INTRODUCTION TO SCIENTIFIC PAPERS Joe Pozdol, MLIS Evans Whitaker, MD, MLIS Norris Medical Library University of Southern California 2003 Zonal Ave. Los Angeles, CA 90089-9130 pozdol@usc.edu ewhitake@usc.edu

Before We Begin… Ask! PowerPoint at www.usc.edu/nml under Key Resources for Students Interactive questions Handouts Article later Evaluation Unwanted handouts

Outline For Today I. Parts of a paper A. Abstract B. Introduction/Background C. Methods D. Results E. Discussion F. References (Bibliography) II. Study types A. Primary 1. Observational 2. Experimental B. Secondary III. Group work IV. Evaluations

PART I Sections of a published scientific paper

Part I Objectives Learn the basic structure of papers Develop an approach to reading papers Learn how to interpret an article citation

The Basic Parts Title Abstract Introduction Methods Results Discussion References

Read In This Order Title Abstract Introduction/ Discussion Methods/ Results

The discussion section occurs before the author presents the results of the study. True False

Which occurs first in a scientific journal article? Abstract Discussion Introduction Methods Results

Abstract Summarizes Often only part read Don’t act on abstracts alone Structured abstracts are norm Background Methods Results Conclusions

Introduction Context What is known Supporting literature (citations) Gaps in literature The research question Newness Relevance to field

Methods Steps taken to Statistical methods Not a “cookbook” Replicable gather data analyze data Statistical methods Not a “cookbook” Replicable

Results Report of data Tables and graphs Statistical results No interpretation

Discussion Interpretation of results Answer to research question Goals met? Often includes relation to previous research limitations future directions

Which should allow other researchers to replicate the study? Abstract Discussion Introduction Methods Results

Limitations of the study are found in the… Abstract Discussion Introduction Methods Results

References List of sources cited in intro Usually other journal articles Previous studies in same field Citation styles differ depending on field of study (e.g. AMA vs. APA) journal EndNote and RefWorks

Understanding Journal Article References Weiss, PA. Does smoking marijuana contribute to the risk of developing lung cancer? Clinical Journal of Oncology Nursing. 2008;12(3):517-519. Journal Volume Number Issue Number Researcher’s Article

Which cannot be determined from a reference list citation? Title of the journal Title of the journal article Number of pages in the journal Number of pages in the journal article None of the above

Whether marijuana use causes lung cancer is still unknown and will likely be a subject of research in the next 5 years. True False

PART II TYPES OF SCIENTIFIC PAPERS

Part II Objectives Learn the common study types Be able to extract the research question Be able to identify an article’s study type Be able to determine the conclusions

Outline For This Section Focus on 4 study designs Case-control Cohort Randomized Control Trial Review Narrative Systematic Meta Analysis There are others but these are the main four; two others are mentioned in your handout

“3 questions to get your bearings” * What was the research question? What was the research design? Was the research design appropriate to the question? Will try to find answers to 1 and 2 in excerpts of 4 articles (A-D) provided These three questions can be asked of any research study. What was the research question? Why was the study needed? (Another way to say “Was the study original? Does it add to our understanding?” What was the research design? Was the research design appropriate to the question?* * - Greenhalgh, T. (2006). How to read a paper: the basis of evidence-based medicine. Malden, MA: Blackwell 24

Study Designs Primary Literature Secondary Literature Observational Case-Control Cohort Experimental Randomized Control Trial Secondary Literature Narrative (Subject/Journalistic) Reviews Systematic Review Meta Analysis Observational means that the researcher does not choose which group a subject is part of – the experimenter observes the subjects as they are and does not manipulate the assignment Experimental means that the researcher assigns subjects to an experimental or control group Many ways to organize this information. This is one way that makes sense to me. Secondary literature is a summary of primary literature. Narrative, Subject, or Journalistic Reviews -- subject to author bias Systematic Review – a transparent, well-defined methodology is used to select and analyze a group of articles Meta Analysis – similar to above but using statistical methods to combine results of studies Primary literature reports the individual investigations/experiments. Primary literature can be divided in two groups: Observational in which the investigator does not control what exposures the subjects have. Experimental in which the experimenter controls exposures that the subjects have. Retrospective looks at previously collected data. May apply to case-control, cohort. It is possible to do retrospective analysis of data from an experiment (questionable practice). Prospective data is collected moving forward in time. Cross-sectional – usually applied to case-control (or cross-sectional) studies. Data are collected at a point in time for a group of subjects. Longitudinal - data is collected over time for a group of subjects Blinding applies to experimental design: 1. the subject does not know whether he/she is in the treatment or the control group. 2. the experimenter who measures outcomes does not know which subjects are in which group. 1 only = Single blind 1 and 2 = Double blind Cross over – subjects act as their own controls. Usually there is a “wash out” period between phases. Qualitative studies Secondary literature – see above 25

Case-Control Patients with a disease or exposure --compared to-- Similar group without disease or exposure Best uses Rare conditions Diseases or conditions that may take a long time to develop

Background: DES Used in the United States from 1947 until 1971 Boston area doctors noted an unusual cancer Study compared the group with the cancer to similar people without the cancer The major difference between the cases and the controls was DES exposure DES is an estrogen approved by US FDA in 1947 to prevent spontaneous or habitual abortion. Two large trials showed it to be ineffective for its proposed uses in 1963. Despite this it was used ‘til ‘71 in US and mid-to-late ‘70s in Europe. In late ‘60s, 8 cases of clear-cell adenocarcinoma (CCAC) of the vagina were reported in women in their teens and twenties. This tumor type had not been seen in this age group before; the cancer was rare in any case and almost always found in those >50. These “cases” of CCAC were compared to other women of same age without CCAC. The use of DES by the case’s mothers during pregnancy was found in the CCAC women but not in the controls. The Case Control study was completed in months, reported in 1971. If the researchers had used other methods it might have taken 20 years to show the relationship between DES and CCAC. 27

Example: DES and Cancer Herbst, A.L., Ulfelder, H., & Poskanzer,D.C. (1971). Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. NEJM, 284(16), 478-481. Look at article: Last sentence in Introductory area = research question First paragraph in methods = research design “case-control retrospective study” – clearly labels itself as a case-control study “four matched controls for each patient…were selected by examination of birth records”. “Females born within 5 days and on the same type of service”.

Why did the authors match cases and controls by the type of service mothers received?* * -see page 879 To reduce socioeconomic differences To examine whether the cancer was related to infectious disease exposures To decide if chemical disinfectants used to clean wards caused cancer All of the above

How many of the 8 cases’ mothers were given estrogen in pregnancy (DES)? All Seven Five Three One None 30

Cohort Two groups compared over time One group with “exposure”, the other without the “exposure” Best used: when exposures can’t be controlled when outcomes occur infrequently when RCT is not ethical Exposure is a broad term, can be a… Drug Environmental exposure Genetic inheritance (parent or parents with a disease; subject with known genetic variant) 31

Example: Smoking vs. Non-Smoking British Physicians Doll, R., Peto, R., Boreham, J., & Sutherland, I. (2004). Mortality in Relation to Smoking: 50 years' observations on male British doctors. BMJ, doi:10.1136/bmj.38142.554479.AE 50 years (and counting) Cohort Study of British doctors Most recent of a series of reports Compared health outcomes of smokers vs. health outcomes of non-smokers Research question = Research design = Amazing study of British MDs now followed for 50 years with 94% follow-up of those still living study ended in 2005 Notice this article never proclaims itself as a cohort study. Compared health outcomes of smokers vs. health outcomes of non-smokers Reports: 1954, 1956, 1964, 1976, 1994, 2004. 35,000 MDs at outset, 10,000 died in first 20 years, 10,000 in the next 20 years, another 5,000 in the last 10 years. Men who smoked throughout the study died on average 10 years earlier than non-smokers. 32

When was there enough evidence from this study to show the link between smoking and lung cancer? 1954 1966 1978 1991

Randomized Control Trial A treatment group is compared to a control group Group members are assigned randomly Best uses: Drug therapies Medical treatments “Cross over” means that subjects become their own controls. Placebo control means that a placebo was used on the control group and compared to an active treatment for the treatment group Single blind means that the subjects did not know which group they were in – control or treatment Double blind means that both the investigators and subjects did not know which group the subjects were part of.

Example: Smoking cessation intervention An, L.C., Klatt, C., Perry, C.L., Lein, E.B., Hennrikus, D.J., et al. (2008). The RealU online cessation intervention for college smokers: a randomized control trial. Preventive Medicine, 47(2)194-199. Look at the article: The last paragraph of the introduction - research question The last paragraph of the introduction - research design Study flow chart - pg. 196 As you can see this study tells you the study type in the title, and in the abstract. It does not say RCT in Methods? Notice the study flow sheet on page 196

25,000 UM students were recruited by email How many UM students ended up in the intervention group? 1. 24,007 2. 2,407 3. 257 4. 107 5. 7

What percent of RealU participants had 30 days of no smoking at week 30? 100% 80% 60% 40% 20% none 30

Narrative (Journalistic/Subject) Reviews The “traditional” or “classic” review “Review” limit in Ovid/PubMed includes: Narrative reviews Systematic reviews Authors choose articles included Author bias is a concern – research verifies this effect When you search MEDLINE you can cut down your number of articles by only including reviews. 38

Systematic Review Reproducible methods to find and select articles are included Should include both inclusion and exclusion criteria Why? Decrease author bias

Example: Is HPV Vaccine Cost-Effective? Techakehakij, W., Feldman, R.D. (2008). Cost-effectiveness of HPV vaccination compared to Pap smear screening on a national scale: a literature review. Vaccine, doi:10.1016/j.vaccine.2008.09.036 Look at article: Pg. 2, Section 3.1, first paragraph = research question Pg. 3, Section 4.1, first to third paragraphs = research design The essence of this article is that cervical cancer remains a killer of a quarter million women a year almost all in the developing world. Two HPV vaccines have been released on the market in the last few years but remain quite expensive, although appear effective. PAP smears have been used for the last 65 years to test women for cervical cancer. The test has problems with the ability to detect problems (low sensitivity) but widespread use in the US has decreased cervical cancer mortality by >70%. How do we decide whether to begin a cervical cancer immunization program? That study examines cost-effectiveness – does the cost of the vaccination program save money compared to the costs of a PAP smear program. The analyses attempt to factor in the obvious costs (cost of the programs), and the less obvious costs (failed vaccines, cost of cancer treatment, incomplete screening and vaccination).

It is recommended that HPV vaccine be given as a 3 shot series It is recommended that HPV vaccine be given as a 3 shot series. How much do 3 doses of vaccine cost? $500-$1000 $300-$500 $200-$300 $100-$200 30

Meta Analysis Similar to Systematic Review except… Numeric data from separate studies combined in meta analysis Uses statistical/mathematical methods to combine numerical data from studies Combining data increases the confidence we have in the conclusions reached by a meta analysis

GROUP WORK

Group Work Groups of 3 Everyone in group gets same article (#1, 2, 3, OR 4) Spend 10 min. working together on questions Class discussion One article from each of these four types: Case-control Cohort Randomized control trial Systematic review

Additional slides

What kind of question is it good for? Identifying Characteristics Article Type What kind of question is it good for? Strengths Weaknesses Identifying Characteristics Case-Control (Herbst, 1971) (Peled, 2008) -Rare disorders or conditions -Slow developing disorders -Causation* -Short time frame to examine correlations between disorder and other factors -Susceptible to bias -Limited validity -Cross sectional Cohort** (Doll, et al, 2004) (Metcalf, 2008) - Prognosis - Feasible when studying conditions or exposures over which the investigator has no control -May require large groups, long durations, great cost -Longitudinal -Usually prospective -Can be retrospective (less cost) Randomized Control Trial (RCT) (An et al, 2008) (Gordon, 1997) -Drug treatment -Medical interventions -Strong level of evidence -Low susceptibility to bias -Feasibility (e.g. Ethical limitations) -Generalizability** -Randomization method -Experimental and control groups Systematic Review (Techakehakij,2008) (Gallicchio, 2008) -Strongest level of evidence -Many topics have no systematic review -Methods section has explicit information about information sources, how articles were chosen or excluded * - used loosely here; not distinguishing between correlation and causation (in medicine etiology is used for the cause of a disease or condition) ** - can results of an RCT be applied to groups that do not match the study group?

Used for Evidence-Based Medicine The Evidence Pyramid Used for Evidence-Based Medicine

Thanks for your attention We will post these slides on the Student Portal on the Norris Medical Library website Contact us with questions Joe Pozdol – pozdol@usc.edu Evans Whitaker – ewhitake@usc.edu Please complete evaluations!

References An, L.C., Klatt, C., Perry, C.L., Lein, E.B., Hennrikus, D.J., et al. (2008). The RealU online cessation intervention for college smokers: a randomized control trial. Preventive Medicine, 47(2)194-199. Doll, R., Peto, R., Boreham, J., & Sutherland, I. (2004). Mortality in Relation to Smoking: 50 years' observations on male British doctors. BMJ, doi:10.1136/bmj.38142.554479.AE Gallicchio, L., Boyd, K., Matanoski, G., et al. (2008). Carotenoids and the risk of developing lung cancer: A systematic review. Am.J.Clin. Nutrit., 88, 372-383. Gordon, C.M., Carey, M.P., & Carey, K.B. (1997). Effects of a drinking event on behavioral skills and condom attitudes in men: Implications for HIV risk from a controlled experiment. Health Psychology, 16(5), 490-495. Greenhalgh, T. (2006). How to read a paper: the basis of evidence- based medicine. Malden, MA: Blackwell. Guyatt, G., Rennie, D. (eds.). (2001). User’s guides to the medical literature: essentials of evidence-based clinical practice. Chicago: AMA Press.

References Herbst, A.L., Ulfelder, H., & Poskanzer,D.C. (1971). Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. NEJM, 284(16), 478-481. Metcalf, B.S., Voss, L.D., Hosking, J., & Wilkin, J.T. (2008). Physical activity at the government-recommended level and obesity- relatedhealth outcomes: a longitudinal study (Early Bird 37). Archives of Diseases of Childhood (Early Bird 37). 93,722-777. Peled, R. Carmil, D., Siboni-Samocha, O., & Shoham-Vardi, I. (2008). Breast cancer, psychological distress and life events among young women. BMC Cancer, 8, 245-250.