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

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

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

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

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

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

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

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

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

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

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

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