Systematic Review by HC121004042246

VIEWS: 5 PAGES: 56

									   EPI-214: Lecture 1
 Designing a Systematic
 Review (Meta-analysis)

        Dejana Braithwaite
       Assistant Professor
UCSF Department of Epidemiology and
           Biostatistics
 8 steps of a systematic review

1 Formulate research question

                                          Lecture 1
     2 Develop review protocol

        3 Initiate search strategy

           4 Apply inclusion /exclusion criteria

             5 Quality appraisal

                   6 Data abstraction


                               7 Analysis

           Lectures 1, 2 & 3         8 Interpret findings
                                                            Bent et al. 2004
What’s a Systematic Review?
“A review of the evidence on a clearly
  formulated question that uses
  systematic and explicit methods to
  identify, select and critically appraise
  relevant primary research, and to
  extract and analyze data from the
  studies that are included in the review.”
              Cochrane Collaboration
    …and meta-analysis?
Statistical combination of >= 2 studies to
produce single estimate of effect of
exposure
          Rapid growth

Pubmed search
  up to 3/29/2010:
  Systematic review   >1.5 million hits
  Meta-analysis       >40,000 hits

  up to 1/1/1990:
  Systematic review   300,994 hits
  Meta-analysis       845
The Cochrane Collaboration
 International systematic review initiative

• Archie Cochrane’s vision
  led to the opening of the
  first Cochrane centre (in
  Oxford, UK) in 1992 and
  the founding of the
  Cochrane Collaboration
  in 1993



     Source: http://www.cochrane.org/cochrane/archieco.htm
Meta-analysis news coverage




   Sattar N, et al. Statins and risk of incident diabetes: a collaborative
   meta-analysis of randomised statin trials. Lancet. 2010 Feb
   27;375(9716):735-42. Epub 2010 Feb 16.
 Systematic Review in context
            Traditional Systematic Meta-
            review      Review     analysis
Author      An           A team     A team
            individual
Search      IndividualBased on      Based on
strategy              a protocol    a protocol
Summary     Author’s  Can be        Summary
Conclusio   judgement qualitative   statistical
n                                   techniques
         Narrative review
Uses informal, unsystematic and subjective
  methods
Searching quality and synthesis not described

Disadvantage
    may have preconceived biases and may
    overestimate value of some studies
           Systematic review
Driven by evidence-based medicine movement
  and Cochrane collaboration

Advantages:
  Reduces bias
  Replicable
  Resolves controversy between conflicting findings
  Provides reliable basis for decision making
Use of meta-analysis as a prelude to
           clinical trials
Define pre-trial expected effect sizes
   sample size estimation

Determine effect estimates in key subgroups
 (e.g. based on gender, race/ethnicity or age)

Identify sources of heterogeneity in prior studies

Addressing these sources in design phase of
 new trial
 Use of meta-analysis in study
designs that are not clinical trials
Observational studies
  (e.g. case control, cohorts, cross-sectional
  prevalence studies, etc.)

 Studies evaluating diagnostic tests
  (sensitivity, specificity, predictive value)

 “IPD” = individual patient data studies

 Qualitative studies (meta-ethnography)
                         Meta-analyses

                                    IPD*




               Systematic reviews




*IPD= individual participant data
     Resources required for
      systematic reviewing
Can be time consuming
Team science (to reduce bias)
Bibliographic software (e.g. Endnote)
Statistical software (if appropriate)
          Step 1
Formulate research question
FINER criteria for research
        question
Feasible
Interesting
Novel
Ethical
Relevant

              Hulley S, et al. 2001 Designing Clinical Research
  Components of a research question (PICOT)
Patient:
   Disease or condition
   Stage, severity
   Demographic characteristics (age, gender, etc.)
Intervention (or “Exposure”):
   Type of intervention or exposure
   Dose, duration, timing, route, etc.
Comparison:
   Absence of risk or treatment
   Placebo or alternative therapy
Outcome:
   Risk or protective
   Dichotomous or continuous
   Type: mortality, morbidity, quality of life, etc.
                 PICOT

Type of Study:
   RCTs
   Cohort
   Case-control
   Cross-sectional
   All
         Formulation of an etiology
                 question
               Exposure                         Outcome



      Is smoking a risk factor for lung cancer?
          Patient   Exposure


Are people who smoke regularly at a greater risk of developing
    lung cancer as compared to those who do not smoke?

                     + cohort & case-control studies
          Outcome                                         Comparison
      Formulation of a diagnosis
              question
           Test (intervention)             Outcome



            Is MRI a good screening test for breast cancer?


Test (intervention)                                       Outcome


  Is MRI a more sensitive and specific test in diagnosing
   breast cancer as compared to mammography among
                     high risk women?
                                                 Comparison
        Step 2
Develop review protocol
                 Protocol
Background
Objectives
Pre-determined selection criteria
Planned search strategy
Planned data abstraction
Proposed method of synthesis of findings

     Establishment of an advisory group
        Step 3
Initiate search strategy
Where to locate studies

   Pubmed
   CINAHL
   Web of Science
   EMBASE
   PsychINFO
  Additional sources to identify
 studies for systematic reviews

Reference lists of retrieved articles
Manual searching of relevant publications
Experts in the field
Corresponding or first authors of published
  studies identified for the systematic review
Issues to consider
   Publication bias
    Search bias
     Pubmed citation example
Title: Interaction between 5-HTTLPR genotype, stressful life events
    and depression

Search terms:
  Life stress
  Life event
  Depression
  Depress
  Serotonin transporter
  5-HTTLPR
  Interaction
  Moderation



                                     Risch et al. JAMA 2010
          Step 4
Apply inclusion /exclusion
          criteria
       Inclusion/exclusion criteria
P - Population
I - Intervention
C - Comparison (if necessary)
O - Outcome
T - Type of study (if necessary)

Subject headings     OR    Textwords

      To find studies using all of the PICO
  elements:
      P and I and C and O (and T)
         Exclusion criteria
Keep log of excluded studies
Note reasons for exclusion
Have eligibility checked by more than one
 reviewer
Develop strategy to resolve
 disagreements
Search strategy example




             Risch et al. JAMA 2010
     Step 5
Quality appraisal
 Principles of quality appraisal

Quantitative studies
    Internal Validity
        allocation bias, confounding, attrition, statistical
        analysis, intervention integrity, withdrawals and
        dropouts

     External Validity (generalizability or applicability)
Are there quality appraisal
          tools?
       QUORUM for trials
Moher et al. Improving the quality of
 reports of meta-analyses of randomized
 controlled trials: The QUORUM
 statement. Lancet 1999;354:1896-1900
  MOOSE for observational
        designs
Stroup et al. Meta-analysis of
  observational studies in epidemiology.
  JAMA 2000;283:2008-12
      Qualitative research

Checklists available to assess the quality of
qualitative research. E.g. CASP appraisal tool
for qualitative research
(http://www.phru.nhs.uk/casp/qualitat.htm)
                         Recruit
                                              SELECTION BIAS
                         participants

                                              ALLOCATION BIAS
                         Allocate to
                         intervention and
                         control groups
Intervention group                                   Control group
                         CONFOUNDING

                         INTEGRITY OF
Implement intervention   INTERVENTION           Implement intervention

                         INTENTION-TO-TREAT
Follow-up participants                           Follow-up participants
                         WITHDRAWALS/
                         DROP OUTS

Measure outcomes         BLINDING OUTCOME          Measure outcomes
                         ASSESSORS

                         DATA COLLECTION
Analyze outcomes         METHODS                    Analyze outcomes

                         STATISTICAL ANALYSIS
     Step 6
Data abstraction
      Data abstraction

Design and pilot data abstraction form

Consider >1 reviewer

Consider blinding of observers to authors,
institutions and journals
 Data abstraction elements

publication details
study design
population details (n, characteristics)
intervention details
setting
outcomes and findings
Summary of study characteristics - example




                       Risch et al. JAMA 2009
Data abstraction examples

http://www.cochrane.org
Step 7
Analysis
   Synthesizing the Evidence
NARRATIVE SYNTHESIS
 primary studies explained qualitatively and
 summarized



META-ANALYSIS
 findings summarized and then combined
 statistically
     Is there heterogeneity?
       No                   Yes


Meta-analysis   Narrative     Deal with
                synthesis     heterogeneity?
                              (e.g. subgroup
                              analysis)
     Guidelines for narrative
            synthesis

Not available yet
     Step 8
Interpret findings
  Interpretation of results

Strength of the evidence
Explanations of effectiveness
Applicability
Trade-offs between benefits and
  harms
Implications for practice
     Strength of the evidence
• Describe the overall strength of the
  evidence
• The quality of the evidence
• The size and consistency of the results
  (particularly important in population based
  studies where a small effect at the
  community level may have much significance
  than the effect of comparable size at the
  individual level)
• Describe biases and limitations of the review
  process (e.g. difficulties in locating articles,
  inability to translate non-English articles)
 8 steps of a systematic review Bent et al. 2004

1 Formulate research question

                                          Lecture 1
     2 Develop review protocol

        3 Initiate search strategy

           4 Apply inclusion /exclusion criteria

             5 Quality appraisal

                   6 Data abstraction


                              7 Analysis

           Lectures 1,2 & 3          8 Interpret findings
        Section 1 Assignment
 Developing a Protocol for a Systematic Review

Homework:

Write a 1-2 page protocol to address the clinical problem
  described in the assignment.

								
To top