8th WorkshopPrática Clinica Baseada em Evidências

Angra do Reis, 2014

REVISÕES SISTEMÁTICAS:Como interpretá-las?

SYSTEMATIC REVIEWS:How to interpret them

Luz M. Letelier Associate Professor

Internal MedicineFaculty of Medicine, P. Universidad Católica de Chile

PLEASE…..Don’t start here…..Sze, Man Wai et al. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapyCochrane Database of Systematic Reviews. Issue 5, 2011.

Meta-analysis might be the most glamorous part of a Systematic Review.DO NOT FORGET it is just a tool to combine the results of included studies.

SYSTEMATIC REVIEWMETA – ANÁLISIS

Navegando pelas RSsSailing arround SRs.....

What is a SR & why are they useful.

How to use / analyze a SR.

Estamos atualizados em relação a conhecimento médico?

Are we up-to-date on medical information?

How many articles do you read a month?

How many should you read?

2005: Medline index 560.000 new articles /year = 1.534/ día.

2013: Medline index 734.000 new articles /year = 2.010/día

Então, tem algum problema?We are in trouble

• Need to handle large amounts of current information to deliver the best care to our patients

• Is difficult to find and then appraise all the information.

You’ve become expert on efficient literature searches.

CLINICAL SCENARIOYour last patient, a heavy smoker, asks if he should start taking vitamin A to prevent lung cancer.

During this workshop

SEARCH FOR EVIDENCE

• P: SMOKERS• I: VITAMIN A • C: NO TREATMENT• O: REDUCE LUNG CANCER

Using PubMed Search Terms

Hits2003

Hits2006

Hits2009

Hits2012

Hits 2014

Beta-carotene or vitamin A

33.000 40.065 45.656 51.468 55.045

(Beta-carotene or vitamin A) and lung cancer

751 875 1107 1.197 1.275

Clinical Query: Therapy & specific =112 hits

BETA-CAROTENE FOR LUNG CANCER PREVENTION

NEJM 1994; 330:1029-1035 • The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and

Other Cancers in Male Smokers. Beta Carotene Cancer Prevention Study Group The Alpha-Tocopherol

• CONCLUSIONS: We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene. In fact, this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects.

N Engl J Med 1996 May 2;334(18):1150-5 • Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and

Cardiovascular Disease. CARET Study

• CONCLUSIONS: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

BETA-CAROTENE FOR LUNG CANCER PREVENTION

Cancer Causes Control 2000 Aug;11(7):617-26

• Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (PHS).

• CONCLUSIONS: The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.

Am J Clin Nutr 2000 Oct;72(4):990-7

Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts

CONCLUSION: Data from 2 cohort studies suggest that several carotenoids may reduce the risk of lung cancer.

BETA-CAROTENE FOR LUNG CANCER PREVENTION

Cancer Epidemiol Biomarkers Prev. 2006 ;15(8):1562-4. • Lung cancer chemoprevention: a randomized, double-blind trial in Linxian, China. • Conclusion: Supplementation with combinations of vitamins and minerals at

nutrient-repletion levels for 5.25 years did not reduce lung cancer mortality in this nutrient-inadequate population in Linxian, China.

Rev Med Suisse. 2010 May 26;6:1046-8, 1050-2.• Nutrition and physical activity: two targets for cancer prevention.

The scientific evidence is presented in a report of the World Cancer Research Foundation (WCRF). Protective factors towards overall cancer risk are fruit and vegetable consumption and physical activity. Overweight and obesity, intakes of alcoholic beverage, fat, salt, high temperature cooked and processed red meat, increase cancer risk. In addition, beta-carotene systematic supplementation could increase lung cancer risk in smokers.

Resumindo (Summarizing) BETA-CAROTENE AND LUNG CANCER PREVENTION

• May have harmful as well as beneficial effects. 1994• No benefit and may have adverse effect on lung cancer 1996• No overall effect of beta-carotene on total cancer 2000• Several carotenoids may reduce the risk of lung cancer. 2000• Supplementation did not reduce lung cancer mortality 2006• Beta-carotene could increase lung cancer risk in smokers 2010• Betacarotene no late effect on cancer incidence. 2014

QUAIS RESULTADOS EU DEVO APLICAR?WHICH RESULTS SHOULD I APPLY?

Why are the studies result so different and even contradictory?

Are the studies similar? In their risk of bias (validity)? Are they looking at the same population? Is it the same intervention? etc

ENTÃO...SO....

Besides handling lots of information we need to decide which results to believe....and apply to our patient.

• Além de lidar com muita informação, precisamos decidir quais resultados para acreditar... e aplicar ao nosso paciente.

SOLUÇÃOS?

• Collect some information and give your best opinion.

• NARRATIVE REVIEW – expert opinion

DESTROY THE EVIDENCEDESTRUIR AS PROVAS

SOLUÇÃO

• Summarize ALL available information using explicit, reproducible methods for finding, selecting and appraising the information.

REVISÕES SISTEMÁTICAS

SYSTEMATIC REVIEW

DEFINIÇÃO

REVISÕES SISTEMÁTICAS SYSTEMATIC REVIEW

Summary of ALL available information regarding a specific clinical question, using explicit methods towards reducing bias.

Questions on Therapy / Diagnosis / Prognosis

META - ANALYSISStatistical method to combine (summarize) the results of studies included in a Systematic Review.

• Método estatístico para combinar (resumir) os resultados dos estudos incluídos em uma revisão sistemática

DEFINIÇÃO

REVISÕES Reviews

Narrative Review a topic in several

different aspects. No explicit method for

searching the evidence. No explicit method for

selecting information. No explicit method for

appraising information Should not have statistical

analysis.

Systematic Answers a specific question. Explicit method for

searching the evidence Explicit method for

selecting information. Explicit method for

appraising information. Might have statistical

analysis (Meta-analysis)

Navegando pelas RSs Sailing arround SRs…next STOP

SRs what are they & why are they useful.

How to use/appraise a SR

Appraising a SR: STEP 1

IS THERE A SENSIBLE SPECIFIC QUESTION?a) Any antibiotic for any infectionb) Any macrolide for any respiratory infectionc) Any dose of claritromicine for Community

Acquired Pneumonia (CAP) ATS I&IId) Claritromicine 250 mg vs 500mg bid for CAP in

patients 20 years old with asthma and allergy to penicillin.

REMEMBER: NOT TOO BROAD NOT TOO NARROW

Appraising a SR: STEP 2SEARCH FOR ALL AVAILABLE EVIDENCE

Broad search strategy: Several databasesHand searches:

References Abstracts from conferences

Ask experts, researchers on the topic and pharmaceutical industry for unpublished data.

AIM: GET ALL AVAILABLE EVIDENCE AVOID PUBLICATION BIAS

Evaluating publication bias:

Funnel plot 1

• A. Symmetric distribution of studies, no publication bias.

• B . Asymmetric distribution. Small studies with negative results undetected. Probably publication bias.

1 Cochrane Handbook for Systematic Reviews of Interventions 5.2. The Cochrane Collaboration, 2009.

Appraising a SR: STEP 3

CRITICAL APPRAISAL OF INCLUDED STUDIES

Very importantAvoid “garbage in” “garbage out”

Could be done:DescriptiveQuantitative: Scores (ie. Jadad score)

COCHRANE COLLABORATION’S APPROACH to assess risk of bias of included studies

Cochrane Handbook for Systematic Reviews of Interventions 5.0.2 The Cochrane Collaboration, 2009.

Appraising a SR: STEP 4

REPRODUCIBILITY OF PROCESS

2 independent reviewers:SelectionInclusionCritical Appraisal

REDUCE BIAS AND RANDOM ERROR

Meta-analysis: statistical tool to combine the results of included studies.Forest Plot

Like any statistics: crucial to use the correct data setBefore looking at the forest plot (meta-analysis) BE SURE the data

is right.Critical appraisal of data gathering process = systematic review

(step 1 to 4).

…E FINALMENTE…META – ANALYSIS

Appraising a SR: STEP 5

STATISTICAL ANALYSIS (META – ANALYSIS)

Test for heterogeneity: Q statistic (χ2) p-value I2 0 to 100

Sources of heterogeneity.

I2=4,21%

I2=8,45%

O que fazer com esta informação?What would you do with this information?

O que fazer agora?What would you do now?

Remember

Always consider all posible outcomes. Consider patients values or preferences. SRs do not make decisions. SRs inform decisions.

Back to our question....

Lung cancer prevention and beta-carotene.

Searching the Cochrane Database of Systematic Reviews.

P: SMOKERSI: VITAMIN A C: NO TREATMENTO: REDUCE LUNG CANCER

BETA-CAROTENO Y PREVENCION DE CANCER PULMONAR

• Drugs for preventing lung cancer in healthy people M Cortés-Jofré, JR Rueda, G Corsini-Muñoz, C Fonseca-Cortés, M Caraballoso, X Bonfill Cosp.

Published Online: 17 OCT 2012. Assessed as up-to-date: 7 DEC 2011

• Includes 9 RCTs of low risk of bias• P: > 203.000 healthy participants with low and high risk (smokers or

exposed to asbestos) of lung cancer.• I/C: Vitamin A, vitamin C and selenio compared to placebo

• Treatment duration 2 - 9 years• O: lung cancer and mortality

• Follow up 4 – 12 years

Drugs for preventing lung cancer in healthy people M Cortés-Jofré et al.The Cochrane Database of Systematic Reviews 2012 Issue 10

MENSAGENS PARA CASATAKE HOME MESSAGES

MENSAGENS PARA CASASYSTEMATICS REVIEWS :Summarizes best evidence regarding a specific

question.Should have explicit methods to minimize bias.Should be critically appraised by consumers (VOCE). If methodologically well done (low risk of bias) =

highest level of evidence. Important tool to evidence based health care as they

help handling large amounts of information.Before looking at the meta-analysis look at the risk of

bias of the SR.SRs do not make decision, they inform decisions.

OBRIGADA

PERGUNTASCOMMENTSCOMPLAINTS

COFFEE BREAK!!!