Challenges in Evidence Synthesis for Gynecologic Care (Text Version)
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 (OAB)
Historically: detrusor instability, urge incontinence.
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.
Comparative Effectiveness Research (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 (CPP)
- 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:
- 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 (AUB)
- 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, Key Questions (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.