Chapter 2-98 Homework Problems Chapter 2-1. Describing variables, levels of measurement, and choice of descriptive Statistics Problem 1) Read in the data file From the Stata menu bar, click on File on the menu bar, find the directory datasets & do-files, which is a subdirectory of the course manual, and open the file: births_with_missing.dta. Problem 2) Listing data List the data for bweight. a) At the first “—more—” prompt, with the cursor in the Command window, hit the enter key a couple of times (notice this scrolls one line at a time). b) With the cursor in the Command window, hit the space bar a couple of times (notice this scrolls a page at a time). c) Click on the “—more—” prompt with the mouse (notice this scrolls a page at a time, as well) d) We have seen enough. Hit the stop icon on the menu bar (the red dot with a white X in the middle of it). This terminates (breaks) the output. Problem 3) Frequency table Create a frequency table for the variable lowbw. Problem 4) Histogram Create a histogram for the variable gestwks, asking for the percent on the y-axis, rather than proportions (density). Problem 5) Kernal Density Plot Create a kernal density for the variable gestwks, overlaying the graphs for male and female newborns. ______________________ Source: Stoddard GJ. Biostatistics and Epidemiology Using Stata: A Course Manual. Salt Lake City, UT: University of Utah School of Medicine. Chapter 2-98. (Accessed January 8, 1012, at http://www.ccts.utah.edu/biostats/ ?pageId=5385). Chapter 2-98 (revision 8 Jan 2012) p. 1 Problem 6) Box plot Create a boxplot for the variable bweight, showing male and female newborns on the same graph. Problem 7) Visualizing Distribution From Descriptive Statistics A variable has the following descriptive statistics: Mean = 45 Median = 50 SD = 3 Is this distribution symmetrical, or is it skewed? If skewed, is it left or right skewed? Problem 8) Visualizing Distribution From Descriptive Statistics A variable has the following descriptive statistics: Mean = 50 Median = 49 SD = 3 Is this distribution symmetrical, or is it skewed? If skewed, is it left or right skewed? Problem 9) Descriptive Statistics Obtain the descriptive statistics, including the median (50th percentile) for the variable bweight. Problem 10) Descriptive Statistics by Group Obtain the short list of descriptive statistics (N, mean, SD, min, max) for variable bweight, for both males and females. Problem 11) Best Choice of Descriptive Statistics to Describe a Variable’s Distribution Suppose you have a variable for race/ethnicity that is coded as: 1) Caucasian (White) 2) African-American (Black) 3) Asian 4) Native American 5) Pacific Islander Given this way of coding it, what is the level of measurement (measure scale) of this variable? What is the best way to describe it in a “Patient Characteristics” table of a manuscript? That is, what descriptive statistics would you choose to use? Chapter 2-98 (revision 8 Jan 2012) p. 2 Problem 12) Best Choice of Descriptive Statistics to Describe a Variable’s Distribution Suppose you have a variable for systolic blood pressure that is coded as actual values of the measurement. What is the variable’s level of measurement? What is the best way to describe it in a “Patient Characteristics” table of a manuscript? Problem 13) Best Choice of Descriptive Statistics to Describe a Variable’s Distribution Suppose you have a variable for sex that is scored as 1) male 2) female What is the best way to describe it in a “Patient Characteristics” table of a manuscript? Problem 14) Best Choice of Descriptive Statistics to Describe a Variable’s Distribution Suppose you have a variable for the New York Heart Association class (NYHA class)(Miller-Davis et al, 2006). The “NYHA class” is a simple scale that classifies a patient according to how cardiac symptoms impinge on day to day activies. It is scored as: Class I) No limitations of physical activity (ordinary physical activity does not cause symptoms) Class II) Slight limitation of physical activity (ordinary physical activity does cause symptoms) Class III) Moderate limitation of activity (comfortable at rest but less than orinary activities cause symptoms) Class IV) Unable to perform any physical activity without discomfort (may be symptomatic even at rest); therefore severe limitation What is the variable’s level of measurement? What is the best way to describe it in a “Patient Characteristics” table of a manuscript? Problem 15) Open up the file births_with_missing.dta in Stata. Compute the frequency tables or descriptive statistics, separately for mothers with and without hypertension, and fill in the following table with the appropriate row labels in column one and the best choice of descriptive statistcs in columns two and three. Table 1. Patient Characteristics Maternal Hypertension Present [N = ] Maternal age, yrs Maternal Hypertension Absent [N = ] Sex of Newborn Chapter 2-98 (revision 8 Jan 2012) p. 3 Chapter 2-2. Logic of significance tests Chapter 2-3. Choice of significance test It was shown in Chapter 2-1 that the decision of which descriptive statistic to use was based on the level of measurement of the data. The most informative measure of average and dispersion (such as mean and standard deviation) was selected after determining the level of measurement of the variable. The choice of a test statistic, also called a significance test, is made in a similar way. You choose the test the makes the best use of the information in the variable; that is, it depends on the level of measurement of the variable, and whether the groups being compared are independent (different study subjects) or related (same person measured at least twice). Problem 1) Practice Selecting a Significance Test Using Chapter 2-3. Selecting a significance test before these tests have been introduced in later chapters is in some sense jumping ahead. Still, it is useful at this point in the course to see that the decision is actually quite simple, which removes a lot of mystery about the subject of statistics. You do not even have to know what the tests are to be able to do this. This problem is an exercise to illustrate how easy it is. In this problem, the study is comparing an active treatment (intervention group) to an untreated control group (control group). These groups are different subjects (different people, animals, or specimens). The outcome is an interval scale, and for this analysis, no control for other variables is desired. What is the best significance test to use? Problem 2) Practice Selecting a Significance Test Using Chapter 2-3. In this problem, the study is comparing a baseline, or pre-intervention measurement, to a post-intervention measurement on the same study subjects. There is no control group in the experiment. The outcome is an ordinal scale variable, and for this analysis, no control for other variables is desired. What is the best significance test to use? Chapter 2-4. Comparison of two independent groups Problem 1) Comparison of a dichotomous outcome Open the file births_with_missing.dta inside Stata. In preparing to test for an association between hypertension and preterm in the subgroup of females (sex equal 2), first check the minimum expected cell frequency assumption. Do this using: tabulate preterm hyp if sex==2, expect Chapter 2-98 (revision 8 Jan 2012) p. 4 <or abbreviate to> tab preterm hyp if sex==2, expect Comparing the results to the minimum expected cell frequency rule, should a chi-square test be used to test the association, or should a Fisher’s exact test be used? Problem 2) Comparison of a dichotomous outcome Compute the appropriate test statistic for the crosstabulation table in Problem 1. Ask for row or column percents, depending on which we would want to report in our manuscript. Problem 3) Comparison of a dichotomous outcome Use the following “immediate” (the data follow immediately after the command name) version of the tabulate command, tabi 5 4 \ 3 10 , expect should a chi-square test be used, or should a Fisher’s exact test be used? Problem 4) Comparison of a nominal outcome In Sulkowski (2000) Table 1, the following distribution of race is provided for the two study groups. Race Black White Other Protease Inhibitor Regimen (n = 211) Dual Nucleoside Analog Regimen (n = 87) 151 (72) 57 (27) 3 ( 1) 71 (82) 13 (15) 3( 3) P value 0.02 The problem is to verify the percents and the p value. Use the tabi command to add the three rows of data as part of the command, with each row separated by the carriage return, or new line, symbol “\”. (See an example for two rows of data in the previous problem above.) First check the expected frequencies, and then use a chi-square test or Fisher’s exact test (more correctly called a Fisher-Freeman-Halton test when the table is larger than 2 × 2), as appropriate. Chapter 2-98 (revision 8 Jan 2012) p. 5 Problem 5) Comparison of an ordinal outcome Body mass index (BMI) is computed using the equation: body mass index (BMI) = weight/height2 in kg/m2 BMI is frequently recoded into four BMI categories recommended by the National Heart, Lung, and Blood Institute (1998)(Onyike et al., 2003): underweight (BMI <18.5) normal weight (BMI 18.5–24.9) overweight (BMI 25.0–29.9) obese (BMI 30) (How to compute BMI and recode it into these four categories is explained in Chapter 111, if you ever need to do this in your own research.) This recoding converts the data from an interval scale into an ordinal scale, since the categories have order but not equal intervals. To compare two groups on BMI as an ordinal scale, a Wilcoxon-MannWhitney test is appropriate. Suppose the data are: BMI, count (%) Underweight Normal weight Overweight Obese Active Drug (n = 100 Placebo Drug (n = 100) 4 ( 4) 30 (30) 50 (50) 16 (16) 0 ( 0) 20 (20) 45 (45) 35 (35) The ranksum command, which is the Wilcoxon-Mann-Whitney test, does not have an “immediate” form, so we have to convert these data into “individual level” data, where each row of the dataset represents an individual subject. To do this, copy the following into the Stata do-file editor and run it. Chapter 2-98 (revision 8 Jan 2012) p. 6 * --- wrong way to do it --clear input active bmicat count 1 1 4 1 2 30 1 3 50 1 4 16 0 1 0 0 2 20 0 3 45 0 4 35 end expand count tab bmicat active Compare the result to data table above to see what is different. Now copy the following into the do-file editor and run it, * --- correct way to do it --clear input active bmicat count 1 1 4 1 2 30 1 3 50 1 4 16 0 1 0 0 2 20 0 3 45 0 4 35 end drop if count==0 // always a good idea to add this line expand count tab bmicat active Now that we have the dataset correctly created, test the two groups using a WilcoxonMann-Whitney test. Write a sentence that could be used to report the results of the test. Chapter 2-98 (revision 8 Jan 2012) p. 7 Problem 6) Comparison of an interval outcome Cut and paste the following into the do-file editor and execute it to set up the dataset. These data represent two groups (1=Patients with Coronary Heart Disease (CHD), 0= Patients without CHD) on an outcome of systolic blood pressure (SBP). 120 140 160 sbp 180 200 220 clear input chd sbp 1 225 1 190 1 162 1 178 1 158 0 154 0 124 0 128 0 165 0 162 end graph box sbp ,over(chd) 0 1 Just by looking at the boxplot, would you guess a two-sample t-test would have a smaller p value (more significant) than a Wilcoxon-Mann-Whitney test? Compute four test statistics: two-sample t-test which assumes equal variances, two-sample t-test which does not assume equal variances, Wilcoxon-Mann-Whitney test, and Fisher-Pitman permutation test for two independent samples. Which was the most powerful test for these data (which had smallest p value)? Chapter 2-98 (revision 8 Jan 2012) p. 8 Chapter 2-5. Basics of power analysis Problem 1) sample size determination for a comparison of two means You have pilot data taken from Chapter 2-4, problem 6 above. clear input chd sbp 1 225 1 190 1 162 1 178 1 158 0 154 0 124 0 128 0 165 0 162 end Designing a new study to test this difference in mean SPB, between patients with CHD and without CHD, given these standard deviations, what sample size do you need to have 80% power, using a two-sided alpha 0.05 level comparison? Problem 2) z score (effect size) approach to power analysis Cuellar and Ratcliffe (2009) include the following sample size determination paragraph in their article, “The study was powered to include 40 participants, 20 randomized to each group. Randomization would include an equal number of men and women in each group. Twenty particpants per group were needed to detect the required moderate effect size of 0.9 assuming 80% power, alpha of 0.05, and using a Student’s t-test.” Come up with the “sampsi” command that verifies the sample size computation described in their paragraph. (hint: review the “What to do if you don’t know anything” section of Chapter 2-5). Chapter 2-98 (revision 8 Jan 2012) p. 9 Problem 3) Verifying the z score approach to sample size determination and power analysis is legitimate In Chapter 2-5, the z score approach was presented, but without a demonstration that it actually gives the same answer as when the data are expressed in their original measurement scale. To verify the approach is legitimate, we will first a) verify that a zscore transformed variable has a mean of 0 and standard deviation of 1. Second, b) we will verify a t-test on data transformed into z-scores gives the same p value as when the original scale is used. Third, c) we will verify the sample size and power calculations are identical for a z-score transformed variable and the variable in its original scale. Note: Verifying with an example is not a formal mathematic proof; but if it is true, it should work for any example we try. We can think of it as a demonstration, or verification, rather than a proof. That is good enough for our purpose. We will use the same dataset used above in Ch 2-5 problem 1, which is duplicated here. Cut-and-paste this dataset into the do-file editor, highlight it with the mouse, and then hit the last icon on the right to execute it. clear input chd sbp 1 225 1 190 1 162 1 178 1 158 0 154 0 124 0 128 0 165 0 162 end sum sbp Variable | Obs Mean Std. Dev. Min Max -------------+-------------------------------------------------------sbp | 10 164.6 29.11739 124 225 a) verify that a z-score transformed variable has a mean of 0 and standard deviation of 1. Using this mean and standard deviation (SD), generate a variable that contains the z scores for systolic blood pressure (sbp), using the formula z X X SD [Hint: to compute z=(a-b)/c, use: generate z = (a-b)/c ] Then, use the command, summarize, or abbreviated to sum, to obtain the means and SDs for sbp and your new variable z. If you do this correctly, the mean of z will be 0, and the SD of z will be 1. Chapter 2-98 (revision 8 Jan 2012) p. 10 b) verify a t-test on data transformed into z-scores gives the same p value as when the original scale is used Using an independent sample t-test, compare the coronary heart disease, chd, group to the healthy group on the outcome systolic blood pressure, sbp. Then, repeat the t-test for the z-score transformed systolic blood pressure. Notice that the p values are identical for both t-tests. c) verify the sample size and power calculations are identical for a z-score transformed variable and the variable in its original scale Using the means and SDs from the first t-test, compute the required sample size for power of 0.80. Do the same for the second t-test. Then, using a sample size of n=7 per group, compute the power for these same means and SDs. You should get the same result for both measurement scales. Clarification of the z-score approach This is not quite how we did it in the chapter, however. In the chapter, we used a mean of 0 and SD of 1 for both groups, and then we used some fraction or multiple of the SD=1 for the effect size. Be sure to look at the solution to this problem in Chapter 2-99, where the clarification is fully layed out. Chapter 2-6. More on levels of measurement Chapter 2-7. Comparison of two paired groups Chapter 2-8. Multiplicity and the Comparison of 3+ Groups Problem 1) working with the formulas for the Bonferroni procedure, Holm procedure, and Hochberg procedure for multiplicity adjustment These are three popular procedures with formulas that are simply enough that you can do them by hand. The procedures are described in Ch 2-8, pp. 9-10. For Bonferroni adjusted p values, you simply multiply each p value by the number of comparisons made. If this results in a p value greater than 1, an anomoly, you set the adjusted p value to 1. For Holm adjusted p values, you first sort the p values from smallest to largest. Than you multiple by smallest p value by the number of comparison, the next smallest by the number of comparisons minus 1, and so on. Do this same thing for Hochberg adjusted p values. If a Holm adjusted p value becomes larger than the next adjusted p value, an Chapter 2-98 (revision 8 Jan 2012) p. 11 anomoly since this conflicts with the rank ordering of the unadjusted p values, you carry the previous adjusted p value forward. For Hochberg, the anomoly adjustment is to carry the subsequent adjusted p value backward. If the Holm adjusted p value exceeds 1, you set it to 1. Fill in the following table, doing the computations and adjustments in your head. Sorted Bonferroni Holm Unadjusted Adjusted Adjusted P value P value P value (before anomoly correction) 0.020 0.025 0.040 Holm Adjusted P value (after anomoly correction) Hochberg Adjusted P value (before anomoly correction) Hochberg Adjusted P value (after anomoly correction) Use the mcpi command, after installing it if necessary as described in Ch 2-8, to check your answers. Problem 2) a published example of using the Bonferroni procedure Kumara et al. (2009) compared five protein assays against a preop baseline. In their Statistical Methods, they state, “In regards to the protein assays, 5 comparisons (all vs. preop baseline) were carried out for each parameter, thus, a Bonferroni adjustment was made….” These authors had several parameters, with five comparisons made for each parameter. The adjustment for the five comparisons was made separately for each parameter, which is the popular way to do it. One might consider if an adjustment needs to be made for all of the parameters simultaneously, so k parameters × 5 comparisons, which would be a large number. Alternatively, you could adjust for all p values reported in the paper. A line has to be drawn somewhere, or all significance would be lost in the paper. Statisticians have drawn the line at a “family” of comparisons, so arises the term “familywise error rate” or FWER. Each parameter represents a family of five related comparisons, so an adjustment is made for those five comparisons to control the FWER. This adjustment is done separately for each parameter, which makes sense, since each parameter is a separate question to study. In the Kumara (2009, last paragraph), we find, “The mean preopplasma level for the 105 patients was 164 ± 146 pg/mL. Significant elevations, as per the Bonferoni criteria, were noted on POD 5 (355 ± 275 pg/mL, P = 0.002) and for the POD 7 to 13 time period (371 ± 428 pg/mL, P = 0.001) versus the preop results (Fig.1). Although VEGF levels were eleavated for the POD 14 to 20 (289 ± 297 pg/mL; vs. preop, P = 0.036) and POD 21 to 27 Chapter 2-98 (revision 8 Jan 2012) p. 12 (244 ± 297 pg/mL; vs. preop, P = 0.048), as per the Bonferoni correction, these differences were not significant. By the second month after surgery the mean VEGF level was near baseline….” This is an example of where two significant p values were lost after adjusting for multiple comparions. The authors reported the results this way, showing the unadjusted p values, while mentioning the adjustment declared them nonsignificant, apparently because they thought the effects were real and they wanted to lead the reader in that direction. Even in their Figure 1 they denote the results as significant. This is a good illustration of investigators being frustrated by “I had significant but lost it due to the stupid multiple comparison adjustment.” It could easily be argued that the authors took the right approach, since not informing the reader might produce a Type II error (false negative conclusion). There is no universal consensus on this point. The exercise is to see if applying some other multiple comparison adjustment would have saved the significance, since we know the Bonferroni procedure is too conservative. For the fifth p value, the last quoted sentence, it was clearly greater than 0.05, so just use 0.50. It makes no difference what value >0.05 we choose, since multiple comparison adjustments cannot create significance that was not there before adjustment. Using 0.50, then, along with the four other p values in the quoted paragraph, use the mcpi command to see if significance would have been saved by one of the other procedures. Problem 3) Analyzing Data with Multiple Treatments An animal experiment was performed to test the effectiveness of a new drug. The researcher was convinced the drug was effective, but he was not sure which carrier solution would enhance drug delivery. (The drug is disolved into a the carrier solution so it can be delivered intravenously.) Three candidate carriers were considered, carrier A, B, and C. The experiment then involved four groups: treat: 1 = inert carrier only (control group) 2 = active drug in carrier A 3 = active drug in carrier B 4 = active drug in carrier C The researcher wanted to conclude the drug was effective if any of the active drug groups were significantly greater on the response variable than the control group. That is, the decision rule was: Conclude effectiveness if (treatment 1 > control) or ( treatment 2 > control) or ( treatment 3 > control). The decision rule, or “win strategy” fits the multiple comparison situation where you want to control the family-wise error rate (FWER), which is the typical situation that Chapter 2-98 (revision 8 Jan 2012) p. 13 researchers learn about in statistics courses. That is, you want to use multiple comparisons to arrive at a single conclusion, and you want to keep the Type I error at alpha ≤ 0.05. To create the dataset, copy the following into the Stata do-file editor and execute it. clear set seed 999 set obs 24 gen treat = 1 in 1/6 replace treat = 2 in 7/12 replace treat = 3 in 13/18 replace treat = 4 in 19/24 gen response = invnorm(uniform())*4+1*treat bysort treat: sum response -> treat = 1 Variable | Obs Mean Std. Dev. Min Max -------------+-------------------------------------------------------response | 6 .2875054 3.057285 -5.066414 2.869501 -> treat = 2 Variable | Obs Mean Std. Dev. Min Max -------------+-------------------------------------------------------response | 6 1.772157 2.48272 -2.487267 4.081223 -> treat = 3 Variable | Obs Mean Std. Dev. Min Max -------------+-------------------------------------------------------response | 6 4.119424 7.105336 -3.477194 15.84198 -> treat = 4 Variable | Obs Mean Std. Dev. Min Max -------------+-------------------------------------------------------response | 6 6.501425 2.198203 2.682323 9.369428 For sake of illustration, let’s now perform a oneway analysis of variance, which many statistics instructors still erroneously teach is a necessary first step. oneway response treat, tabulate Analysis of Variance Source SS df MS F Prob > F -----------------------------------------------------------------------Between groups 133.575257 3 44.5250857 2.51 0.0876 Within groups 354.143942 20 17.7071971 -----------------------------------------------------------------------Total 487.719199 23 21.2051826 The oneway ANOVA is not significant (p = 0.088), so the statistics instructors who advocate this was a necessary first step would say you cannot go any further. You would then conclude that the drug was not effective. Chapter 2-98 (revision 8 Jan 2012) p. 14 As was pointed out in Chapter 2-8, in the section called “Common Misconception of Thinking Analysis of Variance (ANOVA) Must Precede Pairwise Comparisons,” there is no reason to do this. Many statisticians are aware that the ANOVA test is ultra conservative, and so they stay away from it when testing treatment effects. A more correct and more powerful approach is to bypass the ANOVA test, going straight to making the three specific individual comparisons of interest, which are each of the three active drug groups (2, 3, and 4) with the control group (1). A multiple comparison procedure is applied to these three comparisons to control the family-wise error rate. The homework problem is to perform an independent sample t-test between groups 1 and 2, 1 and 3, and 1 and 4, and then adjust the three obtained two-sided p values using the mcpi command. You will need to include an “if” statement in the ttest command, as was shown in Chapter 2-8 (see pp. 44-45). Apply Hommell’s procedure, which is one of the methods used by the mcpi command. From the obtained results, should you conclude the drug is effective? Chapter 2-9. Correlation Chapter 2-10. Linear regression Problem 1) regression equation The regression output, among other things, shows the equation of the regression line. From simple algebra, we know the equation of a straight line is: y a bx where y is the outcome, or dependent variable, x is the predictor, or independent variable, a is the y-intercept, and b is the slope of the line. Fitting this equation is called “simple linear regression.” Extending this equation to three predictor variables, the regression equation is: y a b1 x1 b2 x2 b3 x3 Fitting this equation is called “multivariable linear regression” to signify that more than one predictor variable is included in the equation. Using the FEV dataset, fev.dta, predicting FEV by height, regress fev height -----------------------------------------------------------------------------fev | Coef. Std. Err. t P>|t| [95% Conf. Interval] -------------+---------------------------------------------------------------height | .1319756 .002955 44.66 0.000 .1261732 .137778 Chapter 2-98 (revision 8 Jan 2012) p. 15 _cons | -5.432679 .1814599 -29.94 0.000 -5.788995 -5.076363 ------------------------------------------------------------------------------ We can find the intercept and slope from the coefficient column of the regression table and write the linear equation as, fev = -5.432679 + 0.1319756(height) Listing these variables for the first subject, list fev height in 1 +----------------+ | fev height | |----------------| 1. | 1.708 57 | +----------------+ To apply the prediction equation to predict FEV for this first subject, we can use the display command, where “*” denotes multiplication, display -5.432679 + 0.1319756*57 2.0899302 We can get Stata to provide the predicted values from applying the regression equation, using the predict command. In the following example, we use “pred_fev” as the variable we choose to store the predicted values in. The predict command applies the equation from the last fitted model. predict pred_fev list fev height pred_fev in 1 Chapter 2-98 (revision 8 Jan 2012) p. 16 +---------------------------+ | fev height pred_fev | |---------------------------| 1. | 1.708 57 2.089929 | +---------------------------+ The predicted value that Stata came up with is slightly different from what we got with the display command because it is using more decimal places of accuracy. Now that we see how it works, the homework problem is to fit a multivariable model for FEV with height and age as the predictor variables. Use the display command to predict FEV for the first subject. Then, use the predict command to check your answer. In other words, take all of the Stata commands we used above, regress fev height list fev height in 1 display -5.432679 + 0.1319756*57 capture drop pred_fev predict pred_fev list fev height pred_fev in 1 and modify them for the two predictors, height and age, used together. Problem 2) reporting the results Using the regression model output from Problem 1, which is Source | SS df MS -------------+-----------------------------Model | 376.244941 2 188.122471 Residual | 114.674892 651 .176151908 -------------+-----------------------------Total | 490.919833 653 .751791475 Number of obs F( 2, 651) Prob > F R-squared Adj R-squared Root MSE = 654 = 1067.96 = 0.0000 = 0.7664 = 0.7657 = .4197 -----------------------------------------------------------------------------fev | Coef. Std. Err. t P>|t| [95% Conf. Interval] -------------+---------------------------------------------------------------height | .1097118 .0047162 23.26 0.000 .100451 .1189726 age | .0542807 .0091061 5.96 0.000 .0363998 .0721616 _cons | -4.610466 .2242706 -20.56 0.000 -5.050847 -4.170085 ------------------------------------------------------------------------------ write a sentence that could be used to interpret the the association of height with FEV. Chapter 2-98 (revision 8 Jan 2012) p. 17 Problem 3) Are the signs (positive or negative) of correlations transitive? When we speak of correlation, referring to the regression coefficient or referring to the correlation coefficient is analogous, since the correlation coefficient is simply the regression coefficient computed after transforming the data to standardized scores, or zscores. Both approaches test for a correlation (an association). When the regression coefficient or the correlation coefficient is positive, we say the variables are “positively correlated”, so as you increase on one variable, you also increase on the other. When they are negative, we say the variables are “negatively correlated”, so as you increase on one variable, you decrease on the other. It does not matter which variable is the dependent or independent variable when you test for a correlation or when you interpret whether it is negatively or positively correlated. In mathematics, the transitive property of equality is: If A=B and B=C, then A=C. Similarly, the transitive property of inequality is: If A≥B and B≥C, then A≥C. Suppose you analyze your data, computing correlation coefficients between variables A, B, and C, and you get the following result: A vs B: Pearson r = +0.75 B vs C: Pearson r = +0.70 A vs C: Pearson r = -0.50 Your co-investigator looks at these results and says to you, “This cannot be right. If B increases with increasing A, and C increases with increasing B, then it is impossible for C to decrease with increasing A. Think about it. If I put a beaker of water on a flame, the temperature of the water increases when the temperature of the breaker increases (A increase → B increase). If I put a stone in the water, the temperature of the stone goes up when the temperature of the water goes up (B increase → C increase). Now you are trying to tell me that when the temperature of the breaker increases the temperature of the stone decreases? (A increase → C decrease).” What your co-investigator just did was assume that the sign of the correlation coefficient exhibits the transitive property. Is the co-investigator correct that you must have made a mistake? (hint: You will not find this in the course manual chapters on regression or correlation. It is just an exercise in reasoning. It is included here as a homework problem because this type of “reasoning” is quite common when researchers look for associations.) Chapter 2-11. Logistic regression and dummy variables Problem 1) Read in the data file Chapter 2-98 (revision 8 Jan 2012) p. 18 Open the file births.dta inside Stata. Problem 2) Create indicator variables The data contain maternal ages from 23 to 43. Suppose you have a reason to think the following maternal ages form meaningful categories: age 23 to 30 age 31 to 38 age 39 to 43 Using the “recode” command, with the “gen( )” option, create an maternal age categorical variable that has the scores: 1 = age 23 to 30 2 = age 31 to 38 3 = age 39 to 43 using the command: recode matage 23/30=1 31/38=2 39/43=3 , gen(matage3) Next, use the tabulate command, with the gen( ) option, to create 3 indicator variables. (hint: look at the example on page 16 of Chapter 2-11) Problem 3) Fit a logistic regression Finally, fit a multiple logistic regression model, using two of the three matage age indicator variables as the predictors and low birthweight (lowbw) as the outcome variable. (hint: look at the example on page 20 of Chapter 13) Chapter 2-12. Survival analysis: Kaplan-Meier graphs, Log-rank Test, and Cox regression Chapter 2-13. Confidence intervals versus p values and trends toward Significance Chapter 2-14. Pearson correlation coefficient with clustered data Chapter 2-15. Equivalence and noninferiority tests Problem 1) Difference in two proportions noninferiority test Chapter 2-98 (revision 8 Jan 2012) p. 19 Reboli et al. (N Engl J Med, 2007) conducted a randomized, double-blind, noninferiority trial to test their hypothesis that anidualfungin, a new echinocandin, is noninferior to fluconazole for the treatment of invasive candidiasis. In their article, they stated that their statistical method was, “The primary analysis in this noninferiority trial was a two-step comparison of the rate of global success between the two study groups at the end of intravenous therapy. A two-sided 95% confidence interval was calculated for the true difference in efficacy (the success rate with anidulafungin minus that with fluconazole). In the first step, noninferiority was considered to be shown if the lower limit of the two-sided 95% confidence interval was greater than -20 percentage points. In the second step, if the lower limit was greater than 0, then anidualfungin was considered to be superior in the strict sense to fluconazole.” To set up the data reported by Reboli et al., cut-and-paste the following into the Stata dofile editor, highlight it, and double click on the last icon on the do-file menu bar to execute it. clear all set obs 245 gen anidulafungin=1 in 1/127 replace anidulafungin=0 in 128/245 recode anidulafungin 0=1 1=0 ,gen(fluconazole) label variable fluconazole // turn off variable label gen globalresponse=1 in 1/96 replace globalresponse=0 in 97/127 replace globalresponse=1 in 128/198 replace globalresponse=0 in 199/245 label define anidulafunginlab 1 "1. anidulafungin" /// 0 "0. fluconazole" label values anidulafungin anidulafunginlab label define fluconazolelab 1 "1. fluconazole" /// 0 "0. anidulafungin" label values fluconazole fluconazolelab label define globalresponselab 1 "1. Success" 0 "0. Failure" label values globalresponse globalresponselab tab globalresponse anidulafungin, col tab globalresponse fluconazole, col Part a) Using the noninferiority margin of -20%, where anidulafungin could have an absolute percent success of 20 points (20%) less than fluconazole, test the noninferiority hypothesis using with the appropriate confidence interval. Hint: Use the prtest command. Depending on which direction you want to compute the difference, use either the anidulafungin group variable or the fluconazole group variable. Part b) If justified following the noninferiority analysis, test for superiority of anidulafungin to fluconazole. Chapter 2-16. Validity and reliability Chapter 2-17. Methods comparison studies Chapter 2-98 (revision 8 Jan 2012) p. 20 References Cuellar NG, Ratcliffe SJ. (2009). Does valerian improve sleepiness and symptom severity in people with restless legs syndrome? Alternative Therapies 15(2):22-28. Daniel WW. (1995). 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Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 356;24:2472-2482. Rosner B. (2006). Fundamentals of Biostatistics, 6th ed. Belmont CA, Duxbury Press. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. (2000). Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA 283(1):74-80. {cited in: Ch 2-1, 3-5, 3-9} Chapter 2-98 (revision 8 Jan 2012) p. 21