1. Regulatory Clinical Trials Clinical Trials

2. Clinical Trials Definition: research studies to find ways to improve health Definition: research studies to find ways to improve health Each trial tries to answer scientific questions Each trial tries to answer scientific questions Types of trials Types of trials –Treatment trials: test new treatments (new drug) –Prevention trials: test new approaches to prevent illness (vaccines) –Screening trials: test new methods (new test method) –Quality of Life trials: (supportive care) test for ways to improve comfort and quality of life

3. Pre Clinical Trials Performed on animals Performed on animals –Try to use animal model which most closely relates to human subject i.e. pigs may be used to study effects on skin i.e. pigs may be used to study effects on skin Performed to predict potential toxic effects on humans Performed to predict potential toxic effects on humans –Minimize the risk of harm during clinical trial

4. Clinical Investigation Definition: any experiment that involves a test article and one or more human subjects and that is either subject to requirements for submission to FDA or is not subject for submission but results are intended to be submitted later. Definition: any experiment that involves a test article and one or more human subjects and that is either subject to requirements for submission to FDA or is not subject for submission but results are intended to be submitted later.

5. Clinical Trial: why do it? To understand if the drug or device does what it claims to do (efficacy) To understand if the drug or device does what it claims to do (efficacy) To ensure safety to public To ensure safety to public To ensure safety to participants To ensure safety to participants

6. Clinical Trial: Who oversees? FDA establishes guidelines for clinical trials FDA establishes guidelines for clinical trials –21CFR50: Title 21 Section 50 of Code of Federal Regulations Regulatory Department Regulatory Department –Within any organization this group oversees the actual clinical trial

7. Why did the FDA need to establish guidelines? To ensure patients knew they were participating To ensure patients knew they were participating –Informed consent: was not always obtained –HIPAA came on board to protect the patient’s privacy To ensure guidelines were in place for controlling the drug which was being investigated To ensure guidelines were in place for controlling the drug which was being investigated –Accountability; prevent abuses of drugs and devices

8. Informed Consent Written document Written document Outlines the following: Outlines the following: –Purpose and method of the study –Alternative methods of treatment –Benefits and Risks of participation –Right to refuse or withdraw from study Does not include the right to see the results of the study Does not include the right to see the results of the study

9. International Guidelines ICH: International Conference on Harmonization…. ICH: International Conference on Harmonization…. –Regulatory authorities in Europe, Japan, and US got together to establish guidelines for clinical trials and product registration Declaration of Helsinki Declaration of Helsinki –World Medical Association –1 st adopted in 1964

11. Phases of Clinical Trials Phase 1: small number of patients, (10-20) Phase 1: small number of patients, (10-20) –Can take 9-18 months to complete –May continue with animal studies for long term data Phase 2: continues to test safety and evaluates how well the new drug is working. More patients enrolled (100-300) Phase 2: continues to test safety and evaluates how well the new drug is working. More patients enrolled (100-300) –May take 1-2 years to complete Phase 3: most extensive study,1-3 years Phase 3: most extensive study,1-3 years –Fully assess safety and effectiveness of drug –100-1000 patients involved, diverse group, multiple sites –May compare old and new drug treatments –Evaluating side effects Phase 4: long term side effects and effectiveness Phase 4: long term side effects and effectiveness

13. Participants in clinical trials Investigator Investigator Sponsor Sponsor Sponsor Investigator Sponsor Investigator Human Subject Human Subject Institution Institution Institution Review Board Institution Review Board

14. Investigator Individual who actually conducts the clinical investigation or is the leader of the team conducting the trial Individual who actually conducts the clinical investigation or is the leader of the team conducting the trial Main person responsible for the safety of the human subject participating in the study Main person responsible for the safety of the human subject participating in the study –however, all healthcare workers are responsible for protecting the human subjects Nurse, investigator, IRB, etc. Nurse, investigator, IRB, etc.

15. Sponsor and Sponsor Investigator Sponsor: person who initiates a clinical investigation, but does not actually conduct the investigation Sponsor: person who initiates a clinical investigation, but does not actually conduct the investigation Sponsor Investigator: person who both initiates AND actually conducts the clinical investigation Sponsor Investigator: person who both initiates AND actually conducts the clinical investigation

16. Human Subject and Institution Human participating in the clinical investigation Human participating in the clinical investigation Institution: any public or private entity or facility. Typically the facility where the clinical investigation is being conducted Institution: any public or private entity or facility. Typically the facility where the clinical investigation is being conducted

17. Institutional Review Board Definition: any board, committee or group formally designated by an institution to review biomedical research involving human subjects Definition: any board, committee or group formally designated by an institution to review biomedical research involving human subjects IRB approval MUST be obtained before an investigator can begin a study IRB approval MUST be obtained before an investigator can begin a study

18. Institutional Review Board Usually comprised of medical and lay persons (at least 5 members, no conflict of interest) Usually comprised of medical and lay persons (at least 5 members, no conflict of interest) Established to protect the human subjects and ensure fair enrollment Established to protect the human subjects and ensure fair enrollment Review and Approve Informed Consent Review and Approve Informed Consent Conduct periodic reviews to ensure integrity of the study Conduct periodic reviews to ensure integrity of the study

19. When is IRB not required? Studies for cosmetics Studies for cosmetics Studies for taste of foods Studies for taste of foods Studies for veterinary use Studies for veterinary use New devices (drugs, reagents or hardware such as pacemakers, artificial joints) require IRB New devices (drugs, reagents or hardware such as pacemakers, artificial joints) require IRB

20. Clinical Trial Data Analysis Data analyzed by Statistics or Biostatistics group Data analyzed by Statistics or Biostatistics group Use well defined, accepted and pre- determined data analysis formulas and methods. Use well defined, accepted and pre- determined data analysis formulas and methods. –Looking for levels of significance 99% still means 1% error possible of 1/100 (0.01). Is that good enough? Is that good enough? How do you balance the data with the delay in releasing a product? How do you balance the data with the delay in releasing a product? Outlier: data point outside of the average range and is usually larger or smaller than the rest of the points Outlier: data point outside of the average range and is usually larger or smaller than the rest of the points

21. Clinical Trial Data Analysis INCLUSION/EXCLUSION CRITERIA: The medical or social standards determining whether a person may or may not be allowed to enter a clinical trial. These criteria are based on such factors as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions. It is important to note that inclusion and exclusion criteria are not used to reject people personally, but rather to identify appropriate participants and keep them safe. INCLUSION/EXCLUSION CRITERIA: The medical or social standards determining whether a person may or may not be allowed to enter a clinical trial. These criteria are based on such factors as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions. It is important to note that inclusion and exclusion criteria are not used to reject people personally, but rather to identify appropriate participants and keep them safe.

22. Single and Double Blinded Study Single-Blind study: clinical trial study in which the human subjects do not know if they are receiving the active product or a placebo. Single-Blind study: clinical trial study in which the human subjects do not know if they are receiving the active product or a placebo. Double-Blind study: study in which neither the subject nor the investigator knows the treatment assigned. (usually subjects, investigators, monitors and data analysts are unaware) Double-Blind study: study in which neither the subject nor the investigator knows the treatment assigned. (usually subjects, investigators, monitors and data analysts are unaware)