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H. James Norton

H. James Norton. norton100@bellsouth.net Website: www.jimnortonphd.com. USE OF INTERESTING EXAMPLES FROM MEDICINE & BIOLOGY IN TEACHING AN INTRODUCTORY BIOSTATISTICS COURSE.

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H. James Norton

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  1. H. James Norton norton100@bellsouth.net Website: www.jimnortonphd.com

  2. USE OF INTERESTING EXAMPLES FROM MEDICINE & BIOLOGY IN TEACHING AN INTRODUCTORYBIOSTATISTICS COURSE

  3. Keeping undergraduate biology students and medical residents interested in statistics, when the majority of the students are taking the class as a requirement, can be challenging

  4. The following are examples I use in my course instruction

  5. THEY INCLUDE • Medical & dental papers containing critical mistakes • Fallacies in numerical reasoning • The Will Roger’s Phenomenon • Population estimation using the capture/recapture method

  6. References for Fallacies in Numerical Reasoning: • Andersen B. Methodological Errors in Medical Research • Cohn V. News and Numbers • Colton T. Statistics in Medicine • Huff D. How to Lie with Statistics • Moore D. Statistics Concepts and Controversies

  7. Example (from Colton) Sex and race distribution of 158 cases of abdominal aortic aneurysms at metropolitan hospitals in a Southern city

  8. Authors’ Conclusion: Incidence of AAA is almost 3 times more frequent in Whites than African-Americans.

  9. This fallacy is known as a lack of denominators

  10. Example (from Colton) • A review of medical records for 3000 diabetic patients • Approximately two-thirds of patients at some time were 11% or more overweight • Conclusion: This provides evidence of an association between obesity and diabetes • Do you agree?

  11. This fallacy is known as a lack of a control group

  12. Papadrianos E, Haagnesen CD, Cooley E. Cancer of the breast as a familiar disease. Annals Surg 1967;165:10-19. Hypothesis: “Whether or not the transmission of a predisposition to mammary cancer carries with it a tendency to develop the disease at an earlier age.”

  13. Results: “The mean age of the mothers was 59.7 years: that of the daughters 47.5 years. This difference of 12.2 is convincing evidence that mothers with mammary carcinoma pass on to their daughters a likelihood of developing the disease at an earlier age than they themselves get it.”

  14. Conclusion: “No matter how statisticians may interpret these data, they are too real to be ignored.”

  15. Problems with the study • There was a bias in that they compared only those pairs where the daughter had developed the disease • They did not consider the possibility of new techniques to detect cancer earlier • The phenomenon of anticipation in genetic diseases was not taken into account

  16. Survival-times after cardiac allografts Messmer BJ, Nora JJ, Leachman RD, Cooley DA. The Lancet. May 10, 1969; 954-956.

  17. 57 patients who were eligible for a heart transplant Patients divided into those who did and did not receive a transplant Either time to death or follow-up time was recorded Mean time to death or follow-up was computed for each group The mean was higher in the group who received transplant (111 days vs 74 days)

  18. By utilizing the follow-up times for the patients who are still alive in the data analysis, statistically speaking, what have the authors done to these patients? What statistical procedure correctly accounts for patients who are lost to follow-up or still alive (censored)?

  19. The authors treated the living patients as if they died on their last day of follow-up. Statistically speaking, they murdered the patients still alive!

  20. p = 0.861

  21. “Wonderfully bad” articles • Seven published medical & dental papers with numerous mistakes that undergraduates with one semester of biostatistics can detect • Allow for a wide range of critical ability and insight • Handout – from Colton “Outline for critique of a medical report”

  22. Authors: Walton and Chiappinell Table 1. Incidence of post-treatment symptoms following root canal* * chi-square, df = 28, 95%=5.6324, p = 0.68 (not significant) 1. Is the study blinded? 2. Do you see any problems with their analysis?

  23. What’s the chemical toxin being studied and which character is associated with the toxin?

  24. “The relationship between mercury from dental amalgam and mental health” • Part I of study • 70 volunteers (college students) divided into those with and without any dental amalgams • Given a mental health questionnaire • Two groups compared on measures of mental health

  25. Author’s Conclusion: • “The amalgam group appeared to have a poor lifestyle. They craved and ate more sweets, smoked more cigarettes, consumed more alcohol…” • Do you think this is convincing evidence that the mercury in the amalgams is causing a poorer choice in lifestyle?

  26. Part II of study • Mental health questionnaires sent to 300 subjects who had all of their amalgams removed by a dentist in Utah • 86 returned questionnaires • Vast majority of the 86 stated that their mental health was improved after amalgams removed • I will let you ponder all the problems!!

  27. Ask your students compare the results of the previous study to these two randomized clinical trials: • Neuropsychological and renal effects of dental amalgam in children. Bellinger DC. JAMA, 2006:295:1775-1783. • Neurobehavioral effects of dental amalgam in children. DeRouen. JAMA, 2006:295:1784-1792.

  28. DDT (ppm) in birds by age & location

  29. Questions about DDT & the environment a. What was DDT used for? b. How does it harm the birds? c. Who first warned us of the danger to the birds from ingesting DDT? d. What was the name of the book? e. When was it published? f. When was DDT banned in the US? g. Where in the world do we find the highest concentrations of DDT? h. What environmental/medical/legal/ethical question has recently been discussed in the U.S. concerning DDT? i. What did Time Magazine say about the book when it was first published?

  30. Answers a. DDT is a pesticide b. DDT interferes with the process of depositing calcium in birds’ egg shells. This leaves the shell very fragile, the shell cracks, and the embryo dies. c. Rachel Carson d. Silent Spring e. 1962 f. 1972 g. In the Arctic. Inuit women have extremely high levels of DDT and DDE in their breast milk. h. Whether the US should allow US companies to manufacture DDT for use against mosquitoes to combat malaria. DDT is very inexpensive to produce and many African nations cannot afford more costly pesticides. i. Time magazine said her book was an “emotional and inaccurate outburst deliberately trying to scare people."

  31. In a 2 x 2 factorial design, swine are given either 0 or 40 mg of antibiotics and either 0 or 5 mg of vitamin B12. The dependent variable is the average daily weight gain of the swine (in pounds).

  32. “A glance at the total for the four treatment combinations suggests that with no antibiotics, B12 had little or no effect (3.66 versus 3.57) apparently because the intestinal flora utilized the B12. With antibiotics present to control the flora, the effect of the vitamin was marked (4.63 versus 3.10). Looking at the table the other way, the antibiotics alone decreased gain (4.63 versus 3.10) perhaps by suppressing intestinal flora that synthesize B12; but with B12 added, the antibiotics produced a gain by decreasing the activities of unfavorable flora.”

  33. ParadoxesParadoxes, by their very nature, can be interesting to students.I show them an example of Simpson’s Paradox.

  34. Newly diagnosed cancer patients are classified by stage. Patients with more advanced disease and worse prognosis are assigned to a higher stage. A paradoxical situation can occur over time, where the overall death rate from a cancer may remain constant, but the death rate for every stage can go down. This paradox is known as “The Will Rogers phenomenon.”

  35. As it was Will Rogers who said of the poor farmers who migrated from Oklahoma to California during the dust bowl era of the 1930’s, “When the Okies left Oklahoma and moved to California, they raised the average intelligence of both states.”

  36. Hierarchy for scientific evidence in medical studies • Retrospective case-control studies • Prospective observational studies • Randomized clinical trials

  37. Doll & Hill’s two famous studies • Case-control study of smoking and lung cancer (1950) • Prospective study of 34,000 British physicians (1954). Detailed questionnaires on smoking habits • Student workbook published by CDC at www.cdc.gov/eis/casestudies/xsmoke.student.731-703.pdf

  38. Contrast Nurses’ Heath Study (NHS)& Women’s Health Initiative (WHI) • NHS – observational cohort of 127,000 nurses ages 30 to 55 • WHI – randomized clinical trial of 50,000 women ages 50 to 79 • NHS – women taking estrogen after menopause had reduced risk of heart disease. • WHI – stopped study prematurely. Women taking Prempro had increased risk of heart disease.

  39. “Adenocarcinoma of the vagina:Association of ?? with tumor appearance in young women” • Retrospective study of 8 young women from Boston, ages 15-22, with adnocarcinoma of the vagina • Each case matched to 4 control women born in the same hospital during the same week of birth

  40. Ask students if they were epidemiologists, “What questions would you ask the cases and controls?” • Family history of disease, sexual history, drug use, co-morbid conditions, treatment with chemo-therapy or radiation.

  41. What caused the disease? • Mom’s use of diethylstilbestrol (DES) during pregnancy (7/8 cases, 0/32 controls)

  42. How many fish are in the lake?

  43. How many fish are in the lake? • “Throw many sticks of dynamite and then count the dead fish!” • Use method of capture/recapture • Nice section in Wikipedia http:en.wikipedia.org/wiki/Mark_and_recapture

  44. Capture and tag N1 fish and release • At later date N2 fish are captured • M of these fish were previously tagged • Let N = estimated # of fish in lake • Lincoln-Peterson method: N = (N1 x N2) / M

  45. Dr. Kevin Ward DrummeyJSM 1994 • “How many dinosaurs are there? Or estimating population size using the capture/recapture method” • Drummey used small plastic dinosaurs that he “tagged” with small rubber bands. • I think you could use marbles and replace them with marbles of a different color.

  46. Conclusions: • Hopefully, the use of interesting examples from medicine and biology will improve the learning experience for the students.

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