Methodological Issues in Systematic Reviews: Formulating Questions (Text Version)
Slide Presentation from the AHRQ 2009 Annual Conference
On September 16, 2009, Thomas A Trikalinos made this presentation at the 2009 Annual Conference. Select to access the PowerPoint® presentation (3.3 MB).
Slide 1
Methodological Issues in Systematic Reviews: Formulating Questions
Thomas A Trikalinos, MD, PhD
Co-Director, Tufts Evidence-based Practice Center
Slide 2
Asking the right question
Image: An image of two men is show. One man is in a guillotine.
Slide 3
We will cover
- PICO(TS) approach to generate answerable research questions
- Analytic framework to identify potential questions
- Other considerations in formulating questions
Slide 4
Systematic Review/Meta-Analysis
? Question - Systematic Review/Meta-Analysis - ! Answer
Slide 5
Systematic review protocol
- Well focused study question [ PICO(TS) ]
- Identification of studies (studies design, source, search strategy)
- Eligibility criteria (study, patient, and disease characteristics, treatments, outcomes)
- Data extraction (definition of outcomes, quality assessment)
- Data summary and analysis (outcomes used, intention to treat)
Slide 6
PICO(TS) approach to formulating answerable research questions
- Population (participants)
- Intervention
- Comparator
- Outcome
- Time (duration)
- Study design (experimental / observational, N)
Slide 7
Poorly formulated question:
What drugs should be used to treat patients with hypertension?
Slide 8
Example: The Well - Formulated Question
The Cochrane Collaboration "How to Conduct a Cochrane Systematic Review" 1996
Image: A flowchat is shown that is labeled "Does drug therapy decrease long-term morbidity and mortality in older persons with mild to moderate hypertension?"
Slide 9
Diagnostic test research question - test performance
What is the diagnostic accuracy of sestamibi scan to detect ACI in patients in the ED
Outcomes- Sensitivity
- Specificity
- Technetium-99m sestamibi scan
- Comparator
- AMI
- Unstable angina
- Adults with symptoms suggestive of acute cardiac ischemia and non-diagnostic ECG seen in the ED
Slide 10
Diagnostic test research question - clinical impact -
What is the clinical impact of sestamibi scan to detect ACI in patients in the ED?
Outcomes- False negative discharges from the ED
False positive admits
Deaths
- Technetium-99m sestamibi scan
- Comparator
- AMI
- Unstable angina
- Adults with symptoms suggestive of acute cardiac ischemia and non-diagnostic ECG seen in the ED
Slide 11
We will cover
- PICO(TS) approach to generate answerable research questions
- Analytic framework to identify potential questions
- Other considerations in formulating questions
Slide 12
Approach to (de)constructing research question
- Question of interest is often over-arching and not directly addressable
- Ex. How to manage hypercholesterolemia?
- Need to break it down into answerable subunits
- Multiple questions frequently needed
- Final answers (recommendations) typically involve additional information, balancing the benefits and harms, feasibility, costs, etc
Slide 13
Simplified Evidence Model Linking Biological Effects (intermediate) and Health Outcomes
Image: An model of Linking Biological Effects (intermediate) and Health Outcomes is shown.
Slide 14
USPSTF generic analytic framework for screening topics
Image: The framework for screening topics is shown.
Slide 15
Analytic framework for omega-3 FA intake and CVD
Image: An image of Analytic framework for omega-3 FA intake and CVD is show.
Slide 16
We will cover
- PICO(TS) approach to generate answerable research questions
- Analytic framework to identify potential questions
- Other considerations in formulating questions
Slide 17
Problems defining interventions and comparators
Pulmonary rehabilitation vs conventional care
Exercise training
AND OPTIONALLY
Education
Breathing exercises
Inspiratory muscle training
Psychosocial behavioral interventions
Vs.Conventional care
AHRQ Evidence Report/Technology Assessment
Pulmonary rehabilitation for COPD, 2007; www.ahrq.gov
Slide 18
OK, but there are things that are self-evident, no?
Slide 19
Would You Say You "Had Sex" If ..?
Image: An image of an article titled "Would You Say You "Had Sex" If ..?" is shown.
JAMA 1999;281:275-7
Slide 20
Percentage Indicating "Had Sex" (95% Confidence Interval)
Image: An image of a table is shown The table breaks down the behaviors of women, men, and overal of indivuals perception of having sex.
JAMA 1999;281:275-7
Slide 21
Problems measuring genetic variables: (TA)n in ER alpha
Ann Intern Med 2006;145:255-64
Slide 22
Standardizing across labs
Ann Intern Med 2006;145:255-64
Slide 23
Problems in coming up with questions
- Sometimes you don't know what should be the question because there is not yet agreement among investigators about the meaning
- Pre-emptive analgesia: different investigators have different ideas about what it is
- Solution: Rather than pick an arbitrary definition, try to group what has been studied into several similar categories and address them, this will provide evidence of the spectrum of mechanisms
- Question: What is the effect of timing of analgesics on post-op requirements of pain medication and patient outcomes?
Slide 24
Problems with diagnosis
- Varying definitions (lack of an adequate reference standard)
- Different levels of rigor
- Tradeoffs between rigor and real world practice (sinus puncture to diagnose sinusitis vs. actual clinical practice: efficacy vs. effectiveness)
Slide 25
Image: Skull showing sinus trouble
Slide 26
Possible definitions of acute bacterial sinusitis and their effect
| Duration of symptoms |
< 2 weeks |
< 3 weeks |
< 4 weeks |
|---|---|---|---|
|
Diagnostic criteria |
|||
|
Sinus puncture and culture |
Low likelihood for false positive |
||
|
Radiography |
May include many patients with viral infections |
||
|
Clinical findings |
May include many patients with viral infections |
||
Slide 27
Many diseases have diverse manifestations
Slide 28
Some components of the clinical and paraclinical spectrum of poliomyelitis
Jenicek M. Epidemiology: The logic of modern medicine. Epimed, Montreal, 1995.
Slide 29
B. Hypothetical infectious disease example
Jenicek M. Epidemiology: The logic of modern medicine. Epimed, Montreal, 1995.
Slide 30
Management of Clinically Inapparent Adrenal Mass (Adrenal Incidentaloma): The Evidence Report
NIH State-of-the-Science Conference.February 4, 2002
Slide 31
Incidentaloma is NOT a disease
- The prevalence of this phenomenon and the pathologies and their likelihood will depend on:
- Patients with known cancers or not
- Presenting signs and symptoms
- Patient's age and sex
- Biochemical activity findings
- Initial diagnostic test used (CT, US, MRI)
- Size of the mass (lower limit)
Slide 32
What are the pathologies reported among adrenal incidentaloma?
- Adenoma
- Adrenocortical carcinoma
- Angiomyelolipoma
- Cyst
- Epithelial carcinoma
- Hyperplasia
- Hematoma
- Lymphoma
- Metastases
- Myelolipoma
- Neurinoma
- Pheochromocytoma
- Regenerative hepatic nodule
- Renal angiomyolipoma
- Retroperitoneal fibrosis
- . . . more
Slide 33
Some possible definitions of incidentaloma
Slide 34
Issues in formulating a question
- Narrow versus broad (for individuals/ subgroups or entire population)
- Clinically meaningful and useful (based on sound biological and epidemiological principles)
- Very broadly defined questions may be criticized for mixing apples and oranges
- Very narrowly focused questions have limited generalizability and sometimes may lead to biased interpretations / conclusions
Slide 35
Benefits of getting the questions right at the start
- Improves clarity of the problem
- Facilitates subsequent steps of the systematic review
- Helps select right kind of studies for review
- Anticipates issues, resource needs
- Improves efficiency, reduces needs to revisit questions / re-review papers, minimizes wasted efforts
Slide 36
Summary
- PICO(TS) method is a very useful technique to formulate answerable research questions
- Analytic framework can be useful to visualize and think about related issues
- Defining criteria
- Biologically meaningful
- Question and criteria guide the entire systematic review process


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