Yesterday, today, and tomorrow

Goals of this presentation :

 A look at clinical research from a pharmacy point of view.

 What will NOT be a focus of this presentation:  Social and ethical questions and considerations  Legal and regulatory issues  Protocol development and IND applications  Statistical considerations in clinical trials

Why do we do research?

Improve patient health through improved patient care  Types of studies:  Observational: e.g. epidemiologic, cohort, case control, longitudinal, etc  Interventional

Interventional clinical trials

 Clinical trials allow us to evaluate the efficacy and safety of new medications or agents  Usually in comparison to an established standard of care  Randomized, double-blind studies (the “Gold Standard”)

Why do we do interventional clinical trials?

 To obtain data to present to the FDA !

Drug companies are trading drug (and medical care) for data on patient outcomes

Stages in drug development

 Drug discovery / development  Pre-clinical testing  Investigational New Drug application (IND)  Clinical testing  Phase I  Phase II  Phase III  Phase IV

Phase I trials

 First use of a new drug in humans  Small numbers of patients, usually healthy volunteers  Looking primarily at safety and dose determination  Safety – dose limiting toxicity (DLT)  Dose determination – increase dose to toxicity  Pharmacokinetic and pharmacodynamic studies

Phase II trials

 Determine short-term risks and safety  Looking at effectiveness and best tolerated dose level  Dose(s) based on information from Phase I studies  Also looking at side effects  Study subjects are the types of patients the agent is intended to treat

Phase III

 Large scale trials (e.g. 300 – 1000+ subjects) looking at safety and efficacy usually in a randomized, controlled fashion often involving multiple centers  Seek to assess risk/benefit ratio and gather date for FDA approval of the agent / labeling  If data gathered from Phase I, Phase II, and Phase III trials demonstrate safety and efficacy => New Drug Application (NDA) may be filed with the FDA

Phase IV trials

 Post approval studies  May be required as a condition of approval  Long term safety studies  Comparison studies

Important elements in clinical trials  The protocol  The informed consent  Regulatory bodies  Blinding  Randomization  Finance

The Study Protocol

 Common elements:  Title   Protocol summary or synopsis Background and rationale   Study design / investigational plan Randomization and blinding   The investigational product Inclusion and exclusion criteria   Adverse events Data analysis

Informed Consent Form (the ICF)  Background  Elements  Description of trial  Voluntariness / withdrawal of consent / alternatives  Risk / benefit ratio  Questions  Contacts  Signatures

Regulatory bodies

 Institutional review board (IRB) – patient protection  Institutional bio-safety committee (IBC) and the Recombinant DNA Advisory Committee (RAC)  Food and drug administration (FDA)  Compliance office / office of research integrity (ORI)

Blinding

 Single vs double blind  Physical blinding: Size, shape, taste, appearance, smell, etc.

 Time considerations  Double dummy designs

Randomization

 History  IVR and IWR systems  Stratification  Blocks

Finance

 Contracts and grants (OCGM)  Cost of doing a study  Conflict of interest concerns

The “Players”

 Patients  The PI (and sub I’s), the 1572 form (Statement of Investigator)  Monitors  Research Coordinators  Regulatory entities (IRB, IBC, FDA, ORI / compliance, etc)  CRO’s

The “Players” (continued)

 Support services  Laboratory  Radiology  Pharmacy  Statistics  Finance

In the beginning…

 “What’s this and where did it come from?” (x2)  “…and you’re also in charge of investigational drugs.”  “I think it’s in that cabinet over there next to the sink”  “We are missing a week’s worth of entries on the temp record.”  “Is this the next envelope?”  “I’m going to San Diego for a meeting!”  “Budgets???”

The present

 Personnel  Types of studies  Training  Records and documentation  Monitoring  Disposal of study materials

Elements of a Research Pharmacy  Personnel  Storage space / equipment  Temperature monitoring  Documentation / record retention  The “information sheet” or “summary sheet”  Study budget

Pharmacy study budgets

 Common Elements  Start-up  Maintenance  Randomization  Study drug preparation and dispensing  Close-out fee  On – call fees

What’s ahead?

 Why utilize pharmacy services?

 Exotic agents  Electronic data capture and records  Impact of healthcare systems  Community based research