Challenges in Evidence Synthesis for Gynecologic Care

1. Challenges in Evidence Synthesis for Gynecologic Care Katherine E. Hartmann, MD, PhD Vanderbilt Evidence-based Practice Center September 20, 2011

2. Women’s Health Research • Delayed entry into federally funded research • Industry dominated early clinical trials • Tradition of databases & observational studies • Diagnostic dilemmas • Lack of consensus diagnoses • Use of intermediate measures predominated • Late uptake of patient reported outcomes

3. Scenario #1: Overactive Bladder Historically: detrusor instability, urge incontinence Anticholinergics Creation of a “label” within advertising campaign • Indication marketed to providers, patients, & payers • Norm established and drive for treatment created Research reported as relative improvements • Drugs approved on this basis • Absolute effects extremely modest • Side effects common and adherence untested

4. CER Approaches for OAB • Documented history of the “OAB” indication • Systematically reviewed prevalence literature • Conducted meta-analysis of absolute effects: voids per day, incontinence episode per week • Emphasized on patient satisfaction/PROs • Attended to harms • Noted head-to-head comparisons within company • Included behavioral approaches in review

5. Scenario #2: Chronic Pelvic Pain Large descriptive literature, numerous case series Extreme heterogeneity: • Definition of condition • Inclusion criteria • Conditions excluded • Clinical diagnosis of exclusion Short-term outcomes for a long-term condition No sham surgery comparison groups

6. CER Approaches in CPP Restricted to non-cyclic Documented expected prevalence of comorbidities Grouped findings along three axes: • Intervention • Inclusion methods • Outcomes (category and length of follow-up) Emphasized subsequent medication and surgery Noted absence of natural history and trajectory studies

7. Scenario #3: Uterine Fibroids Size, number, position poorly predict symptoms • Imaging outcomes problematic Patient reported outcomes key Masking of assessors rare Fertility desires influence modality • Age distributions of studies matter • Reproductive outcomes non-ignorable Follow-up too short to capture trajectory

8. CER Approach for Fibroids • Discussed evolution of imaging and relation of characteristics to symptoms • Addressed outcomes with relevance to reproductive intent – highlighted gaps • Covered topic of postmenopausal fibroids and HT • Extracted data about recurrence and timing of recurrence • Noted lack of natural history and trajectory studies • Summarized importance of symptom bother

9. Scenario #4: Abnormal Uterine Bleeding • Multiple biologically distinct pathways to AUB • Many terms imply known biology are applied based only on symptoms • Evaluation paradigms lack uniformity • Failure to respond to treatment often used as part of implicit diagnostic process • Distinctive primary care and surgical pathways • Little literature that informs sequence of care

10. CER Approach for AUB • Aligned framework, KQs, and methods with new consensus terminology • Aimed at informing the primary care frontline rather than surgical “end of the line” • Restricted to clinical trials of currently available modalities (drugs and surgeries) • Used “measles plots” and “multiplication tables” to illustrate the lack of common methods

11. Cross Cutting Recommendations • Compile total participants per intervention/outcome • Exclude observational studies from effectiveness • Quantify the gaps (n, % of studies lacking features, measles charts, other visuals) • Document entangled co-morbidities • Focus on factors that modify applicability • Truncate search to reflect contemporary practice

12. Remember Importance of Mapping Gaps Clearly delineating gaps invites: • Improved education of patients • Greater disclosure of risks/poorly defined risks • Enhancement of research methods • Design and conduct of research to fill gaps