Unit V: Clinical Trial Designs PDF

Unit V: Clinical Trial Designs At the end of the unit, you are expected to: 1. Differentiating various types of clinical trial designs. 2. Describing the components of a clinical trial protocol. 3. Discussing the roles of different stakeholders in clinical trials. Introduction ★ Most errors in clini...

Unit V: Clinical Trial Designs At the end of the unit, you are expected to: 1. Differentiating various types of clinical trial designs. 2. Describing the components of a clinical trial protocol. 3. Discussing the roles of different stakeholders in clinical trials. Introduction ★ Most errors in clinical trials are a result of poor planning. ★ The objective of clinical trials is to establish the effect of an intervention. ★ Key features of clinical trials that are used to meet this objective are : ○ randomization (possibly with stratification), ○ adherence to intent-to-treat (ITT) principles, ○ blinding, ○ prospective evaluation, and ○ use of a control group Key terms Cohort Study- a study used to estimate how often a disease or life events happen in a certain population Cross Sectional Study- type of observational study that are primarily used to determine the prevalence Case Control Study- observational study that compares patients who have disease with patient who do not have a disease Randomized Clinical Trial- epidemiological experiment in which a subjects in a population are randomly allocated into groups, usually called study and control. Non Randomized Clinical Trial- Participants may choose which group they want to be in, or they may be assigned to the groups by the researchers. Clinical Trials Clinical trials (Human testing of a drug) are set of procedure in medical research and drug development that are conducted to allow safety or more specifically; information about adverse drug reaction, adverse effects and efficacy data to be collected for health intervention. E.g. drugs, diagnostics, devices, therapy Clinical Research All scientific approaches to evaluate medical disease in terms: a. Prevention b. Diagnosis c. Treatment HUMAN Types of Clinical Trial 1. Treatment Trials Test experimental treatments, new combination of drugs or new approaches to surgery or radiation therapy 2. Prevention Trials Look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning E.g. medicines, vaccines, vitamins, minerals or lifestyle Types of Clinical Trial 3. Diagnostic Trials Are conducted to find better tests or procedure for diagnosing a particular disease or condition. 4. Screening Trials The best way to detect certain diseases or health conditions 5. Quality of Life Trials (Supportive Care Trials) Explore ways to improve comfort and the quality of life for individuals with chronic illness. Clinical Trial Design A. Parallel Design - A parallel design is a common and straightforward clinical trial design used to compare the effects of two or more interventions or treatments. In parallel-design clinical trials, each group of participants is assigned to one specific treatment or intervention, and they remain on that treatment throughout the study period. This design allows for a direct comparison of the efficacy and safety of the different treatments being tested. Subjects are randomized to one of two or more arm Each arm being allocated a different treatment Most commonly used design Clinical Trial Design A. Parallel Design 1. Placebo Control- A placebo control, often referred to as a placebo group, is a component of a clinical trial where a group of participants receives an inactive substance or treatment with no therapeutic effect. The purpose of the placebo control is to compare the effects of the experimental treatment to the effects of a placebo to determine whether the experimental treatment is effective and to account for the placebo effect. Placebo- inert substance that looks exactly like test drug but contains no drug ○ In trials testing efficacy ○ Double blinded ○ Advantages Minimizes bias Ability to demonstrate efficacy Clinical Trial Design A. Parallel Design 1. Placebo Control ○ Disadvantages: Ethical Issue Lack of Treatment- serious harm (such as death or irreversible morbidity) Declaration of Helsinki Used where minimal risk Patient and Physician concerns Patient may not enroll Withdraw Declaration of Helsinki It is a set of ethical principles and guidelines for conducting medical research involving human subjects. It is considered one of the foundational documents in the field of medical research ethics and was adopted by the World Medical Association (WMA). The primary purpose: to provide ethical guidance for physicians and other researchers involved in human medical research to ensure the well-being, rights, and dignity of research participants. Declaration of Helsinki Here are the key points and principles outlined in the Declaration of Helsinki: Informed Consent: The Declaration emphasizes the importance of obtaining informed consent from research participants. This includes ensuring that participants are fully informed about the research, its purpose, potential risks and benefits, and their right to withdraw from the study at any time. Beneficence and Non-Maleficence: Researchers are required to prioritize the well-being of research participants. This means that any potential risks associated with the research must be minimized, and the potential benefits should outweigh the risks. Declaration of Helsinki Here are the key points and principles outlined in the Declaration of Helsinki: Scientific Validity: Research should be scientifically rigorous and methodologically sound. The Declaration underscores the importance of adhering to high scientific and ethical standards in the design and conduct of research. Independence and Ethics Committee Review: Ethical review by an independent ethics committee is mandatory for all medical research involving human subjects. The Declaration underscores the importance of ethics committee oversight to protect the rights and safety of participants. Declaration of Helsinki Here are the key points and principles outlined in the Declaration of Helsinki: Equitable Participant Selection: The Declaration of Helsinki stresses the need for equitable participant selection, ensuring that vulnerable populations are not unduly targeted or exploited in research. Privacy and Confidentiality: The privacy and confidentiality of research participants should be protected. Researchers should ensure that data and information are kept confidential and that participants are not identified in research reports. Continuing Care: Participants should have access to post-trial benefits and ongoing care, especially if they experience adverse effects as a result of participating in research. Declaration of Helsinki Here are the key points and principles outlined in the Declaration of Helsinki: Placebo Controls: The use of a placebo control group in clinical trials is acceptable when no proven treatment exists, or when the use of a placebo is justified by methodological or ethical considerations. Publication and Dissemination of Results: Researchers have an ethical obligation to publish and disseminate the results of their research, whether positive or negative, for the benefit of the scientific community and public health. Human Rights and Dignity: The Declaration of Helsinki reaffirms the importance of respecting the fundamental rights, autonomy, and dignity of research participants. Clinical Trial Design A. Parallel Design 1. Placebo Control ★ When to use placebo: - in disease which no prior drug has been established as standard therapy - minimal risk, short term study - add-on design Clinical Trial Design A. Parallel Design 2. No Treatment Control ○ Subjects are randomly assigned to test treatment or to no treatment ○ Subjects and investigators are not blind to treatment ○ Bias Clinical Trial Design A. Parallel Design 3. Active Control Clinical Trial Design A. Parallel Design 4. Dose Response Control and External Control- Dose-Response Relationship: In medical and scientific research, a dose-response relationship refers to the relationship between the dose (or level of exposure) of a treatment or intervention and the response or outcome observed in participants. This relationship is critical in areas such as pharmacology, toxicology, and environmental science, where researchers seek to understand how the amount or intensity of an exposure relates to its effects. Dose-response relationships are often used to determine the optimal or safe dosage of a drug or the effect of varying levels of an environmental toxin on health. External Control: The term "external control" is not a standard term in research, but it might refer to the use of external sources or external comparisons to provide context for research results. In some cases, researchers may use external data or control groups from other studies or populations to benchmark their findings or to establish a reference point when internal control groups are not feasible. However, the specific usage of "external control" may vary depending on the context and discipline of the research. Clinical Trial Design A. Parallel Design 4. Dose Response Control and External Control- ○ No comparability ○ No baseline characteristic ○ No randomization ○ Blinding ○ Bias Clinical Trial Design A. Parallel Design 4. Dose Response Control and External Control ❏ Run In Design A "run-in" design is a study design used in clinical trials or research studies that involves a preliminary phase before the actual trial or study begins. During the run-in phase, participants are typically monitored or receive a placebo or standard treatment, and data is collected on their baseline characteristics and response to treatment. The primary purpose of a run-in design is to identify and exclude participants who may not be suitable for the main study, which can help improve the internal validity of the study results. Clinical Trial Design B. Crossover - is a type of clinical trial or research study design in which participants are exposed to multiple interventions or treatments in a sequential and alternating fashion. In a crossover trial, each participant serves as their own control, receiving each intervention at different time points during the study. The primary characteristic of a crossover design is that all participants experience all interventions, which allows for within-subject comparisons and can reduce variability in the data. Each patient gets both drugs The order in which patient gets drug is randomized Each patient serves as his own control Requires a small sample size Assumptions: ○ The effects of intervention during 1st period does not carry over into second period ○ Internal and External Factors are constant over time Clinical Trial Design B. Crossover Prerequisite: ○ Disease- chronic (asthma, osteoarthritis) ○ Effects of drug should be developed fully within treatment period ○ Wash out periods- sufficiently long for complete reversibility of drug effect ○ Wash out period- 5 half lives of drug Clinical Trial Design B. Crossover Problems/Disadvantage ○ Carryover effect ○ Period effect- patients vary from 1 period to another ○ Not useful for acute disease ○ Difficulties in assigning adverse events ○ Not used in vaccine trials- because immune system is permanently affected (for a long time) Application ○ Bioequivalence studies ○ Phase 1 Clinical Trial Design B. Crossover Comparison between Parallel and Crossover Clinical Trial Design C. Factorial Design Two or more interventions Allows study of interactive effects Clinical Trial Design D. Randomized Withdrawal Approach The design is particularly useful in determining how long a therapy should be continued E.g. pots-infarction treatments with a beta blocker Clinical Trial Design Innovations Adaptive Design ○ Allows adaptation or modifications to trial design after its initiation without undermining validity and integrity of trial Superiority Trial ○ Show that new treatment is better than control or standard (maybe a placebo) ○ E.g. Placebo controlled efficacy trials, Active controlled Non- Inferiority Trials ○ Show that new treatment is not worse that the standard by more than some margin ○ Active Control Equivalence Trial Placebo not used Better tolerated less dosing