Selecting Evidence for Comparative Effectiveness Reviews

1. Selecting Evidence for Comparative Effectiveness Reviews Melissa McPheeters, PhD., MPH Associate Director, Vanderbilt University Evidence-based Practice Center

2. Overview • Why use selection criteria? • What do they look like in the context of a systematic review? • When should they be set? • How do they affect the conduct and interpretation of the review?

3. CER Process Overview

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

5. Types of Criteria • Population descriptors • Intervention descriptors • Outcome descriptors • Study design • Study size • Source of literature (including grey lit)

6. Adult, community dwelling females Study of a screening tool for depression United States only Hospital-based studies only N>200 Randomized controlled trials Articles published in English or German Some Example Criteria

7. Selecting Criteria • Review study goals • Assess analytic framework and key questions • Tie criteria to PICO(TS) • Set criteria before beginning abstract review

8. 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 can’t be compared.

9. 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

10. Bias in this context • Distortion of the estimate of effect that comes from how studies are selected to be included • Affects the applicability or “external validity” of the review itself

11. For example, 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 • Or – selection criteria may be set to include more of a certain study type that either over or under estimates effectiveness

12. Basic Questions • What is the relevant population? • What is the intervention of interest? • To what exposure is the intervention being compared? • What outcomes are relevant? • Should time to outcome be limited? • In what setting should the results be applicable?

13. Considerations • Grey literature: New technologies may have substantial grey literature, including govt. reports and trade journals • Non-English articles may be useful for certain types of interventions (e.g. CAM) • Study size limitations may depend on what is available • Easier to set for observational studies • Large bodies of efficacy/effectiveness lit may be made up of small trials

14. Exercise 1 • What would you do … • If you were asked to review the literature on transition support for adolescents with autism entering adulthood? • Before seeing the key questions, consider the categories of criteria that we will want to apply.

15. Apply PICOTS • Population – condition, disease severity and stage, co-morbidities, patient demographics • Intervention – dosage, frequency, and method of administration • Comparator – placebo, usual care, or active control • Outcome – health outcomes, morbidity, mortality, QoL • Timing – Duration of follow-up • Setting - Primary, specialty, in-patient, co-interventions

16. 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? PICOTS

17. 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, about children specifically with Asperger syndrome but not other ASDs?

18. 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?

19. Selection Criteria • Efficacy: RCTs only • Low risk: No prior preterm birth • No. of studies: 11 studies

20. OAB Study • Management of Overactive Bladder among Women • Considerations: • OAB is a fairly difficult condition to define • Treatments include pharmacologic, behavioral, CAM and procedural – and each area includes very different types of studies • Its study is often combined with other types of urological conditions such as stress incontinence or prostate issues

21. Set two criteria and consider the potential implications: Minimum study size Gender of study participants Exercise 2

22. Study Size • 50 at study start • Implications: • Excluded for size only: 79 • Excluded for N < 20: 36 • Excluded for N 20-29 23 • Excluded for N 30-39 8 • Excluded for N 40-49 12

23. 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

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

25. Types of Studies? • Limit to RCTs? • Include observational studies? • If so, which kinds? • What is the value of case series? • What counts as a case series?

26. Example 3 • 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

27. Observational Studies • Types • Cohorts (with comparisons) • Case controls • Case series • Registries/databases

28. Observational Studies • Well-done observational studies can address issues of applicability and need for longer-term outcomes if they: • Include more representative patient populations • Have relevant comparators • Report more meaningful clinical outcomes over longer timeframes • May be a better source of information about harms

29. Positive findings may be more likely to be published in high-profile journals published in English Therefore, to include only English may overestimate the positive effect of an intervention Empirically, the bias associated with limiting one’s review to English only has been shown to be small Some content areas may be more heavily published in the foreign literature (e.g., some CAM interventions) Foreign Literature

30. Cesarean Delivery • NIH-OMAR State-of-the-Science conference on outcomes of cesarean delivery on maternal request

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

32. 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 

33. 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 versus planned vaginal • Lowest rung: Comparisons of maternal and neonatal outcomes from actual modes of delivery

34. Summary • Selection criteria (aka inclusion/exclusion) are an essential tool for setting the scope of the review • 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