Analyzing Randomized Control Trial: ITT vs. PP vs. AT Proceedings from Journal club…..
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Transcript of Analyzing Randomized Control Trial: ITT vs. PP vs. AT Proceedings from Journal club…..
Analyzing Randomized Control Trial: ITT vs. PP vs. AT
Proceedings from Journal club…..
Vikash
Basic Analysis of RCT:• To calculate:
– Relative Risk (RR)– Relative Risk Ratio (RRR)– Attributable Risk (AR)– Absolute Risk Reduction (ARR)– Number Needed to treat (NNT)
• For Time dependant analysis – Survival Analysis by Kaplan- Mier or by Cox
Proportional Model.• Then, Apply test of Significance.
• For Dichotomous Outcome:
• RR = ID (Exposed)/ ID (Unexposed) = a/a +b / c /c +D• RRR = 1 – RR• ARR = ID (Unexposed) - ID (Exposed)
Disease Present
Disease Absent
Total
Experimental Group
a b a + b
Control Group
c d C + d
• Attributable Risk = (OR – 1) PE / 1+ [ (OR-1) PE] x 100• Where OR = Odds Ratio = ad / bc
• Number Needed to treat (NNT) = 1/ARR
• RR = 0. 4 /0.5 = 0.8• RRR = 0.2• ARR = 0.2 – 0.25 = - 0.05• NNT = 1/ARR = 20
TB No TB Total
Cont. Isoniazid
40 160 200
Isoniazid 6 month
50 150 200
Intention to treat Analysis• Also called As randomized or Method Effectiveness
analysis.• Compare outcome according to the randomized group
(Gold Standard).• Adherence to intervention not necessary.
Advantages:• Randomization is maintained:
– Treatment assignment is based on chance alone.– Randomization provides Theoretical foundation for
Statistical test of significance. Disadvantages:
– Doesn’t take into account Protocol violation.
• Group may not be comparable at the end.– Not adhering to treatment or vice versa.– Eligibility for the trial was incorrect.– Loss to follow up.
• Estimates of non – complied in the efficacy dilutes difference between groups.
• Analysis may underestimate adverse effect.
Why gold standard ?
• Randomization is maintained• Difficulty in defining compliance.• Effect in complied group may be due to factor of
compliance.
Per Protocol Analysis:
• Analyze only those who fully complied to protocol.• Doesn’t included cross- over in final analysis.• Provides fair idea of efficacy for treatment.• May be Biased (randomization compromised)
As treated Analysis:
• Subject analyzed according to treatment taken or not. (no relation with randomization).• Non compliant from treatment and vice versa analyzed
accordingly.• AT is shown if ITT shows no effect ( why trial done).
InterventionGroup
ControlGroup
Randomize
GotTreatment
Did NOT gettreatment
GotTreatment
Did NOT gettreatment
YESYES NO NOInterntion-to-Treat
YES
YES
DROP
NO
DROP
YES
NO
NO
Per protocol
As Treated
• Hypothetical Example: RCT to see the effect of Aspirin in incidence of
Myocardial Re-infarction in patient with h/o MI.
• ARR by ITT = 20.833% - 16.66% = 4.17%• ARR by PP = 23% - 16.66% = 6.34%• ARR by AT = 21.25% - 16.25% = 5%
Re- infarct No Re-infarct
Total (adhered to t/t)
Aspirin 40 (5) 200 240 (210)Placebo 50 (4) 190 240 (200)
References:• Redmond C, Armitage P editors. Biostatics in Clinical
Trials. 1st ed. Sussex. John Wiley & Sons ltd. 2001. p243- 6.
• Haynes RB, Sacket DL, Guyat GH, Tugwell P. Clinical Epidemiology. 3rd ed. Baltimore. Lippincott Williams & Wilkins.2006. p 95 & 116.
• Fletcher RW, Fletcher SW. Clinical Epidemiology: the essential. 4th ed. Baltimore. Lippincott Williams & Wilkins. 2005. p 136-9.