Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Clinical trial brownbag session 1 nov 17 2010

651 views

Published on

Published in: Business, Health & Medicine
  • Be the first to comment

  • Be the first to like this

Clinical trial brownbag session 1 nov 17 2010

  1. 1. History & Overview of the Drug Development Process & Timeline<br />Brown Bag lunch series (1/6)<br />JoAnn Pfeiffer<br />November 17, 2010<br />
  2. 2. Goal<br />Through training on the conduct of human subject research the Velos staff will acquire a better understanding and knowledge of the steps and requirements in the day-to-day operations of a clinical trial. Through a better understanding of clinical trial operations the Velos staff will be able to respond more effectively to client requests and requirements.<br />
  3. 3. Session One<br />Agenda<br />History<br />Drug Development Process<br />Key players- roles and responsibilities<br />
  4. 4. Session One<br />Objectives<br />At the end of session the participant will be able to :<br />Describe the drug development process & timeline<br />Identify the key players involved in research<br />Describe the roles & responsibilities of the key players<br />
  5. 5. Historical Events<br />Pre 1906: all drugs could be bought or sold like any other consumer good<br />Pure Food & Drugs Act (1906) <br />Upton Sinclair: “The Jungle”<br />Prohibits interstate commerce of misbranded or adulterated foods, drinks, and drugs<br />Regulated product labeling<br />Did not address drug safety or efficacy<br />
  6. 6. Historical Events<br />The Federal Food, Drug and Cosmetics Act—1938<br />Sulfanilamide: treat streptococcal infections<br />Massengill Co: introduced a liquid form (1937)<br />107 people died that year<br />Contained diethylene glycol<br />First time FDA required that drugs must be safe before being introduced to the market.<br />
  7. 7. Tuskegee Syphilis trial (1932 - 1972)<br />Sponsored by PHS<br />Study the effects of untreated syphilis in black men<br />Exposed by media in 1972<br />Ramifications into late 1990’s<br />$9M, free medical treatment to survivors & descendants<br />Presidential apology in 1997<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />Tuskegee <br />
  8. 8. U.S. Code of Federal Regulations (CFR) <br />Nuremburg Code (1947-1948)<br />Nuremburg war crimes trials: Nazi experimentation<br />Ten points for legitimate medical research<br />Voluntary consent; fruitful results; based on animal experimentation; free of unnecessary physical or mental suffering; end result cannot be death or disability; risk/benefit; conducted by scientifically qualified persons; subject at liberty to withdraw; terminate if cause to believe harm; adequate facilities<br />Declaration of Helsinki (1964)<br />World Medical Association<br />Set of ethical principles for the medical community regarding human experimentation<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  9. 9. Thalidomide<br />Thalidomide (1950’s & 60’s)<br />Approved as sedative in Europe and Japan<br />Mfg. sent “samples” to US physicians<br />Patients not informed that the drug was investigational in US<br />Used for morning sickness<br />> 10,000 children in 46 countries were born with deformities in late 1950’s and early 1960’s<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  10. 10. Milgram Study<br />The Milgram Study (1961 – 1962)<br />67.5% administered the max shock (450 V)<br />Teacher – Learner<br />Teacher ask multiple choice questions<br />Administer a shock if answer incorrect<br />Start at 45 volt, could go up to 450 volt shock<br />All paused to question experiment<br />None refused prior to 300 volt shock<br />Female subjects –same results, higher stress<br />
  11. 11. Kefauver-Harris Amendment<br />Kefauver-Harris Amendment – 1962<br />Subjects informed of experimental nature<br />Informed consent must be obtained<br />Safety and efficacy must be proven prior to approval to market<br />Belmont Report – 1978<br />Respect<br />Beneficence<br />Justice<br />
  12. 12. History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  13. 13. Phase I<br />Primary Objective: <br />First in human<br />Safety and tolerability<br />20 – 80 healthy volunteers<br />Single dose or repeated doses <br />Low dosage, escalate to higher doses<br />Determine maximum tolerated dose <br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  14. 14. Phase II<br />Primary Objectives<br />Determine optimal dose and regimen<br />Safety & efficacy<br />Patients with disease<br />Up to 200 subjects<br />Multi-center<br />Adverse events<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  15. 15. Phase III<br />Primary Objectives<br />Gather additional information to evaluate the overall benefit-risk relationship<br />Large: up to thousands<br />Multi-center : representative of patient pop<br />Most expensive, time consuming<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  16. 16. Key Players<br />FDA<br />Sponsor<br />Principle Investigator (PI)<br />Institutional Review Board (IRB)<br />Study Coordinator <br />Data Manager<br />Study Monitor<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  17. 17. FDA<br />Protect safety of the consumer<br />Code of Federal Regulations <br />IND and NDA (drugs)<br />IDE and PMA or 510k (device)<br />Post-approval <br />Inspections<br />Recalls<br />Fines<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  18. 18. Study Sponsor<br />Academic institution<br />Pharmaceutical company<br />Device/ biologic/ drug<br />Investigator initiated<br />Government<br />NCI/ NIH/ CDC/ NSF, etc<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  19. 19. Sponsor roles<br />Develop Investigator Brochure (IB), protocol, informed consent<br />IND submission to FDA (30 days)<br />IRB approval<br />Site evaluations/ selection<br />Monitor the study sites (compliance)<br />NDA submission<br />Post-market evaluation<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  20. 20. IRB roles<br />Institutional or central IRB<br />Ensure safety of the study subjects<br />Review/ approve protocols<br />Review/ approve consents<br />Review/ approve any marketing materials<br />Review/ approve any amendments<br />Review AE & SAE reports<br />Review periodic reports from each sites<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  21. 21. IRB Operation Procedure<br />A Proposed Research Protocol<br />IRB receives a proposed research protocol with informed consent<br />Requires modification<br />General board reviews, discusses and votes<br />IRB disapprove the protocol<br />IRB notifies investigator of protocol approval<br />IRB conducts ongoing review<br />Research<br />Yes<br />Change protocol?<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  22. 22. Investigator role<br />Understand the IB and protocol<br />Conduct study in compliance with protocol<br />Responsible for the safety of study subjects<br />Delegate work to qualified staff<br />Informed consent process<br />Report any SAE/ AE<br />Maintain accurate records for inspection<br />Ensure protocols, consents, amendments have been approved by IRB <br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  23. 23. Study Coordinator Role<br />Conduct study from screening to close-out<br />Informed consent process<br />Screening process to determine eligibility<br />Schedule/ conduct patient visits<br />Responsible<br />Study documents (drug logs, AE logs, conmeds, medical history, patient procedures/visits, etc)<br />CRF or eCRF<br />Report AE/ SAE<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  24. 24. Data Manager role<br />Oversight data collection<br />Review accuracy and completeness<br />Create queries <br />Oversight for biostatisticians: analyze & report on data<br />Data lock<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  25. 25. Data Flow<br />Data Management<br />Paper CRF or Electronic data<br />PI Approves<br />Data query<br />Automatic or manually<br />CRC<br />Clinical Database<br />Database revised<br />Database lock<br />Resolve all the queries<br />Data Analysis <br />(Statistical analysis)<br />
  26. 26. Study Monitor role<br />Study Monitor represents the sponsor<br />All study documents complete & submitted<br />Review all study related documents for accuracy and completeness<br />Generate queries based on review<br />Drug Accountability logs<br />Conduct trainings<br />Ensure site compliance<br />Study site close-out<br />History<br />Drug Development Process<br />Study Design<br />Roles/ responsibilities<br />
  27. 27. Participant Knowledge Assessment<br />List 2 – 3 roles/responsibilities of each of the following:<br />FDA<br />Sponsor<br />IRB<br />Investigator<br />Coordinator<br />Monitor<br />

×