Announcements • Exams are graded. I’ll hand them back at end of class. Solution will be on the web. Many people did better than I think they’d guess… • Easy optional homework due Thursday. See web. (This is to get you to open the book and take a look at chapter 8.) Can only add to your homework score Example • A toxocologist* conducts an experiment to investigate the relation between PCB (industrial chemical and pollutant) exposure and estrogen production in breast cancer cells. • She conducts the following “concentration / response” experiment. *Following is from the research of Professor Kathleen Arcaro (department of Veterinary and Animal Sciences, Umass) Picture of a plate There are 48 “wells” on each plate. Breast cancer cells are grown in each 32 of them (dark circles). 24 of those wells contain a certain amount of PCB (one of several types of PCBs). White circles are not part of the experiment. After growth, a machine determines the amount of estrogen produced in each well. Left two columns are “controls” (no PCB in these wells) Experiment is repeated on 30 plates. One way to think about the data: Each plate provides one number (we’ll see a better way to analyze the data later): Plate Number 1 2 3 4 5 etc X (Overall Mean) S (Overall Std Dev) Average Average Estrogen Produced by minus Control Cell Estrogen production cells exposed to PCBs X1 = 1146.83 X2 = -95.67 X3 = -60.67 X4 = 160.17 X5 = 509.17 etc 516.24 1078.67 Summary of all 30 plates. Less estrogen in PCB exposed cells. 12 More estrogen in PCB exposed cells (relative to controls). 0 2 4 6 8 10 Each plate contributes one data point to this histogram. -500 0 500 1000 1500 Estrogen Production: PCB Exposed Cells - Control Cells This is an estimate of the distribution of X, not the distribution of X. 2000 Statistical Question: • A x > 0 says that more estrogen is produced by cells that are exposed to PCBs on average. • Observed x = 516.24, but there’s a fair amount of “noise” in the data (s = 1078.67). • Is this x statistically significantly positive? (in other words: If the experiment were repeated, how certain should we be that we’ll see x>0 again?) To answer the question, we need to know the probability distribution of x In general, the central limit theorem says that the sample mean has a normal distribution (when n>30 or so…) X ~ N(m,s2/n) We don’t know m or s, but we do have estimates: x = 516.24, s = 1078.67 This gives us a good guess at the distribution of X (i.e. A model for how X would behave if we took another sample): X ~ N(516.24, 1078.672/30) 0.0020 0.0010 0.0005 0.0 normal density 0.0015 Distribution of X-Bar N(516.24,1078.672/30) 0 500 1000 X-bar Informally, since 0 is in the “tail” of the distribution of X, then seeing an x < 0 is unlikely (i.e. these PCBs cause estrogen production on average) More formally: Confidence intervals for the mean • A 1-a% confidence interval for the mean: x +/- za/2s/sqrt(n) x and s are the sample mean and sample std deviation from n observations za/2 = number such that Pr(Z<za/2) = 1-a/2 Rough Interpretation: interval covers “inner” 1-a% of the best guess at x’s distribution 95% of the area under the curve Distribution of X 0.0010 0.0005 0.0 normal density 0.0015 0.0020 Observed x 0 130.44 500 920.44 1000 X-bar 95% confidence interval (a = 0.05) 516.24 +/- 1.96 (1078.67) / 5.48 516.24 +/- 385.80 = (130.44 , 902.44) x +/- za/2s/sqrt(n) • 95% confidence interval for mean estrogen production in cells + PCB – mean production in control cells • is (130.44 , 902.44). Since 0 is not in this interval, there’s “statistically significant” evidence (at 95% confidence) that mean estrogen production is higher for cells plus PCB. Meaning of 1-a% confidence interval: We can be “1-a% confident” that the true mean is in this interval… Note that the interval is the random thing. The true mean is a fixed number. Order these from narrowest to widest: 90% confidence interval 99% confidence interval 95% confidence interval 80% confidence interval Ordered from narrowest to widest: Narrowest: Widest: 80% confidence interval 90% confidence interval 95% confidence interval 99% confidence interval Common sense: we can say with high confidence that the mean is somewhere within an extremely wide interval… Math: z0.005 is bigger than z0.1 since the subscript describes a “tail” probability… za/2 (quick reference) • za/2 is a number such that Pr(-za/2<Z<za/2)=1-a where Z~N(0,1). • Examples: Area 1-a 1-a a/2 za/2 90% 5% 1.645 95% 2.5% 1.96 99% 0.5% 2.58 Note also: Pr(|Z|<za/2) = 1-a -za/2 area a/2 0 za/2 area a/2 95% of the area under the curve Distribution of X 0.0010 0.0005 0.0 normal density 0.0015 0.0020 Observed x 0 130.44 500 920.44 1000 X-bar 95% confidence interval (a = 0.05) 516.24 +/- 1.96 (1078.67) / 5.48 516.24 +/- 385.80 = (130.44 , 902.44) x +/- za/2s/sqrt(n) Distribution of X-Bar when mean Is lower limit If true mean is at lower confidence limit and the experiment is repeated, the probability of seeing the observed x or something larger is 0.025 (=a/2) 0.0010 This interpretation is more precise because the true mean is not random, the data are… 0.0005 Area 0.025 (=a/2) 0.0 normal density 0.0015 0.0020 A more precise interpretation of the 95% confidence interval 0 130.44 516.24 920.44 1000 If true mean is at upper confidence limit, then if the experiment is repeated, the probability of seeing the observed x or something smaller is 0.025 (=a/2) Distribution of X-Bar when mean Is upper limit 0.0010 0.0005 Area 0.025 (=a/2) 0.0 normal density 0.0015 0.0020 Equivalently… 0 516.24 920.44 1000 Calculation: Pr( X > observed x when lower limit is true mean) =Pr(X > x) Observed number Random variable =Pr( (X – lower limit)/(s/sqrt(n)) > (x – lower limit)/(s/sqrt(n)) =Pr(Z > [x – (x – za/2s/sqrt(n))]/[s/sqrt(n)] ) =Pr(Z > za/2) = a/2 by definition… CONFIDENCE INTERVALS FOR ESTIMATES OF PROPORTIONS • Now that Pedro is health,, what are your expectations for the Red Sox this season? Will make the playoffs 59% 90 wins 16% 80 wins 14% 70 wins 11% • Number polled (when I took poll) = 81 What’s a 90% confidence interval for proportion of people who think they’ll make the playoffs? Is 59% from 81 people significantly greater than ½ (at 90% confidence level?) Review: The CLT for proportions Let Xi = 1 if person i thinks the Sox will make playoffs. = 0 otherwise where i=1,…,81 (indexes people polled). Mean of Xi = p Variance of Xi = p(1-p) Xi~Bin(n=1,p) p = (X1+…+X81)/81 By central limit theorem, P ~ N(p,p(1-p)/n) Confidence Intervals for Proportions • 90% CI for proportion: p +/- z0.10/2sqrt[p*(1-p)/n] 0.59 +/- 1.64 sqrt(0.59*0.41/81) 0.59 +/- 0.0895 [0.505, 0.6795] (uses that p ~ N(p,p(1-p)/n) Confidence Intervals for Proportions • 90% CI for proportion: p +/- z0.10/2sqrt[p*(1-p)/n] 0.59 +/- 1.64 sqrt(0.59*0.41/81) 0.59 +/- 0.0895 [0.505, 0.6795] (uses that p ~ N(p,p(1-p)/n) In general, a 1-a level confidence interval is: estimator +/- za/2std error(estimator) p=0.59 Area=0.05 2 4 Area=0.05 Lower limit 0.505 Upper limit 0.6795 0 normal density 6 Distribution of P when true p = 0.59. 0.4 0.5 0.6 P-hat 0.7 0.8 p=0.59 2 4 Approximate Area=0.05 Lower limit 0.505 0 normal density 6 Distribution of P when true p = 0.505. 0.4 0.5 0.6 P-hat 0.7 0.8 p=0.59 Distribution of P when true p = 0.505. 2 4 Approximate Area=0.05 True p is in mean and variance Lower limit 0.505 0 normal density 6 Approximate because Distn of P is N(true p, (true p)(1- true p)/n) 0.4 0.5 0.6 P-hat 0.7 0.8 If the true p is 0.505, how “rare” is seeing the poll result of 59%? • “Rarity” = Pr( P > 0.59 when true p = 0.505) =Pr[ (P-0.505)/sqrt(.505*.495/81) > (0.59-0.505)/sqrt(.505*.495/81) =Pr( Z > 0.085/0.06) = Pr(Z>1.53) = 0.0630 p=0.59 2 4 Area=0.0630 Lower limit 0.505 0 normal density 6 Distribution of P when true p = 0.505. 0.4 0.5 0.6 P-hat 0.7 0.8 If the true p is 0.5, how “rare” is seeing and poll result of 59%? • “Rarity” = Pr( P > 0.59 when true p = 0.5) =Pr[ (P-0.5)/sqrt(.5*.5/81) > (0.59-0.5)/sqrt(.5*.5/81) =Pr( Z > 0.09/0.06) = Pr(Z>1.62) = 0.0526 (This is the p-value!) p=0.59 2 4 Area=0.0526 0.5 0 normal density 6 Distribution of P when true p = 0.5 0.4 0.5 0.6 P-hat 0.7 0.8 Differences between means • Can people discern a difference between Advil and generic ibuprofen on average? • Experiment: “Double Blind Study” – Randomly separate 80 people into two groups of 40 each. – Give one group Advil and generic ibuprofen to the other group. – “Blinding”: person handing out pills and people being tested don’t know which pill they’re getting (pills were dyed). – People report their opinion of how well the pill works (on a scale of 1 to 10). – When we did the experiment, 2 people from the Advil group dropped out. When might this matter? Results: Generic Group 0 0 2 2 4 4 6 6 8 Advil Group 2 4 6 8 10 2 4 6 score score X Advil = 6.35 S Advil = 2.32 n Advil = 38 X Generic = 6.03 S Generic = 2.47 n Generic = 40 Is X Advil – X Generic = 0.32. Is this “statistically significantly” greater than zero? 8 10 In General: 1-a confidence interval is “Estimate +/- za/2 se(estimate)” Variance of X Advil – X Generic is s2Advil /n Advil + s2Generic /n Generic Variance of X Advil – X Generic is s2Advil /n Advil + s2Generic /n Generic 1-a confidence interval is “Estimate +/- za/2 se(estimate)” When nAdvil and nGeneric are both >30ish, a 1-a confidence interval is XAdvil–XGeneric+/-za/2 sqrt(s2Advil/nAdvil + s2Generic /nGeneric) Not: sAdvil/sqrt(nAdvil) + sGeneric/sqrt(nGeneric) 95% CI for Advil / Generic Example 0.32 +/- 1.96 sqrt(5.38/38 + 6.10/40) = [-0.74,1.38] Can’t claim that people can discern a difference at 95% confidence. Is there a level of confidence at which we could make the claim? Suppose n = 1,000,000. Do you think we could claim a significant difference then?