Phase II Phase II participants may total from 50 to over 200 people who are carefully chosen to meet specific criteria regarding health or disease status, age, gender, previous treatment, current medications or other characteristics. The main focus of Phase II clinical trials is efficacy – whether or not the drug provides a benefit, and if that benefit is qualitatively superior to currently used treatments. Dosage is fine-tuned during this stage. Phase II trials are typically double-blind and use placebos, meaning that neither the participant nor the scientists/doctors know who is receiving the drug and who is receiving the placebo during the course of the study. (In the case of life-threatening diseases, placebos may not be used.) Phase III Phase III is conditional on performance of the drug in Phase II. Phase III research evaluates the clinical benefit and safety of the drug under “real-life” circumstances. Selection criteria for participants include a greater range of characteristics to represent a real population. Phase III studies are typically carried out in a number of locations. Phase III studies are also double- blind and placebo-controlled. Responses to the drug (such as negative side effects or potential interactions with other drug regimens) within the larger population are estimated based on results seen in this phase. oversees clinical research. The local institutional review boards approve the clinical trial protocols, which describe the type of people who may participate in the clinical trial, the schedule of tests and procedures, the medications and dosages to be studied, the length of the study, the study’s objectives and other details. The review boards make sure the study is acceptable, that participants have given consent and are fully informed of their risks, and that researchers take appropriate steps to protect patients from harm. ● Phase 1 studies : These studies are usually conducted in healthy volunteers. The goal is to determine what the drug’s most frequent side effects are and often how the drug is metabolized and excreted. The number of subjects typically ranges from 20 to 80. ● Phase 2 studies : Phase 2 begins if Phase 1 studies don’t reveal unacceptable toxicity. While the emphasis in Phase 1 is on safety, the emphasis in Phase 2 is on effectiveness. This phase aims to obtain preliminary data on whether the drug works in people who have a certain disease or condition. For controlled trials, patients receiving the drug are compared with similar patients receiving a different treatment – usually an inactive substance (placebo), or a different drug. Phase 2 continues to evaluate safety and studies short-term side effects. Typically, the number of subjects in Phase 2 studies ranges from a few dozen to about 300. At the end of Phase 2, the FDA and sponsors try to come to an agreement on how to conduct the large-scale studies in Phase 3. How often the FDA meets with a sponsor varies, but this is one of two most common meeting points prior to submission of a new drug application. The other most common time is pre-NDA – right before a new drug application is submitted. ● Phase 3 studies : Phase 3 begins if Phase 2 shows evidence of effectiveness. These studies gather more information about safety and effectiveness, studying different populations and different dosages and using the drug in combination with other drugs. The number of subjects usually ranges from several hundred to about 3,000 people. ● Post-marketing study commitments : Also called Phase 4 commitments , these are studies required of or agreed to by a sponsor that are conducted after the FDA has approved a product for marketing. The FDA uses post-marketing study commitments to gather additional information about a product’s safety, efficacy or optimal use. ● New drug application (NDA) : This is the formal step a drug sponsor takes to ask that the FDA consider approving a new
drug is referred to as having investigational new drug (IND) status. The following steps in the clinical program are referred to as Phases I, II and III : Phase I The main focus of Phase I clinical trials is the safety and behavior of the drug in the body. Phase I typically involves the use of 15 to 30 healthy participants who receive varying doses of the drug to see if there are any undesirable side effects at different doses. The highest tolerable dosage, referred to as the maximum tolerable dose (MTD), is determined for future studies. While safety is the primary focus of Phase I testing, the drug’s bioavailability and pharmacokinetics are more fully explored. In some cases, Phase I testing is split into Phase 1a and Phase 1b. Phase 1a consists of a short-term study to confirm drug safety before a more extensive and comprehensive Phase 1b. To determine optimum bioavailability of the drug, different formulations and drug administration methods are examined to see whether the drug is ideally delivered, for example, by mouth or injection. Pharmacokinetics are carefully recorded, including a description of how the drug behaves in the body, how it breaks down into other compounds and its elimination from the body. Regulatory approval Results from all previous studies are submitted to the FDA, along with other regulatory agencies. If the data shows the drug to be sufficiently efficacious, safe and a benefit over currently used strategies, the drug is given new drug approval (NDA) status. At that point, the drug can be marketed as a product. The company selling the drug continues to monitor drug use for adverse effects. The period of ongoing review is sometimes referred to as Phase IV . The FDA’s drug review process: ensuring drugs are safe and effective Over the last 150 years, the FDA has evolved from a small division of the U.S. Patent Office to one of the largest consumer protection agencies in the world. Its mission includes ensuring that new medical treatments reach the public as quickly as possible while simultaneously ensuring that new treatments are both safe and effective (Van Norman, 2016). Often, a drug is developed to treat a specific disease. An important use of a drug may also be discovered by accident. For example, Retrovir (zidovudine, also known as AZT ) was first studied as an anti-cancer drug in the 1960s with disappointing results. It wasn’t until the 1980s that researchers discovered the drug could treat AIDS. The FDA approved the drug, manufactured by GlaxoSmithKline, for that purpose in 1987. Most drugs that undergo preclinical (animal) testing never even make it to human testing and FDA review. The drugs that do must undergo the agency’s rigorous evaluation process, which scrutinizes everything about the drug – from the design of clinical trials to the severity of side effects to the conditions under which the drug is manufactured. Stages of drug development and review ● Investigational new drug application (IND) : The pharmaceutical industry sometimes provides advice to the FDA prior to submission of an IND. Sponsors – companies, research institutions and other organizations that take responsibility for developing a drug – must show the FDA results of preclinical testing they’ve done in laboratory animals and what they propose to do for human testing. At this stage, the FDA decides whether it is reasonably safe for the company to move forward with testing the drug in humans. ● Clinical trials : Drug studies in humans can begin only after an IND is reviewed by the FDA and a local institutional review board (IRB). The board is a panel of scientists and non-scientists in hospitals and research institutions that
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