NAPLEX preparation: Biostatistics Ron Lyon, MS, RPH

Learning objectives At the completion of this lecture, you should be correctly answer multiple-choice questions related to: Descriptive statistics Describe the difference between relative and absolute risk and how to calculate Describe number needed to treat (NNT) or harm (NNH) and how to calculate Understand how to interpret a confidence interval Distinguish between the major types of cost-____ analyses

Mean, median and mode

Normal distribution and skew In a normal distribution, the mean, mode and median are all the same. Skew

Skew and standard deviation

Statistics that suggest whether you can trust the results p value (α [alpha]) Example: Probability that the observed differences between two drugs was actually due to chance Type 1 error: False positive First thing you check Power (1-β [beta]) Do you have enough patients or measurements to be able to distinguish actual results from pure chance? Example: The study didn’t show a difference between two drugs but would have if it included more patients. Type II error: False negative

No more bacon? Let‘s discuss statistics with clinical relevance

Relative difference The difference could be improvement or increased risk (e.g., relative risk) “eating 50 grams of processed meat each day -- the equivalent of two slices of ham -- can increase the risk of such cancer by 18%” Know how to calculate Relative Difference: ([incidence % group A]/[incidence % group B]) – 1 Usually reported as a percentage (e.g., 18%) sometimes as a number (e.g., 0.18) Related terms: odds ratio, hazard ratio

Absolute difference “eating 50 grams of processed meat each day -- the equivalent of two slices of ham -- can increase the risk of such cancer by 18%” Baseline incidence: ~1 in 200,000 = 0.000005 = 0.0005% With bacon: ~1.18 in 200,000 = 0.0000059 = 0.00059% Know how to calculate Absolute Difference: ([incidence % group A]-[incidence % group B]) 0.00059% - 0.0005% = 0.00009% increase

Number needed to (treat/harm) NNT: number needed to treat NNH: number needed to harm Know how to calculate Number needed to ____: 1/absolute risk 1/0.00009% = 1,111,111 people need to start eating 50 gm of processed meat each day in order to find one more case of colon cancer

Confidence Intervals Confidence interval of WHO assessment: (95% CI 1.10 to 1.28) 95% certain that the ‘true’ number is between a 10% and a 28% increase in the incidence of colon cancer When evaluating a study look to determine if the confidence interval suggests the ‘true’ number could be an increase OR a decrease. (95% CI -0.20 to +0.20) = (95% CI -20% to +20%)

Cost ______ analysis Cost effectiveness analysis ($ per successful outcome) What is the cost to achieve a successful outcome? Cost benefit analysis ($ only) Compares the benefits (total costs savings) of two or more different outcomes in terms of monetary units, including time value of money (net present value [NPV]) Cost utility analysis Adds a qualitative measure, usually QALY or DALY, to cost effectiveness analysis Cost minimization analysis If both treatments are equal, which one is less expensive

Cost effectiveness analysis What if we want to know how much it costs to achieve an outcome? Incremental cost to prevent a death ICER: incremental cost effectiveness ratio PCSK9-inhibitor example Death Absolute risk reduction: 0.22% Number needed to treat (NNT) to save one life: 455 Calculation: 1/0.22% Incremental cost to save one life? (ICER) 455 (NNT) x $14,144 (incremental medication cost) = $6.4 million What primary endpoint should be our focus? Secondary endpoints? How does this compare to current standard of care? NNT to achieve primary endpoint What’s the incremental cost of therapy per patient to achieve that endpoint? NNT x therapy cost comparison How does that cost/benefit (e.g., saved life, QALY) compare to other unrelated treatments? Pick medical treatment that is broadly accepted as cost beneficial. High risk patient statin example: The pooled estimates show values of $21571 per life year saved for a 10 year coronary heart disease risk of 20% and $16862 per life year saved for 10 year risk of 30%. Did you report absolute or relative risk reduction? Answer should almost always be absolute risk. If price was the entire plan budget would you pay it? Average life insurance policy is:

Cost-effectiveness analysis How much does it cost to achieve a defined outcome, such as quitting smoking or achieve normal body weight. Which one do you choose? Program Cost # of enrollees Success rate # of successes Cost per success (effectiveness) Smoking cessation $50,000 100 10% 10 $5,000 Weight loss $100,000 1,000 2% 20

Cost-benefit analysis Logically, if savings exceed the costs then you should do both programs. But you have limited start-up costs. Which one do you choose? Total Savings Program Cost # of enrollees Net savings per enrollee Net program savings Smoking cessation $150,000 $50,000 100 $1,000 $100,000 Weight loss $250,000 1,000 $150

Cost-utility analysis Adjusts cost-effectiveness to account for patient’s perceived value of their quality of life. QALY: quality-adjusted life year DALY: disability-adjusted life year Cost per success (effectiveness) QALY Cost per adjusted effectiveness Cost-utility Smoking cessation $5,000 0.5 $10,000 Weight loss 1.0

Cost ______ analysis Cost effectiveness analysis ($ per successful outcome) Effectiveness success Cost benefit analysis ($ only) Benefit overall savings Cost utility analysis Utility quality Cost minimization analysis Minimization lowest program cost