS,

UpToDate

• Tertiary resources (meta search engines, databases of databases)– TRIP+ (Translating Research Into Practice),

PrimeEvidence

“Finding Evidence”: Sources • PubMed

– 16 million peer reviewed biomedical articles indexed (note can use PubMed limits to search on particular populations, study types, etc.)

• Cochrane Library– ~3000 clinical systematic reviews (gold standard database)

• Clinical Evidence– ~2500 tsystematic reviews of treatment classified by likelihood of benefit

• InfoPOEMS (www.infopoems.com)– ~3000 regularly updated entries, Patient Oriented Evidence the Matters

(POEM), 100+ journals monitored• UpToDate

– 70,000 pages, evidence based clinical information resource, ~3000 authors, 350+ journals monitored, peer reviewed

• TRIP+– Meta-search of 55 sites of evidence based information

“Finding Evidence”: Searching1. Chuyển câu hỏi lâm sàng thành câu hỏi đúng dễ tìm y văn (e.g. PICOS)

2. Chọn nguồn dữ liệu mà bạn muốn tìm (e.g. PubMed)

3. Áp dụng bộ lọc để khu trú y văn cần tìm (e.g. PubMed limits linked to PICOS

such as gender, age, study type limits)

4. Đánh giá kết quả (e.g. using systematic review worksheet)

5. Xem xét xem liệu bạn có đủ thông tin để ra quyết định không

6. Nếu chưa đủ bạn phải đi lại các bước 1-3 cho đến khi bạn có được câu trả lời

hoặc quyết địnhlà không đủ chứng cứ hoặc có đủ chứng cứ để ra quyết định

ĐÁNH GIÁ CHỨNG CỨ

Assess the Evidence• Kết quả là có giá trị?

– Validity is defined as relative không có sai lệch hệ thống và yếu tố gây nhiễu• Kết quả gì?

– Hệ quả là gì và được đo lường bằng cách nào?– Độ lớn của hệ quả ?– Các Kết quả có ý nghĩa thống kê ?

• Kết quả áp dụng trên bệnh nhân được không?– Does my patient resemble those in the study?– Were all outcomes relevant to my patient evaluated?– Are there other factors (eg, cost, availability) that limit applicability to my

patient?

Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001

Đánh giá chứng cứ (t.t)

• Phân biệt nghiên cứu quan sát và thực nghiệm observational and experimental studies

• Phân biệt 2 major study designs (randomized controlled trial and cohort study) :– How the study is designed– Advantages and disadvantages of design– How to assess validity– How to assess results– How to assess applicability

Nghiên cứu thực nghiệm và nghiên cứu quan sát

• In experimental studies, the investigator controls subjects’ exposure to intervention

– Example: randomized controlled trial (RCT)

• In observational studies, investigator does not control the exposure; it occurs naturally or is initiated by patients or their physicians

– Examples: cohort study, case-control study

Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001.

RCTs

Generally held to be the optimal methodology for determining benefit or harm

Eligible Patients

Randomization

Treatment

Control Outcome

Outcome


RCTs: ích lợi

• Treatment and control groups are likely to have similar distribution of known and unknown prognostic factors (potential confounders)

• Outcomes are determined prospectively in a standardized, systematic fashion


RCTs: Disadvantages

• Costly to perform• Size limitations make detection of rare events

difficult (eg, adverse medication effects) • Eligibility restrictions may reduce applicability to

real patients• Cannot be ethically performed if exposure is

expected to cause harm (eg, smoking)


RCTs: Disadvantages• Costly to perform• Size limitations make detection of rare events

difficult (eg, adverse medication effects) • Eligibility restrictions may reduce applicability to

real patients• Cannot be ethically performed if exposure is

expected to cause harm (eg, smoking)


Đánh giá giá trị các RCTs• Was randomization concealed?• Were patients analyzed in groups to which they were

randomized?• Were patients in treatment & control groups similar with

respect to prognostic factors?• Were patients, clinicians, outcome assessors, and data

analysts aware of allocation?• Were groups treated equally?• Was follow-up complete?Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice . Chicago, IL: American

Medical Association; 2001.

Đánh giá kết quả RCT• Magnitude of result: How large was the treatment effect?

– Relative risk and odds ratio– Absolute risk reduction and number needed to treat (NNT)

• Statistical significance– P value– Confidence interval: How precise was estimate of treatment

effect?• Clinical significance


Calculating the Risk Ratio and Number Needed to Treat (NNT)


Treatment(n = 1000)

Control(n = 1000)

100 have the outcome

120 have the outcome

Risk = 0.1, or 10%(100/1000)

Risk = 0.12, or 12%(120/1000)

Risk ratio = 0.1/0.12 = 0.83, or 83%

Absolute risk reduction = 0.12 - 0.1 = 0.02, or 2%

NNT = 1/0.02 = 50

Đánh giá tính ứng dụng RCT

• Were the study patients similar to my patient?– Eligibility criteria– “Table 1” data (baseline characteristics)

• Were all clinically important outcomes considered?• Are the likely treatment benefits worth the potential

harm and costs?Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago,

IL: American Medical Association; 2001.

Cohort Studies

• Similar to RCTs, except that assignment to intervention is not random

Eligible Patients

Choice or Happenstance

Exposed

Not Exposed

Outcome

Outcome


Lợi ích nghiên cứu đoàn hệ • Outcomes are determined prospectively in a

standardized, systematic fashion• Often includes a larger, more diverse population

than those eligible for or included in RCTs• Can be used to assess effects of harmful exposures

(eg, smoking)

Guyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001

Hạn chế nghiên cứu đoàn hệ

• Costly to perform• Size limitations make detecting rare events

difficult• Exposure and control groups are likely to differ in

factors that may affect outcomes• Control of confounding through statistical analysis

may be inadequateGuyatt et al. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001.

Đánh giá giá trị nghiên cứu đoàn hệ

• Were the exposed and control groups similar in all known determinants of outcome? – Did the analysis adjust for potential differences?

• Were the outcomes measured in the same way in the groups being compared?

• Was follow-up sufficiently complete?


Đánh giá kết quả NC Đoàn Hệ

• How strong is the association between exposure and outcome?– Risk ratio or odds ratio– Absolute risk increase or number needed to harm (NNH)

• Statistical significance– P value– Confidence interval: How precise was estimate of risk?

• Clinical significance


Đánh giá tính ứng dụng Cohort Study

• Were the study patients similar to the patient under consideration in my practice?

• Should I attempt to stop the exposure?

Guyatt et al. Users' Guides A Manual for Evidence-Based Clinical Practice. Chicago, IL: American Medical Association; 2001 to the Medical Literature:.

Nghiên cứu bệnh-chứng

• In contrast to RCTs and cohort studies, participants are selected based on the presence of the outcome rather than the exposure

• Exposure status is determined retrospectively


Case-Control Studies: Design

Select Subjects: Cases (diseased)

Controls(nondiseased)

Exposed Not ExposedObserve: Exposed Not Exposed


Lợi ích Case-Control Studies

• Much more efficient for investigation of rare outcomes

• Take less time to perform than RCTs or cohort studies


Hạn chế Case-Control Studies

• Retrospective assessment of exposure may be inadequate (recall bias)

• Can be performed only after outcomes have occurred (ie, after damage has already occurred)

• Selection of appropriate controls may be difficult• Control of confounding through statistical analysis may

be inadequate


Các bước EBM-5 A’s


Applying EBM

Clinical Expertise

Patient Values and Preferences

Quality of Life

Costs

Best Available Evidence

Xem xét kết quả nghiên cứu điều trịVALIDITY• Clearly focused question? • Randomization• Blinding- subjects, providers, investigators• Groups similar at start and treated the same throughout?• Followed in randomized groups and accounted for at end? (intention to treat)• Enough subjects to minimize chance differences?

REUSLTS AND PRECISION1. What are results? How presented?2. Certainty & precision? (95% CI’s)

APPLICABILITY1. Can the results be applied to my patient?2. All important outcomes addressed?3. Should there by change in policy?

“Therapy”: Intention to treat

• Subjects are analyzed in the groups they were randomized to.– Maintains randomization– Better reflects real world outcomes– Measures efficacy (“Will this work?”)– Detects issues about intervention other than

effectiveness “In the best possible circumstances, do they work?”

“Therapy”: Bias

• Randomization helps lessen patient bias

– Self-selection

• Blinding helps lessen patient and investigator bias

“Điều trị ”: kết quả thế nào ?

• RR OR RRR

• ARR

• NNT / NNH

• P value/ CI

• Clinically significant?

“Điều trị”: Diễn đạt các kết quả

Risk = outcome event rate

= number having event number receiving the intervention

Relative risk = risk in intervention group(RR) risk in control group

Relative risk reduction (RRR) = 1 - RR

“Điều trị ”: Diễn đạt các kết quả

Absolute risk reduction (ARR) = difference in risk (control –

intervention)

“Diễn đạt các Kết quả

Number-needed-to-treat (NNT) = 1/ARR

NNT: là số bệnh nhân cần được điều trị nhằm ngăn ngừa một biến cố, một hệ quả có thể xảy ra trong một thời khoảng nhất định nào đó

“Thí Dụ về N. C Điều Trị

• Một thử nghiệm điều trị bệnh ung thư bằng một loại thuốc mới , sau 4 năm theo dõi cho thấy tử vong như sau:

• Nhóm thử nghiệm: 30%• Nhóm chứng : 50%• Tính RR, RRR, ARR, NNT?

“ Thí dụ .NC Điều Trị”

RR = risk of death in experiment/control groups

= 30%/50% = 0.6 or 60%

RRR = 1 - RR = 1-0.6 = 0.4 or 40%

ARR = risk of death in control – experimental groups

= .50 -.30 = 0.2 or 20%

NNT =1/ARR = 1 ÷ 0.2

= 5 bệnh nhân cần điều trị bằng thuốc mới để ngừa tử vong trong 4 năm

“Therapy”: Relative Versus Absolute Benefits

• Consider – July 3, 2002: Worldcom stock rose 120%

(relative increase)– The stock rose from: $0.10 $0.22 (absolute

increase)

“NC Điều Trị”: Giảm Nguy Cơ tương đối –Giảm nguy cơ tuyệt đối

• Baseline risk 10/100 5/100 RRR = 50% ARR = 5% NNT = 20

• Baseline risk 1/100 0.5/100RRR = 50% ARR = 0.5% NNT = 200

• Baseline risk 0.1/100 0.05/100RRR = 50% ARR = 0.05% NNT = 2000

“Therapy”: RRR Lipid Trials 4S WOSCOPS CARE AFCAPS

for acute myocardial infarction

RRR 27 31 25 40(%)NNT 19 42 40 435(5 year)

“NC Điều Trị”: Khoảng Tin Cậy 95% • Any statistic only an estimate of the “true value” of that

statistic. • Confidence Interval (CI) gives range within which that “true

value” probably lies. • 95% CI - if we repeated the experiment with similar

populations an infinite number of times, the results would fall within the CI 95% of the time. 95% certain that the “true value” will fall within the 95% CI range.

• CI gives us an idea of the precision of the result, since the narrower the CI is, the more certain we can be that the experimental value is close to the “true value”.

• And, generally, the larger the sample size, the narrower the CI

• CI =idea of significance, e.g.– If the 95% CI for the ARR includes 0, no difference between the

experimental and control groups.

– If the 95% CI for the RRR or Odds Ratio includes 1, no difference between the experimental and control groups.

• Similar to P values (e.g., P<0.05) =statistically significant

• CI gives a sense of the size of the differences found in the study.

• e.g., research study - 50% of patients treated with Drug A are cured, compared with 45% of patients treated with Drug B.

• ARR I s thus 5%.• Statistical analysis P<0.001, statistically significant.• But if 95% CI of ARR is 0% to 10%, indicates result is not clinically

significant (includes “0%” - “no difference”).

“NC Điều Trị”: ý nghĩa thống kê

ý nghĩa lâm sàng

• Are the results clinically important?

– Duration of pharyngitis: 8.1 days to 7.4 days

– Weight: 279 lbs to 266 lbs after 3 months

– Survival increased from 4.5 mos to 5.2 mos with 100% mortality at

12 months

– Claudication: Increase in walking distance by 34 ft.

“Bình Luận về Chẩn Đoán”: Bộ Công cụ

TÍNH GIÁ TRỊ :• Câu hỏi có tập trung, rõ ràng không? • Chuẩn có phù hợp không?• Chuẩn tham khảo & test áp dụng cho mọi đối tượng không? (verification

bias)• Kết quả có bị ảnh hưởng bởi sự giải thích kết quả không? (review bias)• Tình trạng bệnh được váo cáo và các thay đổi có không? (spectrum bias)• Phương pháp kiểm có đủ chi tiết để làm lại được không?

KẾT QUẢ VÀ TÍNH CHÍNH XÁC1. Kết quả gì?2. Có chắc và chính xác không ? Certainty & precision? (95% CI’s)

TÍNH ƯNG DỤNG1. Kết quả có áp dụng cho bệnh nhân khác không?2. Nguồn lực địa phương có đủ để triển khai những kết quả nầy không?

“Chẩn đoán ”: Bảng 2X2 Các đặc trưng của test chẩn đoán

• Sensitivity

• Specificity

• Predictive Value

• Likelihood Ratios

DIAGNOSTIC TEST

D I S E A S EPresent Absent TOTALS

Test positive

True

Positive

False

Positive

All positive

Test negative

False

Negative

True

Negative

All negative

TOTALSAll with

disease

All without disease

Entire population

T

E

S

T

“Diagnosis”: What are the Results?

(+) (-)

(+)a b

(-)c d

D I S E A S E

T

E

S

T


Pt has diseaseDz (+)

Dz (-)

Test(+)a b

Test(-)c d


Dz (+) Pt does not have disease Dz (-)

Test(+)a b

Test(-)c d

“Diagnosis”: Sensitivity

Sensitivity is proportion of people with disease who have a positive test

Dz (+) Dz (-)

Test(+)a b

Test(-)c d

Sensitivity = (a/a+c) =(TP/TP+FN)

TP

FN


Dz (+) Pt does not have disease Dz (-)

Test(+)a b

Test(-)c d

“Diagnosis”: Specificity

Specificity is proportion of people without disease who have negative test

Dz (+) Dz (-)

Test(+)a b

Test(-)c d

Specificity = (d/b+d) =(TN/FP+TN)

FP

TN

“Diagnosis”: Tradeoffs of sensitivity & specificity labeling diabetes

Blood sugar

• 70• 100• 130• 160• 200

Sensitivity Specificity

98.6% 8.8%88.6% 69.8%64.3% 96.9%47.1% 99.8%27.1% 100%

“Diagnosis”: Choosing a test

• SnNout-

A sensitive test, if negative, rules out a disease

• SpPin-

A specific test, if positive, rules in a disease

“Diagnosis”: Sensitivity & Specificity

• Useful for picking a test (test properties)– Screening- prefer sensitive test– Diagnosis – prefer specific test

• Less help in making diagnosis


• In patients, what you know are their test results- you are trying to determine whether they actually have the disease.

• Positive Predictive Value :

– Of all who tested positive for a disease, the proportion that actually has it

• Negative Predictive Value :

– Of all who tested negative for a disease, the proportion that actually does not have it


(+) (-)

(+)a b

(-)c d

D I S E A S E

T

E

S

T

“Diagnosis”: Positive Predictive Value

Proportion of people with a positive test who have a disease

PPV = a/a+b=

TP/TP+FP

Dz (+) Dz (-)

Test(+) TPa

FPb

Test(-)c d = true positives

over all positives

“Diagnosis”: Negative Predictive Value

Proportion of people with a negative test who don’t have a disease

NPV= d/d+c=

TN/TN+FN = true negatives

over all positives

Dz (+) Dz (-)

Test(+)a

FPb

Test(-) FNc

TNd


PPV dependent on prevalence, even when using the same test

• Example: Prevalence of a particular disease in a population is 50%. Sensitivity= 90% Specificity= 95%

PPV: = a/a+b

= 95%

Dz (+) Dz (-)

Test(+)a b

Test(-)c d

100 100 200

90

10 95

5

“Diagnosis”: PPV & prevalence

PPV dependent on prevalence using same test

• Example: Prevalence of a particular disease in a population is 5%. Same test, same sensitivity & specificity– Sensitivity= 90% Specificity= 95%

PPV: = a/a+b

= 47%

Dz (+) Dz (-)

Test(+)a b

Test(-)c d

10 190 200

9

1 180

10

“Diagnosis”: PPV & NPV

• Useful for diagnosis– Probability of disease after (+ ) or (–) test

• Drawbacks:– Sensitive to prevalence of disease– Prevalence of disease in general population may not be

the same as that of patients you see in clinic/ER.– Not all test results can be categorized as “+” or “-”.

For these reasons, some consider PPV & NPV “Old School”.


Likelihood Ratios

• Likelihood Ratio is how much more likely is it that someone with this finding has the disease, compared to someone who doesn’t. It does NOT vary with prevalence.

Technically, the + LR is how much more likely someone is to get any positive test result if they have disease, compared to someone who doesn’t.

“Diagnosis”: Likelihood ratio

LR = SENSITIVITY 1 - SPECIFICITY

“Diagnosis”: What do all the numbers mean?

The Likelihood Ratio is a diagnostic weight;

It tells you by how much a given diagnostic test result will raise or lower the probability of having the disorder.

Pretest Probability: the chance that the pt has disease, prior to ordering any tests. This is often an estimation based on clinical experience

Post-test Probability: the chance that the pt has disease, given the results of the test


What do all the numbers mean?

A LR of 1.0 means the post-test probability is exactly the same as the pretest probability.

A LR >1.0 increases the probability of having the disorder.

A LR<1.0 decreases the probability of having the disorder.


Likelihood ratios >10 or <0.1 generate large changes from pre- to post-test probability and are generally considered significant.

Strong evidence to rule in/rule out a diagnosis.

Likelihood ratios of 5-10 and 0.1-0.2 generate moderate changes in probability.

Moderate evidence to rule in/rule out a diagnosis.

Likelihood ratios of 2-5 and 0.2-0.5 generate small changes.

Minimal evidence to rule in/rule out a diagnosis

Likelihood ratios 0.5-2 usually have little effect

Figure 1a: Likelihood Ratio Nomogram

LRs = Diagnostic Weights

-45%0.1

-30%0.2

-15%0.5Values between 0 and 1 DECREASE probability of disease

01.0

+15%2

+30%5

+45%10Values greater than 1 INCREASE probability of disease

Change in probability

Likelihood Ratio

From Steve McGee, Evidence Based Physical Diagnosis

Table 2a: Likelihood Ratios of Tests for the Diagnosis of Appendicitis

Likelihood ratio

• DVT– Homan’s sign +LR 1.5– Doppler + LR 39

• ANEMIA– Conjunctival rim pallor +LR 16.7

Summary Diagnostic Test

D I S E A S EPresent Absent TOTALS

Positive True

Positive

False

Positive

ALL Positives

Negative False

Negative

True

Negative

ALL Negatives

TOTALSAll with

disease

All without disease

Entire population

T

E

S

T

Sensitivity Specificity

PPV

NPV

Common pitfalls

• Results reported as relative risk – (ex. Migraines, CVA & OC)

• Results that came from recalculating the data after trial was done – (Post-hoc analysis) (ex. Hot study)

• Over-interpreting results• Relying on just one study (ex. Mg for heart dz),

a poor study, or wrong type of study (ex. HRT)• Confusing statistical significance with clinical

significance (ex. Drugs for BPH)• Not looking at CI’s • Not considering who funded study

Steps of EBM-5 A’s


Core of EBP

“Supposing is goodbut finding out

is better.”

Mark Twain

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Giải quyết các vấn đề lâm sàng: Cơ sở từ y học chứng cứ GiẢNG VIÊN : GS TS BS LÊ HOÀNG NINH