Clinical Research Lecture PDF

# Clinical Research ## Clinical Research - **Clinical research** is a comprehensive study of the safety and effectiveness of the most promising advances in patient care. - **Clinical research** is different than laboratory research. - It involves people who volunteer to help us better understand m...

# Clinical Research ## Clinical Research - **Clinical research** is a comprehensive study of the safety and effectiveness of the most promising advances in patient care. - **Clinical research** is different than laboratory research. - It involves people who volunteer to help us better understand medicine and health. Lab research generally does not involve people, but it helps us learn which new ideas may help people - Every drug, device, tool, diagnostic test, technique and technology used in medicine today was once tested in volunteers who took part in clinical research studies. ## What is clinical research? - **Clinical research** is medical research on human subjects ### **Areas of Interest:** - **Improving or validating the effectiveness of methods for preventing injury/illness.** - **Understanding of clinical conditions.** - **Investigation of the cause of injury/ illness.** - **Improving or validating diagnostic or treatment methods in medicine.** ## Clinical Research - **Clinical research** is a scientific study that involves people. - **Individuals** volunteer to participate in carefully conducted studies which ultimately uncover improved methods and knowledge on screening, diagnoses, treatment and prevention of disease and on the promotion of health and health care. ## What are Clinical Studies? - **Clinical studies** test whether a new medicine, device, procedure or vaccine: - Is safe - Works - They also: - Compare new vs. current treatments - Discover ways to prevent and detect diseases ### You'll find them at: - Hospitals - Universities - Clinics - Cardiology offices ### What are Clinical Studies? - As a volunteer in a study, you could help researchers explore new medical approaches and advance heart care. ### As a volunteer in a study: - **Talk about concerns:** - Risks of NEW THERAPY - Possible SIDE EFFECTS - Amount of TIME OR TRAVEL needed - **Learn about benefits:** - Get access to LATEST TREATMENTS - Receive CLOSER MONITORING - IMPROVE CARE for yourself and others - FIND OUT MORE about your disease ## Design of clinical research - **Clinical research** can be **interventional** or **observational**. ### Observational Studies - **Observational studies** are projects where there is no investigational product assigned to participants, e.g. research on how therapies work, health economic research and qualitative clinical research such as understanding patients' experiences, etc. ### Interventional Studies - **Interventional studies** are controlled experiments, like clinical trials, where every participant is allocated to the treatment or control group at the start of the study. The WHO's International ## What intervention mean? - **Clinical Trials Registry Platform** states that 'interventions can include drugs, cells and other biological products, surgical procedures, radiologic procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc - **Types of intervention:** - **No intervention:** - **Observational:** - **Comparison:** - Yes - analytical study case control - No - Descriptive study - **Intervention:** - **Experimental:** - **Random allocation:** - Yes - Randomized control trial - No - Non Randomized control trial ## Who will be in clinical research? - **Clinical research studies** need people of every age, health status, race, gender, ethnicity and cultural background to participate. - This will increase the chances that scientists and clinicians will develop treatments and procedures that are likely to be safe and work well in all people. - Potential volunteers are carefully screened to ensure that they meet all of the requirements for any study before they begin. Most of the reasons people are not included in studies is because of concerns about safety. - **Both healthy people and those with diagnosed medical conditions can take part in clinical research.** Participation is always completely voluntary, and participants can leave a study at any time for any reason. ## Single vs. multicenter trials - **Single center:** - Participants recruited at one site - Single site usually also responsible for data collection, management, analysis - **Multicenter:** - Participants recruited at >1 site - Usually has data coordinating center and other resource centers - Diagram: A tree structure with a lead research site at the top and three branches with research sites as their end points. ## How Does Clinical Research Differ From Standard Care? - The difference between clinical research and standard care is that clinical research: - Involves human volunteers, these may be patients or can all be healthy individuals who are not suffering from an illness or condition. - Is carried out with the ultimate aim of improving standard care. - The research may be testing an intervention (e.g. a product or procedure) or collecting data through interviews or observations about a topic such as patient experience, disease management etc. - Measures effects over a period of time using robust and reliable methods to identify a lack of knowledge on issues such as costs, improved care, better drugs, treatments or therapies, additional support etc. ## Cont. How Does Clinical Research Differ From Standard Care? - **Clinical research**: - May involve a comparison ‘control’ group, depending on the type of research. - Focuses on unknowns such as the effect of intervention, the likelihood of a community to change their practices, etc. - Must stick to a protocol without deviation (within the investigator's clinical judgement). - **By comparison, standard care is all about clinical judgment, decisions and flexibility.** ## Stages of Drug Development - **Stage 1:** Drug discovery - 10,000 compounds - **Stage 2:** Pre-clinical development - 250 compounds - **Stage 3:** Clinical development - 5 compounds - **Regulatory approval:** - 1 compound ### Phases | Phase | Description | |---|---| | 0 | Effect on body | | I | Safety in humans | | II | Effectiveness at treating diseases | | III | Larger scale safety and effectiveness | | IV | Long term safety | ## Translational approach from basic research to bedside and clinical practice - **Basic Research:** - In vitro studies - Animal research - **T1 Research:** - Translation to humans - Case studies - Phase 1-2 clinical trials - **Bedside:** - Controlled observation studies - Phase 3 clinical trials - **T2 Research:** - Translation to patient - Guideline development - Systematic reviews - **Practice-based research:** - Observation studies - Phase 3-4 clinical trials - **T3 Research:** - Translation to practice - Dissemination research - Implementation research - **Regulation and practice:** - Clinical practice across the system ## Types of translational research - **The first one (T1):** focuses on translating the basic research findings from preclinical studies, animal research and basic health services research into bedside applications, where controlled observational studies and phase III clinical trials occur. - **The second block (T2):** includes the translation from bedside to practice-based research, that mainly focuses on phase III and IV trials, observational studies, and survey research. This block is devoted to guideline development, meta-analysis, and systematic reviews information to patients, regulations and practice - **The last block (T3):** includes the translation from practice-based research to clinical practice across the system, including dissemination and implementation research. ## Preclinical Trials | Type | Description | |---|---| | *In vitro* | Basic research | | *In vivo* | Animal models | | Phase 1 | 20-80 participants | | Phase 2 | 100-300 participants | | Phase 3 | 1000-3000 participants | | Regulatory | Confirm safety and effectiveness | | Phase 4 | 1000+ participants | ### *In Silico* Trials - **Toxicity studies** - Biological mechanism description - **Treatment improvement** - Size reduction - **Data Management** - Personalized models ## In vivo vs. In vitro | In vivo | In vitro | |---|---| | Latin for "within the living" | Latin for "within the glass" | | Refers to experiments conducted on living organisms | Refers to experiments conducted outside of living organisms | | Can be more complex and expensive | Can be less complex and less expensive | | Results may be more applicable to real-life situations | Results may be less applicable to real-life situations | | Commonly used in medical research | Commonly used in laboratory research | *Diagram/Image: A split image with left side showing a microscope with cells next to text "In vitro", and right side showing mouse next to text "In vivo"*. ### Both in vivo and in vitro studies are important in scientific research, but they serve different purposes. In vivo studies provide a more accurate representation of how a treatment or substance will affect a living organism, while in vitro studies allow researchers to study the effects of a treatment or substance on isolated cells or tissues. ## *In vivo* vs. *In vitro* | Type of Study | In vivo | In vitro | |---|---|---| | Definition | Studies "within a living organism" | Studies performed "in the glass" | | Cost | Very expensive | Relatively low cost | | Time | Long and extensive | Relatively fast | | Example | Clinical trials and animal studies | Organ-on-a-chip, microphysiological systems, cell-based screening, diagnostic tests | | Pros | More specific and reliable for observing biological effects in a test subject | Relative simplicity, species specificity, experimental control | | Cons | Strict regulations and compliance standards | Physiologically limited | ## In Vitro - **Systems:** - Gastric or gastrointestinal phases - Static and dynamic controls - **Advantages:** - No ethical concerns - Controllable systems - High repeatability - High-throughput potential - **Challenges:** - Parameter selection - Missing unknown key factors - Lacking physiological feedback loops - Lacking infant gut microbes ## In Vivo - **Common Subjects:** - Mice - Piglets - Human infants - **Advantages:** - Infant-specific biological environment - Providing delicate feedback controls - Revealing overall health outcomes - **Challenges:** - Ethical concerns - Sampling limitations - Subject variations - High costs