Biomedical Literature Evaluation & Statistics Exam Study GuideMichael A. Mancano, Pharm.D. 1. In a randomized controlled clinical trial of a new antihypertensive agent, patients with diastolic blood pressure readings greater than 90 mmHg on their most recent clinic visit are selected as subjects. A patient assigned to the experimental treatment group is normotensive at his first clinic visit after initiating drug therapy. All of the following factors represent plausible explanations for this observation EXCEPT: a) b) c) d) e) Simpsons Paradox Random variation in blood pressure measurements. Regression to the mean. Efficacy of the experimental drug. Measurement error.

2. A study is carried out to compare the effect of two low fat diets on vascular plaque accumulation. The investigator conducting the study obtained a list of individuals who had been continuously enrolled between 1985 and 1990 in one of two commercial weight loss programs based on the two diets. Participants in both diet programs were invited to participate in the study. The protocol described above is an example of which of the following study designs? a) b) c) d) e) Randomized, double-blind Randomized block design Meta-analysis Double-blind, crossover study. Observational study: historical cohort study.

3. A group of patients with coronary heart disease volunteered to participate in a study of the relationship between diet and vascular plaque accumulation. The subjects were randomized to one of three diets: very low fat (< 10% total calories from fat), low fat (< 30% of the total calories from fat), or a reduced calorie diet with no restrictions on fat intake. At the end of a five-year follow-up period, vascular plaque accumulation in the three diet groups was compared to determine which diet achieved the greatest reduction in plaque accumulation. The protocol described above is an example of which of the following study designs? a) b) c) d) e) Randomized clinical trial. Case report Meta-analysis Double-blind, crossover study. Observational study: historical cohort study.

4. A pharmaceutical company conducted a double-blind randomized controlled clinical trial of a new antipruritic drug. One group of subjects received a lotion containing the experimental drug, a second group received an identical lotion lacking the active ingredient, and a third group received no treatment at all. Two weeks later, the itching intensity scores (the lower the score, the less severe the itching) for the three groups were 12 (experimental group), 15 (placebo group) and 65 (no treatment group). Which of the following factors BEST explains the result obtained for the subjects who received the lotion lacking the active ingredient? a) b) c) d) e) The Hawthorn effect Regression to the mean. Selection bias. The placebo effect. Failure to adequately blind subjects and investigators.

Please refer the following scenario to answer questions 5 and 6. In a clinical trial of a novel antihypertensive agent, 60 patients were randomly assigned to receive the new drug for 14 days and 60 patients were randomly assigned to receive a placebo for 14 days. Changes in blood pressure from baseline during the treatment period were recorded for all patients. The primary research objective was to determine if the mean change from baseline in diastolic blood pressure was greater for the new drug than for the placebo. The result was that patients who received the new antihypertensive agent had a reduction in blood pressure of 5 % and the patients who received the placebo had a reduction in blood pressure of 3%, with a p-value for the comparison between the groups of p= 0.8. Upon completion of the study the investigator decided to look at the 10 women who were randomly assigned to each of the two groups and the results were shocking. The 10 women who received the new antihypertensive agent experienced a reduction in blood pressure of 25% and the 10 women who received placebo had a reduction in blood pressure of 8%, with a p-value for the comparison between the two groups of p=0.06. 5. Which of the following statements are TRUE with regard to the study results? a) b) c) d) e) The new antihypertensive agent is very effective in women. Further study is warranted in a study designed to look specifically at the female population. Initial patient selection bias probably accounts for the observed results. The decision to analyze the female data is an example of an a priori hypothesis. None of the above.

6. The results observed in the female sub-group in the above described clinical trial is an example of: a) b) c) d) e) The Hawthorne effect. Bonferroni error. Simpsons paradox The Greenhouse effect. Regression to the mean.

7. A pediatrician wishes to evaluate the efficacy of an experimental formula in infants who fall below the tenth percentile in weight for their age group. Fifty such infants will be randomly assigned to receive either the experimental formula or a standard commercially available formula for three months. Weight gains for both groups will be recorded at the end of this time period in an attempt to answer the research question, Is the average weight gain higher among infants receiving the experimental formula than among those receiving the standard formula? After conducting the study, the pediatrician reports at a research conference that the results are not statistically significant (p>0.05). All of the following statements about this conclusion are true except: a) The average weight gain in the infants fed the experimental formula is EXACTLY THE SAME as the average weight gain among infants fed the standard formula. b) A clinically important difference in average weight gain between the two groups of lower-weight infants may exist, but the power of the test may have been too low to detect it. c) The chance of type II error may be high, i.e. low power. d) The observed difference in average weight gain between the experimental and control groups is likely to be due to random chance.

8. To compare the efficacy of two drugs in lowering serum cholesterol levels, a physician measures serum cholesterol levels in a sample of men receiving drug A and in a sample of men receiving drug B and learns that the average serum cholesterol is lower in those receiving drug B. Plausible explanations for the observed difference in the response to the two drugs include all of the following EXCEPT: a) Drug B is superior to drug A in lowering cholesterol levels among the population of potential recipients. b) The observed difference occurred by random chance. c) Extraneous, uncontrolled differences (other than drug therapy) between the sample of the men receiving drug A and the sample of men receiving drug B account for the observed difference in efficacy. d) The observed difference may be attributed to a small p-value for the statistical test. Please refer the following scenario to answer questions 9 and 10. A pediatrician wished to determine the relationship between chronic otitis media in young children and parental history of such infections. From the records of a large pediatric practice, he identified 50 children between one and three years of age who had experienced at least three middle ear infections during the preceding year. Fifty different children in the same age group, treated by the same practice for other illnesses, were also identified as control subjects. The pediatrician interviewed the parents of the subjects in both groups to determine their history of chronic otitis media as young children. Of the children with recurrent ear infections, 30 had a family history of chronic otitis media, compared to 20 of the children treated for other illnesses. 9. This study is an example of a: a) b) c) d) Meta-analysis Prospective cohort study Case-control study Randomized controlled clinical trial

10. The pediatrician conducting this study reports the existence of a statistically significant association between chronic otitis media in children between the ages of one and three and a parental history of such infections (p0.1). All of the following statements about this conclusion are correct EXCEPT a) It is likely that any observed differences in average serum cholesterol levels in response to the four drug treatments occurred by random chance. b) Average serum cholesterol levels are exactly the same among the four treatment groups. c) The probability of a type II error may be high. d) A clinically important difference in average serum cholesterol levels after the four drug treatments may exist, but the power of the statistical test may have been to low to detect it. 42. The use of multiple t-tests (with a 5% level of significance for each test), rather than an analysis of variance, to analyze the data obtained in this study would accomplish which of the following? a) b) c) d) A decrease in the chance of type I error. A decrease in the likelihood of erroneously declaring a difference in means statistically significant. An increase in the overall type I error rate for the entire set of comparisons. A decrease in the probability of a false positive result.

43. Which of the following statements about the Bonferroni multiple comparison procedure are true? a) It is used to determine which of a set of means are different while simultaneously controlling for the multiple comparison problem (i.e. increased alpha error). b) It is used to control the overall alpha error rate per experiment for the entire set of comparisons. c) It represents a modification of the t test. d) All of the above are true.

Use the following information to complete questions 44, 45, 46 & 47 A study was conducted to assess the prevention of deep vein thrombosis in patients undergoing knee replacement surgery. All patients did not have a history of deep vein thrombosis. A total of 8,152 patients were randomized to receive either Enoxaparin 30 mg subcutaneously every 12 hours (n = 4,096) or heparin 5000 units subcutaneously every 12 hours (n = 4,056). All patients were followed for a total of 2 months after surgery. The primary endpoint of the study was the occurrence of a deep vein thrombosis during the two month postoperative period. The number of patients with the primary endpoint are as follows: Outcome Yes No 614 3482 1622 2434

Enoxaparin Heparin

44. The calculated relative risk (RR) for this study is? a) b) c) d) e) 0.09 0.16 0.37 0.84 Cannot be calculated from the data provided.

45. The calculated absolute relative risk (ARR) for this study is? a) b) c) d) e) 10% 25% 35% 58% Cannot be calculated from the data provided

46. The calculated relative risk reduction (RRR) for this study is? a) b) c) d) e) 0.18 0.27 0.48 0.63 Cannot be calculated from the data provided

47. The calculated number needed to treat (NNT) for this study is? a) b) c) d) e) 1.7 2.8 4 10 Cannot be calculated from the data provided.