How to Analyze Therapy in the Medical Literature

(part 2)

Akbar Soltani. MD.Tehran University of Medical Sciences (TUMS)

Shariati Hospitalwww.soltaniebm.com

Three Step Guide in Using an Article to Assess Therapy

1. Are the results of the study valid?

2. What are the results? What measures of precision of effects were reported (CIs, p-values)?

3. How can I apply these results to patient care?

Measuring Risk: Relative Risk

Treated Placebo

Patients with HT 2365 2371

Strokes 96 149

Rate 0.04 0.06

Relative Risk (RR) = rate in exposed = 0.04 = 0.67

rate in nonexposed 0.06

SHEP. JAMA. 1991;265:3255-3264

Communicating risk:

10%

5%

10%

20% 20%

40%

RRR=?ARR=?

placebo

Measuring Risk: Relative Risk

Treated Placebo

Patients with HT 2365 2371

Strokes 96 149

Rate 0.04 0.06

Relative Risk (RR) = rate in exposed = 0.04 = 0.67

rate in nonexposed 0.06

SHEP. JAMA. 1991;265:3255-3264

4% 6%

Measuring Risk: ARR?

6%

4%

2%

Measuring Risk:Absolute Risk Reduction

Absolute Risk Reduction (ARR) is the absolute difference in event rates between the experimental and control patients.

Calculated by:

ARR = CER - EER = 0.06 - 0.04 = 0.02

In its decimal form the ARR is not easy to use!

Converted to a percentage - there is an absolute risk reduction of 2%

Measuring Risk: RRR?

6%

4%

2%

Measuring Risk:Relative Risk Reduction

Relative Risk Reduction (RRR) is the proportional reduction in event rates between the experimental and control patients.

Two ways to calculate:RRR = (1 - RR) = (1 - 0.67) = 0.33

ORRRR = CER - EER = 0.06 - 0.04 = 0.33

CER 0.06

Therefore, treatment reduced the stroke rate by 33% OR a RRR of 33% means that the new treatment reduced the

risk of death by 33% relative to that occurring among control patients

CER = control event rate

EER = experimental event rate

Usefulness of the ARR:Number Needed to Treat

Number Needed to Treat (NNT) is the number of patients a clinician needs to treat in order to prevent one additional adverse outcome.

NNT is for dichotomous outcomes.

Calculated by:NNT = 1/ARR = 1/0.02 = 50

Therefore, you would have to treat 50 hypertensive patients to prevent one stroke.

Number Needed to Treat

CER=0.06=100----------6

EER=0.04=100----------4

SO: 100-----------2

X------------1

50-----------1Calculated by:

NNT = 1/ARR = 1/0.02 = 50

Therefore, you would have to treat 50 hypertensive patients to prevent one stroke.

Why not just use RRR? PTH trial

CER = 6 % Age =70 + 7

EER = 3 %

ARR = CER – EER = 3%

NNT = 1/ARR = 1/ 0.03 = 33

CER = 1/1000 Age = 55 + 5

EER = 1/2000

ARR=1/1000-1/2000=1/2000

NNT = 1/ARR= 2000

Why not just use RRR?

CER EER RRR ARR NNT

0.6 0.4 33% 20% 5

0.06 0.04 33% 2% 50

0.006 0.004 33% .2% 500

RRR remains the same despite differences in absolute rate of events.

Why not just use RRR?

CER EER RRR ARR NNT

0.6 0.4 33% 20% 5

0.06 0.04 33% 2% 50

0.006 0.004 33% .2% 500

ARRs reflect underlying susceptibility of patients and provides more complete information.

Why not just use RRR?

CER EER RRR ARR NNT

0.6 0.4 33% 20% 5

0.06 0.04 33% 2% 50

0.006 0.004 33% .2% 500

NNTs provide a useful measure of the clinical effort that must be expended to avoid bad events.

Randomised trial of cholesterol lowering in 4,444 patients with CHD: the Scandinavian Simvastatin Survival Study (4S) Lancet 1994: 344; 1383-1389

• 4,444 patients recruited as a sample• inclusion criteria

– CHD and cholesterol 5.5 - 8 mmol/l• exclusion criteria

– planned cardiac surgery, HF, child bearing potential

• simvastatin Vs. placebo• double blind• Outcomes

– mortality, major coronary events, admissions for acute CHD, incidence of revascularisation procedures

4S Study: self evaluation

• Median follow up 5.4 y

• analyse by intention to treat

• Significant reduction in all cause mortality– 11.5% placebo Vs. 8.2% simvastatin– ARR = – RRR = – NNT = patients with CHD and cholesterol

5.5 - 8 need to treated with simvastatin (20 mg) for 5.4 years to save one life

4S Study Cont’d

• Median follow up 5.4 y

• analyse by intention to treat

• Significant reduction in all cause mortality– 11.5% placebo Vs. 8.2% simvastatin– ARR = 11.5 - 8.2 = 3.3%– RRR = (11.5 - 8.2)/11.5 = 29%– NNT = 1/ARR = 30

• 30 patients with CHD and cholesterol 5.5 - 8 need to treated with simvastatin (20 mg) for 5.4 years to save one life

Why NNT is not enough

• NNT for continuous outcome is difficult to calculate

• Time can be added to calculations cautiously • We can not compare NNTs from different

studies easily• Example: 2 RCT (Risedronate) 2 NNT! Can

we say Risedronate is better than Risedronate!

Three Step Guide in Using an Article to Assess Therapy

1. Are the results of the study valid?

2. What are the results? What measures of precision of effects were reported (CIs, p-values)?

3. How can I apply these results to patient care?

P Value or CI?

P Value or CI?

P Value or CI?

P Value or CI?

P Value or CI?

P Value or CI?

Confidence Intervals for Small Numerators

• Example: A new drug is given to 60 people. It seems to work, and has no serious adverse effects.

• The authors conclude it is "safe and effective." The upper limit for the 95% CI for any serious adverse effect is, or 5%.

• 95% confident of adverse event = 0/n – 3/n

Another example from textbooks!

• Based on one observational study in 94 women, no one report adverse reactions.

• Rule of 3: 3/94=upper limit of adverse effects that may not have been seen.

Three Step Guide in Using an Article to Assess Therapy

1. Are the results of the study valid?

2. What are the results? What measures of precision of effects were reported (CIs, p-values)?

3. How can I apply these results to patient care?

How can I apply the results to patient care?

• Were the study patients similar to my patient?

• Were all clinically important outcomes considered?

• Are the likely treatment benefits worth the potential harm and costs?

Thank you!