Methodological Issues in Systematic Review: Formulating Questions (Text Version)

Slide Presentation from the AHRQ 2008 Annual Conference

On September 10, 2008, Joseph Lau, made this presentation at the 2008 Annual Conference. Select to access the PowerPoint® presentation (195 KB).

Slide 1

Methodological Issues in Systematic Review—Formulating Questions

• Joseph Lau, MD
  Tufts Medical Center Evidence-based Practice Center (EPC)
• AHRQ Annual Meeting
  September 10, 2008

Slide 2

Evidence Report/Technology Assessment

• Cover of Evidence Report/Technology Assessment: Effects of Omega-3 Fatty Acids on Cardiovascular Disease.

Slide 3

Analytic framework for omega-3 Fatty Acid (FA) intake and Cardiovascular Disease (CVD)

• Diagram depicts relationships among:
  • Target populations.
  • Omega-3 Fatty Acid Consumption.
  • Adverse Events.
  • Tissue/Plasma Levels.
  • Modifiers.
  • Intermediate Outcomes/Biological Effects.
  • Clinical Outcomes.

Slide 4

Specific Key Questions

1. What is the efficacy or association of omega-3 fatty acids (DHA, EPA or ALA supplements, and fish consumption) in reducing CVD events (including all-cause mortality, CVD mortality, non-fatal CVD events, and new diagnosis of CVD)? In patients without known CVD (primary prevention) and with known CVD (secondary prevention).

Slide 5

Specific Key Questions

2. Relative effects of omega-3 fatty acid sources, with specific emphasis on compositions, dosages, the ratio of omega-6 to omega-3 fatty acids, and potential interactions due to duration of intervention or exposure.
   • What adverse events related to omega-3 fatty acid dietary supplements are reported in studies?

Slide 6

Participants

• Primary Prevention—patients without prior history of cardiovascular disease.
  • Country.
  • Background diet.
• Secondary Prevention—patients with prior history of cardiovascular disease.

Slide 7

Interventions

• Fish:
  • Different kinds, preparation, amount, how intake was estimated.
• Fish oil supplements:
  • Eicosapentaenoic acid (EPA)/ Docosahexaenoic acid (DHA).
• α-linolenic acid [ALA] (walnut, canola oil, flax seed, etc.)

Slide 8

Outcomes (endpoints)

• Clinical outcomes (events).
  • Overall mortality.
  • Stroke.
  • Myocardial infarction.
  • Sudden death.
  • Revascularization.
• Surrogate/intermediate outcomes (biomarkers, measurements).
  • Blood pressure.
  • Lipid levels.

Slide 9

The PICO method to formulate research question on interventions

• Table lists Participants—Interventions—Comparator—Outcomes (PICO):
  • Primary prevention—Fish, fish oil, ALA—Placebo—Overall mortality.
  • Secondary prevention—Dosage—No control—Sudden death.
  • (Blank)—Background intake—Active comparator—Revascularization.
  • (Blank)—Duration—(blank)—Stroke.
  • (Blank)—(blank)—(blank)—Blood pressure.

Slide 10

Study design

• Randomized controlled trial (RCT).
• Cohort.
• Case-control.
• Cross-sectional.
• Other criteria.
  • Study size.
  • Year, language, etc.

Slide 11

Additional inclusion criteria

• Published English language literature.
• Experimental or observational studies.
• Reported original CVD outcome data and evaluated any potential source of omega-3 fatty acids.
• At least 5 human subjects.
• At least 1-year duration.

Slide 12

Issues in formulating a question

• Narrow versus broad (for individual or 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 may have no data or have limited generalizability and sometimes may lead to misinterpretations.