This document discusses pragmatic clinical trials. It begins by defining pragmatic trials and explaining how they differ from explanatory trials. Pragmatic trials are designed to assess effectiveness of interventions in real-world settings, while explanatory trials test efficacy under controlled conditions. The document then introduces the PRECIS-2 tool, which is used to evaluate how pragmatic or explanatory a trial is based on 9 domains. It provides examples of pragmatic and explanatory approaches for each domain to help trial designers achieve the right balance. The goal is to generate evidence that is useful for patients, clinicians and policymakers.
The role of real world data and evidence in building a sustainable & efficien...Office of Health Economics
This presentation defines RWD and RWE in the context of digital health, and looks at potential uses for RWD and RWE. It briefly sets out the current landscape in Malaysia and looks at the challenges in using RWE. In particular, the issues of access, governance and ensuring good quality are considered.
This document discusses patient-reported outcome (PRO) measures and developing PRO instruments. It covers:
- Common diseases where PROs are used like Parkinson's and rheumatoid arthritis
- Applications of PROs in clinical trials, medical practice, and economic evaluations
- Developing a conceptual framework, ensuring content validity, and evaluating reliability
- Modifying existing PRO instruments or developing new ones for specific populations like children
Critical appraisal is the process of carefully and systematically analyze the research paper to judge its trustworthiness, its value and relevance in a particular context. (Amanda Burls 2009)
A critical review must identify the strengths and limitations in a research paper and this should be carried out in a systematic manner.
The Critical Appraisal helps in developing the necessary skills to make sense of scientific evidence, based on validity, results and relevance.
This document provides guidance on writing clinical trial protocols and investigators brochures. It discusses that a protocol is a complete description of a clinical trial that includes objectives, design, methodology, and other key elements. It emphasizes writing clear and unambiguous eligibility criteria. It also reviews important sections of a protocol including study design, safety reporting, statistics, and informed consent. An investigators brochure is a comprehensive document summarizing safety information about an investigational product from preclinical and clinical trials to guide its use in humans.
This document provides an overview of protocol writing for clinical research. It defines a research protocol as outlining the study plan to safely answer research questions while protecting participants. The summary outlines key components of a protocol including objectives, methodology, and management plans. A protocol allows researchers to plan, review steps, and guide the investigation. Developing a protocol requires considering factors like the research question, importance, methods, and resources needed before writing each required component.
The document discusses key concepts in clinical trial designs, including types of trials, phases of trials, and protocol requirements according to ICH-GCP guidelines. It describes the various types of clinical trial designs such as treatment, prevention, diagnostic, and screening trials. It also outlines the different phases of clinical trials from phase I to phase IV and summarizes the key elements that must be included in a clinical trial protocol according to ICH-GCP, such as the trial design, randomization, blinding, treatment regimens and stopping rules.
This document discusses meta-analysis, which involves systematically combining results from multiple studies to derive conclusions about a body of research. It describes the key steps in conducting a meta-analysis, including writing a research question and protocol, performing a comprehensive literature search, selecting studies, assessing study quality, extracting data, and analyzing data. Statistical methods for pooling results across studies using fixed and random effects models are also outlined. The document highlights strengths and limitations of meta-analysis for providing more precise estimates of treatment effects and identifying areas needing further research.
1) Clinical trials involve prospectively assigning human participants to health interventions to evaluate effects on outcomes. They aim to carefully and ethically answer precisely framed questions.
2) Clinical trials are classified into phases based on goals, with Phase 0 trials involving small doses and numbers of participants to assess safety.
3) Randomization, blinding, inclusion/exclusion criteria, and sample size are important design considerations to reduce bias and ensure results reflect the interventions rather than other factors. Statistical analysis then determines if any effects seen are real or due to chance.
The role of real world data and evidence in building a sustainable & efficien...Office of Health Economics
This presentation defines RWD and RWE in the context of digital health, and looks at potential uses for RWD and RWE. It briefly sets out the current landscape in Malaysia and looks at the challenges in using RWE. In particular, the issues of access, governance and ensuring good quality are considered.
This document discusses patient-reported outcome (PRO) measures and developing PRO instruments. It covers:
- Common diseases where PROs are used like Parkinson's and rheumatoid arthritis
- Applications of PROs in clinical trials, medical practice, and economic evaluations
- Developing a conceptual framework, ensuring content validity, and evaluating reliability
- Modifying existing PRO instruments or developing new ones for specific populations like children
Critical appraisal is the process of carefully and systematically analyze the research paper to judge its trustworthiness, its value and relevance in a particular context. (Amanda Burls 2009)
A critical review must identify the strengths and limitations in a research paper and this should be carried out in a systematic manner.
The Critical Appraisal helps in developing the necessary skills to make sense of scientific evidence, based on validity, results and relevance.
This document provides guidance on writing clinical trial protocols and investigators brochures. It discusses that a protocol is a complete description of a clinical trial that includes objectives, design, methodology, and other key elements. It emphasizes writing clear and unambiguous eligibility criteria. It also reviews important sections of a protocol including study design, safety reporting, statistics, and informed consent. An investigators brochure is a comprehensive document summarizing safety information about an investigational product from preclinical and clinical trials to guide its use in humans.
This document provides an overview of protocol writing for clinical research. It defines a research protocol as outlining the study plan to safely answer research questions while protecting participants. The summary outlines key components of a protocol including objectives, methodology, and management plans. A protocol allows researchers to plan, review steps, and guide the investigation. Developing a protocol requires considering factors like the research question, importance, methods, and resources needed before writing each required component.
The document discusses key concepts in clinical trial designs, including types of trials, phases of trials, and protocol requirements according to ICH-GCP guidelines. It describes the various types of clinical trial designs such as treatment, prevention, diagnostic, and screening trials. It also outlines the different phases of clinical trials from phase I to phase IV and summarizes the key elements that must be included in a clinical trial protocol according to ICH-GCP, such as the trial design, randomization, blinding, treatment regimens and stopping rules.
This document discusses meta-analysis, which involves systematically combining results from multiple studies to derive conclusions about a body of research. It describes the key steps in conducting a meta-analysis, including writing a research question and protocol, performing a comprehensive literature search, selecting studies, assessing study quality, extracting data, and analyzing data. Statistical methods for pooling results across studies using fixed and random effects models are also outlined. The document highlights strengths and limitations of meta-analysis for providing more precise estimates of treatment effects and identifying areas needing further research.
1) Clinical trials involve prospectively assigning human participants to health interventions to evaluate effects on outcomes. They aim to carefully and ethically answer precisely framed questions.
2) Clinical trials are classified into phases based on goals, with Phase 0 trials involving small doses and numbers of participants to assess safety.
3) Randomization, blinding, inclusion/exclusion criteria, and sample size are important design considerations to reduce bias and ensure results reflect the interventions rather than other factors. Statistical analysis then determines if any effects seen are real or due to chance.
Clinical trials are important for testing new medical treatments and determining their value. There are various phases of clinical trials, beginning with Phase 0 and Phase 1 safety trials with small groups, then Phase 2 dosage and efficacy trials with larger groups, and finally Phase 3 confirmatory trials with thousands of participants across many sites. Well-designed clinical trials utilize controls, randomization, blinding, predefined endpoints and stopping rules to reliably establish if new treatments are effective and safe for patients.
This document discusses the process of informed consent for clinical research studies. It defines informed consent as a voluntary confirmation by a research subject of their willingness to participate after being informed of all relevant study details. The goal is to provide sufficient information for subjects to make an informed choice about participation. Key aspects of the informed consent process include guidelines from regulatory bodies, ensuring subjects' comprehension and voluntariness, obtaining consent at the right time and place, addressing any questions, and documenting consent with a signed form. The form should include essential elements like the study purpose, risks, benefits, and subjects' rights, as well as additional details like withdrawal criteria and contact information.
Monitoring and auditing in clinical trialsJyotsna Kapoor
Monitoring and auditing are important quality control activities in clinical trials. Monitoring ensures accurate and compliant conduct of trials, while auditing independently evaluates trial conduct and compliance. Key aspects include:
Monitoring involves overseeing trial progress to ensure compliance. Monitors verify participant rights and data accuracy. Auditing independently examines trials and documents to determine GCP compliance. Audit findings help ensure future compliance. Together, monitoring and auditing protect participants and validate trial results.
This document discusses various types of bias, confounding, and causation that can occur in epidemiological studies. It defines a confounder as a variable that is associated with the exposure and affects the outcome but is not in the causal pathway. Three main types of bias are described: selection bias, information bias, and confounding. Specific biases like recall bias, observer bias, and non-respondent bias are explained. Methods for controlling confounding like matching, stratification, and multivariate analysis are also outlined. The document concludes by discussing Hill's criteria for determining a causal association and threats to the internal and external validity of experimental studies.
A Risk Management Plan (RMP) is a documented plan that describes the risks (adverse drug reactions and potential adverse reactions) associated with the use of a drug and how they are being handled (warning on drug label or on packet inserts of possible side effects which if observed should cause the patient to inform/see his physician and/or pharmacist and/or the manufacturer of the drug)
At the time of authorization, information on the safety of a
medicine is relatively limited. This is due to the limitations
of clinical trials, including:
relatively small numbers of subjects in clinical trials compared with the intended treatment population
restricted population in terms of age, gender or ethnicity
The document discusses different study designs used in research, including observational studies like case reports, case series, cross-sectional studies, and cohort studies, as well as experimental studies like randomized controlled trials. It describes the key characteristics and advantages and disadvantages of each design. The highest level of evidence comes from randomized controlled trials, while observational studies are useful for initial hypothesis generation.
This meta-analysis examined the relationship between body mass index (BMI) and incident asthma. It identified 2006 relevant studies and included 12 prospective cohort studies. Inclusion criteria required adult subjects, asthma as the primary outcome, BMI measurement, minimum 1-year follow up of 70%, and BMI data categorized by standard ranges. Random effects models were used to generate summary odds ratios. Results showed overweight individuals had a 38% higher odds of developing asthma compared to normal weight, and obese individuals had 92% higher odds. When stratified by sex, the association was stronger for women. The analysis provided evidence that higher BMI is a risk factor for incident asthma.
Vaccine safety requires careful monitoring both before and after vaccines are approved. Pre-approval clinical trials evaluate efficacy and safety but are too small to detect rare issues. The Vaccine Adverse Event Reporting System (VAERS) monitors safety after approval by collecting reports from healthcare providers and the public. While VAERS detects potential problems, it cannot determine if a vaccine caused a specific adverse event. Additional studies are needed to evaluate potential safety issues found through VAERS. Ongoing research is also important to improve understanding of vaccine safety and adverse events.
Systematic and random errors can affect epidemiological studies. Random errors are due to chance and include individual biological variation, measurement error, and sampling error. Systematic errors, also called biases, are non-random and can distort study results. Selection bias occurs if study groups differ in characteristics unrelated to exposure that influence outcomes. Measurement bias happens if exposures or diseases are inaccurately classified. Confounding is present when a third factor is associated with both the exposure and outcome under investigation. Careful study design and analysis techniques can help reduce biases and errors to obtain more accurate results.
An observational study observes subjects without intervening. A cohort study follows groups over time to compare outcomes based on exposure. This document defines and provides examples of cohort studies. It describes their design, strengths like establishing temporality between exposure and outcome, and ability to study multiple outcomes from one exposure. Examples include Framingham Heart Study, Swiss HIV Cohort Study, and a Danish study on psoriasis and depression.
Regulation Governing Clinical Trials In India,USA and Europe. KapilKumar198
This presentation contain detailed information about the "Regulation Governing Clinical Trials In India,USA and Europe".And about the clinical trails and medical devices regulations in India.
Electronic Data Capture & Remote Data CaptureCRB Tech
CRB Tech is one of the best leading Software Development Company in Pune. We are offering Software Development Services as well as IT Training including Java, Dot Net, SEO and Clinical Research training in pune.
This document discusses the informed consent process. It begins by explaining that informed consent is a process, not just a form. It then provides an IRB submission flow chart and discusses the rules and guidelines that must be followed for informed consent. The document outlines best practices for authoring informed consent forms, including using plain language and avoiding medical jargon. It discusses informed consent considerations for vulnerable populations like children, prisoners, non-English speakers, and cognitively impaired individuals. The document also covers topics like obtaining consent from legally authorized representatives, waiving or altering elements of informed consent, revoking consent, and responsibilities at the end of a study.
An epidemiological experiment in which subjects in a population are randomly allocated into groups, usually called study and control groups to receive and not receive an experimental preventive or therapetuic procedure, maneuver, or intervention .
This document discusses surgical audits, which involve systematically analyzing healthcare quality against standards to improve patient care. Surgical audits aim to ensure standards are met, identify problems, and improve outcomes. They have advantages like identifying issues and guiding improvements, but also disadvantages like taking significant time. The stages of a surgical audit include collecting data, analyzing results against criteria, discussing findings, implementing solutions, and re-auditing to verify improvements.
Dr Ayman Ewies - Clinical audit made easyAymanEwies
This document provides an overview of how to conduct a clinical audit. It defines clinical audit as a process used by healthcare professionals to systematically review, evaluate and improve patient care. The document outlines the key components of an audit, including choosing a topic, selecting standards, planning methodology, collecting data, analyzing results, and implementing changes. It emphasizes that the goal of audit is to compare current practices to standards in order to enhance quality of care and patient outcomes.
Clinical trials are important for testing new medical treatments and determining their value. There are various phases of clinical trials, beginning with Phase 0 and Phase 1 safety trials with small groups, then Phase 2 dosage and efficacy trials with larger groups, and finally Phase 3 confirmatory trials with thousands of participants across many sites. Well-designed clinical trials utilize controls, randomization, blinding, predefined endpoints and stopping rules to reliably establish if new treatments are effective and safe for patients.
This document discusses the process of informed consent for clinical research studies. It defines informed consent as a voluntary confirmation by a research subject of their willingness to participate after being informed of all relevant study details. The goal is to provide sufficient information for subjects to make an informed choice about participation. Key aspects of the informed consent process include guidelines from regulatory bodies, ensuring subjects' comprehension and voluntariness, obtaining consent at the right time and place, addressing any questions, and documenting consent with a signed form. The form should include essential elements like the study purpose, risks, benefits, and subjects' rights, as well as additional details like withdrawal criteria and contact information.
Monitoring and auditing in clinical trialsJyotsna Kapoor
Monitoring and auditing are important quality control activities in clinical trials. Monitoring ensures accurate and compliant conduct of trials, while auditing independently evaluates trial conduct and compliance. Key aspects include:
Monitoring involves overseeing trial progress to ensure compliance. Monitors verify participant rights and data accuracy. Auditing independently examines trials and documents to determine GCP compliance. Audit findings help ensure future compliance. Together, monitoring and auditing protect participants and validate trial results.
This document discusses various types of bias, confounding, and causation that can occur in epidemiological studies. It defines a confounder as a variable that is associated with the exposure and affects the outcome but is not in the causal pathway. Three main types of bias are described: selection bias, information bias, and confounding. Specific biases like recall bias, observer bias, and non-respondent bias are explained. Methods for controlling confounding like matching, stratification, and multivariate analysis are also outlined. The document concludes by discussing Hill's criteria for determining a causal association and threats to the internal and external validity of experimental studies.
A Risk Management Plan (RMP) is a documented plan that describes the risks (adverse drug reactions and potential adverse reactions) associated with the use of a drug and how they are being handled (warning on drug label or on packet inserts of possible side effects which if observed should cause the patient to inform/see his physician and/or pharmacist and/or the manufacturer of the drug)
At the time of authorization, information on the safety of a
medicine is relatively limited. This is due to the limitations
of clinical trials, including:
relatively small numbers of subjects in clinical trials compared with the intended treatment population
restricted population in terms of age, gender or ethnicity
The document discusses different study designs used in research, including observational studies like case reports, case series, cross-sectional studies, and cohort studies, as well as experimental studies like randomized controlled trials. It describes the key characteristics and advantages and disadvantages of each design. The highest level of evidence comes from randomized controlled trials, while observational studies are useful for initial hypothesis generation.
This meta-analysis examined the relationship between body mass index (BMI) and incident asthma. It identified 2006 relevant studies and included 12 prospective cohort studies. Inclusion criteria required adult subjects, asthma as the primary outcome, BMI measurement, minimum 1-year follow up of 70%, and BMI data categorized by standard ranges. Random effects models were used to generate summary odds ratios. Results showed overweight individuals had a 38% higher odds of developing asthma compared to normal weight, and obese individuals had 92% higher odds. When stratified by sex, the association was stronger for women. The analysis provided evidence that higher BMI is a risk factor for incident asthma.
Vaccine safety requires careful monitoring both before and after vaccines are approved. Pre-approval clinical trials evaluate efficacy and safety but are too small to detect rare issues. The Vaccine Adverse Event Reporting System (VAERS) monitors safety after approval by collecting reports from healthcare providers and the public. While VAERS detects potential problems, it cannot determine if a vaccine caused a specific adverse event. Additional studies are needed to evaluate potential safety issues found through VAERS. Ongoing research is also important to improve understanding of vaccine safety and adverse events.
Systematic and random errors can affect epidemiological studies. Random errors are due to chance and include individual biological variation, measurement error, and sampling error. Systematic errors, also called biases, are non-random and can distort study results. Selection bias occurs if study groups differ in characteristics unrelated to exposure that influence outcomes. Measurement bias happens if exposures or diseases are inaccurately classified. Confounding is present when a third factor is associated with both the exposure and outcome under investigation. Careful study design and analysis techniques can help reduce biases and errors to obtain more accurate results.
An observational study observes subjects without intervening. A cohort study follows groups over time to compare outcomes based on exposure. This document defines and provides examples of cohort studies. It describes their design, strengths like establishing temporality between exposure and outcome, and ability to study multiple outcomes from one exposure. Examples include Framingham Heart Study, Swiss HIV Cohort Study, and a Danish study on psoriasis and depression.
Regulation Governing Clinical Trials In India,USA and Europe. KapilKumar198
This presentation contain detailed information about the "Regulation Governing Clinical Trials In India,USA and Europe".And about the clinical trails and medical devices regulations in India.
Electronic Data Capture & Remote Data CaptureCRB Tech
CRB Tech is one of the best leading Software Development Company in Pune. We are offering Software Development Services as well as IT Training including Java, Dot Net, SEO and Clinical Research training in pune.
This document discusses the informed consent process. It begins by explaining that informed consent is a process, not just a form. It then provides an IRB submission flow chart and discusses the rules and guidelines that must be followed for informed consent. The document outlines best practices for authoring informed consent forms, including using plain language and avoiding medical jargon. It discusses informed consent considerations for vulnerable populations like children, prisoners, non-English speakers, and cognitively impaired individuals. The document also covers topics like obtaining consent from legally authorized representatives, waiving or altering elements of informed consent, revoking consent, and responsibilities at the end of a study.
An epidemiological experiment in which subjects in a population are randomly allocated into groups, usually called study and control groups to receive and not receive an experimental preventive or therapetuic procedure, maneuver, or intervention .
This document discusses surgical audits, which involve systematically analyzing healthcare quality against standards to improve patient care. Surgical audits aim to ensure standards are met, identify problems, and improve outcomes. They have advantages like identifying issues and guiding improvements, but also disadvantages like taking significant time. The stages of a surgical audit include collecting data, analyzing results against criteria, discussing findings, implementing solutions, and re-auditing to verify improvements.
Dr Ayman Ewies - Clinical audit made easyAymanEwies
This document provides an overview of how to conduct a clinical audit. It defines clinical audit as a process used by healthcare professionals to systematically review, evaluate and improve patient care. The document outlines the key components of an audit, including choosing a topic, selecting standards, planning methodology, collecting data, analyzing results, and implementing changes. It emphasizes that the goal of audit is to compare current practices to standards in order to enhance quality of care and patient outcomes.
This document provides an overview of randomized control trials (RCTs). It discusses key aspects of RCT design including types of RCTs based on interventions evaluated (explanatory vs pragmatic), participants exposed (parallel vs crossover), number of participants (from n-of-1 trials to mega-trials), blinding of investigators/participants, and accounting for participant preferences. It also covers randomization techniques and their advantages, sample size calculations, and references for further information.
Pillar 6 of clinical governance focuses on clinical effectiveness and ensuring best practices based on evidence. The key elements of clinical effectiveness discussed in the document are: 1) Cost effectiveness analysis to determine value of interventions, 2) Critical appraisal of research evidence before using in decisions, 3) Use of clinical guidelines developed from evidence, 4) Implementation of evidence-based practice through guidelines and evaluation, and 5) Use of integrated care pathways to standardize patient care based on guidelines and monitor outcomes. The document provides details on each of these elements and how organizations can incorporate them to deliver effective, evidence-based clinical care.
Clinical pathways provide a standardized, multidisciplinary care plan for specific diagnoses or procedures. They outline key steps, interventions, and expected outcomes for patients' hospital stays. Developing clinical pathways requires input from physicians, nurses, and other healthcare professionals to establish best practices based on evidence and optimize resource utilization and quality of care. Nurses play an important role in following the clinical pathway for patients, informing the team of any variances, and collaborating with other professionals.
This document provides an overview of conducting drug trials in cardiology. It discusses the definition and types of clinical trials, guidelines for trials including Good Clinical Practice and regulatory guidelines in India. Key elements of trials are covered such as the protocol, investigators, ethics committees, data collection and analysis. Equipoise, randomization, blinding and important considerations for trial design and conduct are also summarized.
Evidence-based applicability in clinical settingElhadi Miskeen
This document discusses the concept and application of evidence-based medicine (EBM). It begins by defining EBM as the integration of best research evidence, clinical expertise, and patient values. It then outlines the five steps of EBM: 1) formulating an answerable clinical question, 2) finding relevant evidence, 3) appraising the evidence critically, 4) applying the evidence to practice, and 5) evaluating performance. The document provides examples of formulating questions in PICO format and searching strategies. It also discusses study designs and hierarchies of evidence, emphasizing that randomized controlled trials provide the strongest evidence when evaluating interventions. The goal of EBM is to improve healthcare quality by incorporating valid and applicable research findings.
This document discusses the principles of conducting drug trials in cardiology. It covers types of clinical trials like randomized controlled trials (RCTs), phases of drug trials from Phase I to Phase IV, objectives of trials, trial design considerations like blinding and use of steering committees, and challenges conducting trials in India like regulatory hurdles and lack of qualified investigators. The overall goal of drug trials is to evaluate new treatments for safety and efficacy.
evidence based practice is the most recent development of the research world. in nursing the utilization of the research is very limited as it contribute to a lots of factors. here i have discussed about the ebp in brief. this is just an short and concise form of the real matter so read extensively for more knowledge.
This document discusses the development of therapeutic guidelines. It defines therapeutic guidelines as clinical practice guidelines written for prescribers to provide treatment recommendations based on current evidence. The document outlines the need for guidelines to improve patient care quality and consistency while controlling healthcare costs. It describes the composition of guideline development groups and the multi-step process involved, including identifying the problem and literature, obtaining expert opinions, reviewing evidence, and disseminating the completed guidelines. Potential limitations of guidelines like complexity and physician acceptance are also discussed.
The document discusses the process of clinical trials, including the phases involved from pre-clinical to post-marketing. It describes the goals of each phase from evaluating safety and efficacy on healthy volunteers to large patient groups. Regulatory authorities ensure quality and protect subject rights through establishing legal frameworks. Pharmacists play roles in storage, supply, patient education and conducting research to improve outcomes.
The document discusses data and safety monitoring boards (DSMBs), which regularly review accumulating data from ongoing clinical trials to monitor safety and scientific validity. A DSMB is typically appointed by the trial sponsor. The document outlines factors in determining if a trial needs a DSMB, how DSMBs are composed, their responsibilities like monitoring safety and effectiveness, and how they make recommendations to sponsors. Not all trials require independent external DSMBs, but all should have a data safety monitoring plan to protect participants.
The document discusses the purpose and operations of a Data Safety Monitoring Board (DSMB). A DSMB regularly reviews accumulating data from ongoing clinical trials to monitor safety and efficacy. It advises the sponsor on risks to current and future subjects. Key responsibilities include monitoring trial conduct, safety, effectiveness, and making recommendations to modify or terminate trials early if necessary. DSMBs are typically composed of experts in relevant clinical specialties and biostatistics who do not have conflicts of interest in the trial.
Real-world evidence can provide insights into current clinical practice and patient populations but has limitations compared to randomized controlled trials. It can help identify unmet needs, safety signals, and populations underrepresented in trials to inform future trial design. While not suitable to approve new interventions, real-world data may validate trial findings or efficacy in broader populations when interpreted carefully due to methodological constraints. An optimal approach balances randomized trials with complementary real-world evidence studies.
Levels of evidence and design of clinical trailSanika Kulkarni
Evidence based medicine involves integrating clinical expertise with the best available external evidence from systematic research. Clinical trials generate safety and efficacy data on treatments and are conducted in multiple phases. Randomized controlled trials are considered the gold standard for clinical research as they minimize bias through randomization and use of control groups. Statistical considerations like sample size, endpoints, and interim analyses are important for clinical trial design.
Randomized controlled trials (RCTs) are experimental studies that assess the effect of an intervention by comparing outcomes between those who receive the intervention and a control group. RCTs minimize bias by randomly assigning participants to groups and concealing group assignments. Key factors in RCTs include sufficient sample size, stratified randomization to balance groups, blinding participants and assessors, and accounting for attrition. RCTs allow for causal inferences but have disadvantages like difficulty with some ethical questions and dropout.
This document outlines the key steps in conducting a clinical trial:
1. Drawing up a detailed research protocol that serves as the trial's operating manual.
2. Selecting and screening participants according to eligibility criteria to identify the study population. Sample size is also calculated.
3. Randomly allocating the study participants into experimental and control groups through a process like randomization to reduce bias.
Paying for performance to improve the delivery of health interventions in LMICsReBUILD for Resilience
This presentation from Sophie Witter & Karin Diaconu of Queen Margaret University, UK outlines the findings from a Cochrane review undertaken by the team on paying for performance to improve the delivery of health interventions in low and middle-income countries.
This document discusses medical audits, including definitions, components, stages, and types of audits. It provides information on the audit cycle and the roles and functions of an audit committee. Some key points include:
- Medical audits systematically analyze quality of care, procedures, resource use, and patient outcomes and quality of life.
- Audits can help provide reassurance that best quality services are being provided given available resources.
- The audit cycle involves setting standards, comparing practice to standards, implementing changes if needed, and closing the audit loop.
- An audit committee coordinates audits, ensures changes are made, and maintains confidentiality.
It bridges the gap between vision and the day -to -day activities of large multidisciplinary organizations.
The vision is transformed into distinct implementation phases and discrete steps, called clinical studies, each with well defined milestones and deliverables.
Fixed Trial Designs Paradigm, in particular for Phase III
-Standard trial designs allow little learningduring the conduct of the trial
-“Established”adaptations are used in group-sequential trialswhere stopping for superiority or futility can be done according to pre-defined rules at interim analyses
-Clearly separated development phases(II and III)
-If applied to all clinical projects one misses opportunitiesfor better use of information and more ethical drug development
The document discusses various clinical trial designs for first-in-human studies. It describes traditional 3+3 designs where dose escalation occurs in cohorts of 3 patients until the maximum tolerated dose is found. It also discusses model-based designs that use statistical models to estimate the dose-toxicity relationship and assign patients to doses. The document provides an overview of factors to consider in clinical trial protocols such as study size, population, dose escalation schemes, and objectives. It also summarizes single ascending dose and multiple ascending dose study designs.
This document provides information on pharmacokinetics, including key terms and concepts. It discusses volume of distribution, clearance, half-life, steady state, and loading/maintenance doses. Volume of distribution relates the amount of drug in the body to its concentration in blood or plasma. Clearance is the rate of drug elimination. Half-life is the time for a drug amount to reduce by half. Steady state is reached when the dosing rate equals the elimination rate. Loading doses are used to quickly reach the target concentration for drugs with long half-lives, while maintenance doses are repeated to maintain steady state. Therapeutic drug monitoring measures drug levels to adjust doses for each patient.
1. The document discusses various aspects of vaccine trials including definitions, the first documented vaccine trial conducted by Edward Jenner in 1796, historical developments in vaccine design, types of licensed vaccines, and the vaccine development process.
2. It provides details on the different phases of clinical trials for vaccines - phase I focuses on safety and immunogenicity in healthy adults, phase II assesses immunogenicity in the target population including age de-escalation studies, and phase III evaluates efficacy in the target population.
3. Accelerated vaccine development strategies are being used for COVID-19 vaccines, with some in clinical trials evaluating safety, immunogenicity, and the ability to elicit immune responses through different mechanisms of
As this herbicide poisoning is frequent with poor outcomes so its management needs to be discussed and awareness should be raised among farmers about its use and pre-hospital treatments.
Pharmacogenetic considerations for cardiovascular drugs 26.03.2022.pptxDr. Nipa Mendapara
Pharmacogenetic considerations for cardiovascular drugs discusses several drugs where genetic factors can influence drug response, including clopidogrel, warfarin, and statins. For clopidogrel, CYP2C19 metabolizer status is important as poor metabolizers have lower drug levels and diminished effects. Warfarin dosing is affected by variants in CYP2C9, VKORC1, and CYP4F2. Statins like simvastatin are affected by SLCO1B1 variants which influence drug transport and risk of muscle symptoms. Clinical guidelines provide recommendations on genotype-guided dosing for these drugs.
Determination of anticonvulsant activity of drugs using animal modelsDr. Nipa Mendapara
This document discusses methods for determining the anticonvulsant activity of drugs using animal models. It begins by defining seizures and epilepsy according to the International League Against Epilepsy. It then describes several in vivo and in vitro animal models used in screening for new anticonvulsant drugs, including the maximal electroshock seizure test, chemically-induced seizure models using substances like pentylenetetrazol or pilocarpine, kindling models, and genetic models using epileptic-prone animals. The goal of these tests is to evaluate a drug's ability to prevent or reduce electrically or chemically induced seizure activity and elucidate new targets for developing improved antiepileptic treatments.
1. The document discusses drug receptors and signaling pathways. It defines receptors and their role in recognizing signal molecules to initiate a cellular response.
2. It describes two main types of receptors - extracellular/transmembrane receptors like G protein-coupled receptors and ion channel receptors, and intracellular/cytoplasmic receptors like nuclear receptors.
3. The key transmembrane signaling pathways discussed are the G protein pathway and its second messenger systems of cAMP, IP3/DAG, and ion channels. It also covers receptor enzyme pathways like receptor tyrosine kinases and Jak-STAT receptors.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
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Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
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NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
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2. CONTENT
• Introduction
• Challenges and limitations of Randomized Controlled Trials
• Defining pragmatic trial
• Explanatory Vs a pragmatic trial
• The PRECIS-2 tool
• Pragmatic features of a trial with example
• Summary
2
3. Introduction
• Pragmatic Clinical Trial was first introduced by Schwartz and Lellouch in
1967. These clinical trials are one of the sources that generate real-world
data.
• At present, most regulators across the world use results from randomized
clinical trials (RCT) for approving drugs. RCT provides proof of the efficacy
of the drug in a controlled environment.
• However, results are usually not enough to prove the effectiveness of the
drugs in real-world situations. Real-world evidence (RWE) generated from
routinely collected data may help to improve generalisability of the results
but have challenges. To fulfil the needs of other stakeholders like patients,
physicians, and policymakers, another approach is required.
3
4. Introduction
• Traditional explanatory randomized controlled trial (RCT) utilizing surrogate
endpoints to establish efficacy and safety in a highly selected population under
optimal conditions has been the gold standard for researchers and regulators
alike for many decades.
• These trials, which generate high-quality robust data with high intrinsic validity
upon which to base conclusions about causal relationships, answer the
explanatory question “is the intervention efficacious and safe in tightly
controlled, artificial conditions?”
• However, they ignore the more pragmatic question “is this an effective and safe
option for my patient?” The pragmatic trial design was developed to answer the
latter, which is a key question that can inform potentially life-altering decisions
required by payers, clinicians, and even patients themselves.
4
6. Definition of Pragmatic Clinical Trial (PCT)
• PCT can be defined as trials “designed for the primary purpose of informing
decision-makers regarding the comparative balance of benefits, burdens, and
risks of a biomedical or behavioural health intervention at the individual or
population level.” (Califf and Sugarman 2015)
• The significant elements of the PCT are:
(1) designed for various decision makers viz. clinicians, regulators, administrators,
and policy-makers
(2) enroll a representative patient population for whom the decision is relevant;
(3) measure a broad range of outcomes that impact clinical practice decisions by
providing comparative benefits of intervention
6
8. Explanatory Vs a Pragmatic trial
Explanatory
: tests
efficacy
Homogeneous
patients
Tightly defined
intervention
Clearly defined
control group,
often placebo
Objective/surrog
ate outcomes
Short-term
follow-up time
(e.g., 6 weeks
Pragmatic :
tests
effectiveness
Real-life patients
Flexible
intervention
with changes
Active comparator
instead of placebo
Clinically
important
outcomes
Longer-term
follow-up times
(e.g., 6 months)
8
9. Designing trials that are fit for purpose
• The original PRECIS (PRagmatic Explanatory Continuum Indicator
Summary) tool was developed in 2005–08 by 25 international trialists
and methodologists to help trialists work through their design
decisions so that they might avoid designing a trial that did not match
their own intentions for the trial.
9
10. The PRECIS-2 tool: designing trials that are fit for purpose
Gartlehner et al proposed a set of
seven domains to evaluate the
explanatory or pragmatic nature of a
trial
Thorpe et al (2009), a few years later,
introduced the PRagmatic Explanatory
Continuum Indicator Summary
(PRECIS) tool.
PRECIS-2(2015)—a validated,
improved version of the tool has been
developed (nine domain)—together
with guidance for how to use it
• Although they acknowledged that efficacy
(explanatory) and effectiveness (pragmatic)
exist in a continuum, they used a binary
system (yes/no) in the evaluation of these
domains.
• PRECIS was created to enable investigators to
design trials acknowledging the
explanatory/pragmatic continuum in 10
domains
• As PRECIS tool weaknesses : no rating scale,
problems with some domains, needing better
guidance, and not validated
10
11. Measuring pragmatism in trials
Score of 1 VERY
EXPLANATORY
Score of 2 RATHER
EXPLANATORY
Score of 3 EQUALLY
PRAGMATIC AND
EXPLANATORY
Score of 4 RATHER
PRAGMATIC
Score of 5 very
pragmatic
11
PRAGMATIC EXPLANATORY CONTINUUM INDICATOR (PRECIS-2) TOOL
Scoring each domain can be done using a 5-point Likert scale
12. • Trials that are predominantly explanatory in their design generate
spoke and wheel diagrams that are close to the hub, whereas those
with a more pragmatic approach produce diagrams that are closer to
the rim.
• In reality, few trials are purely explanatory or purely pragmatic, and
for the most part, a well-designed PRT that maintains high levels of
external and internal validity will seek to strike an optimal balance
between the two study types, thereby producing a diagram that
would be somewhere in the middle of the wheel
12
14. 1. Eligibility criteria—Who is selected to participate in the
trial?
Most extreme pragmatic approach
Inclusion-
• Intervention would likely be used for children,
elderly people, people with a range of
comorbidities
• People with a probable diagnosis rather than
a laboratory confirmed diagnosis
• Narrow eligibility criteria if the particular
narrow criteria are similar to those routinely
used for those participants in their usual care
setting
Exclusion-
• Aged over 80 or with multiple morbidities
would not receive the intervention in usual
care (harm > good)
Approach that reduce the PRECIS-2 score
Excluding people
• Not known or shown to be highly adherent to
the intervention
• Using tests or measures that are not used or
available in usual care
• Not expected to be highly responsive to the
intervention
• Children, people over the age of 65, and
pregnant women
• Whose adherence and follow-up may pose
difficulties
• Dependent on help for activities of daily living
14
16. 2. Recruitment—How are participants recruited into the
trial?
Most extreme pragmatic approach
• Only people who attend a clinic with the
condition of interest are recruited after they
present on their own behalf without any
overt recruitment effort
• Recruit from more than one clinic
Approaches that reduces PRECIS-2 score
• Searching medical record systems for
eligible participants and then mailing
invitation letters
• Media advertising campaigns
• Incentives
16
18. 3. Setting—Where is the trial being done?
Most pragmatic approach
• Trial in an identical setting to which you
intend the results to be applied
• Even settings that seem rather restrictive
could still be a highly pragmatic design choice
if this setting is the usual care setting where
patients are treated for the particular health
condition
Approach that reduces the PRECIS-2 score
• Selecting participating centers from among
only specialist or academic centres
• Running the trial in a single center
18
20. 4. Organisation—What expertise and resources are
needed to deliver the intervention?
Most pragmatic approach
• Slot the intervention into the usual
organisation of care for the condition of
interest, making use of no more than the
existing healthcare staff and resources in that
setting
• Sometimes a change to how care is organised
is itself the intervention being evaluated i.e.
Zwarenstein et al’s trial of directly observed
treatment (DOTS) versus self-supervised
treatment for tuberculosis
Approach that reduces the PRECIS-2 score
• Increasing the number of healthcare or other
professionals
• Providing significant levels of additional
training to increase the expertise of
healthcare professionals
• Requiring healthcare professionals to have
some minimum level of experience
• Requiring healthcare professionals to have a
specialty certification & Increasing the
resources to deliver the intervention
20
22. 5. Flexibility (delivery)—How should the intervention be
delivered?
Most pragmatic approach
• Methodology of how to deliver an
intervention is not rigidly prescriptive in the
protocol
• Ex. details of how to perform a surgical
procedure could be left entirely to the
surgeon, or how to deliver an educational
programme is left to the discretion of the
educator
Approach that reduces the PRECIS-2 score
• Highly specified, protocol driven intervention
• Monitor the compliance of those delivering
the intervention with the protocol and
measures
• Timing of intervention delivery is tightly
defined
• Providers undertake additional interventions
• Restrictions are placed on the number and
types of co-interventions
• Specific direction for applying permitted co-
interventionsmanaging complications or side
effects of the intervention
22
24. 6. Flexibility (adherence)—What measures are in place to
ensure participants adhere to the intervention?
Most pragmatic approach
• Allow for full flexibility in how end user
recipients engage with the intervention
• In usual care, health professionals encourage
patients to take medication or follow therapy
as best they can, and such encouragement
would not count against a pragmatic design
• No special measures to enforce engagement
or compliance
Approach that reduces the PRECIS-2 score
• Having a trial pre-screening stage where
patients are evaluated for adherence with the
intervention
• Withdrawing patients from the trial if their
adherence with the intervention drops below
some specified level
• Having measures in place to monitor patient
adherence with the protocol and measures to
address poor adherence
24
26. 7. Follow-up—How closely are participants followed up?
Most pragmatic approach
• No follow-up contact at all with recipients and
to obtain outcome data by other means or
have minimal additional data collection
• Trials may follow recipients well beyond the
intervention period
Approach that reduces the PRECIS-2 score
• Follow-up visits that are more frequent
• Unscheduled follow-up visits are triggered by
a primary outcome event or by an intervening
event
• Patients are contacted if they fail to keep trial
appointments. This would not reduce the
score if this was also done in usual care
• More extensive data are collected
• Visits are longer than usual care and involve
additional or different staff
26
28. 8. Primary outcome—How relevant is it to participants?
Most pragmatic approach
• To select an outcome that is of obvious
importance from the patient’s perspective &
relevant to commissioners of care
• Measure outcome in a way that is the same
or similar to the way they are measured in
usual care
Approach that reduces the PRECIS-2 score
• Choosing a surrogate outcome (such as blood
test)
• Using a composite primary outcome in which
some of the elements are less important to
patients or participants than others
• Choosing an outcome that is important but
mainly to providers
• Measuring an outcome that is important but
at a time that is earlier than would be normal
in usual care
28
30. 9. Primary analysis—To what extent are all data
included?
Most pragmatic approach
• Most trials are a superiority design so the
most pragmatic approach with regard to the
analysis would be to make no special
allowance in the analysis for non-adherence,
practice variability, etc.
• Analysis would typically be an intention-to-
treat analysis using all available data.
• For some trials taking an explanatory
approach (dose finding trials are an example),
it may be appropriate to have primary
analysis restricted in the ways mentioned
Approach that reduces the PRECIS-2 score
Excluding -
• Non-compliant recipients (per protocol
analysis)
• Data from non-adherent providers
• Data from trial sites or providers who recruit
below expected volume
• Analyse recipients to treatment received
instead of treatment randomised (as treated
analysis)
30
33. References
• Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M.
The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 2015
May 8;350:h2147.
• Anstrom KJ et al. Design and rationale of a multi-center, pragmatic, open-
label randomized trial of antimicrobial therapy - the study of clinical efficacy
of antimicrobial therapy strategy using pragmatic design in Idiopathic
Pulmonary Fibrosis (CleanUP-IPF) clinical trial. Respir Res. 2020 Mar
12;21(1):68.
• Califf RM, Sugarman J. Exploring the ethical and regulatory issues in
pragmatic clinical trials. Clin Trials. 2015 Oct;12(5):436-41.
33
How pragmatic clinical trials bridge the gap between research and care
A toolkit with guidance and practical help is available to download from www.precis-2.org.
The nine PRECIS-2 domains are: 1. Eligibility—To what extent are the participants in the trial similar to those who would receive this intervention if it was part of usual care? 2. Recruitment—How much extra effort is made to recruit participants over and above what would be used in the usual care setting to engage with patients? 3. Setting—How different are the settings of the trial from the usual care setting? 4. Organisation—How different are the resources, provider expertise, and the organisation of care delivery in the intervention arm of the trial from those available in usual care? 5. Flexibility (delivery)—How different is the flexibility in how the intervention is delivered and the flexibility anticipated in usual care? 6. Flexibility (adherence)—How different is the flexibility in how participants are monitored and encouraged to adhere to the intervention from the flexibility anticipated in usual care? 7. Follow-up—How different is the intensity of measurement and follow-up of participants in the trial from the typical follow-up in usual care? 8. Primary outcome—To what extent is the trial’s primary outcome directly relevant to participants? 9. Primary analysis—To what extent are all data included in the analysis of the primary outcome?
PRESCIS-2 tool should be used at the stage of planning and design to ascertain whether the design fits the Real world evidence study requirements. If not, the design can be modified to meet RWE objectives.
The goal is not to make all dimensions completely pragmatic (or explanatory), but to make thoughtful decisions for a given project.
Participants include patients or groups of practitioners or health system
to encourage trialists to consider the match between how care is organised and delivered in the trial and how the intervention would be made available to patients in usual care.
As delivery flexibility is reduced, the trial moves towards a more explanatory approach
trialists focused on applicability consider how probable it is that there will be uptake of the intervention being tested and how recipients will engage with it in the setting in which it will be later applied
As flexibility for recipients is reduced, the trial moves towards a more explanatory approach
As follow-up becomes more intense, the trial becomes more explanatory and the PRECIS-2 score will decrease.
As the primary outcome becomes less recognisably important to patients, or is assessed on criteria seldom used in usual care, the trial becomes more explanatory