Title: Top Trial Cheats
1Top Trial Cheats
- Dr Rod Stables
- The Cardiothoracic Centre
- Liverpool UK
- No Conflicts of Interest to Declare
2Presentation 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
3Identify 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
4Identify 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
5Not 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 ?
6Not 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
7SoS Trial Repeat Revasc Event Curve
8BASIL Trial Amputation - free Survival
9Solutions ?
- Clear exposition of patient flows
10Trial Profile and Patient Flow Diagram
11Solutions ?
- 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
12Odds and Risk
13Odds 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
14Example 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)
15Odds 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 !!
16From the Thesis of Dr R H Stables DM (Oxon) ..
17Relative 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
18Some Basic Rules
- Odds ratio correct in 2 x settings
- Backward investigation - Case control
19Case 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
20Some 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
21Mixing Efficacy and Safety Outcomes
22Mixing 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 ?
23Mixing 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
24Mixing 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
25Questions and Discussion