1. + Module 6: Part Two Experimental Studies

2. + USA Today 3/11/2013: Kraft Macaroni & Cheese too yellow? Two moms “blogging” in NC started petition Obtained 200,000 signatures in 5 days Issue: Petitioners want yellow dye 5 and yellow dye 6 removed from list of additives in Kraft mac & cheese (already being done in Europe without a difference noted in taste) Claim: These two food dyes have been associated with hyperactivity in children, allergies, migraines Other concerns: Because they are petroleum-based, these dyes may be associated with various cancers as well How do we scientifically investigate these claims?

3. “True” Experimental Strategy If you want to draw a cause-effect conclusion, you must run an experimental design or strategy. Key features include: A. Manipulation of an independent variable B. Control condition C. Random assignment of participants to groups

4. + Or, more specifically: 1. Must be manipulation of the independent variable to see the effect on the dependent variable. 2. Must have comparison of the dependent variable results in at least two conditions (experimental and control group) Experimental Group: Receives the manipulation of the independent variable. Control Group: Does not receive the manipulation of the independent variable (everything else is held constant). 3. Must randomly assign participants to the experimental and control conditions before the manipulation of independent variable. 4. Must control the unwanted effects of extraneous variables on the dependent variable.

5. + The experimental design is the considered the “gold standard” of designs because, if done properly, it allows: Causal Inference = a conclusion where one variable or event causes another. Also called a cause-effect conclusion. Cause-effect conclusion can be made if all of the following criteria are met: 1. Co-variation of variables 2. Causal time sequence 3. Elimination of all other plausible causes.

6. + Unwanted sources of variance Sometimes extraneous variables that the researcher was unaware of can influence the dependent variable. Drinking coffee Cardiovascular disease Smoking

7. + Attrition Refers to a loss of participants during the course of the study. Differential attrition refers to the situation when participants are leaving one independent condition at a higher rate than another.

8. + Bias There are 2 main sources of bias: Participant Bias (Hawthorne Effect) Behavior on the part of the subject due to their awareness of being observed Note: Participants often behave the way they perceive the experimenter wants them to behave; called the good-participant effect Experimenter Bias (Rosenthal Effect) The experimenter knows how participants are expected to respond and may unwittingly coach them to respond in a particular way. The optimal approach to the elimination of these biases is to utilize a “Double-Blind” procedure. Neither the participants nor the experimenter knows who is in each experimental condition.

9. + The Clinical Trial National Institutes of Health www.clinicaltrials.gov Biomedical or health-related research studies in human beings that follow a pre-defined protocol Interventional or observational

10. + Interventional studies: Research subjects are assigned by the investigator to a treatment (or other intervention) Outcomes are measured Observational studies: Individuals are simply observed Outcomes are measured

11. + Types of Clinical Trials Treatment trials Prevention trials Diagnostic trials Screening trials Quality of life trials

12. + KEY DEFINITIONS - PROTOCOL A study plan on which all clinical trials are based The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions

13. + Protocol Describes: What types of people may participate in the trial The schedule of tests, procedures, medications, and dosages The length of the study

14. + KEY DEFINITIONS - PLACEBO An inactive pill, liquid, or powder that has no treatment value. Experimental treatments are often compared with placebos to assess the experimental treatment's effectiveness. In some studies, participants in the control group will receive placebo instead of an active drug or experimental treatment.

15. + Phases of Clinical Trials Phase I - researchers test an experimental drug or treatment small group of people (10-80) first time to be evaluated determine safety, safe dosage range, and identify side-effects Phase II - experimental study drug or treatment given to a larger group of people (100-300) see if it is effective, further evaluate its safety

16. + Phases of Clinical Trials Phase III - experimental study drug or treatment given to large groups of people (1,000-3,000) confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely Phase IV - post-marketing studies delineate additional information including the drug's risks, benefits, and optimal use

17. + Participating in a Clinical Trial INCLUSION/EXCLUSION CRITERIA: Medical or social standards determining whether a person may or may not be allowed to enter a clinical trial: Criteria based on such factors as age, gender, type and stage of a disease, previous treatment history, and other medical conditions Criteria not used to reject people personally, but rather to identify appropriate participants and keep them safe

18. + Informed Consent Risks and potential benefits are explained in the informed consent document The participant then decides whether or not to sign the document Informed consent is not a contract, and the participant may withdraw from the trial at any time

19. + Study Type: Interventional Study Design: Crossover Assignment, Double blind In a double-blind, crossover study, participants receive either real treatment or placebo for a time, and then are switched ("crossed over") to the opposite treatment. Thus, researchers can get “double mileage” out of their participants—each person gets both placebo and treatment. The advantage of a crossover trial is that it effectively doubles the number of people in a trial. This makes it easier for researchers to obtain statistically significant results.statistically significant

20. + The Tuskegee Experiment: Ethical concerns in research Public Health Service, working with the Tuskegee Institute 1932: Nearly 400 lower-income African-American men with syphilis from Macon County, Alabama were enrolled in the study. Were never told they had syphilis, nor were they ever treated for it According to the Centers for Disease Control, the men were told they were being treated for "bad blood," a local term used to describe several illnesses, including syphilis, anemia and fatigue For participating in the study, the men were given free medical exams, free meals and free burial insurance

21. + At the start of the study, no proven treatment for syphilis Penicillin became a standard cure for the disease in 1947, medicine was still withheld from the men The Tuskegee scientists wanted to continue to study how the disease spreads and kills Experiment lasted four decades, until public health workers leaked the story to the media. By then, dozens of the men had died, and many wives and children had been infected. In 1973, NAACP filed a class-action lawsuit; $9 million settlement was divided among the study's participants. Free health care was given to the men who were still living, and to infected wives, widows and children. It wasn't until 1997 that the government formally apologized for the unethical study. President Clinton delivered the apology.