Workshop 5: Clinical Trials PDF

Workshop 5 Clinical Trials 3° Medicine Aa 2024-25 Professor: Vittoria Carrabs PhD What is a clinical study? A clinical study involves research using human volunteers (also called participants) that is intended to add to medical knowledge. There are two main types of c...

Workshop 5 Clinical Trials 3° Medicine Aa 2024-25 Professor: Vittoria Carrabs PhD What is a clinical study? A clinical study involves research using human volunteers (also called participants) that is intended to add to medical knowledge. There are two main types of clinical studies: Clinical trials (also called interventional studies) Observational studies https://youtu.be/2bI5pQGXl2o Clinical Trial A clinical trial is a research study that evaluates the safety, efficacy, and side effects of new treatments, drugs, or medical interventions in humans 1. Objective of the clinical trial: Participants receive specific interventions following a protocol defined by the researchers. 2. Types of interventions: These may include drugs, medical devices, procedures, or behavioral changes (e.g., dietary modifications). 3. Possible comparisons: - A new medical approach compared to a standard one. - A treatment compared to a placebo or no intervention. - Comparison between existing interventions. 4. Evaluation of safety and efficacy: Researchers measure outcomes in participants to assess the intervention's impact. E.g.: Administering a drug to individuals with high blood pressure to see if it lowers their blood pressure.  Clinical Trial –the Protocol A clinical trial is conducted according to a research plan known as the protocol. Protocol designed to: -Answer specific research questions 4. Treatment Details- How the drug/procedure will be -Safeguard participants' health administered, Dosage levels Protocol Contains the Following Information: 5. Assessments & Data Collection: -What assessments will be performed 1. Study Rationale -Why the study is being conducted -When assessments will take place -What data will be collected 2. Participant Eligibility Criteria -Inclusion Criteria (factors that allow participation) 6. Data Review & Analysis- How the data will -Exclusion Criteria (factors that disqualify participation) be monitored, reviewed, and analyzed Examples of criteria: Age, Gender 7. Study Duration Type & Stage of Disease Previous Treatment History 8. Sample Size- Number of participants needed Other Medical Conditions 3. Research Design: 9. Participant Information- Which personal details will Control Group: Will there be one? be collected and recorded Methods to Reduce Bias Example of inclusion/exclusion Association of a knock-on effect in Periodontitis to the pathogenesis of Alzheimer’s Disease -Inclusion criteria: Alzheimer's diagnosed subjects, periodontal patients, diagnosed periodontitis subjects, non-periodontal subjects -Exclusion criteria: Pregnant patients, subjects with a history of psychiatric treatment  Clinical Trial-Informed consent Informed consent is a process used by researchers to provide potential and enrolled participants with information about a clinical study. This information helps people decide whether they want to enroll or continue to participate in the study. Participants may withdraw from a study at any time, even if the study is not over. Clinical Trial APPROVAL BY HEALTH AUTHORITIES Submission of Investigational New Drug (IND) application to FDA before beginning clinical research. The FDA review team has 30 days to review the original IND submission. The process protects volunteers who participate in clinical trials from unreasonable and significant risk in clinical trials. FDA responds to IND applications in one of two ways: -Approval to begin clinical trials. -Clinical hold to delay or stop the investigation. FDA can place a clinical hold for specific reasons, including: Participants are exposed to unreasonable or significant risk. Investigators are not qualified. Materials for the volunteer participants are misleading. The IND application does not include enough information about the trial’s risks. What is a clinical study? About 26 million people living in the European Union (EU) suffer from a rare disease. The European Medicines Agency (EMA) plays a central role in facilitating the development and authorisation of medicines for rare diseases, which are termed 'orphan medicines' in the medical world. https://youtu.be/iAv5ZhLcwUg  Clinical Trials PHASES OF CLINICAL TRIALS A clinical trial is conducted only when there is sufficient reason to believe that a new test or treatment could enhance patient care. Before clinical trials, tests and treatments are assessed in preclinical research. Clinical trials are done only after pre-clinical findings suggest that the new drug or treatment is likely to be safe and will work in people. Pre-clinical studies, also called laboratory studies, include: Cell studies “in vitro”: : These are often the initial tests performed on a new treatment. Researchers observe how the treatment affects cells grown in a lab dish or test tube to determine its potential effectiveness. (cytotoxicity studies on cells). Animal studies: Treatments that look promising in cell studies are tested next “in vivo” Clinical trials phases PHASE 0 Phase 0 trials are the first clinical trials done among people. They aim to learn HOW A DRUG IS PROCESSED in the body and how it affects the body (pharmacokinetics and pharmacodynamics) In these trials, a very small dose of a drug is given to about 10 to 15 people. Phase 0 studies aren’t widely used, NOT MANDATORY PHASE I Aims to find the best dose of a new drug with the fewest side effects. The drug will be tested in a small group of 15 to 30 of healthy patients Doctors start by giving very low doses of the drug to a few patients. Higher doses are given to other patients until side effects become too severe or the desired effect is seen. The drug may help patients, but Phase I trials are TO TEST DRUG’S SAFETY. If a drug is found to be safe enough, it can be tested in a phase II clinical trial. Rare side effects may not be seen until later phases of trials when a largest number of people receive the treatment. Clinical trials phases PHASE II Phase II trials further assess SAFETY AND EFFICACY. The drug is often tested among patients with a specific disease. Phase II trials are done in larger groups of patients compared to Phase I trials. Patients are closely monitor to see if the drug works. If a drug is found to work, it can be tested in a phase III clinical trial.  Clinical trials phases PHASE III Phase III TRIALS COMPARE A NEW DRUG TO THE STANDARD-OF-CARE DRUG These trials assess the side effects of each drug and which drug works better. Often, these trials are randomized and double blind* There can be more than two treatment groups in phase III trials. The control group gets the standard-of-care treatment while other groups get a new treatment. Most phase III clinical trials include a large number of patients, at least several hundred. These studies are often done in many places across the country (or even around the world) at the same time. In a Phase III study, each patient is closely monitored. The trial may be halted early if the side effects of the new drug are excessively severe or if one group shows significantly better outcomes. Phase III clinical trials are required for the FDA to approve a new drug for public use.  Clinical trials phases PHASE III *Randomized and double-blind clinical trial: A randomized, double-blind clinical study is a type of research design used in clinical trials to ensure objectivity and minimize bias. Randomized: Participants are randomly assigned to different groups (e.g., treatment group and control group).This helps ensure that the groups are comparable and reduces selection bias. Double-Blind: Neither the participants nor the researchers know who is receiving the treatment and who is receiving the placebo or control. This prevents both groups from being influenced by their expectations or biases about the treatment's effects. Benefits: -Minimizes Bias: Reduces the risk of bias in the results since neither the participants nor the researchers can influence the outcome. -Increases Validity: Enhances the reliability of the findings, making them more applicable to the general population. -Objective Assessment: Allows for a more objective evaluation of the treatment's effectiveness and safety.  Submission for FDA approval: New drug application (NDA) In the United States, when phase III clinical trials (or sometimes phase II trials) show a new drug is more effective or safer than the current treatment, a new drug application (NDA) is submitted to the Food and Drug Administration (FDA) for approval. The FDA reviews the results from the clinical trials and other relevant information. Based on the review, the FDA decides whether to approve the treatment for use in patients If the FDA believes that additional evidence is necessary to demonstrate that the benefits of the new treatment outweigh its risks, it may request further information or require additional studies to be conducted. Clinical trials phases PHASE IV (post-marketing authorization) Phase IV trials test new drugs approved by the FDA. The drug is tested in several hundreds or thousands of patients. This allows for better research on short and long-lasting side effects and safety. These studies may also look at other aspects of the treatment, such as quality of life or cost effectiveness. Observational or registry studies Clinical trials stages https://www.youtube.com/watch?v=kZCzN8FXt3I