Clinical Trials and the Scientific Method

1. Clinical Trials and the Scientific Method

2. Objectives At the end of this session, we hope you will be able to: Describe what a clinical trail is. Describe three different study designs. Define two phases of a clinical trial. Review differences between regular clinical care and treatment provided through research studies.

3. What is the �Scientific Method�? The scientific method is a way to ask and answer scientific questions by making observations and doing experiments. The steps of the scientific method are to: Ask a Question Do Background Research Construct a Hypothesis Test Your Hypothesis by Doing an Experiment Analyze Your Data and Draw a Conclusion Communicate Your Results In an experiment, it is important to change only one factor (variable) and keep all other conditions the same so that you can evaluate the effect of that variable. From www.sciencebuddies.org/mentoring/project_scientific_method.shtml

4. Can scientific methods be used when a question involves people? Yes, but it is not easy. A scientist working with people tries to mimic an experiment as closely as possible. Ideally, the scientist would change only one variable at a time. However, when studying people, it is difficult to keep all other factors the same. The scientist also has to consider often complicated ethical issues when designing experiments that involve people.

5. Can scientific methods be used when a question involves people? An example: a scientist may want to determine if a new medicine helps to improve diarrhea in children. To try to set up an experiment, the scientist hopes to change only one factor at a time. A scientist may decide to take two children with diarrhea, give one the medication, but withhold it from the other to see if there is a different outcome between the children. However, the scientist has changed many more variable than just one�

6. Although it might seem like the scientist changed only one variable (the person), many things have actually changed: The children could have different illnesses. The children could have different severities of illness. The children could be sick for different lengths of time . The children could be different ages. One child might continue to be exposed to the source of the illness while the other child does not. Can you think of other possible differences?

7. Would their be ethical issues to consider in such an experiment? Does the scientist know if the medicine is safe in children? Is it safe for different ages? Is their a better treatment available that would be withheld from the child to test this new product? Do the parents what a new medicine tested on their child? Can you think of other ethical considerations?

8. Given these challenges, what do scientists do when a question involves people? A scientist can conduct a clinical trial: A clinical trial tries to approximate a scientific experiment.

9. A clinical trial is� A research activity that involves the administration of a test regimen to humans to evaluate its efficacy and safety. The term is often applied to a rigorously designed and executed experiment involving test and control treatments and randomization. Based on: Last, J. M: A Dictionary of Epidemiology, 2nd ed. New York: Oxford University Press, 1988, pp 24-25.

10. Types of Studies There are Experimental and Observational Studies: In experimental (intervention) studies, the researcher determines who is exposed. Clinical trials are a type of experimental study. In observational studies, the participants are observed to see what occurs naturally or with exposures selected by the participant.

11. Study Designs Intervention trials (experimental, such as clinical trials) Cohort studies (observational) Case-control studies (observational) Cross-sectional studies (observational)

12. Types of intervention studies Clinical trials � intervention is applied to individuals (patients, students, workers) Community trials � intervention is applied to groups (schools, worksites, communities) /

13. Intervention trials (such as clinical trials) Intervention trials are studies that take place forward through time in which an exposure or exposures are assigned to people and subsequent outcomes observed. The people who do not receive the exposure are usually called the �control group� or the �control�. There is usually a baseline visit to identify conditions before the exposure and one or more follow-up visits to determine how the exposure affected the participant. TIME ??? exposure/intervention assigned

14. Intervention trials (such as clinical trials) Based on scientific experimentation where the scientist changes one variable to find out how the variable affects the outcome. The objective of intervention trials is to create two similar groups of people where only one variable (the intervention) changes making it easier to compare the groups and find out the effect of the intervention. In intervention trials, the investigator assigns the intervention to the study participants.

15. Randomization, Placebos, and Blinding are� Ways of designing a research study to help avoid misleading conclusions. These techniques are used to help make the groups under study similar except for the key factor under investigation. Randomization involves assigning people to study groups in a random order to help keep the composition of the groups similar. Placebos are a medication or procedure similar to the intervention, but which lack the key component under investigation. These may be given to the unexposed group to help keep the groups as similar as possible with the exception of the key factor under study. �Blinding� or �masking� is done to keep the participants and/or the investigator unaware of who is receiving the intervention so that they don�t respond differently based on this knowledge.

16. Cohort Studies Cohort studies are also studies that take place forward through time � they begin before the disease has taken place and follow-up the study population to see who develops the disease. The intervention/exposure is not assigned, but differences in the exposure are recorded to see how they affect development of disease. The goal is to make it as close to a scientific experiment as possible. TIME ?? exposed/intervention (not assigned) ?? not exposed/no intervention (not assigned)

17. Cohort Studies Many diseases occur in only a small number of people so it can be expensive and challenging to observe cases by following people over time. People who choose different interventions may be different from one another in other ways so this is less like a scientific experiment than a clinical trial.

18. Case-Control Studies Involves identifying people with the disease and people without the disease and comparing the information to see what is different between the groups. A short-cut. Backwards in time � what were they exposed to before they developed the disease?

19. Case-Control Studies The case-control study offers an efficient way to study rare diseases, since it enrolls people with the disease already and compares these to a sample of people representing the population at risk. Limitations: You may not know when the exposure takes place, higher chance of error such as recall bias.

20. Cross-Sectional Studies Cross-sectional studies measure how frequent the condition is at a given point in time as well as other characteristics. Surveys are cross-sectional. Are harder to determine cause and effect.

21. Example Exposure = lunch Condition = feeling impatient Intervention study: I am going to assign who gets to eat lunch today and who does not and check to see how people feel later in the day. Cohort study: I am going to identify those that eat and those that don�t eat (without assigning) and will check to see how people feel later in the day.

22. Example Exposure = lunch Condition = feeling impatient Case-Control: This afternoon, I am going to identify those who are acting impatient and having trouble concentrating. I will compare them to those who are not acting this way and will find out how many from the two groups ate lunch. Cross-sectional: I will give a questionnaire this afternoon and will ask people if they are feeling impatient, are having trouble concentrating and will ask whether or not they ate lunch.

23. How to choose the design to be used by the study? Is the disease rare or common Prior research Time Money What data or populations are available already

24. How studies can be conducted Single site � interventions provided from a single center Multi-site � multiple centers and a coordinating center

25. What does the �phase� of the study mean? Phase I: The initial introduction of a new product or drug to humans in order to determine the human pharmacology and assess issues of safety and tolerance in a small group of people. For medications and medical devices, pre-clinical studies are usually done before Phase I trials. The preclinical trials involve laboratory studies or studies with animals in order to obtain preliminary efficacy, toxicity and pharmacokinetic information and to decide if it is worth testing further.

26. Phases of a clinical trail Phase II: Controlled clinical studies conducted to evaluate the effectiveness, efficacy, and side effects of the investigational product in a small, well defined group of patients.

27. Phases of a clinical trail Phase III: Expanded trials that are performed after preliminary evidence suggests that the product is safe and effective and that are intended to gather additional information about effectiveness and safety that is needed to evaluate the overall benefit-to-risk relationship of the investigational product.

28. Phases of a clinical trail Phase IV: This is post-marketing surveillance that is conducted to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials.

29. In epidemiologic studies such as clinical trials, Review boards (such as IRBs) judge whether the study is ethical. It can withhold permission to conduct the study or can request changes. Prior to study procedures, participants undergo informed consent. Informed consent is the process by which a patient is fully informed about the study and can decide whether or not to join the study.

30. Are clinical trials similar to clinical treatment? NO

31. How regular clinical care differs from a research study

32. How regular clinical care differs from a research study

33. How regular clinical care differs from a research study

34. If there are controlled clinical trials, is there such a thing as an out-of-control clinical trial? (Probably, but hopefully it won�t be yours�!)

35. Thank you for listening  and Good Luck!