1. Understanding Medical Articles and Reports Linda Vincent, MPH UCSF Breast SPORE Advocate September 24, 2005 lvvincent@earthlink.net 510-527-6720

2. Introduction to Statistics  Mean, average of a set of numbers or values  Median, the number closest to the middle of a set of numbers  Standard Deviation, information on the spread of the numbers from a complex calculation

3. More Statistics  Probability, p-value, comparing sets of numbers from research in another complicated calculation that gives information on statistical significance  p<.05 is the same as 95% Confidence Intervals  Answers question like, how likely is it thatpeople in the study that got the investigational drug got better because the drug did its job, or whether they got better due to some other factor.

4. Risk Ratio  Relative Risk or Risk Ratio, RR is used widely in research papers. Compares the probability of an outcome among individuals who have a specific “exposure” or a specific characteristic to those who have not been exposed  RR is calculated in Cohort or Experimental studies (Clinical Trials)

5. Calculating Relative Risk 2 X 2 Table, see page 51 of Cook Article, Lung Number with disease Number without disease Number of exposed 9019,846 Number of unexposed 11519,827

6. Calculating Relative Risk-2  RR Calculation: RR = Absolute risk in exposed participants Absolute risk in unexposed participants Absolute risk in unexposed participants 90/19,934RR = 0.78 115/19,942CI = 0.59-1.03 p-value =.08

7. Interpretation of RR  RR equal to or greater than one, written as =>1 The higher the number above one the greater the risk/disease is associated with the exposure  RR =< 1 There is no association of the risk/disease to the exposure  RR = 1 The risk is the same in both groups

8. Interpretation of Confidence Intervals  Confidence Intervals, CI  95% CI is current standard  If the CI does not include 1.0 that the RR is statistically significant  Previous example in the Cook article, CI = 0.59-1.03

9. Odds Ratios Case-Control Studies can’t use RR because the OR, Odds Ratios are an estimate of RR Number with disease (cases) Number without disease (controls Number exposed Number not exposed

10. Absolute Risk  Absolute Risk gives an actual number of health problems that happened or were prevented due to a drug  Doctors and patients have difficulty understanding RR and OR

11. Use of NSAIDS and Risk of Breast Cancer: The Case- Control Surveillance Study Revisited  Advantages of Case-Control Studies:  Less expensive and time-consuming than cohort studies especially with rare diseases  Odds Ratio can be used to estimate the Risk Ratio

12. Use of NSAIDS and Risk of Breast Cancer: The Case- Control Surveillance Study Revisited  Disadvantages of Case-Control Studies:  Cases and Controls may come from different groups which will bias the results  Time-related relationships may be difficult to ascertain  There is the always the possibility of recall bias when asking about exposures that occurred in the past

13. Use of NSAIDS and Risk of Breast Cancer: The Case- Control Surveillance Study Revisited  What is the purpose of the study and what question did the authors address?  See first sentences of the abstract  What were the unanswered questions raised by prior scientific work that led to this study?  The meta-analysis of Khuder and Mutgi found an 18% decreased risk in regular NSAIDs users in 8 case-control studies.

14. Critical Evaluation of Zhang Article, Continued  Do the authors state a hypothesis? If so what is it?  Hypothesis is a statement of belief used in the evaluation of population values.  Hypothesis statement: There is an association between the exposure and the outcome.  No hypothesis statement in the Zhang article

15. Zhang, continued What are the results? Table 1-For the most relevant category, regular use of NSAIDs, OR was 0.78, 95% Confidence Intervals (CI) 0.63-0.97  CI dosen’t include 1.0 Table 2-Longer duration of regular NSAIDs use was associated with a lower risk of breast cancer, p- value for trend was 0.02 Table 3-Looked at differences between aspirin, Ibuprofen, and NSAIDs (p-value for trend, not significant)

16. Zhang, continued  What are the conclusions drawn from the results? Are the conclusions supported by evidence in the article?  First paragraph under DISCUSSION, “Our results suggest a modest decrease in the risk of breast cancer associated with regular NSAIDs use….”  Last paragraph, “In summary, the present study found…the effect is relatively weak. Given the conflicting results from large cohort studies…too early to suggest that regular use of NSAIDs could help prevent breat cancer.”

17. Zhang, continued  What methods did the authors use?  Cases were selected from patients living within one hour driving distance to the hospitals  Cases were interviewed by trained nurse interviewers using structured questionnaires  Controls…  Data analysis, relationships of use to risk performed with multiple logistic regression models

18. Zhang, continued  What are the strengths of the paper?  Researchers/authors attempted to validate previous studies on use of NSAIDs and reducing risk of breast cancer  Note on biological mechanism for reducing risk  Note on inconsistencies from other studies

19. Zhang, continued  Are there obvious problems with the article?  The hormone receptor status of the tumors was obtained from only 26% of the cases. Other risk factors for breast cancer were not evaluated, but were similar among cases with data on hormone status suggesting absence of selection bias What additional experiments would strenghten the authors conclusions? Are the findings significant? If so, for who?

20. Resources  Free subscription services  BreastCancer.Net, http://breastcancer.net http://breastcancer.net  Amedeo.com, http://amedeo.com http://amedeo.com  Medscape, http://www.medscape.com http://www.medscape.com  PubCrawler, http://pubcrawler.gen.tcd.ie http://pubcrawler.gen.tcd.ie

21. Resources continued… National Cancer Institute Pub Med, http://pubmed.gov http://pubmed.gov MedLinePlus, http://medlineplus.gov http://medlineplus.gov FDA Center for Drug Evaluation and Research http://www.fda.gov/cder Guidelines National Comprehensive Cancer Network, http://nccn.org San Antonio Breast Cancer Symposium http://sabcs.org American Society of Clinical Oncology http://asco.org

22. Project LEAD  http://natlbcc.org or Google National Breast Cancer Coalition http://natlbcc.org  Check left column links, click on Education and Training, and click again on Project LEAD