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Evidence Based Medicine (EBM)

This guide is designed to walk you through the Evidence Based Medicine process: the elements of a well-formulated clinical question, types of studies, and the key critical appraisal questions that help determine the validity of evidence.

Medline, PubMed and Scopus search strategies

Clinical scenario
Roger, a 26 year old student, has been diagnosed with major depression. He has tried three different antidepressant medications in the past with no improvement. Reluctant to try a further prescribed medication he asks about non-pharmacologic alternatives. You have heard that repetitive transcranial magnetic stimulation has been trialed for treatment resistant depression but you are not sure if its effectiveness has been proven. You tell Roger that you will look into this for him.

PICO

  • Patient: Patients with major, treatment-resistant depression (treatment failure after two or more courses of antidepressants)
  • Intervention: Repetitive transcranial magnetic stimulation (rTMS)
  • Comparison: No rTMS
  • Outcomes: Reduction in depressive symptoms, improved quality of life, remission of illness.

Clinical question
In patients with major, treatment-resistant depression, is repetitive transcranial stimulation effective in treating the depression?

Logic Grid (for exploring synonyms for main concepts in question)

Concept 1:
Treatment-resistant depression
Concept 2:
Repetitive transcranial magnetic stimulation
  • Treatment-resistant depression/depressive disorder
  • Treatment-resistant major depressive disorder
  • Treatment-resistant MDD
  • Treatment-refractory depression/depressive disorder
  • Pharmacoresistant depression/depressive disorder
  • Medication-resistant depression/depressive disorder
  • Repetitive transcranial magnetic stimulation
  • rTMS
  • Deep repetitive transcranial magnetic stimulation
  • DTMS

Medline search strategy
Using both MeSH terms and keywords and applying the Medline 'Reviews' and 'Therapy' Clinical Queries filters (found under 'Additional Limits' button):

PubMed Clinical Queries search strategy

Go to Clinical Queries and enter search string:

(treatment resistant depress* OR treatment resistant major depress* OR treatment resistant MDD OR Treatment refractory depress* OR pharmaco-resistant depress* OR pharmacoresistant depress* OR medication resistant depress*) AND (repetitive transcranial magnetic stimulat* OR rTMS OR DTMS)

Choose Therapy category and Narrow scope for best search specificity and precision.

Important to note:

  • Use brackets to separate strings of synonyms combined with OR from the AND operator
  • Operators AND/OR must be in uppercase in PubMed and PubMed Clinical Queries
  • You can exclude citations already found in Medline by adding NOT Medline[sb] to the end of the search string. This reduces the search set to newly published studies and reviews possibly not yet available in the Medline database. 

E.g. (treatment resistant depress* OR treatment resistant major depress* OR treatment resistant MDD OR Treatment refractory depress* OR pharmaco-resistant depress* OR pharmacoresistant depress* OR medication resistant depress*) AND (repetitive transcranial magnetic stimulat* OR rTMS OR DTMS) NOT Medline[sb]

This finds 5 clinically relevant studies (left column) and 9 systematic reviews (middle column). The third systematic review is a high quality one that was too recently published to appear in Medline.

Scopus search strategy

Will work also in Web of Science

"treatment resistant depress*" or "treatment resistant major depress*" or "treatment resistant MDD" or "Treatment refractory depress*" or "pharmaco resistant depress*" or "pharmacoresistant depress*" or "medication resistant depress*"

AND

"repetitive transcranial magnetic stimulat*" or rTMS or DTMS

AND

"systematic review" or "meta analysis" or metaanalysis or random*

Important to note:

  • Double quote marks are needed around phrases in Scopus to keep words together
  • Deselect subject areas Physical Sciences, Social Sciences & Humanities, and Life Sciences but keep Health Sciences selected for more precise results.

We found several systematic reviews of RCTs in the course of our searching.

Here are two below: 

To critically appraise these systematic reviews, we need to consider the following:

1. Were the methods used in the review valid?

  • Did it address a clearly focused question in terms of participants, interventions, comparisons, and outcomes (your PICO). Did it have clearly defined eligibility criteria?
  • Did the review include high quality, relevant studies
    • of robust study design (for example, randomised controlled trials)?
    • that addressed relevant questions?
    • selected by more than one independent reviewer?
  • Is it unlikely that the review missed important, relevant studies? 
    • Is the search strategy reproducible?
    • Did the search strategy include synonyms for all concepts?
    • Is the search strategy sufficiently comprehensive? 
  • Did the review include an assessment of the risk of bias of included studies and was this assessment incorporated into the review finding?
    • Is the method for assessing risk of bias reproducible and accurate?
    • Was the risk of bias assessment conducted by more than one independent assessor?
    • Was it incorporated into the review findings?
  • Did the review combine the results from studies and, if so, was it reasonable to do so?
    • Were the results similar from study to study (was an examination fo heterogeneity undertaken)
    • Were reasons for variations in results discussed? 

2. What are the results of the review?

  • What are the overall results of the review? 
  • How precise are the results? 

3. How relevant are the results to me? 

  • Were all important outcomes considered (from the points of view of individuals/patients, policy makers, healthcare professionals, family/carers, the wider community)?
  • Can the results be applied to my patient/s? Consider how well your patient(s) and practice setting compare with the review population.

We also located several RCTs. Here is one from Scopus.


To appraise this RCT, we would go through these questions:

  1. Was the assignment of participants to group randomised? 
  2. Was the allocation sequence concealed? 
  3. Were the groups similar at the baseline at start of the trial? 
  4. Were participants, health professionals and study personnel 'blind' to group allocation?
  5. Were all participants who entered the trial properly accounted for at its conclusion, and how complete was follow-up? 
  6. Were participants analysed in the groups to which they were randomised using intention-to-treat analysis?


References

Hoffmann T, Bennett S, Del Mar C. Evidence-based practice across the health professions. 2nd ed. Sydney: Churchill Livingstone; 2013. 416 p.

Straus SE, Glasziou P, Richardson WS, Haynes RB. Evidence-based medicine: how to practice and teach it. 4th ed. Edinburgh: Churchill Livingstone Elsevier; 2011. 293 p.