Where is the evidence? PHRM2010

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Where is the evidence? PHRM2010

• Judith Coombes
• The University of Queensland/Princess Alexandra
  Hospital

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What is evidence based medicine?

• Evidence-based medicine(EBM) is the integration
  of best research evidence with clinical expertise
  and patient values (Sackett et al 1999)

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A model of Evidence Based decisions
Patient Values
Clinical Expertise
Decision
Best research evidence
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Realisations

• Daily need for valid up to date information
• Inadequacy of traditional resources
• Gap between clinical judgment which ? over time
  while up to date theoretical knowledge ? over
  time
• Time limitation for finding evidence

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FIVE steps

• Convert information needs into an answerable
  question
• Find the best evidence
• Appraise validity, impact and applicability
• Integrate appraisal with clinical expertise
• Evaluate performance

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Answerable question

• The patient-73 yr old female
• main intervention-clopidogrel
• comparison treatment-aspirin
• clinical outcome-reduce mortality

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(No Transcript)
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Does an intervention work?

• Case reports
• Clinical experience
• Case series
• Case control study
• Cohort study
• Randomised, placebo controlled clinical study

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FIVE steps

• Convert information needs into an answerable
  question
• Find the best evidence
• Appraise validity, impact and applicability
• Integrate appraisal with clinical expertise
• Evaluate performance

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Find the best evidence

• Merck Manual says Aspirin 650-1300mg no mention
  of clopidogrel
• Cochrane database-1 review 2000 (amendment 2005)
  significant benefit but ? size
• Clinical Evidence (BMJ) viewed 27.4.08 uses
  cochrane 2005 review says doubtful benefit
• Medline-pubmed 66 clinical trials in English
• CAPRIE 1996- significant difference
• CHARISMA 2006- clopidogrel plus aspirin

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Implications for practice

• The cost of treating 100 patients for two years
  with clopidogrel, at about US800 per patient per
  year, totals about 160,000 to prevent one
  vascular event. As this is likely to exceed the
  average cost of the vascular event prevented, it
  seems prudent, at this stage at least, to infer
  that thienopyridines should not replace aspirin
  as the first choice antiplatelet agent for all
  high vascular risk patients. However, clopidogrel
  would seem to have a role for patients who are
  intolerant of, or allergic to, aspirin, provided
  we accept the caveat that we do not have direct
  evidence of the relative effectiveness of
  thienopyridines compared with aspirin in these
  patients because they were excluded from the
  randomised trials.

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Developments

• Strategies for finding and appraising evidence
• Systematic reviews-Cochrane Collaboration
• Evidence-based journals
• Information systems bring info in seconds
• Effective strategies for lifelong learning and
  improving clinical performance
• EBM as a teaching/learning tool

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Systematic reviews

• Different to conventional narrative reviews
• Very useful way of presenting the accumulated
  results from primary research
• Systematic approach used to minimise bias and
  random errors

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Why do we need systematic reviews of the evidence?

• No-one can possibly read, or find, all the trials
  and all the data about all specific clinical
  questions
• Once found, trials may appear to give conflicting
  or contradictory results

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Cochrane Collaboration LOGO
   
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Strength of evidence
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How to obtain access to systematic reviews

• Internet sites
• eg. www.clinicalevidence.com
• www.cebm.utoronto.ca
• The Australasian Cochrane Centre - Flinders
  University, SA
• www.cochrane.org.au
• Evidence Based Guidelines NPS (Aus) and NICE
  (UK)
• National Prescribing service NPS
• www.NPS.org.au
• National Institute of Clinical Excellence
• www.NICE.org.uk

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FIVE steps

• Convert information needs into an answerable
  question
• Find the best evidence
• Appraise validity, impact and applicability
• Integrate appraisal with clinical expertise
• Evaluate performance

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Now we have found some evidence. Can we apply the
evidence to this case?

• Validity
• Impact
• applicability

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Is the systematic review valid?

• Is the review of randomised trials
• do the methods describe-
• finding and including all relevant trials
• how validity of individual trials was assessed
• were the results consistent from study to study

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Validity (CAPRIE)
Was the assignment of patients to treatments randomised? YES
Was the randomisation list concealed? YES
Was follow-up of patients sufficiently long and complete? 1.91 yrs
Were all patients analysed in the groups to which they were randomised? Yes Were patients and clinicians kept blind to treatment? Yes
Were the groups treated equally, apart from the experimental treatment? YES
Were the groups similar at the start of the trial? YES
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Impact

• Calculate the absolute benefit (or risk
  reduction)
• Now the number needed treat (NNT) and for how
  long
• calculate the absolute risk of harm

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Impact
Clopidogrel versus Aspirin Outcomes MI, STROKE, or vascular death combined After 1 year Clopidogrel versus Aspirin Outcomes MI, STROKE, or vascular death combined After 1 year Relative risk reduction (RRR) Absolute risk reduction (ARR) Number needed to treat (NNT)
CER EER CER EER CER CER-EER 1 ARR
5.83 5.32 8.7 0.51 200
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Applicability

• How is our patient different from the study
  patient previous stroke subgroup didnt do as
  well, 72 men mean age 62.5 yrs
• Is this a treatment the patient will form a
  partnership with us to follow- WILL IT BE
  SUBSIDISED- it costs much more

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eTG

• For initial antiplatelet therapy, aspirin alone
  or the combination of aspirin plus dipyridamole
  (modified-release) are acceptable options
• aspirin 100 to 300 mg orally, daily (although
  doses down to 30 mg daily may be adequate)
•    OR
• dipyridamole (modified-release)aspirin 20025 mg
  orally, twice daily. Note 1
•      
• Due to enhanced efficacy, the combination of
  dipyridamoleaspirin is preferred in patients
  with moderate or greater absolute risk of
  recurrent stroke events. It should also be
  considered in patients with recurrent stroke
  events despite aspirin therapy.
• Headache is the most frequent adverse effect with
  combination therapy and may be overcome by
  initiating treatment with smaller doses.
• Dipyridamole alone may be used in patients
  intolerant of both aspirin and clopidogrel

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eTG

• Clopidogrel, a platelet aggregation inhibitor,
  was shown in the CAPRIE trial to be modestly
  more effective than aspirin in the prevention of
  serious high-risk vascular outcomes (stroke,
  myocardial infarction, vascular death). This
  trial showed a relative risk reduction of 8.7
  for clopidogrel over aspirin, with a similar
  magnitude of risk reduction seen for the outcome
  of stroke alone (7.3). However, because of the
  small absolute risk reduction (approximately 0.5
  per year) and the cost of the drug, clopidogrel
  is mainly used as second-line therapy in patients
  who are either intolerant of aspirin (eg those
  with gastrointestinal bleeding) or have developed
  recurrent cerebral ischaemic events while on
  aspirin (so-called aspirin failures). For such
  patients, use
• clopidogrel 75 mg orally, daily (blood monitoring
  is not necessary).
•   More recently, clopidigrel has been tested in
  two clinical trials in combination with aspirin.
  The MATCH trial tested the addition of aspirin
  75 mg daily to baseline clopidogrel in a stroke
  or TIA population comprising a high proportion of
  patients with small-vessel stroke syndromes
  associated with hypertension and diabetes. The
  addition of aspirin to clopidogrel did not
  significantly reduce the risk of the primary
  endpoint (a composite of ischaemic stroke,
  myocardial infarction, vascular death or
  rehospitalisation for acute ischaemia), but did
  result in significantly more life-threatening
  bleeds (2.6 versus 1.3). The CHARISMA study
  tested the addition of clopidogrel 75 mg to
  baseline low-dose aspirin (75 to 162 mg) in two
  study populationsa high-risk primary
  prevention group and a secondary prevention group
  combining patients with cardiovascular,
  cerebrovascular (approximately 35 of patients)
  and peripheral arterial disease. Overall there
  was no reduction in the primary end point of
  stroke, myocardial infarction or vascular death.
  Therefore, clopidogrel plus aspirin should not be
  used for long-term preventive therapy in patients
  with cerebrovascular disease.

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Relevance of evidence based medicine to
pharmacists

• All areas of practice require decisions about
  optimal therapy (including no therapy) to improve
  patient outcomes
• Information often comes to the pharmacist in an
  incomplete fashion
• Pharmacists giving advice and being proactive in
  therapeutics need accurate information sources

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Some limitations of evidence based medicine

• Many questions do not have answers!
• Evidence from populations - ?relevance to
  individual
• Trials - not real usage
• Lack of local ownership of recommendations
• Clinical effectiveness vs cost effectiveness

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Combined approaches

• Evidence based
• Consensus
• Local guidelines
• Pharmacists can act as a focal or facilitation
  point

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Summary

• Evidence based medicine is an effective tool to
  maximise optimal outcomes for our patients
• Pharmacists need to learn how to incorporate
  evidence based principles in their practice
• Pharmacists can contribute to local
  implementation of evidence based guidelines