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Drug development


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Drug Discovery Presentation: …

Drug Discovery Presentation:
Veeda Clinical Research- The Knowledge library

Published in: Health & Medicine, Business

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  • 1. The Best of BOTH worlds
  • 2. Drug Development and Clinical Trials
  • 3. The Problems.... • Product development success rate has declined: – New compounds entering Phase I development today have 8% chance of reaching market, vs. 14% chance 15 years ago. – Phase III failure rate now reported to be 50%, vs. 20% in Phase III, 10 years ago. Source: FDA’s Critical Path Initiative presentation by Janet Woodcock, M.D. Deputy Commissioner for Operations, FDA May 11, 2006
  • 4. Rate of Drug Safety withdrawals...
  • 5. Trial inefficiency.... • According to a report from Cutting Edge Information, drug companies face losses of between $600000 and $8 million (~€460000 and ~€6 million) each day that a clinical trial delays a product’s launch. • With so many parties involved — sponsors, contract research organizations (CROs), site management organizations, patient recruiters, investigators and study participants — trials last 30–42% longer than expected.
  • 6. Drug Development is complex & risky
  • 7. Which strategy will work- Clinical or Non Clinical? Get it right the first time!
  • 8. Drug Development-The Phases
  • 9. Development Process Cost & Complexity Source: PhRMA, Tufts CDD
  • 10. The Process
  • 11. Phases of Drug Development
  • 12. In the Laboratory • A pharmaceutical company decides to develop a new drug aimed at a specific disease or medical condition. • Some specific methods used to begin the development of a new drug include: 1. Assay: In a series of test tube experiments called assays, compounds are added one at a time to enzymes, cell cultures, or cellular substances grown in a laboratory. The goal is to find which chemical compounds show some effect. 2. Computer model: A more high-tech approach is to use computers to simulate an enzyme or other drug target and to design chemical structures that might work against it.
  • 13. In the Laboratory Culture: Another method involves testing compounds made naturally by microscopic organisms. Candidates include fungi, viruses and molds, such as those that led to penicillin and other antibiotics. Scientists grow the microorganisms in what they call a fermentation broth, one type of organism per broth. Sometimes 100,000 or more broths are tested to see whether any compound made by a microorganism has a desirable effect.
  • 14. Animal Testing • Drug companies are required to test promising compounds in animals before they are tested in people. Two or more species are usually tested, since a drug may affect one differently from another. Such tests show whether a potential drug has toxic side effects and what its safety is at different doses. The results point the way for human testing and, eventually if the drug is approved, for product labeling. • A very small number of drugs reach testing in man. The Pharmaceutical Research and Manufacturers of America organization estimates that only five in 5,000 compounds that enter preclinical testing make it to human testing, and only one of those five may be safe and effective enough to reach pharmacy shelves.
  • 15. Planning for the First Use in Humans • FDA first becomes involved when a drug company has completed its testing in animals and is ready to test a drug on humans. • The clinical investigation of a chemical compound that holds commercial promise cannot begin until the manufacturer lets FDA know that it is planning to start testing the drug or biologic in people by filing an "investigational new drug application". If FDA does not take any action to stop or delay the clinical trial within 30 days, the manufacturer can begin to test the product in people.
  • 16. Early Clinical Trials – Phase 1 The object of the first clinical trials in humans is to find out if the new drug is safe. These first trials, called "Phase 1" trials, usually involve a small number of individuals (less than 100) who are healthy.
  • 17. Continuing Clinical Trials (Phase 2) • The results of the Phase 1 trial are analyzed. If they indicate that the new drug is safe enough, the process moves onto the next phases, Phase 2 and Phase 3. • If the new compound is considered safe, testing is expanded to see if it is effective, so trials include people who have the disease or condition against which the researchers think a new compound will be effective. Safety testing continues and is expanded and animal testing also continues
  • 18. Phase 2 Clinical Trials • This second phase of testing may last from several months to 2 years, and involve up to several hundred patients. Most Phase 2 studies are randomized trials. One group of patients will receive the experimental drug, while a second "control" group will receive a standard treatment or placebo. Often these studies are "blinded"--neither the patients nor the researchers know who is getting the experimental drug. MAY-JUNE 2005 THE PHYSICIANEXECUTIVE
  • 19. Phase 2 Clinical Trials • Phase II trials tend to last only a few weeks to, at most, a few months. Initial Phase II trials (sometimes called, IIa) are pilot trials to determine dose range. They tend to be conducted at specialized centers, like university medical centers, by specialized investigators, such as medical school faculty • Subsequent Phase II trials (often called, IIb) are aimed at elucidating dose response relationships, safety and, for the first time, efficacy, of the compound treating the disease or condition for which it is intended. MAY-JUNE 2005 THE PHYSICIANEXECUTIVE
  • 20. The start of Phase III.... Phase II can encompass anywhere from a few to 20 or more clinical trials, and the ―development plug‖ can be pulled—and frequently is— after any of them. Once again, assuming the drug shows sufficient evidence of efficacy and no major safety concerns—whether purely from drug effect, or from drug- drug interactions—a go/no go decision will be made to proceed to Phase III. In a Phase 3 study, a drug is tested in several hundred to several thousand subjects. This large-scale testing provides more information about the drug's effectiveness, possible side effects, and safety in a broader range of people. Most phase 3 studies are randomized and blinded trials
  • 21. Phase III • Few drugs have been approved with data from less than two pivotal trials, and, if so, generally require post-marketing commitments to ensure that safety and efficacy is validated after marketing. These trials are randomized, usually placebo-controlled (unless it would be unethical to use a placebo), and often involve an active comparator. • They are conducted by less specialized investigators in countries all over the world. Thousands of patients may be enrolled and trials can cost a sponsor $50 million to $100 million each. In addition to the two successful pivotal Phase III trials needed before an NDA can be filed, numerous additional special trials are usually demanded by regulatory agencies throughout the course of the IND clinical development period encompassing Phases I through III.
  • 22. NDA
  • 23. Simplified View of the NDA
  • 24. The Risk Benefit ratio
  • 25. NDA & its safety..... • Even when an NDA is approved unconditionally, regulatory scrutiny of a drug does not end. In most countries, yearly safety reports must be filed with the applicable regulatory agencies as long as a drug remains on the market, and these agencies independently monitor drug safety. • If safety concerns arise, the FDA may demand withdrawal of a drug from the market at any time (terfenadine {Seldane®}, cisapride {Propulsid®}, and cervistatin {Baycol}.
  • 26. “Alternative Models”....
  • 27. Summary It takes 10-15 years on average for an experimental drug to travel from the lab to U.S. patients. Only five in 5,000 compounds that enter preclinical testing make it to human testing. One of these five tested in people is approved.
  • 28. “Oscillations” in Drug Discovery