Expressions and illustra0ons of treatment effect. Ka$e Program Dalhousie University

Transcription

1 Expressions and illustra0ons of treatment effect Ka$e Program Dalhousie University

2 The following slides demonstrate how data from clinical trials can be expressed. Slides provide insights regarding how certain expressions can be misleading and other clinically accurate and intui$ve. Details are provided to show how various expressions of effect are calculated (e.g., RR, RRR, ARR, NNT). Also provided are various figures, again to demonstrate how figures can be manipulated to support clinical interpreta$on of results. Finally, sugges$ons for presen$ng data are offered.

3 Understand rela$ve vs. absolute differences

4 Which An$depressant is Most Outcome: suicide anempt Dangerous? A. More than doubles the risk B. Increases the risk by 136% C. Increases the risk by 0.15% D. Leads to a new suicide anempt in 1 person for every 667 treated?

5 Media: Television A study just released today reports that an$depressants more than doubles the risk of suicide anempts.

6 Which An$depressant is Most Dangerous? New suicidality An$depressant 0.26% No an$depressant 0.11% Fergusson et al. BMJ 2005 A. More than doubles the risk B. Increases the risk by 136% C. Increases the risk by 0.15% D. Leads to a new suicidality in 1 person for every 667 treated? 0.26 / 0.11 > % (100%) % (136%) = 0.26% (236%) 0.26% % = 0.15% 15 in 10,000, or 1 in X X = 667

7 A new an$- diabe$c medica$on can reduce the risk of re$nopathy by 75% Baseline risk (no treatment New risk (with treatment) Relative risk reduction Absolute risk reduction Number needed to treat High risk n=64, p=0.05 Moderate risk n=268, p=0.05 Low risk n=848, p=0.05 Negligible risk n=2884, p= % 75% 75% 75%

8 A new an$- diabe$c medica$on can reduce the risk of re$nopathy by 75% Baseline risk (no treatment New risk (with treatment) Relative risk reduction Absolute risk reduction Number needed to treat x y 100(1-y/x) x-y 100/(x-y) High risk 40% 10% 75% 30% 4 Moderate risk 12% 3% 75% 9% 12 Low risk 4% 1% 75% 3% 34 Negligible risk 1.2% 0.3% 75% 0.9% 112

9 Comment: Rela$ve Risk When comparing two treatment op$ons knowing the rela$ve risk is important when you know the baseline risk. It is not helpful, and it can be misleading without knowing the baseline risk. Knowing the rela$ve risk only is not enough.

10 CLASS STUDY Celecoxib vs. NSAIDs: GI symptoms and complica$ons JAMA 2000 Celecoxib is associated with a 41% reduc$on in ulcer complica$ons including bleeding, perfora$on, and obstruc$on and ulcer symptoms (p=0.02)

11 CLASS STUDY Celecoxib vs. NSAIDs: GI symptoms and complica$ons JAMA 2000

12 Rela$ve Risk (RR) and Rela$ve Risk Reduc$on (RRR) of GI complica$ons and symptoms 41% 59%

13 Rela$ve Risk (RR) and Rela$ve Risk Reduc$on (RRR) of GI complica$ons and symptoms Amount risk has been reduced (relative risk reduction) New risk compared to old risk (relative risk) 41% 59% Baseline risk (NSAIDs) New risk (celecoxib)

14 Calcula$ng RR and RRR 3.5% 2.1%

15 Calcula$ng RR and RRR 2.1% 3.5% = 0.59 (x100 = 59% RR) RRR = 100% - RR = 41%

16 In Absolute Terms, What is the Reduc$on in Risk of GI Complica$ons and Symptoms? 3.5% 2.1% 3.5% 2.1% = 1.4% ARR

17 Two Truthful Statements Two Very Different Impressions Relative risk reduction Celecoxib is associated with a 41% reduc$on in ulcer complica$ons including bleeding, perfora$on, and obstruc$on and ulcer symptoms (p=0.02) Absolute risk reduction Celecoxib is associated with a 1.4% reduction in ulcer complications including bleeding, perforation, and obstruction and ulcer symptoms (p=0.02)

18 Know how to calculate and interpret ARR and NNT

19 How many people need to be treated with celecoxib to prevent 1 person from experiencing an ulcer complica$on or symptom? ARR=x%- y% 3.5% - 2.1% = 1.4% NNT=100/ARR 14 cases prevented for every 1000 treated 1000 = X 14 1 X is the number of people you need to treat to prevent one case X = 72 NNT = 72

20 Interpre$ng NNT & NNH The number of people that need to be treated to result in one person benefi0ng from (or being harmed by) the treatment. Am I impressed? 1. What is the number? 2. What is the outcome 3. What is the interven0on? 4. How does this compare with other op$ons 5. How precise is the es$mate? 6. Is the data valid?

21 Interpre$ng NNT Problem Interven0on vs. alterna0ve Outcome NNT CHF (mod- severe) Spironolactone vs. placebo Death (2 y) 9 (7 to 16) Hypertension ASA CV events 176 (90 to 3115) Depression Folic acid + SSRI vs. SSRI only Clinical response 5 (3 to 30) Earwax Docusate vs. triethanolamine Full view of tympanic membrane 3 (2 to 6) Flu Influenza vaccine vs. placebo Flu (clinically diagnosed) 12 (7 to 27) For more, refer to

22 Keep in Mind P- value Provides the probability (p) of anaining the results observed simply by chance P<0.05 and P>0.05 is a false dichotomy (p=0.049 ~~ p=0.051) A p- value does not tell you If study was well designed If bias was present If confounders exist If a drug works or not How well it works Confidence Interval Conven$onally 95% (90%, 99%) If a study was repeated 100 $mes, 95 of 100 calculated confidence intervals would include the TRUE effect. (roughly) we can be 95% confident that the calculated confidence interval of a single study includes the TRUE effect Clinically inspect the width of the interval to determine the precision of the es$mate of effect

23 Estimates and certainty Point estimate and 95% CI p-value A B Small sample size &/or high SD studies C D E Large sample size &/or low SD studies Mean difference in treadmill time (min) Favours CCB Favours ACE inhibitor

24 Which studies show a clinical advantage of CCB over ACE inhibitors? A Statistical significance Yes Clinical significance Yes B No Maybe C Yes Maybe D No Maybe E Yes No Mean difference in treadmill time (min) Favours CCB Favours ACE inhibitor

25 Figures can be crafted craftily

26 Figures Also Can Exaggerate Risk of a Ulcer Complication or Ulcer Symptom Percentage 3 2 Percentage GI Complications & Symptoms GI Complications & Symptoms Celecoxib NSAIDs Celecoxib NSAIDs CLASS STUDY. Celecoxib vs. NSAIDs: GI symptoms and complications. JAMA 2000

27 Cumulative rate of stroke or systemic embolism NEJM Sep 17, 2009

28 Cumulative rate of stroke or systemic embolism NEJM Sep 17, 2009 What s the approx. 2 year risk per group?

29 Which is better for symptoms of schizophrenia? Csernansky et al. NEJM 2002

30 Which is better for symptoms of schizophrenia? PANSS Risperidone Haloperidol Baseline Final Baseline Final Baseline Final Total symptoms Positive symptoms subscale Negative symptoms subscale Csernansky et al. NEJM 2002

31 Ensure your numbers and figures are not misleading

32 Ka$e Program: presen$ng data Shingles Preven$on Study Results Outcome Placebo Event rate Zostavax RRR ARR Time (Yrs) NNT 95% CI Herpes zoster overall 3.3% 1.6% 51% 1.7% 4 yrs Herpes zoster age % 2.2% 37% 1.3% 4 yrs Reference text box 32

33 Ka$e Program: presen$ng data Shingles Preven$on Study Results Outcome Placebo Event rate Zostavax RRR ARR Time (Yrs) NNT 95% CI Herpes zoster overall 3.3% 1.6% 51% 1.7% 4 yrs Herpes zoster age % 2.2% 37% 1.3% 4 yrs PH neuralgia overall 0.42% 0.14% 66% 0.3% 4 yrs PH neuralgia age % 0.21% 67% 0.4% 4 yrs Reference text box 33

34 Ka$e Program: presen$ng data ARBs Reduc$ons in HF Hospitaliza$ons Outcome Placebo Event rate Drug RRR ARR Time (Yrs) NNT 95% CI Hospitaliz ns (candesartan) 24% 20% 18% 4% 3.5 yrs Hospitaliz ns (valsartan) 18% 14% 24% 4% 2 yrs Reference text box 34

35 Ka$e Program: presen$ng figures To use this balloon in your presentations Click on it Press Ctrl-C (copy) Go to the slide where you want to use the balloon Press Ctrl-V (paste) Position the balloon where you want it and change the data In Slide Show view, the balloon will appear with a mouse click. Event rate 24% vs 20% - Hosps RRR 18% ARR 4% NNT 23 (14 41) 3.5 yrs

36 Ques$ons & Further Help Dr Mike Allen Director Evidence-based Programs Dalhousie CME For supportive tools visit: 36