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Top Trial Cheats

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Top Trial Cheats. Dr Rod Stables. The Cardiothoracic Centre. Liverpool UK ... Identify the Denominator: Tracking Trial Subjects. Need to follow the fate of ALL ... – PowerPoint PPT presentation

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Title: Top Trial Cheats


1
Top Trial Cheats
  • Dr Rod Stables
  • The Cardiothoracic Centre
  • Liverpool UK
  • No Conflicts of Interest to Declare

2
Presentation Outline
  • Examples without accusation
  • Three topic areas
  • Establishing the denominators
  • Lost or not evaluated at follow-up
  • Odds ratio v Risk ratios
  • Composite outcome measures
  • Mixing safety and efficacy measures

3
Identify the Denominator Tracking Trial Subjects
  • Need to follow the fate of ALL patients
  • From inclusion to outcomes
  • Warning signs !
  • Results expressed as simple age
  • Smokescreen phrases
  • In patients with outcome data
  • In evaluable (surviving) patients
  • When assessed at follow-up

4
Identify the Denominator Examples
  • Rickards and Stables CABRI long term follow-up
  • Widely presented (but never published)
  • Every result presented as a value
  • Masked incomplete follow-up
  • No data on gt120 Dutch patients
  • More sinister impact - reported outcome measures

5
Not Assessed for the Outcome Measure ?
  • Trial of drug A - exercise capacity in heart
    failure
  • 100 patients randomised 1 1 drug v placebo
  • Outcome measure
  • Mean exercise duration at FUP
  • Baseline exercise duration - equal
  • Follow up Drug 3.2 mins Placebo 2.4 mins
  • Clinical and statistical significance
  • Mechanism ?

6
Not Assessed for the Outcome Measure ?
  • Widespread implications
  • Incomplete QCA follow up in angiographic trials
  • Numerical handling of extreme examples
  • QCA - MLD of occluded vessel ? 0
  • QoL - score of dead patient 0 (?excluded)
  • Competing outcomes
  • ? mortality ? repeat revascularisation
  • Event curve analysis - No of patients at risk

7
SoS Trial Repeat Revasc Event Curve
8
BASIL Trial Amputation - free Survival
9
Solutions ?
  • Clear exposition of patient flows

10
Trial Profile and Patient Flow Diagram
11
Solutions ?
  • Clear exposition of patient flows
  • All event rates expressed n / d (p) (CIs)
  • Describe status of patients not assessed for
    outcome measures
  • Express rates with correct denominators eg
  • Repeat revasc rate per 100 patient years of Fup
  • Full description of complex data handling methods
  • QCA QoL etc

12
Odds and Risk
13
Odds and Risk
  • Throw one of a pair of dice - Aim - To get a
    6
  • Odds against 51 (Odds)
  • Event occurs 16 of all throws (Risk)
  • Scope for confusion and manipulation of data
  • . and audience
  • Most observers interpret odds ratio as relative
    risk

14
Example Relative Risk in a Classic RCT
  • Randomised trial Tx A v Tx B
  • Each group comprises 100 patients
  • Death rate on Tx A 50/100 ( 0.5)
  • Death rate on Tx B 25/100 ( 0.25)
  • Relative risk 0.5 / 0.25 2
  • (p values and confidence intervals)

15
Odds Ratio Calculation
  • Tx A No dead 50 (a) No alive 50 (c)
  • Tx B No dead 25 (b) No alive 75 (d)
  • Odds ratio ad/bc (50 x 75)/(25 x 50)
  • 3
  • Sounds more !!

16
From the Thesis of Dr R H Stables DM (Oxon) ..
17
Relative Risk and Odds Ratio
  • If event rate is low OR is approx RR
  • If OR is interpreted as RR it will overstate the
    risk (benefit)

Reported Ratio
Event Rate
18
Some Basic Rules
  • Odds ratio correct in 2 x settings
  • Backward investigation - Case control

19
Case Control Studies
  • Breast cancer patients - series of 200
  • History of OCP 50 (a) No OCP 150 (c)
  • Odds a/c 0.33
  • Age sex matched controls - series of 200
  • History of OCP 25 (b) No OCP 175 (d)
  • Odds b/d 0.14
  • Odds Ratio (a/c) / (b/d) a/c x d/b
  • Odds ratio ad/bc (50 x 175)/(150 x 25) 2.3

20
Some Basic Rules
  • Odds ratio correct in 2 x settings
  • Backward investigation - Case control
  • Multiple regression analyses
  • Report independent association strength
  • factor and outcome
  • In all others - RCT and cohort studies
  • Risk ratio applicable and best

21
Mixing Efficacy and Safety Outcomes
22
Mixing Efficacy and Safety Outcomes
  • Developing area - Subject of continued debate
  • CVA addition to MACE in revascularisation trials
  • PCI trials - MACE outcomes
  • ? Add in bleeding complications
  • Usually PCI related (puncture adjunct drugs)
  • Seems reasonable ?
  • Value in trials of antithrombotic therapy ?

23
Mixing Efficacy and Safety Outcomes
  • Cloud and confuse
  • Data analysis and reporting
  • Procedural development
  • BENESTENT 1
  • Stent puncture site complications 7 !!
  • Unrelated to coronary efficacy of stent
  • Reduced to current levels - changes in
  • Drugs devices techniques - experience

24
Mixing Efficacy and Safety Outcomes
  • Efficacy and safety issues
  • Parallel tracks - causation and solution
  • Further complicate analysis and reporting
  • Minefield of composite outcomes
  • Perhaps best avoided

25
Questions and Discussion
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