• Briefly explain what is meant by “Evidence Based Medicine”?
  • Give a classification for the levels of evidence used for therapeutic studies in EBM.
  • Explain what is meant by the term “intention to treat analysis”

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College Answer

a) EBM

Evidence-based medicine is the process of systematically reviewing, appraising and using clinical research findings to aid the delivery of optimum clinical care to patients

It involves considering research and other forms of evidence on a routine basis when making healthcare decisions. Such decisions include the clinical decisions about choice of treatment, test, or risk management for individual patients, as well as policy decisions for groups and populations.

b) Levels of evidence

(Any recognised system acceptable)

  • Level I - High-quality, multicentre or single-centre randomized controlled trial with adequate power; or systematic review of these studies
  • Level II - Lesser quality, randomized controlled trial; prospective cohort study; or systematic review of these studies
  • Level III - Retrospective comparative study; case-control study; or systematic review of these studies
  • Level IV - Case series
  • Level V - Expert opinion; case report or clinical example; or evidence based on physiology, bench research.

Level

Therapy/Prevention,  Aetiology/Harm

1a

Systematic review (with homogeneity) of RCTs

1b

Individual RCT (with narrow Confidence Interval)

1c

All or none (ie all patients died before the Rx became available, but some now survive on it; or when some patients died before the Rx became available, but none now die on it)

2a

Systematic review (with homogeneity ) of cohort studies

2b

Individual cohort study (including low quality RCT; e.g., <80% follow-up)

2c

"Outcomes" Research or ecologic studies (studies of group chics)

3a

Systematic review (with homogeneity) of case-control studies

3b

Individual Case-Control Study

4

Case-series (and poor quality cohort and case-control studies )

5

Expert opinion or based on physiology, bench research or "first principles"

Level

I

Evidence from a systematic review of all relevant randomised controlled trials

II

Evidence from at least one properly designed randomised controlled trial

III

III.1 Evidence from well-designed pseudo-randomised controlled trials

III.2 Evidence obtained from comparative studies with concurrent controls and allocation not randomised (cohort studies) or case control studies

III.3 Evidence obtained from comparative studies with historical controls

IV

Evidence from case series, opinions of respected authorities, descriptive studies, reports of expert (i.e. consensus) committees, case studies.

c) Intention to treat analysis

Analysis based on the initial treatment intent not the treatment eventually administered. Everyone who begins treatment is considered to be part of the trial whether he/she completes the trial or not. ITT analysis avoids the effects of crossover and drop-out

Discussion

Evidence based medicine is the system of critical evaluation of published data for applicability to the management of individual patients. David Sackett, a great pioneer of EBM, came up with a definition which seems to be frequently quoted, and therefore probably meets with the approval of the CICM examiners:

"Evidence based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research."

As for levels of evidence, we have several systems to choose from. Here are a couple:

Oxford centre for evidence based medicine:

  • Levels:
    • I - systemic review of all relevant RCTs
    • II - Randomized trial or observational study with dramatic effect
    • III - Non-randomized controlled cohort/follow-up study
    • IV - Case-series, case-control studies, or historically controlled studies
    • V – mechanism-based reasoning (expert opinion, based on physiology, animal or laboratory studies)
  • Grades:
    • A – consistent level 1 studies
    • B – consistent level 2 or 3 studies or extrapolations from level 1 studies
    • C – level 4 studies or extrapolations from level 2 or 3 studies
    • D – level 5 evidence or troubling inconsistent or inconclusive studies of any level

NHMRC levels:

  • Level I: systematic review of RCTs
  • Level II: RCT
  • Level III-1: pseudorandomised trial of high quality
  • Level III-2: cohort studies or case control studies - but with a control group
  • Level III-3: cohort studies with historical controls, or no control group
  • Level IV: case series

Intention to treat analysis:

This is the practice of preserving the bias-controlling benefits of randomisation by performing analysis of all patients according to which group they were randomised to, rather than according to which treatment they actually received.

  • "Once randomised, always analysed"
  • All enrolled patients have to be a part of the final analysis
  • This preserves the bias-protective effect of randomisation

Advantages

  • A more reliable estimate of treatment effectiveness
  • Prevents bias
  • Minimises Type 1 errors (false positives)
  • Supported by the CONSORT statement
  • When intention-to-treat analysis agrees with per-protocol analysis, it increases the validity of the study

Disadvantages

  • Treatment effect is diluted (ends up underestimated)
  • ITT is inaccurate unless there are negligible protocol violations
  • ITT alone is inappropriate for non-inferiority trials

References

References

Sackett, David L. "Evidence-based medicine." Seminars in perinatology. Vol. 21. No. 1. WB Saunders, 1997.

Sackett, David L., et al. "Evidence based medicine: what it is and what it isn't."Bmj 312.7023 (1996): 71-72.