Introduction to clinical trial

Introduction to clinical trial

• 1.
  Introduction to Clinical Trial SubmittedBy : Abu Bakr Ansari Pharm. D 5th Year Roll No. 1601096001 Enroll No. 1600100627 Submitted To : Dr. Mohd Ajmal Sir Assistant Professor Integral University, Lucknow Faculty of Pharmacy PRY – 501 Clinical Research
• 2.
  Table of Content Definition and Importance  Role of Clinical trials in Clinical Product Development Different types of Clinical trials and their phases Important Regulations and Guidelines – ICH & GCP Design of a Clinical Trial
• 3.
  What is ClinicalTrials • Clinical trials are scientific investigations that examine and evaluate safety and efficacy of different therapies in human subjects. There are various definitions available as different individuals have tried to which try to capture the essence of clinical trials at different times, e.g.  Meinert (1986) indicates that a clinical trial is a research activity that involves administration of a test treatment to some experimental unit in order to evaluate the treatment.  Piantadosi (1997) simply defined a clinical trial as an experimental testing o f medical treatment on human subject.
• 4.
  • The Codeof Federal Regulations (CFR) defines a clinical trial as the clinical investigation of a drug that is administered or dispensed to, or used involving one or more human subjects (21 CFR ). • Three important key words in these definitions of clinical trials are experimental unit, treatment, and evaluation of the treatment.
• 5.
  Experimental Unit • Anexperimental unit is usually referred to as a subject from a targeted population under study. Therefore the experimental unit is usually used to specify the intended study population to which the results of the study are inferred. For example, the intended population could be patients with certain diseases at certain stages or healthy human subjects.
• 6.
  Treatment • identity (e.g.,a compound or drug), a new diet, a surgical procedure, a diagnostic test, a medial device, a health education program, or no treatment. Other examples include surgical excision, radiotherapy, and chemotherapy as a combination of surgical procedure and drug therapy for breast cancer; magnetic resonance imaging (MRI) with a contrast imaging agent as a combination of diagnostic test and a drug for enhancement of the efficacy of a diagnostic test.
• 7.
  Evaluation • In additionto the traditional evaluation of effectiveness and safety of a test treatment, clinical trials are also designed to assess quality of life, pharmacogenomics, and pharmacoeconomics such as cost- minimization, cost-effectiveness, and cost- benefit analyses to human subjects associated with the treatment under study. It is therefore recommended that clinical trials should not only evaluate the effectiveness and safety of the treatment but also assess quality of life, impact of genetic factors, pharmacoeconomics, and outcomes research associated with the treatment.
• 8.
  Differnet Phases ofClinical Trials • Clinical trials involving new drugs are commonly classified into four phases (I, II, III and IV). Each phase of the drug approval process is treated as a separate clinical trial. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV are 'post-approval' studies. Before pharmaceutical companies start clinical trials on a drug, they conduct extensive pre- clinical studies.
• 9.
  • Clinical ProductDevelopment - Phases
• 10.
  The Phases  PRE-CLINICAL- It involves in vitro (test tube or cell culture) and in vivo (animal) experiments using wide- ranging doses of the study drug to obtain preliminary efficacy, toxicity and pharmacokinetic information. Such tests assist pharmaceutical companies to decide whether a drug candidate has scientific merit for further development as an investigational new drug (IND).  PHASE I TRIALS: Initial studies to determine the metabolism and pharmacologic actions of drugs in humans, the side effects associated with increasing doses, and to gain early evidence of effectiveness; may include healthy participants and/or patients.  PHASE II TRIALS: Controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks.
• 11.
   PHASE IIITRIALS: Expanded controlled and uncontrolled trials after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide and adequate basis for physician labelling.  PHASE IV TRIALS: Post-marketing studies to delineate additional information including the drug's risks, benefits, and optimal use.
• 12.
  • Important Terms INVESTIGATIONALNEW DRUG (IND): A new drug, antibiotic drug, or biological drug that is used in a clinical investigation. It also includes a biological product used in vitro for diagnostic purposes. INSTITUTIONAL REVIEW BOARD (IRB): 1. A committee of physicians, statisticians, researchers, community advocates, and others that ensures that a clinical trial is ethical and that the rights of study participants are protected. All clinical trials in the U.S. must be approved by an IRB before they begin. 2. Every institution that conducts or supports biomedical or behavioral research involving human participants must, by federal regulation, have an IRB that initially approves and periodically reviews the research in order to protect the rights of human participants. It is similar to the Independent Ethics Committee (IEC) outside the United States.
• 13.
  NEW DRUG APPLICATION(NDA): An application submitted by the manufacturer of a drug to the FDA - after clinical trials have been completed - for a license to market the drug for a specified indication. TREATMENT IND: IND stands for Investigational New Drug application, which is part of the process to get approval from the FDA for marketing a new prescription drug in the U.S. It makes promising new drugs available to desperately ill participants as early in the drug development process as possible. Treatment INDs are made available to participants before general marketing begins, typically during Phase III studies. To be considered for a treatment IND a participant cannot be eligible to be in the definitive clinical trial.
• 14.
  Important Guidelines -ICH • ICH (International Conference on Harmonisation of Technical Requirements for Pharmaceuticals for Human use) is a unique undertaking that brings together the drug regulatory authorities and the pharmaceutical industry of Europe, Japan and the United States. • Regulatory harmonisation offers many direct benefits to both regulatory authorities and the pharmaceutical industry with beneficial impact for the protection of public health. Key benefits include:  Preventing duplication of clinical trials in humans and minimising the use of animal testing without compromising safety and effectiveness;  Streamlining the regulatory assessment process for new drug applications;  Reducing the development times and resources for drug development.
• 15.
   Q –Quality Guidelines: Defining relevant thresholds for impurities testing and a more flexible approach to pharmaceutical quality based on Good Manufacturing Practice (GMP) risk management.  S – Safety Guidelines: ICH has produced a comprehensive set of safety guidelines to uncover potential risks like carcinogenicity, genotoxicity and reproductive toxicity.  E – Efficacy Guidelines: The work carried out by ICH under the Efficacy heading is concerned with the design, conduct, safety and reporting of clinical trials.  M – Multidisciplinary Guidelines: Those are the cross- cutting topics which do not fit uniquely into one of the Quality, Safety and Efficacy categories. It includes the ICH medical terminology (MedDRA) and the Common Technical Document (CTD)
• 16.
  Principles of GCP(Good Clinical Practice)  Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).  Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.  The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.
• 17.
   The availablenonclinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.  Clinical trials should be scientifically sound, and described in a clear, detailed protocol.  A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favourable opinion.  The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.
• 18.
  THANK YOU