Systematic Review Module 3: Systematic Review Module 3: Study Eligibility CriteriaStudy Eligibility Criteria

Melissa McPheeters, PhD, MPH Melissa McPheeters, PhD, MPH Associate Director Associate Director

Vanderbilt University Evidence-based Practice CenterVanderbilt University Evidence-based Practice Center

Learning ObjectivesLearning Objectives

To understand the role of selection criteria in framing a systematic review

To know when and how to set selection criteria

To understand the effect of selection criteria on interpretation of a review

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CER Process OverviewCER Process Overview

Prepare topic:

· Refine key questions

· Develop analytic frameworks

Search for and select

studies:

· Identify eligibility criteria

· Search for relevant studies

· Select evidence for inclusion

Abstract data:

· Extract evidence from studies

· Construct evidence tables

Analyze and synthesize data:

· Assess quality of studies

· Assess applicability of studies

· Apply qualitative methods

· Apply quantitative methods (meta-analyses)

· Rate the strength of a body of evidence

Present findings

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Study Selection CriteriaStudy Selection Criteria

Function the same in systematic reviews as in primary research

Should reflect the analytic framework and key questions

Are powerful tools for widening or narrowing the scope of a review

Provide information to determine whether reviews can be compared or combined

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Some Example CriteriaSome Example Criteria

Adult, community-dwelling females Study of a screening tool for depression United States only Hospital-based studies only N > 200 Randomized controlled trials

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Using Broad CriteriaUsing Broad Criteria

Can be as broad as all related studies Helpful for exploring “what is known” May result in too much literature to

feasibly review or disparate literature that cannot be compared

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Using Narrow CriteriaUsing Narrow Criteria

May return too little literature Can result in inability to answer the

intended question Helpful in culling homogenous literature Can reduce size of the literature to a

manageable scope

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Bias in this ContextBias in this Context

Distortion of the estimate of effect that comes from how studies are selected for inclusion

Affects the applicability or “external validity” of the review itself

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Examples of Bias in this ContextExamples of Bias in this Context

Included studies may not have been conducted in the patient population whose care the review is intended to affect– e.g., the use of studies of twin pregnancies

in a review of preterm labor management for low-risk women

Selection criteria may be set to include more of a certain study type that either overestimates or underestimates effectiveness

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Selecting CriteriaSelecting Criteria

Review study goals Assess analytic framework and key

questions Tie criteria to PICOTS Set criteria before beginning abstract

review

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Basic Questions Basic Questions

What is the relevant population?What is the relevant population? What is the intervention of interest?What is the intervention of interest? To what exposure is the intervention To what exposure is the intervention

being compared? being compared? What outcomes are relevant?What outcomes are relevant? Should time to outcome be limited?Should time to outcome be limited? In what setting should the results be In what setting should the results be

applicable?applicable?

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Exercise 1Exercise 1

What would you do if you were asked to review the literature on transition support for adolescents with autism spectrum disorders (ASD) entering adulthood?

Before seeing the key questions, consider the categories of criteria that we will want to apply.

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Apply PICOTSApply PICOTS

Population—condition, disease severity and stage, comorbidities, patient demographics

Intervention—dosage, frequency, method of administration

Comparators—placebo, usual care, or active control

Outcomes—health outcomes, morbidity, mortality, quality of life (QoL)

Timing—Duration of followup Setting—Primary, specialty, in-patient,

cointerventions

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PICOTSPICOTS

Population

Intervention Comparators

Outcomes

Timing

Setting

What constitutes an adolescent? What constitutes a diagnosis of ASD?

How is transition support defined? Do we compare to no transition support or

directly compare types of support? What are the goals for adolescents with ASD

as they transition to adulthood? Should they be individually focused?

How quickly should the outcomes be apparent?

Is transition support provided in multiple settings, such as schools, clinics, and the community?

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What Would You Do with…What Would You Do with…

A paper that was about “individuals over age 10”?

A paper that was about an intervention for individuals with a range of developmental disabilities?

Or, conversely, a paper that was specifically about children with Asperger’s syndrome but not other ASDs?

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Example of a Narrow ScopeExample of a Narrow Scope

What is the efficacy of home uterine activity monitoring for preventing preterm birth among women at low risk of a preterm birth?

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Implications of a Question Implications of a Question with Narrow Scopewith Narrow Scope

Efficacy: RCTs only Low risk: no prior preterm birth No. of studies: 11

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Overactive Bladder StudyOveractive Bladder Study

Management of OAB among women Considerations

– OAB is a fairly difficult condition to define– Treatments include pharmacologic,

behavioral, complementary and alternative medicine (CAM) and procedural—and each area includes very different types of studies

– Study of OAB is often combined with other types of urological conditions, such as stress incontinence or prostate issues

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Exercise 2Exercise 2

Set two criteria and consider the Set two criteria and consider the potential implicationspotential implications– Minimum study size

– Gender of study participants

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Study SizeStudy Size

50 at study start Implications

– Excluded for size only: 79

– Excluded for N < 20: 36

– Excluded for N 20 to 29: 23

– Excluded for N 30 to 39: 8

– Excluded for N 40 to 49: 12

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GenderGender

Studies had to include at least 75% women

This decision was based on expert opinion and the size and scope of the literature

40 studies were excluded with less than 75% women

27 additional studies would have been excluded had the review been limited to studies of only women

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Other ConsiderationsOther Considerations

What study designs should be What study designs should be included?included?

Include foreign studies? Other Include foreign studies? Other languages? Studies conducted in languages? Studies conducted in specific parts of the world?specific parts of the world?

Include “grey” or “fugitive” literature?Include “grey” or “fugitive” literature?

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Types of Studies?Types of Studies?

Limit to RCTs? Include observational studies?

– If so, which kinds?

What is the value of a case series? What counts as a case series?

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Example of Maternal-fetal Surgery Technical Brief

Included case series with N ≥ 2 Only 3 of 169 studies were RCTs, and

122 were case series Because of the relative newness of this

area of research, it was important to capture data even from studies without comparison groups

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Observational StudiesObservational Studies

Types– Cohorts (with comparisons)

– Case controls

– Case series

– Registries/databases

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Observational StudiesObservational Studies

Well-done observational studies can address issues of applicability and the need for longer-term outcomes if they:– Include more representative patient

populations– Have relevant comparators– Report more meaningful clinical outcomes

over longer time frames Observational studies may be a better

source of information about harms

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Foreign LiteratureForeign Literature

Positive findings may be more likely to be published in high-profile journals published in English

Therefore, to include only English-language journals may overestimate the positive effect of an intervention

Empirically, the bias associated with limiting one’s review to English has been shown to be small (Moher et al., 2000; Gregoire et al., 1995)

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Systematic Review on Cesarean Systematic Review on Cesarean DeliveryDelivery

Systematic review on outcomes of cesarean delivery on maternal request

Conducted for the National Institutes of Health-Office of Medical Applications of Research State-of-the-Science conference

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Exercise 3Exercise 3

Define the appropriate population group and comparator.

What other limitations would you put on included literature?

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The ChallengeThe Challenge

No evidence on outcomes of CDMR vs. other modes of delivery

Urgent need for actionable evidence Need to recognize and account for

confounders 

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SolutionSolution

Expand search to include proxies Weight rungs of evidence to account for

confounding– Highest rung: Trials of breech delivery, but only for

maternal outcomes

– Next rung: Planned cesarean vs. planned vaginal

– Lowest rung: Comparisons of maternal and neonatal outcomes from actual modes of delivery

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SummarySummary

Selection criteria are essential for setting Selection criteria are essential for setting the scope of the reviewthe scope of the review

They should be tied to the analytic They should be tied to the analytic framework, key questions, and PICOTS framework, key questions, and PICOTS

When properly applied, selection criteria When properly applied, selection criteria can reduce bias and support the can reduce bias and support the applicability of the reviewapplicability of the review

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