1. Systematic Review Module 3: Study Eligibility Criteria Melissa McPheeters, PhD, MPH Associate Director Vanderbilt University Evidence-based Practice Center

2. Learning 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 1

3. CER Process Overview 2

4. Study 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 3

5. Some 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 4

6. Using 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 5

7. Using 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 6

8. Bias 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 7

9. Examples 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 8

10. Selecting Criteria Review study goals Assess analytic framework and key questions Tie criteria to PICOTS Set criteria before beginning abstract review 9

11. 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 being compared? To what exposure is the intervention 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 applicable? In what setting should the results be applicable? 10

12. Exercise 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. 11

13. Apply 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 12

14. PICOTS 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? 13

15. 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? 14

16. Example 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? 15

17. Implications of a Question with Narrow Scope Efficacy: RCTs only Low risk: no prior preterm birth No. of studies: 11 16

18. Overactive 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 17

19. Exercise 2 Set two criteria and consider the potential implications Set two criteria and consider the potential implications – – Minimum study size – – Gender of study participants 18

20. Study 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 19

21. Gender 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 20

22. Other Considerations What study designs should be included? What study designs should be included? Include foreign studies? Other languages? Studies conducted in specific parts of the world? Include foreign studies? Other languages? Studies conducted in specific parts of the world? Include “grey” or “fugitive” literature? Include “grey” or “fugitive” literature? 21

23. 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? 22

24. 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 23

25. Observational Studies Types – – Cohorts (with comparisons) – – Case controls – – Case series – – Registries/databases 24

26. Observational 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 25

27. Foreign 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) 26

28. Systematic Review on Cesarean Delivery 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 27

29. Exercise 3 Define the appropriate population group and comparator. What other limitations would you put on included literature? 28

30. The Challenge No evidence on outcomes of CDMR vs. other modes of delivery Urgent need for actionable evidence Need to recognize and account for confounders 29

31. Solution 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 30

32. Summary Selection criteria are essential for setting the scope of the review Selection criteria are essential for setting the scope of the review They should be tied to the analytic framework, key questions, and PICOTS They should be tied to the analytic framework, key questions, and PICOTS When properly applied, selection criteria can reduce bias and support the applicability of the review When properly applied, selection criteria can reduce bias and support the applicability of the review 31