Study Designs, Sample Size, Statistics, Data Repositories and Registries

1. Study Designs, Sample Size, Statistics, Data Repositories and Registries

2. Topics Study Designs Statistical terms and concepts Databases and Repositories Registries

3. Study Designs and Statistical Terms and Concepts

4. Experimental research provides the opportunity to identify cause-and-effect relationships. Non-experimental research is non-manipulative observational research usually conducted in natural settings. .

5. Experimental and Non-Experimental Research Experimental research provides the opportunity to identify cause-and-effect relationships. Higher in internal validity – how confident one can be that the effects were caused by the dependent variable. Non-experimental research (case studies, surveys, correlation studies) is non-manipulative observational research usually conducted in natural settings. Higher in external validity – the extent to which a study's results can be generalized or applied to other people or settings . .

6. Most experimental research can be identified by three important characteristics: • Subjects are randomly assigned to experimental conditions. • The researcher manipulates an independent predictor variable. • Subjects in different experimental conditions are treated similarly with regard to all variables except the independent variable

7. A variable refers to some specific characteristic of a study that assumes one or more different values. For example, in clinical research, differences in the ethnic make-up or gender of the study population could affect the way a new drug acts.

8. • Independent variable - the variable whose values (or levels) the experimenter selects to determine what effect this independent variable has on the dependent variable. (Intervention) • Dependent variable - some aspect of the subject’s behavior assessed to reflect the effects of the independent variable.

9. Predictor variable is the variable used to predict values of the response. In some studies, you might even believe that the predictor variable has a causal effect on the response. Response variable - an outcome variable whose values you want to predict from one or more predictor variables. The “response” to whatever predictor you are evaluating.

10. A population is the entire collection of a carefully defined set of people, objects, or events. Example: If it is estimated 1000 individuals were treated for a certain condition being studied, then those 1000 individuals would be the population.

11. A sample is a subset of the people, objects, or events selected from that population. For example, the 100 of the 1000 individuals discussed on the lat slide could be a sample.

12. The research question is a statement of the information the research will provide when it is complete.

13. A hypothesis is a statement about the predicted relationships among events or variables.

14. A null-hypothesisis the assertion that the things you were testing are not related and your results are the product of random chance events.

15. A statistic is a numerical value that describes some characteristic and can be used to make inferences about a population .

16. Statistical significance is defined as the probability that it will reject a false null hypothesis. • Statistical power is the likelihood that a study will detect an effect when there is an effect to be detected. If statistical power is high, the probability of concluding there is no effect when, in fact, there is one, goes down (Type II Error) • The bigger the effect, the easier it is to detect • The larger the sample size the greater the test sensitivity

17. Preclinical Studies 3 -6 years Drug activity is evaluated in tissue cultures and in animals. • Phase I – Assess safety,pharmacokineticsand pharmacodynamicsin healthy volunteers. Clinical Trials 6 -7 years • Phase II– Controlled studies (usually randomized, double blind) in a limited number of volunteers to obtain data on short-term safety and effectiveness. • Phase III– Controlled & uncontrolled studies with larger number of volunteers to study effectiveness and long-term safety. • Phase IV – Conducted after FDA approval. In most instances, the objective is to collect additional safety data

18. Controlled study is a study were one or more group receives the investigational substance and one ore more groups receive placebo or a different treatment. The groups are often referred to as “arms.”

19. Placebo is an inactive substance that looks the same as the drug under investigation

20. Randomized means the participants are assigned to a study arm by chance.

21. Double-Blinded means the study doctor and participant do not know whether the participant is receiving the active drug or placebo.

22. A crossover study is a controlled, randomized trial in which participants are given more than one treatment in an effort to get the most accurate results. The participants cross over from one treatment to another.

23. Dose Escalation (dose findings)means one group of participants receive a very low dose of study drug and each subsequent group receives slightly higher doses until the side effects become intolerable. The dose below the last dose is considered the ideal dose.

24. Washout is when participants stop taking their usual medication for a period of time before they start taking the treatment they are assigned to.

25. Question • Study of investigational drug XIX to test safety and efficacy in 500 subjects. One-half of the participants will be randomly assigned to receive XIX. Half will be randomly assigned to receive placebo. Neither the participant nor the investigator/research staff will know which group the participant is in. How will this study be described?

26. Answer • Phase II, randomized, double-blinded, placebo controlled study of XIX

27. Question • Study of XIX –Participants will be randomly assigned to one of three arms. Arm 1 receives 50mg of XIX; and Arm 2 receives placebo. After three months the participants in Arm 1 receive placebo and the participants in Arm 2 receive 50mg of XIX. Neither the participant nor the investigator/research staff know which drug the participant is taking.

28. Answer • A Phase II, randomized double-blind placebo controlled crossover design study of XIX.

29. Question • Study of XIX – The first 10 Participants will be assigned to 10 mg; the next 10 participants will be assigned to 20 mg; the next 10 participants will be assigned to 30 mg and each subsequent group will be assigned to a dose 10mg higher than the last group until a group experiences a frequent or severe side effects that are intolerable.

30. Qualitative Research Gather in-depth understanding of human behavior and the reasons for certain behaviors. Investigates the why and how of decision making. Open ended questions are used in focus groups and interviews. Used in social sciences and market research. Issue – Results could reflect unfavorably on a group - stigmatize

31. Databases and Repositories

32. Terms: Database, registry, data bank, repository, and tissue bank are often used imprecisely, and sometimes interchangeably. • A repository – Collection of data or biological specimens whose organizers • – Receive data or specimens from multiple sources; • - Maintain data or specimens over time • – Control access to and use of data or specimens

33. Collection of Data Samples Storage of Data or Samples Release of Data or Samples • Informed consent • IRB review • Agreements • Informed consent • IRB review • Certificate of Confidentiality • Informed consent • IRB review • Agreement from Recipient

34. Informed Consent • Operation of the database • Types of research to be conducted • Conditions under which data will be released to recipient-investigators; and • Procedures for protecting the privacy of subjects • How subjects may request their data/specimens be withdrawn/destroyed, or that identifiers be removed • Length of time data will be stored- may be indefinite • Consequences of genetic testing, if applicable

35. Submittal Agreements • Data collection policies should ensure that the data was collected in an ethical manner • Adequate informed consent • IRB review when necessary

36. Repository Protocol or Policies • Should describe • Requirements for submission (informed consent, irb review) • Physical and procedural mechanisms for the secure receipt, storage, and transmission of information and specimens • Policies on release of information and specimens • Coding • Release of identifiers • Certificates of Confidentiality

37. Recipient Agreements • Recipients should enter into an agreement • Conditions for release of data or specimens to investigator • Whether release requires IRB Oversight • Agreement to not attempt to identify individuals from whom data or specimens were obtained

38. Registries

39. A registry has been defined as a file of documents containing uniform information about individual persons, collected in a systematic and comprehensive way, in order to serve a predetermined purpose.

40. Examples • Registries of exposure to drugs during pregnancy • Device registries • Disease registries • Patient outcome research • Epidemiological studies • Impact of physician behaviors on quality care